Ophthalmology Explorer 1st Edition

Ophthalmology Explorer 1st Edition Dhaval Patel

MD (AIIMS)

Ophthalmology Post-PG Examination Guide

Ophthalmology Explorer Ophthalmology Post-PG Examination Guide Dhaval Patel MD (AIIMS) [email protected] by ophthalmologyexplorer.blogspot.com 1st edition, April 2014

This is a compilation effort from my preparation notes and other sources, thus any contributions or comments are welcomed in the effort to improve this book. Therefore, feel free to e-mail me at [email protected]

Ophthalmology Explorer

Dhaval Patel MD

PREFACE

The CLASS is knowing what to say, when to say and when to stop.

Dear Friends, If you are reading this, then either you are approaching your final ophthalmology exams or you are preparing for further study courses in ophthalmology. So first thing I want you to know is the course for this exam include all aspects of ophthalmology in different amounts and nobody knows it perfectly. This preparation manual I have prepared during my residency and added up while preparing for senior residency/ fellowship examinations preparation which may serve as a small guide to your preparation. It will also serve as a good collection of facts which we might forget/neglect during overall MD/MS exam preparation. So whatever it may serve you, I am proud of what I have prepared and I feel it worth sharring with all emerging ophthalmologist friends. All the Best..!!

-Dhaval Patel MD

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Dhaval Patel MD

INDEX

Exploring EYE .................................. 6 Basic Sciences ............................... 90 Optics & Refraction ......................... 122 Cornea........................................ 160 Lens ........................................... 192 Glaucoma .................................... 205 Retina ......................................... 226 Uvea .......................................... 264 Strabismus ................................... 275 Neurophthalmology ......................... 284 Oculoplasty .................................. 310 Community Ophthalmology................ 337 Miscellaneous ............................... 342 Lateral Thinking ............................. 356 The Class Questions ....................... 364 Important History ............................ 369 Recalls from previous papers ............. 370

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Dhaval Patel MD

Exploring EYE .................................. 6

Genes ....................................... 29

AAO Color Codes of Topical Medication: 6

Giant Cells .................................. 35

Age Related Changes ...................... 6

Growth Factors ............................ 35

Aquaporins ................................... 7

Half Life ..................................... 36

Acquisition time .............................. 7

HLA .......................................... 37

Axis and Angles ............................. 8

HLA wise Diseases ..................... 37

Bimodal Age Distribution ................... 8

Disease wise HLAs ..................... 37

Blocks ......................................... 9

Host Cell Receptors ....................... 38

Cell Cycle Phase Facts ..................... 9

Host for Parasites ......................... 39

Collagen Collection ....................... 10

Hypersensitivity in Eye .................... 39

Contents of Important Fluids ............ 11

IHC Markers ................................ 40

Chromosomes for Eye .................... 13

Inheritence .................................. 41

Connexins .................................. 19

Inside Retinal Layers ...................... 42

Craniosynostosis .......................... 20

Interferons Therapy & Eye ............... 43

Diameters .................................. 20

Intraocular Gases .......................... 44

Drug Resistance ........................... 21

Intracameral Dosages .................... 44

Dye for Eye................................. 21

Intrastromal Dosages ..................... 45

Electromagnetic Spectrum ............... 21

Intravitreal Dosages ....................... 45

Evolutions of anesthetic techniques for cataract surgery ........................... 22

Intravitreal Implants ....................... 46

FDA Approved Drugs ..................... 23 FDA Device Classification ............... 26 Field of View ............................... 27 First in Genetics ........................... 27 Fellow Eye Risk ........................... 28 Frequency of Probes ..................... 29

Iris Nodules & Pathology ................. 48 Laser Facts ................................. 48 Brief History.............................. 48 Instrument Wavelengths ............... 49 Therapeutic Wavelengths ............. 49 Laser settings for glaucoma ........... 50 Laser settings in Retina ................ 51 3


Dhaval Patel MD

Laser Parameters for PTK ............ 51

DME ...................................... 74

Modes of Laser ......................... 51

ROP....................................... 76

Laser Mediums ......................... 52

ARMD .................................... 77

Laser Safety Classification ............ 52

Vitreomacular interface (VMI) diseases ............................................ 81

Latest Drugs ............................... 53 Mechanism of Action ..................... 57 MIP .......................................... 58 MMPs ....................................... 58 Molecular Weights ........................ 59 MUCins ..................................... 59 NV % ........................................ 60 OCT Review ............................... 61 Optic Nerve Segments ................... 62 Orders of Abberations .................... 63 Percentages % Primer ................... 63 Phacomatosis .............................. 65 Principles ................................... 66 Radiation and Eye......................... 67 Rates ........................................ 67 Recurrence %.............................. 68 Refractive Indices ......................... 69 Resolutions................................. 70 RB Stats .................................... 71 Racial predilection of Diseases ......... 72 Studies and Trials ......................... 72 DR ........................................ 72

Glaucoma ................................ 82 ON ........................................ 83 NAION .................................... 83 MISC ...................................... 83 Surface Tension ........................... 84 Specific Gravity ............................ 84 Surface Area ............................... 85 Survival Rates.............................. 85 Test Distances ............................. 86 Thickness ................................... 87 VEGF Facts ................................ 88 Vitreous cavity volume displacement ... 89 Water Content.............................. 89 Basic Sciences ............................... 90 Optics & Refraction ........................ 122 Cornea ....................................... 160 Lens .......................................... 192 Glaucoma ................................... 205 Retina ........................................ 226 Uvea.......................................... 264 Strabismus .................................. 275 4


Dhaval Patel MD

Neurophthalmology ......................... 284

Lateral Thinking ............................ 356

Oculoplasty .................................. 310

The Class Questions....................... 364

Community Ophthalmology ................ 337

Important History ........................... 369

Miscellaneous ............................... 342

Recalls from previous papers ............ 370

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Dhaval Patel MD

Exploring EYE

AAO Color Codes of Topical Medication: Based on the American Academy of Ophthalmology recommendations to the FDA to aid patients in distinguishing among drops and thus minimize the chance of using an incorrect medication 

Purple Cap: Alpha-Adrenergic Receptor Agonists



Yellow or Blue Cap: Beta-Blockers



Green Cap: Cholinergic Agonists, Miotics



Orange Cap: Carbonic Anhydrase Inhibitors



Turquoise/Teal Cap: Prostaglandin Analogues



Red Cap: Mydriatic/ cycloplegic agents



Tan Cap: Anti-infectives



Pink Cap: Steroids/ Anti-inflammatory



Gray Cap: Nonsteroidal anti-inflammatories



Dark Blue: beta-blocker combination

Age Related Changes 

Ganglion cell loss: 5000/year



Endothelial cell loss: 0.6%/year



Decrease in ACD due to increase LT: 20 microns/year



Age related loss of VF sensitivity: 1 db/year



15.6-μm decrease in choroidal thickness for each decade of life



LENS thickness increases 0.2 mm per 10 year. 20 year: 3.8 mm 40 year: 4.4 mm 6


Dhaval Patel MD

60 year: 4.8 mm 80 year: 5.2 mm 

central anterior chamber depth decreases 0.01 mm/year

Aquaporins



Water channels are known as aquaporins and lens epithelial cells contain an abundance of these.



MIP26 is believed to be a very old (and not very efficient) member of the aquaporin family and is termed aquaporin O.



Types o

AQP0 (MIP) in lens fiber

o

AQP1 in cornea endothelium, ciliary and lens epithelia and trabecular meshwork

o

AQP2 is not present in eye and is restricted to the kidney collecting duct

o

AQP3 in conjunctiva

o

AQP4 in ciliary epithelium and retinal Müller cells

o

AQP5 in corneal and lacrimal gland epithelia



AQP1 protects against vascular leakage by stabilizing the formed vessels.



NMO-IgG is a disease-specific autoantibody for neuromyelitis optica (NMO) and its target antigen is aquaporin-4 (AQP4) water channel.

Acquisition time 

Pentacam: 2 sec



OCT: 1 to 5 sec



Visante ASOCT: 3.3 sec o

Anterior segment scan ( 16×6mm): 256 A-scan/ 0.125 sec

o

High resolution scan: 512 A-scan/ 0.25 sec 7

Ophthalmology Explorer o

Dhaval Patel MD

Pachymetry scan: 128 A-scans/0.5 sec



Dynamic light scattering DLS for lens pathology: 5 sec



CSLO: 1.6 sec

Axis and Angles Axis of the Eye FOVea o

Fixation Axis: This is a straight line that joins center of rotation of eyeball with fixation point

o

Optical Axis: A line passing through center of cornea, center of lens and posterior pole of retina is the optical axis of eyeball

o

Visual Axis: A line joining point of fixation with fovea and passing through nodal point of eyeball is called visual axis. Nodal point of eyeball is just anterior to posterior capsule of lens. Fixation point is the point which is being seen with fovea at any particular moment.

o

Pupillary Line: This is a straight line that passes through center of pupil

Angles of the Eye o

Angle Alpha is the angle formed between optical axis and visual axis. AOV

o

Angle Kappa is the angle formed between visual axis and pupillary axis. KaVPa

o

Angle Gamma is the angle formed between optical axis and fixation axis. GOF

POsitive angle Kappa results in pseudoeXotropia. K-POX

Bimodal Age Distribution 

Craniopharyngioma (peaking in the first 2 decades and again in the years 50 to 70



Thyroid orbitopathy (for women occur from ages 40 to 44 years and 60 to 64 years; for men from ages 45 to 49 years and 65 to 69 years)



Hodgkin's lymphoma (early peak at 15 to 35 years of age and a second peak after 50) 8

Ophthalmology Explorer 

Glaucoma in SWS: (early-onset/congenital-type and later-onset)



Ocular Trauma

Dhaval Patel MD

Blocks

Facial Blocks: LOAN 

van Lint‘s block: Blocking the peripheral branches of facial nerve



O‘Brien‘s block: Facial nerve trunk block at the neck of mandible



Atkinson‘s block: In it superior branches of the facial nerve are blocked by injecting anaesthetic solution at the inferior margin of the zygomatic bone.



Nadbath block: facial nerve is blocked as it leaves the skull through the stylomastoid foramen.

Other Blocks 

Retrobulbar block was introduced by Herman Knapp in 1884



Peribulbar block was described in 1986 by Davis and Mandel

Cell Cycle Phase Facts 

Thymocyte- T cells: G0 arrest



Stem Cells: G0 arrest



Endothelial Cells: G1 arrest



central zone epithelial cells of lens capsule: G0 arrest



In the G1 phase of the cell cycle, the RB-protein is hypophosphorylated. In S, G2, and M, it is hyperphosphorylated. 9


Dhaval Patel MD



p53 mediates arrest of the cell cycle in the G1 phase after sublethal DNA damage



Rb gene arrests cells in the G1 or G1/S-phase of the cell cycle, and stops further proliferation.



Mitomycin C acts on all phases of cell cycle.

Collagen Collection 

Type 1: corneal stroma, tarsal plate



Type 2: vitreous



Type 3: ciliary process



Type 4: Descemet membrane, lens capsule, PNBZ, basal lamina of corneal epithelium



Type 5: Bowman membrane



Type 7: ABZ



Cornea total Collagen 15% o

o

fibrous collagens types I, II, III and V 

Type I 50-55%



Type III ~ 1%



Type VI 25-30%

non-fibrous collagen type IV 

Type IV 8-10%

o

filamentous collagens types VI, VIII, IX and X

o

basal lamina of the epithelium contains type IV collagen

o

Bowman‘s layer: type V

o

predominant collagen (about 90%) of the stroma is type I

o

Descemet's membrane contains predominantly type IV collagen, with about 10% type V 10


Dhaval Patel MD



BM of ciliary process and ciliary muscles ECM: laminin and collagen types I, III, and IV



human trabecular meshwork: collagen types I and III and elastin



Juxtacanalicular Tissue: collagen type III but no collagen type I or elastin



steroid-induced glaucoma shows increase in fine fibrillar material stains for collagen type IV in the subendothelial region of the Schlemm canal



anterior uveitis: reducing the density of collagen type I in the extracellular matrix of the ciliary body leading to increase in uveoscleral flow



lamina cribrosa of the human optic nerve head: collagen types I through VI, laminin, and fibronectin



Topical prostaglandin F2alpha treatment reduces collagen types I, III, and IV in the monkey uveoscleral outflow pathway

Contents of Important Fluids



BSS: Na, K, Ca, Mg, Cl, Citrate, Acetate BSS plus: ―+ HCO3, PO4, Glucose, Glutathione Aqueous: ―+ Lactate, Ascorbate, Protein



M.K. Media (4days): Tc199, Dextran, PH 7.0-7.5, Osmolality 295-355, gentamycin sulphate 75-150 micro gm/ml, HEPES as buffer, Phenol red as indicator



K-Sol: Tc 199, MEM & Earles media, HEPES, Gentamicin, Chondroin sulphate 2.5%



Dexol: MEM, 1.35% Chondrotin Sulphate, 1mM Sodium pyruvate, 1mM non- essential amino acids, Antioxidants, 1% dextran40.



Optisol GS: MEM, 1.35% Chondrotin Sulphate, 1mM Sodium pyruvate, 1 mM non-essential aminoacids, Antioxidants, 1% dextran40, ATP, Iron, cholestrol, L-hydroxyproline, Vitamins, 2 antibiotics- Gentamycin, Streptomycin



Procell: MEM,1.35%chondrotin sulphate,1mM sodium pyruvate1mM,Non-essential aminoacids,Antioxidants,Dextran40, Humen insulin 10 ug/ml & Human epidermal growth factor hEGF 10ng/ml to improve long term endothelial survival after PKP



Eusol-C: Store at 4 deg.C, Dextran, Sodium Piruvate, Glucose, Essential & non-essential aminoacids, mineral salts, Vitamins, Gentamin, hepes buffer, Bicarbonate, Phenol Red 11


Dhaval Patel MD



Organ culture medium: Fetal Bovine Serum, L-Glutamine, Earle's salts and 0.44% Mercaptoethanol in addition to the other constituents present in most intermediate storage media



Aqueous contents Relative to plasma, aqueous humor has



o

Slight hypertonicity and acidity (pH 7.2 in AC)

o

Marked excess of ascorbate (15 times greater than arterial plasma)

o

Marked deficit of protein (0.02% in aqueous vs. 7% in plasma)

o

Only calcium and phosphorus are in concentrations of about one-half that in plasma.

o

Chloride and bicarbonate vary from 20% to 30% above or below plasma levels.

o

Sight excess of lactic acid

o

Slight deficit of sodium, bicarbonate, carbon dioxide, and glucose

o

Protein and antibodies in aqueous equilibrate with those in serum when a plasmoid aqueous occurs with an anterior uveitis

o

Albumin/globulin ratio is similar to plasma, although there is less gamma globulin

Tear contents o

Lipid layer 

o

Wax, cholesterol, fatty acid esters

Aqueous layer 

Water



electrolytes (Na+, K+ Cl–, HCO3–, Mg2+)



proteins (albumin, lysozyme, lactoferrin,transferrin, ceruloplasmin),



immunoglobulins (IgA, IgG, IgE, IgM)



cytokines



growth factors (EGF, TGF-α, TGF-β1, TGF-β2, bFGF, HGF, VEGF, substance P) 12

Ophthalmology Explorer  o

others (glucose, vitamins)

Mucinous layer 

o

Dhaval Patel MD

Sulfomucin, cyalomucin, MUC1, MUC4, MUC5AC

IgD has not been detected in any study of human tears.

Chromosomes for Eye Chromosome 1: 

Fuch‘s dystrophy, COL8A2, AD



Posterior polymorphous dystrophy, PPCD2, AD



Stickler syndrome, COL2A, AD



Gelatinous drop like dystrophy, TYACSTD, AR



Schnyder corneal dystrophy, MJNFR, AD



EDS, EDS6, AR



Congenital glaucoma, GLC3B, AR



JOAG, Myocillin, AD



Stargardt‘s, ABCA4, AR



ARMD, CFH1



Usher syndrome, AR



Chediak higashi syndrome, LYST, AR



Leber‘s congenital amaurosis, RPE65, AR

Chromosome 2: 

Congenital Glaucoma, CYP1B1, AR



Oguchi‘s disease, Arrestin, AR 13


PXE, laminin/fibrillin, AR



Autosomal dominant drusen, EFEMP1, AD



Fleck dystrophy, PIP5K3, AD

Dhaval Patel MD

Chromosome 3: 

BPES 1 (with premature ovarian failure) and BPES 2 (without premature ovarian failure) are caused by type 1 mutations in FOXL2 gene



Von Hippel–Lindau syndrome Inheritance is AD condition caused by a mutation of the VHL gene clusterin



Retinitis pigmentosa, Rhodopsin, AD



Xeroderma pigmentosa, NER enzyme, AR



Alkaptonuria, homogentisate 1-2 dihydroxygenase, AR



Kjer autosomal dominant optic atrophy, OPA1, AD

Chromosome 4: 

Axenfield Rieger syndrome, PITX2, AD



CSNB, PDE6, AR



Wolfram syndrome, WFS1, AR



Hurler syndrome, alpha L iduronidase, AR



Bietti dystrophy, CYP4V2, AR



Fraser syndrome, FRAS1, AR

Chromosome 5: 

Treacher Collins syndrome (mandibulofacial dysostosis) Inheritance is AD with high penetrance and variable expressivity, although 60% of cases occur with no family history and are thought to arise by de novo mutation. The gene involved is the ‗treacle‘ gene TCOF1 on chromosome 5q. 14


Dhaval Patel MD



Cri du chat syndrome (partial deletion of 5p)



Mutations in TGFB1 on chromosome 5 cause CDB1, CDB2, lattice type 1, lattice type 3A, Avellino, and granular dystrophy. These are therefore allelic variants.

Chromosome 6: 

Adult-onset macular vitelliform dystrophy is caused by mutation in the RDS gene on chrn Dysromosome 6p, as well as the BEST1 gene in common with juvenile-onset Best dystrophy.



VEGF



Pattern dystrophy, RDS/ peripherin, AD



Axennfeld reiger syndrome, FOXC1, AD

Chromosome 7: 

Galactosemia classic, galactose 1 phosphate uridyl transaferase, AR



Pigment dispersion syndrome, AD

Chromosome 8:

Chromosome 9: 

Lattice 2, gelsolin, AR



Nevoid BCC syndrome, PTCH, AD



Rilet Day syndrome, IKBKAP, AR

Chromosome 10: 

Crouzon syndrome Inheritance is usually AD, but 25% of cases represent a fresh mutation. The gene (FGFR2) has been isolated to chromosome 10.



Thiel behnke dystrophy, AD 15


MEN2B, RET proto-oncogene, AD



Gyrate atrophy, OAT, AR



NTG-COAG, optineurin, AD

Dhaval Patel MD

Chromosome 11: 

Aniridia, peter‘s, AD keratitis, Axenfed reiger: PAX6, AD



Nanophthalmos, NNO1, AD



Best disease, 11q13 bestrophin, AD



FEVR, frizzled 4 gene, AD



OCA, TYR/OCA2, AR



CFEOM2: 11q13

Chromosome 12: 

CFEOM-1:



Cornea plana, KERA, AR



CHSD, DCN, AD



Meesman dystrophy, KRT3, AD



Fundus albipunctatous, RDH5, AR

Chromosome 13: 

Retinoblastoma, 13q14, AD



Sclerocornea, HCCS, AD



Microphthalmos, Trisomy 13



Congenital microcornea, AD



Oguchi disease, rhodopsin kinase, AR 16


Late onset fuchs dystrophy, FECD2, AD



CFEOM-3

Dhaval Patel MD

Chromosome 14: 

Oculopharyngeal dystrophy Inheritance is AD caused by mutation on chromosome 14q.

Chromosome 15: 

Marfan syndrome: FBN1, AD

Chromosome 16: 

Posterior Polar Cataract: mutation of PITX3 gene



Macular dystrophy, CHST6, AR



Pseudo xantoma elasticum, ABCC6, AR



Fish eye disease, LCAT, AR



Tyrosenemia, tyrosine amino transferase, AR

Chromosome 17: 

Meesman dystrophy, AD



NF1, NF1, AD



Cystinosis, CTNS, AR

Chromosome 18: 

Edwards syndrome (trisomy 18)



Transthyretin

17


Dhaval Patel MD

Chromosome 19:

Chromosome 20: 

CHED AD, CHED1 20911, AD



CHED AR< CHED2 20p13, AR



PPMD2, VSX1, AD

Chromosome 21: 

Down syndrome (trisomy 21)



Homocystinuria: Inheritance is AR with the gene locus on chromosome 21q.22.3.

Chromosome 22: 

NF2, NF2, AD



Sorsby dystrophy, TIMP3, 22q13, AD

Chromosome X: XR 

Fabry disease, alpha galactokinase



CSNB, calcium channels



Megalocornea, LTBP2



Coat‘s disease, NDP



FEVR, NDP



Retinitis pigmentosa, RPGR



Choroderemia, REP1



Norrie disease, NDP gene on chromosome Xp11. 18


Dhaval Patel MD

XD 

Lowe syndrome, OCRL1



Alport‘s syndrome, COL4A3



Aicardi syndrome



Incontinentia pigmenti: NEMO gene on chromosome Xq28.



Ichthyosis, STS

Chromosome Y:

Connexins 

At electrical synapses a cytoplasmic bridge is formed by specialized proteins called connexins. Six connexins form a hexagonal tube that projects out of the plane of the plasma membrane of one participating cell; this unit is called a connexon.



Connexin 43:



o

gap junctions of lateral membranes of lens epithelial cells

o

oculodentodigital syndrome

Connexin 46 and 50: o

Transmembrane proteins forming lens fiber gap junction is typically 16 nm thick

o

connexin 50 or MP70 is most prevalent in outer cortical fibers, where it undergoes age-related degradation to MP38, which continues in functional gap junctions.



connexin mutations can give rise to congenital cataracts



Connexin 50, connexin 37, and connexin 40 are all encoded by genes consisting of a single exon on chromosome 1q21



A zonular pulverulent cataract has been localized to chromosome 13 near the connexin 46 gene.

19


Dhaval Patel MD

Craniosynostosis

SPOT: Scaphocephaly: sagittal suture closure (aka 'dolichocephaly') Plagiocephaly: unilateral Coronal suture (anterior) or Lamboid (posterior) Oxycephaly: coronal suture plus any other suture, like the lambdoid Trigonocephaly: metopic suture closure

Syndromes Apert syndrome Crouzon syndrome Pfeiffer syndrome Saethre-Chotzen syndrome

Diameters



Collagen fibres in corneal stroma: 25 nm diameter, 60 nm spacing between each pair



Collagen fibres in vitreous: 10 nm diameter



Lens fibre diameter: 10.5 um



Zonular fibres: 70-80 nm diameter, grouped into bundles of 5-50 um diameter



Cone diameter: 2 um with 0.3 um spacing



Cochet and Bonnet esthesiometer wire: 0.12 mm

20


Dhaval Patel MD

Drug Resistance 

CMV UL97 mutations (a CMV DNA polymerase mutation that confers ganciclovir resistance) were detected in 3% of patients treated with ganciclovir over 3 months and in none treated less than 3 months.

Dye for Eye





Anterior Segment (Capsule staining) o

0.5% indocyanine green

o

0.15% trypan blue (less costly when compared to the cost of ICG)

Posterior Segment o

ICG: ILM staining  0.05%

o

IFCG: 0.05%

o

TB: ERM stain  0.06%

o

BBG: ILM staining  0.05%, 0.025%

o

TA

o

PB

o

BrB

o

NaF

Electromagnetic Spectrum (part of spectrum which is important in ophthalmology) 21


Dhaval Patel MD



Ultraviolet C rays: This band is blocked by the ozone layer of atmosphere.



Ultraviolet B rays: This band is responsible for snow blindness and photo keratitis caused by welding arc. Prolonged exposure to these rays can cause formation of pingicula and pterigium.



Ultraviolet A rays: This band of UV rays is absorbed by crystalline lens and thus retina is protected against their bad effects. Prolonged exposure to these rays causes cataract formation. IOLs implanted during cataract surgery have chromophores [inhibitors of UV rays] to protect retina against UV rays.



Visible Rays: VIBGYOR



Infrared A rays are responsible for macular burn in solar eclipse [photo retinitis].



Infrared rays B and C can cause corneal opacity and cataract formation on prolonged exposure.

Evolutions of anesthetic techniques for cataract surgery



General anesthesia 1846



Topical cocaine 1881 Koller



Injectable retrobulbar cocaine 1884 Knapp



OrbicuIaris akinesia 1914 Van lint, O'Briens Atkinson



Hyaluronidase 1948 Atkinson



Peribulbar 1970 kelman (but not published)



Posterior peribulbar 1985 Davis and Mandel



limbal 1990 Furata et al.



Anterior peribulbar 1991 Bloomberg



Pinpoint anesthesia 1992 Fukasawa and Furata



Topical tetracaine 1992 Fichman



Topical plus intracameral 1995 Gills



No anesthesia 1998 Agarwal 22


Cryoanalgesia 1999 Gutierrez-Carmona



Xylocaine jelly 1999 Koch and Assia



Hypothesis, no anesthesia 2001 Pandey and Agarwal



Viscoanesthesia 2001 Werner, Pandey, Apple et al

Dhaval Patel MD

FDA Approved Drugs

Drugs Approved in 2012 

Cystaran (cysteamine hydrochloride); Sigma Tau Pharmaceuticals; For the treatment of corneal cystine crystal accumulation due to cystinosis, Approved October 2012



Jetrea (ocriplasmin); Thrombogenics; For the treatment of symptomatic vitreomacular adhesion, Approved October 2012



Lucentis (ranibizumab injection); Genentech; For the treatment of diabetic macular edema, Approved August 2012



Zioptan (tafluprost ophthalmic solution); Merck; For the treatment of elevated intraocular pressure, Approved February 2012


Eylea (aflibercept); Regeneron Pharmaceuticals; For the treatment of neovascular (wet) age-related macular degeneration, Approved November 2011


Zymaxid (gatifloxacin ophthalmic solution); Allergan; For the treatment of bacterial conjunctivitis, Approved May 2010


Acuvail (ketorolac tromethamine); Allergan; For the treatment of pain and inflammation following cataract surgery., Approved July 2009



Bepreve (bepotastine besilate ophthalmic solution); Ista Pharmaceuticals; For the treatment of itching associated with allergic conjunctivitis, Approved September 2009



Besivance (besifloxacin 0.6% ophthalmic suspension); Bausch & Lomb; For the treatment of bacterial conjunctivitis, Approved June 2009 23


Dhaval Patel MD



Ozurdex (dexamethasone); Allergan; For the treatment of macular edema following branch retinal vein occlusion or central retinal vein occlusion, Approved June 2009



Zirgan (ganciclovir ophthalmic gel); Sirion Therapeutics; For the treatment of acute herpetic keratitis, Approved September 2009


Akten (lidocaine hydrochloride); Akorn; For anesthesia during ophthalmologic procedures, Approved October 2008



Astepro (azelastine hydrochloride nasal spray); Meda Pharmaceuticals Inc.; For the treatment of seasonal and perennial allergic rhinitis, Approved October 2008



Durezol (difluprednate); Sirion Therapeutics; For the treatment of inflammation and pain associated with ocular surgery, Approved June 2008


AzaSite (azithromycin); InSite Vision; For the treatment of bacterial conjunctivitis, Approved April 2007


Lucentis (ranibizumab); Genentech; For the treatment of neovascular (wet) age related macular degeneration, Approved June 2006


Macugen (pegaptanib); Pfizer / Eyetech Pharmaceuticals; For the treatment of wet agerelated macular degeneration., Approved December 2004


Restasis (cyclosporine ophthalmic emulsion); Allergan; For the treatment of low tear production., December 2002


Lumigan (bimatoprost ophthalmic solution); Allergan; For the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension, Approved March 2001



Travatan (travoprost ophthalmic solution); Alcon; For the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension, Approved March 2001

24


Dhaval Patel MD

Valcyte (valganciclovir HCl); Roche; For the treatment of cytomegalovirus retinitis in patients with AIDS, Approved March 2001


Betaxon; Alcon; For lowering IOP in patients with chronic open-angle glaucoma or ocular hypertension, Approved February 2000



Quixin (levofloxacin); Santen; For treatment of bacterial conjunctivitis, Approved August 2000



Rescula (unoprostone isopropyl ophthalmic solution) 0.15%; Ciba Vision; For the treatment of open-angle glaucoma or ocular hypertension, Approved August 2000



Visudyne (verteporfin for injection); QLT; For the treatment of wet age-related macular degeneration (wet AMD), Approved April 2000


Alamast; Santen; pemirolast potassium ophthalmic solution, Approved September 1999



ZADITOR; Ciba Vision; Treatment for the prevention of itching of the eye, Approved July 1999


Alrex; Bausch & Lomb, Pharmos; Treatment for seasonal allergic conjunctivitis, Approved March 1998



Cosopt; Merck; Treatment for glaucoma or ocular hypertension, Approved April 1998



Lotemax; Bausch & Lomb, Pharmos; Treatment for post-operative eye inflammation, Approved March 1998



Salagen Tablets; MGI Pharma; Treatment for Sjogren's Syndrome, Approved February 1998



Viroptic; King Pharmaceuticals; Treatment for inflammation of the cornea in children due to herpes simplex virus, Approved February 1998



Vitravene Injection; Isis Pharmaceuticals; Treatment for CMV in AIDS patients, Approved August 1998


Acular (ketorolac tromethamine ophthalmic solution) 0.5%; Allergan; Treatment for postoperative inflammation in patients who have undergone cataract extraction, Approved January 1997 25


Dhaval Patel MD



Acular (ketorolac tromethamine ophthalmic solution) 0.5%; Allergan; Treatment for postsurgical inflammation following cataract extraction, Approved November 1997



BSS Sterile Irrigating Solution; Alcon; Treatment during ocular surgical procedures, Approved December 1997


AK-Con-A (naphazoline ophthalmic); Akorn; Over-the-counter combination vasoconstrictor/antihistamine product for opthalmic use, Approved January 1996



Alphagan (brimonidine); Allergan; Treatment for open-angle glaucoma and ocular hypertension, Approved September 1996



Ocuflox (ofloxacin opthalmic solution) 0.3%; Allergan; Treatment for corneal ulcers, Approved May 1996



OcuHist; Pfizer; Over-the-counter antihistamine eye drop, Approved January 1996



Vistide (cidofovir); Gilead; Treatment for cytomegalovirus (CMV) retinitis, Approved June 1996



Vitrasert Implant; Chiron; Drug delivery system for the treatment of cytomegalovirus, Approved March 1996

FDA Device Classification 3 classes of ophthalmology devices 1. Class I devices (eg, refractometers, perimeters, sunglasses, visual acuity charts) are usually considered minimal-risk devices. Although these devices are subject to general controls, most of them are exempt from premarket review by the FDA. With few exceptions, manufacturers can go directly to market with a class I device. 2. Class II devices (eg, phacoemulsification units, tonometers, vitrectomy machines, dailywear contact lenses) are usually considered moderate-risk devices. Class II devices are those for which general controls alone are insufficient to ensure safety and effectiveness and for which methods exist to provide such assurances. These devices, in addition to general controls, are subject to special controls, which may include special labeling requirements) mandatory performance standards, and postmarket su rveillance. With few exceptions, class II devices requi re premarket review by the FDA. 26


Dhaval Patel MD

3. Class III devices (eg, excimer lasers, intraocular lenses, extended -wear contact lenses, intraocular fl uids) are considered significant-risk devices that present a potential unreasonable risk of illness or injury. Class III devices are those for which insufficient information exists to ensure safety and effectiveness solely through general or special controls. Class III devices cannot be marketed in the United States until the FDA determines that there is a reasonable assurance of safety and effectiveness when used accordi ng to the approved indications for use. Most class III devices come to market through the premarket approval (PMA) process and require an extensive review by the FDA before approval is granted for marketing.

Field of View 

Standard Fundus Camera: 20, 30 and 50 degrees



RetCam: 130 degrees



Optos: 200 degrees of retina (equator is at 180 degrees)



First in Genetics

Wow…!! It’s amazing that all of following diseases first described in each category has an eye manifestation…!!! (Ref: Alex Levin MD, WEI, PA, USA)

1st AD: Piebaldism 1st AR: alkaptonuria 1st XR: red green colour deficiency 1st XD: Incontigenta pigmenti 1st Mitochondrial: LHON 1st digenic: RP 1st trigenic: bardet biedel 27


Dhaval Patel MD

1st two-hit hypothesis: Retinoblastoma 1st contiguous gene deletion syndrome: anridia syndrome of wagner

Fellow Eye Risk



Keratoconus: 50% of normal fellow eyes will progress to keratoconus within 16 years



PXG: A patient with unilateral PXG and only PXF in the fellow eye is at high risk (50% in 5 years) of developing glaucoma in the fellow eye. A patient with unilateral PXG who does not have PXF in the fellow eye has only a low risk of developing glaucoma in the normal eye.



Patients with advanced AMD (late ARM) in one eye, or even moderate vision loss due to non-advanced AMD in one eye, have about a 50% chance of developing advanced AMD in the fellow eye within 5 years.



In Age related Macular Hole, risk of involvement of the fellow eye at 5 years is around 10%.



In NAION, Involvement of the fellow eye occurs in about 10% of patients after 2 years and 15% after 5 years.



AAION affects 30–50% of untreated patients of which one-third develop involvement of the fellow eye, usually within 1 week of the first.



7% of patients with CRVO develop a nonsimultaneous venous occlusion of the fellow eye within 2 years



The risk of any vascular occlusion in the fellow eye is estimated to be 0.9% per year.



The Macular Photocoagulation Study (MPS) reported that the 5-year risk of neovascularization in fellow eyes of individuals with unilateral neovascular AMD was 10% in those without large drusen and 30–46% in those with large drusen



POHS with CNVM, 20% risk over a 2-3-year period of developing choroidal neovascularization in the macula of the fellow eye



50-75% of patients with angle closure in one eye will have an attack in the fellow eye often within 1 year (up to 10years) despite miotic treatment. Prophylactic laser iridotomy in fellow eyes of patients presenting with unilateral acute PAC also appears to be safe and effective in preventing acute PAC in 100%, and in preventing long-term rise in IOP in 89%

28


Dhaval Patel MD



Acute retinal necrosis may occur in the fellow eye in approximately 30% of patients at an average interval of 4 weeks.



Chances of RD in fellow eye varies from 9-40%.

Frequency of Probes 

USG: 10 MHz



Ultrasonic Pachymetry: 10-20 MHz



UBM: 50 MHz



HI-SCAN: 35 MHz

Genes 

Genotypic heterogeneity: multiple genes causing single disease



Phenotypic heterogeneity: single gene causing multiple disease



PXF: LOX L1



BPES: FOX L2



Pterygium: KL-6



Lowe‘s syndrome: OCRL1 gene



TGFB1: aka BIGH3 o

5q31.2

o

Protein produced by corneal epithelium

o

Phenotypic heterogeneity GREAT 

Granular



Reis Buckler 29








EBMD



lAttice



Thiel Behnke

Dhaval Patel MD

PAX6, 11p13: phenotypic heterogeneity o

Aniridia

o

Gillespe

o

WAGR

Axenfield Reiger Spectrum (AD) – genotypic heterogeneity, multiple genes causing same disease o

GJA1 (connexin 43)  6p21

o

FKHL7/ FOXC1  6p25

o

PITX2/ RIEG1 4q25

o

RIEG2  13q14

o

COL4A1  13q34 (MCQ: all except type question, so remember its Chromosomes 4, 6 and 13)



Fuchs: genetic heterogeneity o

Following all genes do cause Fuchs and other diseases mentioned below. 

COL8A2: PPMD



SLC4A11: CHED



ZEB1: PPMD



PITX2: homeobox gene  Peters, ARS, AN, Iris hypoplasia



KCNJ13: upregulates ZEB1

30


Dhaval Patel MD

Keratin genes: cytokeratin 12 + 3 o

KRT3: 12q13  Meesman

o

KRT12: 17q12  Stocker Holt



Keratoconus: VSX1, SOD1



Glaucoma Genes nosology: o

GLC is name given to primary gene loci by HUGO: Human Genome Organisation, Geneva

o

GLC1: open angle (only 10% pt): AD 

Only 3 genes are known till now



GLC1A: JOAG 36%, POAG 4%  1q23-25  MYOC/TIGR



GLC1B: POAG  2q  nI IOP



GLC1C: POAG 3q  high IOP



GLC1D: POAG  8q23  high IOP



GLC1E: POAG/NTG 16%  10p14  Optineurin (OPTIc NEURopathy INducing), nI IOP



GLC1F: POAG  7q



GLC1G: POAG 5%  5q  WDR36 (WD Region 36)

o

GLC2: close angle

o

GLC3: congenital (>25%): AR

o



GLC3A: 2p21  CYP1B1, cyrochrome P450 gene



GLC3B: 1p36



GLC3C: 14q24



MYOC is responsible for 5.5% PCG

Pigment Dispersion Genes: AD, 7q35 31


Pseudoexfoliation syndrome: LOXL1, 15q24-25

o

Genes associated with MMP

o

o



Dhaval Patel MD



MMP9 downregulated during acute PACG



SNP rs17576 of MMP9 at chromosome 20q11 is strongly associated with acure PACG.

Genes Causing Early-Onset or Familial Glaucoma 

CYP1B1, Cytochrome p450  Congenital glaucoma



LTBP2, Latent transforming growth factor beta binding protein 2  Congenital glaucoma



PITX2, Paired-like homeodomain 2  Axenfeld-Riegers



FOXC1, Forkhead box C1  Anterior segment dysgenesis



PAX6, Paired box 6  Aniridia



MYOC, Myocilin  Primary open-angle glaucoma (juvenile and familial)



OPTN, Optineurin Familial normal-tension glaucoma



TBK1, TANK-binding kinase 1  Familial normal-tension glaucoma



LMX1B (9q34, glaucoma associated with nail-patella syndrome)

Glaucoma Gene Testing 

Congenital glaucoma  CYP1B1, LTBP2



Anterior segment dysgenesis  FOXC1, PITX2, PAX6



Primary open-angle glaucoma  MYOC



Normal-tension glaucoma  OPTN, TBK1, OPA1

Eyelid Tumors genes o

o

BCC: 

Sonic hedgehog pathway



PTCH1 (patched 1): in BCNS or Gorlin syndrome

SeCA: 32

Ophthalmology Explorer 

o

Muir Torre Syndrome 

MMR- Mismatch Repair genes (MSH-2, MSH-6, MLH-1)



MSI- high frequency of Micro Satelite Imbalance

Merkel Cell Carcinoma 

MCPyV: Merkel Cell Polyoma Virus  70% cases 

o





Dhaval Patel MD

LTA: Large T Antigen binds to host proteins, forces cell into Sphase

Cutaneous Malignant Melanoma 

C-KIT activating mutations  chronic sun damage MM (Acral MM, Mucosal MM)



BRAF activating mutations V600E (90%)  Non chronic sun damage MM  Nevi



P16INK4a-Rb pathway: loss of function mutation of CDKN2A  Familial melanoma (dysplastic nevus syndrome)



Melanocortin receptor (MC1R) varients  increased risk of MM and BCC independent of cutaneous pigmentation

ARMD o

Complement factor H gene (CFH): 1q32

o

Apolipoprotein E: 19q13.2

o

Many others..BIG BIG list!!

Retinal/Macular Dystrophies o

Best macular dystrophy

o

Stargardt disease ABCA4, Chr 1

o

Stargardt-like dominant macular dystrophy

o

Pattern dystrophy PRPH2

o

Sorsby fundus dystrophy TIMP3 Chr 22 AD

BEST1,

Chr11 AD/AR AR ELOVL4 Chr 6 AD

Chr 6 AD

33




Dhaval Patel MD

o

Autosomal dominant radial drusen

EFEMP1

Chr 2 AD

o

North Carolina macular dystrophy

Unknown

Chr 5 and 6

o

Spotted cystic dystrophy Unknown

Unknown

AD

o

Dominant cystoid macular edema

Unknown

Chr 7 AD

o

Fenestrated sheen macular dystrophy

Unknown

Unknown

o

Glomerulonephritis type II CFH

AD

AD

Chr 1 AR

Mutations of LHON o

11778: 98% patients, VA < 20/200, worst prognosis

o

14484: 10-15% patients, high incidence of spontaneous VA recovery, best prognosis

o

3460: 8-15% of patients, high incidence of visual recovery, family history positive



Gene therapy: for LCA, RPE 65 gene, NEJM 2008 study, Lancet 2009



Ocular development genes: o

Sonic hedgehog

o

Paired box

o



PAX2: (during optic vescicle, causes ocular-renal coloboma syndrome)



PAX6 (eye development)

Other downstream genes  CHX10, FKHL7 (6p15, forkhead transcription factor, ? neural crest), PITX2



Genes causing Diabetes: ALR2, RHGE, TGF beta1



Uveal melanoma gene: DDEF1 gene, chromosome 8q



The ATP-binding cassette o

Subfamily A:ABCA 

Adrenoleukodystrophy 34


o



Zellweger syndrome



Stargardt disease (ABCA4)



Autosomal recessive retinitis pigmentosa



Cone-rod dystrophy

Dhaval Patel MD

Subfamily G: ABCG 

ABCG2: limbal stem cells



Giant Cells 

Langhans giant cells: peripheral ring of nuclei, associated with tuberculosis, sarcoidosis



Touton giant cells: midperipheral ring of nuclei surrounded by a peripheral ring of lipid, associated with xanthogranulomatous disease



Foreign body giant cells: randomly dispersed nuclei, associated with foreign material and fungi

Growth Factors 

INF-Y: decreases angiogenesis



PEGF: decreases neovascularisation



Angiopoeitin: decreases leakage o

Angiopoietins-1–4 (Ang1–4) form a family of growth factors involved in angiogenesis

o

only Ang1 and Ang2 currently are known to have roles in ocular neovascular disease

o

Endothelial cells are a primary source of Ang2 production where it is stored in Weibel–Palade bodies (WPB) from which it can be released by a variety of stimuli



Myofibroblasts are derived from keratocytes under influence of TGF beta1.



HGF and KGF are predictor of corneal epithelial healing.



Keratocytes apoptosis is mediated by IL-1. 35


Dhaval Patel MD



PKC beta is most important in DR pathogenesis. It increases basement membrane permeability.



Angiogenesis is regulated by a balance between VEGF and PEDF (pigment endothelium derived factor), as evidence is emerging that PEDF may inhibit new blood vessel growth.



PDGF-B is a growth factor structurally related to VEGF. The contributions of PDGF-B to angiogenesis are mediated largely through its effects on mural cells such as pericytes and vascular smooth muscle cells.



Half Life









IVTA o

Normal eye: 41 days

o

Vitrectomised eye: 16 days

o

Aphakic eye: 6.5 days

PST o

Aqueous: 11 days

o

Vitreous: 17 days

o

Plasma: 25 days

Intravitreal Bevacizumab 1.25mg o

4.32 days rabbit

o

5 days in humans

Intravitreal Ranibizumab 0.5 mg o



3 days in monkeys

Strontium-90: 28 years

36


Dhaval Patel MD

HLA HLA wise Diseases 

A2: JIA



A11: Sympathetic ophthalmia



A29: birdshot chorioretinopathy (90-100% association)



B5, B12: behcet's dz



B7: toxoplasmosis, POHS, serpiginous choroidopathy, ankylosing spondylitis, APMPPE



B8: Sjögren‘s syndrome, sarcoidosis



B12: Ocular cicatricial pemphigoid



B13: sarcoidosis



B27: PAIR  Ankylosing spondylitis (88%), Reiter‘s syndrome (85–95%), inflammatory bowel disease (60%), psoriatic arthritis (also B17).



B51: behcet‘s disease, eales



Bw54: Posner-Schlossman syndrome, VKH?



DR2: POHS, intermediate uveitis, APMPPE



DR4: VKH, SO, OCP.



DR2/15: pars planitis and Multiple Sclerosis

Disease wise HLAs 

Keratoconus: A9/10/12, B5/21



PXF: A1/33, B8



OHT progression to Glaucoma: B7/12



AMD: A3, CW02/07



Diabetic Retinopathy (DR) development: DR1/7



Diabetic Retinopathy (DR) proliferation: DR4, DQ8 37


Dhaval Patel MD



Retinal vasculitis: B44



Eales: B51, DR1/4



IU: B8/51, DR2



Pars Planitis: DR15/17/51



VKH: HLA-DR4 and HLA-Dw53 are more common in Chinese patients, HLA-DR1 and HLA DR4 more common in Hispanic patients, and HLA DRB1 in Indian patients



SJS: significantly increased incidence of HLA-B12, HLA-Aw33, and DRw53



HSV EM: HLA-DQw3



TEN: HLA-B12



ocular lesions of SJS: HLA-B44



Birdshot choroidopathy: White, HLA-A29, 96%



Ankylosing spondylitis: White and asians, HLA-B27, 89%



Behçet's disease: Japanese, HLA-B5, 68%



Reiter's syndrome: White, HLA-B27, 80%



POHS: White, HLA-B7-77%, HLA-DR2-81%

Host Cell Receptors 

Adenovirus type 37: CD46



Epstein–Barr virus: CD21



Herpes simplex virus: Heparan sulfate



Human cytomegalovirus: Heparan sulfate



Human papillomavirus: Integrin a6



Influenza virus: Sialic acid



Rhinovirus: ICAM-1



Vaccinia virus: EGF receptor 38


Dhaval Patel MD

Host for Parasites







Definitive: o

Toxoplasma gondii: domestic and wild cats

o

Echinococcus granulosus: dog

o

Taenia solium: human

Intermediate host o

Taenia solium: pig

o

Toxoplasma gondii: animals including humans

o

Echinococcus granulosus: sheep, cattles, pigs

o

Francisella tularensis: rabbit, squirrels, cats, foxes, raccoons

o

Brucellosis: veterinarians and abattoir workers

o

Oncocerca volvulus: many species of black fly simulium

Both definitive and intermediate: o

Taenia solium: human

Hypersensitivity in Eye Gell, Coombs, and Lackmann‘s classification of Hypersensitivity Reactions o

Type 1: VKC, AKC, SAC, GPC

o

Type 2: OCP, PV, DH

o

Type 3: SJS, RA, SLE, PAN, RP

o

Type 4: TB, WG, Contact dermatitis, herpes disciform keratitis, sarcoidosis, transplant rejection

39


Dhaval Patel MD

IHC Markers 

Melanoma markers: HMB45, melan A, tyrosinase, S-100 , MITF



Epithelial markers: Cytokeratins (CAM 5.2, AE1, AE3, CK7, CK20, involucrin, etc.)



Endothelial markers: Factor VIII, CD34



Muscle markers: Muscle specific actin (MSA), smooth muscle action (SMA), desmin, myogenin



Neuroendocrine tumors: Chromogranin



Melanoma: HMB45, S100



Neural tumor: S100, Leu7



Fibrous histiocytoma: CD68



Spindle cell carcinoma: Cytokeratin



Rhabdomyosarcoma: Desmin, Vimentin, Muscle specific actin, Myoglobin, Myogenin, MyoD1, Caveolin-3



lymphoid tumors o

CD3: T cells

o

CD5: T cells, mantle cells, SLL/CLL

o

CD10: follicular lymphoma

o

CD20: B cells

o

CD23: follicular dendritic cells

o

Bcl-2: follicular, anti-apoptosis

o

Bcl-1: cyclin D1, mantle cell



Retinoblastoma is positive for neuron-specific enolase (also found in aqueous of RB), class III tubulin isotype (h4), microtubuleassociated protein 2 (MAP2), and synaptophysin; they are negative for glial fibrillary acidic protein and S-100 protein



Retinal stem cell marker: nestin, CD 34



Mitosis specific marker in cornea: Ki67

40


Dhaval Patel MD



Limbus Stem Cells: CK 5/14+ve, CK 19+ve, P63+ve, Vimentin+ve, ABCG2, alpha-enolase (5+14 =19)



Central Corneal Cells: CK 3/12+ve, Connexin 43+ve (3 x 4 = 12, 4.3)

 

Inheritence



All vitreoretinopathy are AD except o

Norrie  XL

o

XLRS  XL

o

Glodman favre  AR

o

Stickler  AD but rarely AR

o

FEVR  AD AR XR



All MPSs are transmitted by the AR mode, except MPS II (Hunter syndrome) which is XR.



albinism inheritance



o

All OCA are AR except ADOCA

o

OA are XR.

All corneal dystrophies are AD except o

Macular  AR

o

Gelatinous droplike  AR

o

LCD type 3  AR 41




Dhaval Patel MD

CHED type 2  AR

Microcornea: AD Megalocornea: XR



Familial ectopia lentis is AD Ectopia lentis et pupillae is AR.



Simple myopia and simple hypermetropia: AD

Inside Retinal Layers 

The nuclei of the Müller cells lie in the inner nuclear layer, whereas the nuclei of the photoreceptors lie in the outer nuclear layer.



The nerve fiber layer contains the axons of the ganglion cells.



The inner plexiform layer has axons of the bipolar and amacrine cells and the synapses of the ganglion cells.



The outer plexiform layer has connections between the photoreceptors, horizontal cells, and bipolar cells.



The footplates of the Müller cells form the internal limiting membrane.



cell bodies whose processes project into the lateral geniculate and pretectal nuclei ganglion cell layer



Müller's cell nuclei  inner nuclear layer



Photoreceptors nuclei  Outer nuclear layer



horizontal and bipolar synapses  outer plexiform layer



amacrine and bipolar cell synapses  inner plexiform layer



storage of dietary vitamin A  retinal pigment epithelium (RPE)



cell bodies whose processes form spherules and pedicles  outer nuclear layer 42


Dhaval Patel MD



high baseline cyclic guanosine monophosphate (cGMP) levels and membrane depolarization  photoreceptor layer



flame-shaped retinal hemorrhages  nerve fiber layer



dot hemorrhages  inner nuclear layer



Hard exudates  OPL



Soft exudates/ CWS  NFL

Interferons Therapy & Eye



Alpha 2a: capillary hemangioma



Alpha 2b: papilloma



Beta 1a:



o

Avonex: for MS, intramuscular, once weekly

o

Rebif: for MS, subcutaneous, thrice weekly, EVIDENCE Trial

Beta 1b: o



Betaseron and Extavia: for MS, subcutaneous

Gamma o

chronic granulomatous disease, kidney tumors and leishmania and other parasites.

43


Dhaval Patel MD

Intraocular Gases Physical characteristics

Gases

Mol wt.

Purity (mole%)

Expansion

Longevity (days)

Nonexpansile conc. (%)

Air

29

99.99

0

5-7

----

SF6

146

99.9

1.9-2.0 times

10-14

18

C3F8

188

99.7

4 times

55-65

14

Intracameral Dosages 

Vancomycin: 1 mg/ml



Cefazolin: 1 mg/0.1 ml



Cefuroxime: 1 mg/0.1 ml (ESCRS Study)



Gatifloxacin: 100 mcg/0.1 ml



Moxifloxacin: 100 mcg/ 0.1 ml



Amphotericin B: 5-10 mcg/0.1 ml



Irrigating fluid o

Vancomycin: 25-50 mcg/ml

o

Gentamycin: 0.008 mg/ml



Adrenaline tartarate: 1:10,000 (0.1 ml of 1:1000 is diluted with 0.9ml)



Pilocarpine: 0.1 ml of the drug (25 mg/ml) is diluted in 0.1 ml ringer lactate

44


Dhaval Patel MD

Intrastromal Dosages 

Voriconazole: 50 microgram/ 0.1 ml



Amphotericin B: 5-7.5 microgram/0.1 ml



Ciprofloxacin: 0.3 mg/0.1 ml



MMC: 0.02-0.04% for 15-30 sec to reduce post-operative interphase haze

Intravitreal Dosages 









Antibiotics o

Vancomycin: 1mg/0.1ml

o

Ceftazidime: 2.25mg/0.1ml

o

Amikacin: 400 migrogram/0.1 ml

o

Gentamycin: 200 migrogram/0.1 ml

Antifungals o

Voriconazole: 50-100micrgram/0.1ml

o

Amphotericin B: 5 migrogram/0.1 ml

Antivirals o

Ganciclovir (Cytovene): 200–400 mg/0.1 mL

o

Foscarnet (Foscavir): 1200 mg/0.05 mL

o

Cidofovir (Vistide): 20 mg/0.1 mL

Steroids o

Dexamethasone: 400 mcg/0.1 ml

o

Triamcinolone acetonide: 1-4 mg/ 0.1 ml

Anti VEGFs o

Pegaptinib MACUGEN: 0.3 mg in 0.09 ml pre-filled syringe 45


Dhaval Patel MD

Bevacizumab AVASTIN: 1.25 mg in 0.05 ml 

1 ampoule: 0.2 ml



1 vial: 4 ml or 16 ml of 25 mg/ml

o

Ranibizumab LUCENTIS: 0.5 mg in 0.05 ml

o

VEGF Trap EYELEA: 0.05, 2, 4 mg in 0.05 ml

o

SiRNA: 70-300 mcg

Intravitreal Implants 





Dexamethasone intravitreal implant (DEX implant; Ozurdex, Allergan, Irvine, CA) o

delivers the steroid intravitreally for 6 months

o

consists of poly (lactic-co-glycolic acid), a DEgradable polyester and dexamethasone

o

single-use applicator through a 22-gauge

o

uveitis and macular edema caused by retinal vein occlusion

o

350 µg and 700 µg version

o

Uses NOVADUR Delivery system

o

GENEVA (dexamethasone implant) study: Global Evaluation of implantable dexamethasone in retinal Vein occlusion with macular edema (GENEVA) study

Vitrasert ganciclovir implant o

poly(vinyl alcohol) and poly(ethylene vinyl acetate)

o

delivers the medication for approximately 32 weeks (8 months) and has been shown to halt the progression of CMV

o

nondegradable

o

5/4.5 mg implant

o

Releases 1 mcg/ hour

o

Approaches concentration of 4 ug/ml intravitreal

Retisert fluocinolone implant 46










Dhaval Patel MD

o

blend of the drug with poly(vinyl alcohol) and methylcellulose

o

0.59 mg pellet embedded in a nonbiodegradable scaffold designed to be implanted in the vitreous cavity via a sclerotomy and anchored by a suture to the eye wall

o

releases drug at steady state between 0.3 and 0.4µg/day for approximately 30 months

o

used most commonly for treatment of chronic non-infectious posterior uveitis.

o

Studied for DME also

Iluvien fluocinolone implant o

narrow cylinder 3.5 × 0.37 mm

o

25-gauge

o

lowest dose format (0.2 µg/day)

o

higher-dose (0.5 µg/day) system

o

FAVOR (iluvien) study

I-vation triamcinolone implant o

helical screw coated with triamcinolone acetonide that delivers the drug intravitreally for 36 months

o

25-gauge

o

drug is entirely within the coating on the helical structure and not within the bulk of the device

ECT CNTF Implant o

which allows the intravitreal implantation of a chamber containing live cells programmed to release CNTF

o

1.5 ng/day

o

possible efficacy for age-related macular degeneration (AMD) involving geographic atrophy and for RP

o

2 years or more

ECT technology anti-VEGF implant o

NT-503 47

Ophthalmology Explorer o 

Dhaval Patel MD

For ARMD

Brimonidine Intravitreal Implant o

Patients With Geographic Atrophy Due to Age-related Macular Degeneration (AMD)

o

This is a randomized, double-masked, dose-response, sham-controlled evaluation of the safety and efficacy of brimonidine tartarate intravitreal implant in patients with geographic atrophy from age-related macular degeneration. It is hypothesized that the implant may promote the release of neuroprotective factors that may slow the progression of retinal degenerative disease.

Iris Nodules & Pathology



Lisch nodule, neural crest hamartoma: NF 1



JXG nodules are composed of histiocytes and Touton giant cells: JXG



Koeppe nodules are collections of inflammatory cells, near pupillary margin: granulomatous and non-granulomatous uvetis



Bassaca Nodules are seen at base: only in granulomatous uveitis (sarcoid, Tb, syphilis, VKH); often look gelatinous



Brushfield spots are stromal hyperplasia: Downs syndrome



Berlin nodules are seen in angle: granulomatous uveitis

Laser Facts Brief History 

1917 - A. Einstein: Laser possible.



1958 - C.H. Townes, A.L. Schawlow: Theoretical basis for lasers.



1960 - T. Maiman: Built first laser. 48


1963 - C. Zweng: First medical laser trial (retinal coagulation).



1965 - W.Z. Yarn: First clinical laser surgery.

Dhaval Patel MD

Instrument Wavelengths (Chronological order in nm) 

SWAP: 440, blue light



Retinal Thickness Analyser RTA: green, 540-nm HeNe laser



Hertmann Shack‘s Aberrometer: 575 nm



HRT- CSLO: 670 diode



GDX-SLO: 780 diode



IOL Master: 780 diode



Lenstar: 820, SLD



Macular OCT (Posterior Segment OCT): 830



RNFL OCT: 810/850, SLD



AS-OCT: 1310, SLD



Swept Source OCT: 1050

Therapeutic Wavelengths (nm) 

Excimer laser: 193, Argon Fluoride (ultraviolet)



Excimer laser: 308, Xenon Cloride (ultraviolet)



Excimer laser trabeculostomy ELT: 308, Xenon Cloride



Argon blue-green: 488



Df Nd YAG: 512 (green)



ND YLF laser: 527 (in the treatment of diabetic macular edema) 49


Argon green: 514



Yellow dye laser: 577 for DME



Krypton red or Dye red: 620-630



He Ne Gas laser: 632, for Laser interferometry



Rostaporphin PDT: 664 nm



Diode: 689, PDT (its verteporphin‘s peak absorption)



Ruby laser: 694, red



Infrared diode laser: 780, IOL Master



Transpupilary thermotherapy, DLCP: 810



subthreshold micropulse STMP diode 810nm: for DME



Intralase: Nd: YLF, wavelength is 1053 nm



Nd YAG: 1064



Ho YAG: 2100, used for laser thermokeratoplasty



Erbium YAG: 2940, for laser phacoemulsification



CO2 laser: 10600

Dhaval Patel MD

Laser settings for glaucoma 

ND YAG PI: 500u, 5-15mJ, 12ns pulse, 1-3 pulse/sec



Argon PI: 50u, 1000mW, 0.1-0.2s,



Laser pupilloplasty: 200u, 0.2s, 400mW



Laser sphincterotomy: 50u, 0.01-0.05s, 1.5W



ALT: 50u, 100ms, 1000mW



SLT: 400u, 0.5-1.2mJ



DLCP: 810 nm, 2 mm from limbus, 8 spots per quadrent, 2000 ms, 1200-2000 mW 50


Dhaval Patel MD

Laser settings in Retina 



PRP: df NdYAG o

200-500 micron spot size

o

200-500 ms

o

200-500 mW

Macular Grid Laser: df NdYAG o

50-100 micron spot size

o

50-100 ms

o

50-100 mW

Laser Parameters for PTK 

Fluence: 160 ± 10 mJ/cm2



Repetition rate: 5 Hz



Ablation rate: 0.20-0.35 mm per pulse



Ablation diameter: 5.5–6 mm including a 0.5 mm transition zone



Ablation depths: o

Epithelium 40 mm (default value) or as determined by pachymetry

o

Stroma: Depth of scar or opacity (postoperative corneal thickness should be at least 250 mm)

Modes of Laser There are three modes of laser: continuous, Q-switched and mode-locked. o

Laser from continuous mode has a constant power and is measured in watts.

o

Q-switched and mode-locked increases the energy by compressing the energy in time and the energy is best measured in joules.

51


Dhaval Patel MD

Mode-locked laser compresses the laser more than Q-switched laser and therefore produces more energy.

Laser Mediums 

Solid state lasers have lasing material distributed in a solid matrix, e.g., the ruby or neodymium-YAG (yttrium aluminum garnet) lasers. The neodymium-YAG laser emits infrared light at 1.064 micrometers.



Gas lasers (helium and helium-neon, HeNe, are the most common gas lasers) have a primary output of a visible red light. CO2 lasers emit energy in the far-infrared, 10.6 micrometers, and are used for cutting hard materials.



Excimer lasers (the name is derived from the terms excited and dimers) use reactive gases such as chlorine and fluorine mixed with inert gases such as argon, krypton, or xenon. When electrically stimulated, a pseudomolecule or dimer is produced and when lased, produces light in the ultraviolet range.



Dye lasers use complex organic dyes like rhodamine 6G in liquid solution or suspension as lasing media. They are tunable over a broad range of wavelengths.



Semiconductor lasers, sometimes called diode lasers, are not solid-state lasers. These electronic devices are generally very small and use low power. They may be built into larger arrays, e.g., the writing source in some laser printers or compact disk players.

Laser Safety Classification The International Safety Classification of Lasers divides the lasers into 4 groups. Group 3 is subdivided into 3a and 3b. Class 3b and above is damaging to the eye and their powers are 5MW and above. All lasers used in ophthalmology are classed as 3b and above. Safety goggles should always be worn by people in the vicinity. Class I: Do not emit hazardous levels. Class II: Visible light lasers that are safe for momentary viewing but should not be stared into continuously; an example is the aiming beam of ophthalmic lasers, or laser pointers. Class III: Unsafe for even momentary viewing, requiring procedural controls and safety equipment. 52


Dhaval Patel MD

Class IV: Also pose a significant fire and skin hazard; most therapeutic laser beams used in ocular surgery are in this class

Latest Drugs



Lampalizumab: new monoclonal antibody that inhibits complement factor D, which is a ratelimiting enzyme of the alternative complement pathway, first positive treatment result for patients with dry age-related macular degeneration and geographic atrophy.



Pazopanib is a small molecule lipophilic potent and selective multitargeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/β, and c-kit that inhibits angiogenesis.







o

Pazopanib eye drops

o

5-10 mg/ml TID

o

failed to reduce as-needed ranibizumab injections by ≥ 50%

AGN-150998: o

Designed Ankyrin Repeat Proteins (DARPins)

o

Concept Study

o

Selectively binds to vascular endothelial growth factor-A with high binding affinity.

ROCK inhibitors:

o

Rho-kinase inhibitors (ROCK)  novel drug in glaucoma

o

human trabecular meshwork and Schlemm‘s canal cells to produce reversible changes in cell shape, focal adhesions and decreases in stress of the actin fibers. This resulted in an increase in permeability of the Schlemm cells‘ monolayer by 80%

o

decrease intraocular pressure by 25% to 32% and have a duration of action of 10 to 12 hours

o

ATS907, ATS8535, AR-12286, AR-13324, AMA0076

nitric oxide-donating prostaglandin F2-alpha analog  BOL-303259-X o

comparable to latanoprost 53




Dhaval Patel MD

Aganocides: novel class of compounds that mimic the body‘s natural defense against infection o

NVC-422  Phase IIb clinical trial to treat adenoviral conjunctivitis.



Voclosporin (Luveniq): novel immunomodulatory drug that inhibits the calcineurin enzyme, was originally developed to prevent organ graft rejection and to treat autoimmune diseases. The chemical structure of voclosporin is similar to that of cyclosporine A, but with a difference in one amino acid, leading to superior calcineurin inhibition and less variability in plasma concentration.



Mapracorat:



o

selective glucocorticoid receptor agonist (SEGRA)

o

similar anti-inflammatory and immunosuppressive effects as the glucocorticoids but with a decreased potential of the steroid side effects

o

Phase II study is evaluating its effectiveness in preventing the signs and symptoms of allergic conjunctivitis. In addition, a Phase III study is underway for the treatment of ocular inflammation after cataract surgery.

CF101: adenosine A3 receptor agonist o

Adenosine has been shown to inhibit leukotriene B4 (LTB4), which is part of the arachidonic acid cascade for the synthesis of prostaglandins and leukotrienes

o

For patients with moderate to severe dry eye



Lifitegrast: lifitegrast is a potent and selective small molecule drug being investigated for the treatment of dry eye and ocular allergy. It inhibits T-cell inflammation by blocking the binding of two key cellular surface proteins that mediate the chronic inflammatory cascade.



SMO Inhibitors (Smoothin): for advanced BCC o

Cyclopamine (SMO Inhibitors): 54


o





naturally occurring sterol alkaloid, topical drug is in clinical trials



it is obtained from Veratum calnifornicum (rocky mountain corn lily) ingestion of which causes serious malformation known as cyclopia and hence the name given cyclopamine

Vismodegib (GDC-0449): 

Synthetic small molecule



Orally active

o

Statins

o

Vitamin D3

Downstream SHH pathway inhibitors o

o

Rapamycin (sirolimus) 

Macrolide antibiotic



Inhibits MTOR in GLI1-transforme cells



No human stdies for BCC

MYCN anti-sence oligonucleotides 





No human studies for BCC

BRAF inhibitors: for Malignant Melanoma o

Sorafinib (pan BRAF)

o

PLX4032 (V600E-BRAF)

C-KIT inhibiors o



Dhaval Patel MD

Imatinib

Sutent: Sunitimab o

orally available multi-kinase inhibitor

o

Inhibits c-Kit, VEGFR, PDGFR etc

o

Activity against c-kit mutations that render OMs resistant to Gleevec 55


Synergistic effects with radiation and chemotherapy

o

Combination of Sutent, tamoxifan, cisplatin



Tegretin (Bexarotene): for CTCL (Mycosis Fungoides)



FOVISTA: Binds PDGF-B, phase 3 trials going on for wet AMD and CNVM.



Natalizumab: alpha 4 integrin



NT- 501

Dhaval Patel MD

o intra-vitreal implant is a Ciliary Neurotrophic Factor (CNTF) secreting encapsulated cell device

o CNTF is a cytokine, which is a survival factor for various neuronal cells and seems to prevent neurodegeneration. o

CNTF may act through the IL-6 receptor.

o A semi-permeable membrane encapsulates genetically engineered human RPE cells that secrete CNTF. It prevents host antibodies and immune cells from entering the device but allows nutrients to diffuse in, to nourish the cells within and CNTF to diffuse out. This holds promise for retinitis pigmentosa and dry age related macular degeneration



Bevasiranib (CAND5) is a siRNA which switches off VEGF production, but clinical effect is not seen till the preexisting VEGF is cleared. It has a potentially longer duration of effect than currently available anti-VEGF agents. It is well tolerated at multiple doses.



Vatalanib is a VEGF receptor tyrosine kinase inhibitor given orally.



Fenofibrate is drug of the fibrate class used to treat dyslipidemia. Raises HDL and lowers LDL and triglycerides and typically is used in combination with a statin. It lowers lipid levels by activating peroxisome proliferator-activated receptor alpha (PPARα). PPARα activates lipoprotein lipase and reduces apoprotein CIII, which increases lipolysis and elimination of triglyceride-rich particles from plasma.



Fenretinide in Dry AMD: This drug is an oral vitamin A binding protein antagonist and is being studied in patients with geographic atrophy (GA).It halts the accumulation of retinol (vitamin A) toxins through affinity for retinol-binding protein. One of the hallmarks of dry macular degeneration is the accumulation of lipofuscin that is responsible for drusen formation and geographic atrophy. One year interim data showed that fenretinide slowed the growth of geographic atrophy lesions by 45% in the 300 mg dose. 56


Dhaval Patel MD



Copaxone (glatiramer acetate): weekly vaccination, Macular degeneration, Alzheimer‘s disease and Multiple sclerosis



Citicholine (Cytidin-5-diphposphocholine): It is similar in action to levodopa. When administered in adult patients with strabismic amblyopia (1gm\day i.m for 15 days), it has showed improvement lasting over 6 months including improvement in contrast sensitivity and VEP.

Mechanism of Action 

Local anesthetics block the generation and conduction of nerve impulses



General Anesthetics: multiple



Fluoroquinolones: bactericidal agents that act by inhibiting DNA replication. They have dual targets, topoisomerase II (DNA gyrase) and topoisomerase IV



Tetracyclines: broad-spectrum antibiotics that inhibit bacterial protein synthesis by binding to the 30-S ribosomal subunit of the bacteria



Aminoglycosides: inhibit bacterial protein synthesis by binding irreversibly to the bacterial 30S ribosomal subunit.



Glycopeptides (Vancomycin and teicoplanin): inhibit peptidoglycan synthesis in the bacterial cell wall by complexing with cell wall precursors



Macrolides: bacteriostatic agents that inhibit bacterial RNA-dependent protein synthesis by binding reversibly to the 23S tRNA of the 50S ribosomal subunits



Chloramphenicol: bacteriostatic agent that inhibits protein synthesis by binding reversibly to the peptidyltransferase component of the 50S ribosomal subunit and prevents the transpeptidation process of peptide chain elongation



SMX-TMP: competitively inhibit the bacterial modification of p-aminobenzoic acid into dihydrofolate, and trimethoprim inhibits bacterial dihydrofolate reductase



Bacitracin and gramidicin: Bacitracin disrupts bacterial cell-wall synthesis by inhibiting the dephosphorylation of a lipid pyrophosphate, while gramicidin interferes more with cell membrane permeability



Polymyxins: interact with the phospholipids of the bacterial cell membrane, which increases the cell permeability and disrupts osmotic integrity. This process results in leakage of intracellular constituents, leading to cell death 57


Dhaval Patel MD



Trifluridine: potent inhibitor of thymidylate synthetase and therefore inhibits DNA synthesis



Vidarabine: interfere with the early steps of viral DNA synthesis and arrests the growth of the viral deoxynucleotide chain



Acyclovir: inhibits viral dependant TK (thymidine kinase)



Ganciclovir: competition with deoxyguanosine for incorporation into viral DNA



Polyenes: binds esterols in the fungal cell wall, forming ‗blisters‘ and causing lysis of the cell



Imidazoles: affect the formation of ergosterol needed by the cell membranes by inhibiting the enzyme lanosterol 14 α-demethylase



Caspofungin: inhibits synthesis of B(1,3)-D glucan,a component of fungal cell wall

MIP 

major intrinsic membrane protein



The most abundant membrane protein of the lens is intrinsic membrane protein 26 (MP26, MIP). It is a lens-specific single polypeptide with a molecular mass of 28,200 kDa (263 residues) that makes up about 50% of the lens membrane protein.



MIP26 is a member of the aquaporin (AQP) family, members of which transport small molecules such as water and glycerol.



MIP26 is termed aquaporin O



A locus for autosomal dominant cataracts has been mapped to chromosome 12q12-14.1 near the MIP gene

MMPs 

MMP 1: collagen 1,2,3



MMP 2,9: collagen 4,5,7 and laminin



MMP 3: GAGs and Fibronectin



Only MMP 2 is found in normal cornea.

58


Dhaval Patel MD

Molecular Weights 

Sodium fluorescein: 376.27 daltons



Indocyanine green: 775 daltons



VEGF: 45kDa



Bevacizumab: 149 kDa



Ranibizumab: 48 kDa



Sodium Hyaluronate: 2–5 million d



Chondroitin Sulfate: 50,000 d



Silicone oil: 28,000 (1,000 centistokes)



Air: 29



Sulfur hexafluoride (SF6): 146



Perfluoroethane (C2F6): 138



Perfluoropropane (C3F8): 188



PMMA IOLs: 2.5 to 3 million Da



Acylic IOLs: 80 000 to 140 000 Da



Botulinum toxin: 900 000 Da

MUCins 

Mucins are classified by the nomenclature MUC1–21 and are divided into secreted and membrane-spanning categories o

Membrane-spanning mucins consist of a short intracellular tail, membranespanning domain, and large, extended extracellular domain that forms the glycocalyx.

o

Secreted mucins are either gel-forming or small soluble. 

Gel-forming mucins are large molecules (20–40 million Da) secreted by exocytosis from Goblet cells.



Small soluble mucins are secreted by the lacrimal gland. 59


Dhaval Patel MD



MUC 1, MUC 4, and MUC 16: apical surface of the corneal epithelium



MUC 5AC and MUC 2: aqueous layer of the tear film (membrane-spanning, gel-forming mucins)



MUC16 protein levels decreased in conjunctival epithelium and increased in tears of patients with Sjogren's syndrome



MUC1 splice variants also play a role in dry eye



MUC5AC is the gel-forming mucin forming mucous layer backbone

NV %

BRVO NVI: 1 NVD: 10 NVE: 30

Ischemic BRVO 40% of patients with an ischemic BRVO develop NVE or NVD. 60% of the patients with NVE-NVD develop VH/PRH.

Ich CRVO NVI: 50 NVD: 30-35 NVE: 20-25 NVG: 45

CRAO 60


Dhaval Patel MD

NVI: 20 NVD: 2

OIS NVI: 67 NVD: 35 NVE: 8

EALES‘ DISEASE NVI: 0.5-0.8 % NVD: 10-18 % NVE: 50 % Sec RRD: 8-11 %

OCT Review 





Time Domain OCT (TD-OCT) o

Light echoes from each time delay measured sequentially

o

Slow acquisition speeds, high signal-to-noise ratio, poor view of the choroid

o

400 A-scans per minute, 6 B-scans per macula, 10-μm resolution

Spectral Domain OCT (SD-OCT) o

Light echoes from each time delay, all measured simultaneously (high-speed spectrometer)

o

Fast acquisition speeds, low signal-to-noise ratio, view to the choroid possible

o

52,000 A-scans per minute, 20-40 B-scans per macula (up to 100), 5-μm resolution

Enhanced Depth Imaging OCT (EDI-OCT) 61






Dhaval Patel MD

o

Zero delay line (ZDL) positioned at the inner retina

o

The further from the zero-delay line (ZDL), the lower the signal resolution.

o

EDI moves the ZDL closer to the choroid; negative images when the ZDL is crossed.

o

Thinner layers permit deeper tissues to be closer to the ZDL.

Full Depth or Combined Depth Imaging OCT (CDI-OCT) o

100 B-scans averaged for a single line scan.

o

50 in standard SD-OCT mode and 50 in EDI mode

o

Maximizes resolution of vitreoretinal and choroidal structures in a single scan

Swept Source OCT o

Topcon DRI OCT-1 Atlantis

o

Longer wavelength light source (1050 nm)

o

Fast (100,000 A scans per second)

o

Uniform sensitivity, allowing excellent visualization of structures from vitreous to sclera in one scan

o

Automated segmentation (7 layers)

o

100,000 A-scans per second, 1-μm resolution

o

12-μm wide scans (vs. 9- and 6-μm scans)

o

Image depth of 2.6 mm vs. 1.9 mm for EDI—even more ideal for choroidal tumors

Optic Nerve Segments

Longest segment  intraorbital Shortest segment  intraocular Segment with the most variable length  intracranial Divided into three subsegments  intraocular Most vulnerable to indirect trauma  intracanalicular 62


Dhaval Patel MD

Most redundant segment  intraorbital The only segment not bathed in cerebrospinal fluid  intraocular

Orders of Abberations

0. Piston 1. Vertical and horizontal prisms 2. Myopia (positive defocus), hyperopia (negative defocus), Regular (cylindrical) astigmatism 3. Coma, trefoil 4. Spherical astigmatism 5. rosette 6. pentacle, axial coma

Percentages % Primer



50% of patients with scleritis have systemic disease



Steroid-induced increases in intraocular pressure occur in about 6% of patients on topical dexamethasone



30–50% of individuals with glaucomatous optic nerve damage and visual field loss have an initial intraocular pressure measurement less than 22 mmHg.



sporadic inheritance of aniridia need to be evaluated for Wilms‘ tumor, which is associated with 25% of cases.



BCC 3% mortality rate



83% of macular holes are idiopathic, and 15% are due to some sort of trauma



Deuteranomaly is present in approximately 5% of the population; deuteranopia, protanopia, and protanomaly in 1% each; and tritanopia or tritanomaly in only 0.002%. 63


Dhaval Patel MD



ACUTE ACG: 40–80% chance of an acute attack in the fellow eye over the next 5–10 years.



PPMD: Glaucoma is associated in 15%.



Axenfeld‘s syndrome is the anomaly with coincident glaucoma in 50% of cases.



Glaucoma in hyphema: Secondary glaucoma occurred in o

13.5% of those eyes in which blood filled half of the anterior chamber,

o

in 27% of those eyes in which blood filled greater than half of the anterior chamber, and

o

in 52% of those eyes in which there was a total hyphema.



Angle recession is found in 60–90% of patients with a traumatic hyphema



Up to 10% of patients with greater than 180 degrees of angle recession will eventually develop a chronic traumatic glaucoma



Expulsive choroidal hemorrhage after cataract surgery: 0.2%



Retinal detachment after cataract surgery: 1–2%



PCO: 8-50%



HLA-B27–associated conditions account for approximately 45% of acute NGAU.



The incidence of HLA-B27 in the general population is 8%.



HLA B27 is present in 90% of patients with AS and 80% of those with Reiter‘s disease.



16% of patients of intermediate uveitis may develop multiple sclerosis



Sympathetic ophthalmia incidence: o

perforating ocular injury (0.2%)

o

ocular surgery (0.01%)

o

80% of cases develop within 3 months of injury, and 90% develop within 1 year.



Among patients whose CD4+ count is less than 50 cells/mL, 20% per year develop CMV retinitis.



A daily dose of >8 mg/kg/day of hydroxychloroquine produces retinopathy in 40% of cases.



Posttraumatic endophthalmitis incidence after penetrating ocular trauma: 7% of cases 64


Dhaval Patel MD



complement factor H gene is a single nuclear polymorphism responsible for nearly 50% of ARMD risk.



90% of infants who develop acute ROP undergo spontaneous regression



The risk of bilaterality in retinal arterial obstruction is approximately 10%.



Approximately 10% of patients with a BRVO will develop a retinal vein occlusion in the fellow eye.



The prevalence of endophthalmitis is 1.4% after intravitreal triamcinolone injection. However, this also includes cases of pseudoendophthalmitis. Excluding pseudoendophthalmitis, the prevalence is approximately 0.6%.



The cilioretinal artery is present in up to 20% of individuals.



In uveal melanoma, if no epithelioid cells are present, the expected survival at 15 years is 72%. If epithelioid cells are present (mixed, epithelioid, or necrotic cell type), the survival at 15 years drops to 37%.



Liver metastases occur in 93% of patients who develop metastatic uveal melanoma. Other sites include the lungs (24%) and bone (16%).



15% of eyes with symptomatic PVD develops retinal tear.



Untreated symptomatic retinal tear causes RD in 35-50% cases.



Pharyngoconjunctival fever: 30% keratitis Epidemic keratoconjunctivitis: 80% keratitis

Phacomatosis The 9 Phacomatosis: (there are total 9 phacomatosis which are numbered as follow)

1. neurofibromatosis type I - autosomal dominant - chromosome 17 2. NF type II - autosomal dominant - chromosome 22 3. tuberous sclerosis – autosomal dominant - chromosome 9 4. Sturge-Weber's syndrome – sporadic 65


Dhaval Patel MD

5. von Hippei-Lindau's syndrome - autosomal dominant - chromosome 3 6. Louis-Bar syndrome-autosomal recessive - chromosome 11 7. Wyburn-Mason syndrome - sporadic 8. Klippel-Trenaunay-Weber syndrome – autosomal dominant – chromosome unknown 9. cutis marmarata telangiectasia congenita - sporadic.

Phakomatosis is an outdated term and concept and term. Neither the AAO‘s monograph on Inherited Diseases and the Eye (Traboulsi) nor the WHO‘s text on CNS Tumors includes the term in the index. The WHO lists the disorders as familial cancer syndromes

Principles



CSLO: light projected toward the plane of interest through a conjugated set of pinholes allows the light to reach the detector only from the desired plane, while light coming from all other locations is blocked.



4 Δ prism test: Hering law and convergence, this test differentiates bifoveal fixation (normal BSV) from a central suppression scotoma (CSS) in microtropia.



Faden procedure: suture the muscle belly to the sclera posteriorly so as to decrease the pull of the muscle in its field of action without affecting the eye in the primary position.



VEP: recording of electrical activity of the visual cortex created by stimulation of the retina.



Laser: Stimulated emission of a photon of electromagnetic radiation



Nd-YAG: photodisruption.



Pinhole: It decreases size of blur circle. A narrower pupillary aperture decreases the angle of the cone of light that produces the blur circle. Ultimately the blur circle, albeit dimmer, is the size of the limiting cluster of photoreceptors (i.e., pixel-size or grain-size equivalent). A stenopeic slit may be considered as a line of pinholes.



Jackson Cross-Cylinder (JCC) test: placing the circle of least confusion on the retina



Keratometer: The cornea (with its overlying tear film) acts as a convex mirror to produce a virtual, erect image of the ring. The size and position of the virtual image are measured 66


Dhaval Patel MD



Scheiner‘s disc: Light enters the two pinholes and produces two images on the retina until the light is brought to a focus.



OPD-Scan optical path difference scanning system: dynamic SkiaScopy and involves acquisition of 1440 data points to produce a map of the optics of the whole eye



Allegretto wave analyzer: Tscherning principle of wavefront sensing.



Hartman-Shack devices: direction of propagation of light rays will be perpendicular to the wavefront.



Non-contact pachymeters: optical low – coherence reflectometry

Radiation and Eye 

The most sensitive ocular structure is the lens. (The minimum cataractogenic dose was 5.5 Gy and the maximum noncataractogenic dose was 11 Gy)



The sclera is the most resistant: easily tolerating >1000 Gy. Even up to 5000 Gy has been given to the sclera without causing perforation



lacrimal gland, cornea, and conjunctiva: can tolerate up to 50 Gy (5000 rad) of radiation



retina tolerates: >55 Gy o

The retinal pigment epithelial (RPE) cells were more radioresistant than photoreceptors and RPE cell loss was only observed at doses of more than 1500 cGy

o

Most radioresistant in retina: Ganglion cell layer (?)

Rates 

Aqueous humor production: 2 to 2.5 µL/min o



Approximately 1% of the anterior chamber and 1.5% of the posterior chamber volume of aqueous humor are replaced each minute

Outflow facility of fetal eyes: o

0.09 µl/min/mmHg before 7 month 67




o

0.3 µl/min/mmHg at 8 months

o

Average human value for C: 0.28 µl/min/mmHg.

Dhaval Patel MD

Pseudofacility: o

0.06 µl/min/mmHg

o

20% of the normal human C value



Uveoscleral pathway: 0.5 µL/min



Tear fluid production: 1.2 µL/minute



Choroidal blood flow: 800 to 2000 mL/min/100 g of tissue



blood flow for the entire retina: 80 ± 12 µL/min



Tear Evaporation: o

Normally: 0.14 µL/min

o

In dry eye: 0.43 µL/min

Recurrence % 

Weiss procedure (transverse tarsotomy) alone for entropion: 11%



Pterygium Surgeries o

Bare sclera type procedure for pterygium: 8% to 94%

o

Sliding Flaps for pterygium: 5%

o

Free flaps: 5%

o

Thiotepa: 11%

o

beta radiation:0% to 16%



surgical excision of CNV in pterygium: 38%



secondary membrane after Nd:YAG capsulotomy: 34-57%



meningioma: 22% 68


idiopathic facial nerve palsy: 12%



Epithelioid sarcoma: 66%



IOID: 21% to 52%



orbital hemangiopericytomas: 30% upto 7 years



epithelioid hemangioma after surgical excision: 33%

Dhaval Patel MD

Refractive Indices 

Water: 1.33



Cornea: 1.375 (for power calculation it is fudged to 1.337 to take into account negative posterior curvature)



Aqueous 1.336



Lens cortex 1.386



Lens core 1.406



Vitreous 1.336



silicone oil: 1.400 and 1.405



PFCL: 1.27-1.33



IOLs o

Silicon IOLs: 1.33 

1st generation  Polydimethylsiloxane: 1.41



2nd generation  Polydimethyl diphenyl siloxane: 1.46



3rd generation  Biosil: 1.43 (Crystalens)

o

PMMA IOLs: 1.49

o

Acrylic IOLs: 1.55 69




o

STAAR Surgical Collamer IOL, ICL: 1.45

o

CeeOn: 1.46

o

Array lens by AMO: 1.46

o

Akkommodative 1CU: 1.46

o

ThinLens (ThinOptX): 1.47 (acrylic)

o

Crystalens: 1.43

o

SmartIOL: 1.47

o

Light-Adjustable Lens: 1.43 (silicone)

o

Medennium Phakic Refractive Lens: 1.46

Dhaval Patel MD

Glasses o

Crown glass: 1.52

o

CR-39: 1.49

o

Polycarbonate: 1.58

o

Flint glass: 1.66

Resolutions 

Slit Lamp: 20 μm (Transverse)



Specular microscope: 2-5 μm (Lateral and Axial)



Confocal microscope: 1-2 μm (lateral), 5-10 μm (axial)



ASOCR: 18 um (axial), 60 um (transverse)



Stratus TD OCT: 8-10 um (axial), 20 um (transverse)



Cirrus FD/SD OCT: 5 um (axial), 16 um (transverse)



HR-OCT: 3 um (axial), 10 um (transverse)



SL-OCT: <25 um (axial), 20-100 um (transverse) 70


USG: 150 um (axial), 450 um (transverse)



UBM: 25 um (axial), 50 um (transverse)

Dhaval Patel MD

RB Stats 

RB1gene: 13q14



2 forms of mutations o

o



Germline (Hereditary): 40% 

Germline RB1 mutation in all cells



Mostly bilateral, 10-15% unilateral



More multifocality



All patients with bilateral RB have heretable form



Only 10% has family history

Somatic (Sporadic): 60% 

Sporadic RB1 mutaion only in retinal cells



Unilateral only



Non heritable, no family history

Laterality o

Unilateral: most cases ~75%  germline 15% and sporadic 85%

o

Bilateral: usually synchronous ~25%  germline mutation only

o

Trilateral: ~1%



90% non familial and 10% familial.



About 40% of all retinoblastomas are caused by germinal mutation and are therefore heritable. (this occurs due to very high mutation rate of RB gene)



Deletion of 13q14 occurs in about 1% of cases and is associated with systemic malformation.



The risk of offspring having RB is as follows. 71


o

o



Dhaval Patel MD

if one parent has retinoblastoma: 

40% of sibling are at risk



40% of offspring of affected patient

if both parents are normal and one sibling has unilateral retinoblastoma: 

1% of sibling



8% of offspring

If both parents are normal and one sibling has bilateral retinoblastoma 

6% of sibling (how?  due to gonadal mosaicism)



40% of offspring

RB is inherited as an autosomal- recessive trait at the cellular level; nevertheless, retinoblastoma behaves clinically as if it has an autosomal-dominant inheritance pattern with 90% penetrance.

Racial predilection of Diseases



Riley-Day syndrome: Ashkenazi Jews



Glucose-6-phosphate dehydrogenase deficiency: Mediterraneans



Oguchi disease: Japanese



Sickle cell hemoglobinopathy: African Americans



Diabetes mellitus, type 2: Pima Indians



Pseudoexfoliation: Scandinavian descent

Studies and Trials (Includes important and latest facts only)

DR 

DCCT: Diabetes Complication Control Trial 72










Dhaval Patel MD

o

Type 1 Diabetes Mellitus

o

No baseline retinopathy: Intensive control therapy reduced the risk of retinopathy by 76%.

o

Mild baseline retinopathy: Intensive control therapy slowed the progression of retinopathy by 54% and reduced the development of severe nonproliferative retinopathy by 47%.

UK Prospective Diabetes Study (UKPDS) o


o

Tight glycemic control reduces risk of retinopathy.

o

A 1% decrement in HbA1c equated to a 31% reduction in retinopathy.

Action to Control Cardiovascular Risk in Diabetes (ACCORD) o


o

Highly intensive glycemic control and combination of fenofibrate 160 mg q.d. and simvastatin reduced the proportion whose retinopathy progressed by about one-third at 4 years

Fenofibrate Intervention and Event Lowering in Diabetes (FIELD Study) o


o

Fenofibrate 200 mg q.d. vs. placebo.

o

A FIELD study analysis found that fenofibrate reduces the first laser treatment by 31%; reduced macular edema by 31% and proliferative retinopathy by 30%. Fenofibrate reduced the development or progression of retinopathy by reducing 22% in all patients and 79% in patients with pre-existing retinopathy.

Effects of Intravitreal Ranibizumab on Diabetic Retinopathy in the RIDE/RISE Trials o

Anti-VEGF Therapy

o

1:1:1: randomization  Sham: Ranibizumab 0.3: Ranibizumab 0.5

o

Ranibizumab therapy induces regression of diabetic retinopathy

o

Ranibizumab therapy retards the progression of diabetic retinopathy

o

Approximately 3-fold higher risk of PDR in shamtreated eyes

73




Dhaval Patel MD

European controlled trial of lisinopril in insulindependent diabetes mellitus (EUCLID) study o

RCT studying whether lisinopril, an ACE inhibitor, would reduce the rate of diabetic retinopathy progression in type-1 diabetes

o

showed that patients randomly assigned to lisinopril treatment had a lower risk of diabetic retinopathy progression than controls.

o

However, the investigators found that at baseline patients in the lisinopril group had lower baseline hemoglobin A1C levels than control patients.

DRCR.net o

Protocol F: Observational Study of the Development of DME Following Scatter Laser Photocoagulation 

o

Clinically meaningful differences are unlikely in OCT thickness or visual acuity following the application of pan-retinal photocoagulation (PRP) in 1 sitting compared with 4 sittings spread over 12 weeks. These results suggest PRP costs to some patients, in terms of travel and lost productivity, as well as to eye care providers could be reduced.

Protocol J: Laser-Ranibizumab-Triamcinolone Study for DME + PRP 

The addition of 1 intravitreal triamcinolone injection or 2 monthly intravitreal ranibizumab injections in eyes receiving focal/grid laser for DME and PRP for proliferative diabetic retinopathy is associated with better visual acuity and decreased macular edema by 14 weeks. Whether continued long-term intravitreal treatment is beneficial cannot be determined from this study.

DME 

DRCR.net o

Protocol B: Randomized Trial Comparing Intravitreal Triamcinolone Acetonide and Laser Photocoagulation for DME 

o

Over 2 years, focal/grid photocoagulation is at least as effective and has fewer side effects than 1- or 4-mg doses of preservative-free intravitreal triamcinolone.

Protocol E: Pilot Study of Peribulbar Triamcinolone Acetonide for DME 74


o

Diabetic Macular Edema and VEGF Trap-Eye: Investigation of Clinical Impact

BOLT o



ranibizumab compared with sham injection

DA VINCI o



Ranibizumab compared with laser

RIDE and RISE o



Sixteen weeks after focal/grid laser for DME in eyes with a definite reduction, but not complete resolution, of central edema, it is likely that somewhere between 23% and 63% of these eyes will continue to improve without additional treatment.

RESTORE o



Intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser is more effective through 2 years in increasing visual acuity compared with focal/grid laser treatment alone for the treatment of DME involving the central macula, although there is a small risk of endophthalmitis. Ranibizumab should be considered for patients with characteristics similar to those enrolled in this trial, including DME involving the center of the macula and decreased visual acuity.

Protocol K: The Course of Response to Focal Photocoagulation for DME 



The results demonstrated that intravitreal bevacizumab can reduce DME in some eyes, but the study was not designed to determine whether or not the treatment was superior to focal/grid laser.

Protocol I: Laser-Ranibizumab-Triamcinolone Study for DME 

o

In patients with DME who have good visual acuity, peribulbar triamcinolone, with or without focal photocoagulation, is unlikely to be of substantial benefit to pursue with additional trials.

Protocol H: Phase 2 Randomized Trial of Bevacizumab for DME 

o

Dhaval Patel MD

A Prospective Randomized Trial of Intravitreal Bevacizumab or Laser Therapy in the Management of Diabetic Macular Edema

VISTA o

VEGF Trap-Eye: Investigation of Safety, Treatment Effect, and Anatomic Outcomes in Diabetic Macular Edema 75


Dhaval Patel MD

Ozurdex Diabetic Macular Edema Study o

1:1:1 (700 μg, 350 μg, sham injection)

o 

Extended Follow-up of Patients With Macular Edema due to Retinal Vein Occlusion (Diabetic Macular Edema) (RETAIN) o

Group 1: RBZ TE + laser photocoagulation

o

Group 2: RBZ TE

o

Group 3: RBZ p.r.n.

ROP 



CRYO- ROP o

Treatment of avascular zone in threshold ROP reduces poor visual and structural outcomes

o

31.6% cryo vs. 51.4% obs had poor structural outcome

o

44.4% cryo vs. 62.6% observed <20/200 and 27.2% vs. 47.9% had unfavorable structural outcomes (p<0.001)

Light Reduction in ROP Study (LIGHT-ROP) o



Supplemental Therapeutic Oxygen to Prevent prethreshold ROP (STOP-ROP) o



Use of supplemental oxygen did not did not significantly reduce the number of infants requiring peripheral ablative surgery.

High Oxygen Percentage ROP (HOPE-ROP) o



A reduction in the ambient-light exposure does not alter the incidence of ROP

Not statistically different than outcome of STOP-ROP.

Early Treatment for ROP (ETROP) o

Unfavorable visual outcome reduced from 19.8% to 14.3% (p<0.05) and unfavorable structural outcome from 15.6% - 9.0% (p<0.0001) at 9 months in type I ROP.

o

Supported wait and watch policy for type II ROP.

o

Six year data consistent with 9 month data. 76


Dhaval Patel MD

Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity (BEATROP) o

significantly higher rate of recurrence with Zone I disease when treated with conventional laser therapy compared to intravitreal bevacizumab (42 percent vs. 6 percent, p=0.003)

ARMD 



AREDS 1 o

Vitamin C: 500 mg

o

Vitamin E: 400 mg

o

Beta carotene: 15 mg

o

Zinc: 80 mg

o

Cu: 2 mg

AREDS 2 o

Vitamin C: 500 mg

o

Vitamin E: 400 mg

o

Lutein 10 mg

o

Zeaxanthin 2 mg

o

Zinc: 25 mg

o

DHA: 350 mg

o

EPA: 650 mg

o

substituting lutein/zeaxanthin for beta-carotene in the AREDS formulation provides a safer and more efficacious supplement for the treatment of AMD in those who are at high risk of developing advanced AMD.



OMEGA study: Othera Eye Drops (antioxidant, anti-inflammation and anti angiogenic)



ENVISION Clarity trial in geographic atrophy: Pills for Dry AMD-Acucela (ACU-4429) 77


Dhaval Patel MD



Role of CCR3 (chemokine receptor): Anti-CCR3 antibodies may prevent tube formation prior to vascularization and reduce the proliferation of CECs following laser-induced injury.



ANCHOR=Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration o



CATT=Comparison of AMD Treatment Trial o

more systemic adverse events requiring hospitalization were found in the bevacizumab-treated groups compared to the ranibizumabtreated groups

o 

DAWN=Genetic Substudy of HORIZON o



DAWN sought to explain differential response to ranibizumab therapy based on genotype

DENALI=[US and Canada] o

24-month randomized, doublemasked,multicenter trial in patients with subfoveal choroidal neovascularization secondary to wet AMD (all lesion types)

o 

EVEREST=[Asia] multicenter, double-masked, indocyanine green angiography-guided randomized controlled trial with an angiographic treatment outcome designed to assess the effect of verteporfin PDT alone or in combination with ranibizumab compared with ranibizumab alone in patients with symptomatic macular polypoidal choroidal vasculopathy



PrONTO o

first prospective study to investigate PRN anti-VEGF treatment of nAMD.

o

VA increased after 3 months by a mean of approximately 2 lines and was maintained at that level through 2 years, with patients receiving an average of 5.6 injections in year 1 and 4.3 injections in year 2.



FOCUS=RhuFab V2 Ocular Treatment Combining the Use of Visudyne® to Evaluate Safety



HARBOR=Study of Ranibizumab Administered Monthly or on an As-Needed Basis in Patients With Subfoveal Neovascular Age-Related Macular Degeneration o

The 0.5-mg dose of ranibizumab appears to be the most effective, but HARBOR also showed us that in those rare cases in which we might need a higher dose 2.0 mg or every-2-weeks dosing, it may be safe. 78


Dhaval Patel MD



HORIZON=Extension Study to Evaluate the Safety and Tolerability of Ranibizumab in Subjects With Choroidal Neovascularization Secondary to AMD or Macular Edema Secondary to RVO



IVAN=Inhibit VEGF in Age-related Choroidal Neovascularization o

compared bevacizumab and ranibizumab for age-related macular degeneration

o

bevacizumab was found to suppress systemic VEGF much more than ranibizumab

o

both medications are similarly effective



MARINA=Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration



MONT BLANC=[Europe] Randomized, double-masked, multicenter trial to compare the efficacy and safety of same-day verteporfin PDT and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular AMD



RADICAL=Reduced Fluence Visudyne Anti-VEGF-Dexamethasone in Combination for AMD Lesions



SAILOR=Safety Assessment of Intravitreal Lucentis for Age-Related Macular Degeneration





o

PRN treatment with ranibizumab

o

Outcomes were not as good as in PrONTO

o

At 1 year, patients received an average of only 4.9 injections and had 9 office visits, and mean VA declined continuously after patients completed the 3-dose initiation phase

o

SAILOR identified prior stroke, cardiac arrhythmias, and a history of congestive heart failure as risk factors for stroke while receiving anti-VEGF therapy

SUSTAIN o

European study just like SAILOR in USA

o

mean number of treatments per patient was 5.6 at 1 year

o

mean gain of about 4 letters at 1 year

Lucentis Compared to Avastin Study (LUCAS) o

―inject-and-extend‖ protocol

o

comparing bevacizumab and ranibizumab 79












Dhaval Patel MD

Study to Observe the Effectiveness and Safety of Ranibizumab in the Real-life Setting (LUMINOUS) o

5-year, prospective, global, multicenter

o

wAMD, DME, BRVO, CRVO, CNV secondary to pathologic myopia (PM)

Pazopanib Eye Drops vs. Ranibizumab Intravitreal Injections for the Treatment of Neovascular AMD o

Pazopanib is a small molecule lipophilic potent and selective multitargeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/β, and c-kit that inhibits angiogenesis.

o

5-10 mg/ml TID

o

failed to reduce as-needed ranibizumab injections by ≥ 50%

VIEW 1 and 2 o

VIEW 1=[North America] VEGF Trap-Eye Investigation of Efficacy and Safety in Wet AMD VIEW 2=[International]

o

Intravitreal Aflibercept Injection (IAI) in Neovascular AMD

o

BCVA increase of about 10 letters over baseline BCVA

ASSESS Study o

intravitreal aflibercept injection (IAI) in subjects who were previously treated with ranibizumab and/or bevacizumab for exudative AMD

o

2 mg of IAI every month for the first 3 months, followed by 2 mg once every 2 months

o

improved functional and anatomic endpoints in patients with exudative AMD following previous anti-VEGF treatment.

MIVI-5 trial o

Ocriplasmin in Exudative AMD

o

single intravitreal injection of 125 μg ocriplasmin or sham treatment

o

At Day 28, 24% of ocriplasmin-treated eyes achieved VMA resolution, compared to 12% of placebo-treated eyes

INTREPID Trial

80




Dhaval Patel MD

o

looking at safety and efficacy of stereotactic radiotherapy in patients with age-related macular degeneration who are receiving anti-vascular endothelial growth factor (antiVEGF) injections.

o

The 2-year follow-up data showed that radiotherapy treatment was associated with a significant 25% reduction in the number of anti-VEGF injections over 2 years. "With appropriate case selection, injections were reduced by 45% and there was a trend for better visual acuity,"

trials comparing bevacizumab and ranibizumab o

Comparison of AMD Treatment Trial (CATT)

o

IVAN

o

MANTA

o

Groupe d‘Evaluation Français Avastin versus Lucentis (GEFAL)

o

Lucentis Compared to Avastin Study (LUCAS)

Vitreomacular interface (VMI) diseases 

Ocriplasmin Trials o

MIVI

o

Single intravitreal injection of ocriplasmin (125 μg) with placebo injection in patients with symptomatic VMA 

VMA resolved in 26.5% of ocriplasmin-injected eyes vs. 10.1% placebo 

VMA diameter ≤ 1500 μm: 34.7% resolution in ocriplasmin-injected eyes; 14.6%, placebo



Total PVD at Day 28 was achieved in 13.4% of ocriplasmin-treated eyes vs. 3.7% placebo



Nonsurgical closure of macular holes was achieved in 40.6% of ocriplasmininjected eyes vs. 10.6% placebo 

FTMH width ≤ 400 μm: closure at Month 6 (48.8% ocriplasmin vs. 18.2% placebo) 81

Ophthalmology Explorer  o

o

FTMH width > 400 μm: 0% for both groups

Microplasmin in Children (MIC) trial 

o

Dhaval Patel MD

175 μg was well tolerated when administered as a single intravitreal injection in pediatric patients before vitrectomy

MIVI-5 

Ocriplasmin for Treatment of Patients with VMA and Wet AMD



At Day 28, 24% of ocriplasmin-treated eyes achieved VMA resolution, compared to 12% of placebo

OASIS Trial 

Ocriplasmin for treatment of patients with symptomatic VMA including macular hole

Glaucoma (ONE CAGe) 

OHTS: 20% lowering of IOP reduced risk of glaucomatous VF loss from 9.9% to 4%



NTGS: Reduction of normal pressures by 30% slowed the rate of glaucomatous progression in a significant number of patients



EMGT: 25% decrease in IOP from baseline and maximum absolute 25mmHg reduced risk of progression by 50%.



CIGTS: No difference in VF change between treatment modalities. IOP lower with surgery. Higher rate of cataracts with filtering surgery



AGIS: Greater IOP reduction with trabeculectomy first. For black patients; better visual preservation with laser first. For white patients better visual preservation with trabeculectomy first. Low IOP associated with reduced visual field defect progression



GLT: Initial laser trabeculoplasty found as effective as initial topical Timolol to lower IOP and preserve vision



CNTGS: found that by reducing the intraocular pressure by 30% the rate of visual-field progression was reduced from 35% to 12%.

 82


Dhaval Patel MD

ON 

ONTT: Optic Neuritis Treatment Trial: Oral steroids alone did not have a significant difference in visual recovery compared with the control group; however, the recurrence rate of optic neuritis was increased. The IV steroid group had faster recovery of visual acuity and a slight improvement in acuity over the control group.

NAION 

IONDT: Ischemic Optic Neuropathy Decompression Trial: Patients in the surgery group did no better when compared with the observation group regarding improved visual acuity of three or more lines at 6 months. Approximately one third of the surgery patients had improvement in acuity, whereas over 40% of the observation patients improved. Moreover, surgery was associated with a higher risk of loss of three or more lines of acuity (surgery: 24%, observation: 12%). The IONDT conclusively states that optic nerve sheath decompression is not effective.



MISC 





VEGF Trap-Eye in CNV Secondary to Pathological Myopia (MYRROR) o

IVT AFL treatment for myopic CNV started with 1 dose of IVT-AFL and induced significant and clinically meaningful improvements in visual and anatomic parameters compared with sham injections.

o

IVT-AFL is an effective treatment for myopic CNV.

The North American Symptomatic Carotid Endarterectomy Trial (NASCET) o

For TMVL

o

demonstrated that endarterectomy is effective in reducing the risk of stroke in those symptomatic patients with greater than 70% stenosis.

o

A subgroup analysis of those individuals with TMVL treated medically had 50% lower risk of ipsilateral stroke than those patients with hemispheric TIA.

Astigmatic Reduction Clinical Trial (Arc-T) outcomes 83




Dhaval Patel MD

o

61% residual astigmatism 1 D or more

o

25% had no residual astigmatism

o

Greater effect with paired incisions, increasing age, longer incisions, smaller OZ

o

Second paired AK effect is not directly additive

Prospective Evaluation of Radial Keratotomy (PERK) outcomes o

88% 20/40 or better uncorrected (all patients)

o

90% 20/40 or better (Preop 6D or less)

o

19% residual myopia of 1 D or more (all patients)

o

43% progressive hyperopic shift 1 D or more after 10 years

Surface Tension Gases: 70 SiO (1000 cs): 21.2 SiO (5000 cs): 21.3 PFCL: 14

Specific Gravity 



Silicon Oil o

SiO (1000 cs): 0.971

o

SiO (5000 cs): 0.973

PFCL: 1.76-2.03 o

perfluoro-n-octane (C8F18): 1.76

o

perfluorodecaline (C10F18): 1.94

o

perfluorophenanthrene (C14F24): 2.03 84


Dhaval Patel MD

Surface Area 

Globe: 22.86 cm2



Cornea: 130 mm2



Corneal endothelial cell: 250um2



Pars plicata: 600 mm2



Pars plana: 245mm2



Retina: 266 mm2



Fovea: 1.75-mm2



Disc: 2.34 ± 0.47 mm2



RPE: 240 mm2 at the fourth month 800 mm2 by 2 years of age



Conjunctival sac: 16 cm2 (roughly 17 times more surface area than the cornea)



Sclera: 16.3 to 17 cm2



Shunts (mm2) o

o

Nonvalved 

Molteno (Polypropylene): Single plate  135, Double plate  270



Baerveldt (silicone): 350, 250, 425

Valved 

Krupin (silicone): 184



Ahmed (polypropelene): 184, 96, 364 (for double plate)

Survival Rates 

craniopharyngioma: 10-year actuarial survival rates were 52% for subtotal resection alone and 87% for subtotal plus radiation 85


Dhaval Patel MD



Wilms tumor (nephroblastoma): 90% with multimodality approach



rhinocerebral mucormycosis: 14% when untreated, 57% with amphotericin B and surgery



Graft survival in FECD: 5 year and 10 year  97% and 90% respectively

Test Distances



Snellen‘s Test: 20 feet/ 6 meter



Near Vision: 14 inches or 1/3 meter



Hand Movement checking: 3 feet away



Bruckner test: an arms length



Hirschberg‘s Test: 14 inches (30 cm)



Teller acuity card test o

0-6 months – 38 cm

o

7-12 months- 55 cm

o

>12 months-84 cm



Cardiff test: 50 cm or 1 meter



Catford drum test: 2 feet



OKNOVIS: 60 cm



STYCAR graded ball test: 10 feet in front of child



Sheridan letter test: 10 feet



Ishihara: 75 cm



Arden gratings plate for contrast sensitivity: 57 cm



Cambridge low contrast gratings: 6 m 86


Pelli-robsons chart: 1 m



Keeler LogMAR crowded test/ Glasgow acuity test: 3 m



ETDRS: 4 m



VisTech contrast chart: 3 m



FACT chart: 1 m



Amsler chart: 30 cm

Dhaval Patel MD

Thickness



Tear film: 7 um



CCT: 544 um (average)



Corneal epithelium: 50-90 um



Bowman‘s layer: 10-14 um



Corneal stroma: 500 um



Descemet‘s membrane: 4 um at birth and 10-12 um in adults o

ABZ: 3 µm

o

PNBZ: 9 µm



Corneal endothelium: 6 um



posterior vitreous cortex: 100 to 110 µm



suprachorodial space: 30 µm



tarsal plate: 1 mm



inner limiting membrane of Elschnig: 50 nm



Bruch‘s membrane:145 nm in periphery and 55 nm at fovea

87


Dhaval Patel MD

VEGF Facts



VEGF is 45 kD molecular weight



Hypoxia is major regulator of VEGF expression.



EphrinA/EphA Interactions Modulate the Angiogenic Effects of VEGF



After successful PRP, intraocular concentration of VEGF decreases by 75%



VEGFR1: pericytes for vessels survival VEGFR2: endothelium VEGFR3: lymphangiogenesis









Pegaptanib o

an aptamer, which is a single strand of RNA or DNA (RNA in the case of pegaptanib) that folds up in such a way that its shape meshes with the VEGF molecule like a lock and key.

o

There are several isoforms of VEGF, all of which are active in the angiogenesis process. Pegaptanib selectively inhibits only the VEGF-165 isoform of VEGF, which may explain the relatively lower efficacy of this drug compared with others in the class.

Bevacizumab o

full-length antibody that binds all isoforms of the VEGF-A family.

o

It was developed as a systemic antineoplastic therapy but has been used off-label for neovascular AMD since 2005, first systemically and then intravitreally.

Ranibizumab o

antibody fragment adapted from bevacizumab.

o

Like its parent molecule, ranibizumab binds all isoforms of the VEGF-A family.

Aflibercept o

known as VEGF Trap-Eye

o

recombinant protein in which the binding domains of VEGF receptors 1 and 2 have been combined with the Fc portion of IgG. 88


Dhaval Patel MD

The molecule has a very high binding affinity for all VEGF-A isoforms as well as for the related molecules placental growth factor-1 and factor-2 and VEGF-B

Vitreous cavity volume displacement (ml) 

Half of 5-mm sponge: 0.09–0.15



3 × 5 mm sponge: 0.11–0.20



5-mm round sponge: 0.14–0.22



#240 style (circumferential): 0.47–0.48










Water Content 

Cornea: 80%



Sclera: 70%



Lens: 65%



Vitreous: 99%



Aqueous: 99.9%



Contact Lenses



o

Low: 37.5% to 46% water, used for daily wear only

o

Medium: 46% to 58% water, used for both daily and extended wear

o

High: 59% to 76%, used for extended wear

IOLs o

Hydrophobic acrylic: <2% 89


Dhaval Patel MD

Hydrophilic Acrylic: 18% to 38% 

Bausch and Lomb Hydroview IOL: 18% water



IOLtech MemoryLens: 20% water



Staar Collamer material IOL: 34% water

o

Acrylic PMMA IOLs: <1%

o

ThinLens (ThinOptX) lens: 18%

o

Acri.Smart lens: 25%

o

STAAR ICL: 34%

Basic Sciences 

Copper accumulates in Descemet's membrane, the lens capsule, and other basement membranes, whereas iron accumulates in basal epithelial cells.



Intact oculovestibular reflexes in a patient with gaze palsy implie a supranuclear disturbance.



Optic pit forms as outpounchings from diencephalon part of neural tube.



At birth, weight of the lens is 90 mg. it increases 2mg/year.



The dimensional characteristics of the optic nerve can be remembered with the mnemonic phone number 125-1017, which stands for the lengths of the intraocular (1), intraorbital (25), intracanalicular (10), and intracranial (17) portions of the optic nerve.



The inferior nasal retinal fibers cross in the anterior chiasm and were thought to loop anteriorly in the contralateral optic nerve before traveling posteriorly, leading to the term 90


Dhaval Patel MD

Wilbrand's knee (NI=Nasal + Inferior). It is now thought that Wilbrand's knee may be an artifact.



the inferior fibers of the optic radiations pass extremely close to the internal capsule.



Compared with plasma, aqueous is slightly hypertonic and acidic. Aqueous has a marked excess of ascorbate (15 times greater than that of arterial plasma) and a marked deficit of protein (0.2% in aqueous as compared to 7% in plasma).



The four divisions of the optic nerve head correlate roughly with a four-part blood supply.

o

The surface fiber layer is supplied mainly by branches of the central retinal artery.

o

The prelaminar region is supplied by capillaries of the short posterior ciliary arteries.

o

The lamina cribrosa region is also supplied by vessels that come directly from the short posterior ciliary arteries to form a dense plexus in the lamina.

o

The retrolaminar region is supplied by both the ciliary and retinal circulations, with the former coming from recurrent pial vessels. The central retinal artery provides centripetal branches from the pial region.



Loteprednol is an ester steroid with minimal to no cataractogenous properties. The other steroids are ketone steroids, which have more potential to cause a cataract.



The superior orbital fissure transmits the branches of cranial nerve V1, III, IV, and VI. Cranial nerve V2 enters the orbit through the inferior orbital fissure.

91


Dhaval Patel MD



The optic pits first appear on day 23 of gestation. Evagination of the optic vesicle occurs on day 25 with induction of the lens on day 28. Closure of the optic fissure occurs on day 33.



Lid colobomas do not occur from failure of the fetal fissure to close.



Anterior and posterior radii of curvature o

Lens: 10 and 6 mm

o

Cornea: 7.8 and 6.5 mm



Myelination of the optic nerve starts in the seventh month of gestation and is completed about 1 month after birth. Myelination starts at the LGB optic tract chiasm and progresses toward the lamina cribrosa.



The inferior or superior muscular branches of the ophthalmic artery provide all or part of the blood supply to all the extraocular muscles except the lateral rectus. The lateral rectus blood is supplied by a single vessel derived from the lacrimal artery. Each rectus muscle, except the lateral rectus, receives two anterior ciliary arteries that communicate with the major arteriole circle of the ciliary body.



The trigeminal nerve divides into three segments: ophthalmic (V1), maxillary (V2), and mandibular (V3). o

The ophthalmic nerve is divided into three branches: nasociliary, frontal, and lacrimal. O-NFL 

o

The frontal nerve, a branch of the ophthalmic (V1) segment, divides into the supraorbital and supratrochlear nerves. F-SS

The maxillary (V2) segment divides into the infraorbital, zygomatic, and superior alveolar nerves. The zygomaticofacial and zygomaticotemporal nerves are branches of the zygomatic nerve (V2). M-IZS

92


Dhaval Patel MD



Bowman's membrane represents a compact collagen layer at the anterior aspect of the corneal stroma. It is not a true basement membrane.



All of the recti muscles originate from the annulus of Zinn. The superior oblique and levator palpebrae originate superior to the annulus.



The accessory lacrimal glands are the basic secretors. These include the glands of Krause and Wolfring. The reflex secretor is the main lacrimal gland.



Although type I collagen exists in the stroma, it is associated with normal stroma. Type III collagen is associated with stromal wound healing.



The reasons for relatively miotic pupils in infancy include immaturity of dilator pupillae muscle.



The optic nerve is generally myelinated to the lamina cribrosa 4 to 6 months before foveal maturation.



Congenital colobomas of the eyelids are associated with Goldenhar



The lower lids are more frequently involved by congenital ectropion and congenital entropion.



70% of pregnant women are seronegative for toxoplasmosis. Placental transfer of organism is common in the newly infected mother; however, many infected infants will not have systemic manifestations.



most common clinical finding in infants with congenital rubella syndrome  SNHL

93


Dhaval Patel MD



Although children with congenital rubella syndrome may develop either cataract or glaucoma, their coincidence in an infant is rare.



In rubella cataract after surgery, Excessive rebound uveitis is caused by live virus retained within the residual lens cortex.



The most common congenital infection in humans is CMV. Approximately 2% of human infants are infected. Most cases are silent.



In HSV, A posterior inflammatory component is far more common in congenital disease, with severe retinitis and vitritis. This is unusual in acquired disease but may be the cause of some cases of acute retinal necrosis.



Microphthalmia is an unusual manifestation of congenital syphilis.



Hutchinson's triad of congenital syphilis: peg-shaped teeth, eighth nerve deafness, and interstitial keratitis.



Pharyngoconjunctival fever (adeno type 3) generally spares the cornea.



M Pathway subserves: motion & pursuit, direction, speed judgement, coarse stereopsis Occipitoparietal: magnocellular, WHERE pathway  localization and movement P Pathway subserves: fine acuity, shape, colour, fine stereopsis OccipitoTemporal: parvocellular, WHAT pathway  color, shape and pattern



The central retinal artery arises from the ophthalmic artery after ophthalmic artery passes through the optic canal. The central retinal artery then dives into the center of the optic nerve where it travels until it exits from the optic nerve head.

94


Dhaval Patel MD



Volume of conjunctival cul de sac is 7 uL. Ideal drop size should be 20 uL. Ideal drop viscocity should be 12-15 cps.



The ciliary ganglion receives three roots: 1. A long sensory root that contains sensory fibers from the cornea, iris, and ciliary body— this root delivers sensation to the central nervous system (CNS) through the nasociliary nerve (V1). 2. A short motor root that carries preganglionic parasympathetic axons to the iris sphincter—these are the only fibers that synapse here. This root arises from the lower division of CN III, the oculomotor nerve (which also supplies the inferior oblique). 3. A sympathetic root that innervates the blood vessels of the uvea—this root arises from a plexus around the internal carotid artery and passes through the optic foramen (with the ophthalmic artery).



The sclera, like the cornea, is virtually avascular except for two areas: (i) the superficial vessels of the episclera, and (ii) the intrascleral vascular plexus located immediately posterior to the limbus.



The trabecular meshwork consists of thin, perforated connective tissue sheets arranged in a layered pattern. The connective tissue ―beams‖ are lined by a monolayered endothelium. The trabecular meshwork is derived from the neural crest tissue. Animal outflow studies have shown that the juxtacanalicular trabecular meshwork (TM), which is immediately proximal to Schlemm's canal, is the primary limiting factor for outflow facility.



Retinal pigment epithelium (RPE) cells in the foveal area are taller, more closely packed, and have more and larger melanosomes, contributing to the relative hypofluorescence of this area during fluorescein angiography.



Rods and cones are characterized by three components: the synaptic body, the inner segment, and the outer segment. The synaptic body of a rod is called a spherule, whereas that of the cone is called a pedicle. Photopigment is stored in discs in the outer segments.

95


Dhaval Patel MD

In rods, the discs are not attached to the cell membrane, but cone discs are continuous with it.



PBG: Intraretinal processing occurs from photoreceptors to bipolar cells to ganglion cells, with modulation by horizontal (outer plexiform layer) and amacrine (inner plexiform layer) cells.



Approximately 120 million rods and 6 million cones interact with 1.2 million ganglion cells in an eye. Therefore, the ratio of rods to cones is approximately 20:1. (Some studies cite a ratio as low as 12:1.)



A cilioretinal artery contributes to the vascular supply of the retina in approximately 50% of individuals and 30% of eyes. In 15% of individuals, it contributes to macular circulation.



The outer plexiform layer is composed of interconnections between photoreceptor synaptic bodies, horizontal cells, and bipolar cells. The inner plexiform layer is composed of connections between bipolar cells, amacrine cells, and ganglion cells. Outer PHoB Inner BAG



Levator is served by a single subnucleus. It sits dorsal, central, and at the inferior end of the group of subnuclei that compose the two third-cranial nerve nuclei. The superior recti have two subnuclei, each controlling the contralateral nerve. In contrast, the inferior obliques and the medial recti each have individual subnuclei that control the ipsilateral nerves. The superior oblique is served by the fourth nerve. The lateral rectus is supplied by the sixth cranial nerve.



The pupillomotor fibers of the third cranial nerve run in the inferior division, which carries them to the ciliary ganglion. They are among the axons in the periphery of the nerve, making them easily susceptible to compression.

96


Dhaval Patel MD

Neural crest cells give rise to ciliary musculature, corneal stroma, and endothelium (but not corneal epithelium), most of the sclera (except for a temporal portion which is of mesodermal origin), choroidal stroma, some of the orbital bones, orbital cartilage, orbital connective tissue, nerve sheaths, and uveal melanocytes. Extraocular muscles form from paraxial mesoderm. Blood vessel endothelia, extraocular muscles, and temporal sclera are all mesodermal in origin. The mesoderm also contributes to the formation of the vitreous. The pupillomotor muscles are neuroectodermal in origin. The trochlea originates from the neural crest. Conjunctival epithelium is derived from surface ectoderm, but the substantia propria is derived from the neural crest.



Sporadic aniridia is associated with Wilms' tumor (usually because of deletion of the PAX6 gene and the adjacent Wt1 Wilms' tumor gene). Aniridia is not typically found in patients with autosomal-dominant Wilms' tumor.



Aqueous humor provides most of the glucose needed by the endothelium, stroma, and epithelium. Hydrophobic molecules penetrate the epithelium most easily, whereas hydrophilic molecules penetrate stroma more easily.



Topical administration of type E and type F prostaglandins, as well as arachidonic acid, causes miosis. High doses of prostaglandins will cause an increase in intraocular pressure (IOP). Low doses of some prostaglandins, in contrast, appear to lower IOP in some animal species.



By blocking phospholipase, corticosteroids effectively inhibit both the lipoxygenase (LOX) and cyclooxygenase (COX) pathways.



Enzymes in Aqueous: Carbonic anhydrase, although present in only trace amounts in the aqueous humor, has a high enough turnover that it is felt to be functionally significant. Hyaluronidase is present in aqueous humor and may participate in the regulation of resistance to aqueous outflow. Lysozyme is present and provides antibacterial protection. 97


Dhaval Patel MD

Lactate dehydrogenase, not normally detectable in aqueous humor, may be a marker for retinoblastoma.



Lens epithelium cells are located anteriorly underneath the lens capsule. Epithelium cells in a ring around the anterior lens, or the germinative zone, exhibit the highest level of deoxyribonucleic acid (DNA) synthesis (the S phase in the cell cycle). Newly formed cells migrate toward the lens equator, where they differentiate into lens fiber cells.



The water-soluble proteins of the lens are divided into three types of crystallins that are fractionated into four electrophoretic groups. Alpha crystallins are the largest, with molecular weights of >500,000 daltons. Beta crystallins are the most abundant, making up approximately 55% of the water-soluble protein. Gamma crystallins are the smallest.



Unlike the retina, the lens can function without oxygen but not without glucose, primarily because the lens mostly relies on anaerobic glycolysis to generate adenosine triphosphate (ATP). In a glucose-depleted environment, the lens will become hazy after several hours.



Syneresis (vitreous liquefaction) is associated with a focal decrease in collagen concentration. Both collagen and hyaluronic acid concentration are decreased by 20% to 30% in myopic eyes (axial length >26 mm).



Vitamin A, stored hepatically, is transported in serum as all-trans retinol. Conversion between aldehyde and alcohol (and vice versa) occurs in the photoreceptors, whereas the trans to cis isomerization takes place in the retinal pigment epithelium (RPE).



Photoreceptors are more active electrically (depolarized) in the dark! With light absorption, transducin (via phosphodiesterase [PDE]) lowers cyclic guanosine monophosphate (cGMP) concentration, which hyperpolarizes the cell and decreases synaptic exchange with bipolar cells. 98


Dhaval Patel MD



Clinically, carbonic anhydrase must be >99% inhibited to decrease aqueous humor secretion significantly.



Aspirin causes inhibition of cyclooxygenase (COX); therefore, arachidonic acid is diverted to the lipoxygenase (LOX) pathway. This is thought to be the underlying mechanism for the asthma attacks and hypersensitivity reactions (by increased production of leukotrienes).



Cromolyn sodium is a mast cell stabilizer and has no direct antihistaminic effect (receptor blockade). It is only effective if used prophylactically.



Probenecid competitively inhibits penicillin excretion by the kidney.



Angioid streaks can be seen in hemochromatosis but not in sarcoidosis.



Combination of Angioid streaks and pseudoxanthoma elasticum is known as GronbladStrandberg syndrome.



Because of increasing resistance to vancomycin, the Center for Disease Control and Prevention (CDC) has recommended avoidance of the use of empiric vancomycin in patients with neutropenia unless clear evidence for a beta-lactam-resistant Gram-positive infection can be demonstrated.



Serum purine levels in patients with Down's syndrome are typically elevated. The enzymes required for the biosynthesis of purities are coded by genes present on the long arm of chromosome 21. The presence of a third set of these genes presumably results in the elevation of serum purine levels.



The expression of multiple discrete anomalies in various organs caused by a single gene mutation is termed genetic pleiotropism. 99




Dhaval Patel MD

The iris sphincter receives parasympathetic innervation by the inferior division of the oculomotor nerve (which also supplies the inferior oblique muscle) (These are the only fibers that synapse in the ciliary ganglion). The iris dilator is supplied by sympathetic fibers running with the nasociliary and long ciliary nerves, branches of the first division of the trigeminal nerve (V1).



Motor units, defined as one terminal motor nerve branch and all the muscle fibers it serves, are smaller in the extraocular muscles than anywhere else in the body. This permits the finest control of force generation and muscle action possible.



There are approximately 20 short posterior ciliary arteries, which enter the sclera in a circle around the optic nerve. There are two long posterior ciliary arteries, which usually enter the sclera on either side of the optic nerve at the 3- and 9-o'clock positions. The posterior ciliary arteries supply the uveal tract, the sclera, conjunctiva, and cilioretinal arteries. There are seven anterior ciliary arteries, which provide muscular feeding branches (supplying the extraocular muscles) and terminate in the major arterial circle of the iris.



Ganglion cells are the first retinal cells to differentiate into a recognizable level.



Rod outer segment shedding in animal models will persist even after several days in the dark. On the contrary, dark deprivation (i.e., constant light adaptation) will rapidly ablate normal rod disc shedding.



Rod OS shedding occurs in morning and Cone OS shedding occurs in evening.



The cell most commonly used for karyotypic analysis is the T lymphocyte.



Nuclear third-nerve palsy may feature contralateral upgaze palsy because SR is served by a contralateral brainstem subnucleus. 100


Dhaval Patel MD



Pregnancy usually lowers intraocular pressure. Uveoscleral outflow is enhanced. Lowered episcleral venous pressure may contribute to enhanced trabecular outflow as well.



The level of retinopathy before pregnancy is the strongest risk factor for significant progression during pregnancy. NPDR to PDR 5%



The corneal and retinal pigment epithelium (RPE) damage is limited to historical reports of patients treated with much higher dosages of tamoxifen, where the chance of toxicity is much higher. Ocular toxicity has not been reported with cumulative doses of <10 g.



As per DCCT, once progression occurs, patients who rigorously control their blood sugars are twice as likely to recover, compared with less-controlled diabetics. Therefore, “early worsening” is a temporary effect among patients undergoing intensive treatment.



5% of patients with diabetes will develop asymmetric retinopathy. (difference of two stages is taken as asymmetric)



Studies have shown that preoperative (72 hours) antibiotic reduces bacterial counts to a greater degree than 3 days of preoperative povidone-iodine. Adding povidone-iodine at the time of surgery exerts a synergistic effect. Some studies have suggested that saline flushes actually increase bacterial colony counts.



Cigarette smoking has been most strongly associated with choroidal neovascularization. (also with RPE hyperplasia as per beaver dam study.)



55 minutes is the shortest duration of cataract surgery that has resulted in photic maculopathy.

101


Dhaval Patel MD



A human metabolite of a bioflavonoid found in grapefruit juice, but not in orange juice, inhibits several cytochrome components of the P450 isozyme group.



Naphazoline and antazoline are traditional antihistamines. Levocabastine is a cyclohexylpiperidine. It is topical H1 blocker with no chemical or structural relation to other antihistamines. Lodoxamide is a mast cell stabilizer used for prophylaxis of atopic conditions, not for acute treatment. Ketorolac is a traditional nonsteroidal anti-inflammatory drug. Nordihydroguaiaretic acid (NDGA) is a lipoxygenase (LOX) inhibitor.



Hyperbaric oxygen (HBO) exposure: myopic shift, cotton-wool spots, cataract. Hyperbaric oxygen (HBO) has been used successfully to help treat: arterial gas embolism, chronic cystoid macular edema, rhino-cerebral-orbital, mucormycosis, radiation optic neuropathy. NOT CRAO.



Carbonic anhydrase inhibitors are most likely to be of benefit in disorders of the retinal pigment epithelium (RPE) and significantly less likely to help in cases of primary retinal vascular disease.



CME: Fishman and colleagues have established that 500 mg/day of acetazolamide is more effective than 250 mg/day. They have subsequently demonstrated that methazolamide 50 mg twice daily is less effective than acetazolamide.



No urine test results have been found to be affected by recent fundus angiography. Cortisol, thyroxine, and quinidine are affected for up to 3 hours, with digoxin being affected for up to 12 hours. Serum creatinine levels may be affected, but this appears to be shortlived (<3 hours).

102


Dhaval Patel MD



Interferon retinopathy: cotton-wool spots and retinal hemorrhages, particularly around the optic disc, which usually appear within 3 months of the onset of therapy. Ischemic optic neuropathy and proliferative retinopathy have also been reported.



Flurbiprofen is used to prevent prostaglandin-mediated miosis during surgery.



Calcification of Retinoblastoma is due to: RPE Hyperplasia Calcification of Cysticercosis is due to: Calcified Corpuscles



Lens nuclei are not retained in Alport‘s syndrome



Lacy vacuolization is a pathologic finding of glycogen-filled cysts in the Iris pigment epithelium: seen in diabetes.



In pathology specimen, a fold at the ora serrata-is a fixation artifact found in newborn eyes called Lange's fold.



Corneal ―Swirl‖ Keratopathy Chloroquine Suramin (used in AIDS patients) Tamoxifen Amiodarone



Transient Myopia Sulfonamides Tetracycline Perchlorperazine (Compazine) 103


Dhaval Patel MD

Steroids Carbonic anhydrase inhibitors



Rifabutin is a derivative of rifampin that may create an autoimmune abnormality and is associated with a high prevalence of uveitis that can be bilateral, recur with rechallenge, and improve upon withdrawal.



Steroids can be a cause and a treatment of Pseudotumor cerebri.



Drugs that can give nystagmus include: Barbiturates Tranquilizers Anticonvulsants



Drugs that can cause RPE dysfunction (hydroxyl) chloroquine, phenothiaztne and desferroxamine



Drugs that can cause macular oedema nicotinic acid, latanoprost and topical adrenaline



Drugs that can cause crystalline retinopathy tamoxifen, methoxyflurane and canthaxanthine



Iris Heterochromia o

Congenital: 

Hypochromic: congenital Horner‘s syndrome, Waardenburg‘s syndrome, Hirschsprung‘s disease, Perry- Romberg hemifacial atrophy. 104


o

Dhaval Patel MD

Hyperchromic: ocular or oculodermal melanocytosis, iris pigment epithelium hamartoma.

Acquired: 

Hypochromic: acquired Horner‘s syndrome, juvenile xanthogranuloma, iris metastatic carcinoma, Fuchs‘ heterochromic iridocyclitis, stromal atrophy (glaucoma or inflammation).



Hyperchromic: siderosis, hemosiderosis, chalcosis, medication (topical prostaglandin analogues for glaucoma), iris nevus or melanoma, iridocorneal endothelial syndrome, iris neovascularization



Ciliary processes are the most vascular structure of the eye.



The trem protan, deutran and tritan are derived from Greek word meaning first, second and third.



The term CALOTTE is used in ocular histopathology for the two hemispheres which are cut from the globe.



Visual field background illumination = 31.5 apostilb



Photopic maximum sensitivity = 555 nm Scotopic maximum sensitivity = 507 nm



Fischer–Khunt spot: (Senile scleral plaque) blue–gray area of hyalinized sclera anterior to horizontal rectus muscle insertions in elderly individuals



Purkinje shift: Shift in peak spectral sensitivity from photopic (555 nm, cones) to scotopic (507 nm, rods) conditions.

105


Dhaval Patel MD



Recurrent nerve loop of Axenfeld: Described in 1895 by T. Axenfeld was a nerve that makes a loop in the sclera anteriorly. The nerves travel through the sclera usually originating from the long ciliary nerves and some may approach the surface of the sclera about 1-6 mm from the limbus. The nerves bend 180 degrees creating a mushroomed loop at the surface. They may produce symptoms of irritation and tenderness.



Vigabatrin (VGB) is an irreversible inhibitor of gamma-aminobutyric acid (GABA) transaminase and is a highly effective antiepileptic drug for treating partial-onset seizures and infantile spasms. Vigabatrin is associated with visual field defects (as many as one-third of patients) but the mechanism is unknown. It should be avoided in patients with pre-existing visual field defect. Ophthalmoscopy appearance in patients taking vigabatrin includes narrowing of the retinal arterioles, wrinkles on the retina surface and optic atrophy in the presence of visual field defects. It causes a characteristic form of peripheral retinal atrophy and nasal or „„inverse‟‟ optic disc atrophy in approximately 10% of children being treated with VGB resulting in severely constricted visual fields. Discontinuation of VGB should be strongly considered in these children.



Steps to reduce OCR- OculoCardiac Reflex: use of atropine and light sedation



The inner layer of the optic cup contains the pluripotent retinal progenitor cells, which differentiate in a specific chronologic sequence and defined histogenic order into the final seven retinal cell types. In general, the RGCs differentiate first, followed by the cone photoreceptors, amacrine cells, horizontal cells, and finally, the rod photoreceptors, bipolar cells, and Müller cells. GCAHRBM  God Can Always Help Revealing Best Messages.



High doses of digoxin can cause objects to appear yellow (xanthopsia). Withering reported visual side effects of digoxin in his classic paper in 1785



Emsley Fincham test: The stenopic slit is kept in front of the eye and the patient is asked to look at a light source. The slit is then moved in front of the eye In conjunctivitis and in glaucoma, there is no fan effect. In cataract, there is fan effect. 106


Dhaval Patel MD

Colored halos caused by cataract (lenticular) seem to break into a moving fan but not that caused by glaucoma (corneal) which only become slightly dim. Moreover, the VIBGYOR of the rainbow is within outwards in lenticular halos and without inwards in corneal halos. This is because; in glaucoma colored halo is due to corneal edema which is homogeneous. In cataract, it is due to accumulation of water droplets in lens; which is a heterogeneous phenomenon.



Pseudomonas is a rare commensal.



C.diphtheria is not a part of normal commensals. C.xerosis and other corynebacteria are there.



Space of Mortegiani: extends posteriorly over ONH.



Nerves which escapes after retrobulbar block: trochlear, conjunctival sensory nerves and few sympathetics



Optic nerve has 1.5 million axons whereas trochlear nerve has 1500 axons. Its smallest cranial nerve.



Orbital lobe of lacrimal gland is anterior and Palpebral lobe is posterior. REMEMBER This. Else you can remember orbital lobe is superior and palpebral lobe is inferior.



Lacrimal gland structures are post-septal structure whereas lacrimal sac structures are pre-septal.



Russel bodies: plasma cells (activated B lymphocytes)



Morula cell (of Mott): Contains multiple grape-like Russell bodies 107




Dhaval Patel MD

Inflammation: Acute (exudative): Polymorphonuclear leukocytes, Mast cells and eosinophils Chronic (proliferative): Nongranulomatous: Lymphocytes and plasma cells NLP Granulomatous: Epithelioid histiocytes, giant cells GEG



Doxycycline changes the lipid viscosity of the meibomian gland secretions, improving oil secretion from the gland into the tear film. This superficial lipid layer is needed to keep the tears from evaporating too quickly.



Color of the Fundus: The color of the fundus depends on the melanin content of the retinal pigment epithelium, the melanin content of the melanocytes in the choroidal stroma, and the hemoglobin in the choroidal and retinal vasculature. The melanin contribution to the color parallels the complexion of the patient's skin and hair, the fundus being darker in black races and lighter in whites.



Cilioretinal vessels originate from the circle of Zinn, which is formed around the optic nerve in the sclera from the short posterior ciliary arteries.



The small white light reflex at the center of the fovea centralis is produced by the reflection of the ophthalmoscope light from the concavity of the fovea.



With the pupil widely dilated, the peripheral fundus can be seen with the direct ophthalmoscope up to the equator only. You cannot see beyond the equator by direct ophthalmoscope. The patient must be instructed to move the eyeball in the appropriate direction so that each quadrant of the retina can be brought into view.



Fixative for electron microscope is: glutaraldehyde

108


Drug for myopia: pirenzepine, atropine (in research)



Chlamydia o

Both DNA + RNA

o

No cell wall

o

No energy production

o

Elementary body is infective form

o

Basophilic cytoplasmic inclusion body

Dhaval Patel MD



White cyst of pars plana on HP Slide is diagnostic of multiple myeloma.



The human retina is able to detect a difference of 1 nm in wavelength between blue-green (490 nm) and yellow (585 nm). At the violet (430 nm) and red (650 nm) ends of the visible spectrum a greater difference exceeding 4 nm is required for a difference to be appreciated.



The optic nerve fibers are separated from the retinal layers by a ring of glial tissue, the intermediary tissue of Kuhnt. The continuation of this glial tissue, the border tissue of Jacoby (glial), separates the choroid from the optic nerve fibers Ring of collagenous tissue of scleral derivation, the marginal tissue of Elschnig (fibrous, temporal), lies outer to the glial sheaths.



Striated muscle of the leg can contain several hundred muscle fibers per motor unit; in the extraocular muscles, each axon innervates 3 to 10 fibers. This dense innervation provides for precise fine motor control of the extraocular muscles resulting in high velocity ocular movements, necessary in saccades, (up to 1000 degrees per second) and very accurate pursuits (velocities of 100 degrees per second) and fixations.

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Dhaval Patel MD



Afferent information regarding extraocular muscle proprioception is thought to be mediated by a receptor that is unique to extraocular muscle, the myotendinous cylinder (palisade ending) in contrast to Muscle spindles and Golgi tendon organs of typical striated muscles.



Metarhodopsin II is the rate limiting step in visual cycle.



Thickest BM of body is lens capsule.



STYCAR: Sheridan/Screening Tests for Young Children and Retardates, Sheridan 1973



Zone S/ Smooth Zone:



o

Anterior border - transition from trabecular to corneal endothelium and the termination of Descemet's membrane

o

Posterior border - elevation formed by the oblique insertion of uveal trabeculae into limbal stroma

o

50-150 microns

Ligamentum Hyaloideocapsulare of Wieger: insertion of cilioposterior fibers, tractus hyaloideus, peripheral boundary of Berger‘s space. Spatium retrolentalis Berger: potential space between posterior lens capsule and patellar fossa=anterior cortical gel Canal of Petit: Space between posterior zonules and anterior cortical gel. May contain pigment, blood, air Orbiculohyaloidal Space of Hannover: between anterior and posterior zonules. Cloquet‘s Canal: posterior to central cortical gel, funnel to area of Martegiani. Area of Martegiani: circular vitreous cortical defect above optic nerve=papilla



The uvea has mechanical attachments to sclera o

at the entry of the long and short posterior ciliary vessels 110




Dhaval Patel MD

o

the border layer of Jacoby (choroidal, prelaminar level) at the disc,

o

the vortex veins and

o

the major perforating branches of the anterior ciliary arteries at the ciliary body level.

o

The main attachment of the uvea however is at the scleral spur where the longitudinal muscle of Brucke (tensor choroidalis) inserts.

o

These attachments determine the configuration of choroidal elevations: 

shallow anterior=supraciliary



quadrilobed=to vortex insertion



kissing=scleral spur to short posterior ciliaries.

Clinicians‘s limbus: Transition of clear cornea to opaque sclera (corneolimbal junction) Histologist‘s limbus: transition of regular corneal stromal lamellae to irregular scleral stromal lamella. (Peripherally convex line) Pathologist‘s limbus: tissue roughly between external and internal scleral sulcus, 12mm wide. Internal scleral sulcus bordered by end of Decemet‘s membrane (corneolimbal junction) and scleral spur (limboscleral junction)



No epithelium covers the anterior iris surface. Anterior border layer is composed of fibroblasts and melanocytes. Both iris sphincter and dilator are neuroectodermal derivations. Sphincter and dilator are attached to each other at the central Fuchs‘ spur and peripheral Michael‘s spur.



Longitudinal muscle of ciliary body is also known as Brucke‘s muscle or tensor choroidalis.



Lens zonules (capsular fibers) can be divided into o

Cilioanterior 111




Dhaval Patel MD

o

Cilioequatorial

o

Cilioposterior

o

orbiculoanterior and orbiculo posterior: these fibers originate from the dentate processes of the retina, form the orbiculohyaloidal interspace of Hannover, rest on the anterior hyaloid and ―suspend‖ the anterior vitreous.

Subretinal space borders: border tissue of Kuhnt (posterior cul-de-sac) – ora serrata (anterior cul-de-sac) Suprachoroidal space borders: border tissue of Elschnig (posterior cul-de-sac) – scleral spur (anterior cul-de-sac)



Middle limiting membrane: junctional complexes between rod spherules and cone pedicles. Mueller cells elaborate the internal limiting membrane which is their cell base (base in, apex out). The Mueller cell apex points to the photoreceptors and elaborates the external limiting membrane, a desmosomal junctional system.



The inner 1/3 and outer 2/3rd of OPL is separated by the middle limiting membrane which is composed of synapses and their junctional systems connecting the axons of rods and cones (inner fibers of Henle) to the outer neurons. The middle limiting membrane denotes the limit of retinal capillaries as well as a barrier to exudates.



Dentate processes of the retina are more prominent nasally. Blessig Ivanoff cysts: Cystoid degeneration of retina is more prominent temporally.



Typical peripheral cystoid degeneration (TPCD) o

inevitable in adult eyes

o

The cystoid spaces develop first at the outer plexiform layer. If these spaces coalesce, typical degenerative retinoschisis results. 112


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Dhaval Patel MD

o

In most cases, this is without clinical consequence.

o

Very rarely, a retinal detachment can develop in the presence of holes in the inner and outer layers of the schisis cavity.

o

In contrast, reticular cystoid degeneration is less common and develops in the nerve fiber layer.

Vitreous components, 3-fold origin: Lens (surface ectoderm), retina (neuroectoderm) and vascular endothelium (mesoderm) Primary vitreous <6 weeks (<13mm): "Cellular", Hyaloid canal remnants Secondary vitreous <8 weeks (13-65mm): "Vascular", Vitreous body Hyaloid vessels, collagen fibrils (Mueller cell footplates) and hyaluronic acid (neuroectodermal) More fibrils and hyaluronic acid Tertiary vitreous at >12 weeks (>65mm): Zonules and Marginal Bundle of Druault = future vitreous base.



The anterior margin of the optic cup is called the ―Marginal sinus of von Szily‖. It advances on the posterior surface of the iris stroma. Pupillary ruff: Marginal sinus of von Szily reaches pupil in the 4th month and forms the iris sphincter and dilator. If it fails to do so, the condition is called Aniridia.



Internal ulcer of von Hippel: If endothelial (Descemets) defect occurs related to incomplete separation of lens



The differentiation of the macula is not complete until 4–6 months after birth. Ganglion cell nuclei are initially found directly over the foveola and gradually are displaced peripherally, leaving this area devoid of accessory neural elements and blood vessels as neural organization develops to adult levels by age 6 months. This delay in macular development is one factor in the inability of newborns to fixate, and improvement in visual activity parallels macular development.

113


Dhaval Patel MD



The superior orbital fissure at the orbital apex lies between the greater and lesser wings of the sphenoid bone.



Paranasal Sinuses: o

All paranasal sinuses are normally present at birth (apart from the frontal sinus which is rudimentary until 2 years of age).

o

All sinuses are lined by a pseudostratifieci columnar ciliated epithelium, which aids the passage of mucus into the nasal cavity.

o

The maxillary sinus drains via the hiatus semilunaris into the middle meatus of the nose.

o

The anterior and middle ethmoidal air cells, along with the frontal air cells, also drain into the middle meatus of the nose.

o

The posterior ethmoidal air cells drain into the superior meatus whereas the sphenoidal air cells drain into the sphenoethmoidal recess.

o

All lymph drainage from the paranasal sinuses is to the submandibular nodes, except the sphenoidal sinuses and posterior ethmoidal sinuses which drain into the retropharyngeal group of nodes.



The osseous canal for the nasolacrimal duct is formed by the maxilla, the lacrimal bone, and the inferior nasal concha; it opens into the inferior meatus of the nose.



The conjunctiva becomes continuous with the keratinised skin epithelium along the posterior margins of the tarsal gland openings and not at the grey line, which lies anterior to these openings. The grey line marks the tissue plane along which the eyelid may be split into an anterior lamella consisting of skin, subcutaneous tissue and orbicularis, and a posterior lamella consisting of the tarsal plate and conjunctiva.



The stratified squamous epithelium of the palpebral conjunctiva becomes a stratified columnar layer in the bulbar region before again becoming stratified squamous in continuation with the corneal epithelium.

114


Dhaval Patel MD



The final diameter of the cornea is determined by the diameter of the optic cup.



Corneal Development: o

The initial step in comeal development is the production of a bilayered epithelium and basement membrane separate from a bilayer (or occasionally a trilayer) of endothelial cells and associated basement membrane

o

At approximately 7 weeks gestation a primitive stroma is formed, which is infiltrated by fibroblasts producing; collagen fibrils.

o

By the third month the stroma is a structure of 25—30 layers a thin Descemet‗s membrane is present and the endothelium is now a single layer.

o

Bowman's layer is the last of the five corneal layer to form.

o

Corneal nerves are present by five months.

o

The cornea has reached its adult form by seven months.

o

The cornea is not transparent throughout development but becomes so gradually as its stmcture becomes more ordered.



Cold and pain are the only stimuli of the corneal epithelium.



The palisades of Vogt are formed by epithelial cells, which are thrown into folds by the subepithelial connective tissue at the limbus.



The ciliary epithelium is a bilayered cuboidal epithelium that forms an integral part of the blood aqueous barrier. The two cell layers lay apex to apex, the inner layer being rich in golgi apparatus and rough endoplasmic reticulum while the outer layer contains numerous melanocytes. There are numerous tight junctions between the cells of the inner layer but not between cells of the two layers. The basement membrane of the inner layer is continuous with the internal limiting membrane of the retina, whereas the basement membrane of the outer layer is continuous with that of the retinal pigment epithelium. 115


Dhaval Patel MD



The sphincter and dilator muscles arise from the anterior epithelial layer.



Sclera is thickest (1 mm) at its posterior pole, thins to 0.6 mm at the equator and is thinnest (0.3 mm) immediately posterior to the tendinous insertions of the recti.



The outer plexiform layer is the watershed region of the retina: structures that lie peripheral to this layer (rods and cones in the outer nuclear layer) receive their nutrients by diffusion from the choroidal circulation, whereas the inner two-thirds of the retina receive nutrients directly from the central retina artery and its tributaries.



parasympathetic fibers to the lacrimal gland: superior salivatory nucleus- nervus intermedius (glossopalatine) nerve- geniculate ganglion- greater superficial petrosal nerve- joined by the secondary sympathetics from the deep petrosal nerve and enter the pterygoid canal (vidian canal)- vidian nerve emerges from the pterygoid canal and enters the sphenopalatine ganglion (pterygopalatine) where the primary parasympathetic fibers synapse and then exit as secondary parasympathetic fibers- join the zygomatic nerve which sends a communicating branch that enters the lacrimal gland





Medial Canthal Area o

The medial canthal tendon has anterior and posterior portions.

o

The anterior portion attaches to the frontal process of the maxillary bone and serves as the origin of the superficial head of the pretarsal orbicularis.

o

The posterior portion inserts on the posterior lacrimal crest and fossa. The posterior limb of the medial canthal tendon, the deep head of the pretarsal orbicularis, and the deep head of the preseptal orbicularis muscles are important in maintaining apposition of the eyelids to the globe.

o

The lacrimal sac is positioned anterior to the orbital septum and, therefore, does not lie within the orbit.

Lockwood's ligament (Lockwood's suspensory ligament) 116






Dhaval Patel MD

o

suspensory system for the globe.

o

It is the lower eyelid retractor system with contributions from intermuscular septae and Tenon's capsule.

o

Posteriorly, it arises from fibrous attachments to the inferior side of the inferior rectus muscle and continues anteriorly as the capsulopalpebral fascia (lower eyelid retractors).

o

Medial and lateral horns extend to attach to the retinacula. 

The medial retinaculum attaches to the posterior lacrimal crest



The lateral retinaculum attaches to the lateral orbital tubercle of Whitnall. These tissues form a suspensory hammock for the globe.

The superior transverse ligament, or Whitnall's ligament o

arises from the compaction of the sheath of the anterior portion of the levator muscle.

o

Medially, it arises from the connective tissue of the trochlea.

o

Laterally, it attaches to the capsule of the orbital lobe of the lacrimal gland and to the lateral orbital wall above the lateral orbital tubercle.

o

There are extensions to the medial and lateral retinacula. This structure acts to change the direction of pull of the levator muscle from horizontal to vertical and serves to limit the elevation of the eyelid.

o

Although Whitnall's ligament attaches to the fascia on the superior and medial surfaces of the lacrimal gland; it does not pass anteriorly to the lacrimal gland.

o

The lacrimal gland is divided into orbital and palpebral lobes by the lateral horn of the levator aponeurosis.

The lacrimal gland is supported by four fascial structures o

Soemmering's ligaments

o

Whitnall's ligament

o

Inferior ligament of Schwalbe

o

lateral horn of the levator palpebrae aponeurosis. 117




Dhaval Patel MD

The orbicularis muscle o

Divided into orbital parts and palpebral parts (pretarsal, preseptal)

o

The orbital portion is involved in forced eyelid closure. It originate from the anterior medial canthal tendon and periosteum.

o

The palpebral portion of the muscle is also responsible for reflex blinking (as opposed to the orbital portion, which ―screws‖ the eyelids tightly together)

o

The pretarsal portion arises from the posterior lacrimal crest and anterior limb of the medial canthal tendon. The lateral portion of the pretarsal muscle becomes the lateral canthal tendon. The deep head of the pretarsal muscle (tensor tarsi muscle of Horner) encircles the canaliculi to facilitate tear drainage.

o

The preseptal orbicularis originates from the fascia around the lacrimal sac and posterior lacrimal crest. Superficial origins arise from anterior fibers of the medial canthal tendon. Laterally, it forms the lateral palpebral raphe overlying the lateral orbital rim.

o

It is a muscle of facial expression that is derived from the second branchial arch and is therefore supplied by a branch of the facial nerve.



Lateral wall is the strongest orbital wall.



Commonest soluble protein in the vitreous is acid glycoprotein.



Multifocal ERG charts 61-103 focal retinal points.



Foveola: 1.25 degrees Fovea: 5 degrees Macula: 15-20 degrees



C-peptide is the marker for insulin production. 118




O2 tension o

Aqueous: 72 mmHg

o

Tear with lid closed: 55 mmHg

o

Tear with lid open: 155 mmHg



Minimum O2 tension to prevent cornea from swelling is 11 mmHg.



RQ of cornea is 1.



Ocular immune privilege



Dhaval Patel MD

o

Complement inhibition by membrane cofactor protein (MCP), decay-accelerating factor (DAF), and CD59

o

Clonal deletion: Fas ligand expressed in uveal tissue causes deletion of the Fas+ T cells that enter that tissue and recognize antigen

o

Clonal anergy: TGF-ß2, free cortisol, and IL-1 receptor antagonist

o

Immune deviation: ACAID or anterior chamber-associated immune deviation.

o

T-cell suppression: TGF-b, a-MSH, VIP, CGRP, MIF, free cortisol

Gene Therapy o

Demonstration of efficacy/cureof severe combined immunodeficiency (―bubble-boy disease‖) using ex vivo gene replacement has provided proof of principle for gene therapy.

o

Glybera: approved to treat lipoprotein lipase deficiency

o

For recessive diseases, replacement with ―wildtype‖ gene or gene correction resulting in production normal enzyme: eg, RPE-65, peripherin/RDS(Prph2)

o

For dominant disease, neutralization of toxic ―dominant‖ substance (eg, ribozyme therapy for rhodopsin mutants causing dominant RP) 119






o

Current trials are going on for AMD, Leber congenital amaurosis type2, Stargardt disease, choroideremia, Usher syndrome 1B, choroideremia, and retinitis pigmentosa due to MERTK mutations.

o

Gene Therapy for Wet AMD 

Retinostat: Phase I Testing in 2013



sFlt01: Phase I Testing in 2013

Classification of Cell Death o

Apoptosis

o

Autophagy

o

Necrosis

Caspase-Dependent Apoptosis o

External death signals such as tumor necrosis factor (TNF) or Fas ligand (FasL) 

o

o



Dhaval Patel MD

RIP kinase (RIPK) signaling is closely connected to both the extrinsic caspase signaling pathway and the NF-κB survival pathway

intrinsic signals such as mitochondria damage and reactive oxygen species (ROS). 

Apoptosis-inducing factor (AIF) is an intrinsic factor involved in initiating a caspase-independent pathway of apoptosis



play a role in photoreceptor cell death after RD

Caspases are also involved in pyroptosis, a distinct mechanism of cell death associated with inflammation

Neuroprotection Strategies o

Caspase inhibition 

o

Fas-mediated apoptosis pathway becomes activated after RD, and inhibition of Fas activation (with anti-FAS-receptor antibodies) can decrease caspase-9 activity

Combined inhibition of apoptosis and necroptosis: RIPK-mediated necrosis 120


Ciliary neurotrophic factor (CNTF): act through the IL-6 receptor

o

Brimonidine

Dhaval Patel MD



Rabl's lamellae: radiating pattern of lens fibres in periphery, fibers being more uniform beneath the epithelium and becoming thicker and irregular as they age and approach the nucleus



Arrestin is also known as S-antigen.



Oguchi's disease is a nonprogressive autosomal-recessive congenital stationary night blindness that maps to chromosome 2 with candidate gene in that region is the arrestin gene.



Resistance to diffusion of solutes and bulk fluid flow are of considerable importance to maintaining normal corneal function (resistance to diffusion of solutes and fluid flow: epithelium [2000] ≫ endothelium [10] > stroma [1])



The nasolacrimal duct derives from ectodermal tissue in the nasolacrimal groove between the lateral nasal and maxillary processes. This tissue is known as the nasolacrimal ectodermal cord. Mesenchymal tissues from the maxillary process cover the ectodermal tissue medially, before it canalizes. The central cells of the cord degenerate until there is a superior membrane composed of canalicular and conjunctival epithelium, as well as an inferior membrane of nasolacrimal and nasal epithelium. These superior and inferior ends are usually patent at the time of birth.



The lacrimal gland arises from an outpouching of the conjunctiva as a modified salivary gland.



Primary lymphoid organs: Thymus and bone marrow Secondary lymphoid organs: Lymph nodes, spleen, MALT 121


Dhaval Patel MD

Cmax: The maximal concentration of drug in the tissue is Cmax. Tmax: The time to reach a maximal level of drug in the tissue is Tmax. Area under the curve (AUC): The AUC yields the total amount of drug absorbed from an applied dose. The bioavailability of a drug is computed from the AUC, which is most important in determining therapy for chronic medication.



Ocular Effects of PGs o

D: Stimulates vasodilation and chemosis

o

E1, E2: Increase inflammation, Increase intraocular pressure, Increase capillary permeability, Stimulate vasodilation, Stimulate miosis

o

F2: Reduces intraocular pressure, Has minimal effect on inflammation, Has minimal effect on miosis

Optics & Refraction



In streak retinoscope, when para-stop is at Down position, rays coming out are Divergent from convex/ plane mirror. If position of para-stop is up, rays coming out are convergent from concave mirror.



Hard contact lens fitting: 1. Base curve = flattest K + 0.5 (for tear lens) 2. Convert manifest sylinder to minus lens 3. Disregard the cylinder 4. Correct for vertex distance if sphere is >= 4D 122


Dhaval Patel MD

5. Substract +0.5 tear lens (created by fitting +0.5 overflattened contact lens)



Toric Transposition for CL: The steps for toric transposition is as follow: 1. Make sure the cylinder has the same sign as the base curve 2. Obtain the required power of the spherical surface by subtracting the base curve power from the spherical power. Here the result is +3-(-5) = +8.00DS 3. Specify the axis of the base curve and this axis is 90 degrees to that of the required cylinder. The result in this case is: -5.00DC axis 180. 4. Finally add the required cylinder to the base curve power with its axis. The result is -5 (1.00) = -6.00DC axis 90.

Example: –2.00 DS/–0.50 DC*90° Base Curve + 5.00 Rule No 1: Sign of cylinder should be same as sign of base curve. Sign of cylinder needs to be changed by simple transposition. –2.50 DS/+0.50 DC*180° Rule no 2: Power of new sphere= –2.50–(+5.00) = –7.50 DS Rule no 3: Power of cylinder no 1= +5.00 DC*90° Rule no 4: Power of cylinder no 2= + 0.50 DC + (+5.00 DC) = + 5.50 DC*180°

• Practical problem of Near Add: Point to be remembered is that ‗add‘ is algebraically added to the spherical power for distance and there is no change in power and axis of cylinder. So when you are prescribing separate glasses, near vision glasses contains add of near on whatever distance correction patient has.

•

Most commonly used material for glasses is CR-39 (C stands for Columbia and R stands for resin). This material can withstand heat up to 100° C. Its refractive index is 1.498. Chemically it is Allyl Diglycol Carbonate. (ADGC) 123


Dhaval Patel MD

•

V-value Constringence or Abbe‘s number: The degree to which the material has the same refractive index for different wavelengths of light. Lenses made with lower V values more quickly show rainbows, color fringes and degradation of best acuity when the eye turns towards the periphery of a spectacle lens, the effect being proportional to the power of lens. In simple language it is a positive value that indicates the degree of transverse chromatic aberration. High V-value means low dispersive power and vice versa. Thus Crown glass has V-value of 59 and CR-39 has V-value of 57.8 and thus patient does not complain of colored fringes due to their low dispersive power. In contrast-high index lenses and polycarbonate lenses have a low V-value thus high dispersive power and cause colored fringing of objects.

•

A lens with base curve of 6D is known as deep meniscus lens and with a base curve of 1.25D is known as Periscopic lens.

•

Photochromatic lenses darken on exposure to light and become colorless in dark again. This is because silver chloride crystals which change into free silver on exposure to sunlight. This free silver forms silver colloids which absorb UV radiations to cause darkening of lenses. In indoor conditions silver particles, combined with trapped halides and silver halide crystals are reformed and lens appears clear. These lenses darken only in sunlight but not in artificial light because UV radiations are required for the darkening effect. Hence car windows which block UV rays also render these lenses less effective inside the car.

•

AR coating decreases reflection of incident light on lens and increases its transmittance. As the AR coating absorbs ultraviolet rays hence less light is available for activation of photochromic property of lens. Thus a photochromic lens with AR coating becomes less dark on exposure to light as compared to a normal photochromic lens.

•

Balance Lens: This type of lens is used to balance the weight of the other lens in the spectacle frame where one eye is practically blind. For better cosmetic appearance, the balance lens power and style should match the other lens.

• Lenses with refractive index between 1.64 and 1.73 are called high index lenses 124


Dhaval Patel MD



Vergence is defined as the reciprocal of the distance from a reference point (in meters) to the point of focus. By convention, divergence is given in minus (-) vergence power and convergence is given in plus (+) vergence power.



A diopter is a unit of accommodative amplitude; it describes the vergence of a waveform and describes the vergence at a specific distance from the source; and it is also defined as the power of the lens. A diopter is the reciprocal of the distance in meters.



Converging lenses have real/inverted images that are on the opposite side of the lens from the object. Diverging lenses create virtual/erect images that are on the same side as the object.

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Basic Lens formula: U+D=V 100/u (cm) + D = 100/v (cm) U = vergence of object at the lens u = object position = 100/U (cm) D = lens power V = vergence of image rays v = image position = 100/V (cm)

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Fnew = Fcurrent/(1-dFcurrent) where F is in Diopters and d is in meters.

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The primary focal point (F1) of a lens is also called the Object-Space Focus. For a plus lens, this is the point from which light must originate to emerge parallel from the lens. Thus, the image is at infinity. For a minus lens, this is the point towards which the incident light must be directed in order for the image rays to emerge parallel. 125


Dhaval Patel MD

Secondary focal point (F2) of a lens is also called the Image-Space Focus. For a plus lens, this is the point where parallel rays from a distant point object are rejoined to form an image at that point. When parallel rays enter the optical surface, they will focus at the secondary focal point. For a minus lens, this is the point from which diverging rays seem to come from, after a parallel bundle of rays are refracted by a negative lens.

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The anterior focal point is approximately 17mm (1/-60 = -16.67mm in front of the cornea) and the eye is 22.6mm in length with the nodal point 5.6mm behind the cornea. The nodal point is the point in the eye where light entering or leaving the eye and passing through the nodal point, is undeviated. This allows similar triangles to be used to determine the retinal image size of an object in space. For example, to determine the retinal image size of a Snellen letter (viewed at 6 meters), the following formula would be used: Retinal image height/Snellen letter height = 17mm/6000mm The far point of the eye is the object point imaged by the eye onto the retina in an unaccommodated eye. The near point of the eye is found when the uncorrected refractive error of the eye is added to the accommodative ability of the eye. If the amplitude of accommodation is 10D, the near point is 10cm in front of the eye (specifically, 10cm in front of the vertex of the cornea which is used as a convenient reference point).

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According to Knapp‘s Law, the retinal image size will not be different between the two eyes, no matter what amount of axial ametropia exist, when the spectacle lens is placed at the eye‘s anterior focal point.

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The Amplitude of Accommodation, also known as the accommodative response, is the maximum increase in diopter power obtainable by an eye. The amplitude of accommodation is measured monocularly.

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The Range of Accommodation denotes the linear distance (expressed in centimeters or meters) over which the accommodative power allows an individual to maintain clear vision. The range lies between the near point of accommodation and the far point of accommodation. 126


Dhaval Patel MD

This is considered the most useful clinical measurement of accommodation. It helps answer the question as to whether an individual‘s accommodative range comfortably encompasses his visual needs.

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When wearing contact lenses, the convergence requirement is the same as that of an emmetrope, because the lenses rotate with the eye and the line of sight remains relatively well directed through the center of the lenses. As a myope converges to bi-fixate a near object, his line of sight departs from the center of his spectacle lenses and encounters increasing amounts of base in prismatic effect. The spectacle wearing hyperope encounters base out prismatic effect, as he converges to bifixate a near object. Thus, to bi-fixate a given object at a distance less than infinity, the bespectacled myope converges less than the emmetrope or the contact lens wearer, while the hyperope wearing spectacles converges more than the emmetrope or the contact lens wearer. Therefore, the myope who discards his spectacle lenses in favor of contact lenses, must converge more to bi-fixate a given near object, while the hyperope will converge less under the same conditions.

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Relative Distance Magnification = r/d where r = reference or original working distance and d = new working distance Relative Size Magnification = S2/S1 where S1 = original size and S2 = the new size The ratio of the image size to the object size or image vergence to object vergence is called transverse or linear magnification. MT = I/O=U/V = v/u

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The power of a lens is an indication of how ―strongly‖ it refracts (bends) incoming light rays. The power, P, is equal to one over the focal length in meters and has units of Diopters (D). P (diopters) = 1/f (m)



The Airy's disc is a diffraction pattern when light passes through the edge of an obstacle. It contains a bright central disc ie. Airy's disc that receives about 90% of the luminous flux. This disc is surrounded by concentric light and dark rings. The radius of the disc is proportional to the wavelength of the light but inversely proportional to the pupil size. Sir George Airy, (1801–1892) Astronomer, was the first to calculate the energy distributions in the pattern. 127


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Approximately 84% of the total energy of the diffraction pattern is in the Airy disc. The remaining energy is distributed in the surrounding rings that become progressively fainte Two object sources of light (S1 and S2) cannot be resolved if their diffraction patterns (Airy discs) overlap substantially. Rayleigh‘s criterion: central maxima of one diffraction pattern falls on the first minima of the diffraction pattern from the second source, and the two images can just be resolved.

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Polarimetry uses the birefringence of the NFL (nerve fibrelayer) to quantitate its thickness indirectly. The change in the polarization of light as it passes through the NFL, or ―retardation,‖ is measured and linearly correlated to the NFL thickness.

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Illuminance and irradiance are terms used to refer to the amount of light arriving at a given point. Radiance refers to the amount of light leaving a certain point.

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Catoptric images are images reflected from the surfaces of the eye. It is other name of commonly known purkinje images.

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To appreciate difference in stimuli, human eye requires 10% difference in stimuli.

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The eye can accommodate in the absence of convergence. However, in normal daily life a patient with normal binocular vision will convergence when he/she accommodates. The normal ratio is 3:1 to 5:1.

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The refractive index of a material is different for different wavelength and in general it is usually measured with yellow sodium flame.

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The frequency of a light does not change as it travels from one medium into another but the wavelength become shorter.

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The vergence power of a lens is affected by 128


vergence power of each surface

o

thickness of the lens and

o

medium on either side of the lens.

Dhaval Patel MD

The later explain why cornea has a stronger refractive power than lens in human eye although its refractive index is less. The wavelength of the light also affects the vergence power of the lens.

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The first focal length has the same length as the second focal length only if the media on either side of the lens are the same. The first focal length of a convex lens is to the left of the lens whereas that of the concave lens is to the right of the lens. By convention, the second focal length has a positive sign for convex lens and a negative sign for concave lens. As lenses are designated by their second focal lengths, a convex lens is also called a plus lens and a concave lens a negative lens.

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Image magnification can be defined in various ways: Linear magnification is the quotient of the image height divided by the object height. Axial magnification is the magnification of the depth of the image along the optical axis. Angular magnification is the quotient of the angle subtended by the image divided by the angle subtended by the object.

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Maddox rod is used to measure distant phoria and Maddox wing for near phoria. Double Maddox rod can be used to measure cyclotorsion.

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Spectacle cannot correct irregular astigmatism. It is treated by substituting a new surface and this can be achieved with a contact lens usually RGP lens, corneal graft or laser surgery.

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Placed before an ametropic eye, the cross-cylinder does not alter the spherical equivalent, but it will enlarge or contract the interval of Sturm, blurring or clarifying the 129


Dhaval Patel MD

image, as it increases or decreases the net astigmatic ametropia. The power of the cylinder is twice that of the sphere and of opposite sign.

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High-order aberrations are ones that cannot be corrected by simple spherocylindrical systems, such as spectacles or contact lenses. They are caused by minute misalignments of the eye's optical components and include, in order of visual significance, spherical aberration, coma, higher-order astigmatism, and others. They can be detected with wavefront analysis performed with an instrument called aberometer. Theoretically, an ablation that removes aberrations increases visual contrast and the spatial detail of images seen by the eye.

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Anisometropia of more than 1D in hypermetropic patients can not be controlled with unilateral accommodation because accommodation is a binocular process. Therefore the image in one eye is often blurred and is a cause of amblyopia.

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The image is moved forward when a correcting lens is moved forward irrespective if the lens is concave or convex.

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The accommodation is the sum of the patient's refractive state + 4D. For comfortable near vision, one-third of accommodation should be kept in reserve.

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The Franklin design is a split bifocal in which a distance lens is mounted on a near lens. The cemented design involves attaching a supplementary lens to the surface of a distance lens of the same refractive power. Fused bifocal is made by heat-fusing a near portion made of flint glass into a depression on a crown glass with a lower refractive index.

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Varifocal glasses have three sections: distance, intermediate (for VDU or working at arm length) and near (for reading).

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Contact lens with the following numbers 8.9/13.8/-4.25: base curve/diameter/power (BDP)

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The radiuscope is the traditional instrument used by practitioners and laboratories to measure the radius of spherical base curves.

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Piggyback contact lens involves the use of two lense; the soft contact lens provides the fitting surface for the rigid gas permeable lens.

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Corneal warpage refers to change in the corneal curvature associated with contact lens wear. Corneal oedema is absent. It is commoner with rigid gas permeable contact lens than soft contact lens. The result is reversible. Biometry or refractive surgery should be avoided until the cornea returns to its normal shape otherwise the results of the measurement or surgery will be inaccurate.

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Wollaston prism is used in the Javal-Schiøtz instrument to double the image formed by reflection on the cornea.

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Astigmatic keratotomy is placed perpendicular to the steepest meridian. Coupling is a problem and it is defined as steepening of cornea at 90 degrees perpendicular to the meridian that has been flattened by the incision though not to the same degree.

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As neutrality is approached, the reflex becomes Faster, brighter and thinner. When the refractive error is neutralized, the pupil is suddenly filled with light.

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When the retinoscopy reveals +2.00-1.75 X 180 at working distance of 67cm, the final refraction will be +0.50 -1.75 X 180. This cylinder portion of the correction is unchanged. 131


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Dhaval Patel MD

2 basic methods of retinoscopy: 1. neutralize one meridian with sphere and the other with the cylinder If you are working at a distance of 67cm, and you find that with the streak at 90 degrees +2.00 D sphere neutralized the reflex; with the streak at 180 degrees (with the sphere in place) a -2.00D cylinder neutralizes the reflex. The patient's final refraction is +0.50 2.00 X180. 2. sphere to neutralize both axis With the streak at axis 90 degrees, a +3.00D lens neutralizes the reflex. With the streak at axis 180 degrees, a +6.00D lens neutralize the reflex. If the working distance is 67 cm, the final refraction is +4.50 -3.00 X 90.

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Duochrome or binocular balance tests is not needed in aphakic, pseudophakic and patients over 50 as they have no or little accommodation making the tests unnecessary.

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Binocular balance procedure o

In monocular refraction one aims to obtain the maximum positive correction with the accommodation fully relaxed. However, if the eye not being examined accommodates behind the cover, then the maximum correction will not be achieved. Binocular balancing is a check for this small amount of accommodation.

o

Prism dissociation balance

o

With the patient binoculary viewing a block of letters at a 6 m distance

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Remember to give maximum positive sphere equal to best visual acuity and minimum negative sphere.

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Cross compound lens: a combination of lens in which power of cylinder is more than power of spherical lens with opposite signs.

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Patient having mixed astigmatism may not complain of defective vision as the circle of least diffusion falls on his retina and hence his visual acuity is very good even without glasses. 132


Dhaval Patel MD



A difference of 1D in refractive status of two eyes creates a difference of 2% in size of retinal image of two eyes. Up to 5% difference in retinal image size of two eyes is well tolerated. Thus an anisometropia of up to 2.5D is acceptable. Anisometropia of up to 4D may be acceptable in some individuals and more than 4D creates diplopia.

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Purkinje Images are also known as Catoptric imagery. 4 images: 1,2,3 are virtual and erect while 4th is real and inverted. 1,2 are near pupillary plane, 3rd is in the vitreous whereas 4th is in the lens.

Clinical Applications 1. To diagnose presence or absence of lens. 2. Keratometry makes use of first Purkinje image. 3. Type of cataract: In MSC and HMSC, Fourth Purkinje image is absent. 4. Hirschberg test: First Purkinje image is used for estimation of angle of squint.

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Remember that while checking a lens if its convex or concave, if image seen by it moves in same direction, then its concave lens which is used in myopia. Don‘t confuse this with refraction in which reflex moves in opposite if its myopia >1.5D. Concave mirror converges parallel rays of light and convex mirror diverges parallel rays of light. This is in contrast to concave lens which diverges parallel rays of light and convex lens which converges parallel rays of light.

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Reflex convergence is of four types: FAT-P 1. Proximal convergence: Psychological awareness of a near object initiates this type of convergence. 2. Tonic: It means that when the patient is awake there is an inherent tone in the extraocular muscles. 133


Dhaval Patel MD

3. Fusional: It is initiated by a bi-temporal retinal image disparity and is not associated with change in refractive status of eyeball. It ensures that image of an object falls on corresponding retinal points in the two eyes.

4. Accommodative: It is initiated by act of accommodation. It means that when we accommodate; we converge. It is a part of near reflex. One dioptre of accommodation is accompanied by 4-5 prism diopters of accommodative convergence and it remains fairly constant. Abnormalities of accommodative convergence are associated with squint.

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Speed of light is the fastest anything has been observed to move. In vacuum, the speed is three lakh kilometers per second or one lakh eighty six thousand miles per second. At this speed, it takes light one ten thousandth of a second to travel around the earth.

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The angle of incidence, for which angle of refraction is 90° is known as critical angle. For example, fibre-optic cables, gonioprisms, diamond shining at night.

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A sound wave, by contrast, vibrates back and forth along its propagation direction and thus is not polarizable.

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LAW OF INVERSE SQUARE:



o

applies to light, sound, electricity, gravitation

o

It states that the intensity of light, i.e. luminance radiating from a point source is inversely proportional to the square of the distance from the source.

o

E = 1/d

2



E = Energy at one particular point



d = Distance of point from the source of light

Positive angle kappa represents a slight temporal position of the fovea relative to the optical axis. This causes a slight temporal rotation of the globe to keep the image on the fovea. This, in turn, causes the corneal light reflex to be displaced nasally. The deviated light reflex remains stable with cover testing as the fovea never spontaneously moves relative to the optical axis 134


Dhaval Patel MD



Centrad is that strength of a prism which produces a deviation of 1 cm of arc at a distance of 1 meter. It is old unit and no more in routine use now.

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How to Detect and Measure Strength of a Prism o

Manual Method: See a straight line through a prism. It appears broken. Line appears to be deviated towards its apex. Now place a prism of known strength in such a way that base is towards apex of test prism. When prism of correct power is chosen, straight line appears unbroken again.

o

With Lensometer: Place a prism on the platform. Look through eyepiece of lensometer. The green target appears deviated. Now combine a prism of known power with prism of unknown power placed apex to base. Place this combination on the platform and see through the lensometer. The target has moved towards the center.

o

Another Method: Check prism by using the Prism Reference Point (PRP), also called the Prism Compensation device in the lensometer by noting the displacement of the mires from the central ring of the PRP. Each ring is marked with a number, the center is zero. Each ring represents one diopter of prism. If the mires are located two rings from the center, the prescription contains 2 diopters of prism.

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In PST (photostress recovery test), Patients who have a maculopathy will take longer (90 to 180 seconds) to recover pretest vision after looking into a bright light for 10 seconds. Patients with optic nerve disease will have a normal recovery time (<60 seconds). The test is probably only valid for patients with vision better than 20/80.

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A pattern VER (as opposed to a flash VER) is required for visual acuity assessment in preverbal children.

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In patients with macular disease VA is frequently worse when the patient looks through a pin-hole.

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A lens is a transparent medium bound by two surfaces which are part of spheres. 135


Dhaval Patel MD

A mirror is a part of a hollow sphere whose one side is polished.

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Aspheric Lens and Achromatic Lens o

Aspheric or aplanatic glasses are grinded in such a way that their curvature (and hence power) is maximum in the center and gradually decreases towards periphery. Thus an aspheric lens of +10 DS has a power of +10 DS at the center and +6 DS at the extreme periphery

o

An achromatic lens can be manufactured by combining two glasses of different dispersive power and different refractive index. Flint glass has a refractive index of 1.65 but dispersive power double than that of crown glass. Ref. index of crown glass is 1.5. Thus if a + 2.00 DS lens of crown glass with +2d dispersive power is combined with –1.00 DS lens of flint glass which has –2d dispersive power, a +1.00 DS lens with zero dispersive power is obtained

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Maximum resolving power of human retina (smallest distance between cones) = 20 seconds of arc

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Accommodative insufficiency is associated with systemic processes such as hypothyroidism, anemia, pregnancy, nutritional deficiencies, and chronic illness.

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Aberrations of Thick lenses: CCODS 1. Spherical aberration: 2. Coma: 3. Astigmatism of oblique incidence: 4. Chromatic aberration: 5. Distortion:

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The reciprocal of the best Snellen acuity is equal to the plus power of the lens required. For example, if a patient can read 20/60, a +3.00 D will suffice. The reciprocal of the diopter power gives the reading distance (i.e., 33 cm). 136


Dhaval Patel MD



Geneva lens clock: A device to determine the base curve of the back surface of a spectacle. It is often used clinically to detect plus cylinder spectacle lenses in a patient used to minus cylinder lenses. It is specifically calibrated for the refractive index of crown glass. A special lens clock is available for plastic lenses.

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Snell's law (law of refraction) = the incident and refracted rays and the normal to the surface at the point of incidence lie in the same plane and the ratio of the sine of the angle of incidence i to the sine of the angle of refraction r is a constant for any two media. This constant is called the relative index of refraction ie. sin i / sin r = refractive index

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Apex angle in degrees of a 10 dioptres prism is 10 degrees.

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The nodal point of a lens is at the intersection between the principal axis and the principal plane.

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The image produced by a negative lens is virtual, erect and diminished.

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A focimeter measures the back vertex power of a lens.

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A decentration of 10 mm from the optical centre of a +5 dioptre lens produces a prismatic effect of 5 prism dioptres

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A X8 loupe has an equivalent power of 32 dioptres.

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In trifocals the intermediate lens usually has an addition of 1 dioptre over the distance correction or half of near add.

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The LTF stands for luminance transmission factor when considering tints. 137


Dhaval Patel MD

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Relative spectacle magnification = Actual size corrected with spectacle/size seen by the emmetropic eye

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0.50 Jackson cross cylinder: +0.50DS/-1.00DC at 135

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Lister‘s bulb: in retinoscopy with Pristley Smith mirror

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Porro–Abbe prism: type of reflection prism used in some optical instruments to alter the orientation of an image. It is made from a piece of glass shaped like four right-angled reflecting prisms joined face-to-face in a twisted fashion. Light enters one flat face, is internally reflected four times from the sloping faces of the prism, and exits the second flat face offset from, but in the same direction as the entrance beam.

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Antireflective coatings use destructive interference.

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Total hyperopia = manifest hyperopia (absolute hyperopia + facultative hyperopia) + latent hyperopia. T=MAFL Manifest: Both part of hyperopia that can and cannot be corrected by the power of accommodation Absolute: That part of hyperopia that cannot be corrected by the power of accommodation Facultative: That part of hyperopia that can be corrected by the power of accommodation Latent: That part of hyperopia that can be corrected by the tone of ciliary muscle

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In DO, the optic disc may not be focused as you see it, as hypermetropic patients require more ―plus‖ (green numbers) lenses for clear focus of the fundus while myopia patients require more ―minus‖ (red numbers).

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Direct Ophthalmoscope provides linear magnification of 1x. 138


Dhaval Patel MD

15x is an angular magnification of Direct Ophthalmoscope.

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It has generally accepted that 0.25 diopter difference of refraction causes 0.5% differences in image size.

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Six meters is accepted from practical point of view because most rays from a distance of 6 meter and more are as good as parallel rays.

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The angle of minimum deviation is produced by a prism when light undergoes equal bending at the two faces. When light strikes the prism perpendicular to one of its surfaces (Prentice position), the angle of deviation is greater.



Glass prisms are usually calibrated in the Prentice position, in which one face is perpendicular to the incident light. Plastic prisms and prism bars are usually calibrated with the angle of minimum deviation Frontal position. When measuring strabismus with glass prisms, they must be held in this position to be accurate; that is, glass prisms must be held with one surface perpendicular to the visual axis. Real images are deviated toward the prism base. Virtual images are deviated toward the apex.

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The absolute value of the back vertex power of a meniscus spectacle lens is always greater than that of the front vertex power. Because the focal length measured from the ―rear‖ vertex of a meniscus lens is always shorter than the corresponding ―front‖ focal length, the absolute value of the back vertex power (P = n/f, where n = 1 in air) is always greater than that of the front vertex power. The true power is somewhere between the two.

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The flatter (not steeper) peripheral cornea tends to counteract spherical aberration. The total interval of chromatic aberration in the human eye is approximately 1.25D. Tilting a lens along its horizontal axis induces cylinder of the same (not opposite) sign and along the same axis, as well as sphere of the same sign. Shorter wavelengths of light are refracted more than longer wavelengths. When polychromatic light is focused on the retina (as is the case in emmetropia or proper spectacle correction), blue light is 0.87D anterior to the retina, green light is 0.37D anterior to the retina, and red light is 0.37D posterior to the retina. 139


Dhaval Patel MD



A Maddox line produces two line images of a point light source: a real image that is too close to the eye to be seen, as well as a virtual image running through the light source. The real image is parallel to the cylinders' axes, whereas the virtual image is perpendicular. This is true for all spherocylindrical lenses (even those with no power in one meridian).

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The angular size of the field of view for an observer looking at a plane mirror is independent of the observer's position.

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Hyperacuity is of two types: Stereoacuity and vernier acuity. Vernier acuity refers to the ability of a normal human eye to discriminate between two line segments in the frontal plane separated by as little as 8 seconds of arc (one third the diameter of a cone). Determination of accurate end points with the keratometer, lensometer, and applanation tonometer relies on this degree of spatial discrimination. Normal Stereo Acuity is 10-60 seconds of arc.

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Conjugate planes are related by being the object and image of one another.

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The binocular amplitude of accommodation usually exceeds the monocular amplitude of accommodation.

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Accommodative amplitude decreases with age with the following approximations: 1. Accommodative amplitude at age 40 = 6.0D, at age 44 = 4.5D, and at age 48 = 3.0D. 2. Below age 40, accommodative amplitude increases by 1.0D for every 4 years. 3. Above age 48, accommodative amplitude decreases by 0.5D for every 4 years.

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Cylindrical lenses produce minor monocular distortions caused by differential meridional magnification, which may produce intolerable binocular spatial distortions. The sources of differential meridional magnification can be minimized by: 1. Prescribing in minus cylinder form. 140


Dhaval Patel MD

2. Minimizing vertex distance. 3. Decreasing cylinder power (while maintaining the proper spherical equivalent). 4. Rotating the axis of the correcting cylinder toward 90 or 180 degrees.



Most distortions of aphakic spectacle lenses stem from their position anterior to the pupil and include image magnification, ring scotoma, pincushion distortion, and the so-called jackin-the-box phenomenon. Aphakic spectacle lenses can also create cosmetic problems not only because of their size but also because they can make the patient's eyes look magnified.

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The magnification associated with any corrective lens diminishes as the lens approaches the eye's nodal point.



o

IOL decreases image magnification to <4%

o

20% to 30% with aphakic spectacle correction

o

7% to 12% with aphakic contact lens correction.

At the correct axis, the following are true: 1. The break phenomenon disappears (the intercept and reflex are parallel). 2. The width of the streak is narrowest. 3. The intensity is brightest. 4. Skew motion is no longer observed. Intensity and skew are primarily useful for small astigmatic errors, while break and width are best judged with an enhanced streak. Astigmatic errors of <1.0D do not enhance well, so break and width are not readily appreciable.

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The spherical equivalent is discovered by fogging the eye (adding a lot of plus sphere) to relax accommodation, then adding minus sphere until vision is sharpest. At this point, the circle of least confusion is on the retina. Then, the cross-cylinder is introduced to find axis and power. The circle of least confusion must remain on the retina throughout cross-cylinder testing. When fogged, the circle of least confusion is anterior to the retina. 141


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Dhaval Patel MD

The sphere end point can be verified by the duochrome test, but this test does not relax accommodation. Therefore, the test should be introduced with the patient slightly fogged, such that the letters on the red side are clearer (the red letters will focus behind the green letters, closer to the retina). Then, minus sphere is added until letters on the green and red sides are equally clear.

An emmetropic person sees red and green colors equally sharp. After giving correction patient is asked to read FRIEND. FIN letters are written in green and RED letters are written in red color. If myopia is over corrected or hypermetropia is under corrected patient will appreciate green letters much better than red letters. On the other hand if myopia is under corrected or hypermetropia is over corrected patient will appreciate red color much better. Or simply you can remember, If RED clear, add MINUS If GREEN clear, add PLUS.

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Image jump can occur in any correction whose add does not have its optical center at the top of the segment. Round-top segments typically produce more image jump than flattop segments, as they have much lower optical centers. Image displacement occurs in all corrections as gaze moves away from the optical center of the correcting lens; this is unlikely to be significantly distressing unless an imbalanced displacement occurs, as in anisometropia. The other situation where image displacement is troublesome is when an increased demand is made on already taxed vertical fusional system ability, as in compensated vertical phoria.



Holding the radius of curvature constant, larger diameter lenses are effectively steeper. At a given diameter, radius of curvature and lens steepness is inversely proportional.



If the center of curvature of the refracting surface is on the same side as the medium of higher index of refraction, the surface is positive, regardless of direction of light propagation.

142


Dhaval Patel MD

Candela is the unit of measure of luminous intensity, which is defined as the light emitted per unit of solid angle. Luminous flux is the quantity of light leaving a source or passing through a region of space, and it is measured in lumens. Illuminance is the quantity of light per unit area incident on a surface or at an image, and it is measured in lux. Luminance is the light reflected or emitted by a surface per unit area and per unit solid angle, and it is measured in apostilbs.

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Why vision is 6/6? Two points discriminable as long as they stimulate two separate cones. Width of a foveal cone = 2.5u (30sec angular separation) Individual part of 6/6 letter = 1 min angle at fovea In order to properly represent the peaks and troughs in the intensity profile of a sinewave, there must be at least two cones for each cycle of the grating. This is known as the Nyquist limit.



Types of Visual Acuity 

Minimum visible: Best threshold is 1 sec arc



Minimum resolvable/recognizable: Best threshold 30 sec arc



Minimum discriminable(hyperacuity): Best threshold is 2 sec arc



optical correction of presbyopia can also be achieved with hyperopic [orthokeratology] lenses, bringing the advantages of waking hour visual correction without the need for glasses or contact lenses to a rapidly growing sector of the optical market.

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MRI Prism Glasses: Non-Magnetic Prism Glasses allow the patient to see the room outside the bore of magnet during their scan, allowing a companion or scenic picture to be viewed. A simple and cost effective comfort measure to be used alone, or in conjunction with a sound system for ultimate relaxation in an MR environment. Also known as recumbent spectacles. 143


Dhaval Patel MD



The development of presbyopia is independent of ocular parasympathetic nerve paresis.



Visual acuity is usually better in blue cone monochromatism than rod monochromatism.



Becker's test: A test for astigmatism that uses diagrams of sets of three lines radiating in different meridians.



Retina is most sensitive to yellow light in photopic conditions. In scotopic conditions it is most sensitive to blue light.



The Sloan Letters: 10 letters C, D, H, K, N, O, R, S, V, Z



X notation for magnification:



o

Multiply the amount of magnification by 4 to get the ―Dioptric Power‖ of the lens. Divide the Dioptric power into the number 40 to get the number of inches from the eye.

o

For example, a 4X lens is 16 Diopters. Divide into 40, we get a 2.5" working distance; a 5X lens is 20 Diopters and has a reading distance of 2 inches

Aspheric lenses are lenses which have a relatively flat surface, yet still offer the same vision quality as non aspheric lenses. This is because although the lens is thinner and flatter, it still refracts light to exactly the same degree as a conventional lens. Double aspheric lenses are essentially an even better version of the already useful aspheric lenses. Not only is the front of the lens aspheric, but the back of the lens has the same aspheric design, hence the name, ‗double aspheric‘. Typically, when you look out from the edge of your lenses, the image you see can be distorted. Double aspheric lenses limit this distortion of image right up to the edges of the lens. This is done by ensuring that a large area of the lens is the focal point.

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Photoreceptors: 144


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o

"red" cones (64%), "green" cones (32%), and "blue" cones (2%)

o

The green and red cones are concentrated in the fovea centralis.

o

The "blue" cones have the highest sensitivity and are mostly found outside the fovea, leading to some distinctions in the eye's blue perception.

o

The cones are less sensitive to light than the rods

o

visual acuity or visual resolution is much better with the cones, the rods are better motion sensors

o

Rods Do Not See Red!  The light response of the rods peaks sharply in the blue; they respond very little to red light. 

The ship captain has red instrument lights. Since the rods do not respond to red, the captain can gain full dark-adapted vision with the rods with which to watch for icebergs and other obstacles outside.



Dispersion is the variation of refractive index with wavelength. In general, the shorter the wavelength, the higher the refractive index. For instance, in spectacle crown glass, light of wavelength 656 nm (corresponding to red) has an index of 1.520, whereas light of wavelength 480 nm (corresponding to blue) has an index of 1.531. In the crown glass example, the dispersion is 0.011 (= 1.531 - 1.520).



Light scattering:



o

If light strikes a structure larger than 1000 nm, the light is absorbed.

o

If the structure is less than 1 nm, the light passes by unaffected.

o

However, if the object has a size between 1 and 1000 nm, light will be absorbed and re-emitted as a ray of similar wavelength, but in a different direction.

Magnesium fluoride (MgF2), a durable substance with an index of 1.38 at 550 nm, is the most commonly used coating material for single-layer antireflection coatings. Instead of one reflection at the air-glass interface, there is now a reflection at the air-MgF2 interface and a second reflection at the MgF2-glass interface. These reflections interfere destructively, resulting in a minimum reflectance within the visible spectrum (at normal incidence) of 1.5% or less, as compared with the original 4% for the uncoated glass surface

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

The rods have peak sensitivity at 500 nm that corresponds to blue-green, and the foveal cones have peak sensitivity at 562 nm or in yellow-green. The significance of this shift in sensitivity is that the foveal cones respond more strongly to longer wavelengths where chromatic aberration gradually increases, whereas rods respond more strongly to the region of rapidly increasing chromatic aberration.



When a glassblower or other glass worker heats glass directly in a flame, the flame surrounding the glass emits a yellow light termed sodium flare. Didymium or neodymium glass absorbs this light, which is emitted at approximately 589 nm, making it easier for the glass worker to view his or her work.



Most common mirror coating materials are chromium, aluminum, and copper.



Laser light is mainly absorbed in ocular tissue by three pigments



o

Melanin strongly absorbs all ultraviolet and invisible wavelengths. However, this absorption by melanin decreases with increasing wavelengths.

o

Hemoglobin has strong absorption in the violet (420 nm) and green (514 nm) wavelength. Deoxygenated hemoglobin absorbs red more strongly than does oxyhemoglobin.

o

Xanthophyll which is the pigment most densely distributed in the macular area, absorbs the blue wavelength (460 nm).

Factors that modify color perception o

Brightness (bezold-brücke phenomenon): As brightness increases, most hues appear to change. At low intensities, blue green, green, and yellow green appear greener than they do at high intensities, which make them appear bluer. At low intensities, reds and oranges appear redder, and at high intensities, they appear yellower. The exceptions are a blue of about 478 nm, a green of about 503 nm, and a yellow of about 578 nm. These are the wavelengths of invariant hue.

o

Saturation (abney effect): As white is added to a hue, the hue appears to change slightly in color. The effect is similar to adding yellow. Blue greens become greener and yellow greens become yellower. Reds and oranges also become yellower. The exception is a yellow of 570 nm. 146


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State of dark adaptation (purkinje effect): The relative luminosity curve illustrates the eye's sensitivity to different wavelengths of light. When the eye is light adapted (daytime), yellow, yellow green, and orange appear brighter than do blues, greens, and reds. The cones' peak sensitivity is to light of 555 nm. A relative luminosity curve can also be constructed for the rods in a dark-adapted eye. The lights are so dim that the observer cannot name the various wavelengths used. Rods are most sensitive to light of 505 nm (blue). It has been postulated that rods share the pathways used by blue cones. As the eye dark adapts and rods begin to send messages, more blue messages are sent to the hue center. Therefore, at dusk, although the brightness of all colors decreases, blues and greens appear to gain in relative brightness when compared with yellows and reds. This phenomenon is called the Purkinje effect after the Czechoslovakian scientist Purkinje, who first described it while watching blue and green flowers become relatively brighter (as compared with red and yellow) at dusk.



Power of air filled eye: (-150) D



Eigengrau: (―dark light,‖ retinal ―self-light‖): Complete dark adaptation of the eye does not produce a sensation of absolute black. Instead, a uniform gray with superimposed phosphene-like dots is generally noted. The dots observed in this entoptic phenomenan are more mobile than phosphenes and may form colored patterns that drift about the field.



Troxler fading o

refers to the spontaneous suppression of the visibility of an image that occurs when one stares intently at a point in a scene. After some seconds or even minutes, parts (but not all) of the field will lose contrast and merge into a misty blur. Moving the eyes restores clear vision.

o

Ignaz Paul Vital Troxler 1804

o

E.g: Lilac chasec (card with disappearing dots)



Haag-streit slit lamp decreases binocular viewing angle from 13.5 degrees to 4.5 degrees.



Cornea absorbs rays shorter than 295 nm. Therefore rays between 600 and 295 nm only can reach the crystalline lens. 147


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The normal human eye is insensitive to wavelengths between 400 and 350 nm (ultraviolet rays) because they are absorbed by the crystalline lens of the eye. In aphakic eyes the light rays between 350 and 400 nm can also pass on the retina. Therefore, the Aphakic eyes are sensitivc to those wavelengths which give rise to the sensation of blue or violet colour so the newly aphakic patients often complain that every thing looks bluer than visualized before the operation.



Persistence of the eye is 0.1 second: i.e. if the time interval between two successive light pulses is lesser than 0.1 second, eye cannot distinguish them separately



Raman Effect: The light (or photons) impinging on a molecule interacts in various ways but the final outcome always results in the scattering of light. For example, we do not see light directly. We always see light and objects as a result of scattered light. Scattering is absorbance of incident light used in exciting the atom and reradiation of this light. The Raman scattering is the result of inelastic collisions in which the scattered photons exchange energy with the vibrational energy modes of an atom.



In a toric surface, one principal meridian is more curved than the second principal meridian. The principal meridian with minimum curvature, and therefore with minimum power, is called base curve of a toric lens.



A reduction of 1 mm in the depth of the anterior chamber (through a forward shift of the crystalline lens) would increase the eye's total power by about 1.4 D.



Accommodation in uncorrected myopes is not developed normally. Since they need not accommodate to see the near objects clearly. For this reason they may suffer from convergence insufficiency, exophoria and early presbyopia as they grow older.



Night myopia or twilight myopia: The shift from photopic to scotopic vision at twilight is associated with increased sensitivity to the shorter wavelengths of light. The emmetropic eye, if accommodated for the middle range of the visual spectrum, will be slightly myopic for the shorter wavelengths.

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

Symmetric astigmatism: refers to the regular astigmatism in which the principal meridia in each eye have similar but opposite axes, e.g. 15° in left eye and 165° in right eye which together add up to 180 +- 15°.



Depth of field: the range of distance from the eye in which an object appears clear without change of accommodation.



Depth of Focus: The range at the retina in which an optical image may move without impairment of clarity is termed as depth of focus.



Reaction time: Accommodation: Far to near: 0.64 s Accommodation: Near to Far: 0.56 s Direct light reflex: 0.26 s Convergence response: 0.2 s



Causes of premature presbyopia o

Uncorrected hypermetropia

o

Premature sclerosis of the crystalline lens

o

General debility causing presenile weakness of ciliary muscle

o

Chronic simple glaucoma



Angle of convergence becomes smaller with increasing fixation distance and becomes larger with increasing IPD.



In air, the speed of light remains relatively constant. When the light passes through a higher index of refraction, its properties change and aberrations are formed. This can be explained by the following equation: F = Vn/ λ 149


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F = frequency, V = velocity, n = index of refraction, λ = wavelength.



The waves of light are joined at a single point in time by what is called a wavefront and always travel perpendicular to it. The distorted shape that a wavefront takes after emerging from an irregular optical media is called a wavefront aberration.



A practical example of spherical aberration is the comparison between the optical properties of the +20D trial frame lens and the aspheric indirect binocular ophthalmoscope (IBO) +20D lens. Both lenses focus light coming from infinity to a focal point of 5 centimeters behind the lens. However, when analyzing the quality of the entire image, one can observe a deformity in the periphery of the image formed by the trial frame lens, which is not present with the aspheric lens. The higher the power of a lens, the more the distortion produced by spherical aberration.



Point spread function (PSF) is the intensity with which an optical system distributes an image from a point source onto the retina. The point source is influenced by the pupil size. The larger the pupil, the more irregular the shape of the point source imaged on the retina



Modulation transfer function (MTF): MTF is the ability of the eye's optics to focus a sharp image on the retina with high contrast. As light passes through optical structures of the eye, it undergoes a process of ―degradation‖ which can be measured by MTF.



Optical limitations to vision • Pupil size • Nyquist sampling limit: The spatial frequency of the images entering the eye can be influenced by the pupil size – the wider the pupil, the higher the spatial frequency of an object that can be perceived by the eye. However, the highest spatial frequency that can be detected by the visual system is also limited by the number of photoreceptors densely packed in the fovea also known as the Nyquist Sampling Limit. • Diffraction: a phenomenon which occurs when light waves are bent as they enter an aperture – in the case of the human eye, the pupil. In 1896, the German physicist, Arnold Sommerfeld, defined diffraction as ―any deviation of light rays from a rectilinear path which cannot be interpreted as a reflection or refraction‖. 150


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• Styles-Crawford effect: This is the effect of light entering the cones transversely from the pupil margin, which is perceived half as bright as the light entering the center of the pupil. In simpler terms, light that passes through the edge of the pupil contributes less to image quality than light entering the center of the pupil.



There are two classes of aberrations: chromatic and monochromatic. Theoretically, correcting both chromatic and monochromatic aberrations increases the contrast of images focused on the retina (contrast sensitivity). o

o

Chromatic aberrations 

also known as ―achromatism‖



inability of a lens to focus all colors of light on a single point.



arises because the index of refraction of the media is not the same for all wavelengths.

Monochromatic aberrations 

defects of an image caused by the nature of a lens



Types:

1. Piston 2. Tilt 3. Defocus 4. Spherical aberration 5. Coma 6. Astigmatism



Wavefront sensing devices 1. Shack–Hartmann 2. Tscherning aberrometer 3. Laser ray tracing 4. Slit skiascopy 151


Dhaval Patel MD



The main focus of laser refractive surgery nowadays is to not only correct refractive errors such as defocus and astigmatism, but to create customized ablations which compensate for induced higher-order aberrations (HOA) such as spherical aberration (optimized ablation) and also correct pre-existing aberrations (customized ablation).



Visual effects of aberrations o

Glare

o

Starbursts

o

Haloes

o

Ghost images

o

Poor image contrast

o

Poor night vision



The term ―aberrometry‖ is used to describe the science of the detection and analysis of wavefront aberrations.



optical path length (OPL) is defined by the number of oscillations of these light waves from a point source of light, traveling through a media of x index of refraction at any given length.



The tear film contributes to up to 70% to the corneal refractive power. Dry eyes, for example, have greater coma and spherical aberrations compared to non-dry eyes.



With an increasing market and demand for super sharp vision (i.e. ―super-vision‖), scientists have worked hard at making this technology clinically available in many different forms. There are two types of wavefront customized ablations: wavefront guided ablations (WGA) and wavefront optimized ablations (WOA). o

Both types of treatment aim to correct for HOAs in the eye. In WGA, the treatment is aimed to correct the pre-operative HOAs, while in WOA, the treatment attempts to reduce HOAs generated during surgery. The WOA profile corrects expected HOAs 152


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for an average eye, and those that are anticipated as a result of the surgery. This means that an eye with higher than normal HOAs, will end up with near equally high HOAs after treatment in WOA. o

Excimer lasers used to treat wavefront-customized ablations typically use a smalldiameter and circular flying spot laser.

o

Ophthonix, Inc. (Vista, CA), has designed a lens available for commercial use, which consists of a three-layer structure with a refractive index of 1.6. The middle layer consists of a patented photo-polymer in between two coated lenses. The lens corrects HOAs from the 2nd to 6th order using wavefront guided technology. The company's aberrometer measures both lower- and higher-order aberrations using the ―Talbot‖ effect.

o

To compensate for positive spherical aberration, aspheric IOLs were designed and are commercially available, such as the Tecnis-Z9000 (Pfizer, New York, NY) and SN60WF (Alcon, Fort Worth, TX). These lenses are designed with a prolate anterior surface, hence the term aspheric, and have the same radius of curvature at every point on the surface.



Larsen noted that the axial length of the neonate's eye was 17 mm and that it increases 25 percent by the time the child reaches adolescence.



Neonate's visual appreciation for fine detail at birth is one-thirtieth (2/60) or approximately 3 percent & by the age of 12 months, the infant's level of visual acuity is 25 percent (20/80).



Most cases of myopia have an elongated eye. The stretching and weakening of the sclera seems to depend on two major factors.



o

First, that the intraocular pressure maintains a constant force on the sclera.

o

Second, there is digestion of sclera architecture (collagen I fibers and extracellular matrix) by metalloproteinase enzymes.

The coordination of the power of the cornea, crystalline lens, and axial length to process a sharp retinal image of a distant object is known as emmetropization.

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

The cornea, which averages 48 diopters of power at birth and has an increased elasticity, loses about 4 diopters by the time the child is 2 years of age. One may assume that the spurt in growth of the sagittal diameter of the globe during this period pulls the cornea into a flatter curvature. The fact that the average corneal diameter is 8.5 mm at 34 weeks of gestation, 9 mm at 36 weeks, 9.5 mm at term, and about 11 mm in the adult eye supports this ―pulling, flattening‖ hypothesis.



The crystalline lens, which averages 45 diopters during infancy, loses about 20 diopters of power by age 6 years. To compensate for this loss of lens power, the axial length increases by 5–6 mm in that same time frame. (In general, 1 mm of change in axial length correlates with a 3-diopter change in refractive power of the eye.)



Specifically, the size of the retinal image depends on an entity known as the nodal distance, which averages 11.7 mm in the newborn and 16.7 mm in the adult emmetropic schematic eye, giving a ratio of adult to infant retinal images of 1.43.



A partial list of giants of physiologic optics who have created schematic or reduced eyes includes Listing, Helmholtz, Wüllner, Tserning, Matthiessen, Gullstrand, Legrand, Ivanoff, and Emsley.



Significant amount of astigmatism develops in 56 percent of the infants. The transient astigmatism just described tends to elongate tiny dots of the retinal image into lines. In essence, these create the equivalent of a line drawing of the retinal image.



Line orientation receptors o

In many infants the amount of astigmatism can rise to a level of greater than 2 diopters in the first year of life. The orientation of the distortion is usually horizontal (180 degrees) initially. In the course of the next 2 years, the meridian of distortion rotates to the vertical and the amount of the astigmatism diminishes. This slow rotation of the axis of exaggeration can help activate different groups of brain cells, which become sensitive to features in the retinal image with different tilts.

o

Drs. Hubel and Wiesel were awarded the Nobel Prize for Medicine in 1981.

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Role of the cornea o

most powerful focusing element

o

Miller & Benedek proved that if the spaces consisting of glycosaminoglycan and the size of the collagen fibers were smaller than one-half a wavelength of visible light, the cornea is clear, even if the fibers were arranged randomly. An orderly arrangement of the fibers also helps maintain corneal transparency.

Role of the crystalline lens o

50 percent protein solution is cloudy

o

large protein molecules known as crystallins (large protein molecules ranging in size from 45 to 2000 kD) seem to repel each other



Because the index of refraction of water is greater than air, objects underwater appear about one-third closer and thus one-third larger than they would in air (i.e. magnification = 1.33×)



The act of accommodation is fast, taking only about one-third of a second.



Parenthetically, the cornea of many birds, from pigeons to hawks, can change shape to accommodate. The avian cornea does not change flexibility with age; therefore these birds do not become presbyopic. However, there is no ―free lunch‖ in nature. The human lens, sitting within the eye surrounded by protective fluid is far less vulnerable to injury than the cornea.



Role of the retina o

The bird retina does not have blood vessels. The human retina has retinal blood vessels that cover some of the retinal receptors and produce fine angioscotomas. A bird's retina obtains much of its oxygen and nutritive supply from a tangle of blood vessels (the pectin), which is covered with black pigment and sits in the vitreous in front of the retina and above the macula (so as to function as a visor).

o

Probably the earliest chemical relative of rhodopsin is to be found in a primitive purple-colored bacteria called Holobacterium halobium. Only one quanta (the smallest possible amount of light) of visible light is needed to trigger the molecule. 155


Dhaval Patel MD

o

The fovea itself subtends an arc of about 0.3 degree.

o

distance between the centers of these tightly packed cones is about 2 µm. The cone diameters themselves measure about 1.5 µm (a dimension comparable to three wavelengths of green light) and are separated by about 0.5 µm.

o

One minute of arc is the spacing between the bars of a 20/20 symbol. Interestingly, the sizing of the symbol was originally determined empirically.



chart luminance between 80 and 320 cd/m2 meet such criteria (160 cd/m2 is a favorite level of illumination).



Clean printed charts using black characters on a white background usually have a character-to-background luminance contrast ratio between 1/20 and 1/33. For projected charts, the contrast ratio drops to a range of 1/5 to 1/10.



A patient happy with his or her vision but with visual acuity worse than 20/20 has been described as a ―20/happy‖ patient. With physical evaluation alone it may not be possible to diagnose such ―happiness,‖ but subjective tests such as a quality of life questionnaire may help identify it.



Contrast may be considered as the difference in the luminance of a target against the background: photometer to measure the luminance of a target against the background. For example, a background of 100 units of light and a target of 50 units of light yields the following. A young, healthy subject may have a contrast threshold of 1 percent, or 1/100 (i.e. a contrast sensitivity of 100) In the visual psychology literature, the contrast threshold is described in logarithmic terms. Therefore a contrast sensitivity of 10 is 1, a contrast sensitivity of 100 is 2, and a contrast sensitivity of 1000 is 3.



When a transparent structure loses its clarity, the physicist describes it as a light scatterer rather than a light transmitter. 156


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o

The word opaqueness conjures up the image of a cement wall that stops light.

o

most cataracts scatter light rather than stop light, the most graphic involves the science of holography.

o

LeClaire et al observed that many patients with cataracts showed good visual acuity but had poor contrast sensitivity in the face of a glare source.

o

first clinical glare tester – the Miller–Nadler glare tester:

Clinical conditions affecting glare and contrast sensitivity o

Corneal edema: The stroma may increase in thickness by up to 30 percent before the epithelium becomes edematous.

o

Patients with significant corneal astigmatism who wear thin soft contact lenses experience blur that affects their contrast sensitivity.

o

Contrast sensitivity or glare testing may also be useful in detecting the earliest signs of graft rejection.



The lens of a typical 20-year-old absorbs about 30 percent of incident blue light. At age 60, the typical lens absorbs about 60 percent of incident blue light.



a yellow pigment effectively absorbs or scatters away most of these harmful wavelengths, thus diminishing the potential damage to the macula.



Vernier acuity: there is a visual task (Vernier acuity), which has a threshold of about 5 seconds of arc (1/12th of a minute of arc)



Some human studies have shown that use of atropine drops in children partially inhibits the development of myopia. Human use of topical pirenzepine was reported in two studies which showed a small but statistically significant reduction in myopia and axial length.

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

Tyndall effect, also known as Tyndall scattering, longer-wavelength light is more transmitted while the shorter-wavelength light is more reflected via scattering.



Rayleigh scattering, in that the intensity of the scattered light depends on the fourth power of the frequency, so blue light is scattered much more strongly than red light



A lens free from distortion exhibits orthoscopy (or no distortion). The excess minification in the periphery of minus lenses generally produces barrel distortion, while the excess magnification of plus lenses generally produces pin-cushion distortion



Vogel‘s formula for selecting base curve: For plus lens, Base curve = SE + 6 For minus lens, Base curve = (SE +6) /2



In Pelli–Robson contrast sensitivity letter chart, there is decreasing contrast of 0.15 log units for groups of three letters.



There are 400 smaller 5 mm squares in AMSLER GRID and when viewed at about one-third of a metre, each small square subtends an angle of 1°.



For FAF, a pre-injection study is performed with both the excitation and barrier filters in place.



Pseudoisochromatic plates: falsely or apparently isochromatic; plates that appear isochromatic to individuals with color-vision abnormality but they are not isochromatic in real.



Antimetropia: hypermetropia in one eye and myopia in other eye.

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

Optics of corrected Aphakes is like Galilean telescope and so image is magnified, while optics of overcorrected myopes if like Reverse Galilean telescope and hence the image is minified.



Phi Phenomenon: optical illusion of perceiving continuous motion between separate objects viewed rapidly in succession. The phenomenon was defined by Max Wertheimer in the Gestalt psychology in 1912 and along with persistence of vision formed a part of the base of the theory of cinema, applied by Hugo Münsterberg in 1916.



Jackson cross cylinder (JCC): o

To define the astigmatic axis: the handle of the lens parallel to the axis

o

To define the astigmatic power: the handle is 45 degrees to the axis.

o

Define the axis before the power



Maddox rods are cylinders of high plus power. Light is focused very close to the rods forming real image (too close to actually see); and a virtual image perpendicular to these lights is visible at some distance.



In direct ophthalmoscope, field of vision is always smaller than field of illumination. (D: I>V) In INDIRECT ophthalmoscope, field of vision is always larger than field of illumination. (I: V>I)



In near vision jaeger chart, one point is equal to 1/72 of an inch.



A person who did not receive optical correction for severe astigmatic refractive error in childhood sometimes shows persistent impairment of corrected vision that is confined to the more ametropic meridians. This phenomenon is known as meridional amblyopia.

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

Polaroid is made of an extremely thin layer of many fine crystals of iodine and quinine sulfate. This compound, known as herapathite, after its discoverer W.B. Herapath, is unique in that it strongly absorbs one of its double-refracted beams so that light vibrating in only one direction gets through.



Weber's law: for a difference to be detectable, that is, to exhibit a just noticeable difference, it must be a nearly constant fraction of the background luminance, or /\L/L = constant. This ratio is about 1% for brightness discrimination and was extended it to other senses



Drop-ball test: o

To be considered impact resistant, a lens must pass the dress ophthalmic lens dropball test.

o

lens must be able to withstand the impact of a 5/8-inch (15.875-mm) steel ball dropped from a height of 50 inches (1.27 m) onto the lens front surface.

o

The FDA-mandated drop-ball test results in an impact energy of 0.2 joules (J) or 0.15 foot-pounds (ft-lb) on the lens front surface. Many simple accidents and sports missiles result in energies that exceed this value by anywhere from 2 to 100 times.



Cornea 

The cornea of the body‘s highest densities of nerve endings; and the sensitivity of the cornea is 100 times that of conjunctiva. Thus cornea is MOST sensitive structure in the body and BRAIN is the LEAST sensitive structure in the body..!!

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Fungal hypopyon has convex upper border, hyphae seen, low mobility with head posture and yellow in color. Bacterial hypopyon has a concave border, mobile with head posture, no hyphae seen and whitish in color.



Most abundant GAG in cornea: keratin sulfate 65%



Cornea is Meniscus Lens. (Convex Concave). It‘s minus meniscus lens. But in the body is acts as converging lens i.e. plus lens. If in vitro, it will act as real minus meniscus lens i.e. diverging lens. Plus Meniscus: Steep anterior, Flat posterior converging Minus Meniscus: Flat anterior, Steep anterior  divergent



Prolate: (eg. Egg on its Tip) Steeper front, flat side  causes positive spherical abberations. (CORNEA is prolate) Oblate: (eg. Egg on its Side) Flat front, steep side.  causes negative spherical abberations.



Cornea has positive spherical aberrations. Lens has negative spherical abberations.



In placido based topography, central point cannot be measured this is in contrast to Scheimpflug imaging which measures central point most accurately.



Identifying Ectasia on pentacam: Elevation on anterior float: 12-15 um suspicious, >15 um abnormal Elevation on posterior float: 17-20 um suspicious, >20 um abnormal



After placing INTACS, cornea becomes more prolate.

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Keratitis with lid lesions: zoster, chickenpox, molluscum contagiosum, and ulcerative blepharitis with keratitis caused by staphylococcal infection. Keratitis without lid lesions: vaccinia, adenoviral infections (types 3, 7, and 8 and 19), chlamydial infections, herpes zoster and Epstein-Barr keratitis.



Papillae in lower fornix are generally not found in vernal conjunctivitis.



Common causes of DLK are: Meibomitis, bacterial endotoxin, marker ink, microkeratome blade debris, preservatives in drops, interface hemoglobin.



Important complication of trachoma is dry eye due to fibrosis of the upper fornix affecting accessory lacrimal glands.



In angular conjunctivitis caused by Moraxella axenfield diplo bacillus, maceration of skin is due to proteolytic enzymes secreted by the bacillus.



The cornea magnifies the image of iris by 10%.



Hirschberg‘s sign: Pale round spots (Koplik spots) on conjunctiva and caruncle in measles



Basal tear secretion = 2 μL/min



Keratinization of the caruncle is a common early sign of mucous membrane pemphigoid.



In GPC, In contrast to VKC, keratopathy is rare due to less secretion of toxic cytokines. 162


Dhaval Patel MD



In SJS, contrast to ocular pemphigoid, immunosuppression is not required prior to conjunctival or lid surgery.



In PUK, Unlike Mooren ulcer the process may also extend to involve the sclera.



Rizutti‘s sign: Triangle of light on iris from oblique penlight beam focused by cone in keratoconus



In Thygeson superficial punctate keratitis, conjunctiva is uninvolved and vascularization is not a feature. The most common differential diagnosis is staphylococcal hypersensitivity, punctate epitheliopathy or adenoviral keratitis.



Central cloudy dystrophy of François is similar to crocodile shagreen but is differentiated by its posterior location and AD inheritance.



Kayes‘ dots: Subepithelial infiltrates in corneal allograft rejection



Khodadoust line: Corneal graft endothelial rejection line composed of inflammatory cells



Deficiency of the mucin layer may be a feature of both aqueous deficiency and evaporative states. Goblet cell loss is associated with cicatrizing conjunctivitis, vitamin A deficiency, chemical burns and toxicity to medications.



Follicles are usually seen in viral and chlamydial Conjunctivitis. F-VC Trachoma Acute follicular conjunctivitis 163


Dhaval Patel MD

Chronic follicular conjunctivitis Benign (School) folliculosis

Papillae are usually seen in allergic and bacterial conjunctivitis. P-AB Trachoma Spring catarrh Allergic conjunctivitis Giant papillary conjunctivitis



Epithelial downgrowth has been reported most commonly as a complication of cataract surgery, but it can occur after penetrating keratoplasty, glaucoma surgery, penetrating trauma, and partial removal of epithelial cysts of the anterior segment. Irradiation and photocoagulation have been abandoned as ineffective. Excision of involved iris tissue with cryotherapy to remaining corneal membranes is currently the best technique, although good vision is maintained in only a few cases. Prevention is much more effective than the treatment of established disease.



Keratoconus is rare in diabetes. Diabetes, Aging and Smoking increases corneal collagen cross linking just like C3R.



Membrane on conjunctiva: o

o

True membrane: 

Greyish white dense membrane covering both the bulbar and palpebral conjunctiva



Densely adherent, bleeds on attempting to remove



Corynebacterium Diphtheria

Pseudo membrane:

164


Dhaval Patel MD



Whitish membrane, not as dense, irregularly covering bulbar and palpebral conjuoctiva.



Not as densely adherent, comes off comparatively easily



Streptococcus pyogenes



Infectious Crystalline Keratopathy ICK is most commonly seen after  post keratoplasty.



MCC of ICK is streptococcus viridans.



The corneal endothelium and stroma are derived from the neural crest, but the epithelium is derived from surface ectoderm.



Keratoconus is typically associated with Marfan's syndrome. Keratoglobus is typically associated with Ehlers-Danlos syndrome.



In congenital hereditary stromal dystrophy, the cloudy stroma is of normal thickness, and the epithelium is normal. In congenital heriditary endothelial dystrophy (CHED), there is epithelial edema and a thickened stroma. In both conditions, intraocular pressure (IOP) is usually normal.



Arcus senilis shows deposition of lipid in all layers of cornea.



The limbal lesions in vernal keratoconjunctivitis are more papilliform because they have a central vascular core. When a central pit full of degenerated eosinophils forms, the term Horner-Trantas dot is applied.



Horner-Trantas dots are clumps of degenerated eosinophils, whereas Herbert's pits are depressed, necrotic follicles at the limbus. 165


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Dhaval Patel MD

Small changes in corneal shape do occur throughout life: o

In infancy, the cornea is fairly spherical

o

In childhood and adolescence, probably due to eyelid pressure on a young tissue, cornea becomes slightly astigmatic with the-rule (WTR)

o

In the middle age, cornea tends to recover its sphericity

o

Late in life, against-the-rule (ATR) astigmatism tends to develop.



Unlike Scheimpflug based topographers, Placido-based topographers measure angle kappa.



The cornea transmits radiation from approximately 310 nm in the ultraviolet to 2500 nm in the infrared region. The cornea is extremely sensitive to UV radiation at 270 nm and corneal absorption of this radiation results in photo keratitis after exposure to welding arcs.



Conjunctival papillae form whenever there is conjunctival swelling of any cause in certain areas. The tarsal and limbal conjunctiva is unique because their subepithelial substantia propria contains fibrous tissue septa that interconnect to form polygonal lobules with a central vascular bundle. Any inflammation in these regions will result in papillae. Papillae <1 mm in diameter are entirely nonspecific. When papillae are >1 mm in diameter (giant papillae), they are more specific. Most young people with healthy eyes will have small conjunctival papillae along the superior margin of the upper tarsus



Conjunctival follicles represent focal lymphoid aggregates in the substantia propria.



In GPC, the inferior fornix is generally the least involved, whereas in viral conjunctivitis, it tends to be the most severely involved.

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Dhaval Patel MD

Follicular conjunctivitides are typically more severe inferiorly than superiorly except for trachoma. This is in stark contrast to inclusion conjunctivitis, another chlamydial disease, which is more severe inferiorly.



Neonatal inclusion conjunctivitis may be pseudomembranous or membranous, but this is rare in adults.



Typical microcystic corneal epithelial edema is in the intercellular space and results from an imbalance between corneal turgescence (swelling due to intraocular pressure [IOP]) and deturgescence (drying due to endothelial pumping). Intracellular epithelial edema does occur, as a result of epithelial hypoxia, but this appears different clinically— as a fine, frosted-glass appearance (Sattler's veil), generally associated with contact lens use.



Sattler‘s veil: Superficial corneal edema (bedewing) caused by hypoxia (contact lens)



Development of corneal epithelial filaments—increased mucus production along with increased, deranged epithelial turnover. The filaments themselves are composed of mucus and desquamated epithelial cells.



KPs: Lymphocytes & PMNs Mutton-fat KPs: Macrophages, greasy look



Endophthalmitis rates are higher with laser-assisted in situ keratomileusis (LASIK) than with photorefractive keratectomy (PRK). LASIK does offer a reduced incidence of stromal haze and more rapid epithelial healing. Photorefractive keratectomy (PRK) can have significant postoperative pain. PRK offers a reduced incidence of endophthalmitis and corneal perforation.

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Dhaval Patel MD

fluorescent treponemal antibody-absorption (FTA-ABS) and microhemagglutination of Treponema pallidum (MHA-TP), are the closest to a ―gold standard‖ for syphilis testing. The Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR) tests reflect treponemal infection and revert to normal when treated. The value of these tests is primarily to monitor response to treatment because they are less sensitive and specific. The fluorescent treponemal antibody (FTA) and microhemagglutination of Treponema pallidum (MHA-TP) offer greater sensitivity and specificity and do not normalize with treatment. They are lifelong markers of previous or active treponemal infection.



Fusarium has septate hyphae, whereas Mucor has nonseptate hyphae.



Intranuclear inclusion bodies of herpes simplex virus (HSV) epithelial infection: Lipschütz bodies (Papanicolaou (Pap) smear)



multinucleated giant cells seen in epithelial herpes simplex virus (HSV) infection: Tzanck prep (Giemsa stain)



A granulomatous reaction to Descemet's membrane (including multinucleated giant cells) is most frequently seen with disciform keratitis with a history of herpes simplex or herpes zoster keratitis. This peculiar reaction to Descemet's membrane may be related to an altered antigenicity of the membrane and subsequent development of an autosensitivity reaction. This reaction is very uncommon with other etiologic agents.



There are five anti-Epstein-Barr virus (EBV) antibodies: 1. viral capsid antigen (VCA)-IgG 2. VCA-IgM 3. early antigen-diffuse (EA-D) 4. EA-R (early antigen-restricted) 5. Epstein-Barr nuclear antigen (EBNA) Only EBNA does not peak in the first 6 to 8 weeks of infection. 168


Dhaval Patel MD

Viral capsid antigen (VCA)-IgG and Epstein-Barr nuclear antigen (EBNA) provide lifelong evidence of Epstein-Barr virus (EBV) infection.



Like bacteria (and unlike viruses), chlamydiae have both DNA and RNA, replicate by binary fission, have lipopolysaccharide cell walls, and respond to certain antibiotics. Unlike bacteria, chlamydiae do not possess all organelles and require a host cell for replication.



Difficult to culture: lyme dz, chlamydia, acanthameba



Double walled cyst appearance: acanthameaba



In neonatal inclusion conjunctivitis, the likelihood of finding cytoplasmic or intranuclear inclusions is higher than adult one.



Acyclovir is activated by viral thymidine kinase and is relatively nontoxic to mammalian cells. Trifluridine (Viroptic) inhibits another virus-specific enzyme, thymidylate synthetase.



Acyclovir is not effective against CMV.



presumed filamentous keratomycosis: topical natamycin TOC



Amphotericin has less predictable activity against filamentous species than natamycin.



polyene class: renal toxicity (POLY-uria) imidazole: hepatic (ICTerus)



Suspensions must be shaken to be effective. Acetate preparations (suspensions) are more potent than phosphate preparations. 169


Dhaval Patel MD



Local steroids do not reactivate latent virus, but caution should be exercised because intermittent shedding of the virus from the trigeminal ganglion (unrelated to steroid use) may coincide with steroid use and exacerbate subsequent disease.



Pedunculated conjunctival papillomas are generally associated with human papilloma virus (HPV) types 6 and 8. sessile conjunctival papillomas are associated with HPV-16 and HPV-18.



Blephroconjunctivits: Collarettes indicate Staphylococcus. Scurf indicates seborrhea. Sleeving of the lashes is a sign of Demodex infestation.



The most common cause of phlyctenulosis is Staphylococcus, followed by active or latent tuberculosis.



Neisseria gonorrhoeae is the only bacterial conjunctivitis that causes preauricular adenopathy.



Gonococcal conjunctivitis: ceftriaxone 1 g intramuscularly daily for 5 days and doxycycline orally twice daily for 3 weeks. Doxycycline (or tetracycline) is added to treat potential chlamydial infection (sexually transmitted diseases tend to run together).



Although neonatal inclusion conjunctivitis usually responds to topical therapy, systemic erythromycin is recommended because of associated chlamydial infections, such as otitis media and pneumonitis.



Topical antihistamines do not work well in atopic keratoconjunctivitis; systemic antihistamines are critical for its control. 170




SAC & VKC: SAC response to topical antihistamines & has giant papillae



Type 2 herpes usually resides latently in spinal ganglia.

Dhaval Patel MD

Type 1 herpes: The gasserian (or trigeminal) ganglion, located in Meckel's cave, contains the cell bodies of the trigeminal nerve.



Wessely's ring: circular, superficial distribution of neutrophils around an area of corneal edema or inflammation. It is identical to the immunoprecipitate formed in the Ouchterlony gel.



Topical steroids in disciform keratitis: 1. the visual axis must be involved 2. neovascularization must be progressing



Reactivation and not Reinfection has been reported to lead to typical herpes zoster ophthalmicus (HZO).



Postherpetic neuralgia: oral TCA & Steroids (7 to 10 days after eruption of active dermatitis)



Herpes zoster ―dendrites‖ (pseudodendrites) are typically smaller and less branching than their simplex counterparts.



Cogan's syndrome is frequently associated with polyarteritis nodosa.



About one half of patients with superior limbic keratoconjunctivitis (SLK) have some form of thyroid disease. 171


Dhaval Patel MD

Treatment of the thyroid disorder, however, has little effect on the SLK. A recent study suggests that orbital decompression for thyroid optic neuropathy is required more frequently in patients with thyroidassociated SLK. steroids are not effective therapy for superior limbic keratoconjunctivitis (SLK). Surgical resection of the superior bulbar conjunctiva is definitive.



Episcleritis rarely progresses to scleritis; however, episcleritis nearly always accompanies scleritis. o

Generally, episcleritis causes minimal pain, whereas scleritis is moderately to severely painful.

o

Episcleritis is usually of rapid onset as opposed to scleritis, which is usually gradual, over days.

o

In scleritis, the scleral (deep episcleral) plexus is immobile and bluish-red in color; episcleritis appears salmon pink.

o

Scleral vessels do not blanch with phenylephrine, as do those in episcleritis.

o

Lastly, scleritis is frequently seen with systemic connective tissue disorders; this is not true of episcleritis.



Posterior uveitis occurs in virtually all patients with posterior scleritis and is not uncommon in patients with anterior scleritis. Anterior uveitis occurs in about one third of all patients with scleritis.



Chronic dacryoadenitis is sometimes accompanied by inflammation and swelling of the salivary glands, which is referred to as ―Mikulicz's syndrome.‖



Silent dacryocystitis is usually produced by Streptococcus pneumoniae and may present with no clinical symptoms other than occasional epiphora.



Eyes without any astigmatism will not have any wavefront aberration. Wavefront analysis is used to analyze irregular astigmatism. 172




Dhaval Patel MD

Munnerlyn's formula: The ablation depth (in microns) is equal to the diopters of myopia divided by 3 and multiplied by the square of the optical zone (in millimeters). It is most useful with low amounts of correction (<7 diopters). Sometimes, 15 microns ablation per diopter of myopia is taken.



Natamycin is a polyene antifungal that is the drug of choice for filamentous fungi. Topical miconazole is the drug of choice for Paecilomyces lilacinus. Topical amphotericin is used to combat infections caused by Aspergillus and Candida spp. Flucytosine is used as an adjunctive agent for treatment of Candida spp.



Cornea verticillata: amiodarone, chlorpromazine, chloroquine, indomethacin, meperidine, and tamoxifen.



Kayser-Fleischer ring: Wilson's disease, primary biliary cirrhosis, chronic hepatitis, or progressive intrahepatic cholestasis of childhood, but only patients with Wilson's disease will show neurologic findings. KF ring will disappear with appropriate treatment, thereby providing a means to monitor therapy.



Spheroidal degeneration involves proteinaceous deposits (not lipid) in the superficial stroma.



In PMD, protrusion of the cornea above the area of maximal thinning inferiorly in the cornea, whereas in keratoconus, corneal protrusion is at the point of maximal thinning.



CHED: Nystagmus is associated with the recessive, but not the dominant form of the disease.

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Dhaval Patel MD



CHSD is a rare, autosomal dominant condition presenting at birth as a central, anterior stromal feathery opacity that may cause reduced visual acuity. The corneal periphery is clear. There is no pain, photophobia, or tearing because IOP is normal.



Dystrophies at birth-natal age groups: CHED, PPCD and CHSD. PPCD may be differentiated from CHED by the presence of other anterior segment abnormalities such as endothelial vesicles and bands, a characteristic endothelial pattern on specular microscopy (if possible), and bridging synechiae in the patient or family. In CHSD the corneal opacification appears as full-thickness, feathery clouding of the stroma with a normal corneal thickness. In addition, the histopathology in CHSD shows a normal epithelium, Bowman's layer, endothelium, and Descemet's membrane. The stroma consists of tightly packed lamellae with rigidly ordered small-diameter collagen fibrils alternating with loosely aligned and haphazardly arranged larger-diameter collagen fibrils, distinctive for CHSD.



Harboyan syndrome (CHED 2 and perceptive deafness (CDPD)) is an autosomal recessive disease mapped at overlapping loci 20p13.



The most common stromal dystrophy is lattice, followed by granular and macular.



Recurrence in the graft is common in both Reis-Bucklers' dystrophy and lattice dystrophy.



Patients with Fuchs' endothelial dystrophy have malfunctioning Na-K ATPase pumps in the lateral cell wall of the endothelial cells. This diminished pump function results in swelling of the corneal stroma. Cytochrome oxidase is also reduced, which may indicate a decrease in the metabolic activity of the endothelial mitochondria.



Coroneo Effect: Nasal segment of cornea gets highest UV exposure effect which is responsible for pterygium.



Most serious ACID INJURY is hydrofluoric acid & MC is sulfuric acid. (Survey ophth) 174


Dhaval Patel MD



Most serious ALKALI INJURY is ammonia/ lye & MC is Lime. (Survey ophth)



precipitation of ciprofloxacin onto the corneal surface do occur. Not with other FQ.



Thygeson's superficial punctate keratitis: HLA-DR3 have a 5.65 greater relative risk.



A number of features are shared between dendritic infection from HSV and HZV. Both may have an accompanying skin rash (along a dermatome in HZV) and corneal anesthesia. The active viral replication causes sloughing of epithelial cells in HSV, whereas in HZV, the epithelial cells are swollen and heaped up. Both conditions may recur. Iritis and elevation in IOP can be found with both viral infections; however, iris atrophy is more common with HZV.



Herpes: intranuclear inclusion bodies (Lipschütz bodies or Cowdry type A inclusions). Chlamydia: Intracytoplasmic inclusions.



interstitial keratitis o

bilateral: Congenital syphilis

o

unilateral: Tuberculosis, herpes simplex, and acquired syphilis

o

Cogan's syndrome affects middle-aged adults with hearing loss, vertigo, and interstitial keratitis.



thinnest paracentral quadrants of cornea (in descending order) are the temporal (28%), inferior (19%), nasal (11%), and superior (4%). TINS



Pingueculae: ultraviolet light, changes in the subepithelial collagen. Although these fibers stain with some elastin stains, the fibers are not true elastin and will not be degraded by elastase. This finding is known as ―elastosis.‖

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Dhaval Patel MD



Epithelial downgrowth is usually more aggressive than fibrous downgrowth.



Agents that have been used for Acanthamoeba include- neomycin, natamycin, miconazole, propamidine, dibromopropamidine, polyhexamethylene biguanide, and chlorhexidine.



Oval graft with the long axis at 90° produces against-the-rule astigmatism (and therefore neutralizes with-the-rule astigmatism common to circular grafts).



Rapid onset of corneal stromal opacity following episcleritis  sclero-keratitis.



Epikeratoprosthesis (forerunner of epikeratoplasty techniques): used in Aphakic bullous keratopathy-it relieves pain and improves vision. Complications are Stromal vascularisation, infection, growth of epithelium beneath lens causing it to become dislodged.



Coats‘ ring: White granular corneal stromal opacity containing iron from previous metallic foreign body



Although keratitis is not universal in patients with herpes simplex virus (HSV) uveitis, it is usually present in affected children.



More than 50% of uveitis in the pediatric population has a posterior component.



The brain and retina (a part of the brain) are the sites where Toxoplasma organisms survive best.



TBUT should be done first as a Schirmers would create an artificial dry spot to appear at the point of its contact with the eye, thus falsely reducing the TBUT.

176


Dhaval Patel MD

Schirmer's test: Schirmer's II (with anesthesia) has been purported to measure ‗basal‘ tear secretion, i.e. nonstimulated tears. Values below 5.5 mm of wetting are diagnostic of aqueous tear deficiency. A Schirmer's I (without anesthesia) has become the generally accepted method for assessing aqueous tear production. It measures both basal and reflex tear secretion. REMEMBER this by test 1 measures 2 things and vice versa. Test 3 is with nasal irritation.



Systemic conditions associated with posterior scleritis are: rheumatoid arthritis, Ankylosing Spondylitis, Reiter's syndrome, polyarteritis nodosa and systemic lupus erythematosis.



In case of GPC, in vernal catarrh the reaction is IgE mediated and in Giant papillary conjunctivitis the reaction is type 1 or type 4 hypersensitivity reaction.



Recurrence of corneal dystrophy: Reis-Bückler > macular > granular > lattice



Corneal dystrophy associated with glaucoma: PPCD



TC- 199 = tissue culture medium 199



Riboflavin is hydrophilic solution so during C3R, ideally epithelium should be removed.



The Athens Protocol: The management of keratoconus and post-LASIK ectasia by means of combined, same-day, topography-guided partial PRK and collagen cross-linking.



The excimer laser was originally applied to the cornea to produce more accurate RK incisions, not for surface ablation or laser in situ keratomileusis (LASIK), for which the excimer laser is now used. 177


Dhaval Patel MD



Arcuate keratotomy differs from LRIs by its midperipheral location and its greater relative depth.



Studies have demonstrated that up to 15° of cyclotorsion can occur when patients move from an upright to a supine position.



Ligneous conjunctivitis is actually a genetic disease. It results from homozygous mutations in the PLG gene (6q26) that codes for plasminogen and therefore is inherited in an autosomal recessive pattern. Tears contain plasminogen activators that convert plasminogen into the fibrinolytic enzyme plasmin which normally clears conjunctival and corneal fibrin deposits. The lack of normal plasminogen allows fibrin to accumulate on all mucosal surfaces.



Pingecula are histologically ACTINIC ELASTOSIS.



Concretions are collection of inspissated protein within the pseudoglands of henle.



Most accurate method for RSBT measurement: intraoperative measurement after creating flap by UBM.



Corneal infection with bloody looking perfotation  Moraxella



McCoy cell culture is highly specific for TRIC.



Tobramycin is better than gentamycin only in pseudomonas, but as pseudomonas is one of the infections we should worry about, we start generally tobramycin instead gentamycin. If you are sure that it‘s not going to be pseudomonas, you can start gentamycin also.

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Dhaval Patel MD

Tsukamurella keratitis o

gram-positive bacilli

o

severe eye pain, typical of bacterial keratitis

o

infiltrates in the peripheral parts of the cornea near the limbus, resembling that of marginal keratitis.

o

relatively less virulent nature

o

microtrauma to the epithelial surface of the cornea

Corneal Nerves o

o

Prominent corneal nerves: 

Keratoconus.



Ichthyosis



Fuchs corneal (Reis-Buckler's ) dystrophy



Corneal edema



Congenital glaucoma



Acanthamoeba Keratitis



corneal graft failure.



Trauma.



Idiopathic.

Enlarged Corneal Nerves: 

MEN IIb



Phytanic acid storage dis (Refsum syndrome).



Hansen dis (leprosy,beading of nerves



Familial dysautonomia(Riley- Day)



Neurofibromatosis.



Acanthamoeba perineuritis. 179


Dhaval Patel MD

primary amyloidosis



sequential sector conjunctival epitheliectomy (SSCE): for partial LSCD involving the visual axis



Corneal Hysteresis: measure of viscous damping of cornea



Corneal resistance Factor: measure of resistance/rigidity of cornea



Boston scleral lens= PROSE: Prosthetic Replacement of the Ocular Surface Ecosystem, sed for irregular corneas



Concentration of riboflavin for C3R: 0.1%, in 20% dextran, 30 min, 370 nm, 3 mW/cm2



In corneal blood staining, hemoglobin products accumulate in corneal stroma. (not RBCs)



Progression of bacterial corneal ulcers: Proteases released by bacteria



Most stable flap in femtosecond laser: zig-zag



Flat cornea: <41D, Free cap, thick flap Steep cornea: >50D, Buttonhole, thin flap



Q value: Corneal asphericity o

By applying certain mathematical equations, eccentricity can be calculated and given a value from which Q-value can be derived. 180


Dhaval Patel MD

o

Positive: center of the cornea is flatter than the periphery, oblate cornea

o

Zero: center equals the periphery, sphere cornea

o

Negative: center is steeper than the periphery, prolate cornea

o

Q-value is considered normal when it falls between 0 and -1 [-1, 0].



PPMD: AD, incomplete penetrance, variable expression, 20q11



Macular dystrophy: hypo/non-sulfated keratin



Bacterial ulcer simulating fungal ulcer: Hyphate edges, satellite lesion o

Nocardia: calcerous bodies

o

Actinomyces

o

Streptomyces



Corneal sensations are normal in adenoviral keratitis.



Goblet cells are most dense in inferonasal quadrent.



Acanthameba transport media: page‘s medium Virus transport medium: Hank‘s medium Chlamydia transport medium: 0.2M sucrose phosphate medium



w3 fatty acid  anti inflammatory products like PGE3, LBT5 w6 fatty acid  pro inflammatory prodcts like PGE1, PGE2, LBT4



HBID: Hereditary benign intraepithelial dyskeratosis 181


Dhaval Patel MD

o

Also called Witkop von Sallman syndrome, red eye disease

o

Acanthotic and dyskeratotic epithelium of conjunctiva and oral mucosa

o

Rare, autosomal dominant disease with incomplete penetrance, which usually appears in first decade of life

o

Originally described in Haliwa Indians in North Carolina (USA), also elsewhere in US and Europe

o

Gray-white, inflamed, horseshoe shaped elevated lesions of conjunctiva and oral mucosa; bilateral corneal involvement



ProClear Contact Lens: biocompatible omafilcon, a material with phosphorylcholine integrated into lens polymer. PC molecule attach to H2O allowing the lens to resist deposits and thus function better.



Acid injuries causes less damage than alkalies in general except Hydrofluoric acid used in glass etching and cleaning also tends to rapidly penetrate the eye, whilst sulphuric acid may be complicated by thermal effects and high velocity impact after car battery explosions.



Unlike CHQ-HCHQ retinopathy, vortex keratopathy caused by them bears no relationship to dosage or duration of treatment. The changes are usually reversible on cessation of therapy, although they may clear despite continued administration.



Phenol red thread test uses a thread impregnated with a pH sensitive dye. The end of the thread is placed over the lower lid and the length wetted (the dye changes from yellow to red in tears) is measured after 15 seconds. A value of 6 mm is abnormal. It is comparable to Schirmer test but takes less time.



Zidovudine, an anti-retroviral agent, may be beneficial in primary Sjögren syndrome.



The adenoid superficial layer of the conjunctiva does not develop until about 3 months after birth, hence the inability of the newborn to produce a follicular conjunctival reaction. 182




Dhaval Patel MD

In hyperacute conjunctivitis caused by Neisseria, drug of choice is o

Ceftriaxone 1 gm IM + azithromycin 1 gm PO

o

Azithromycin is given to treat concurrent chlamydia infection.

o

Even if concurrent chlamydia is not suspected, treat with both drugs as azithromycin covers ceftriaxone resistance.



Hertoghe sign is characterized by absence of the lateral portion of the eyebrows. It is seen in Atopic Keratoconjunctivitis.



Mucus fishing syndrome: in a variety of underlying anterior segment disorders, patients develop or exacerbate a chronic papillary reaction due to repetitive manual removal of mucus which results into GPC like state.



Ocular Protection Index (OPI): OPI = BUT/IBI. Values below 1 are characteristic of tear film instability and dry eye disease. Blink rate, which is calculated by dividing 60 by the number of observed blinks per second. (IBI: InterBlink Interval)



Meibography is a technique that uses transillumination biomicroscopy of the everted eyelid with infrared photography Meibometry is used to measure the amount of lipid on the lid margin by determining the degree of translucency induced on plastic tape applied to the lid margin.



Tetracycline reduces lipase production in S. epidermidis, S. aureus, and P. acnes. It also decreases serum cholesterol in mice, has antichemotactic effects on neutrophils, and has activity against collagenase and other metalloproteinases. Any of these properties may produce a marked therapeutic effect in many patients with meibomian gland dysfunction and rosacea.

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Dhaval Patel MD



The currently accepted WHO guidelines include community-wide antibiotic treatment if there is >10% active trachoma in children aged 1–9 years. This treatment should be reinstituted annually for 3 years, with reassessment at that time.



In contrast to VKC, the papillary hypertrophy of AKC is more prominent in the inferior conjunctival fornix.



keratotorus = Schlappi’s pellucid marginal degeneration



Cause of the foamy appearance of the Bitot's spot: due to gas production by Corynebacterium xerosis in the horny epithelium



Types of xerosis: o

Xerosis epitheliasis - Due to vitamin A deficiency and associated with protein energy malnutrition.

o

Xerosis parenchymatas - Sequale of ocular inflammation  Trachoma, Chemical injury, Diphtheria, Ocular pemphigoid



Anterior stromal cautery: Application of light burns to Bowman's layer using a thermal cautery (Salleras procedure)



Unlike meibomian gland secretion, sebum contains more triglycerides and free fatty acids and considerably less sterol esters. Squalene is present in sebum and absent in meibomian gland secretion. The wax ester proportion is similar in both secretions. Overall, sebum is much more polar and will contaminate the tear film when mixed with it.



Large-diameter lamellar grafts: Malbran procedure  advanced keratoconus Malbran‘s ―peeling off‖ technique is the safest lamellar keratoplasty procedure and yields postoperative visual results equal to the more risky deep lamellar techniques.

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Dhaval Patel MD



Follicular reactions are not seen in the neonate because of the immaturity of the immune system and adenoid layer of conjunctiva is not matured till 3 months.



Corneal Collagen Cross-linking C3R: 1. Biomechanical stabilization: 

primary and secondary keratectasia



4-fold increase of stiffness of the anterior cornea

2. Biochemical stabilization: 

crosslinked collagen is more resistant against digesting enzymes



crosslinks are produced in the outer surface of the collagen molecule, blocking the docking stations for enzymes, and therefore the enzymatic activity is blocked



melting can be stopped

3. Cytotoxic effect:





killing keratocytes up to 350 μm deep in the cornea



also used to kill germs

Enhancers for Epi-On C3R o

Trometamol (Tris-[hydroxymethyl]aminometane)

o

Sodium ethylenediaminetetraacetic acid (EDTA)

o

Benzalkonium chloride BAC



Contact lens cornea is seen in rheumatoid arthritis.



Keratoconus indices o

Keratoconus Severity Index KSI >0.15

o

Keratoconus Predicctability Index KPI >0.23 185


Dhaval Patel MD

Keratometry Inferior Superior Asmmetry KISA >100%



Posterior elevation >40um on orbscan precludes LASIK.



INTACS o

150 degrees

o

PMMA segments

o

7.5 to 8.1 mm

o

68% depth

o

250-400 microns thick



CALAK: Corneal Augmentation Lamellar Keratoplasty, combination of LASIK and keratophakia



Post PRK stromal Haze increases after UV-B exposure.



DLK can induce hyperopia.



Most common cause of acute conjunctivitis: streptococcus pneumonia Most common cause of chronic conjunctivitis: staphylococcus aureus Most common cause of blephroconjunctivitis: staphylococcus aureus Most common cause of chalazion: staphylococcus aureus



Conjunctival SCRAPPING is done for chlamydia and viruses as they are intracellular, conjunctival SWAB is taken for bacteria.

186


Dhaval Patel MD

Newer therapy to prevent graft rejection: o

FK 506

o

Rapamycin

o

15-deoxypergualin

o

Anti CD-154 antibody

o

antiVEGFs

o

leflomide



The ring-shaped stromal infiltrate seen in herpes simplex keratitis is thought to be similar to the line of precipitation in the Ouchterlony test. Antigens diffuse from one area of the gel and antibodies diffuse from another. The line forms at the meeting point of the diffusing antigen and antibodies.



All hyperlipoproteinemias except TYPE I are associated with arcus.



Conjunctival Sickle Sign: Abnormalities of the bulbar conjunctival blood vessels provide direct evidence of the vaso-occlusive process and were one of the earliest reported ocular changes.



Acanthameba Stains:



o

The trichrome-eosin and iron-hematoxylin stains showed good color contrast for detecting all three stages, the trophozoite, cyst and flagellate

o

Giemsa and Gram stained the trophozoite and flagellate stages;

o

Modified Field‘s and modified AFB stains stained only the trophozoite stage.

o

Depending on the purpose, all these stains (except the AFB stain) can be used.

In pterygium, IL-7 is decreased.

187




LASIK Interface Fluid Syndrome o

first described by Lyle and Jin in 1999

o

accumulation of fluid in the LASIK flap interface due to steroid induced IOP spike, uveitis, and vitreoretinal and cataract surgery, as well as endothelial decompensation

Corneal Inlays o

o

o



Dhaval Patel MD

Pinhole Corneal Inlays 

small-aperture corneal inlay (Kamra, AcuFocus; Irvine,Calif., USA)



for the correction of presbyopia is based on the principle of changing the depth of focus



ACI 7000

Refractive Corneal Inlays 

intracorneal inlay Flexivue Microlens



Presbia



Hydrophilic acrylic

Nonrefractive Inlays 

Raindrop (Vue+; Revision Optics)



Hydrogel

Corneal Laser Surgery in Presbyopia o

o

Multifocal ablations 

Supracor (Bausch + Lomb Technolas; Munich, Germany),



PresbyMAX (Schwind Eye-Tech-Solutions GmbH and Kleinostheim, Germany)



Pseudoaccommodative cornea (PAC; Nidek Co. Ltd.; Gamagori, Aichi, Japan)

Monofocal ablations 188


classic monovision LASIK



laser blended vision (Carl Zeiss; Germany)

Dhaval Patel MD



A rare clinical syndrome consisting of a fixed dilated pupil, iris atrophy, and glaucoma, known as Uretts-Zavalia syndrome, has been observed following penetrating keratoplasty and deep lamellar keratoplasty for keratoconus.



Photochemical keratodesmos o

method of producing sutureless adhesion by applying a photosensitizer to wound surfaces followed by low energy laser irradiation.

o

The laser promotes crosslinking between collagen molecules on opposing surface to produce a tight seal without inducing thermal damage to adjacent tissue.

o

It uses rosebengal dye, which activated by low energy argon ion laser at a wavelengtyh of 514 nm.

o

This Photochemical keratodesmos system may be useful adjunct to sutures in immediate postoperative period



A randomized, masked clinical trial of 18 participants allergic to grass pollen found that signs of allergic conjunctivitis were reversed most effectively by CCs plus ATs or EH drops; however, hyperemia was reduced more by ATs combined with CC than other treatments.



Prospective Review of Early Cataract Outcomes and Grading (PRECOG) study



o

designed to test new approaches for the measurement of cataract surgical quality in settings with poor rates of follow-up.

o

The study, conducted at 40 centers in 11 countries in Asia, Africa, and Latin America, shows that visual outcome measured at 3 days after cataract surgery correlates well with long-term outcome and can be used as a measure of surgical quality in regions of the world in which longer-term follow-up is rare.

Brown-McLean Syndrome: 189


Dhaval Patel MD

o

rarest and most benign form of corneal edema

o

peripheral corneal stromal and epithelial edema that spares the central and superior cornea with pigment deposits are present on the underlying endothelium

o

A central zone of 5–7 mm remains clear and compact indefinitely despite the peripheral edema.

o

The peripheral iris may show transillumination, but the trabecular meshwork is not necessarily hyperpigmented.

o

If the patient is bilaterally aphakic, the syndrome is usually present in both eyes.

o

There is no clinical inflammation, and the cause is unknown.

o

Although the classic presentation follows intracapsular cataract extraction, it may occur after extracapsular cataract extraction



The adenovirus test, which detects the most common cause of viral conjunctivitis, requires only 10 minutes to develop after sample collection. It uses direct sampling microfiltration, similar to a home pregnancy test, to produce visual results, with a blue control line and, if positive, a red test line. Compared with cell culture, the traditional definitive test for adenovirus infection, this rapid test has a 90% sensitivity and a 96% specificity.



The ‗pump-leak‘ hypothesis: When the rate of fluid leakage into the stroma is balanced by the rate of fluid pumped out of the stroma, normal corneal architecture and thickness are maintained.



Indications for Simultaneous Keratoplasty in Cataract Surgery



o

Frank epithelial edema, or

o

Blurry vision in the morning, or

o

Corneal thickness above 0.70 mm, or

o

Endothelial cell density less than 500 cells/mm2

Location of corneal epithelial stem cells (SC): basal layer of the limbus

190


Thoft and Friends‘ X, Y, and Z hypothesis of corneal epithelial maintenance o





X+Y = Z 

X= proliferation of basal cells



Y= centripetal movement of cells



Z=cell loss from the surface

Specular Microscopy Finding in Posterior Corneal Disorders o

Fuchs‘: decreased ECD, polymegathism, pleomorphism, disruption from guttae

o

PPMD: Pleomorphism, irregular large cells with scalloped edges as dark rings around lighter center, vescicles/pits in DM, Disrupted by crater-like focal lesions

o

ICE: enlarged ICE cells, white reflections in center of dark cells ‗dark-light reversal‘, no disruption from craters or guttae

TYROSINEMIA o

o



Dhaval Patel MD

type 1 

most common



hepatorenal tyrosinemia



deficiency of fumarylacetoacetate hydrolase



no corneal involvement

type 2 

oculocutaneous tyrosinemia or Richner–Hanhart syndrome



deficiency of hepatic tyrosine aminotransferase, the gene for which is located on chromosome 16q22



can develop superficial punctate crystalline lesions, often in a dendritiform pattern, that may mimic HSV keratitis

Left eyes seem to be affected more commonly than right eyes because neonates usually present in the left-occiput-anterior position 191




Dhaval Patel MD

Peters‘-plus syndrome: Peters‘ anomaly + short stature, brachymorphy, mental retardation, abnormal ears, and, in some patients, cleft lip and palate Krause-Kivlin syndrome: Peters‘ anomaly + facial abnormalities, disproportionate short stature, retarded skeletal maturation and developmental delay (probably inherited in an autosomal recessive manner)



Unlike meibomian gland secretion, sebum contains more triglycerides and free fatty acids and considerably less sterol esters. Squalene is present in sebum and absent in meibomian gland secretion. The wax ester proportion is similar in both secretions. Overall, sebum is much more polar and will contaminate the tear film when mixed with it.



Lens 

Juvenile xanthogranuloma (JXG) can cause spontaneous hyphemas. However, in any infant that presents with ―spontaneous hyphema,‖ an ophthalmologist must consider child abuse. Other causes of spontaneous hyphema include bleeding diatheses, leukemia, and retinoblastoma.



Lens does not contain hydroxyProlene, Cysteine and Tryptophan. (PCT)



Predominant cation in lens is K+ and anion is PO4-.

192


Dhaval Patel MD

Cataracts may occur both in galactosemia (galactose-1-phosphate uridyltransferase deficiency: GAL1PUT) and galactokinase deficiency. Galactosemia, however, also can feature hepatosplenomegaly, mental retardation, and other systemic manifestations.



Neurofibromatosis type 2, not type 1, may be associated with posterior subcapsular cataracts (and acoustic neuromas as well).



Posterior capsule opacification, glaucoma (angle closure caused by excessive inflammation), and retinal detachment (caused by vitreous loss) are more common postoperative complications in children undergoing cataract extraction. The incidence of cystoid macular edema (CME) is lower in children than in adults.



Polyopia, pupillary block, and corneal-lenticular touch are indications for medical or surgical intervention in lens subluxation (which can be accomplished with the implantation of a Morcher endocapsular tension ring). Decreased vision often can be corrected solely with an aphakic refraction.



Pyramidal cataracts are a distinct and more severe form of anterior polar opacity, named because the shape of the anterior opacity resembles a pyramid. A more accurate and modern description is a likeness to the shape of the chocolate candy called the Hershey's Kiss. The tips of these opacities extend into the anterior chamber and rarely have even been known to be fused with the cornea. They are fibrous and may be associated with an anterior subcapsular cataract that, when present, often progresses to become visually significant. At surgery, the fibrous ―Hershey's Kiss” is not easily removed with the vitreous cutter. After it is detached from the anterior capsule, it usually spins around the anterior chamber and has to be delivered through the incision using forceps. These pyramidal cataracts are almost always bilaterally symmetric and may be dominantly inherited.



Homocystinuria o

It is AR with the gene locus on chromosome 21q.22.3.

193


Dhaval Patel MD

o

Affected patients are generally tall with osteoporosis, scoliosis, and chest deformities.

o

About 50% of the time there is associated mental retardation.

o

These patients are at increased risk of thrombotic vascular occlusions, and this should be taken into consideration if general anesthesia is planned.

o

Lens dislocation occurs in 90% of patients and is generally inferior and bilateral.

o

Homocystinuria may lead to angle closure glaucoma if the lens dislocates into the anterior chamber.

o

In homocystinuria, serum levels of homocystine and methionine are elevated. Patients are normal at birth but develop seizures, osteoporosis, and mental retardation. Classic lens dislocation is bilateral, symmetric, usually inferonasal.

o

Decreased hepatic activity of cystathionine beta-synthase results in systemic accumulation of homocysteine and methionine.

o

Normal lens zonules have a high concentration of cysteine, and deficiency results in abnormal, brittle zonules.

o

A diet low in methionine and high in cysteine can reduce lens dislocation.

o

Vitamin B6 supplementation have shown promise in treating these patients and in reducing ectopia lentis.



The Malyugin ring is a device to enlarge a small pupil and/or stabilize an atonic iris. This may be necessary in patients with pilocarpine treatment, pseudoexfoliation, and IFIS. Pupillary dilation is usually not an issue in ectopia lentis.



Z-syndrome refers to a complication of the Crystalens in which the plate haptics are bent asymmetrically so the lens has a ―Z‖ configuration. Z phenomenon: earliest models of foldable IOLs were too long, so that when they were well fixated within the capsular bag they caused wrinkling of capsule centrally because of capsule contraction.



Coloboma of the lens is not a true coloboma. Instead the notch in the equator resulted from an absence of zonular fibers from an underlying colobomatous ciliary body. This absence results in a lack of tension on the lens capsule in that region. The lens tissue is not missing. 194




Dhaval Patel MD

Ectopia lentis associated with mental retardation: o

Hyperlysinemia

o

Weill-Marchesani syndrome

o

Homocystinuria



Young, myopic males may be predisposed to pigmentary dispersion syndrome.



Amiodarone and phenothiazine cause stellate cataracts in the anterior lens capsule. All forms of steroids have been associated with cataract formation.



Persistent hyperplastic primary vitreous (PHPV) is a congenital, nonhereditary ocular malformation. Associated findings include elongation of ciliary processes, prominent radial iris vessels, persistent hyaloid artery, microphthalmia, and ectopia lentis.



Monocular visual deprivation, most likely with nuclear cataract, is the most ―amblyogenic.‖



Vitamin B6  homocystinuria Coenzyme Q  Leber's hereditary optic neuropathy Vitamin A  retinitis pigmentosa



20% of patients with cataract have significant preexisting astigmatism.



Three kinds of aspiration systems exist in phacoemulsification machines. o

The peristaltic pump has rollers that move along tubing and create a relatively rapid rise in vacuum.

o

The diaphragm pump has valves over both the inlet and outlet of a fluid chamber covered by a diaphragm. This system allows a slower build of vacuum. 195


Dhaval Patel MD

The Venturi pump produces the most rapid increase in vacuum. This, however, can be the most dangerous because it allows almost instantaneous engagement of unwanted tissues such as capsule or iris.



PMMA lenses, when packaged, may pick up static charges that attract dust and debris when opened. Therefore, the lens may be rinsed with balanced salt solution before insertion. Silicone lenses do not require this and, in fact, may be more difficult to handle once they have gotten wet. Application of a viscoelastic, such as sodium hyaluronate, may facilitate insertion of a lens, especially a foldable one, through a small incision.



IOL implantation is contraindicated in patients with juvenile rheumatoid arthritis-associated iridocyclitis. Development of cyclitic membranes and subsequent ciliary body detachment following extracapsular cataract extraction suggest the need for complete capsular removal. Therefore, combined lensectomy and subtotal vitrectomy is recommended either through the limbus or pars plana. But recent data suggests that IOL can be implanted in JIA associated uveitis without significantly affecting post operative uveitis incidence. (Foster’s Uveitis Book)



Lane and colleagues evaluated IOP elevation associated with three commonly used viscoelastic agents (sodium hyaluronate, chondroitin sulfate, and hydroxymethylcellulose) and all produced significant pressure elevations at 4 ± 1 hours postoperatively. Removing the viscoelastic did not eliminate significant postoperative IOP elevation, although when chondroitin sulfate was removed, the pressure elevation was slightly less.



The ciliary sulcus is only 0.83-mm posterior to the limbus vertically and 0.46-mm posterior horizontally



The incidence of clinical cystoid macular edema is less than 1% following uncomplicated cataract extraction. The incidence of angiographic evidence of cystoid macular edema is approximately 10 times this.



Congential epicapsular pigment stars: its can be seen normally on anterior lens capsule. They are remnants of the anterior tunica vasculosa. 196




Dhaval Patel MD

Systemic Investigations for subluxated lens: o

Echocardiogram may show enlarged aortic roots or mitral valve prolapse in Marian's syndrome.

o

High serum methionine is seen in homocystinuria.

o

Serum FTA-ABS for Syphilis as it is a known cause of ectopia lentis.

o

Urine thiosulphate is seen in sulphite oxidase deficiency, in which the disulphide bond is disrupted and can cause ectopia lentis



Myotonic dystrophy: These patients have polychromatic cataract which is classically described as "Christmas tree" cataract.



youngster with bilateral cataracts and epilepsy Check Serum calcium. The disease is hypoparathyroidism or psuedohypoparathyroidism. Both these conditions are associated with epilepsy and bilateral cataracts and the blood test shows a low serum calcium and a high serum phosphate. In the former condition the parathyroid glands do not produce parathyroid hormone while in the latter, parathyroid hormone is produced but the tissues especially the kidneys are resistant to its actions. The two conditions can usually be differentiated by measuring the parathyroid hormone concentration in the serum. They are both treated with calcium supplements and vitamin D supplements.



What clinical condition leads to phimotic anterior capsule opening? Pseudoexfoliation, because zonules can get stretched and your rhexis is made smaller than you intended.



Singh signs for PPCD o

A deep anterior chamber

o

White to chalky-white spots are produced, which are seen in front of and around the posterior capsular defect. 197


Dhaval Patel MD

o

The capsule behind the opaque lens may show a partial or a complete white ringshaped opacity. This opacity is contained within the posterior cortex, while the posterior capsule shows a hole with chalky-white spots on and around the defect.

o

Rarely, an opening in the posterior capsule shows pigment along the margins. Fine dustlike pigment along with fine dense white opacities may be seen in the Berger space. The presence of pigment suggests widespread movement of the fluid beyond the posterior capsular defect.



Argentina flag sign: complication when performing capsulorrhexis in intumescent cataracts stained with trypan blue



In diabetic cataract, hyperglycaemia results in myopia and vice versa.



Steroid induced cataract: 10 mg prednisolone/day for > 2 years can cause cataract. 100% incidence with 20 mg prednisolone/day > 4 year



Wrinkling of capsule at the start of capsulorrhexis is pathognomonic sign of inadequate capsular support.



Membranous cataract is rare and may be associated with Hallermann–Streiff–François syndrome. It occurs when the lenticular material partially or completely reabsorbs leaving behind residual chalky-white lens matter sandwiched between the anterior and posterior capsules.



Advantages of capsulorrhexis: o

Traps the lens inside bag

o

Better control of surgery

o

ELP better

o

Resists tearing 198


Dhaval Patel MD

PCO is decreased when overlap of IOL

Disadvantage of capsulorrhexis: o

Phimosis

o

Sphincter effect leading to bag-IOL dislocation in PXF



Bryan Little‘s manouevre: capsule tear out and rescue manouere.



CRYSTALENS does not have UV bocking property.



The predominant yellow chromophores in the young human lens are metabolites of tryptophan, especially N-formyl kynurenine glucoside.



Calib chop: preoperatively calculated the calibrated tip not only marks the entry point on lens surface, it also measures as it reaches the desired depth when a vertical chop can be effectively and safely executed called a calibchop.



The IDEM lens or the ―IDeal EMmetropia lens‖, was that IOL power which when implanted within the eye restored emmetropic status after cataract surgery. The power of this lens was mathematically deduced to be +17.0 D for an AC lens, +19.0D for an iris fixated lens and +21.0D for a posterior chamber lens.



The Third and fourth generation IOL power calculation formulae incorporate a bit of both theoretical and regression types which was called the ―Fudge factor‖ by duke elder.



The Haigis formula o

4th generation formula which was an adaptation of the formula first suggested by Gernet, Ostholt and Werner as early as 1970

o

also called the GOW 70 formula

199


Dhaval Patel MD

o

The versatility of the formula lies in the three individualized A constants namely a0, a1 and a2.

o

The a0 is linked to the manufacturers lens constant.

o

The a1 is linked to the pre operative ultrasonically measured ACD (this has a default value of 0.4).

o

a2 which is linked to the axial length measurements and which has a default value of 0.1



Desmosomes of lens epithelial cells contain VIMENTIN whereas most epithelial cells in the body contain cytokeratin.



Prechopping techniques:



o

Akahoshi technique: using special prechopper created by akahoshi

o

Preslice technique

o

Ultrachopper technique: Luis Escaf, ultrasonic knife that cuts the nuclear substance

CDI = cohesion- dispersion index (%aspirated/mm Hg): o

Cohesive OVDs: CDI >30

o

Dispersive OVDs: CDI <30



The patients who are left with < 1.0 D of astigmatism remain comfortable after surgery, particularly if the astigmatism happens to be against the rule (ATR), as the patient will experience increased depth of focus due to pseudoaccomodation.



With accumulation of the water-insoluble fraction of lens protein, a marked browning of the lens nucleus occurs. The amount of accumulation correlates with the degree of opacification.

200


Dhaval Patel MD



Vitamin A does not have protective mechanism against oxidation in the lens.



LOCS III:



o

The LOCS III contains an expanded set of standards that were selected from the Longitudinal Study of Cataract slide library at the Center for Clinical Cataract Research, Boston, Mass.

o

It consists of six slit-lamp images for grading nuclear color (NC) and nuclear opalescence (NO),

o

five retroillumination images for grading cortical cataract (C), and

o

five retroillumination images for grading posterior subcapsular (P) cataract.

o

Cataract severity is graded on a decimal scale, and the standards have regularly spaced intervals on a decimal scale.

Persistant Pupillary Membrane PPMs: o

PPMs are the remnants of a normal embryologic structure of the eye.

o

During fetal development they are continuous with the blood supply of the developing lens.

o

The pupillary membrane begins to atrophy during fetal life, but atrophy may not be complete until 4 to 8 weeks of age.

o

These strands are considered to be "persistent" when they do not regress by 8 weeks of age.

o

There are four variations of PPMs: 1. Iris to iris. The strand is attached to only iridal tissue, not touching the lens or cornea. 2. One end attached to iris, the other not attached (free floating). 3. Iris to lens. 4. Iris to cornea.

201


Dhaval Patel MD



Anterior and posterior ―Y‖ sutures are formed by FETAL nucleus and not EMBRYONIC nucleus.



In posterior subcapsular cataracts, there is posterior migration of lens epithelial cells, which swell along the posterior capsule. These swollen cells are called Wedl or bladder cells. In cortical cataracts, there is hydropic swelling of lens fibers. The eosinophilic, globular material between lens fibers is called morgagnian globules.



Anterior polar cataracts are usually small and nonprogressive, do not usually impair vision, and may be seen in association with microphthalmos, a persistent pupillary membrane, and anterior lenticonus. Posterior polar cataracts cause more visual impairment and tend to be larger than anterior polar cataracts. Both can be autosomal dominant or sporadic. Posterior polar cataracts may be associated with posterior lenticonus or a remnant of the tunica vasculosa lentis.



Raman spectroscopy is used for normal aging and pathologic processes in the lens.



LPR: Laser for Presbyopia Reversal



o

Ron Krueger who first investigated the effect of intralenticular femtosecond laser surgery on accommodation

o

Rowiak Femtosecond Laser for Presbyopia Reversal

o

low-energy (2.0 μJ to 5.0 μJ per pulse) and high-frequency (100 kHz) infrared laser (1040 nm).

o

The width of each single laser pulse is less than 400 femtoseconds.

o

The laser process is controlled by an integrated OCT imaging system. The laser is able to cut 3-dimensional patterns with a working field diameter of up to 9.0 mm within the crystalline lens. The presbyopia reversal cutting process is characterized by an extremely low gas bubble production due to a low energy threshold.

FDA-Approved Accommodative Lenses 202








Dhaval Patel MD

o

Crystalens AT-45: The First FDA-Approved Accommodating IOL (Nov. 2003)

o

Crystalens 5-O (Nov. 2006)

o

Crystalens HD and AO

o

Not approved: Tetraflex

Dual-Optic Accommodative IOLs o

Hara et al

o

Synchrony IOL

o

dual-optic, silicone, single-piece, foldable, accommodating IOL

o

5.5-mm high-plus powered anterior optic connected to a 6.0-mm variable negative power optic by haptics that have a spring-like action

o

optical power of the anterior optic is +32.0 D

Types of Diffractive Multifocal IOLs o

Alcon ReSTOR

o

Abbott Medical Optics Tecnis MF

o

Carl Zeiss Meditec AG Acri.Lisa 366D

o

Hanita SeeLens MF

o

Physiol IOL

o

FineVision IOL

o

Ari. Tec TwinSet

Zonal (Segmental) Refractive Multifocal IOLs o

Lentis Mplus

o

Lenstec SBL-3

203


Trifocal IOLs o

FineVision, Physiol; Belgium 

o

25% hydrophilic acrylic IOL has, in addition to a near foci (+3.50 D), a foci for intermediate vision (+1.75 D) to provide treated patients with a full range of correction.

AT LISA tri 839MP, Zeiss; Germany 



Dhaval Patel MD

(+3.33 D near add and +1.66 D intermediate add at the IOL plane

The pulsed electron avalanche knife (PEAK-fc, Carl Zeiss Meditec) is an electrosurgical cutting device that allows precise "cold" and traction-free tissue dissection The PEAK-fc appears to be a helpful cutting device for complicated cases of cataract surgery, especially for mature and congenital cataracts.



Ultraviolet radiation-absorbing IOL o

o

Two types of these compounds are commonly used in IOLs 

Hydroxybenzophenones



Hydroxyphenylbenzotriazoles

Both absorb UV light energy and transform it into harmless heat energy (only a fraction of a degree) by a process known as photoautomerism.



Statin users had a 9% increase in cataracts. (controversial)



Compared with no surgery, timely cataract surgery that improved the patient's vision was associated with a 40% reduction in mortality risk.



204


Dhaval Patel MD

Glaucoma 

Mucopolysachharides is glaucoma: 1,4,6



Eclipse Sign is seen in shallow AC.



Inspite of prophylactic PI, 15% will develop increase IOP.



Power of koeppe gonioscopy lens is +50D.



Evaluation of the CD ratio by ophthalmoscopy use of the 5° aperture of the Welsh-Allyn ophthalmoscope (Gross‘ technique) use of the grid (Hitchings‘ technique)



Sensitivity of automated Perimetry: (Quigley AJO 1997) o

Loss of 5 db in sensitivity occurs when 20% of ganglion cells are gone from that area.

o

Loss of 10 db is associated with loss of 40% of ganglion cells.

205


Dhaval Patel MD

TOP: Tendency Oriented Perimetry o

For OCTOPUS, more popular in Europe.

o

Test each point once

o

Interpolate information to surrounding area

o

Highly correlated to standard octopus

o

4.1 minute for TOP vs 14.7 min for standard octopus

o

95% of points within 3 db of threshold

o

Defects tend to be wider and spread out



Ciliary body ablation should not be considered in NLP eyes because of the risk of sympathetic ophthalmia.



Failure to relieve postoperative angle closure with iridotomy suggests malignant glaucoma, which often responds to potent cycloplegics. If medical management fails, laser treatment to open the anterior hyaloid face, or even pars plana vitrectomy, is necessary.



Imbert Fick‘s Low: P = W/A So W = P x A Assumptions - object perfectly spherical, dry, perfectly flexible, and infinitely thin Modified formula: W+S = (PxA) + B At A = 7.35 mm2 or the diameter of external corneal applanation = 3.06 mm, then S =B W= PxA (P=W/A) W: external force S: surface tension 206


Dhaval Patel MD

P: IOP A: area of applanation B: force needed to bend the cornea





Disinfection of applanation tips (immediately after use): o

Thoroughly wipe with 70% isopropyl alcohol swab or 70% ethanol

o

Soak in 70% isopropyl alcohol solution for 5 minutes

o

Allow alcohol to evaporate or dry prism head to prevent corneal epithelial toxicity

o

Soak in a 1:10 sodium hypochlorite (household bleach) or 3% hydrogen peroxide solution for 5 minutes. Follow by rinsing and drying to prevent damage to corneal epithelium

Outflow facility = Rate of loss of aqueous per mm Hg of raised IOP per minute Total outflow facility = C value = True outflow facility + Pseudo facility C averages 0.28 microliters / min / mmHg (abnormal C < 0.20)



Topiramate (Topamax) is associated with acute secondary angle-closure glaucoma. Most cases are bilateral, and can lead to blindness if not treated or recognized. Peripheral iridectomy is ineffective for this type of angle-closure glaucoma.



Miotics cause a paradoxical rise in IOP in angle recession glaucoma due to reduction in the uveoscleral outflow.



Vogt‘s sign: White anterior lens opacities (glaukomflecken) caused by ischemia of lens epithelial cells from previous attacks of angle-closure



Range of HVF is 0.08 asb to 10000 asb. Decibel range is 0-51 db.

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Dhaval Patel MD

Aqueous humor production: 2-3 µl/min Outflow facility in normal eyes ranges from 0.22 to 0.28 µL/min/mm Hg, and decreases with age, ocular surgery, and trauma. Patients with glaucoma often have decreased outflow facility. Volume of Anterior Chamber: 250 microliters Volume of Posterior Chamber: 60 microliters Turnover of aqueous: 1.5 - 2 hours



Decreased aqueous humor formation with increased IOP (pseudofacility) has been disputed by studies indicating that rate of aqueous formation is relatively pressureinsensitive (Shields, 1992).



Miotics lower intraocular pressure (IOP) by increasing trabecular outflow facility. Cycloplegic agents, epinephrine, and prostaglandin analogs have been shown to increase uveoscleral flow, whereas miotics decrease uveoscleral flow.



Koeppe gonioscopy is considered best for evaluating a patient with potential angle recession because this system allows easier comparison of one eye with the fellow eye, or one portion of the angle with another.



Scheie‘s line: Pigment on lens equator and posterior capsule in pigment dispersion syndrome



Split fixation is the presence of visual field loss that comes close to fixation. A typical pattern of progression is (i) loss near fixation (paracentral scotoma) to (ii) split fixation to (iii) loss of fixation. Thus, the eye at greatest risk is not one with a 5-degree central field, but one with the split-fixation in the horizontal meridian.



It is important to correlate changes in visual field with changes in the optic disc. The following should raise suspicion about the diagnosis of glaucoma: (i) an optic disc that is less cupped than would be expected for observed field loss, (ii) pallor of the disc that is more impressive than the cupping, (iii) markedly asymmetric dyschromatopsia, or (iv) 208


Dhaval Patel MD

visual field defects uncharacteristic for glaucoma (e.g., respecting the vertical meridian). A relative afferent pupillary defect (APD) can occur with glaucoma.



Pseudoglaucomatous optic nerve cupping, namely: (i) chiasmal compression, (ii) arteritic anterior ischemic optic neuropathy (AAION), (iii) toxic optic neuropathies (such as methanol toxicity), and (iv) hypotension (―shock‖ optic neuropathy).



The sine qua non of PDS is radial defects in the iris pigment epithelium.



The patient with very narrow angles and elevated pressure may have ―mixed mechanism‖ glaucoma with partial angle closure caused by pupillary block superimposed on open-angle glaucoma. To determine if an angle-closure component is present, the effect of minimizing pupillary block on intraocular pressure (IOP) must be determined. Cholinergic miotics (pilocarpine) will cause miosis and lessen pupillary block and will also exert traction on the trabecular meshwork (TM) and lower IOP by this unrelated mechanism. Thymoxamine, a selective alpha-adrenergic antagonist, causes miosis and lessens pupillary block, without affecting outflow facility. A decrease in pressure after thymoxamine (lessened pupillary block) implies partial angle closure, and iridotomy is indicated. No change in IOP after thymoxamine-induced miosis implies that an iridotomy may not be helpful.



Following heavy panretinal photocoagulation, choroidal effusion may cause anterior rotation and swelling of the ciliary body resulting in closure of the angle.



In central retinal vein occlusion (CRVO), there may be transudation of serum into the vitreous, driven by the elevated intravascular pressure. This hydration causes vitreous swelling with subsequent secondary angle closure. There may also be ciliary body swelling associated with CRVO.



Direct-acting miotics interact directly with the acetylcholine receptor, whereas indirect-acting agents increase the activity of native acetylcholine at the synaptic junction (by blocking its enzymatic degradation). Pilocarpine is a purely direct agent, whereas carbachol is felt to exhibit both direct and indirect effects. Miotics: indirect-acting agents-echothiophate, carbachol, demecarium. 209


Dhaval Patel MD

S/E: cataractogenesis, punctal stenosis, retinal tears and detachment.



The most common complication of both Nd:YAG and argon laser iridotomies is acute glaucoma. Malignant glaucoma has been reported after a variety of seemingly benign ocular laser procedures.



Posttrabeculectomy pain and decreased vision require evaluation for endophthalmitis, malignant glaucoma, and suprachoroidal hemorrhage.

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Short-term fluctuation (SF) and Corrected pattern standard deviation (CPSD) are not available on SITA.



Central corneal thickness is increased in eyes with aniridia which may result in incorrect measurement of IOP.



When performing laser trabeculoplasty a pigmented Schwalbe line should not be confused with the posterior pigmented trabeculum. In laser trabeculoplasty it is important to identify the scleral spur because the application of burns posterior to it will result in greater inflammation, with consequent increased risk of early post-laser rise in IOP and the formation of peripheral anterior synechiae.



A pupillary diameter of less than 3 mm can cause general depression of the field.



The Humphrey automated perimeter has a number of ways to test the reliability of the test taker. A fixation loss occurs when the patient responds as if seeing a light when a target is displayed in his blind spot. A false-negative response occurs when the patient fails to respond to a suprathreshold stimulus at a location that would be expected to be seen. This response may indicate a patient who is falling asleep or losing interest. Intermittently, the perimeter will pause and the motorized light will change position, but no stimulus will be presented. If the patient presses the button, a false-positive response is recorded. A nervous or trigger-happy patient may have a high false-positive rate. Short-term fluctuation describes the change in sensitivity when the same point is retested. 210


Dhaval Patel MD



For the early detection of glaucomatous optic nerve damage, the most important variable appears to be focal narrowing or notching of the neuro-retinal rim. Other important variables are optic cup size in relation to optic disc size, disc asymmetry, and presence of disc hemorrhages. However, disc hemorrhages can occur in other conditions (e.g., anterior ischemic optic neuropathy [AION]) and disc asymmetry may be a normal finding if the difference is slight (<0.2 difference).



Up to 50% of optic nerve axons can be lost before any change is detected on the Goldmann visual field.



Ocular inflammation can lead to glaucoma via a variety of mechanisms including 1) obstruction of the trabecular meshwork by inflammatory debris, 2) increased viscosity of aqueous humor, 3) neovascularization, 4) uveal effusion, 5) pupillary block, and 6) formation of peripheral anterior synechiae.



The common pathogenesis of glaucoma in the Sturge-Weber syndrome, thyroid eye disease, and carotid-cavernous sinus fistula is an increase in episcleral venous pressure through elevated venous outflow pressure or orbital congestion.



Corticosteroids are thought to raise IOP by lowering outflow facility perhaps due to an accumulation of glycosaminoglycans in the trabecular meshwork.



Patients at particular risk for aqueous misdirection are those with crowded anterior segments (i.e., angle closure, nanophthalmos). Postoperative inflammation may cause swelling of the ciliary body and ciliary processes leading to aqueous misdirection.



Ocular side effects of pilocarpine include conjunctival vascular congestion, miosis, induced myopia, cataract formation, and temporal or periorbital headaches. Rarely, pilocarpine can be associated with retinal detachment. Pilocarpine does not cause hyperopia.



Latanoprost and travoprost lower IOP by increasing uveoscleral outflow. (these 2 are ProDrugs.) 211


Dhaval Patel MD

Bimatoprost decreases IOP by increasing uveoscleral and trabecular outflow. Unoprostone appears to lower IOP by increasing trabecular outflow only.



Acute myopia is the only ocular reaction commonly associated with carbonic anhydrase inhibitors.



The most frequent cause of failure after filtration surgery is bleb scarring due to episcleral fibrosis.



In addition to inhibiting fibroblast proliferation, 5-FU also inhibits the growth of epithelial cells of the conjunctiva and cornea. It is associated with several undesirable complications including conjunctival wound leaks, corneal epithelial defects, thin-walled ischemic blebs, hypotony, and suprachoroidal hemorrhage.



Laser trabeculoplasty effectively lowers IOP in patients with POAG, pigmentary glaucoma, or pseudoexfoliation. It is ineffective and may actually worsen the IOP in eyes with inflammatory glaucoma, recessed angles, or membranes in the angle, and in young patients with developmental defects.



When treated with SLT, a primarily biologic response is induced in the trabecular meshwork. This response involves the release of cytokines, which trigger macrophage recruitment and other changes leading to IOP reduction. The laser beam bypasses surrounding tissue, leaving it undamaged by light. This is why, unlike ALT, SLT is repeatable several times. ALT patients can receive two treatments in a lifetime, whereas SLT patients can receive two treatments a year. Even though SLT is a promising new technology, further studies need to be done to prove that SLT is in fact better than ALT at decreasing IOP pressure; at best, SLT is currently equivalent to ALT at reducing IOP.



In some cases, it may be advantageous to use both lasers: the argon for its coagulative effects and the Nd:YAG for its disruptive properties.



The incidence of hypotony is highest with full-thickness procedures such as a posterior lip sclerectomy. Because of this, these procedures are performed less commonly today. 212


Dhaval Patel MD

Partial thickness procedures, including trabeculectomies with antimetabolites, have lower rates of hypotony. Setons are intermediate in incidence depending on the type of implant and whether a ligature or other device is used to occlude the drainage tube.



Antifibrotic agents should be used with caution in young myopic patients due to the risk of hypotony.



Modulation wound healing post glaucoma surgery o

BAPN (beta-aminoproprionitrile), an inhibitor of lysyl oxidase, blocks collagen cross-linking

o

5-FU inhibits fibroblast proliferation by acting selectively on the S phase of the cell cycle

o

mitomycin-C is an alkylating agent that decreases DNA synthesis by causing DNA cross-linking

o

Colchicine affects collagen cross-linking and thereby decreases scar formation.



Cyclodialysis clefts occur after traumatic injuries. Chronic hypotony usually results. These clefts close spontaneously weeks to months later, usually resulting in a sudden increase in the IOP. Usually, the trabecular outflow system will begin functioning more normally a short period of time after the pressure spike has occurred.



In traumatic hyphema, Rebleeding is not an indication to operate unless elevated pressure and corneal blood staining are threatened.



An intensely pigmented meshwork may be caused by pseudoexfoliation, pigment dispersion syndrome, inflammation (uveitis), malignant melanoma, trauma, surgery, and hyphema.



The Glaucoma Laser Trial study has demonstrated that ALT is a reasonable alternative to medication (timolol) in the initial treatment of POAG. However, 2 years into the study, 56% of laser-treated eyes needed supplemental medical therapy to control IOP. Laser-treated eyes had a lower mean IOP. 213


Dhaval Patel MD



In acute angle closure glaucoma, hydropic degeneration and impaired axoplasmic flow cause swelling and hyperemia of the optic nerve.



Transscleral cyclophotocoagulation is useful in many types of refractory glaucoma, such as glaucoma in aphakia or pseudophakia, neovascular glaucoma, glaucoma associated with inflammation, and glaucoma in eyes with multiple failed filtering procedures. Observations in animal and human eyes suggest that the most likely mechanism of IOPlowering is reduced aqueous production through destruction of ciliary epithelium.



If corneal astigmatism is greater than 3 D, IOP is underestimated for with-the-rule astigmatism and overestimated for against-the-rule astigmatism.



Patients with POAG and relatives of POAG patients have a higher incidence of elevated IOP in response to topical or systemic corticosteroids, but this is not a risk factor for POAG; rather, it is a risk factor for steroid-induced secondary open angle glaucoma.



Ketamine and trichloroethylene can cause IOP to increase.



Thick cornea overestimates IOP & Thin cornea underestimates IOP.



Thick Mires overestimates IOP.



In Aqueous Humor, Only calcium and phosphorus are in concentrations of about one-half that in plasma. Sodium, potassium, magnesium, iron, zinc, and copper all approximate levels found in plasma. Chloride and bicarbonate vary from 20% to 30% above or below plasma levels.



In lactating women, concentration of timolol in breast milk is higher than serum level.

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Dhaval Patel MD



Intercalary staphyloma occurs in absolute glaucoma. It is lined by root of the iris.



In infantile glaucoma, an affected parent has about a 5% chance of having a child with infantile glaucoma, and the next subsequent sibling has approximately a 5% chance of being affected.



Corneal clouding or tearing is more likely to be the presenting symptom in patients with glaucoma in whom the onset is before the age of 3 months, whereas corneal enlargement will probably be the presenting finding in older infants.



Unlike adults, pressures in children >20 mm Hg must raise a suspicion of glaucoma.



The 3 syndromes that comprise ICE have the common features of iris distortion, corneal edema, and secondary angle-closure glaucoma due to angle endothelialization and peripheral anterior synechiae formation. The specific findings of each syndrome are: o

Iris nevus (Cogan-Reese) syndrome: flattening and effacement of the iris stroma, pigmented iris nodules (pseudonevi) composed of normal iris cells that are bunched up from the overlying membrane, corectopia, and ectropion uveae.

o

Chandler‘s syndrome: corneal edema often with normal IOP, and mild or no iris changes (minimal corectopia, iris atrophy, peripheral anterior synechiae).

o

Essential iris atrophy (Progressive iris atrophy): proliferating endothelium produces broad PAS, corectopia, ectropion uveae, and iris holes (stretch holes [area away from maximal pull of endothelial membrane is stretched so thin that holes develop] and melting holes [holes in areas without iris thinning due to iris ischemia]).



ICE is a unilateral, nonhereditary, progressive abnormality of the corneal endothelium that is not associated with any systemic abnormalities. It most commonly affects middle-aged women. Mesodermal dysgenesis is bilateral, congenital, and hereditary.



Mesodermal dysgenesis syndromes o

Axenfeld‘s anomaly: posterior embryotoxon (anteriorly displaced Schwalbe‘s line) with iris processes to the scleral spur. Glaucoma develops in 50%. 215


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Dhaval Patel MD

o

Alagille‘s syndrome: Axenfeld‘s plus pigmentary retinopathy, corectopia, esotropia, and systemic abnormalities (absent deep tendon reflexes, abnormal facies, pulmonic valvular stenosis, peripheral arterial stenosis, biliary hypoplasia, and skeletal abnormalities).

o

Rieger‘s anomaly: Axenfeld‘s plus iris hypoplasia with holes. Glaucoma develops in 50%.

o

Rieger‘s syndrome: Rieger‘s anomaly plus mental retardation and systemic abnormalities (dental, craniofacial, genitourinary, and skeletal).

o

Peter‘s anomaly: central corneal leukoma (opacity due to defect in Descemet‘s membrane with absence of endothelium) with iris adhesions, may have cataract and develop glaucoma (50%), and is associated with cardiac, craniofacial, and skeletal abnormalities. It is usually sporadic and bilateral (80%).

Riluzole and Lifarazine are neuroprotective as they inhibit the release of glutamate. Memantine and Felbamate are neuroprotective as they block the NMDA receptors.



BAD and BAX genes: Stimulate retinal ganglion cell death BCL-2 and BCL-Xl genes: Inhibits retinal ganglion cell death



Each 1 mmHg reduction in IOP leads to a 10% reduction in the rate of nerve fibre loss.



Rate of ganglion cell loss in normal population is approximately 5000/year.



Inferior PI is also known as Ando‘s PI.



MOST important medication to discontinue as far before glaucoma surgery as possible: Echothiophate (causes breakdown of BAB) >> dipivefrine



Total internal reflection: Total internal reflection at the tear-air interface prevents a direct view of the anterior chamber. To overcome this limitation, the critical angle must be 216


Dhaval Patel MD

increased for the tear-air interface by applying a plastic or glass goniolens to the surface. Total internal reflection also occurs in fiberoptic tubes and indirect ophthalmoscopes.



Causes of VH after trabeculectomy o

Haemorrhage from iridectomy which tracked itself into the vitreal cavity

o

During the iridectomy, the ciliary body was inadvertently cut resulting in vitreous haemorrhage.



Ocular hypertension leads to ocular tissue damage, and hence to glaucoma, at an incidence of about 1% per year.



Applanation Prism diameter: 3.06mm Tonopen: 1.02mm NCT: 3.6 mm Dynamic Contour Tonometer – Pascal: The probe has a radius of curvature of 10.5 mm, contact surface of 7 mm diameter and sensor diameter of 1.2 mm.



4-2-1 Rule of Glaucoma The sensitivity of the visual field is by determining the threshold value at each point by the bracketing technique (4-2 on the Humphrey and 4-2-1 on the Octopus perimeter). After presenting a light stimulus the machine waits for a yes / no response. If the stimulus is not seen, the intensity of the light seen is increased in steps of 4dB, till it is seen (machine records this as supra threshold level). Subsequently, light stimuli are decreased in steps of 2dB till the stimulus is not seen (infra-threshold). Octopus perimeters make one more movement in steps of 1dB. The actual threshold is between the supra-threshold and infra threshold.



Systemic evaluation of the neonate with glaucoma: urinalysis for proteinuria and aminoaciduria.(LOWE‘S SYNDROME)



antiarthritis agents to increases in intraocular pressure  Glucosamine 217


Dhaval Patel MD



Aqueous flow, outflow facility, and episcleral venous pressure are thus the primary determinants of IOP. In the eye, the driving pressure for aqueous outflow equals the difference between intraocular pressure (IOP) and episcleral venous pressure (Ve). The outflow facility is the reciprocal of resistance.



Uveoscleral outflow is pressure-independent.10-50% of total outflow.



Cycloplegic agents, epinephrine, and prostaglandin analogs have been shown to increase uveoscleral flow, whereas miotics decrease uveoscleral flow.



Episcleral venous pressure: 8 to 12 mm Hg.



Applanation measurements are essentially independent of ocular rigidity.



Digital pressure on a Goldmann lens  may tend to narrow the angle. Zeiss lens  opens angle



Blood may enter Schlemm's canal when episcleral venous pressure exceeds intraocular pressure (IOP). It occurs in carotid-cavernous fistula, severe thyroid eye disease, excessive digital pressure on a Goldmann gonioscopic lens, ocular hypotony.



If a patient has glaucomatous visual field-type defects, corresponding optic nerve head abnormalities should exist.



high risk factors for ultimate damage to the optic nerve: elevated IOP, positive family history of glaucoma, myopia, diabetes mellitus, cardiovascular disease, race (i.e., African American), asymmetric cupping, large cups, and early nonspecific visual field changes. 218


Dhaval Patel MD



the situation that may be the one most frequently misdiagnosed as ―normal-tension‖ glaucoma is primary open-angle glaucoma (POAG) in which intraocular pressure (IOP) fluctuations have obscured the actual nature of the disease. In addition, there are other disorders that can feature pseudoglaucomatous optic nerve cupping, namely: (i) chiasmal compression, (ii) arteritic anterior ischemic optic neuropathy (AAION), (iii) toxic optic neuropathies (such as methanol toxicity), and (iv) hypotension (―shock‖ optic neuropathy).



pigmentary glaucoma: The sine qua non of this condition is radial defects in the iris pigment epithelium. Pigmentary glaucoma usually occurs in young myopic men, typically in their third or fourth decade of life. For obscure reasons, women with the disease tend to be older than men. Exercise or pupillary movements may induce a shower of iris pigment release, with resultant increased intraocular pressure (IOP).



In hemolytic glaucoma, hemoglobin-laden macrophages block the trabecular meshwork (TM), whereas in ghost cell glaucoma, rigid, degenerated khaki-colored red blood cells from the vitreous enter the anterior chamber and obstruct the TM. Hemolytic glaucoma may occur within days of hemorrhage, whereas ghost cell glaucoma is seen weeks to months later.



Both mydriatics and miotics can precipitate angle-closure in eyes with shallow anterior chambers. This is true for both topical medications and systemic drugs that affect the pupil. Examples include antihistamines, which can have anticholinergic activity.



narrow anterior chamber angles and normal IOP  DRPPT (most predictive but no prospective study yet), darkness will induce pupillary dilation, and prone positioning will move the lens forward. narrow anterior chamber angles and elevated IOP  thymoxamine test. Patients may have “mixed mechanism” glaucoma with partial angle closure caused by pupillary block superimposed on open-angle glaucoma. To determine if an angle-closure component is present, the effect of minimizing pupillary block on intraocular pressure (IOP) must be determined. Cholinergic miotics (pilocarpine) will cause miosis and lessen pupillary block and will also exert traction on the trabecular meshwork (TM) and lower IOP by this unrelated mechanism. Thymoxamine, a selective alpha-adrenergic antagonist, causes miosis and lessens pupillary block, without affecting outflow facility. A decrease in pressure after thymoxamine (lessened pupillary block) implies partial angle closure, and iridotomy is 219


Dhaval Patel MD

indicated. No change in IOP after thymoxamine-induced miosis implies that an iridotomy may not be helpful.





suspicion of plateau iris if: o

deep anterior chamber centrally.

o

a young patient with myopia.

o

a flat iris plane.

Contraindicated in paroxysmal tachycardia  epinephrine, dipivefrin, propine Contraindicated in depression/ psychiatric illness  timolol, acetazolamide Caution in a patient with narrow angles  epinephrine, apraclonidine (due to mydriatic action)



The blood-aqueous barrier allows formation of the gradient necessary to draw fluid from the vitreous. Interruption of this gradient as in inflammation decreases the effectiveness and duration of osmotic effects.



Mannitol is distributed only in the blood compartment, whereas urea moves freely in total body water, so mannitol is more effective.



Argon laser trabeculoplasty (ALT) o

Response appears to be better for pigmentary glaucoma and pseudoexfoliation and poorer for inflammatory diseases, recessed angles, membranes in angles, young patients with developmental defects, and aphakic eyes.

o

It is applied to the anterior half of the trabecular meshwork. Application of laser to the posterior half risks the development of anterior synechiae.

o

The effect on pressure reduction depends on the pre-treatment pressure, age of the patient and type of glaucoma.

o

It is less effective in pseudophakic and aphakic patients. The effect of pressure reduction tends to decrease with time and retreatment tends to be less effective. 220


Dhaval Patel MD



The Tonopen appears to have more accurate pressure readings in patients after laserassisted in situ keratomileusis (LASIK) surgery. Goldmann readings can be artificially low after LASIK.



Topiramate (Topamax) is associated with acute secondary angle-closure glaucoma. Most cases are bilateral, and can lead to blindness if not treated or recognized. All of the findings are reversible if recognized early and the drug is discontinued. Peripheral iridectomy is ineffective for this type of angle-closure glaucoma.



Generally, uncomplicated cataract surgery (Phaco/PCIOL) lowers intraocular pressure (IOP) by 1 to 2 mm Hg.



Iridencleisis: Historical procedure, from observation that that inadvertently incarcerated iris in the wound after intracapsular cataract extraction or surgical iridectomy sometimes resulted in IOP lowering



Frequency-doubling technology, FDT o

targets the magnocellular ganglion cells, which are damaged early on in the course of glaucoma. It does this by utilizing the illusion of frequency doubling produced by a low spatial frequency grating undergoing high temporal frequency reversal.

o

It is much quicker and easier to perform than conventional automated perimetry



The anterior border of the trabecular meshwork is defined by Schwalbe's line and the scleral spur defines the posterior border.



The anatomical limbus is defined by Schwalbe's line.



Pilocarpine increases the aqueous outflow through the trabecular meshwork and therefore is ineffective in the presence of raised episcleral pressure like SWS. 221


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Iris transillumination defects: PDS: near pupillary margin (you can remember this by margin is most pigmented which is lost in PDS) PXF: at midperipheral iris



Blitz anesthesia: combined anterior sub-Tenon's, topical, and intracameral ("Blitz") anesthesia used for surgery at Wills Eye Institute.



Incidence of aniridia in patients with Wilms' tumor is 1/73 (1.4%) Incidence of Wilms' tumor in sporadic aniridia is 34%



Boussinesq model of natural convection in the human eye and the formation of Krukenberg's spindle: When paths of pigment particles are calculated based on the predicted flow field, the particles circulate throughout the anterior chamber but tend to be near the vertical centerline of the eye for a greatest period of time. Further, the particles are usually in close proximity to the cornea only when they are near the vertical centerline. We conclude that the convective flow pattern of aqueous humor is consistent with a vertical pigment spindle.



STAR Calculator:

o Scoring Tool for Assessing Risk o Dr Mederios, Dr Weinreb and colleagues at Hamilton glaucoma center o to calculate the likelihood to conversion to glaucoma from ocular hypertension based on the 6 risk factors identified by OHTS



Causes of false field defects o

Ptosis and dermatochalasis

o

tilted optic disc

o

small pupil 222


rim of the trial lens

o

Media opacities

Dhaval Patel MD



Ghost cells represent hemolyzed red blood cells and not Hemosiderin-laden macrophages.



Pathways Served by Retinal Ganglion Cells o

o

o

ParvoCellular 

Midget ganglion cells



Small field



High spatial resolution



Conveys information regarding red green opponency



Static firing system



Ring/High pass resolution Perimetry (HPRP) tests this system

Magnocellular 

Parasol ganglion cells



Large field



Low spatial resolution



Conveys information regarding motion



Tonic firing system



Frequency doubling Perimetry (FDP) tests this system

KonioCellular 

Bistratified ganglion cells



Large field



Low spatial resolution



Conveys information regarding blue yellow opponency



Short wavelength Automated Perimetry (SWAP) tests this system 223


Dhaval Patel MD



Swap USES size V stimulus.



Some of the new-technology IOLs have a yellow filter which may conceivably interfere with blue on yellow perimetry, also known as short wavelength automated perimetry (SWAP). A recent study confirmed there was no interference by the yellow filter in the IOL as determined by SWAP.



1 mmHg increase in episcleral venous pressure increases IOP by 0.8 mmHg.



Co-efficient of ocular rigidity K = 0.0215



Prostaglandin analogs such as latanoprost (Xalatan) more commonly produce conjunctival hyperemia than true allergic conjunctivitis. From 1% to 5% of patients taking dorzolamide (Trusopt) may have allergic symptoms. Up to 20% of patients taking brimonidine (Alphagan) may show such symptoms.



The continuous-wave argon laser was the unit most commonly used for creating iridotomies in the early days of laser surgery; however, the pulsed Nd:YAG laser is probably the more commonly used today. Iridotomies created with an argon laser have more extensive early edema and tissue destruction at the margins of treatment histologically as compared with those created with the Nd:YAG laser. Argon laser has the disadvantage of more iritis, pupillary distortion, and late closure of the iridotomy. Clinically, the Nd:YAG laser has the disadvantage of frequent bleeding. In general, Nd:YAG laser iridotomies require fewer total applications with a marked reduction in total energy as compared with argon laser iridotomies. In some cases, it may be advantageous to use both lasers: the argon for its coagulative effects and the Nd:YAG for its disruptive properties.



Colchicine affects collagen cross-linking and thereby decreases scar formation.



Patients with Fuchs' heterochromic iridocyclitis typically have abnormal vessels present in the angle without peripheral anterior syndrome (PAS), but they do not have a hyperpigmented meshwork. 224


Dhaval Patel MD



Isolated depressed quadrantic defects result if the patient misses the early portion of the test in which the machine attempts to determine the threshold for each quadrant.



A tube shunt can be placed in the presence of a scleral buckle. In post vitrectomy cases, the tube can be placed through the pars plana.



GDx VCC is not useful in patients with associated macular pathology like ARMD.



Trabectome o

Ab-Interno Trabeculotomy

o

trabecular bypass device that re-establishes the natural outflow passageway, allowing aqueous to drain directly into the Schlemm canal from the anterior chamber

o

The ablation of trabecular meshwork and inner wall of the Schlemm canal create a cleft that is theoretically less prone to fibrosis than goniotomy or trabeculotomy

o

FDA approved in 2006



chromatic visualevoked potential (VEP), which utilizes red-green flicker, was found to be altered in nonglaucomatous optic neuropathies, but not in glaucomatous optic neuropathies.



Diabetes has not yet been shown to increase the incidence of glaucoma. Although the weight of available evidence suggests that diabetes is probably a risk factor for glaucoma, this has not been a consistent finding. Self- reported diabetes was associated with COAG progression in the AGIS and the CIGTS (Collaborative Initial Glaucoma Treatment Study) but not in the CNTGS or the EMGT.



CB1: Increases outflow CB2: decreases production The CB1 receptor is present in the ciliary body of rat and human. 225


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Dhaval Patel MD

Glaucoma vaccines under development o

glatiramer acetate (Cop-1)

o

brimonidine

o

MK-801, which is an NMDA receptor antagonist



In a multicenter British study of trabeculectomy, retrospective, cross-sectional study found the total incidence of shallow or flat anterior chambers to be 0.9%, and the incidence of hypotony maculopathy was less than 1%, compared with 10% and 4%, respectively, in the Tube vs Trabeculectomy Study.



Patients with sleep apnea were 1.67 times more likely to develop glaucoma than patients without apnea



Women who have used oral contraceptives for 3 years or more and who have additional risk factors for glaucoma should be checked annually for the disease during their eye exams as OCPs doubled their risk for glaucoma.



Retina 

In CME, The fluid is accumulated between the outer plexiform layer and the inner nuclear layer.



The organised vitreous haemonhage blood is called Ochre membrane. 226


Dhaval Patel MD



Retina has no sensitivity to pain and sensitivity of retina is limited to light generally, that‘s why any flashes or sudden shower of floaters becomes significant.



Elschnig spots: focal choroidal infarcts in HTN retinopathy



Siegrist streaks: Linear chain of hyperpigmented spots over sclerosed choroidal vessel in chronic hypertension or choroiditis



CRAO: 20% emboli, rest thrombi, mechanical, vasculitis, trauma BRAO: 90% Emboli, rest intraocular inflammations such as toxoplasmosis or herpes retinitis (the acute retinal necrosis syndrome) can lead to BRAO.



Henle‘s layer: OPL, Obliquely oriented cone fibers in fovea



Flame-shaped hemorrhages and cotton-wool spots are ophthalmoscopic changes indicative of acute, severe hypertension. When these features occur in the absence of arteriolar sclerotic changes (i.e., AV crossing phenomenon), the hypertension is most likely of recent onset. In such cases, hypertension may be associated with renal insufficiency, encephalopathy, and impairment of cardiac function. Controlled reduction of blood pressure should be initiated immediately.



van Trigt‘s sign: Venous pulsations on optic disc (normal finding)



Autofluorescence is produced when certain tissues/material are stimulated with monochromatic blue light and emit in the yellow-green range, as fluorescein does. The two optic nerve lesions that may autofluoresce are astrocytic hamartomas and drusen. Large accumulations of lipofuscin (i.e drusens) also may autofluoresce. To demonstrate this, fundus photographs should be obtained through the standard fluorescein setup, but without fluorescein injection. Lesions will appear bright, as if they had absorbed fluorescein, although none was injected. Note that this is not the same as a “red-free” photograph 227


Dhaval Patel MD

(which is produced with a green filter that does not provide sufficient blue light to stimulate autofluorescence). On the other hand, pseudo-autofluorescence results from reflection of light from lightcoloured or white fundal structures such as myelinated nerve fibres, sclera, hard exudates or cotton wool spots.



Nodular (hard) drusen consist of a focal thickening of the basement membrane of the retinal pigment epithelium. Clinically, they appear as small yellow or yellow-white spots measuring 50 µm in diameter. Soft (exudative, fluffy) drusen are bigger and appear less dense and fluffier Basal laminar deposits consist of banded basement membrane material (wide-spaced collagen) located between the basal plasmalemma of the retinal pigment epithelium and its basement membrane. Basal linear deposits refer to material located external to the basement membrane of the retinal pigment epithelium.



The characteristic ocular lesion of angiomatosis retinae, or von Hippel's disease, is a retinal angioblastoma. This is a retinal capillary hemangioma (hemangioblastoma). The cavernous hemangioma of the retina is a rare lesion that can be associated with similar skin and central nervous system (CNS) lesions. Diffuse choroidal hemangiomas (tomato ketchup fundus) are associated with SturgeWeber syndrome (encephalofacial angiomatosis).



White lines of Vogt: Sheathed or sclerosed vessels seen in lattice degeneration



The etiology of Coats' disease is unknown, and there does not appear to be any genetic, familial, racial, or ethnic predisposition. However, Coats'-type retinal vascular changes have been noted in patients with facioscapulohumeral muscular dystrophy, Turner's syndrome, Senior-Loken syndrome, and one variant of the epidermal nevus syndrome. In addition, Coats'-like retinopathy has been noted in up to 3.6% of patients with retinitis pigmentosa.

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Dhaval Patel MD



The retinopathy of Alport's syndrome is generally mild and nonprogressive and resembles fundus albipunctatus clinically.



Although angiographically detectable cystoid macular edema (CME) is present in 10% to 20% of patients following extracapsular surgery, visual loss only occurs in 1% to 2%. For intracapsular surgery, the percentages are 40% to 60% and 2% to 10%, respectively.



Klein‘s tags: Yellow spots at base of macular hole



CSME is defined as one or more of the following criteria: 1. Retinal thickening within 500 µm of the fovea. 2. Hard exudates within 500 µm of the fovea with associated retinal thickening. 3. Retinal thickening 1 disc area or greater, part of which is within 1 disc diameter of the fovea.





DME o

Diabetic macular edema apparently: No apparent retinal thickening or hard exudates absent in posterior pole

o

Diabetic macular edema apparently: Some apparent retinal thickening or hard exudates present in posterior pole 

Mild diabetic macular edema: Some retinal thickening or hard exudates in posterior pole but distant from the center of the macula



Moderate diabetic macular edema: Retinal thickening or hard exudates approaching the center of the macula but not involving the center



Severe diabetic macular edema: Retinal thickening or hard exudates involving the center of the macula

Medical Risk Factors for Progression of Diabetic Retinopathy o

Hyperglycemia 229


Hypertension

o

Hyperlipidemia

o

Pregnancy

Dhaval Patel MD



A chorioretinal rupture and necrosis is known as sclopetaria.



Paton‘s sign: Conjunctival microaneurysms in sickle cell disease



Paton‘s lines: Circumferential peripapillary retinal folds due to optic nerve edema



Foveal hypoplasia has been associated with aniridia and albinism.



The radiating fibers of Henle in the outer plexiform layer lead to the cystic spaces in CME.



POHS is thought to be more prevalent in the Ohio-Mississippi river valley than in the rest of the United States. The San Joaquin valley has been linked to coccidiomycosis, and the Rocky Mountains have been linked with Lyme disease or Rocky Mountain spotted fever.



Approximately 10% of patients with dry ARMD will progress onto the wet form.



In contrast to Vogt-Koyanagi-Harada disease, the choriocapillaris is uninvolved with the inflammation in sympathetic ophthalmia. ??One of the classic findings in both sympathetic ophthalmia and the Vogt–Koyanagi– Harada syndrome is the preservation of the choriocapillaris.



Conditions that may have CME without leakage of fluorescein include Goldmann-Favre, retinitis pigmentosa, and nicotinic acid maculopathy. Epiretinal membranes may cause a CME that leaks from traction and distortion of paramacular capillaries. 230


Dhaval Patel MD



Goldmann–Favre vitreoretinal degeneration is an autosomal recessive condition characterized by a combination of night blindness, cataract, optically empty vitreous cavity, peripheral pigmentary retinal changes, peripheral and macular retinoschisis, lattice degeneration, and characteristic changes on electroretinography.



Depression sign of Goldberg: Focal loss of nerve fiber layer after resolution of cotton-wool spot



In patients with higher degrees of myopia, more substantial fundus changes may occur. The enlarged temporal crescent's width may exceed one third of a disc diameter. A crescent light finding known as the Weiss-Otto reflex may become apparent on the nasal aspect of the disc. This reflex results from concentric ―piling up‖ of the nasal retina and choroid, and it is best appreciated in young persons.



True silent choroid is defined as the blockage of underlying choroidal fluorescence during fluorescein angiography by material in the RPE cells. This occurs classically in patients who have Stargardt's disease. Lipofuscin accumulation within RPE cells results in the blockage of underlying choroidal fluorescence and gives the appearance of a very dark or silent choroid. Systemic argyrosis, which occurs in patients who are receiving systemic silver (e.g., from tanning agents), can also cause an angiographically dark choroid.



In a patient without a vitreous hemorrhage, the argon laser allows the placement of excellent laser burns. The wavelength of krypton red (647 nm) is best able to penetrate vitreous hemorrhages and deliver the energy necessary to create photocoagulation scars. This laser also penetrates nuclear sclerotic cataracts better than the argon. The xenon arc emits a large spectrum of wavelengths and has been replaced with the monochromatic lasers. The CO2 laser is well-absorbed by water and is used for surface tissue ablation.



Commotio represents an actual disruption or destruction of retinal photoreceptor elements and photoreceptor cells in the outer layers of the retina. It does not represent retinal edema.

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Dhaval Patel MD



The most common traumatic retinal tear is an inferotemporal retinal dialysis. The vast majority of retinal dialyses occur in this quadrant. After trauma, the most common retinal tear is inferotemporal dialysis, followed by giant tears, flap tears, and tears around lattice. These statistics are true only for blunt ocular injury.



Fluorescein leakage is not a feature of either solar maculopathy or photic injury. Both may be associated with intense staining of the damaged RPE, particularly in the acute phases of the injury. As the injured RPE heals, the fluorescein angiogram would be characterized by persistent window defects.



White-centered hemorrhages can be found in conditions with septic emboli (endocarditis, Candida bacteremia), leukemia, and collagen-vascular diseases.



Fluorescein angiography of APMPPE is characterized by early hypofluorescence of lesions, followed by late hyperfluorescence of the entire lesion.



Fluorescein angiography in MEWDS is characterized by early punctate hyperfluorescence, often in a wreath-like configuration, followed by late staining of the same punctate areas of hyperfluorescence. These areas of hyperfluorescence correspond to the white spots seen clinically. Late disc staining is also a common feature.



Adult onset foveomacular vitelliform dystrophy is not associated with an abnormal EOG.



Juvenile X-linked retinoschisis typically is associated with schisis at the level of the nerve fiber layer. (spoke wheel pattern) Reticular retinoschisis is characterized by an involutional splitting of the retina in the nerve fiber layer. Involutional retinoschisis has splitting at the outer plexiform layer. Because the photoreceptors are unaffected, the a-wave on the ERG is intact, but both the scotopic and photopic b-waves are reduced in proportion to the amount of retinal schisis.

232


Dhaval Patel MD

The EOG and dark adaptation test are normal or abnormal depending on the stage of disease. The macula is involved early, showing microcysts and radiating retinal folds, but fluorescein angiography exhibits no leakage. Perimetry may also be helpful in the differential diagnosis of retinoschisis. Relatively flat retinoschisis can be readily differentiated from shallow retinal detachment in that the former invariably causes an absolute field defect, while the latter causes only a relative defect. Perimetry is less specific for bullous detachment, because an absolute field defect could be found in either detachment or retinoschisis.



Oguchi's disease is an X-linked recessive form of congenital stationary night blindness. It is associated with the Mizuo-Nakamura phenomenon, which is the appearance of a golden brown fundus in the light adapted state with a normalization of the color of the fundus on dark adaptation.



Gyrate atrophy is a metabolic disorder that is associated with a deficiency in the ornithine aminotransferase enzyme, critical in the urea cycle.



Surface tension of silicone oil is significantly less than the surface tension of all gases, including air.



Ganglion cells do not contribute to the ERG response. The ERG may be normal in the presence of total disc cupping. The negative a-wave (late receptor potential) originates in the photoreceptors. The positive b-wave originates in the bipolar cell layer, probably in response to increased potassium concentration in the extracellular space of the bipolar cells. The positive c-wave appears to originate from the RPE.



Ocular structures that autofluoresce include the corneal epithelium and endothelium, lens, macular and RPE pigments, optic nerve drusen, and RPE deposits in Best disease.

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Dhaval Patel MD



Partial PVD, detected with OCT has been shown to start perifoveally and progressively detach in stages, leaving the foveal and the optic nerve attachment to separate last.



Flashes of light that appear as jagged lines or ―heat waves‖• often lasting 10 to 20 min and present in both eyes, are more likely to be a migraine. These fortification lines may or may not be followed by a headache. Visual function returns to its premigraine baseline.



development of choroidal effusion following panretinal photocoagulation: short axial length (<23 mm)



ETDRS found that twice as many untreated patients lost vision. It is not accurate to conclude that laser treatment is likely to improve vision in diabetic macular edema.



The degree of pigmentation observed ophthalmoscopically in any human fundus depends on the number of pigmented melanocytes in the choroid. Retinal pigment epithelium (RPE) pigmentation contributes to a lesser degree.



Rods and cones are characterized by three components: the synaptic body, the inner segment, and the outer segment. The synaptic body of a rod is called a spherule, whereas that of the cone is called a pedicle. Photopigment is stored in discs in the outer segments. In rods, the discs are not attached to the cell membrane, but cone discs are continuous with it.



Intraretinal processing occurs from photoreceptors to bipolar cells to ganglion cells, with modulation by horizontal (outer plexiform layer) and amacrine (inner plexiform layer) cells.



A cilioretinal artery contributes to the vascular supply of the retina in approximately 50% of individuals and 30% of eyes. In 15% of individuals, it contributes to macular circulation.

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Dhaval Patel MD



Normally, axons of ganglion cells do not become myelinated until after they pass through lamina cribrosa, as part of the intraorbital optic nerve. When myelinated fibers are visible ophthalmoscopically, oligodendrocytes have migrated anteriorly.



Multiple Branch retinal artery occlusion  suspect Susac's syndrome.



The results of the EVS study indicated the following: 1. There was no difference in final visual acuity/media clarity whether or not patients

received systemic antibiotics. 2. Hand motions or better visual acuity on presentation did equally well with immediate

vitreous biopsy or vitrectomy. 3. Eyes with light perception-only vision had much better visual outcome with immediate

vitrectomy rather than vitreous biopsy.



RPE degenerations have been identified in patients with Hunter's, Hurler's, Sanfilippo's, and Scheie's mucopolysaccharidoses. Maroteaux-Lamy syndrome is not usually associated with RPE degeneration.



Rhegmatogenous detachments occur in up to 25% of patients with CMV retinitis. They are associated with a diffusely necrotic peripheral retina with numerous small retinal holes.



RPE cells comprise the outer blood-retinal barrier; the inner blood-retinal barrier consists of the endothelium lining the retinal blood vessels.



The retina is attached at the ora serrata and the optic nerve. The uvea has attachments at the optic nerve, scleral spur, vortex veins, and long and short posterior ciliary vessels. This anatomic difference helps to separate choroidal detachments from retinal detachments on ultrasonography.



Among the causes of decreased concentration of hyaluronate in vitreous are syneresis, myopia, aphakia, diabetes mellitus, and injury with hemorrhage, inflammation, or surgery. 235


Dhaval Patel MD



Each photoreceptor renews its outer segment every 10 days.



The ATP-dependent Na+-K+ pump can be found on the Apical surface of the RPE cell.



The rods are 100 to 1000 times more sensitive to light than the cones, allowing better vision in dim light. The highest concentration of rods is actually 20° from the fovea.



Most consistent finding in RP is  reduced ERG response



Best disease is disorder of RPE.



The 4 characteristic findings of POHS are:



o

punched-out chorioretinal lesions (histo-spots)

o

peripapillary atrophic pigmentary changes

o

lack of vitritis

o

CNV

Doses >3 mg/kg/day or 300 g total of chloroquine, and >6.5 mg/kg/day (<400 mg/day appears safe) or 700 g total of hydroxychloroquine may produce the bull‘s eye maculopathy. The total daily dose seems more critical than the total cumulative dose. The maculopathy often progresses after medications are discontinued because the drug concentrates in the eye. Hydroxychloroquine appears safer since it does not readily cross the blood–retinal barrier (toxicity rarely occurs with use <7 years). Check visual acuity, red Amsler grid and visual fields (central 10 with red test object) at baseline and every 6 months (chloroquine) or 12 months hydroxychloroquine) while patient is taking medications; color fundus photographs (especially if abnormalities seen) and color vision (preferably including the blue-yellow axis) are optionally checked. The two most sensitive tests for detecting these defects are the Adams Desaturation15 test and the Hardy-Rand-Rittler test. 236


Dhaval Patel MD

High risk patients with drug use >5 years with high fat level body habitus, renal or liver disease, and age >60 years old especially if frail or extremely thin are at higher risk of developing toxicity and should be checked more frequently. Low-risk patients (defined as nonobese individuals under age 60 years old, using less than 3 mg/kg/day of chloroquine or 6.5 mg/kg/day of hydroxychloroquine for fewer than 5 years, and without concomitant renal, hepatic, or retinal disease) require no additional screening evaluations.



Chronic vitreous cells are likely to be absent in Ocular Histoplasmosis.



Ocular inflammatory disease most commonly associated with multiple sclerosis is Intermediate Uveitis.



Most common cause of vision loss in ARMD is fibrous scarring. (not CNVM ??)



Leopard-spot pigmentation may appear in systemic large cell lymphoma, leukemia, bilateral uveal melanocytic proliferation, and organ transplant chorioretinopathy



Origin of the myopic crescent. As the eye enlarges, the choroid and retina gradually pull away from the temporal optic nerve head. Thus, in extreme cases, sclera is seen. In less extreme enlargement, choroid or a rim of pigment epithelium can be seen.



Patients with soft drusen are more likely to develop choroidal neovascular membrane.



A longitudinal study including 447,407 people with diabetes but without macular edema found that diabetic neuropathy (hazard ratio [HR], 1.59) was second only to type 1 diabetes in predicting which patients would progress to macular edema. Diabetic nephropathy had an HR of 1.41, Latino race had an HR of 1.28, and black race had an HR of 1.14.

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

AREDS2 found a 5-year rate of progression to age-related macular degeneration (AMD) of 31% for patients receiving placebo. No significant difference in rate of progression to AMD was seen among these groups: antioxidants (rate of 29%), omega-3 fatty acids (31%), both (30%).



An analysis of AREDS found that, compared with those without AMD, the odds of death associated with circulatory disease in men with advanced AMD was about 2 times greater.



AREDS found that high-dose antioxidants protect against AMD. A new analysis of data from the AREDS population found that high-dose antioxidants do not affect intraocular pressure.



study of AMD in Wisconsin found 512 incident cases of early AMD and 117 incident cases of late AMD. The routine use of aspirin 10 years before the study was significantly associated with the incidence of late AMD. The estimated incidence was 1.76% in those who regularly used aspirin and 1.03% in nonusers. Early AMD was not significantly associated with aspirin use.



myopic patients with diabetes may be up to 60% less likely to develop diabetic retinopathy than patients without myopia.



Myopia >2D is protective for DR.



Aldose reductase gene mutation causes more susceptibility of type 2 DR patients for developing retinopathy.



In all, 13.4% of the patients receiving ocriplasmin and 3.7% of the placebo group achieved nonsurgical resolution of vitreomacular adhesion at day 28. intravitreal injection of ocriplasmin (125 µg).

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Dhaval Patel MD



IOFB with >90% copper generally cause an acute inflammatory response (including intraocular necrosis), concentrations of 70% to 90% cause chalcosis leading to a copper ring (identical to the Kayser-Fleischer ring in Wilson's disease) and sunflower cataract. Concentrations <70% can be tolerated; however, other factors such as location and fibrous encapsulation modulate the tissue reaction.



general immune response, similar to what is seen in onchocercisis (Mazzoti reaction) or in some cases of syphilis (Herxheimer reaction)



Gunn‘s dots: Light reflections from internal limiting membrane around disc and macula



Gunn‘s sign: Arteriovenous nicking in hypertensive retinopathy



22% of eyes had vitreous detachment by age 65. This number increased to 60% by age 75.



Retinal attachment: 1. negative pressure in the subretinal space created by the metabolic pump of the retinal pigment epithelium and 2. the relatively higher oncotic pressure in the choroid, 3. interdigitation of the pigment epithelial cell processes and the outer segment of photoreceptors, and 4. mucopolysaccharide ―glue‖ between the pigment epithelium and the sensory retina



Retinoschisis is frequently accompanied by atrophic holes. Inner-layer holes are generally small and difficult to see. Outer-layer holes, which are larger and therefore more easily seen, are much more significant in the pathogenesis of retinal detachment.



A retinal dialysis is a circumferential linear tear, the anterior margin of which is at or near the ora serrata. The retina is thinnest and least developed at the ora, especially in the inferior temporal quadrant. Dialyses occur at any age, but they are particularly common in youth— hence the well-known clinical entity of inferior temporal dialysis of the young. 239


Dhaval Patel MD

About 75% of retinal breaks that occur after blunt ocular trauma are retinal dialyses.



The distribution of retinal breaks throughout the quadrants of the fundus is different for each type of break. Horseshoe tears are most common in the superior temporal quadrant; the second most susceptible site is the superior nasal quadrant. Operculated tears are also located most frequently in the superior quadrants, although they tend to occur more posteriorly than horseshoe tears. Atrophic retinal breaks are also usually located in the superior temporal quadrant, but the second most common quadrant is the inferior temporal. Dialyses are found most frequently in the inferior temporal quadrant



Natural history of untreated detachment 1. Usually, most untreated clinical rhegmatogenous detachments progress to near total or total detachment and blindness. 2. Occasionally, a detachment remains indefinitely as a subtotal detachment with stable borders and the creation of demarcation lines. This is most apt to occur in detachments caused by inferior breaks, particularly small breaks or dialyses. 3. Rarely, subretinal fluid due to a superior retinal break settles inferiorly away from the break, and the site of the original break flattens. 4. Very rarely, spontaneous reattachment occurs, usually associated with a very small break and excellent presumed ―pumping‖ of the retinal pigment epithelium or closure of the break by scar tissue.



30% of the retina lies anterior to the equator.



The pupil should be dilated to the maximum possible diameter. Mydriatics, such as 2.5% or 10% phenylephrine, used alone are totally inadequate; the moment the bright light is projected into the eye, the strong stimulation to sphincter contraction will overcome the action of the dilator muscle, and the pupil will become miotic. On the other hand, cycloplegics used alone, while much more satisfactory than mydriatics alone, do not give maximum dilation but they do result in a dilation that is not affected by the strong light. 240




Dhaval Patel MD

In approximately 12% of symptomatic posterior vitreous detachments, however, a careful search of the periphery reveals a tear of the retina. If the flashes are associated with floaters, it is wise to assume that a retinal tear exists, until proved otherwise.



Laser test: Laser intensity is adjusted to create a medium-intensity laser spot in normal retina. This same intensity is then applied to the area of the retina in question. Where retinoschisis is present, a white spot will result, but where retinal detachment is present, there will be no visible reaction to the laser.



Photomydriasis: Laser application in at least eight meridia is sometimes sufficient to achieve adequate dilation. Laser spots are placed midway between the pupillary margin and the iris root, causing contraction of the dilator muscle. If pupillary fibrosis is present, it may be amenable to Nd: YAG laser transection.



If the choroidal detachment is not in the area of the retinal break, the surgeon should simply proceed with retinal surgery. If, however, the choroidal detachment is in the area of the retinal break or in the area where subretinal fluid must be drained, the surgeon should begin the operation with drainage of the suprachoroidal fluid. Normal intraocular pressure can be maintained during drainage with use of a pars plana cannula for the continuous infusion of a balanced salt solution into the vitreous cavity. The surgeon may then proceed immediately with conventional retinal reattachment surgery.



The ora serrata is the anterior limit of the sensory retina. It is characterized nasally by prominent ora teeth, which point anteriorly. Between each pair of teeth is an ora bay. There are approximately 48 ora teeth per eye. The pattern of serration is not present temporally, where the ora teeth are small or absent



Detachment of the pars plana is more common on the nasal side, apparently because of the narrower retinochoroidal adhesion. Detachment of the pars plana epithelium is an important feature, and the pars plana must be carefully examined with scleral indentation to detect the presence of breaks in the area, particularly along the anterior limit of the vitreous base. 241


Dhaval Patel MD



It is helpful to recall that the distance from the ora to the equator is approximately 4 disc diameters and that the equator is just slightly anterior to the vortex ampullae.



Drusen are more common in the equator than in the macula. Equatorial drusen may be associated with reticular pigmentary degeneration and are most often found in the elderly.



Existence of narrow funnel shape is evidenced by indirect opthalmoscopy when anterior end of funnel can be seen within 45° field of 20D condensing lens.



Lesions that might be confused with retinal detachment include degenerative retinoschisis, choroidal detachment, tumors of the choroid, vitreous membranes, and whitewith-pressure or white-without-pressure.



A diagnostic feature of retinoschisis is the ―white Swiss cheese‖ appearance of the outer layer of the schistic retina as it is frozen. In contrast, the retinal pigment epithelium deep to an overlying detached retina appears dull orange when viewed during cryopexy. Type 1 schisis detachment refers to detachment that does not extend beyond the area of retinoschisis, whereas type 2 schisis detachment extends beyond the schisis. Type 2 schisis detachments generally require retinal detachment repair, whereas type 1 generally do not.



Asymptomatic eyes include those with and without additional risk features. Cases in which lesions are diagnosed in a second (―fellow‖) eye following a detachment in the first eye are discussed in a separate section below. The term ―non-fellow eye‖ indicates absence of a history of retinal detachment in the other eye.



three basic steps in closing retinal breaks and reattaching the retina: 1. Conducting thorough preoperative and intraoperative examinations with the goal of locating all retinal breaks and assessing any vitreous traction on the retina. 242


Dhaval Patel MD

2. Creating a controlled injury to the retinal pigment epithelium and retina to produce a chorioretinal adhesion surrounding all retinal breaks so that intravitreal fluid can no longer reach the subretinal space. 3. Employing an appropriate technique, such as scleral buckling and/or intravitreal gas, to approximate the retinal breaks to the underlying treated retinal pigment epithelium.



Factors considered in the selection of a drainage site include (1) the distribution of subretinal fluid when the eye is in a position at which drainage will be performed, (2) the location and size of the retinal break(s), (3) the location and configuration of the buckle, (4) the vascularity of the choroid, (5) features of vitreoretinal and epiretinal membrane traction, and (6) the ease of exposure of the proposed drainage site. The optimal locations for drainage are usually just above or below the lateral rectus muscle, because major choroidal vessels are avoided and exposure of sclera is excellent.



Uveitis is rare in Still's disease, which is more common in boys.



The reduction in visual acuity caused by epiretinal membrane is related to distortion produced in the outer retinal layers and does not depend on the size or degree of transluscency of the membrane.



A positive Watzke Allen sign is seen in 95% of eyes with full thickness macular hole.



All patients of Macular Hole will report a positive laser beam (50—microns) sign.



Congenital cyst of retina: bilateral, same location, may look like RD, DD is melanoma.



Vascularization of the nasal retina is complete by (approximately) the eighth gestational month. The temporal retina is completely vascularized 1 to 2 months later.

243


Dhaval Patel MD



The risk of retinopathy of prematurity (ROP) does not correlate with the postdelivery age but with gestational age (postconception age).



ROP is not DIRECTLY related with arteriolar oxygen level and not related to NEC.



Zone 1 is a circle of radius (not diameter ..!!) 30 degrees (twice the distance from optic disc to macula) centered on the optic disc. Zone 2 extends to the nasal ora and the temporal equator (radius 60 degrees). Zone 3 is the remaining crescent-shaped region anterior to zone 2 in the temporal retina.



In ROP, Pseudostrabismus results from a change in angle kappa caused by macular ectopia from peripheral cicatrization. Pseudoexotropia is more common than pseudoesotropia.



Benson‘s disease is Asteroid hyalosis.



65% of premature infants with birth weight <1,250 g will develop some stage of ROP.



Guiat‘s sign: Tortuosity of retinal veins in arteriosclerosis



In acute leukemic oculopathy, Flame-shaped nerve fiber hemorrhages are the one most common funduscopic finding. White-centered hemorrhages (Roth's spots), cotton-wool spots, optic disc swelling, and perivascular infiltration also may be seen but are less common.



Diffuse arteriolar attenuation is not a characteristic finding in renal failure, although it may occur if there is severe associated hypertension.



In albinism, fewer ganglion cell fibers decussate at the chiasm than in normal visual pathways. 244




Dhaval Patel MD

juvenile retinoschisis from Goldmann-Favre dystrophy: The electrooculography (EOG) is abnormal in Goldmann-Favre disease and normal in Xlinked juvenile retinoschisis. Goldmann-Favre disease is autosomal recessive. Both diseases have abnormal electroretinograms (ERGs). In mild forms of juvenile retinoschisis, the scotopic b-wave is lost, with preservation of the a-wave. In severe cases, the ERG is extinguished, as it is in most cases of Goldmann-Favre. Both diseases are characterized by foveal and peripheral retinoschisis, as well as retinal pigment epithelial disturbances, although the latter are more severe in Goldmann-Favre.



Cone dystrophy (not Stargardt‘s..!!) is the most common ―bull's-eye‖ maculopathy.



Retinitis punctata albescens is not a form of congenital stationary night blindness (CSNB) but is progressive (although more slowly than typical retinitis pigmentosa).



Visual function in the pattern dystrophies of the retinal pigment epithelium (RPE) is usually good.



Aicardi's syndrome is limited to the female sex because it is X-linked dominant. It is lethal in male infants or fetuses.



In CSR, The early FFA finding is the presence of smoke stack or ink blot and the late FFA finding is the presence of mushroom or umbrella shape accumulation of dye



Think of Diabetic Retinopathy in a case of recurrent stye with peripheral neuropathy.



In pneumatic retinopexy, Grade C PVR is a contraindication as the retina is usually rigid in these cases. The success rate is higher in Phakic than pseudophakic patients. 245


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Dhaval Patel MD

Risk factors for expulsive suprachoroidal hemorrhage include increased axial length, glaucoma, atherosclerosis and previous expulsive suprachoroidal haemorrhage. It may be reduced by o

Small incision surgery

o

Control of IOP

o

Control of HTN



It is polycythemia and not thrombocytopenia which may be associated with VHL. It is due to erythropoietin secretion from cerebellar hemangioblastoma.



Early CMV retinitis and CWS can be differentiated by presence of hemorrhage and enlargement of the lesion in case of former.



ROP like condition but without history of prematurity: FEVR (it is AD condition)



ERG: o

Reduction in b wave: diffuse degeneration or dysfunction of cells in the inner nuclear layer (Muller or bipolar cells)  siderosis, CRVO, vigabatrin

o

Reduction in both a and b wave: Cancer associated retinopathy CAR



Becker's phenomenon: Pulsation of the retinal arteries in Basedow's disease (Grave’s disease)



Coats'-type retinal vascular changes have been noted in patients with facioscapulohumeral muscular dystrophy, Turner's syndrome, Senior-Loken syndrome, and one variant of the epidermal nevus syndrome. In addition, Coats'-like retinopathy has been noted in up to 3.6% of patients with retinitis pigmentosa.

246


Dhaval Patel MD



Salmon in Sickle cell patients: actually they have Smoked salmon. Salmon patch haemorrhages (and therefore red as in smoked salmon cf. with poached salmon which is pink) occur from pre-retinal and internal lining membrane haemorrhages occurring near an occluded arteriole.



Asteroid Hyalosis is distinguished from vitreous haemorrhage on ultrasound by



o

The asteroid hyalosis opacities are dense and uniformly high reflective

o

They are separated from the retina by an echolucent space.

Macropsia (due to crowding of photoreceptors): ARMD, Macular scar Micropsia (due to separation of photoreceptors): Macular oedema, CSR, Chorioretinitis





Gregg's syndrome: Congenital Rubella Embryopathy o

Congenital cataracts, deafness, cardiac defects (patent ductus)

o

Retention of lens nuclei in embryonic nucleus (not pathognomonic)

o

Virus remains viable in lens for several years

o

"Salt and pepper" retinopathy

o

May have congenital glaucoma, inflammation

PRN: Pro Re Nata = Treat and Observe o

Regular follow up

o

Treat if signs of exudation

TAE: Treat And Extend



o

Treat at every visit

o

Gradually extend treatment interval

Photosensitisers for PDT: 247


o

Dhaval Patel MD

1st generation 

Photofrin (porfimer sodium)



transient-induced photosensitivity of the skin for 6 to 8 weeks after injection



less than optimum activation wavelength (630 nm) for maximizing tissue penetration



relatively low extinction coefficient

2nd generation 



benzoporphyrin derivative (BPD): 

absorption maximum at about 690 nm



formulated in liposomes as its hydrophobic

Purlytin 

Hydrophobic



chlorin-type photosensitizer that has shown minimal cutaneous toxicity



Dilated NON TORTUOUS retinal veins:  always think for Ocular Ischemic Syndrome.



Diabetes is not an independent risk factor for BRVO.



AREDS is the only study in medicine showing benefit of dietary supplements ??



Electrodes for ERG: o

Hard contact lens electrodes

o

DTL- Dawson Trick Litzkow fiber electrode

o

anomalous polyvinyl alcohol gel electrode

o

Dermal electrodes 248






Dhaval Patel MD

Electronegative B wave in ERG: o

CSNB

o

XL retinoschisis

o

CRAO

o

MAR

Antibody against alpha-enolase o

Autoimmune retinopathy

o

CAR

o

Wet ARMD

o

Behcet‘s disease



ESCS: AR, NR2E3, loss of transcription inhibitor by photoreceptor cell



Anecortave acetate, marketed as Retaane 15 mg for the treatment of AMD, is a synthetic analog of cortisol with angiostatic but not glucocorticoid receptor mediated activity. Anecortave acetate is delivered as a posterior juxtoscleral depot (PJD) onto bare sclera near the macula. Anecortave acetate is administered outside the globe with a curved, blunttipped cannula. The cannula is inserted between Tenon‘s capsule and the sclera and the drug forms a depot directly behind the macula where it is slowly released over 6 months. A counter-pressure device (CPD) is used to prevent reflux of the suspension.



Copper was added to the AREDS formulations containing zinc to prevent copper deficiency anemia, a condition associated with high levels of zinc intake.



Multiple sub-ILM hemorrhges: shaken baby syndrome (abusive head trauma)

249


Dhaval Patel MD



OPL is the watershed zone for retinal circulation.



Verhoff‘s membrane = COST, Cone Outer Segment Tips



Absolute risk of RD in lattice degeneration is 1% over 10 years.



Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy. (journal of clinical investigations, 2012, 122/7)  trial of EPLERENONE 25 mg OD for 1 week and 50 mg OD for 3 weeks.



o

Specific mineralocorticoid receptor antagonist

o

Used for HTN, CHF, aldosterone secreting adenoma

o

CSCR may be related to mineralocorticoid receptor (MR) activation (glucocorticoid bind to MR)

Seven rings of blunt trauma to eye 1. Central iris: Sphincter tear 2. Peripheral iris: Iridodialysis 3. Anterior ciliary body: Angle recession 4. Separation of ciliary body from the scleral spur: Cyclodialysis 5. Trabecular meshwork: Trabecular meshwork tear 6. Zonules/lens: Zonular tears with possible lens subluxation 7. Separation of the retina from the ora serrata: Retinal dialysis



A positive scotoma, in which patients complain of something obstructing their central vision, is a symptom of macular disease. This is in contrast to optic neuropathy which typically causes a missing area in the visual field (a negative scotoma).

250


Dhaval Patel MD



Despite its close association with the choroid, the RPE is considered a part of the retina because it is from the same embryologic germ cell layer—neural ectoderm.



Glutamate is the excitatory neurotransmitter released by photoreceptors, bipolars, and ganglion cells. Glycine and GABA are inhibitory neurotransmitters released from amacrines; it is unclear what neurotransmitter horizontal cells secrete (?GABA)



Cleft palate can be associated with stickler syndrome.



Nonsyndromic congenital retinal nonattachment (NCRNA) comprises congenital insensitivity to light, massive retrolental mass, shallow anterior chamber, microphthalmia, and nystagmus.



In choroideremia, in contrast to primary retinal dystrophies, the fovea is spared until late.



The internal elastic lamina separates the intima from the media. Retinal arterioles contain smooth muscle within their walls, but unlike arteries the internal elastic lamina is discontinuous.



Dynamic traction: pathogenesis of retinal tears and rhegmatogenous RD. Static traction: pathogenesis of tractional RD and proliferative vitreoretinopathy. 3 types  tangential, anteroposterior and bridging (trampoline)



Pan Retinal 2.2 is a hybrid lens which uniquely combines magnification nearly that of the 20D lens with a field of view approaching that of the 30D lens. Excellent for virtually every examination procedure, including small pupil examinations.



Myopia: recent evidences o

Outdoor activity is protective 251


o

Dhaval Patel MD



Vitamin D (regulation of eye growth via retinoic acid receptors)



Less divergent light



Ambient light levels



Less peripheral defocus light

Peripheral retinal defocus



Myodesopsia: perception of eye floater is known as myodesopsia.



CAR: deceased rod-cone amplitude in ERG MAR: selective loss of scotopic B wave (similar finding seen in CSNB)



the indirect ophthalmoscope can be used to see the „forest‟ and the slit lamp to see the individual „trees‟.



The retina itself is a thin transparent tissue, which is thickest near the optic nerve, where it measures 0.56 mm. It thins to 0.18 mm at the equator and to 0.1 mm at the ora serrata. At the foveal area, it has thinned to about 0.2 mm. The nerve fiber layer increases at the edge of the disc and is the only retinal structure that continues into the disc to become the optic nerve.



Issues in naming cones: Two schemes have been used: RGB (red, green, blue) and LMS (long-, mid-, and shortwave) The LMS system denotes a cone's relative spectral peak to avoid confusion between perceptual names (red, green, blue) and VP absorption peaks (yellow-green, green, violet)



The primate retina possesses three image-forming photoreceptor chromatypes. Rods express the RH1 opsin group VP 499, have a unique rod structural phenotype, and selectively contact rod BCs and HC axon terminals. 252


Dhaval Patel MD

Blue cones express the SWS1 opsin group VP 420, have a subtle but unique blue cone morphology, contact cone BCs and HCs, with a strong preference for a blue ON BC. Red and green cones express VP 530 or VP 560 from the LWS opsin group, are structurally indistinguishable from each other, contact cone BCs and HCs, but avoid the blue ON BC.



The resolution limit set by the packing density of the cones is similar to, but slightly higher than, the limit set by the optics of the eye. As a result, under ideal conditions, an observer with excellent vision can just resolve fine detail whose angular subtense approaches that of a single cone. The exact shape of the fall in acuity with eccentricity depends on the type of target used, but acuity falls roughly to half at 1° and to one-fourth at 5°.



Cone dystrophy implies a panretinal disorder and not a localized dysfunction, such as in macular degeneration, where the photopic ERG is normal. Cone dystrophies are characterized by a decreased or nonrecordable photopic ERG and a normal scotopic ERG.



Normal human color vision is trichromatic, mediated by three well-separated classes of cone photoreceptor commonly referred to as the blue, green, and red cones. Calling them short-, middle-, and long-wavelength sensitive, abbreviated S, M, and L cones minimizes confusion that can arise from giving them color names. Photopigment molecules within each cone are responsible for the spectral properties of the cones. Each photopigment molecule is composed of two parts; a protein termed the opsin, and an 11-cis-retinal chromophore. The official names for the genes encoding the L, M, and S cone opsins are OPN1LW, OPN1 MW, and OPN1SW respectively. Both OPN1LW and OPN1 MW are on the X-chromosome at position Xq28, OPN1SW is located on chromosome 7 at 7q32.1. The location of OPN1LW and OPN1 MW on the X-chromosome accounts for the great gender difference in the prevalence of color vision deficiencies.



The suffix -opia denotes dichromacy. The suffix -anomaly denotes anomalous trichromacy in which two of the cone classes are more similar in spectral sensitivity than the corresponding normal cones:

253


Dhaval Patel MD



In ∼25% of humans a cilioretinal artery hooks around the temporal margin of the optic disk and provides a portion of the macula with the arteriolar supply.



Retinal circulation: Low level of flow (15 – 34 mg/min), High O2 extraction (40%) Choroidal circulation: High level of flow (677 – 735 mg/min), Low O2 extraction (4%)





Kimmelstiel-Wilson (K.W.) syndrome: These patients had hypertension, generalised edema and renal involvement as indicated by the presence of protein, casts and R.B.Cs in their urine with or without pyuria. Majority had raised blood urea.

Common Ocular Fluorophores o

Lipofuscin in the retinal pigment epithelium (RPE) (A2E)

o

Extracellular vitelliform material

o

Crystalline lens

o

Optic nerve head drusen

o

Astrocytic hamartoma

o

Sclera



Coats disease may be part of a spectrum of related genetic disorders known as retinal hypovasculopathies which includes Norrie disease, familial exudative vitreoretinopathy (FEVR), fascioscapulohumeral muscular dystrophy (FSHD), and the osteoporosis pseudoglioma syndrome



melanocytoma appears to have an equal incidence in all races, whereas uveal melanoma is uncommon in black people



Ablatio fugax: photocoagulation and cryotherapy of peripheral tumors in VHL can often lead to massive retinal hard exudate accumulation and retinal edema in the macula, contributing to further decrease in vision following treatment. 254


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Dhaval Patel MD

2RT: Nonthermal Retina Regeneration Therapy (2RT; Elex, Adelaide, Australia)

o short-pulsed laser treatment (pioneered by John Marshall and Peter Hamilton of UK)

o to treat diabetic maculopathy and macular edema at an earlier stage o Q-switched, green Nd:YAG laser with a wavelength of 532 nm o pulse duration is 3 nanoseconds with energy of 1 J per pulse which causes the RPE cells to release matrix metalloproteinase enzymes, which are believed to 'clean up' the bruch's membrane. The laser thus triggers what is described as photoregeneration of the retinal pigment epithelium and Bruch's membrane.



Low Fluence PDT: o

PDT by itself also causes upregulation of VEGF and induces fibrosis

o

Low fluence photodynamic therapy is done using

o



light intensity of 50mJ/m2



300mW of power



83 seconds



compared to standard fluence where 100 mJ/m2 at 600mW of power for 83 seconds.

For CNVM, CSR etc



Pseudoxanthoma elasticum and myopia may cause spontaneous defects in bruch‘s membrane, making the patient prone to development of choroidal neovascularization.



Diffuse pigmentary retinal changes in congenital rubella syndrome may be confused with retinitis pigmentosa. However, the ERG is normal in congenital rubella.

255


Dhaval Patel MD



The pattern electroretinogram (PERG) measures the electrical response to an alternating pattern stimulus that has a constant overall retinal luminance, and the response appears to be localized to retinal ganglion cells.



abnormal ERG and a normal EOG: o

congenital stationary nightblindness

o

X-linked retinoschisis

o

cone dysfunction



The choriocapillaris does not communicate freely with the optic disc capillaries. The choroidal circulation is from the posterior ciliary arteries; the optic disc and retinal arterioles are branches of the ophthalmic artery.



choroidal hemangioma



o

This is an uncommon hamartoma that has been reported to exhibit two clinical growth patterns:

o

1) circumscribed tumors without systemic disease, and

o

2) diffuse tumors often associated with the Sturge-Weber syndrome.

o

The lesion is histologically benign; however, the lesion can lead to an exudative retinal detachment if untreated.

o

Therapeutic options are photocoagulation and cryotherapy.

o

The solitary type is histologically characterized by a cavernous hemangioma with sharply demarcated pushing borders, often compressing surrounding melanocytes and choroidal lamellae. This is visible clinically as a ring of hyperpigmentation in the periphery of the lesion and on fluorescein angiography as a ring of blockage of the underlying choroidal fluorescence.

o

von Hippel-Lindau disease has vascular lesions of the retina and cerebellum; however, these are capillary hemangioblastomas.

Retinal Dialysis and Detachment 256






Dhaval Patel MD

o

Approximately 10% of dialysis-related detachments present immediately

o

30% within 1 month

o

50% within 8 months

o

80% within 2 years

Shifting Fluid: o

Exudative RD

o

Old RD

o

Aphakic RD

Lattice Degeneration: o

10% of the population and is bilateral in 30-50% of affected patients

o

Crisscrossing, fine, white lines that account for the name lattice degeneration are present in roughly only 10% of lesions and most likely represent hyalinized blood vessels

o

Various pigmentary disturbances occur in more than 80% of lattice lesions. Whiteyellow flecks, similar to that seen with degenerative retinoschisis, are an additional common associated feature.

o

Atrophic retinal holes and tractional retinal tears may complicate lattice degeneration and increase the risk of retinal detachment.

o

When retinal thinning and pigmentary disturbances are found along retinal vessels, these lattice lesions are referred to as radial perivascular chorioretinal degeneration and are classic findings in Wagner and Stickler disease, a familial vitreoretinal degenerative syndrome

o

Retinal detachment is a relatively rare complication of lattice degeneration (<1% of patients with lattice degeneration) but is associated with as many as 40% of all rhegmatogenous retinal detachments.

o

Retinal detachments caused by lattice degeneration occur most commonly by a tractional tear at the cuff or posterior margin of the lattice lesion, or less commonly by means of an atrophic hole within the zone of lattice.

257


o





Dhaval Patel MD

o

Tractional tears located at the margin of lattice account for 55-70% of retinal detachments in lattice degeneration and are the result of a posterior vitreous detachment.

o

Atrophic holes account for 30-45% of retinal detachments in lattice degeneration.

3 invariable features: thinning or atrophy of the inner retinal layers, vitreous liquefaction overlying the area of thinned retina, and vitreous condensation and exaggerated vitreoretinal attachments at the borders of the lesions.

Different RDs: o

Subclinical RD: subclinical retinal detachment (SCRD), which is defined as a retinal break with surrounding subretinal fluid extending at least 1 disc diameter (DD) away from the break, but no more than 2 DD posterior to the equator.

o

If there is less than 1 DD of fluid, then it is a break without detachment.

o

Subtotal RD: atleast one quadrant is attached.

o

Total RD: complete detachment of Retina

Iridofundal Coloboma o

Incidence-0.14%,2\3 B\L, 40% develop retinal detachment (0.6-1.7% of all RD)

o

60% are bilateral

o

Aymptomatic

o

Diminished vision - coloboma involving macula or assoc. with Nystagmus/RD

o

Leucocoria

o

Scotoma corresponding to area of coloboma

o

Appears as vertically oval ,glistening white defect of varying size can be associated with microphthalmos, cataract and myopia.

o

In the normal eye, optic fissure closes 33 to 40 days after conception.

o

Failure of the embryonic fissure to close along the inferonasal aspect of the optic cup and stalk 258




Dhaval Patel MD

Endophthalmitis o

Endogenous Endophthalmitis: A 17-year prospective series and a review of 267 cases published in 2003 found that 67% of patients had an extraocular focus of infection. Liver abscess was the most common extraocular focus for endogenous bacterial endophthalmitis, followed by endocarditis.

o

Diabetes mellitus (DM) is a risk factor for both types of endophthalmitis. Both types of endophthalmitis are associated with pain and decreased long-term visual acuity. Vitrectomy and/or vitreous tap with intravitreal antibiotics can be used to treat both forms of endophthalmitis. In endogenous endophthalmitis, Streptococcus and Staphylococcus aureus predominate. Intravenous antibiotics may be indicated for endogenous endophthalmitis to treat the source, whereas they usually play no role in the management of postoperative endophthalmitis (especially postoperatively in patients who have undergone cataract surgery, as per the Endophthalmitis Vitrectomy Study [EVS] study).

o

Saccular Endophthalmitis: Delayed-onset endophthalmitis following cataract surgery develops when an organism of low virulence becomes trapped within the capsular bag. The infection is caused most frequently by P. acnes and occasionally S. epidermidis, Corynebacterium spp. or Candida parapsilosis.

o

Cluster endophthalmitis is a term defined as the occurrence of two or more than two infections at a time, or the occurrence of repeated postoperative infections under similar circumstances, i.e with the one surgeon, same staff, same operation theatre, same equipments, etc. These infections usually occur as a result of a breach in standard protocol of pre-operative, intraoperative and postoperative care. Cluster post-operative endophthalmitis is generally exogenous in origin.

o

Filtering bleb—associated Endophthalmitis: The most common organisms responsible for this condition include Streptococcus species (Gram-positive cocci in pairs or chains) and Haemophilus influenzae (Gram-negative coccobacilli). Other organisms, such as Staphylococcus epidermidis (Gram-positive cocci in clusters) and Gram-negative species, have been implicated less frequently. Fungal causes are rarely associated with filtering bleb—associated endophthalmitis.

o

Delayed-onset endophthalmitis after cataract surgery include Staphylococcus epidermidis, fungal species such as Candida, and Propionibacterium acnes. Endophthalmitis caused by P. acnes typically presents from 3 months to 2 years after surgery, whereas S. epidermidis generally presents within 6 weeks and Candida within 3 months. The presence of a white plaque within the capsular bag specifically suggests the diagnosis of P. acnes.

259


Dhaval Patel MD



Schwartz's syndrome is high IOP associated with a rhegmatogenous retinal detachment. Photoreceptor outer segments migrate transvitreally into the aqueous, block the trabecular outflow pathways, and result in IOP elevation.



SCHLEIRENING: drainage of SRF through breaks of retina in RD cases during PFCL assisted surgery



GLUT-1 is the most common transporter of glucose in retina.



With 1 ml of gas bubble, IOP by schiotz tonometry shows error of 8 mmHg in range of 10-20 mmHg and 15 mmHg in range of 30-40 mmHg.



In macular translocation, retina is rotated around optic nerve by 35-50o.



Ocular ischemic syndrome o

dot and blot hemorrhages in the midperipheral retina that may extend into the posterior pole

o

Ocular perfusion pressure on ophthalmodynamometry is reduced substantially with collapse of the central retinal artery with minimal pressure.

o

Anterior segment manifestations include a limbal flush, anterior chamber cell and flare, neovascularization of the iris and angle, and cataract.

o

Hypotony from decreased aqueous production or elevated IOP from neovascularization of the angle may be present.

o

High-grade carotid stenosis is the usual cause.

o

Many of these patients also have systemic hypertension, atherosclerosis, and diabetes mellitus.

o

The prognosis of this condition is usually poor, especially if neovascularization is present.

260


Dhaval Patel MD



The natural course of Leber's stellate neuroretinitis is spontaneous resolution over several months. The prognosis is excellent, and over 80% of patients have visual acuity better than 20/40.



Floaterectomies:





o

FFQ 22 test: Well-Being-Index of WHO (5 questions) together with 17 questions of the Frankfurt Floater Questionnaire

o

National Eye Institute Visual Function Questionnaire-25 test (NEI-VFQ-25)

o

1-step single-incision-site core vitrectomy (Intrectomy) procedure

Approaches for to anti-VEGF treatment o

―treat-and-extend‖ protocol: the patients are treated during each visit regardless of activity. If there is no sign of activity, the control and treatment intervals are extended gradually, whereas if there are signs of recurrence, the intervals are shortened.

o

As needed treatment (PRN- Pro Re Nata): where patients are seen monthly and treated if signs of exudation appear.

Adaptive Optics Scanning Laser Ophthalmoscopy (AO-SLO) o

For AMD

o

Liquid crystal on silicone spatial light modulator

o

Measure and correct subject‘s aberration

o

Photoreceptor analysis: 0.34 x 0.34 mm, 32 frames per second

o

Blood flow analysis: 0.82 x 0.41 mm, 64 frames per second



EOG shows reduced Arden ratio in autosomal dominant CME



Vitreomacular interface (VMI) diseases o

Full thickness macular hole (FTMH) 261


Lamellar macular hole (LMH)

o

Epiretinal membrane (ERM)

o

Vitreomacular traction (VMT)

Dhaval Patel MD

International Vitreomacular Traction Study (IVTS) Group Classification System o

In 2012

o

designed to reflect new insights derived from SD-OCT and, as such, is strictly anatomy-based (derived from OCT images alone). 

Vitreomacular Adhesion: perifoveal vitreous separation with continuing vitreomacular attachment within a 3-mm radius of the foveal center, and completely normal retinal anatomic morphology.



Vitreomacular Traction: same as VMA but with abnormal retinal anatomic morphology



Full Thickness Macular Hole: foveal lesion with interruption of all retinal layers from the ILM to the RPE



Fingolimod-associated macular edema (FAME) generally occurs within 4 months of initiating therapy and affects 0.5% of users. It appears to be dose-dependent (observed in only 2 patients taking the FDA-approved 0.5-mg dose) and typically resolves upon cessation of therapy.



OCT is VEGF-meter of retina. It identifies 3 basic types of fluid collection in the retina.



o

Intra-retinal fluid

o

Sub-retinal fluid

o

Sub-RPE fluid

Two types of reactions can be caused by photosensitizer: o

type I reaction: it can react directly with substrates to form radicals or radical ions

o

type II reaction: it can react with endogenous ground state oxygen (3O2) by means of an energy transfer mechanism in producing excited oxygen species, such as singlet oxygen (1O2). This latter reaction is known as the photodynamic reaction. 262


Dhaval Patel MD



The risk for retinal detachment is 4-fold greater after pseudophakic cataract surgery than in the patient's untreated eye, according to a large, population-based Danish study.



A reanalysis of data from AREDS has identified genetic polymorphisms that predict which patients with moderate to severe age-related macular degeneration (AMD) are most likely to respond to antioxidant or zinc supplementation. In a related calculation, the researchers estimate that "genotype-directed therapy of the study population would have more than doubled (>200%) the reduction in AMD progression rate compared with treatment with the AREDS formulation."



The Atherosclerosis Risk in Communities (ARIC) study found that patients with moderate to severe retinopathy had 2.37 times the risk for stroke compared with those with no retinopathy. Patients with mild retinopathy had 1.35 times the risk.



The Post-Injection Endophthalmitis Study Team conducted a retrospective case-control study of endophthalmitis cases. Topical antibiotic use was associated with a greater than 50% increased risk for endophthalmitis and culture-positive endophthalmitis.



Argus II Retinal Prosthesis System o

Mark Humayun, MD

o

designed by Second Sight

o

epi-retinal

o

patients with severe to profound outer retinal degeneration, whose remaining visual acuity is worse than 2.3 logMAR in both eyes

o

best visual acuity attained was 20/1260 (1.8 logMAR)

263


Dhaval Patel MD

Uvea 

Review of Uveitis Therapy



Local Therapies o

o







FDA approval for ―endogenous anterior uveitis‖: 6/12



Efficacy compared with prednisolone acetate



Potential side effects: IOP, cataract; use in pediatrics

Ozurdex and Retisert 

FDA approved for intermediate and panuveitis



Multicenter Uveitis Steroid Treatment (MUST) trial results for Retisert

o

Intravitreal methotrexate for uveitis: Efficacy for cystoid macular edema

o

Intravitreal TNF inhibitors: Caution re: intravitreal infliximab

Emerging Local Treatment: Sirolimus o

Periocular administration preliminary trial

o

Intravitreal trial: Sirolimus as Therapeutic Approach to Uveitis (SAVE) trial

New Systemic Agent Using Classical Immunomodulatory Pathways: Voclosporine o



Status of difluprednate

LX211 LUMINATE trial → Uveitis development Withdrawn

Biologics o

o

Tumor necrosis factor inhibitors 

Relative efficacy of infliximab, adalimumab, and etanercept for uveitis



Golimumab, certolizumab

Anti-CD20 

Rituximab 264


Use in granulomatosis with polyangiitis



Use in uveitis/scleritis

o

Anti-IL17: AIN457 clinical trial

o

IL-1 inhibitors: Gevokizumab, anakira, canakinumab, rilocept

o

IL-6 inhibitors: Toclizumab



Scleritis is not a feature of Behçet's disease.



Diffusely distributed keratic precipitates over the corneal endothelium: o

Fuchs' heterochromic iridocyclitis

o

Sarcoidosis

o

Syphilis

o

kerato uveitis

o

toxoplasmosis



In ocular histoplasmosis, there is no vitreous inflammation.



IRIS ROSEOLA: dilated iris capillaries o



Dhaval Patel MD

Occurs in granulomatous iridocyclitis especially syphilis like

WSS with Female predominance  MAMA o

MEWDS

o

AZOOR

o

MFC

o

AIBSE

265


Dhaval Patel MD

ddx of uveitic glaucoma HSV, HZV, posner-schlossman syndrome, fuchs' heterochromic iridocyclitis, sarcoidosis, rarely toxo, syphilis, S.O.



DD of Hypopyon uveitis: HLA-B27 associated (most common), infection, FB, Behcet's, VKH, malignancy (leukemia, Rb), toxic (RIFABUTIN)



HLA-B27-associated DZs: PAIR o

Ankylosing Spondylitis

o

Reactive arthritis (Reiter's)

o

Psoriatic arthritis

o

IBD



Blau syndrome: familial granulomatous arthritis, AD, granulomatous uveitis, dermatitis, arthritis, defect in NOD2/DARD15 gene, autoinflammatory dz, may respond to anakinra (IL1RA)



drug-related uveitis: rifabutin and cidofovir, bisphosphonates, Bactrim, topical prostaglandins



eye drop which causes drug-induced uveitis: metipranolol



sugiura's sign: perilimbal vitiligo seen in VKH



primary intraocular lymphoma (PIOL): IL10>IL6 (10>6  which should not confuse you now)



ibopamine: increases aqueous production (Italy) 266


Dhaval Patel MD



drug which may worsen MS: infliximab



drug-induced lupus caused by: infliximab



Jenson‘s Juxtapapillary Choroiditis: histoplasmosis should be considered, differentiate it from papilledema.



'Cracked mud appearance' of Progressive outer retinal necrosis (PORN), choroideremia??



Uveitis and poliosis: 1. sympathetic ophthalmia 2. VKH



Arlt‘s triangle: (Ehrlich–Türck line) base-down triangle of central keratic precipitates in uveitis



Kunkmann–Wolffian bodies: Small white peripheral iris spots that resemble Brushfield spots but occur in normal individuals. They are more peripheral than brushfield‘s apots which are around midperiphery.



Kyreileis‘ plaques: White–yellow vascular plaques in toxoplasmosis



Lander‘s sign: Inferior preretinal nodules in sarcoidosis



Patient with uveitis undergoing cataract surgery, Prophylactic systemic steroid treatment is only recommended in patients with previous macular oedema caused by the uveitis. 267


Dhaval Patel MD



JIA is not the same as juvenile rheumatoid arthritis (JRA); the former is negative for rheumatoid factor whereas the latter is positive. JRA is the same disease as rheumatoid arthritis except that it occurs before the age of 16 years.



In Fuchs‘ heterochromic iridocyclitis, the fine ‗‗stellate‘‘ KP are found scattered diffusely on the entire posterior surface of the cornea, unlike most KP, which are located in the inferior cornea.



In Uveitis, Low intraocular pressure (IOP) may occur as a result of reduced secretion of aqueous by the ciliary epithelium. Occasionally the intraocular pressure may be elevated (hypertensive uveitis) as in herpetic uveitis and Posner–Schlossman syndrome.



In CAU, Aqueous flare may be more marked than cells in eyes with prolonged activity and its severity may act as an indicator of disease activity (contrary to previous teaching). The classical teaching that only cellular reaction in the anterior chamber represents active inflammation has been challenged. Flare is caused by chronic break-down of the blood– aqueous barrier, but the intensity of the flare can also indicate an active process, which may respond to therapy.



Iris atrophy that is sectoral occurs characteristically in herpes simplex and herpes zoster. Diffuse iris atrophy occurs in Fuchs uveitis syndrome.



Large KPs in granulomatous disease have a greasy (‗mutton-fat‘) appearance. They are often more numerous inferiorly and may form in a triangular pattern with the apex pointing up = Arlt triangle



DUSN is thought to be caused by migration of a nematode under the retina.



Onchocerciasis: Also known as river blindness, this is caused by infection with the filaria parasite Onchocerca volvulus, which is transmitted by the bite of species of Simulium flies (so-called buffalo gnats). Clinically there are skin changes, nodules and eye changes that can lead to blindness. The nodules develop in subcutaneous tissue especially near bony 268


Dhaval Patel MD

structures and contain living or dead adult worms. Fundus of oncocerciasis is known as Ridley‘s fundus.



MAGIC Syndrome: Mouth and genital ulcers with inflamed cartilage syndrome is a cutaneous condition with features of both Behçet's disease and relapsing polychondritis



Dadizumab (Zenapax): A completely humanised IL- 2 receptor antibody used in kidneytransplant recipients, has shown encouraging clinical results in uveitis patients. In a phase 2 trial, subcutaneous daclizumab was injected at the dose of 2 mg/kg separated by 2 weeks and then 1 mg/kg subcutaneous(SC) every 2 weeks for 26 weeks. The objective of the trial was to reduce the load of the other immunosuppressive agents by half. Immunosuppressive therapy was tapered off in a staggered fashion to SO% or less in 8 to 12 weeks. At 12 weeks, 10 of the lS patients (67%) receiving SC daclizumab successfully achieved the primary end point of reducing concomitant immunosuppression load by SO%.



Anakinra: Anakinra is a recombinant, human, nonglycosylated IL-1 receptor antagonist (IL-1RA). It inhibits IL-1 activity, downregulating the proinflammato1y functions of IL-1 including chemotaxis, activation of antigen-presenting cells, and the upregulation of cell surface adhesion molecules involved in leucocyte trafficking. The use of Anakinra has so far been reported in few cases of scleritis associated with rheumatoid arthritis and few cases of posterior uveitis. It has been used in the dose of 100 mg/ day and the main side effects have been the injection site reactions.



taches de bougie is a French of candle-wax drippings.



Phacoanaphylactic uveitis is an immune complex disease that develops when normal tolerance to lens protein is lost, not a cell-mediated rejection of "foreign tissue" (Contrary to prior teachings lens proteins are not totally sequestered or organ specific. They are normally found in aqueous and expressed in other extraocular tissues. Anti-lens antibodies are found in some normal individuals).



AC flare: Tyndal effect  focused beam of light illuminating the anterior chamber becomes visible, just as a projector beam is visible in a smoky room. This phenomenon, which is termed aqueous ―flare‖ or ―ray,‖ is caused by the Tyndall effect. 269


Dhaval Patel MD



AC cells: The cells normally move with the convection currents in the aqueous. (They sink anteriorly where the aqueous is cooled by the cornea and rise posteriorly where the aqueous is heated by the iris.) Absence of cellular convection currents may indicate clotting of fibrin-rich aqueous in a case with severe vascular permeability.



Blood level of cyclosporine: 100-150 ug/ml



Nozik technique: a 25-gauge, 1/2-inch needle is used. If the injection is given in the superote m poral quadrant (the preferred location), the upper eyelid is retracted and t he patient is instr u cted to look down and nasally. After anesthesia is applied with a cotton swab soaked in propa racaine or tetracaine, the needle is placed bevel-down against the sclera and advanced through the conjunctiva and Tenon capsule using a side-to- side movement, which allows the physician to deter mine whether the needle has entered the sclera or not. As long as the globe does not torq ue with the side-to-side movement of the needle, the physician can be reasonably sure t hat the needle has not penet rated t he sclera. Once the needle has been advanced to the hub, t he corticosteroid is injected into the sub-Tenon space. Complications of the superotem poral approach include upper lid ptosis, periorbital hemorrhage, and globe perforation.



The Goldmann-Witmer (GW) coefficient is a test that compares the levels of intraocular antibody production to that of serum, as measured by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay. The coefficient is defined as GW = X/Y; where GW = Goldmann-Witmer coefficient; X = specific antibody in aqueous or vitreous divided by total IgG in aqueous or vitreous; and Y = specific antibody in serum divided by total IgG in serum. A GW ratio > 4 is diagnostic of local antibody production to a specific microbial pathogen. It‘s especially useful for ARN.



7 g of protein/100 mL of blood, but only 11 mg of protein/100 mL of aqueous.



pink hypopyon: Serratia marcescens endophthalmitis. Cytologic examination reveales no erythrocytes, and the pink color is due to the bacteria.



KPs 270


o

Dhaval Patel MD

Types of KPs 

Fine/coarse (lymphocytes and plasma cells) – found in allergic or acute iridocyclitis.



Mutton fat (Macrophage and epitheloid cells) – found in granulomatous uveitis – e.g. TB, sarcoidosis.

fresh KPs/Old KPs 

Fresh KPs – Solid, round, white, fluffy



Old KPs – Faded, shrunken, pigmented, crenated edge



The absence of CME distinguishes Fuchs‘ heterochromatic iridocyclitis from other uveitis syndrome with chronic vitritis.



Aspirin is the treatment of choice for patients with Kawasaki syndrome. Systemic corticosteroid therapy use is associated with an increased rate of coronary artery aneurysm formation and is therefore contraindicated.



Serpiginous choroidopathy (geographic helicoid peripapillary choroidopathy GHPC) is a chronic, recurrent, indolent disease of unknown etiology. It usually affects adults with painless loss of vision. Lesions are peripapillary or perimacular and, in the active phase, have inflammation along the edges. Centrifugal spread in a snake-like pattern occurs over months to years. Treatment with steroids or immunosuppressive agents has had variable success.



Inflammation in Behçet's disease o

affects the anterior and posterior segments and is generally a bilateral process.

o

Recurrent explosive inflammatory episodes are typical with active episodes that range from 2 to 4 weeks.

o

A chronic, lingering inflammatory stage typically does not develop.

o

A nongranulomatous anterior uveitis with formation of a transient hypopyon is common.

271






Dhaval Patel MD

o

Posterior inflammation is characterized by recurrent vascular occlusive episodes with retinal hemorrhage and vitreous inflammation. The inflammation is typically confined to the retina and retinal vasculature. Choroidal involvement is rarely seen.

o

The retinitis of Behçet's disease is very suggestive of a viral retinitis and must be considered in the differential.

Toxoplasmosis drugs o

Pyrimethamine actually inhibits dihydrofolate reductase.

o

Sulfadiazine blocks the production of dihydrofolate from para-aminobenzoic acid.

o

Clindamycin is an antibiotic that can effectively kill Toxoplasma organisms.

o

Systemic and periocular steroids can be used in the treatment of ocular toxoplasmosis in immunocompetent patients.

Fuchs' heterochromic iridocyclitis o

an insidious, chronic intraocular inflammation that may not respond well to topical corticosteroids.

o

Characteristic findings include diffusely distributed stellate keratitis precipitates and mild anterior segment cell and flare with loss of iris crypts and detail.

o

Blue irides become more blue, and brown irides become less brown in cases of Fuchs' heterochromic iridocyclitis.

o

Gonioscopy will reveal evidence of abnormal bridging vessels in the angle, although neovascular glaucoma with angle closure does not develop.

o

A paracentesis of the anterior chamber may result in a small, splinter-shaped filiform hemorrhage in the angle.

o

Fifty percent of patients with Fuchs' heterochromic iridocyclitis develop cataracts; 60% develop glaucoma.

o

Cataract surgery is not associated with any higher rate of vitreous loss or posterior capsular rupture compared to normal eyes.

o

No posterior synechia, no increased risk of CME after cataract surgery

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Dhaval Patel MD

Iris mammilations are seen in o

Nevus of ota

o

NF-1

o

Peter‘s

o

Axenfield Reiger‘s



Gordon‘s dictum for systemic steroids in uveitis – ―Use enough, soon enough, taper and discontinue‖



Although syphilitic uveitis may mimic any other form of uveitis, intermediate uveitis is a distinctly uncommon presentation.



Rod dysfunction seen in birdshot retinochoroidopathy leading to electroretinogram reveals diminished scotopic responses.



Cystoid macular edema is not typically seen in patients with Vogt-Koyanagi-Harada syndrome.



Diffuse unilateral subacute neuroretinitis DUSN is thought to be caused by numerous different types of roundworms. Baylisascaris species have been implicated most consistently.



Polymyalgia rheumatica is an inflammatory condition but it does not manifest as scleritis.



Primary intraocular lymphoma: leopard skin pattern of yellowish retinal pigment epithelium and subretinal infiltration of lymphomatous cells are typically seen in patients over the age of 70 years

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Dhaval Patel MD



Onchocerca volvulus infection results in widespread dissemination of the microfilarial larvae. These microfilaria can be seen swimming in the anterior chamber. The live organisms may cause a mild uveitis and obstruct the trabecular meshwork; however, dead organisms incite a vigorous inflammatory reaction, which causes much more ocular damage.



An eosinophilic granuloma occurs with Toxocara intraocular infection. On histopathology, the reaction may be so vigorous that the Toxocara organism may not be visible.



Retinal antigens to induce EAU (Experimental Anterior Uveitis)



o

retinal S-antigen, also known as ―arrestin,‖ found in the photoreceptor outer segments and in the pineal gland of some species; it competes with transducin for rhodopsin in its photoexcited and phosphorylated state

o

interphotoreceptor retinoid-binding protein (IRBP), a major soluble protein in the interphotoreceptor matrix

o

rhodopsin, a well-defined transmembrane protein of rod outer segments, participating in visual transduction

o

recoverin, a calcium-binding protein that selectively localizes to the retina and pineal gland, associated with cancer-associated retinopathy

Combination therapy with cyclosporine A, azathioprine and prednisolone was first described by Hooper and Kaplan to control inflammation rapidly and promote visual recovery in five patients with bilateral serpiginous choroiditis.



274


Dhaval Patel MD

Strabismus 

The Bruckner test is a bilateral red reflex test, and if strabismus is present the brighter reflex is in the deviated eye. This is because the light reflects from peripheral retina in the deviated eye. Because there is less pigment in the peripheral retina than the macula, there is more reflection of light from the peripheral retina of the deviated eye.



Alexander‘s law: Jerk nystagmus, usually increases in amplitude with gaze in direction of the fast phase



Enthesiotomy: tenotomy and reattachment of muscle. It is done as nystagmus surgery.



The inferior and superior obliques are abductors of the eye in synergy with the lateral rectus. The superior, inferior, and medial recti are all adductors.



A very important thing to understand about Moebius is that many other characteristics have been found in patients who have the signal features of lack of abduction (or in some cases, gaze palsy) and weakness of the facial muscles. These include: deafness, webbed fingers or toes, supernumerary digits, defects in the muscles of the chest (Poland syndrome), neck and tongue, missing fingers or toes and more. Because of the wide list of associated features some would prefer to call this the Moebius sequence.



The parieto-occipital lobe controls the slow pursuit component, whereas the frontal lobes control the saccadic component.

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Dhaval Patel MD

Exception to Sherrington‘s law: DRS, Retraction nystagmus Exception to Hering‘s law: DVD



Several ocular and systemic anomalies have been associated with DRS: cataracts, iris anomalies, Marcus Gunn jaw winking, microphthalmos, crocodile tears, Goldenhar's syndrome, maternal thalidomide use, and Klippel-Feil syndrome.



There are three and possibly 4 classes of CFEOM that are genetically defined and have different characteristics. Class 1 has aligned eyes in down gaze which become esotropic on attempted up gaze. Class 2 characterized by limited up gaze, ptosis and exotropia. Class 3 is a milder form that can be a mixture of class 1 and 2 and may be unilateral. A new classification of CFEOM called Turkel has an added finding of missing fingers. CFEOM is a rare genetic disorder that results in varying degrees of inability to look up along with ptosis and a chin up head posture. Treatment of any of the classes of CFEOM presents a significant challenge and is usually done in stages.



Large vertical fusional amplitudes (>5 prism diopters) and facial asymmetry from childhood headtilting suggest a decompensated congenital lesion.



In case of Restrictive Myopathy, A rectus muscle should never be resected but only recessed.



Positive forced ductions indicate a restrictive process that may be caused by thyroid eye disease, blow-out fractures, fat adherence syndrome, and Brown's syndrome, among others.



Amblyopic eye functions better in mesopic condition.



A strabismic deviation can be neutralized by orienting an appropriate power prism with the apex in the same direction as the deviation. 276


Dhaval Patel MD



A prism diopter is defined as the amount of deviation of a light by the prism measured at 100 cm.



Prism power can be represented by vectors and added as this mathematical entity.



All rays parallel to the lens axis will converge on the secondary focal point whose location can be calculated as 100 cm/Power = distance cm.



extraocular muscle is commonly involved in a dog bite: The superior oblique muscle: This result from direct trauma (from the lower teeth of the dog) to the trochlear causing paralysis of the superior oblique muscle and a Brown's syndrome due to scarring. This condition is also called dog-bite syndrome or canine tooth syndrome.



The normal range of fusion as measured from 0° on the major amblyoscope is that of 30-35 convergence, 5° of divergence and 3-4 of vertical vergence.



Incidence of amblyopia in myopia is much less almost unknown for the reason that myopia at least sees the near objects more clearly than in hypermetropia where all accommodation reserve is up for distance and he neither sees dist/ance nor see near objects clearly. Therefore, near vision stimulus is not deprived in myopia.



4-PD base-in prism test  differentiates convergence insufficiency [near vision improves] from accommodative insufficiency [near vision worsens]



Faden: The lever arm of the muscle is weakened thus decreasing its action. Best for MR and not for LR. (as MR has 6.0 mm arc of contact, LR has 15 mm arc of contact.) o

Non accomodative convergence excess esotropia

o

Nystagmus blockade syndrome

o

Paralytic strabismus 277




o

Duane retraction syndrome

o

Dissociated vertical deviation

Dhaval Patel MD

Hummelsheim‘s procedure: For LR palsy Lateral halves of sup and inf recti are dissected and reinserted near LR insertion



Jensen‘s procedure: For LR palsy Lateral halves of sup and inf recti and upper and lower halves of LR dissected free



In the presence of microtropia "with identity," the cover test result is negative but the 4 prism diopter base-out test reveals a foveal suppression scotoma in one eye that generally is also amblyopic.



The limbal incision for squint surgery may be done at the limbus for MR-LR-IR - but allow a 1.5 to 2.0 mm "cuff" for SR to avoid increasing pannus at superior limbus.



A compensatory head posture with the chin elevated and pointing toward the opposite shoulder permits fusion in Brown syndrome.



Pleoptoscope: Opthalmoscope fitted with a projected fixation target.



o

Used for Small-angle strabismus , with fixation anomaly and amblyopia.

o

It can also be treated by Occlusion of the amblyopic eye, followed by foveal stimulation. Rotating blue polarised light, light ablation of the fixation zone followed by repetitive foveal stimulation. Treatment unlikely to be successful if the other eye has normal vision.

Bielschowsky phenomenon: Downdrift of occluded eye as increasing neutral density filters are placed over fixating eye in dissociated vertical deviation (DVD)

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Dhaval Patel MD

DVD o

present in 60% to 80% of patients with congenital esotropia.

o

DVD is usually bilateral and asymmetric.

o

The etiology is unknown but appears to be associated with an early disruption of binocular development. Thus, high-grade stereopsis and bifoveal fixation are not seen.

o

During times of visual inattention, the nonfixating eye slowly drifts up, extorts, and abducts without a corresponding hypotropia of the fellow eye on alternate cover testing. This is the hallmark of this disorder—it does not obey Hering's law.

o

DVD can simulate Inferior Oblique Overaction (IOOA) in side gaze when the nose acts as an occluder. The hyperdeviation in DVD is of the same amount in adduction, abduction, and primary position. This is in contrast to IOOA, in which the hyperdeviation is greatest in its field of action.

Duane Retraction Syndrome (DRS) can be associated with Anisometropia, coloboma, microphthalmos and heterochromia. o

Two syndromes associated with this are: Goldenhar and Wildervanck syndrome. The child can have a hearing or a speech disorder as well

o

The phenomenon commonly seen is the leash phenomenon and a severe leash is treated with Y splitting of the lateral rectus muscle with posterior fixation sutures of the lateral rectus muscle.



A right superior oblique palsy can result in vertical or torsional diplopia. Vertical diplopia may be treated with either ipsilateral inferior oblique myectomy or anterior transposition, contralateral inferior rectus recession or ipsilateral superior oblique tuck (sometimes in combination}. Torsional diplopia can be treated with anterior transposition of the superior oblique muscle.



Differentiation of unilateral from bilateral fourth nerve palsy is essential for successful surgical management. o

Features of unilateral fourth nerve palsy include: head tilt to the affected side, unilateral hypertropia on lateral gaze, less than 5 of exocyclotorsion.

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Dhaval Patel MD

Features of bilateral fourth nerve palsy Include: chin down posture with eyes looking up, alternating hypertropia on right and left gaze respectively, large exocyclotorsion of more than 10



Infantile esotropia has large angle esotropia. Binocular single vision is usually poor despite early treatment. The temporal-to-nasal movement is usually better than nasal-totemporal movement on optokinetic testing. Dissociated vertical deviation and inferior oblique overaction are common and have been reported in about 90% of patients. Post-surgical esotropia may be caused by an accommodative component.



Optokinetic response tests the pursuit and saccadic movements. When the drum is rotated to the right, the pursuit movement is mediated by the right parietal lobe and the saccadic movement by the right frontal lobe, i.e. the optokinetic response tests the pursuit and saccadic movement on the side towards which the drum is moving. Parinaud's syndrome causes up-gaze palsy and vertical rotation of the drum will elicit convergence retraction nystagmus. In a patient with a frontal lobe lesion, there may be deviation of his or her eyes to the side of the lesion. However, provided the contralateral frontal lobe is intact, rotating an optokinetic drum away from the side of the frontal lobe will elicit a response.





How to dissociate two eyes? o

Septum so that one half of the field is seen by one eye exclusively and the other by the other eye.

o

Two tubes one in front of each eye.

o

Red-green glasses, which are complementary in the sense that with red filter sees only red light other with green filter sees only green.

o

Polaroid dissociation, each eye views through polaroid filters each one at 90 degrees to each other.

o

Bagolini's striations, a spot light scattered striations, the two glasses set at 90° to other.

Mary Maddox: English Strabismologist o

Maddox tangent scale 280


Maddox rod

o

Maddox hand frame: uniocular and binocular

o

Maddox Wing

Dhaval Patel MD



The torsional eye movements occur around the anteroposterior or Fick's Y axis. This does not pass through the centre of cornea but at a point on the lateral limbus as shown by Linwong.



Magician Forceps Phenomenon: On passive adduction of the dominant eye, the other eye's exodeviation gets corrected. This reflex is present even in the dark. This reflex is abolished by deep retrobulbar anesthaesia.



Phospoline iodide: medicine that affects accommodative convergence and used as a therapy sometimes.



Isolated agonist model was described by Duane for eye movements. However, it is important to remember that during eye movements, all six extraocular muscles are in some state of contraction or relaxation, and it is strictly hypothetical to discuss the movement of the eye as if only one muscle contracts.



Paired Antagonist Model was described by Boeder.



Aging chages in EOM



o

Both horizontal rectus muscles are displaced inferiorly with age (MR >> LR)

o

The superior rectus and inferior rectus muscles do not change locations

o

greater variety in fiber sizes, increased connective tissue in the muscle, increased adipose tissue in the bundles, deposits of lipofuscin, and degenerative changes.

amblyopia ex anopsia: amblyopia due to media opacity 281


Dhaval Patel MD



Antepodean Strabismus: It is present when the patient has esotropia while fixing with one eye and exotropia when fixing with the other eye. This occurs with anisometropia and an improperly corrected refractive error. Some cases are believed to be due to unequal accomodation.



Principle of Faden: Point of posterior fixation is new insertion for action. As antagonist entire muscle acts. Therefore limits muscle action only in field of its action.



Adherence syndrome: The orbital fat is separated from the globe by Tenon‘s capsule. If an accidental opening is made in the portion of Tenon‘s capsule that separates the orbital fat from sclera, orbital fat may be pressed through the opening and adhere to the globe. This adherence often results in limited eye moments. It is best treated by prevention. The orbital fat comes forward around the equator of the globe to within 10 mm of the limbus. Care should be taken not to cut Tenon‘s capsule more than 10 mm from the limbus.



Only fusional convergence (i.e. overcoming exophoria) dampens nystagmus. Accommodative convergence does not dampen nystagmus and even works against the patient by increasing accommodative demands and may cause the near point to recede with reduced visual acuity at near. So minus glasses does not improve nystagmus.



Centre for voluntary convergence: Frontal oculogyric area (area 8) Centre for reflex convergence: peristriate area of occipital cortex Lower convergence centre: nucleus of Perlia



NPC is usually <8 cm. Normal convergence amplitude is 10.5 Ma. (0.5 prism diaoptre correspond to 1 Ma)



Convergence insufficiency is NPC > 11 cm or inability to maintain 30 degree convergence on synaptophore.

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Dhaval Patel MD



In class 7 SO palsy, traumatic paresis plus restriction of relaxation of the superior oblique, also known as the canine tooth syndrome because it is most frequently caused by a dogbite injury to the trochlear area, requires surgery to correct the Brown syndrome first, with a subsequent attempt at correcting paresis of the superior oblique if possible.



Cooper's Dictum: Stretched scar may have been the mechanism behind Cooper's report of failure of advancing previously recessed medial recti for consecutive exotropia. He advocated instead recessing the antagonist lateral recti. This principle is known as Cooper's Dictum.



Liquid crystal glasses have recently been developed as a new treatment for amblyopia. They provide an electronic, controlled, intermittent occlusion of the sound eye allowing for visual stimuli input to the amblyopic fellow eye. A liquid crystal glass in the sound eye is used as an intermittent flickering shutter switched between ―on‖, or occlusion and ―off‖ or light transmission. The flickering sequence can be adapted to the depth of amblyopia, the length of treatment, and the patient‘s age.



CAM Vision Stimulator - Amblyopic eye is stimulated by slowly rotating, high contrast, square wave gratings of different spatial frequencies for 7 minutes but the results are not much promising.



Hertle Dell‘ Osso proceduce: tenotomy and re attachment (rectus muscle) surgery done for nystagmus.



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Dhaval Patel MD

Neurophthalmology 

Location of Lesion: o

WEBINO (wall-eyed bilateral internuclear ophthalmoplegia): riMLF and 3rd CNN (Involvement of the paired medial rectus subnuclei)

o

Internuclear ophthalmoplegia: Ipsilateral MLF, i.e. the same side as the eye that has adduction restriction.

o

Down-gaze palsy: riMLF

o

The lesion for skew deviation is in the brain stem but the exact location is unknown.

o

One and a half syndrome - ipsilateral MLF and 6th CNN



Aberrant regeneration of the oculomotor nerve occurs in ‗surgical‘ third nerve palsy and not in 'medical' third nerve palsy such as diabetes mellitus or hypertension. Retraction of the upper lid on down-gaze is called pseudo von Graefe's sign and miosis of the pupil on adduction is termed pseudo Argyll-Robertson pupil.



Kollner‘s Rule: o

Retinal Disease causes Blue-yellow defects 

o

Optic nerve disorders causes Red Green defects 



Exceptions: Stargardt‘s and Cone dystrophy

Exceptions: Glaucoma and autosomal dominant optic atrophy

The Pulfrich phenomenon probably reflects delayed conduction in the demyelinated nerve. Oscillating objects perceived by the affected eye appear to be behind the image seen with the healthy eye, simulating three-dimensional movement where there is only movement within one plane.

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Dhaval Patel MD



Cogan's lid twitch - overshoot on moving from depression to primary position in myasthenia.



Heidenhain variant of Alzheimer disease of CJD causes visual hallucinations.



lce test- reduced ptosis after ice pack applied for 2 minutes.



Alternating Anisocoria:





o

Aka See-saw anisocoria

o

One pupil larger in light and other is larger in dark  3rd nerve palsy and horner‘s syndrome

Benign alternating anisocoria: o

discreet entity not found in normal subjects but which may be present in more than one member of a family

o

some patients in whom apparently physiological anisocoria appears to change from side to side with the larger pupil appearing on occasion in one eye and on occasion in the fellow eye

Alternating Horner‘s syndrome: o

Cervical cord lesions, syringomyelia, radiation myelopathy, shy-daeger syndrome



Horner syndrome with 6th nerve palsy together: cavernous sinus lesion



Reasons for Light near dissociation  o

30 times more fibres serve miosis through accommodation than through light.

o

Aberrant innervation of iris sphincter by accommodative neurons 285


Dhaval Patel MD

Causes: Unilateral Afferent conduction defect Adie pupil Herpes zoster ophthalmicus Aberrant regeneration of the 3rd nerve Bilateral Neurosyphilis- Argyll Robertson pupils Type 1 diabetes Myotonic dystrophy Parinaud (dorsal midbrain) syndrome Familial amyloidosis Encephalitis Chronic alcoholism



There is no clinical condition in which the light reflex is present but the near response absent but vice versa is not true.



The midbrain centre for the near reflex is probably located more ventrally than the pretectal nucleus and this is why compressive lesions such as pinealomas, preferentially involving the dorsal internuncial neurones involved in the light reflex, spare the near reflex fibres until later.



Pupillary sphincter has atlease 20 segments each of this innervated by different branches of short ciliary nerve.



Wernicke‘s hemianopic pupil occurs in  optic tract lesion

286


Dhaval Patel MD



In afferent (sensory) lesions, the pupils are equal in size. Anisocoria (inequality of pupillary size) implies disease of the efferent (motor) nerve, iris or muscles of the pupil.



blurring of vision worse on waking: Impending central retinal vein occlusion Papillophlebitis NAION



Reverse RAPD: When the pupil of the involved eye is nonreactive or nonfunctional, observe the fellow, normal eye for a ―reverse‖ RAPD (dilation when light is on nonreactive eye, constriction when light is shined on reactive eye).



Morning glory disc is a congenital coloboma of the disc or glial tissue of the disc head. o

It may be associated with congenital forebrain anomalies including basal encephalocele, frontonasal dysplasia and NF-2.

o

May be associated with the papillorenal syndrome, a PAX2 gene mutation.

o

Approximately 30% patients can have subsequent serous RD.

o

PHACE syndrome characterized by posterior fossa brain malformations, large facial haemangiomas and cardiovascular anomalies. It almost exclusively affects females. It is also associated with morning glory disc.



Ophthalmic artery obstruction usually does not produce a cherry-red spot due to underlying choroidal ischemia.



Approximately half of the fibers of the optic nerve decussate in the optic chiasm, and the input to each of the parasympathetic nuclei in the brain stem remains equal. Therefore, relative afferent pupillary defects do not cause anisocoria because any changes in light input are distributed equally to both pupils.

287


Dhaval Patel MD



Retinal migraine: ―Ocular‖ migraine, rare; monocular scotoma or visual loss for minutes to an hour due to retinal or optic nerve ischemia.



Willebrandt‘s knee: Inferonasal optic nerve fibers that decussate in chiasm and loop into contralateral optic nerve before traveling back to optic tract



Inadvertent ocular exposure to anticholinergic agents also has been reported. Patients using scopolamine patches have been noted to have self-limited mydriasis, which has been dubbed ―cruise ship anisocoria‖. Anticholinesterases- flea collar anisocoria



Oculodigital sign of Franceschetti is seen in Leber congenital amaurosis. They also have severe visual impairment from birth. Vision remains stable or worsens slowly over time. These individuals tend to be hyperopic and have photophobia. They also are likely to engage in eye poking or oculo-digital massage, presumably to create light flashes. This behavior is called blindism.



Collier‘s sign: Bilateral eyelid retraction associated with midbrain lesions

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Clonazepam and suboccipital craniotomy have been used in the treatment of downbeat nystagmus in patients with Arnold-Chiari malformation.



The differential diagnosis for posterior ischemic optic neuropathy (PION) should include radiation optic neuropathy, status post-coronary artery bypass graft, anemia, acute systemic hypotension, giant cell arteritis (GCA), and syphilis. Well-controlled essential hypertension is associated with anterior ischemic optic neuropathy (AION) but not PION.



In Giant cell arteritis: CRP > 2.45 mg%, ESR >47 mm/hour

288


Dhaval Patel MD



Optic disc drusen may be associated with retinitis pigmentosa, pseudoxanthoma elasticum, angioid streaks and allagile syndrome.



In general, optic nerve compression >1 cm posterior to the globe does not cause disc edema.



A skew deviation is a motility disturbance with a vertical component that does not have a pattern consistent with a discrete muscle underaction or nerve palsy. They are generally due to supranuclear or vestibuloocular dysfunction and generally reflect brainstem disease. They are typically comitant but not always.



Although transient changes in vertical eye movements and slowing of vertical saccades can result from lesions of the paramedian pontine reticular formation, nuclei crucial for the initiation of vertical eye movements are the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (INC).



Isolated sixth nerve palsy in children is most commonly attributable to postviral inflammation occurring 1 to 3 weeks following a nonspecific viral illness of the upper respiratory tract. Recovery is generally complete and occurs within 10 to 12 weeks.



Czarnecki‘s sign: Segmental pupillary constriction with eye movements due to aberrant regeneration of cranial nerve III



Medial rectus contracture is distinctly uncommon in Duane's syndrome. In congenital sixth nerve palsy, it is quite common and results in esotropia in primary position.



Exotropia in primary position can occasionally occur in association with a bilateral INO (A lesion that involves both medial longitudinal fasciculi near their junctions with the third nerve nuclei) resulting in a syndrome called wall-eyed bilateral INO - WEBINO.

289


Dhaval Patel MD



Sixth nerve palsy caused by an intracavernous lesion may present as abduction palsy plus miosis because within the cavernous sinus, sympathetic branches of the paracarotid plexus join the sixth nerve briefly.



In the cavernous sinus, cranial nerves III, IV, and V are relatively protected within the walls of the sinus, but cranial nerve VI runs in the middle of the sinus and is more prone to injury.



Horizontal saccades originate in the contralateral frontal lobe, but either hemisphere can produce ipsilateral saccades if the other hemisphere is damaged.



Oculomotor apraxia is an inability to initiate voluntary horizontal saccades. Congenital oculomotor apraxia is characterized by striking compensatory head movements, and acquired lesions (e.g., resulting from bilateral frontal lobe strokes) usually produce defects in initiation of bidirectional saccades—patients may blink to break fixation and then turn their head to fixate on something else. Pursuits remain relatively unaffected.



Opsoclonus consists of nonstop, random, directionally unpredictable saccades. Ocular flutter consists of spontaneous groups of back-and-forth horizontal saccades that may occur during fixation or at the end of a normal horizontal saccade. Both ocular flutter and opsoclonus may be associated with malignancy, such as metastatic neuroblastoma in children or small cell cancer of the lung in adults. These eye movements may be the first presenting sign of cancer. Multiple sclerosis (MS) also can cause ocular flutter. Square-wave jerks are a microsaccadic fixation disturbance associated with cerebellar diseases of various kinds. Ocular motor dysmetria is a back-and-forth saccadic motion about the point of fixation that occurs following an otherwise normal saccade. It is felt to represent ―overshooting‖ of the intended fixation point. Ocular bobbing is most commonly seen in comatose or quadriplegic patients with large infarcts or brainstem hemorrhages.

290


Dhaval Patel MD



In progressive supranuclear palsy (PSP), downward gaze is generally affected, becoming smaller and slower. Saccades are affected more than pursuits. This is in distinction to the dorsal midbrain syndrome, in which upward saccades are generally affected.



The period between detection of movement and the beginning of smooth pursuit (for tracking) is between 125 and 135 milliseconds. Initiation of saccadic movement requires from 150 to 200 milliseconds from the first perception of a target. The latency in generating a pursuit movement is shorter than that for a saccade movement.



Skew deviation is, by definition, a vertical misalignment of gaze that cannot be assigned to a single nerve or muscle weakness. In the presence of an internuclear opthalmoplegia (INO), the hypertropic eye is often on the same side as the adduction deficit (medial rectus dysfunction).



Upward gaze paresis, light-near dissociation, lid retraction, accommodative abnormalities, and convergence-retraction nystagmus, fixation instability, small-amplitude skew deviation, and papilledema (if ventricular outflow has been compromised) are all features of the dorsal midbrain (Parinaud's) syndrome. Furthermore, skew deviation and papilledema may be seen, depending on the etiology. Lid retraction—the Collier sign—may worsen with attempted upgaze. Convergence-retraction nystagmus is also a response to an effort at upgaze that triggers medial rectus contractions. Hence, this form of ―nystagmus‖ is worsened by upward optokinetic nystagmus (OKN) testing.



Monocular nystagmus has been associated with chiasmal and hypothalamic gliomas. It is also seen in blind eyes, multiple sclerosis (MS), and spasmus nutans—a transient, fastbeating, but low-amplitude nystagmus found during the first 5 years of life.



The classic triad of spasmus nutans includes monocular or dissociated small-amplitude nystagmus, head bobbing, and torticollis. The differential diagnosis for this disorder includes patients with chiasmatic gliomas and subacute necrotizing encephalomyopathy. Features of these two disorders may include optic atrophy, irritability, vomiting, and increased intracranial pressure. Spasmus nutans should be considered only after these two disorders are excluded. Spasmus nutans usually disappears within 2 years of onset.

291


Dhaval Patel MD



Alexander's law describes the increased frequency and amplitude of nystagmus movements accompanying gaze in the direction of the fast-beating component. Of the various forms of nystagmus, downbeat nystagmus most frequently violates Alexander's law.



Upbeat nystagmus can be caused by lesions of the anterior vermis and lower brainstem, as well as drugs and Wernicke's encephalopathy. Downbeat nystagmus may be localized to anatomic structures at the craniocervical junction (e.g., Arnold-Chiari malformation) and may be seen in certain intoxications (alcohol, lithium). Vestibular nystagmus has its etiology within the vestibular system. Periodic alternating nystagmus also can localize to the craniocervical junction but may be seen in other forms of posterior fossa disease. Seesaw nystagmus results from third ventricle tumors or diencephalic lesions involving the connections to the interstitial nucleus of Cajal (INC) and is therefore the most localizing.



Vergence eye movements are felt to have a pathway of their own for stimulating the brainstem motor nuclei. Saccades originate in the contralateral frontal lobe, whereas pursuits arise in the ipsilateral parietal lobe.



Marcus Gunn's ―jaw-wink‖ reflex is an example of synkinesis (abnormal innervation connecting two groups of normally unrelated muscles, such that they contract together), but it is not synkinesis because of aberrant regeneration, which usually follows a peripheral neuropathy or trauma to the nerve. The ―jaw-wink‖ is a congenital/neurogenic phenomenon.



three most common causes of facial nerve overactivity: 1. only essential blepharospasm is believed to be related to basal ganglia dysfunction. 2. Compression of the facial nerve in the cerebellopontine angle by anomalous vessels has been demonstrated in 90% of cases of hemifacial spasm. Tumors in the cerebellopontine angle also can cause hemifacial spasm. 3. Facial myokymia is caused by disease in the pons involving the facial nucleus or fascicle. The most common causes include multiple sclerosis (MS) in adults and pontine glioma in children. 292


Dhaval Patel MD



The afferent pupillomotor fibers exit the optic tracts just before the lateral geniculate body (LGB); they do not pass through the LGB. Although postganglionic pupillomotor fibers in the sympathetic pathway do arise from the superior cervical ganglion, the sympathetic pathway leading to these fibers is thought to originate in the posterior hypothalamus. In addition, postganglionic sympathetic fibers enter the orbit with the ophthalmic division of the trigeminal nerve through the superior orbital fissure. The consensual pupillary response is seen because of decussation at the pretectal nuclei. Were the chiasm split in half, consensual responses would be preserved.



In uncal herniation and basilar meningitis, pupil dilation may be the only sign of third nerve palsy. In the case of a cerebral aneurysm, the pupil is usually involved, along with other functions of the third nerve. If the pupil is not involved, it is less likely that an aneurysm is the cause of the palsy. Total oculomotor palsy with a spared pupil in elderly patients usually suggests a microvascular etiology.



Horner's syndrome is defined as ipsilateral ptosis and miosis. Ptosis is secondary to lack of Müller's muscle function. Anhidrosis may or may not be present. Localization of the lesion in Horner's syndrome is part of the clinical workup and sometimes guided by the extent of anhidrosis. First-order lesions (central nervous system) cause ipsilateral anhidrosis of the entire body. Second-order lesions (Pancoast's tumor, neck trauma) cause ipsilateral facial anhidrosis. Third-order lesions (carotid dissection) cause anhidrosis only around the affected eye or none at all. 1. In response to 4% cocaine, a normal pupil will dilate, but a Horner's pupil will dilate poorly. 2. Hydroxyamphetamine (Paredrine) will cause a similar response in preganglionic Horner's syndrome only. Painful Horner's syndrome may be caused by many disorders (neck trauma, migraine, cluster headaches), but spontaneous dissection of the common carotid artery must be ruled out with angiography or magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA)

293


Dhaval Patel MD



It is important to examine the optic disc carefully in all patients with suspected central serous retinopathy. (a/w Optic Disc Pit)



The temporal 30 degrees of a binocular visual field is perceived by the nasalmost retina of the ipsilateral eye only. These ―temporal crescents‖ are represented in the anterior-most occipital lobe. Therefore, a lesion in this area will produce a monocular visual field defect in the far temporal periphery of the contralateral eye, the so-called temporal crescent syndrome. For example, a right anterior occipital lobe lesion would produce a far temporal field defect in the left eye. Similarly, a right posterior occipital lobe lesion may spare the far temporal field in the left eye.



Inferior nerve fibers from the superior retina course anteriorly in Meyer's loop; therefore, lesions affecting Meyer's loop will result in pie-in-the-sky defects contralateral to the lesion.



Although loss of spontaneous venous pulsations is an early sign of papilledema, approximately 20% of normal patients lack venous pulsations.



Pseudotumor cerebri is characterized by (i) increased intracranial pressure on lumbar puncture, (ii) normal neuroimaging studies (although the ventricles may be small), and (iii) normal cerebrospinal fluid (CSF). Papilledema need not be present for the diagnosis.



The various ways to differentiate the NAION from optic neuritis include (i) the absence of pain with eye movement, (ii) the age group affected, and (iii) delayed optic disc filling present in 75% of NAION cases (whereas filling should be normal in optic neuritis).



Collateral vessels (optociliary shunt vessels) at the disc connecting the retinal and choroidal vascular systems may be seen in association with optic nerve meningioma, central retinal vein occlusion (CRVO), sphenoid wing meningioma, long-standing primary openangle glaucoma (POAG), optic gliomas, or chronic papilledema.



Patients with ―papillophlebitis‖ have normal or near normal visual acuity. It may be a form of incomplete central retinal vein occlusion (CRVO) and usually resolves spontaneously within 12 months. 294


Dhaval Patel MD



Optic nerve hypoplasia is seen with greater incidence in children of diabetic mothers and following fetal exposure to antiepileptic medications, quinine, or lysergic acid diethylamide (LSD). Optic nerve hypoplasia, particularly bilateral involvement, has been associated with other midline developmental anomalies—that is, absence of the septum pellucidum and hypothalamic-pituitary abnormalities. Endocrine dysfunction is manifested as hypoglycemic seizures and growth retardation. This combination of clinical findings is known as DeMorsier's syndrome in 10% (septo-optic dysplasia).



Babies of IDDM mothers more likely to have superior segment hypoplasia giving rise to inferior field defects.



Nonsecreting pitutary tumors often present with visual field loss, whereas secreting tumors present with endocrine dysfunction. An exception is prolactin-secreting tumor in male patients because the decreased libido and impotence are often not reported early in their course.



Bitemporal macular hemianopia can only arise from compression of the posterior chiasm. Although most lesions responsible for this compression are parasellar, a lesion distant from this site (e.g., a tumor at the base of the brainstem) also may lead to chiasmal compression. This occurs if the lesion causes obstructive hydrocephalus, which enlarges the third ventricle, compressing the chiasm.



The most common location for a cerebral aneurysm with third nerve palsy is the junction of posterior communicating artery and internal carotid artery. PCA-ICA



Third nerve aberrant regeneration never occurs with diabetic oculomotor neuropathy. Aberrant regeneration of the third nerve implies another etiology, such as aneurysm, tumor, inflammation, or trauma. Other classic findings of aberrant regeneration include persistent vertical gaze limitation secondary to simultaneous contraction of superior and inferior recti, and pupillary miosis with elevation, adduction, or depression.



The earliest loss of visual field in chronic papilledema is typically in the inferior nasal quadrant. 295


Dhaval Patel MD



Retinal and optic nerve lesions produce field defects that do not generally respect the vertical midline. The presence of a field defect that respects the vertical midline should always arouse suspicion of a neurologic lesion (e.g., cerebrovascular accident, tumor), especially when the disc and field changes do not correspond.



The only location at which oculomotor superior division nerve palsy could occur without affecting additional cranial nerves or the inferior division of cranial nerve III is in the orbital apex.



The location of a lesion affecting the oculomotor nerve can be determined by the associated neurologic deficits. An oculomotor nuclear lesion also involving the ipsilateral cerebral peduncle causes contralateral hemiparesis (Weber's syndrome). Cranial nerve III palsy with contralateral decreased sensation and contralateral tremor (red nucleus affected) is Benedikt's syndrome.



The parasympathetic pupillomotor fibers controlling the pupil are found on the outside of the oculomotor nerve and are the first to be injured with external pressure. Diabetic microvascular insults affect the central fibers of the nerve to a greater degree than the outer fibers, and as a result, pupil involvement is less common (<20%).



A contralateral relative APD would be present if the optic tract was damaged because relatively more nasal fibers from the contralateral eye cross in the chiasm.



A relative afferent pupillary defect never causes anisocoria because the pupillary fiber decussations in the chiasm and posterior commissure ensure equal efferent input to both iris sphincter muscles.



Adie's tonic pupil is hypersensitive to parasympathomimetics and will constrict with pilocarpine 0.1%.



The mnemonic COWS—cold-opposite-warm-same—helps to give the direction of the fast phase of the nystagmus. Slow phase would be just opposite of fast phase. 296


Dhaval Patel MD



Louis-Bar syndrome (ataxia-telangiectasia) is not associated with any CNS abnormalities detectable with neuroimaging.



Uhthoff's symptom occurs with optic neuritis and is a decrease in vision with an increase in body temperature. Exercise or hot showers may trigger this symptom. Lhermitte's sign is the electric shock sensation with neck flexion and is found in patients with multiple sclerosis. The Riddoch phenomenon occurs in patients with cortical blindness who are able to perceive objects in motion, but cannot see stationary objects.



A bilateral medial occipitotemporal lesion causes prosopagnosia, the inability to distinguish faces.



The nuclei controlling the superior rectus and superior oblique muscles have crossed projections.



Horner's syndrome can be confirmed with the cocaine test and damage to the second order neuron is supported with the hydroxyamphetamine test. In the cocaine test, 4% (not 10% as some advocated) cocaine is instilled into both eyes. Horner's pupil dilates little or none at all. Reuptake of the norepinephrine occurs normally in the synaptic cleft. Cocaine blocks the reuptake, causing rapid accumulation within the synaptic cleft resulting in dilation of a normal pupil. The presynaptic nerve endings in Horner's syndrome have impaired sympathetic tone and therefore respond poorly or none at all to the effect of cocaine. Hydroxyamphetamine stimulates the release of norepinephrine from the presynaptic nerve endings resulting in dilatation of the pupil. If the nerve is damage, the nerve will not release norepinephrine as is the case with third order neurone lesion. In the case of first and second order neurone lesion, the pupil will dilate as the third order neurones are intact.



Optic Pit commonly involves temporal part of the disc.

297


Dhaval Patel MD



Anton‘s Syndrome: denial of Blindness



Metabolic acidosis is the hallmark of optic neuropathy induced by methanol.



The optic nerve is generally myelinated to the lamina cribrosa 4 to 6 months before foveal maturation.



It should be emphasized that in afferent (sensory) lesions, the pupils are equal in size. Anisocoria (inequality of pupillary size) implies disease of the efferent (motor) nerve, iris or muscles of the pupil.



Visual evoked potentials (VEPs) document 20/20 acuity by the age of 6 to 8 months. Preferential looking testing (PLT) cannot document 20/20 until 24 to 30 months.



superior rectus and medial rectus are closely attached to the dural sheath of optic nerve, at their origin. This accounts for the characteristic pain felt on moving the eyeball up and in, in a case of retrobulbar neuritis.



Hemifacial spasm is differentiated from blepharospasm in that it is unilateral and the spasm will persist during sleep. Unlike in blepharospasm, oral sedatives are usually of no benefit in hemifacial spasm. The pathogenesis is thought to be irritation along the course of the facial nerve. Therefore, neuroimaging to rule out a mass or narrowing of the skull base foramen is necessary. If imaging is negative, the usual therapy is botulinum toxin injections to dampen the spasms of the offending muscles. Facial nerve decompression is also helpful in patients with compression at a foramen or in whom a blood vessel crosses over and compresses the nerve.



photostress recovery test: to differentiate between macular and optic nerve disease. Patients who have a maculopathy will take longer (90 to 180 seconds) to recover pretest vision after looking into a bright light for 10 seconds. Patients with optic nerve disease will have a normal recovery time (<60 seconds). The test is probably only valid for patients with vision better than 20/80. 298




Dhaval Patel MD

Tests for factitious monocular blindness: major loss: OKN, the rocking mirror test, and the base-up prism test, fogging refraction minor loss: fogging refraction



intact oculovestibular reflexes in a patient with a gaze palsy implies a supranuclear disturbance. If the vestibular system can drive the eyes in the direction of the paretic field of gaze, the gaze paresis must be supranuclear in nature. Impaired oculocephalic responses indicate that the infranuclear, end-organ function is responsible for the motor disturbance.



In the setting of an upgaze paresis, upturning of the eyes on forceful opening of closed eyelids implies a supranuclear lesion.



Although there is some redundancy of the optic nerve within the orbit, the intracranial optic nerve has little ―slack.‖



53% of the retinal ganglion cells cross in the chiasm (this difference is occasionally important clinically). The macular fibers constitute a large portion of the optic chiasm and most decussate in the posterior chiasm. The inferior nasal retinal fibers cross in the anterior chiasm and were thought to loop anteriorly in the contralateral optic nerve before traveling posteriorly, leading to the term Wilbrand's knee. It is now thought that Wilbrand's knee may be an artifact. The chiasm lies approximately 1 cm (not 1 mm) above the anterior pituitary gland.



ipsilateral ganglion cells synapse in layers 2, 3, and 5, whereas the contralateral ganglion cells synapse in layers 1, 4, and 6.



Inferior fibers of the optic radiations pass extremely close to the internal capsule. 299


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





Dhaval Patel MD

Parietal lobe lesions o

Agnosia

o

Right-left confusion

o

slow-phase pursuit movements toward the ipsilateral side

o

hemianopia that are denser inferiorly

o

nondominant lobe: constructional and dressing apraxia

o

dominant lobe: GERSTMANN SYNDROME  agraphia, acalculia, left-right confusion, finger agnosia

o

Asymmetric OKN

temporal lobe lesion o

seizures

o

formed visual hallucinations

o

pie-in-the-sky defects contralateral to the lesion

occipital lobe lesion o

unformed hallucinations

o

macular sparing

o

sparing of the temporal crescent

o

Occipital lobe infarcts can be associated with visual hallucinations, denial of vision loss (Anton-Babinski syndrome), and the ability to perceive moving but not static objects (Riddoch phenomenon).

o

OKN Sign?

80% of patients with cavernous sinus-dural fistulae will develop ocular hypertension.

300


Dhaval Patel MD

Nonarteritic anterior ischemic optic neuropathy (NAION) is far more common than arteritic anterior ischemic optic neuropathy (AAION) (approximately 95% vs. 5%) and patients have a lower mean age at diagnosis than patients with AAION (60 years vs. 70 years). It usually occurs in a younger age group and may resemble optic neuritis. The various ways to differentiate the NAION from optic neuritis include o

the absence of pain with eye movement,

o

the age group affected, and

o

delayed optic disc filling present in 75% of NAION cases (whereas filling should be normal in optic neuritis).

Although aspirin may prevent further strokes in patients with NAION, its effect on the contralateral eye is unclear.



16% of patients with an initial attack of optic neuritis with a negative magnetic resonance imaging (MRI) will develop multiple sclerosis (MS) at 15-year follow-up. More than 50% of patients with three or more lesions that are visible on MRI will develop MS at 15-year follow-up.



CSF in multiple sclerosis shows increased immunoglobulin/albumin ratio.



Imaging of choice in multiple sclerosis is MRI with FLAIR.



Optic nerve drusen occur almost exclusively in white individuals.



Best method for detecting decompensated congenital fourth nerve palsy is: vertical fusional amplitude measurements.



Within the cavernous sinus, sympathetic branches of the paracarotid plexus join the sixth nerve briefly. Sixth nerve palsy caused by an intracavernous lesion may present as abduction palsy plus miosis.

301


Dhaval Patel MD



Congenital motor nystagmus has several features, including normal visual acuity, paradoxic optokinetic nystagmus (OKN) (caused by the abnormal movements of nystagmus appearing ―slow‖ and against the expected direction of target tracking), dampening by convergence, and aggravation by fixation. Fortunately, oscillopsia (the sensation of the world moving) is not normally a problem.



Bitemporal hemianopia may be seen in acquired seesaw nystagmus because the posterior chiasm is most vulnerable to diencephalic lesions, which may provoke it.



Neurosarcoidosis: 7th CN > 2nd CN



The consensual pupillary response is seen because of decussation at the pretectal nuclei. It will be preserved even if chiasma would be split in half from centre.!! Whereas Marcus-Gunn Pupil is seen because of crossing at chiasma.



Four signs constitute complete Kearns-Sayre syndrome: (i) progressive external ophthalmoplegia (PEO), (ii) mild pigmentary retinal degeneration, (iii) onset before 20 years of age, and (iv) heart block, potentially lethal and among the last signs to develop. Some studies indicate that elevated cerebrospinal fluid (CSF) protein levels correlates with the presence of heart block.



Although 75% of all myasthenics will have eye findings at presentation, only 33% to 50% will have ocular myasthenia only. A higher percentage (90%) of patients with myasthenia gravis (MG) will develop ocular symptoms during the course of the disease. Ptosis is the most common. 5% of patients bwith Graves' disease will develop myasthenia gravis (MG) as well. 10% of myasthenic patirnts have thymomas.



For a patient to be reassured that systemic disease is unlikely, ocular myasthenia should remain localized for 2 years.



Patients with embolic central retinal artery occlusion (CRAO) are at great risk of myocardial infarction (MI). 302


Dhaval Patel MD



Vertebrobasilar insufficiency typically causes binocular visual blurring or oculomotor symptoms. Other symptoms of vertebrobasilar insufficiency include transient dysarthria, drop attacks, photopsias, and hemisensory defects.



So-called tobacco-alcohol amblyopia seems to be seen only in heavy smokers/drinkers with poor nutrition.



The development of diabetic papillopathy appears to be independent of serum glucose levels. Diabetic papillopathy is classically seen in young adults with type 1 diabetes with moderate to severe retinopathy (although it can be seen in patients with type 2 diabetes as well). It is painless, and associated visual loss is generally mild. The disorder generally resolves spontaneously. Diabetic papillopathy does not leak on FFA.



In grave‘s ophthalmopathy, Systemic corticosteroids are thought to be effective only in the acute congestive phase and not in the fibrotic period. Therefore, if no response is noted within 3 weeks, systemic steroids should be tapered and another modality should be considered.



Painful Horner's is an acute dissection of the internal carotid artery until proven otherwise. The diagnosis of exclusion then becomes migraine if the angiogram is normal.



Aicardi's syndrome features mental retardation, lacunar retinopathy, and/or congenital absence of the corpus callosum.



Precocious puberty may be a part of polyostotic fibrous dysplasia (Albright's syndrome).



The ―-triptan‖ antimigraine drugs are used for symptomatic relief of migraines but are contraindicated in patients with basilar artery migraine.

303


Dhaval Patel MD



Binding (not blocking) antibodies to acetylcholine receptors are found in 90% of patients with generalized myasthenia gravis (MG).



drug-induced myasthenia: d-penicillamine



Pupillary fibers from the optic tract exit before reaching the lateral geniculate body (LGB) and exit into the pretectal olivary nuclei.



Pseudotumor cerebri does not recur during pregnancy.



Craniopharyngioma is the most common cause of seesaw nystagmus.



Myelinated nerve fibres: o

Myelinated fibres may represent a choristoma resulting from ectopic oligodendrocytes.

o

About 1 % prevalence

o

More common in boys

o

Bilateral in 20%

o

An enlarged blind spot may be present with a peripapillary lesion, and peripheral lesions may give corresponding field defects. Myopia and amblyopia may be associated, and symptomatic macular involvement has been reported. Rarely, associated retinal vascular abnormalities can be present.

o

Systemic associations include NF1 and Gorlin (basal cell naevus) syndrome.



Optic nerve pits are usually in the inferotemporal quadrant or central part of the disc.



Just Red-free photographs and VF are of no value in distinguishing pseudopapilledema with buried drusen from true papilledema. 304


Dhaval Patel MD

Botulinum Toxin o

Botox A

o

causes irreversible blockage of the pre-synaptic neurone and thus inhibits the release of acetylcholine.

o

The onset of action is 72 hours, with a mean duration of action of 4 months.

o

Termination of action is the result of regeneration of new dendrites.

o

Muscle atrophy occurs in prolonged use of botulinum toxin.



Optic nerve drusen occurs in 2% of optic nerve specimens on histopathology and is bilateral in 50%. Pathologic studies have revealed intra-axonal calcification of mitochondria. The nerve head may be elevated, but no axonal swelling or edema exists. Optic nerve drusen may be inherited in an autosomal dominant fashion and occur more frequently in whites. Visual loss can occur and is thought to result from axonal compression, subretinal hemorrhage, or choroidal neovascular membrane formation. Systemic conditions associated with optic nerve drusen include Paget's disease, Ehlers-Danlos, sickle cell, and pseudoxanthoma elasticum.



Foster Kennedy's syndrome: it is classically produced by a large subfrontal meningioma which compresses one optic nerve (causing ipsilateral optic atrophy) and foramen of Monro (causing hydrocephalus and contralateral papilloedema). Dr. Foster (first name) Kennedy (last name) was a well-known American neurologist in the beginning of 20th century and was once the president of the American Neurological Association.



3rd CN comes out in between posterior cerebellar and superior cerebellar arteries.



Palinopsia (or paliopsia) is the perseveration of a visual image in time.



Tuberculomas account for 40 % of space occupying intracranial masses. However isolated brainstem tuberculomas are rare and account for only 5% of all intracranial tuberculomas in endemic area.

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Premature baby has no pupillary light reaction until 3 weeks of gestational age



Ethambutol toxicity: up to 6% at a daily dose of 25 mg/kg and rare with a daily dose not exceeding 15 mg/kg. Toxicity typically occurs within 3–6 months of starting treatment.



Demyelinating Optic neuropathy is caused by Amiodarone. It affects just over 1% of patients during the initial 8 years of therapy and just under 2% during the subsequent 10 years.



Schilder disease, which is a very rare, relentlessly progressive, generalized disease with an onset prior to the age of 10 years and death within 1–2 years. Bilateral optic neuritis without subsequent improvement may occur.



Two important risk factors for fellow eye involvement in NAION are poor visual acuity in the first eye and diabetes mellitus.



In GCA, the severity and extent of involvement are associated with the quantity of elastic tissue in the media and adventitia. Intracranial arteries, which possess little elastic tissue, are usually spared.



Chromophobe adenoma is the most common primary intracranial tumour to produce neuro-ophthalmological features.



As the optic radiations pass posteriorly, fibres from corresponding retinal elements lie progressively closer together. For this reason, incomplete hemianopia caused by lesions of the posterior radiations are more congruous than those involving the anterior radiations.



Cogan dictum: If the lesion is in the occipital lobe, the smooth pursuit pathways are intact and OKN will be symmetrical. If a homonymous hemianopia is due to a lesion in the parietal lobe, the smooth pursuit pathways towards the side of the lesion are likely to be affected, making this component of OKN defective. 306


Dhaval Patel MD



An important sign of cavernous sinus lesions is sensory loss over the distribution of the first division of the trigeminal nerve.



elephantiasis nervosa = Diffuse plexiform neurofibromas



Meige syndrome is a combination of blepharospasm and involvement of the lower facial and neck muscles.



Brueghel syndrome is blephrospasm associated with severe mandibular and cervical muscle involvement.



Even with a Complete Homonymous Hemianopia, visual acuity should still be 20/20..!! as half a macula is still intact.



Thus the cuneus gyrus receives projections from the superior retina and the lingual gyrus from the inferior retina.



NMO: Devics diaease o

NMO, Aquaporin4 antibody

o

Severe visual loss to start with

o

No improvement in 3 days of IVMP

o

Normal MRI at onset

o

Spinal cord MRI showing 3 or more segment involvement

o

Absence of cortical demyelination in NMO in contrast to MS

o

CSF pleosytosis > 50 cells

o

Ask patients about urinary retention

o

Nausea, vomiting and hiccups 307


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Dhaval Patel MD

Interferon-beta makes NMO worse in contrast to MS

Blind spot of mariotte o

physiological blind spot, "blind point", or punctum caecum

o

The first documented observation of the phenomenon was in the 1660s by Edme Mariotte in France. At the time it was generally thought that the point at which the optic nerve entered the eye should actually be the most sensitive portion of the retina; however, Mariotte's discovery disproved this theory.

o

It is not present in octopus eye.



Kestenbaum's number: Kestenbaum proposed a test that is loosely based on the Gunn phenomenon, in which the patient fixes in the distance with one eye, while the other eye is occluded by the palm of the hand. The examiner holds a handlight with fresh batteries 1 inch from the uncovered eye for 5 seconds to allow the pupils to stabilize. The size of the uncovered pupil is then measured with a pupil gauge to the nearest 0.25 mm. The size of the opposite pupil is then measured in the same fashion, and the difference between the two eyes is determined after correcting for any initial anisocoria. This result is called ―Kestenbaum's number.‖



Supranuclear Imbalance: o

Nystagmus: always has slow phase

o

Saccadic ossilation: they are rapid.



PCA: Posterior cortical atrophy is visual variant of Alzheimer disease.



Saccadic eye movements in neurological lesions are reduced in velocity, while restrictive defects manifest normal saccadic velocity with sudden halting of ocular movement.



Patients with tonic pupil may also sweat excessively, sometimes only on one side of the body. The combination of these 3 symptoms – abnormal pupil size, loss of deep tendon 308


Dhaval Patel MD

reflexes, and excessive sweating – is usually called Ross‘s syndrome. Mx: Thoracic sympathectomy



Any lesion anterior to the lateral geniculate body would cause the ganglion axon cells to degenerate leading to optic atrophy.



A junctional scotoma is a unilateral central scotoma associated with a contralateral superior temporal field defect. In a patient that comes in with poor vision in one eye, it is very important to check the contralateral visual field for superior temporal field loss. Inferonasal retina fibers cross in the chiasm, passing into the contralateral optic nerve (Willebrand‘s knee). The contralateral optic nerve is compressed near the chiasm. These patients have decreased visual acuity and a relative afferent visual defect.



Monocular defects are prechiasmal except that the far temporal visual field is seen only by one eye. Watch this in an anterior occipital infarct, which can produce a monocular temporal defect.



Patients with postchiasmal defects typically have normal visual acuity, normal pupils, and a normal exam of the ocular fundus. Papilledema, however, may be seen in patients with space-occupying lesions.



Optic nerve sheath decompression does not relieve the orbital congestion and would not be effective in thyroid eye disease.



Alexia and agraphia can occur in dominant angular gyrus involvement.



D15 testing can help distinguish the usual red-green color blindness from tritan axis defects, which are commonly found in dominant optic atrophy.



The inability to initiate voluntary saccades is known as ocular motor apraxia. The patient with the congenital onset of this disorder is unable to initiate voluntary horizontal saccades, 309


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but can make normal vertical saccades. Acquired ocular motor apraxia usually occurs with bilateral cerebral hemisphere disease. Patients with Parkinson's disease show difficulty in initiating multiple repetitive saccades.



Oculoplasty 



Valves in Lacrimal System o

The valve of Rosenmüller is located between the common canaliculus (sinus of Maier) and the lacrimal sac and prevents reflux back into the canalicular system.

o

The valve of Bochdalek is at proximal end of common canaliculus.

o

The valve of Krause (and sinus of Arlt) is located at the junction of the nasolacrimal sac and duct.

o

The spiral valve of Hyrtle and the valve of Taillefer are located within the nasolacrimal duct.

o

Valve of Hasner is at the end of NLD at opening in inferior meatus.

Enophthalmos o

Metastatic schirrous breast carcinoma

o

Malignant syringomas (rare forms of sweat gland carcinoma of eyelid) 310


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Blow-out fracture



A rare variant of dermoid cyst, which has been termed a ―conjunctivoid‖ occasionally, is found in the nasal orbit. These unusual dermoids are lined by conjunctival epithelium and has goblet cells which are PAS positive.



Festoons: malar bags, seen in patients with thyroid orbitopathy



Kimura‘s disease is a rare inflammatory disorder of unknown cause, primarily seen in young Asian males. The disease is characterized by a triad of painless subcutaneous masses in the head or neck region, blood and tissue eosinophilia, and markedly elevated serum immunoglobulin E levels.



Rosai-Dorfman disease: Sinus histiocytosis with massive lymphadenopathy. Large histiocytes in orbital infiltrate have phagocytized lymphocytes, a process called emperipolesis. The histiocytes are S-100 positive.



Algernon Reese 50-50 Rule of Lacrimal Gland Pathology



o

~50% of the lesions originate from epithelial elements of the lacrimal gland and 50% are of nonepithelial origin.

o

Of nonepithelial lesions, 50% are lymphoid tumors and 50% are comprised of various infections and inflammatory pseudotumors. (though now inflammatory are more common 60-80%)

o

Among the epithelial tumors of the lacrimal gland, ~50% are pleomorphic adenomas (benign mixed tumors) and 25% adenoid cystic carcinoma, while the remaining tumors are composed of other types of carcinoma.

Rundle Curve: According to the Rundle's curve, Graves' ophthalmopathy (GO) worsens during an initial phase up to a peak of maximum severity, to then improve and reach a static plateau, with the activity curve preceding the severity curve by a few months.

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

Detection of mild pulsatile proptosis: Mild pulsation is best detected on the slit-lamp, particularly during applanation tonometry.



The Zimmerman-McLean-Foster hypothesis: o

In 1979, Zimmerman and colleagues proposed that enucleation of a globe with choroidal melanoma may actually decrease survival, noting the rise in the mortality rate in the years following enucleation from a baseline of 1% per year to a peak of 8% per year during the second year following enucleation.

o

The rate subsequently returned to its baseline level of 1% per year over the next 3 to 5 years.

o

The authors suggested two possible explanations:

o







overwhelming tumor dissemination during surgery



lowering of the host‘s immunologic defense.

data from the COMS published in 1998 demonstrated that no survival advantage was gained by pre-enucleation radiation in more than 1,000 patients with large choroidal melanomas. This result suggests that metastasis occurs prior to enucleation.

Choroidal melanoma o

Mixed type is most common

o

Spindle A has best prognosis

o

Epithelioid has worst prognosis

Pseudoretraction is ruled out by elevating the other side eyelid (appearing ptotic) and making that eye to fixate. In case of pseudoretraction the retracted appearing eyelid assumes normal position once the contralateral eye is made to take up fixation. Causes of pseudoretraction are: ptosis of the other eye, namely acquired apponeurotic type, facial palsy of the same side causing unopposed action of the levator and hemifacial spasm on the opposite side.

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

Floppy eyelid syndrome would have a papillary conjunctival reaction. Filaments are not associated with this condition.



Although Marfan's disease is a disorder of collagen synthesis, blue sclera is not seen in this condition? (This is controversial! some reference says it is a cause of blue sclera and some says it is not. I also found one MCQ which answers marfans as an exception of cause of blue sclera. Oh Dear GOD!)



Dermoids are choristomas containing ectodermal elements (skin, hair, fat, and sebaceous glands). Muscle tissue is not expected to be found in such a lesion.



Fraser Syndrome (cryptophthalmos-syndactyly syndrome): cryptophthalmos, renal agenesis, laryngeal stenosis, syndactyly, aural and genital anomalies



Parry‘s sign: Exophthalmos in thyroid disease



Pseudo–von Graefe sign: Lid elevation on adduction or downgaze due to aberrant regeneration of cranial nerve III.



von Graefe's sign: slow or restricted descent of the lid on attempted down gaze seen in thyroid ophthalmopathy.



Limbal dermoids are usually an isolated abnormality but may on occasion be part of Goldenhar's syndrome, Treacher Collins' syndrome or the naevus sebaceous syndrome of Jadassohn.



Very rarely, capillary haemangioma is part of a wider syndrome Maffucci's (multiple systemic haemangiomata and bone lesions) or Kasabach-Merritt (haematological abnormalities).

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

JACOB‘s ulcer: BCC or rodent ulcer of an eyelid.



Multiple endocrine neoplasia, type IIb (Sipple-Gorlin syndrome), is associated with enlarged corneal nerves, not type 1.



Phthirus pubis (crab louse) infests pubic hair and eyelashes and is transmitted by sexual contact. Treatment is by mechanical removal or with bland ointments applied to the lids to suffocate adult lice. Physostigmine is effective as a respiratory poison against the lice but has many ocular side effects, limiting its effectiveness. Demodex is a normal commensal in adults living in meibomian glands. Classically, ―sleeves‖ are found at the base of lashes, indicating Demodex infestation. Treatment is through lid scrubs. Collarettes are found more commonly with staphylococcal blepharitis.



Conjunctival lymphoma: painless, salmon-colored lesion on the bulbar conjunctiva.



Mucoepidermoid carcinoma: aggressive variant of squamous cell carcinoma. It should be suspected in cases involving recurrence after primary excision or in which no invasion into the globe occurs. It typically occurs in patients over age 60 and involves cells that are able to produce malignant mucussecreting cells (goblet cells).



Basal cell carcinoma is the most common malignant tumor of the eyelid skin, but squamous cell carcinoma is the most frequently occurring malignancy of the conjunctiva. Squamous papillomas are benign lesions that can, on rare occasions, undergo malignant transformation.



Conjunctival malignant melanoma: pigmented elevated lesion, enlarges progressively with time. It occurs most commonly on the bulbar conjunctiva. These tumors are very vascular, and dilated vessels may be seen feeding the tumor. The prognosis is generally better than cutaneous melanomas. A systemic metastatic work-up is necessary to direct treatment. Conjunctival melanomas can arise de novo (30%), from nevi (40%), or from primary acquired melanosis (30%). A conjunctival nevus: flat or slightly elevated pigmented lesion of the bulbar conjunctiva. It may have epithelial inclusion cysts within its substance. These lesions can grow or 314


Dhaval Patel MD

enlarge during adolescence or with pregnancy. Suspicious lesions should be biopsied to rule out melanoma. Primary acquired melanosis (PAM): unilateral condition found in middle-aged white people. These multiple, superficial, flat patches of pigmentation develop into malignant melanoma in 20% to 30% of these patients. Excisional biopsy should be performed on any suspicious nodular lesions. Racial or ocular melanosis: most commonly in pigmented individuals and represents benign collections of melanin in the conjunctiva. It appears as a perilimbal dusting of light brown pigment. No malignant potential exists.



Congenital NLDO: o

It is estimated that congenital nasolacrimal duct obstruction occurs in 73% of newborns but only 6% are symptomatic.

o

The most common site of obstruction is at the valve of Hasner.

o

In a dacryocystocele, there is concurrent obstruction in the common canaliculus - therefore, compression of the sac does not show reflux.

o

A mucocele increases the risk of orbital cellulitis and early probing is recommended. The success of first probing in congenital nasolacrimal duct obstruction approaches 90%.

o

Probing for congenital NLDO should not be done before 9 months??

o

In dacryocystocele, early NLD probing is required.



Synophrys is extension of the eyebrows to the midline. It can occur in naturally hairy individuals who are otherwise normal. It also occurs in Cornelia de Lange syndrome which is characterized by mental retardation, limb reduction, flared nostrils, and hirsutism.



Involutional ptosis should not be confused with myasthenic ptosis because it frequently worsens towards the end of the day. This is because of fatigue of Müller muscle, which has to work harder to keep the lid elevated.



After permanent punctal occlusion with cautery, 20-30% rate of recanalization is expected. 315


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Dhaval Patel MD

potential ocular complications associated with nevus of Ito & nevus of Ota: a. Open-angle glaucoma. b. Malignant melanoma.



Squamous cell carcinoma is the most common malignant tumour of the conjunctiva and typically affects the limbus. It typically occurs in people over the age of 50. Because of its limbal location, it may sometimes be misdiagnosed as pterygium or pingueculae.



SCC is rare amongst healthy young people, its occurrence in patients under the age of 50 should raise the possibilities of AIDS. In African countries where AIDS is endemic, SCC conjunctiva is now recognized as an AIDS defining disease.



Basal cell carcinoma that involves the medial canthus is the most likely to invade the deep orbital structure.



Recently, intralesional injection of OK-432 (group A Streptococcus pyogenes of human origin which is used as an anticancer agent) has been reported to shrink orbital lymphangioma.



Axis of optic canal make 36 degree angle with the midline.



Melanoma with best prognosis: Iris. (can be excised completely) If isolated to the iris, malignant melanoma behaves in a more benign fashion than does melanoma of the choroid. Involvement of the ciliary body or choroid portends a poorer prognosis. Metastases are rare, and localized iridectomy may remove the tumor entirely. These lesions may be pigmented or amelanotic. Ipsilateral hyperchromia may be present. Iris melanoma has spindle B cells(?)



Epiphora is watering due to lacrimal outflow abormality. 316




Complications of chronic dacryocystitis are all except entropion.



Everbusch operation for Ptosis: Skin side

Dhaval Patel MD

Blascovisc operation for Ptosis: Conjunctiva Side



ROPLAS: Regurgitaion over pressure on lacrimal sac



Entropion does not have any subtype like paralytic entropion.??



Congenital acquired fistula: probe test positive, both opening probe touch…why to differentiate?  as it does not close its own.. whereas acquired one closes once u treat the cause.



Sac dilatation: atonicity, long term



Quikert suture: entropion and ectropion: place knot where u want lid to be.If entropion, at margin and vice versa.



RB patients will least likely to have low IOP, microphthalmos, Cataract.



Iris Nevus and Melanoma: o

An iris nevus can be distinguished from a melanoma by: size (<3 mm in diameter), thickness (<1 mm thick), and the absence of vascularity, ectropion uveae, secondary cataract, secondary glaucoma, and growth.

o

Iris fluorescein angiogram (a nevus has a filigree filling pattern that becomes hyperfluorescent early and leaks late or is angiographically silent, whereas a malignant melanoma has irregular vessels that fill late), and B-scan ultrasound or UBM to rule out ciliary body involvement. Transillumination may also be helpful. 317


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

Dhaval Patel MD

Cornelia de Lange's syndrome: o

dysmorphic features are characterized by bushy eyebrows, long curly eyelashes, hirsutism, long philtrum, thin upper lip and down turned angles of the mouth. Late eruption of widely spaced teeth. Limb anomalies are common and consisted of micromelia, phacomelia and oligodactyly. There are growth and mental retardations.

o

chromosome 13q deletion syndrome

Patients with extensive haemangiomas may have: (1) Kasabach–Merritt syndrome, which is characterised by thrombocytopenia, anaemia and low levels of coagulant factors; (2) Maffucci syndrome, which is characterised by enchondromata of hands, feet and long bones as well as bowing of long bones; (3) high-output heart failure.



The orbit is pear-shaped. Its widest dimension approximately 1 cm posterior to the anterior rim.



Blunt cranial trauma is often transmitted to the sphenoid, with secondary indirect traumatic optic neuropathy as a consequence.



In hypertelorism, the medial orbital walls are separated excessively. In exorbitism, the lateral walls diverge excessively (>90 degrees).



The most frequent cause of bilateral proptosis in adults is thyroid ophthalmopathy. The most common cause of bilateral proptosis in children is not definitively established, but metastatic neuroblastoma and/or leukemia should be considered. The most common cause of unilateral proptosis in adults is thyroid ophthalmopathy. The most common cause of unilateral proptosis in children is orbital cellulitis.

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

Although computed tomography (CT) scan does use greater radiation than plain films, it involves less than plain film tomography, which requires multiple exposures. An orbital CT scan administers a dose of 1 to 2 centigrays per scan.



Long T1 times render a substance hypointense (dark) on magnetic resonance images (MRI). Orbital fat behaves opposite to vitreous. To determine the type of magnetic resonance imaging (MRI), look for which is brighter. If the fat is brighter, it is a T1weighted image. If the vitreous is brighter, it is a T2-weighted image.



A bluish bulge above the medial canthal tendon (MCT) is typically a meningocele, whereas one below is typically a dacryocele.



most common risk factor for the development of preseptal cellulitis- recent skin trauma most common risk factor for the development of orbital cellulitis- ethmoid sinusitis



First-generation cephalosporins (e.g., cefazolin, cephalexin, cephalothin) are only effective against half of the isolates of Haemophilus influenzae, and are generally insufficient to cover anaerobes. Second-generation agents (cefuroxime) are preferred. Also note that third-generation cephalosporins (e.g., cefotaxime) have less activity than first-generation cephalosporins against Gram-positive organisms, especially Staphyloccocus aureus.



Orbital studies are incomplete without coronal sections (preferably nonreconstructed, which requires the patient to lie prone).



Hamartomas are abnormal tissue in a normal place (think of ―hammer home‖); choristomas are comprised of normal tissue in an abnormal location.



Capillary hemangiomata will blanch with pressure, whereas the nevus flammeus does not.

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

Mucor, Rhizopus, and Aspergillus can lead to necrotizing orbital cellulitis.



The atrophy of myofibrils is felt to be secondary to compression by surrounding edema. The latter occurs with deposition of glycosaminoglycans in the presence of inflammatory cell and fibroblast infiltration. Antibodies to the thyroid-stimulating hormone (TSH)-receptor expressed on fibroblasts may make them target cells for the inflammation observed in Graves' ophthalmopathy. Primary destruction of myocytes does not seem to occur.



The fragile pial vessels supplying the optic nerve are easily disrupted by any attempt to remove optic nerve meningoma. Surgery is usually undertaken if there is intracranial extension or severe proptosis and severe visual loss.



what percentage of lacrimal gland lesions will be inflammatory/lymphoid? general ophthalmologist's practice: 10% orbit specialists: 50%



Fibrous dysplasia may be monostotic (affect only one bone) or polyostotic. The polyostotic variety may present with precocious puberty and dermal hyperpigmented macules. This disorder, Albright's syndrome, rarely involves the orbit. Orbital disease is nearly always monostotic and rarely associated with precocious puberty, regardless of age. Surgical curettage or excision is usually undertaken. Only woven bone, not cancellous, is found microscopically.



Eosinophilic granuloma frequently involves the orbital bones. The classic triad of HandSchüller-Christian disease consists of proptosis, lytic skull lesions, and diabetes insipidus. Orbital involvement is rare in Letterer-Siwe disease.



It is impossible to differentiate clinically or radiologically between benign reactive lymphoid hyperplasia and orbital lymphoma. Biopsy with light microscopy, immunochemical staining, and electron microscopy is necessary to distinguish between them.

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

The central nervous system (CNS) is not routinely surveyed in patients with orbital lymphoma. This is in contrast to patients with intraocular lymphoma.



Both orbital inflammatory syndrome and lymphoproliferation are composed of polyclonal lymphocytes (although lymphoma contains a monoclonal subpopulation). Cellular heterogeneity is a feature of both orbital inflammatory syndrome and reactive lymphoid hyperplasia. The key features separating the two are (i) prominent fibrovascular stroma and (ii) hypocellularity, both seen in pseudotumor and not in lymphoid activation.



The three orbital deposits that are hyperintense on T1-weighted images are blood, melanin, and mucous. (Fat..?)



The tripod complex is produced by three distinct fractures along suture lines— zygomaticofrontal, zygomaticomaxillary, and the zygomatic arch. Ocular motility may or may not be normal in pure tripod fractures, but upgaze should be spared. Repair is indicated when there is marked cosmetic deformity or potential mandibular instability.



Telecanthus and rounding of the medial canthus are characteristic findings in direct naso-orbital-ethmoid fractures.



The deep head of the pretarsal muscle (Horner's tensor tarsi) is a localized bundle of pretarsal orbicularis that is critical to adequate tear drainage. It surrounds the lacrimal sac and, with each blink, pumps tears downward into the nasolacrimal duct.



The lacrimal sac fossa is formed by the frontal process of the maxilla and the lacrimal bone. It cradles the lacrimal sac and is continuous with the nasolacrimal canal. The lacrimal gland fossa lies in the anterolateral orbital roof within the zygomatic process of the frontal bone.



nodules with central craters: keratoacanthoma & molluscum contagiosum  keratoacanthoma shows more inflammation

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

The syringoma is derived from sweat gland tissue.



An alternate name for pilomatrixoma is the ―calcifying epithelioma of Malherbe.‖



Ephelis: increased melanin content of normal (or decreased) numbers of melanocytes. Lentigo: increased number of melanocytes Nevi: Melanocytes in nevi are referred to as ―nevus cells‖ to reflect this difference. Nevus cells are rounder, with distinct margins and more abundant, eosinophilic cytoplasm.



sebaceous cell carcinoma: not a/w chronic sun exposure



Cogan‘s sign: Upper eyelid twitch when patient with ptosis refixates from downgaze to primary position; nonspecific finding in myasthenia gravis; also refers to venous engorgement over lateral rectus muscle in thyroid disease



plexiform neurofibroma of the upper eyelid: bag of worms.



Epibulbar dermoids are solid choristomas. Adnexal dermoids are generally cystic.



BHID: benign hereditary intraepithelial dyskeratosis: Oral mucosal leukoplakic lesions, bilateral bulbar leukoplakia  obscure, dominantly inherited condition found in a very few number of North Carolinians.



Noninvasive way to reduce Lid Retraction temporarily o

2.5% topical phenylephrine to increase the palpebral aperture of the contralateral eyelid to reduce the differences

o

chin can be lowered

o

sitting position with her eyes looking up 322


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congenital skin crease asymmetry: o

The eye that does not have the skin crease appears smaller because the upper eyelid skin forms a hood over the lid margin

o

The height of the skin crease is due to the interplay of several structures: the level of the orbital septum, the amount of subcutaneous fat and the level of insertion of the levator aponeurosis to the skin. In the East Asians (mainly Chinese, Koreans and Japanese), the skin crease is lower or absent in comparison with other races for the following anatomical reasons:

o



Dhaval Patel MD



the fusion of the orbital septum to the levator aponeurosis is lower (usually below the superior tarsal border);



the presence of a thick subcutaneous fat layer and preaponeurotic fat protrusion prevent the levator fibres from inserting into the skin near the superior tarsal border;



the primary insertion of the levator aponeurosis into the orbicularis muscle and the eyelid skin occurs closer to the eyelid in the East Asians.

To achieve eyelid symmetry, the best way is to create a symmetrical skin crease in the eye without one. This may be achieved by two means: 

Surgical method: The skin crease may be created by excising a strip of skin +/- orbicularis oculi or by the buried suture method.



Non-surgical method: The skin crease may be formed using sticker or glue. This may be or by other cosmetic means (sticker or glue).

The most common vascular lesions of the orbit o

Cavernous haemangioma typically present in patient over the age of 30 and the lesion tends to be intraconal. Blood fluid level is uncommon.

o

Capillary haemangioma usually becomes appear ant at birth or within the first 8 weeks of birth. The lesion typically gives a red cutaneous appearance.

o

Orbital varix shows positional proptosis and typically involves the superior ophthalmic vein.

o

Lymphangioma most commonly presents in patient under the age of 10. On CT or MRI scan the lesion is usually extraconal but may show intraconal extension. The lesion has ill-defined edges but with time partial encapsulation may occur due to the 323


Dhaval Patel MD

attempt of the body to form barrier to limit its growth. Bleeding into cystic spaces gives a blood-fluid level. Clinically, lymphangioma causes a slowly progressive proptosis with globe displacement, ptosis, and restrictive eye movement. The eyelid may have a bluish discoloration from subcutaneous involvement. Sudden worsening of the proptosis may be caused by bleeding into the cystic spaces. Enlargement of the lesion following upper respiratory tract infection is a characteristic feature; this is caused by lymphoid reaction in response to infection. Macroscopically, the lesion usually appears dark red with cystic spaces which may contain dark blood. Histologically, the lesion is made up of bloodless ectatic lymph channels and contain spaces lined by a single layer of flat mesothelial cells.



In Conjunctival lymphoma, If the histology shows a reactive lymphocytic hyperplasia (B-cell type) and within the classification of pseudo B- tumor, then systemic involvement is unlikely. If there is associated Proptosis, then DD should be Systemic lymphoma-with orbital involvement, B-cell replication most common of a rare condition; leukaemias with orbital involvement are a more common association; pseudo-tumours and lacrimal tumours.



Boston‘s sign: Lid lag on downgaze in thyroid disease



Enroth‘s sign: Eyelid edema in thyroid disease



Prognosis for histiocytosis is poor in Children with disease onset younger than 2 years with multifocal disease (especially those with compromised liver or lung function, or impaired hematopoiesis).



The distinction between fibrous dysplasia and ossifying fibroma is generally made histologically. If osteoblasts are present, then the lesion is called an ossifying fibroma; if absent, the term fibrous dysplasia is applied.



Blood stagnation and phleboliths are characteristic of cavernous, not capillary, hemangiomas.

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Dhaval Patel MD



pathology of the nevus flammeus (port-wine stain): dilated capillaries without the endothelial cell proliferation which accounts for their flat clinical appearance.



proptosis with the Valsalva maneuver: orbital lymphangioma, capillary hemangioma, orbital varix. NOT IN Orbital CAVERNOUS Hemangioma



Rhabdomyosarcoma o

Pleomorphic or well-Differentiated rhabdomyosarcoma is the least common type but has the best prognosis.

o

The embryonal type is the most common.

o

The alveolar type has the worst prognosis.

o

Rhabdomyosarcoma originates from undifferentiated pluripotential mesenchymal cells in the orbit. The tumor does not arise from malignant transformation of extraocular muscle (EOM).

o

The cell of origin is presumably an undifferentiated, pluripotent cell of the soft tissue. These cells have the capacity to differentiate toward muscle with production of myosin and actin and to show cross-striations.

o

Immunohistochemistry shows positivity for vimentin, myosin, myoglobin, musclespecific actin, and desmin.

o

Children with rhabdomyosarcoma present with rapidly progressive unilateral, painless proptosis. Swelling and ecchymosis may resemble orbital cellulitis.



Plexiform neurofibroma is most specific for neurofibromatosis. Unlike schwannomas, neurofibromas grow independent of peripheral nerves. In addition, they are generally osteolytic. The association of neurofibroma with congenital glaucoma is strongest with lesions of the upper eyelid.



Positive staining for S-100 is characteristic of any cell derived from the neural crest.



Drugs causing myasthenia or exacerbating the condition are: penicillamine, aminoglycosides, quinidine and propranolol 325


Dhaval Patel MD



Most important two tests in pre-surgical work-up of PTOSIS are corneal sensations and bell‘s phenomenon, as if abnormal, they are contraindications to surgery.



Two common surgical procedures for senile entropion will be: Bick procedure modified by Reeh and Jones, Reeh and Wobig procedure.



The distance between the lateral orbital rim and the anterior corneal surface is measured while doing exophthalmometry. The corneal reflex that is seen in the mirror of the exophthalmometly is then taken as the reading.



Naugle exophthalmometer uses the upper and lower orbital rims for fixation of the instrument



Lesion of actinic keratosis is premalignant whereas those of seborrhic keratosis are not.



In involutional ptosis, there is dehiscence of the levator aponeurosis resulting in an elevated skin crease. The ptosis is constant in up- or down-gaze. The up-gaze is not affected as in some congenital ptosis. Levator advancement is the treatment of choice.



DCR involves removing most of the lacrimal bone.



Naso-orbito-ethmoidal fracture has been discovered as the main cause of traumatic NLDO.



Orbital emphysema usually results from medial wall fractures (not floor fracture..!!) such that sneezing or nose-blowing forces air from the paranasal sinuses into the orbital tissue. Prophylactic antibiotic prevents orbital cell ulitis. The fracture is often small and difficult to locate even with a CT scan. The majority of cases resolve spontaneously and surgery is rarely required. 326


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

Dhaval Patel MD

The Ellebogens' criteria for the ideal eyebrow position and contour are: o

the brow ends laterally at an oblique line extending from the ipsilateral alar base and ipsilateral medial canthus

o

the brow ends laterally at an oblique line extending through the ipsilateral alar base and lateral canthus

o

the medial and lateral ends of the eyebrow lie at about the same horizontal level

o

the apex of the brow lies directly above the lateral limbus of the eye

o

the brow arches above the supraorbital rim in women and lies about at the level of the rim in men

Zimmerman‘s tumor: Phakomatous choristoma o

Lower nasal eyelid or anterior orbital tumor of infants, probably congenital

o

A choristoma of lenticular anlage composed of cells resembling lens

o

epithelium surrounded by thick PAS + lens capsule-like basement membrane, expresses lens proteins

o

The epithelial cells of the phakomatous choristoma stained positively for S-100 protein and vimentin, the intermediate filament normally found in lens epithelial cells. Keratin markers were negative.



Steroid Injection for Chalazion: A steroid injection can lead to permanent depigmentation or atrophy of the skin at the injection site. The manufacturer of triamcinolone has recently recommended against its use intraocularly and in the periocular region. Vigorous injection can rarely result in retrograde intraarterial injection with resultant central retinal artery occlusion. Use of triamcinolone injection for chalazion treatment must include a detailed discussion between physician and patient, as well as adequate documentation in the patient's record.



Papilloma is benign eyelid tumor but remember that it is not caused by human papilloma virus.

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Dhaval Patel MD



Conjunctival amyloidosis is typically composed of immunoglobulin light chains but patients usually do not have systemic disease.



Conjunctival melanoma arises 75% from PAM, 26% mortality and they metastatise to regional noded unlike uveal melanoma which metastatise to liver.



Oncocytoma of cauncle arises from accessory lacrimal glands of popoff. o

Also known as adenolymphomatous tumor, apocrine cystadenoma, oxyphilic cell adenoma

o

rare, mostly benign neoplasms and are mostly found on the caruncle.

o

This tumor arises from accessory lacrimal glands in the caruncle, especially in elderly women. It also can arise from accessory lacrimal glands.

o

Histologic examination reveals solid nests and cords of polyhedral cells exhibiting abundant, finely granular acidophilic cytoplasm and round to oval paracentral nuclei, usually containing a single prominent nucleolus. Cystic cavities are identified within the tumor.

o

Electron microscopic examination shows a cytoplasm densely packed with mitochondria. The mitochondria are sometimes atypical. This is characteristic of oncocytomas.



Mesotherapy: In this technique drugs or nutrients are injected in the skin and subcutaneous tissue to obtain a therapeutic effect. This modality of therapy has not yet received FDA approval.



Chemical Peeling agents: Alfahydroxy acid peel, Trichloracetic acid peel, Phenol peel.



Fillers: Temporary fillers are- Zyderm and Zyplast, Cosmodum and Cosmoplast, Hyaluronic acid gel, Restylane, Radiance FN, Revidum intra, Cymetra sculptra Permanent fillers are- Artecoll- PMMA microspheres in 3.5% collagen. Sheba – Injectable microionised humandermis. 328




Dhaval Patel MD

Botulinum toxin A

o nature‘s strongest blocker of nerve impulses o apporoved by FDA for use in blepharospasm, strabismus and hemifacial spasm o stored at -5 degree celsius and is available in 50-100 unit vials. o reconstituted with 0.9% sodium chloride and should be ideally used in 4hrs and stored at 2-8 degree



Mille‘s Syndrome: facial nevus flammeus and angioma of the choroid in absence og glaucoma.



‗panda eyes‘: always suspect skull base fracture



Centurion syndrome is characterized by anterior malposition of the medial part of the lid, with displacement of puncta out of the lacus lacrimalis due to a prominent nasal bridge.



Sump syndrome complication of DCR, in which the surgical opening in the lacrimal bone is too small and too high. There is thus a dilated lacrimal sac lateral to and below the level of the inferior margin of the ostium, in which secretions collect, unable to gain access to the ostium and thence the nasal cavity.



Giant fornix syndrome: This is due to retained debris in the upper fornix that is colonized by S. aureus, usually in elderly patients with levator disinsertion. Secondary corneal vascularization and lacrimal obstruction are common. Treatment involves thorough cleaning of the fornix, and topical and systemic antibiotics.



The brow fat-pad continues into the upper lid as filmy areolar tissue found posterior to the orbital and preseptal orbicularis muscle, termed the retro-orbicularis oculi fat (ROOF), located within the superficial musculoaponeurotic system (SMAS).

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Dhaval Patel MD



In lower lid, deeper suborbicularis oculi fat (SOOF), less substantial than the malar fat, extends over the body of the zygoma and is continuous inferiorly with the fat deep to the zygomatic major and minor muscles. The suborbicularis oculi fat is located deep to the SMAS and may also droop with aging. In cases of paralytic ectropion from Bell's palsy, ptosis of the suborbicularis oculi fat may need to be addressed in the surgical management.



Lymphoedema–distichiasis syndrome: AD with high penetrance but variable expressivity. Congenital distichiasis along with primary lymphoedema of the legs.



Summerskill sign: eyelid retraction in uremia



In retinoblastoma aqueous to serum LDH ratio is >1, phosphoglucose to isomerase ratio should be >2.



Molluscum contagiosum: large poxvirus o

Syndrome associated are weskott-aldrich syndrome and AIDS



PIEZOMETRY: orbitometry



Hypotelorism is seen in patau syndrome.



Iliff's sign: This involves everting the eyelid and asking the patient to look up. Failure of the eyelid return to its normal position when the patient looks up indicates poor LPS muscle function.



The ETA as described by Baylis is an accurate technique for ptosis correction in patients with poor EPMs. o

External Tarsal Aponeurectomy ETA

o

millimeter for millimeter correction of ptosis 330


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Dhaval Patel MD

not only elevates the upper eyelid but also provides a spacer or graft for the lower eyelid

dictyoma o

A benign tumor of the ciliary epithelium with a netlike structure resembling embryonic retina.

o

aka medulloepithelioma

o

Nonteratoid and teratoid varieties (presence of heteroplastic elements) are known. Both can be benign or malignant.

o

The teratoid type may contain cartilage and/or rhabdomyoblasts.



Cicatricial entropion is seen in  trachoma, due to cicatritial contraction of conjunctiva.



Removal of the palpebral part of lacrimal gland leads to the gland becoming non-secreting.



The Neosynephrine test is an evaluation of the effect of Muller‘s muscle contraction on the degree of ptosis. One drop of 2.5% phenylephrine is placed in the eye. After 5 minutes, the degree of ptosis is reevaluated. The phenylephrine causes contraction of the sympathetic Horner‘s muscle, sometimes causing dramatic improvement in the degree of ptosis. If phenylephrine corrects the ptosis completely, many surgeons elect to perform a Muller‘s muscle resection as opposed to a levator resection.



Whitnall's orbital tubercle is located entirely on the zygomatic bone approximately 2 mm inferior to the frontozygomatic suture line.



Rosengren-Doane‘s Lacrimal Pump Mechanism: o

Contraction of the orbicularis muscle provides a positive pressure in the tear sac, forcing tears into the nose through the valve of Hasner.

o

Once the eyelids open and move laterally, a negative pressure is produced in the tear sac, which is maintained by the valve of Hasner. 331


Dhaval Patel MD



The lacrimal sac fossa is bordered by the anterior lacrimal crest of the maxillary bone and the posterior lacrimal crest of the lacrimal bone. In a dacryocystorhinostomy (DCR), the ostomy is created at the maxillolacrimal suture line located in the lacrimal sac fossa.



Pseudostratified columnar epithelium lines the nasolacrimal sac, duct, and canaliculi.



The slight indentation or groove in the central aspect of the eyelid margin is the sulcus intermarginalis of Graefe or the gray line which corresponds to the lid's orbicularis muscle layer, the muscle of Riolan. It is not the mucocutaneous junction of the eyelid margin. The mucocutaneous junction occurs posterior to the eyelashes near the opening of the meibomian glands.



The Reese-Ellsworth classification was developed in the 1950s as a guide for predicting visual prognosis in eyes treated by methods other than enucleation. It has been used erroneously to predict patient prognosis for life.



The capillary hemangiomas are characteristically high flow lesions, in contrast to cavernous hemangiomas, which are hemodynamically low flow.



Erdheim-Chester disease is a multisystem disease with lipogranuloma formation in the liver, heart, kidneys, and bones. Histologically, these lipogranulomas contain histiocytes, Touton giant cells, lymphocytes, and plasma cells. Ophthalmic manifestations of this disease can include proptosis and xanthelasma-like skin lesions



Euryblepharon is a horizontal widening of the palpebral fissure. Epiblepharon is commonly seen in Asian children and is caused by altered lower eyelid retractor (aponeurosis) attachments, which allow overriding of the pretarsal orbicularis above the eyelid margin. The result is posterior misdirection of the lower eyelashes and potential keratopathy.

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Dhaval Patel MD

Blepharochalasis is a rare inherited condition that occurs more commonly in young females than in males and consists of repeated bouts of eyelid inflammation and edema. Recurrent idiopathic eyelid swelling eventually leads to blepharoptosis secondary to dehiscence or attenuation of the levator aponeurosis. Anterior bulging of the lacrimal gland or orbital fat may also occur. Dermatochalasis refers to the excess eyelid skin that occurs with aging. Steatoblepharon refers to the bulging of orbital fat that also commonly occurs with aging or attenuation of the orbital septum. Blepharospasm may be associated with blepharoptosis and entropion caused by aponeurotic dehiscence. Dermatochalasis, steatoblepharon, and blepharospasm typically are not associated with repeated bouts of eyelid edema and inflammation.



A retroblepharoplasty (transconjunctival blepharoplasty) or blepharoplasty via the transconjunctival approach is used in lower eyelid blepharoplasty, NOT upper eyelid blepharoplasty.



The two most common causes of DCR failure are obstruction at the common canaliculus and obstruction at the bony ostomy site.



Studies have demonstrated that in up to 50% of patients tested, creation of a monocanalicular state resulted in symptomatic epiphora. So upper or lower, canalicular repair should be done leaving open the possibility of future trauma and disease to the remaining canaliculus, and considering present surgical techniques with a high success rate of repair, many recommend attempted repair of all recent canalicular lacerations.



Pneumococci are the most common organism causing acute dacryocystitis. Other organisms include streptococci, diphtheroids, Klebsiella pneumonia, Haemophilus influenzae, Pseudomonas aeruginosa, and mixed organisms. Actinomyces and fungi, such as Candida, are also frequently seen.



Although Actinomyces israelii is associated most frequently with acute canaliculitis, multiple organisms have been shown to cause this disorder. Streptomyces, Arachnia 333


Dhaval Patel MD

propionica (previously Streptothrix), Nocardia, and fungi, such as Candida albicans and Aspergillus niger, have been documented to cause canaliculitis.



Chronic dacryoadenitis: nocardia



Nocardia is acid fast, actinomyces is non acid fast.



Of patients with mucormycosis, 70% have diabetes mellitus, 5% have renal disease, 18% have other immunosuppressed states, 3% have leukemia, and only 4% have no systemic illness.



The clinical signs of thyroid-related orbitopathy can be generally grouped into two independent manifestations: type 1 and type 2 orbitopathy. Type 1 orbitopathy comprises symmetric proptosis with symmetric eyelid retraction, minimal orbital inflammation, and minimal extraocular muscle inflammation or restrictive myopathy. Type 2 orbitopathy comprises extraocular muscle myositis, restrictive myopathy, orbital inflammation, and chemosis. Compressive optic neuropathy is more commonly a feature of type 2 orbitopathy.



Fuchs' adenoma: o

Fuchs' reactive hyperplasia, coronal adenoma, Fuchs' epithelioma, benign ciliary epithelioma

o

proliferative rather than neoplastic

o

The lesion is composed of basement membrane material (type IV collagen and laminin), acid mucopolysaccharides, glycoproteins, and proliferating cells of the nonpigmented ciliary body epithelium.

o

It rarely may cause localized occlusion of the chamber angle.

o

A metastatic lesion from a malignant melanoma would display mostly pleomorphic, pigmented cells with malignant features (high nuclear-cytoplasmic ratio, nucleoli, and mitotic figures). 334


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Dhaval Patel MD

Homer-Wright rosettes are characterized by cells that line up around an area containing cobweb-like material, but no acid mucopolysaccharides are present. These rosettes are not specific for retinoblastoma and are found also in neuroblastoma and medulloepithelioma. Rhabdomyosarcoma displays no rosette formation. In contrast, Flexner-Wintersteiner rosettes are the characteristic rosettes of retinoblastoma but are not always present. The presence of Flexner Wintersteiner rosettes makes the diagnosis of a well-differentiated retinoblastoma. In Flexner-Wintersteiner rosettes, the cells line up around an apparently empty central lumen. However, special stains show hyaluronidase-resistant acid mucopolysaccharides in the lumen.





Malignant Melanoma Eyelid Skin o

all are rare representing less than 1% of eyelid tumors.

o

Superficial spreading melanoma accounts for 80% of cases. Superficial spreading melanoma occurs both in sun-exposed and in nonexposed areas.

o

lentigo maligna and nodular melanoma each occur in 10% of cases. Lentigo maligna, also known as melanotic freckle of Hutchinson, is sun induced.

o

Both have a long horizontal growth phase before invading the deeper tissues.

o

Nodular melanoma is more aggressive with earlier vertical invasion and has worst prognosis.

Fibrous histiocytoma o

slightly more common in men

o

Most are benign (>90%), and have a storiform, or matlike, pattern on histopathology.

o

Most common mesenchymal tumor of orbit in adults

o

It is usually very firm and can displace other orbital structures.

o

Ten percent have metastatic potential. Another 16% are termed ―locally aggressive‖ but not frankly malignant.

o

CD 34 positive on IHC, vimentin +, S100 -

o

Most common site is superonasal orbit 335


Dhaval Patel MD



Pagetoid spread: Sebaceous cell carcinoma and PAM



Papilloma is treated with interferon alpha 2b. in recurrent cases oral cimetidine can be used.



Capillary hemangioma in PHACE syndrome:



o

Caution while using Propanolol

o

Due to Increased stroke risk

IgG4-Associated Orbital Inflammatory Disease o

first recognized by the Japanese in 2001 in autoimmune pancreatitis (AIP)

o

number of diseases have now been recognized as part of the spectrum of IgG4-RD, and these include sclerosing cholangitis, Mickulicz disease, Küttner tumor (sclerosing sialadenitis), Riedel thyroiditis, multifocal fibrosis, Ormond disease (idiopathic retroperitoneal fibrosis), and others

o

evidence of a role for Helicobacter pylori

o

Several recognizable patterns of orbital disease may occur with IgG4-ROD

o



Dacryoadenitis,



Dacryoadenitis (bilateral) with enlarged parotid and submandibular glands (previously called Mickulicz disease



Orbital myositis



Sclerosing orbital disease

Treatment 

empirical use of corticosteroids



methotrexate, mycophenolate, and cyclophosphamide.



rituximab.

336


Dhaval Patel MD

Community Ophthalmology 



WHO declared the year 1976 as "The Year of Prevention of Blindness" and stated that the 6 main causes of blindness were: o

Cataract

o

Trachoma

o

Xerophthahnia

o

Onchocerciasis

o

Glaucoma and

o

Trauma

Severe visual loss is defined as a vision of 20/200 or worse. Profound visual loss is defined as visual acuity worse than 20/400. The World Health Organization (WHO) defines blindness as vision worse than 20/400. The World Health Organization (WHO) defines low vision as vision worse than 20/60. Eyes with severe visual loss (20/200 or worse) are considered legally blind in the United States.



In 1948, the first randomized clinical trial (RCT) was published on the use of streptomycin in pulmonary tuberculosis.



The Consolidated Standards of Reporting Trials (CONSORT) statement, which is ascribed to by leading peer-reviewed journals, sets a high standard of quality in the 337


Dhaval Patel MD

reporting of randomized clinical trials (RCTs) in order to allow the reader to adequately judge the quality of the study.



Average visual acuity is significantly better than 20/20 in individuals younger than 60 years.



Worldwide, more adults than children are blind.



Pediatric blindness most commonly occurs from corneal scarring and retinal diseases.



Studies have shown that ethnicity does not affect the incidence of ophthalmia neonatorum, but socioeconomic status certainly does.



Ophthalmia neonatorum treatment: o

Chlamydiae trachomatis: Oral erythromycin 50 mg/kg in four divided dose for 14 days

o

Gram-positive bacteria: Erythromycin 0.5% e/o QID

o

Gram-negative bacteria: gonococcal 

Systemic: Inj. ceftriaxone 25–50 mg/kg IV or IM single dose X 7 days



Inj. cefotaxime 100 mg/kg IV or IM single dose X 7 days



Topical: saline lavage hourly, bacitracin eye ointment qid, or penicillin drops 5000-10,000 IU/ml



Worldwide, 135 million people have vision <20/60, and approximately 45 million have vision <20/400. (?)



Eighty percent of global blindness either can be treated or avoided.

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Dhaval Patel MD



National Fortnight on Eye Donation is celebrated from 25th August to 8th September. Late Prime Minister Shri Rajiv Gandhi pledged his eyes for donation on the 25th August to motivate people. Since then a fortnight is celebrated every year.



Hospital Cornea Retrieval Programme Ramayamma International Eye Bank initiated HCRP IN 1990 to concentrate on death that occurs in hospitals and encourage eye donations using a combined method of motivation and grief counselling. HCRP focuses on hospital because:



o

Availabilty of medical history

o

Availability of tissues from younger individuals

o

Reduction of time interval between death and corneal excision

Childhood Blindness o

Globally prevalence is 0.75/1000 children (75 per one million)-varied from .3 to 1.2/1,000 children.

o

1.4 million blind children in the world-1 million in Asia

o

Prevalence of childhood blindness in India: 0.17%

o

Refractive error is major causes: 33.3%



prevalence of uncorrected refractive error (myopia) among age groups 7 -15 years is around 7.3% in urban and 4% in rural.



The prevalence of ocular trauma in a study urban slums Delhi s= 2.4% (2008) In South India (Andhra Pradesh Eye Disease Study) = 3.97% (2000)



Field of vision restricted to 20 degree around central fixation- equivalent to <6/60 Field of vision restricted to 10 degree around central fixation- equivalent to <3/60

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

Dhaval Patel MD

DR in community: o

Prevalence of diabetes: 3% - 20%

o

Prevalence of diabetic retinopathy: 15 - 25%

o

Prevalence of sight threatening DR- 20%

o

Proportion of DR becoming blind- 2%

Blindness Prevalence: o

Prevalence of blindness (1986-89)- 1.49%

o

Prevalence of Blindness ( 2001-02)- 1.1%

o

Percentage of decline of Prevalence – 26%

o

Percentage of blindness due to Cataract (1986-89) – 80 %

o

Percentage of blindness due to Cataract (2001-02) – 62 %

o

Cataract blindness as per NPCB criteria in 50+population- 5.32% (8 % as per 198689 Survey)

o

Cataract surgical coverage – 65.7%

o

16.6% individual are socially blind after cataract surgery.

o

33.6% presenting vision < 6/60 after cataract surgery

NPCB Financial Assistance: o

NPCB Supports Rs. 2000/- per pair of eyes collected

o

Rs. 275 per spectacle by NPCB

o

Assistance for Cataract Surgery @ Rs.1000/- per cataract operation/per eye

o

Assistance of Rs. 1500/- per case for management of diseases like diabetic retinopathy, glaucoma, childhood blindness including squint and ROP etc

o

Assistance of Rs. 5000/- per case for corneal transplantation, vitreo-retinal surgery

o

Rs.30 Lakhs to NGOs for insfrastructures development

o

To Eye Banks in Government/Voluntary Sector (upto maximum Rs. 15.00 lakhs); 340


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Dhaval Patel MD

o

Eye Donation Centres in Government/Voluntary Sector (upto maximum Rs. 1.00 lakhs).

o

Development of Mobile Ophthalmic Units with Tele-Ophthalmic Models (upto maximum Rs. 60.00 lakhs).

o

Assistance for Mobile Van with ophthalmic equipments Rs.20 lakh.

o

Tele- Ophthalmic Network Rs.40 lakh

NPCB-100% centrally sponsored In 1994-95, Program was decentralized with formation of DBCS





Proposed structure for Vision 2020 (4 Tier structure) o

Centre's of Excellence: 20, One for 50 million

o

Training Centre's: 200, One for 5 million

o

Service Centre's: 2000, One for 5 lakhs

o

Vision centre's: 20000, One for 50,000

Ophthalmologist:1 per 50,000 population MLOA: 1 per 5,00,000 population



India Study of Age-related Eye Disease (INDEYE study) (RPC and LAICO) o

Prevalence of cataract in 60+ 

Men: 70.1 (68.0-72.1)



Women: 76.7 (74.9-78.5)



Total: 73.6 (72.0-75.2)

 341


Dhaval Patel MD

Miscellaneous 



Preparation of tissue for EM: o

Primary fixation: 2.5% glutaraldehyde in distilled water

o

Wash: distilled water

o

Secondary fixation: 1-4% osmium tetroxide in distilled water

o

Wash: distilled water

o

Dehydration: 70% ethanol

Oculo Cutaneous Albinism o

o

OCA1: TYROSINASE-NEGATIVE OCA 

AR



Classic and most severe form



second most common type of OCA



do not have clinically or histopathologically discernible pigmentation



In vitro hair bulb incubation in L-tyrosine does not produce melanin.



skin and hair reveals no melanization of melanosomes.



decreased number of crossing nerve fibres at the optic chiasm, as well as other central visual pathway anomalies.



Not associated with syndromes

OCA2: TYROSINASE-POSITIVE OCA 

AR



most common form of albinism 342


Dhaval Patel MD



presence of some pigment in the hair, skin, and eyes of all patients beyond infancy



lightly melanized melanosomes in the skin and hair of older patients



maps to 15q11



region associated with Prader-Willi's and Angelman's syndrome



Chediak-Higashi and Hermansky-Pudlak syndromes are potentially lethal forms of albinism, both of which are inherited in an autosomal recessive fashion.



Chediak-Higashi syndrome is characterized by neutropenia, lymphocytosis, anemia, and thrombocytopenia. Neutrophils and other lysosome-containing cells characteristically have large granules and have impaired chemotaxis and microbial killing caused by poor fusion of lysosomes to phagosomes. Patients suffer from recurrent infections and are at increased risk of developing lymphoreticular malignancies.



Hermansky-Pudlak syndrome is more common in Puerto Ricans, and patients with this syndrome have abnormal platelets and a susceptibility to bleeding and bruising.

Ocular Albinism: o

XR

o

Nettleship–Falls type

o

eyes show hypomelanosis with nystagmus, and the hair and skin have no or little clinical manifestation

o

mother is carrier

o

Five tests can be performed to diagnose XLOA or to detect the carrier state: iris illumination, fundus examination, skin biopsy, VEP, and DNA tests

Latest Nosology of Albinism OCA 1: tyrosine related (HPS,CHS) OCA 2: p gene OCA 3: TYRP1 343


Dhaval Patel MD

OCA 4: MATP OA 1: XL



The hallmark of nasopharyngeal carcinoma is its propensity to involve multiple cranial nerves noncontiguously.



There are nine distinct subtypes of EDS but type 6 and, rarely, type 4, are associated with ocular features.



Eye-Protective Mechanisms



o

Tear production

o

Blink frequency and adequacy

o

Eyelid movement and position

o

Corneal sensation

o

Ocular motility

o

Bell's phenomenon

Gadolinium and fat suppression are T1 techniques and both should be used together as no use of giving only gadolinium. FLAIR is T2 technique that suppreses water (CSF). It may be confused with T1.



Most of orbital mass are dark (hypointense) on T1 MRI Exceptions are  Fat, Blood and melanin o

Fat: lipoma, liposarcoma

o

Mucus: dermod cyst, mucocele

o

Subacute blood (3-14 day old)

o

Melanin: melanoma 344




o

Some fungal infections

o

Gadolinium enhancement

o

Retinoblastoma also hyperintense on T1

Dhaval Patel MD

Ophthalmic association of OSA o

Floppy Eyelid Syndrome

o

CPAP associated red eye

o

NAION

o

Papilledema

o

Normal Tension Glaucoma



Heavy eye syndrome: This condition occurs when the globe enlarges on the basis of axial myopia. This globe enlargement results in dehiscence of the intermuscular membrane in the superior temporal area which in turn results in the superior rectus shifting nasally and the lateral rectus inferiorly. In some cases the eye is also hypodeviated in this condition. A relatively new procedure described by Yokoyama unites the belly of the nasally displaced superior rectus muscle with the inferiorly displaced lateral rectus with reported good results. If the medial rectus is tight, it could be recessed or some would consider the use of Botox.



Hutchinson‘s pupil: Fixed, dilated pupil in comatose patient due to uncal herniation and compression of cranial nerve III Hutchinson‘s sign: Involvement of tip of nose in herpes zoster ophthalmicus (nasociliary nerve involvement) Hutchinson‘s triad: Three signs of congenital syphilis – interstitial keratitis, notched teeth, and deafness



In USG, Gain adjusts the amplification of the echo signal, similar to volume control of a radio. Higher gain increases the sensitivity of the instrument in displaying weak echoes such as vitreous opacities. Lower gain only allows display of strong echoes such as the retina and sclera, though improves resolution because it narrows the beam.

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Dhaval Patel MD



Ophthalmia nodosa is a cutaneous condition characterized by inflammation of the eye due to lodging of (for example) caterpillar hairs in the conjunctiva, cornea, or iris.



Ophthalmomyiasis: Myiasis is coined from the Greek word ‗myia‘ denoting fly. It refers to the infestation of tissues by the larvae (maggots) of diptera (two-winged) flies. The condition is well recognised in animals but rare in humans. Cases of human myiasis have been reported in various parts of the world and could be attributed to one of the three dipteran families: Oestriade, Calliphroidae and Sarcophagidae. In South-East Asia, animal myiasis is endemic and the main causative agent is Chrysomya bezziana, also known as screwworm fly of the Old World. This fly belongs to the Calliphoridae family and causes obligatory myiasis (it requires a living host for the development of the larval stages). It infests mainly domestic animals and may cause great losses in livestock industry if not treated rapidly. Screwworm infestation is transmitted by the female fly that lays her eggs on a superficial wound, but occasionally on unbroken soft skin, especially if it has blood or mucous discharge on its surface. Eggs are deposited in batches of 150 to 500 and hatch in about 15 hours. The larval bodies, measuring 10 to 15mm are armed with broad, encircling bands of spines. The larvae feed on blood and serum and burrow deep into the tissue with their mouth-hooks causing considerable destruction. Infested wounds often attract other female screwworms resulting in multiple infestations. After feeding for 5 to 7 days, the larvae leave the wound and fall to the ground where they burrow and pupate for one week or more to emerge as adult flies. The life cycle from egg to egg takes about 24 days. The sclera of a child is easier to penetrate than that of an adult.



After thyroidectomy, the complication can be hypoparathyroidism with consequential hypocalcaemia leading to cataract and corneal clouding. Ca2+ ions are essential for corneal metabolism-note the sub-epithelial clouding.



Draize eye test: Justified by an exigency for public protection, the Draize eye test became a governmentally endorsed method to evaluate the safety of materials meant for use in or around the eyes. The test involves a standardized protocol for instilling agents onto the cornea and conjunctiva of laboratory animals. A sum of ordinal-scale items of the outer eye gives an index of ocular morbidity

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Dhaval Patel MD

The hallmark of nasopharyngeal carcinoma is its propensity to involve multiple cranial nerves noncontiguously. Nasopharyngeal carcinoma is common in Chinese men. The least differentiated forms are also known as Schmincke's and Regaud's tumors. NPC has its highest incidence in southern China escpecially in Hong Kong and Guangzhou, with documented rates of 10 to 150 cases per 100,000 population per year. For this reason, this cancer is often referred to as "Cantonese cancer" or "Kwangtung tumor."



Apart from hypertensive choroidopathy, decreased vision in eclampsia (also in preeclampsia) are usually caused by: o

serous retinal detachment (from the breakdown of the retinal pigment epithelium barrier)

o

occipital cortex involvement (this may be caused by vasospasm, ischaemia or oedema from increased vascular permeability, most cases of cortical blindness resolved within 4 hours to 8 days) Less common causes include: 

acute ischaemic optic neuropathy



retinal vasospasm or oedema



It was thought at the time that animal eyes actually generated light and that the more excited the animal, the brighter the light. This idea was ultimately put to rest by Prevost (1818) who showed that one never saw a luminous eye when the animal and observer were in a totally dark room. At about the same time Gruithuisen discovered that the eyes of some animals (e.g., dogs and cats) contain a unique layer behind the retina, the tapetum lucidum that reflects light and is responsible for the luminous appearance of animal eyes.



Key idea in the invention of the ophthalmoscope: the illumination axis and the observer‘s viewing axis have to be as close as possible.



Since the maximum resolving power of the direct ophthalmoscope is 60 µm, many of the small red dots observed in the fundus are not microaneurysms but microhemorrhages. The effect of body size as a risk factor for primary open angle glaucoma (POAG) is unclear. In fact, the Barbados Eye Study found that lean body mass may be a risk factor for POAG in the African American population. 347


Dhaval Patel MD



The Singaporean Chinese community, in particular, has a very high incidence of primary angle-closure glaucoma.



Echothiophate iodide is an irreversible cholinesterase inhibitor whose effects may persist for days after discontinuation of the drug. It prolong respiratory paralysis caused by SCh.



Mydriatic recovery in normal eyes is as follows: atropine (7-10 days), scopolamine (3-7 days), homatropine (1-3 days), cyclopentolate (1 day), and tropicamide (6 hours).



Cyclosporine is a potent immunosuppressive agent that acts by suppressing T cells. This is helpful in many ocular surface conditions from atopic keratoconjunctivitis to dry eyes to graft rejection.



The IOP-elevating potential, in decreasing order, is dexamethasone > prednisolone > loteprednol etabonate > fluorometholone > hydrocortisone > tetrahydrotriamcinolone.



Ciprofloxacin has broad gram-positive and gram-negative bacterial activity by interfering with DNA gyrase; however, recent reports have described the growing resistance of streptococci to ciprofloxacin.



Natamycin is available as a 5% topical ophthalmic solution. It is active against filamentous fungi including Aspergillus, Cephalosporium, Curvularia, Fusarium, Penicillium, and Candida albicans. Mucor is better treated with amphotericin B.



Proparacaine is a topical ester anesthetic. Its duration of action is about 20 minutes**. In injectable form, lidocaine lasts 1 to 2 hours, mepivacaine lasts 2 to 3 hours, and bupivacaine (Marcaine) lasts up to 8 hours.

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Dhaval Patel MD



During the procedure C3R, 0.1% Riboflavin eye drops in Dextran solution are applied to the cornea for 30 minutes followed by exposure to UV-A light (365 nm) at 3mW/cm2 to achieve cross-linkage of the corneal collagen fibres.



The term lagophthalmos comes from the Greek word for hare (lagos) because rabbits were thought to sleep with their eyes open.



Color blindness was not recognized as a congenital defect until 1794 when the famous chemist John Dalton described his own red-green deficiency.



Cost-Effective Eye Care: Avoid These 5 Tests and Treatments 1. "Preoperative Medical Tests: Don't perform preoperative medical tests — such as an electrocardiogram or blood glucose test — prior to eye surgery unless there are specific signs indicating a need for them. 2. Imaging Tests: Don't routinely order imaging tests when there are no symptoms or signs of significant eye disease. 3. Antibiotics for Pink Eye: Don't prescribe antibiotics for pink eye that is caused by an adenovirus. 4. Antibiotics for Eye Injections: Don't routinely provide antibiotics before or after injections into the vitreous cavity of the eye. 5. Punctal Plugs for Dry Eye: Don't treat dry eye by inserting punctal plugs before attempting other options, such as medical treatments with artificial tears, lubricants and compresses."



AD/ MCI/ Normal Cognition: Patients with probable AD had significantly narrower retinal veins and decreased retinal blood flow compared with those with MCI and normal controls. But the MCI group had significantly lower blood flow and blood speed than those with normal cognition.



Bionic Eye: US Food and Drug Administration (FDA) approved a retinal prosthesis that may help blind people with advanced-stage retinitis pigmentosa avoid obstacles and read large letters. It does not restore normal vision, but it does produce patterns of light that the brain learns to interpret as specific objects in the environment 349


Dhaval Patel MD



Taiwanese researchers developed a fungus-specific oligonucleotide probe for a molecular hybridization assay to look for a conserved region of the 5.8S rRNA gene common to various fungi species. The hybridization assay identified the fungi species within 1 day and had a sensitivity of 100% and specificity of 96.7%, compared with 50% sensitivity and 100% specificity for cultures



Sweet syndrome: key clinical features in this case are the abrupt onset of fever, bilateral ocular inflammation nonresponsive to topical steroids, and tender skin nodules in a patient with a known diagnosis of ulcerative colitis. Two features are absolutely required for diagnosis: the abrupt onset of a typical skin eruption that consists of tender erythematous plaques, nodules, or pustules, and the histologic finding of neutrophilic infiltration in the dermis without leukocytoclastic vasculitis on skin biopsy.



surfaces of the globe and cornea: 12000 km & 12000 microns



Glues used in Ophthalmology o

o

Fibrin  conjunctival closure 

Antibiotic impregnated



Pterygium  Graft



Clear corneal incisions



Ptosis: Muller conjunctival resections

Tranforming growth factor beta 

o

Chorioretinal adhesion

Cyanoacrylate 

N-butyl-2-cyanoacrylate  clear corneal incisions



Octyl-2-cyanoacrylate



Adal-1 cyanoacrylate



Iso-amyl-cyanoacrylate 350


Dhaval Patel MD



experimental use of oral rifampin and mifepristone (RU486) has recently been suggested especially in chronic or bilateral cases of CSCR.



investigational drug selumetinib, an MEK inhibitor under development by AstraZeneca, systemic therapy has shown efficacy in a rare form of melanoma that affects the eye, uveal melanoma.



An ancient eye test-using the stars: Vision testing in ancient times was as important as it is today. The predominant vision testing in some cultures was the recognition and identification of constellations and celestial bodies of the night sky. A common ancient naked eye test used the double star of the Big Dipper in the constellation Ursa Major or the Big Bear. The second star from the end of the handle of the Big Dipper is an optical double star. The ability to perceive this separation of these two stars, Mizar and Alcor, was considered a test of good vision and was called the "test" or presently the Arab Eye Test. This article is the first report of the correlation of this ancient eye test to the 20/20 line in the current Snellen visual acuity test. This article describes the astronomy, origin, history, and the practicality of this test and how it correlates with the present day Snellen visual acuity test.



Fishhook contains the barb at its end, so once inside, it‘s difficult to remove it in cases of eye injury.



Glaucoma Research Foundation (GRF): 2011, Researchers employed a range of techniques including molecular biology, electron microscopy and image analysis to uncover three interconnected new discoveries about glaucoma: Glaucoma Reveals New Similarities to Parkinson's Disease: Glaucoma is characterized by formation of protein aggregates called gamma-synuclein. Most other neurodegenerative disorders, like Parkinson's and Alzheimer's diseases and Amyotrophic Lateral Sclerosis (ALS), are characterized by the aggregation of proteins. In Parkinson's disease, a very similar protein called alphasynuclein is aggregated. This finding provides evidence that glaucoma acts more like protein aggregation neurodegenerative diseases than like other blinding eye diseases. New Cellular Mechanism Discovery: A subpopulation of support cells, called astrocytes, have been found to have a highly unexpected role in cleaning up the byproducts or waste of the cells that die in glaucoma, the retinal ganglion cells. This type of "degradative" activity was not previously known to exist, and its existence may help explain perplexing findings in many neurodegenerative disorders besides glaucoma. Underlying Cause of Vision Loss: 351


Dhaval Patel MD

Previous work by scientists had pointed to an anatomical location, the optic nerve head, where vision loss most likely occurs in glaucoma. This study is the first to pinpoint where within the optic nerve head the blinding insult is likely to be, which would explain the very characteristic pattern of blindness in glaucoma



AAO Suggested Routine Eye Examination Guidelines Ages 0-2: screening during regular pediatric appointments. Ages 3-5: screening every 1–2 years during regular primary care appointments. Ages 6–19: schedule examinations as needed. Ages 20–29: one examination Ages 30–39: two examinations Ages 40–65: examination every 2–4 years Ages 65 and over: examination every 1–2 years. (More frequent examinations may be recommended if any of the following risk factors exist: history of eye injury, diabetes, family history of eye problems, African Americans older than 40 years of age.)



In shaken baby syndrome, Neurological deficits occur in about one-third of patients. Visual impairment is usually caused by cerebral damage.



Ramsey Hunt syndrome: Sudden onset of pain in the ear and who cannot shut the eye on the same side. The involvement of the seventh cranial nerve with the herpes zoster virus. There may be an eruption in the external auditory meatus, as this area receives a sensory supply from the seventh cranial nerve.



Paget's disease: the patient who need a bigger hat develop an afferent pupillary defect

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Dhaval Patel MD

This causes enlargement of the skull due to disorganization of the bony structure. This can cause compressive optic atrophy in the optic canal.



Visual claudication woman complains of discomfort in both arms and a transient loss of vision which occurs on exercises Takayasu's syndrome with involvement of the carotid and axillary arteries. Exercise causes a "steal" syndrome leading to retinal ischaemia.



VITAL Study: VIsion TriAL for depression management, related to low vision aids.



Charles Bonnet syndrome: o

condition that causes patients with visual loss to have complex visual hallucinations, first described by Charles Bonnet in 1760 and first introduced into English-speaking psychiatry in 1982.

o

Sufferers, who are mentally healthy people with often significant visual loss, have vivid, complex recurrent visual hallucinations (fictive visual percepts). One characteristic of these hallucinations is that they usually are "lilliputian" (hallucinations in which the characters or objects are smaller than normal). The most common hallucination is of faces or cartoons. Sufferers understand that the hallucinations are not real, and the hallucinations are only visual, that is, they do not occur in any other senses, e.g. hearing, smell or taste



Serif fonts and Sans Serif fonts are two broad categories of letters.



National Institute for the Visually Handicapped NIVH is situated at 116 Rajpur Road, Dehradun - 248 001, Uttaranchal, India. Phone: + 91 135 274 4491



Coenurosis is a parasitic infection that results when humans ingest the eggs of dog tapeworm species Taenia multiceps, T. serialis, T. brauni, or T. glomerata. There are many different tapeworm species belonging to the genus Taenia, but these four in particular are responsible for the rare human disease, coenurosis. 353


Dhaval Patel MD



In 1974, US National Institutes of Health held a conference on the naming of diseases and in 1975, JAMA published an article and decided to drop the possessive ―s‖ in all its publications (Down syndrome not Down‟s Syndrome) but has not been able to convince journal editors.



Tyndall effect: A very sensitive way to detect particulates is to bathe the air with intense light. The scattering of light by particulate impurities in air and other gases, and in liquids, is known today as the Tyndall Effect or Tyndall Scattering.



ALARA concept: As Low As Reasonably Achievable, for radiation exposure in imaging.



HEPA filters remove particles <0.3 microns.



blood level of vitamin A: 150–300 IU/dl (30–65 µg/dl retinol)



Uyemura‘s syndrome: xerophthalmic fundus, White spots of the fundus combined with night blindness and xerosis



detection of foreign body based on electrical conduction



o

Bermann‘s locator

o

Roper Hall‘s locator

o

Carnays locator

o

Ophthalmometalloscope of Hale

Limbal ring method for detection of FB was described by Stallard and Somerset. It was used basically to detect FB is intraocular or extraocular.

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Dhaval Patel MD

types of magnets o

Hand held RARE EARTH magnet: small and low powered.

o

Electromagnet: strong magnetic field

FUGO Blade:

o ―electromagnetic plasma‖ cutting device o developed by an ophthalmic surgeon, Dr.Richard Fugo o It works on 4 rechargeable battery cells. One charge allows a cutting time of 40 minutes

o The working end of the tool is the blunt tip of a steel wire, varying in size from 100 micron to 600 microns

o plasma energy from the activated working tip is transferred to the molecules of the tissues, by the process of resonance



Mast cell inhibitors o

Lodoxamide (Alomide)

o

Cromolyn sodium (Crolom)

H1 receptor antagonists o

Levocabastine (Livostin)

o

Emedastine (Emadine)

Combination H1 antagonists/mast cell inhibitors (POKAN) o

Ketotifen (Zaditor)

o

Olopatadine (Patanol)

o

Nedocromil sodium (Alocril)

o

Azelastine hydrochloride (Optivar)

o

Pemirolast (Alamast) 355


Dhaval Patel MD



Echothiophate iodide is an irreversible cholinesterase inhibitor whose effects may persist for days after discontinuation of the drug.



Ciprofloxacin has broad gram-positive and gram-negative bacterial activity by interfering with DNA gyrase; however, recent reports have described the growing resistance of streptococci to ciprofloxacin.



The eye-popping reflex is a neonatal reflex described by Perez in 1972. It involves a pronounced widening of the palpebral fissures after an abrupt decrease in ambient illumination primarily, or after loud noises. It is present within the first 3 weeks of life in 75% of infants born after 28 weeks' gestation. In contrast, eye pressing, or gouging, and light gazing are abnormal behavioral mannerisms in visually-impaired children. A paradoxical pupillary response is rare but when present, it is highly suggestive of congenital stationary night blindness, achromatopsia, or optic nerve hypoplasia. A paradoxic response refers to an immediate constriction during the first 20 seconds after room lights are turned off, followed by a slow dilation after 1 minute.

Lateral Thinking 

Stigler's Law of Eponymy, which states, "No scientific discovery is named for the original discoverer" As proof, Stigler freely admits that others postulated the idea before he named it for himself. In describing Stigler's Law, Malcolm Gladwell stated, "We think we're pinning medals on heroes. In fact, we're pinning tails on donkeys.‖



"Domino" effect: chain reaction that occurs when a small change causes a similar change nearby, which then causes another similar change, and so on in linear sequence. The term is best known as a mechanical effect, and is used as an analogy to a falling row 356


Dhaval Patel MD

of dominoes. It typically refers to a linked sequence of events where the time between successive events is relatively small. It can be used literally (an observed series of actual collisions) or metaphorically (causal linkages within systems such as global finance or politics).



Butterfly effect is the sensitive dependency on initial conditions in which a small change at one place in a deterministic nonlinear system can result in large differences in a later state



Lewis Carroll conceives of Alice seeing things smaller than they were was because of Migraine in which he had episodes of micropsia during his migraine attacks.



Vision of Quicksands: Thomas de Quincey experienced visions of a girl sinking in quicksands while he was under the influence of opium.



licensed ophthalmologist: Syria‘s President Bashar al-Assad, and Kentucky Senator Rand Paul



Turk disease is another name of Duane Retraction Syndrome.



Strumple Marie Disease is another name of Ankylosis Spondylitis.



The concept of removing clouded cornea was described by Erasmus Darwin, grandfather of Charles Darwin.



Twilight Blindness or Aknephascopia is an abnormally reduced vision in low level of illumination.



Samuel Thomas van Sommerring was a german anatomist, who first described importance of macula and in older literature, macula is also referred as Sommerring‘s spot. 357


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Dhaval Patel MD

Sir jonathan Hutchison was an English surgeon, ophthalmologist, dermatologist, venerologist and pathologist. o

Senile Degeneration of choroid is known as Hutchinson's disease

o

Hutchinson's facies is a peculiar, rigid facial expression produced by drooping eyelids and unmoving eyes.It occurs due to tension of the muscles of the forehead attempting to counterbalance ptosis in external ophthalmoplegia



William Conner and Richard Alexander started a small pharmacy  Alcon (AL from Alexander and CON from Conner, in texas in 1949 making sterile medical appliances and drugs. It grew over time and was bought by a swiss company and sold off again recently to NOVARTIS as one of the biggest business deal 28 billion USD.



ALLERGAN: The innovative spirit that infuses Allergan today can be traced back to Allergan's founder, pharmacist Gavin S. Herbert. In 1948, Mr. Herbert was already the successful owner of a chain of drug stores in Los Angeles. But his interest and entrepreneurial instincts were ignited when a close friend and chemist, Stanley Bly, approached him with an idea for an anti-allergy nose drop containing the antihistamine neoantergan (aka MEPYRAMINE). They set up a small laboratory on the balcony of Mr. Herbert's drugstore in Los Angeles to make the solution, which they named ALLERGAN® Nasal Drops. Responding to the suggestion of an ophthalmologist friend, Mr. Herbert and Mr. Bly later reformulated the product as an eye drop to treat allergic conjunctivitis (inflammation of the eye). The result was ALLERGAN®, the first antihistamine eye drop in the United States.



Norma Jeane Mortenson became Marilyn Monroe after cosmetic –aesthetic surgery.



Literal meaning of cul-de-sac is a road with one end blocked or dead end.



In 1850s, ―Eye Mirror‖ or ―Eye Speculum‖ was a popular name for an emerging ophthalmic instrument among the Europe  augenspiegel (german name of eye mirror) which later become ophthalmoscope. o

Augenspiegel (eye mirror) and Augenspiegeln (eye mirroring). 358


Dhaval Patel MD

The word ophthalmoscope was first introduced by Maressal de Marsilly from Calais, France, in 1852.



The term daltonism was described for color blindness of John Dalton, the great chemist who first described his own anomaly.



Duke-Elder in 1936 honored Sjogren by naming KCS with Sjogren‘s Syndrome.



It was Sir Isaac Newton who first proposed that binocular vision results from partial decussation of optic nerve fibres at optic chiasm.



Another term suggested for ICE syndrome is NUDE syndrome..!! (not approved still) Now the syndrome described by Al Reese and me is characterized by nodules, unilateral glaucoma, Descemet's membrane and endothelial extension; why not call it by the acronym NUDE syndrome.



Elschnig: o

Elschnig's pearls (Elschnig's bodies): Pearl-like clusters formed by growth of Equatorial epithelial cells onto the posterior lens capsule of the eye following cataract surgery. (A type of After cataract)

o

Elschnig's conjunctivitis: Chronic conjunctivitis associated with hyperplasia of the tarsal gland and the frothy secretions.

o

Elschnig's spots: In malignant hypertension, blood vessels in Retina& Choroid may be damaged leading to fibrinoid necrosis(presence of fibrin thrombi in vascular lumen). So when choroid vessels are damaged, it produces choroidal infarcts& necrosis of overlying Retinal Pigment Epithelium (since the outer 4 layers of retina are supplied by Choriodal blood vessels).These spots appear as small isolated circular areas having central retinal pigment, epithelial pigment clumping, and a surrounding halo of de-pigmentation.These are known as Elschnig spots.(So seen when choroidal blood vessels damaged in Malignant hypertension-Hypertensive choriodopathy)

o

Z-plasty (Elschnig's operation): It is useful to correct mild to moderate degree of cicatricial Ectropion. 359


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Dhaval Patel MD

o

Elschnig's syndrome (Elschnig‘s complex): Also known as Blepharo-cheilodentin (BCD) syndrome. Features include ectropion of lower eyelids, distichiasis of upper eyelids, euryblepharon(symmetrical enlarge-ment of the palpebral aperture associated with large eyelids), bilaterally cleft lip/palate, oligodontia, and conical crown form. Initially known under the eponym Elschnig syndrome.

o

Elschnig's theory: Elschnig suggested the anaphylactic theory of the pathogenesis of sympathetic ophthalmia. According to this theory, it is not a question of a particular infection, but of an anaphylactoid inflammation against the body‘s own uvea tissue. Under certain conditions, uvea tissue damaged by trauma will act as an antigen and subsequently occasion a sensibilisation of the body‘s own uvea albumin. This causes an anaphylactic uveitis on the undamaged eye.

o

Elschnig's intracapsular forceps: fine untoothed forceps for holding tissue, swabs, sutures, etc; removing things like clots, capsule fragments, lens, etc; used in cataract surgery

o

Elschnig's scleral ring: Scleral ring is a white circular band that separates the intrapapillary region of optic disc from the peripapillary area.The scleral ring itself does not belong to optic disc.This is important for all optic disc measurements because the inclusion of scleral ring as part of optic disc falsely enlarges the neuroretinal rim & decreases cup/disc ratio.Loss of nerve fiber layer in Glaucoma can make the scleral ring more visible due to loss of overlying tissue.

Vogt: o

Vogt white limbal girdle: Age related corneal degeneration, Characterized by bilateral, narrow cresentic lines composed of chalky white deposits(present in Bowman‘s membrane) in the interpalpebral fissure along the nasal& temporal limbus.

o

Vogt's striae: Seen in keratoconus, With thinning of the cornea vertical lines in the Descemet's membrane become visible. They disappear with pressure on the globe

o

Vogt's anterior mosaic crocodile shagreen: Age related corneal degeneration, Anterior mosaic crocodile shagreen appears as bilateral, polygonal, grayish-white opacities separated by relatively clear spaces in the deep layers of the epithelium and in Bowman's layer

o

Vogt-Koyanagi-Harada (VKH) syndrome: Vogt-Koyanagi-Harada (VKH) disease is a multisystem disorder characterized by granulomatous panuveitis with exudative retinal detachments that is often associated with neurologic and cutaneous manifestations.

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Dhaval Patel MD

Lucid interval of vogt: Seen in Arcus senilis(Age related corneal degeneration), Arcus senilis appears as a single greyish ring compose of lipid deposits parallel to the limbus and separated from it by a 1 mm lucid interval of Vogt, The classic theory concerning the appearance of arcus cornealis is that lipids migrate from the limbal vascular arcade to the peripheral cornea and the clear interval of Vogt is formed due to absorption of the lipids that are closer to the vascular arcade.



Ophthalmic conditions having Cogan's name - Cogan's congenital oculomsotor apraxia, Cogan's lid twitch, Cogan's microcystic dystrophy, and Cogan's syndrome.



Arctic explorer develops disc swelling due to Vitamin A toxicity from eating polar bear liver. The liver of polar bear is dangerously high with vitamin A.



Acute angle closure glaucoma can present with abdominal pain with nausea and vomiting.



Crocodile Tears: Following damage to the facial nerve as in Bell's palsy, misdirection of the regenerating fibres may innervate the lacrimal gland rather than the mouth muscles and the parotid glands. Consequently, chewing food causes weeping. Legend has it that the crocodile has compassion and remorse for its prey and wept with sorrow when it eats its prey.



Bungee jumper with blurred vision: Valsalva's retinopathy. The build-up of pressure in the venous cava causes the retinal vein to burst and produce haemorrhage.



Tool maker's eye: Argyrosis. It is a term applied to the deposition of silver salts in the tissue. In the conjunctiva, the deposition of silver turns black on oxygenation.



Famous Victorian writer who is also an ophthalmologist: Sir Arthur Conan Doyle, the creator of Sherlock Holmes. Apparently not a good one, as he had plenty of time for writing due to lack of patients.

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Dhaval Patel MD



Albert Einstein's eyes were removed by his ophthalmologist Dr. Henry Abrams during the autopsy in 1955 and stored in a safety deposit box. The eyes were put up for auction in 1994.



Uvea means a grape. The term was first used by Galen, a Roman physician to include both the choroid and the iris because they resemble a grape from which the stalk had been torn out leaving a hole in front, the hole being the pupil of the eye.



Carotid is derived from a Greek word meaning "to put to sleep" because pressure on the carotid arteries can cause loss of consciousness. Rufus of Ephsus said (about 100 AD):" The ancients called the arteries of the neck carotid because they believed that when they were pressed hard the animal became sleepy"



Atropine poisoning: "hot as a hare, blind as a bat, dry as bone, red as a beet, mad as a hen".



down-and-out went blind because of Ingestion of methylated spirit. Methylated spirit contains 5% methanol and 95% ethanol. When drunk for its ehtanol content, the breakdown products of methanol are extremely toxic to the eye causing optic atrophy



coast of Maine: Fibrous dysplasia (Albright's syndrome) It is characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction, with precocious puberty in females. The borders of the pigmentation has an irregular or jagged edge (coast of Maine). The involvement of the orbit can lead to shallowing and proptosis.



coast of California: Neurofibromatosis. The pigmentation has a smooth edge (coast of California). In some patients, the congenital absence of sphenoid bone leads to encephalocele and proptosis 362


Dhaval Patel MD



Iago blandly warns Othello that jealousy is "a green-eyed monster which doth mock the meat it feeds on." In China, covetousness is "red-eye disease".



H.G.Wells‘ one of the story, a sighted man fell into the Valley of the Blind and fell in love with a blind girl. When faced with the threat of losing his sight, he fled. The famous quote is in the country of the blind, the one-eyed man is King.



Ella Wheeler Wilcox (1850-1919): Laugh, and the world laughs with you; Weep, and you weep alone



Ovid advised man to shed tears. "They move the most adamant natures. Let her, if possible, see tears on your cheeks, in your eyes." And if you can't produce tears at will, he says, bring a vial of water and fake it.

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Darwin observed that the English wept less than the Mediterranean. One recent survey found that Israelis cry less than Britons, possibly, the authors suggest, because of mandatory military service in Israel, which "encourages an active and resourceful approach to the solution of problems and produces someone better able to cope with difficulties. Women cry more often and longer than men. In one study they wept 5.3 times a month, compared to 1.4 for men. They also use tears more commonly as a coping device, to win sympathy and shame malefactors. Grief is not the sore cause of tears. Glory, success after extreme effort, can bring tears. Perhaps the oddest of all, music can cause tears. One duct-squeezing trick entails repeating a musical theme a step higher or lower than when the listener first heard it, as in Albinoni's Adagio for Strings. Another, even more effective, is the appoggiatura, or delay in resolving a musical theme. The Beatles' "Yesterday" begins with one, and appoggiaturas abound in tear jerking tunes. They build a kind of anxiety, which the melody finally resolves

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In La Vita Nuova, Beatrice flashes love from her eyes and inflames Dante.

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Love at first sight usually involves eye contact, and the Greek poet Meleager (1st century B.C) placed Cupid inside the eyes, whence he aimed his barbs. In much subsequent lover poetry, and later among Arab poets and Provencal Versifiers of the 12th century, the eyes shoot arrows, darts, or fiery beams that wound the soul and infect with longings

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BACCIO BANDINELLI Vasari describes repeatedly the poor color quality of Baccio‘s paintings, but without specifying why. The paintings tend to use a monochrome yellow or ochre for flesh tone.

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EAGLES HAVE TWO FOVEAS: One fovea optimizes monocular vision to the side and the other optimizes binocular vision to the front. An extremely soft lens of the eye allows for rapid accommodation

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Valetudinarians are sometimes confused with hypochondriacs. They couldn't be more different. The hypochondriac thinks he's always ill, but the valetudinarians takes excessive care to make sure that he doesn't fall ill.

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Artificial electric eye: developed by William dobelle, in USA. It iacamera implanted on spectacles with electrodes on retina.

The Class Questions 

What are the causes of cyclotorsion in supine position?

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Dhaval Patel MD

o

This is the fact which you will use in Toric IOLs and all your other kind of LASIK procedures. The reasons I found are..

o

unmasking of cyclophoria during monocular fixation (Tjon-Fo-Sang et al., 2002; Borish & Benjamin, 2006)

o

fusion loss (Park et al., 2009; Hori-Komaii et al., 2007; Fea et al., 2006; Chernyak, 2004; Swami et al., 2002);

o

dynamic cyclotorsion: blurring of the fixation target happens during ablation (after epithelium removal in surface ablation and following flap lifting in LASIK)

o

(average cyclotorsion resulting from the shift from the upright to the supine position is about ±4°)

Why 30-1 field is not used? 30-1 program measures points along the vertical and horizontal meridian and then every 6° (Fig. 6-20). The problem with this strategy is that the points along the horizontal and vertical meridian may fall either on the affected or unaffected side. For example, in a patient with a neuro-ophthalmologic deficit with a vertical field cut, points exactly on the vertical meridian may either be seen or not seen and thus are not particularly helpful. Similarly, in the case of optic nerve lesions, points along the horizontal meridian may either be seen or not seen, making that particular row rather unhelpful. This problem was corrected with the -2 strategy. For example, in the 30-2 program the points are tested 3° above and below the horizontal meridian, 3° to the left and right of the vertical meridian, and then every 6° (Fig. 6-21). This eliminates the ambiguity of the points that are tested right along the vertical and horizontal meridian. In general, strategies using the -2 terminology are more appropriate than the -1 strategies for both optic nerve and neuro-ophthalmologic examination.

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Why FADEN operation works only in direction of action of muscle? Point of posterior fixation is new insertion for action. As antagonist entire muscle acts. Therefore limits muscle only in field of action

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Why capsular phimosis does not always occur? Capsular opening wants to contract but zonules are opposing the force for it. So when zonules becomes weak, capsular opening beigns to shrink.

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Why Myopia should be Slightly under Corrected? Myopia is corrected with a concave lens. A concave lens is a minifying lens. More is the power more is the minification caused by it. Thus myopia is always slightly under corrected to avoid minification of image and consequent eyestrain symptoms. Also if overcorrected, patient will use his or her accommodation to overcome it and it will give eyestrain symptoms.

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Why Hypermetropia should be Fully Corrected? Hypermetropia should always be fully corrected so as to relax accommodation and avoid eyestrain symptoms. This is much more important in case of a squint. However it should be born in mind that correction is not done at the cost of producing eyestrain symptoms.

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Why Presbyopia Should be Slightly under Corrected? When we read near objects accommodation and convergence both are required. Presbyopia is always under corrected so as to encourage accommodation. Accommodation is accompanied by accommodative convergence. Thus patient does not complain of eyestrain symptoms. Full correction of presbyopia causes eyestrain symptoms due to lack of accommodative convergence.

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Why sea/water is blue? o

Multiple theories

o

Duane 2006: The longer wavelengths of light penetrate water more deeply than do the short wavelengths and are eventually absorbed. The shorter wavelengths are reflected about in the superficial layers of water and reflected back to the observer, making the water appear blue. In addition, the water is illuminated by the blue sky. Some of this blue light is reflected toward the observer, contributing to the blueness. (This is not believed now.I checked in physics book and article)

o

Reflection of color of sky

o

coloration by dissolved impurities - Cu2+

o

Now it is proved that it is due to: The longer wavelengths of light like red and orange are absorbed in superficial layers of water and short wavelengths like blue penetrate better which then get reflected and this is how water appears blue.

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Dhaval Patel MD

Latest theory just like above: intrinsic blueness of water is the only example from nature in which color originates from vibrational transitions

How does accommodation ‗know‘ it has achieved the sharpest focus? by a sensing system in the brain, However, some have suggested that the system takes advantage of the naturally occurring chromatic aberration of the primate eye to fine-tune focusing.

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What happens if the cornea is spherical? When light rays pass through a spherical refractive surface, the para-axial rays are less refracted than the peripheral rays; that is because the angle of incidence (and therefore the angle of refraction) is wider in the periphery than that in the para-axial part of the spherical surface. This results in multi foci and is responsible for what is known as "spherical aberrations."

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Why in HZV, we start 800 mg five times a day? In HZV, 800 mg five times a day Acyclovir is strted for the following reasons:



o

Virus shedding period is decreased

o

Healing is accelerated by 50 %

o

Postherpetic neuralgia is decreased

More regression after LASIK seen in Myopic or Heperopic LASIK? Hyperopic LASIK. Hyperopic LASIK almost always regresses after first year because o

Latent hyperopia masked by accommodative spasm

o

Epithelial hypertrophy

o

Intrinsic biomechnical effect of hyperopic LASIK that results in mid peripheral steepening and central flattening

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Why Does Cataract Surgery Lower IOP in Some Patients? o

Exact mechanism by which this occurs is largely unknown

o

IOP reduction does not vary based on ethnicity

o

improved aqueous humor outflow through the trabecular meshwork, ie, increased aqueous outflow facility.

o

Trabecular meshwork endothelial cells from glaucomatous eyes that were exposed to ultrasound had increased interleukin-1α (IL-1 α), a stress hormone and pathologic marker for primary open-angle glaucoma, through NFκB translocation from the cytoplasm into the nucleus.

Latanoprost is one kind of gene therapy for glaucoma. How? Metalloproteinase gene increased transcription in human ciliary muscle cells with latanoprost is seen. (Weinrub RN, IOVS 2002:43) Remodeling of ECM in the TM via MMP2 and MMP3

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Povidone Iodine application before surgery: Povidone–Iodine Antisepsis for Cataract Surgery and Ophthalmic Procedures (Scott WJ AJO, Volume 151, Issue 5, May 2011, Pages 914) In the operating room, a 5% polyvidone iodine solution must be applied on the eyelids and a 5% solution in the conjunctival sack, respectively, and should dry out for at least 3 minutes to guarantee adequate disinfection

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Interval between drops: Drop size and initial dosing frequency problems of topically applied ophthalmic drugs. (Sukhbir S Chrai. Journal of Pharmaceutical Sciences Volume 63, Issue 3, pages 333–338, March 1974) Multiple drops administered at short time intervals have the advantage of increasing drug concentration in the precorneal film but the disadvantage of considerable drug loss through drainage, which for potent drugs can lead to systemic toxicity. When using radioactive technetium (99mTc) as the test substance in unanesthetized albino rabbits, it was shown that a 5-min interval between drops minimizes drainage loss of drug and the drug 368


Dhaval Patel MD

concentration buildup in the precorneal film as compared to the corresponding dosage regimen of drops administered at shorter time intervals.

Important History 

The term ―astigmatism‖ is the joining of ―a‖ and ―stigmata,‖ a term suggested by Dr. William Whewell (1794-1866)

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In 1837, the astronomer Sir George Biddle Airy made a cylindric lens and used it to correct astigmatism.

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History of JCC: o

Stokes lens: consisted of two cylinders, one planoconvex and one planoconcave, with flat surfaces approximated and arranged so that they could be rotated in opposite directions.

o

Edward Jackson realized the instrument's potential for determining cylinder power

o

modified Stokes lens with axes fixed perpendicular to one another came to be known as the ―Jackson crossed cylinder‖

o

W. H. Crisp, a more prolific writer, to bring this device to worldwide attention



In 1984, Mazzocco et al introduced the first foldable plate haptic silicone lens produced by STAAR Surgical. It became known as the ―Mazzocco Taco‖ because of the way it appeared when folded.

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―One of the most important and challenging tasks in IOL power calculation is to predict the ELPo for a given eye‖ - Dr. Haigis



Vitrectomy History o

Machemar: introduction of pars plana vitrectomy in the early 1970s. Machemer initially performed pars plana vitrectomy with the use of a 17-gauge (1.5mm diameter) multifunctional instrument capable of cutting and aspirating the vitreous. This instrument utilized a fiberoptic sleeve and required a 2.3mm scleral incision.

o

In 1974, O‘Malley designed a smaller vitreous cutter with a diameter of 0.9mm (20gauge). This less invasive 3-port 20-gauge cannula-entry system is still used today.

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o

In 1990, de Juan and colleagues designed a variety of 25-gauge (0.5mm diameter) vitreoretinal instruments for more delicate and precise surgical maneuvers.

o

Fuji et al designed a 25-gauge microcannular system and an array of 25-gauge instruments referred to as transconjunctival sutureless vitrectomy system (TSV).

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Trantas (1907) first coined the term Gonioscopy.

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Salssmann (1914) was first to perform direct gonioscopy & is known as Father of Gonioscopy.

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―Goldmann‖ (1938) was first to introduce Gonioprism.

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Recalls from previous papers 

Rho kinase inhibitor-fausidil

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Maximum tolerated dose of a new drug is evaluated in: PHASE 1

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no.of vision centres under npcb ans.20000

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ExPRESS glaucoma shunt is made up of stainless steel.

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Ahmed glaucoma valve for children: FP8

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Duration of light stimulus in HVF: 0.2 sec

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High resolution pass Perimetry: P cells

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Flicker Perimetry: M cells

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Normative database not present in stratus OCT: ONH 370


Dhaval Patel MD



High IOP may directly damage ganglion cell layer of retina.

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Mucormycosis Rx Amphotericin B

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Which is true- brimonidine decrease aqueous production

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Brinzolamide: non-competitive and reversible

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rhabdomyosarcoma marker- desmin

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not a risk factor for rhegmat rd  hyperopia

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orbit involvemnt in  b cell lymphoma

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Ocriplasmin is a recombinant protease - vitreomacular adhesion

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Tonometer with variation in application surface  Maklakov tonometer

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Pigmentatory changes between posterior pole and equator [salt and paper retinopathy] are seen in all of following except? Resolving retinal detachment, Rubella, Phenothiazine toxicity, Fundus flavimaculatus  Fundus flavimaculatus

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Which of the following procedure most commonly performed by eye surgeon at district level  Phacoemulsification

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Lacrimal gland supplied by  Greater petrosal nerve

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A patient diagnosed with chalazion c/o pain. True statement is  chalazion is lipogranuloma

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True about pterygium  resection via bare sclera technique cause recurrence of 30-70%

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Ophthalmology Explorer 1st Edition

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