KERATOKONJUNGTIVITIS LIMBIK SUPERIOR (KLS)
PENDAHULUAN Epitel keratitis dan hipertrofi papil konjungtiva tarsal superior sering mengacaukan
karakteristik
dari
keratokonjungtivitis
limbus
superior
yang
berhubungan erat dengan limbus superior. Pada tahun 1963 Thygeson dan Kimura mendeskripsikan keratokonjungtivitis limbus superior sebagai konjungtivitis filamen yang kronis dan terlokalisir. Pada saat ini oleh Theodore penyakit ini diberi nama yang lebih dikenal dengan istilah keratokonjungtivitis limbus superior. Lima tahun yang lalu Tenzel dan Corwin melaporkan bahwa adanya kaitan tiroid yang abnormal dengan keratokonjungtivitis limbus superior. (5)
ANATOMI KONJUNGTIVA KONJUNGTIVA Konjungtiva merupakan membran yang menutupi sklera dan kelopak bagian belakang. Bermacam-macam obat mata dapat diserap melalui konjungtiva ini. Konjungtiva mengandung kelenjar musin yang dihasilkan oleh sel goblet. Musin bersifat membasahi bola mata terutama kornea.
Konjungtiva terdiri atas tiga bagian, yaitu : -
Konjungtiva tarsal yang menutupi tarsus, konjungtiva tarsal sukar digerakkan dari tarsus.
-
Konjungtiva bulbi menutupi sklera dan mudah digerakkan dari sklera dibawahnya.
-
Konjungtiva fornises atau forniks konjungtiva yang merupakan tempat peralihan konjungtiva tarsal dengan konjungtiva bulbi. Konjungtiva bulbi dan forniks berhubungan dengan sangat longgar dengan
jaringan dibawahnya sehingga bola mata mudah bergeerak. (8)
DEFINISI Keratokonjungtivitis limbus superior adalah suatu peradangan konjungtiva bulbi dan konjungtiva tarsus superior yang tidak diketahui sebabnya, disertai kelainan-kelainan pada limbus bagian atas. (8,10)
EPIDEMIOLOGI Penyakit ini biasanya bilateral, simetris, terletak pada limbus sekitar jam 12.. dapat juga unilateral. Lebih sering terdapat pada wanita. Dapat mengenai penderita berusia antara 4 – 81 tahun. Kelainan ini bersifat menahun, disertai remisi dan eksaserbasi dan diduga ada hubungannya dengan hipertiroid. (8,10)
ETIOLOGI Tidak diketahui penyebabnya. Dianggap merupakan infeksi viral dan gangguan kelenjar thyroid. (8,9,10)
PATOFISIOLOGI Baru-baru ini ada pendapat yang mengemukakan bahwa keratokonjungtivitis limbik superior terjadi karena longgarnya konjungtiva bulbi superior, yang menyebabkan terjadinya peradangan dari kerusakan jaringan oleh mikrotrauma. Pengaturan toleransi fisiologi dari penghancuran jaringan permukaan mata yang sangat halus, peradangan yang kronis akan mengakibatkan menebalnya konjungtiva dan timbulnya keratinisasi, yang kemudian akan menjadi inflamasi. Peristiwa ini (5)
SLK is believed to be present secondary to superior bulbar conjunctiva laxity, which induces 4
inflammatory changes from mechanical soft tissue microtrauma. In settings where the physiological tolerance of mechanical forces on the delicate ocular surface is exceeded, chronic inflammation results in thickening of the conjunctiva and keratinization, which is then cyclical in perpetuating the inflammation. Eventually, a filamentary response may be induced on the affected cornea. Factors inducing conjunctiva laxity include thyroid eye disease, tight upper eyelids, and prominent globes. Immunochemical histopathologic examination of the abnormal conjunctiva in SLK lends credence to microtrauma being of most significance to the development of SLK.
HISTOPATOLOGIK Secara histopatologik kerokan epitel konjungtiva tarsus memperlihatkan epitel normal dan kadang-kadang ditemukan sel polimorfonuklear. Tidak pernah ditemukan sel eosinofil ataupun inklusi sel epitel. Dengan pewarnaan Giemsa ditemukan kreatinisasi sel-sel epitel yang ditandai dengan pengerutan dan hialinisasi sitoplasma dan nukleus yang berdegenerasi dan piknotik. Pada biopsi konjungtiva bulbi, ditemukan kreatinisasi dan akantosis, sel epitel membengkak dan berdegenerasi. Terdapat degenerasi balon pada nukleus sel-sel radang neutrofil, sel limfosit dan sel plasma.(8,10)
GAMBARAN KLINIS Gejala subjektif: Pada keadaan yang ringan terdapat rasa tidak enak pada mata, sedangkan pada keadaan yang berat dapat sampai terjadi blefarospasme dan rasa seperti ada benda asing, lakrimasi dan fotofobia. (8,9,10) Gejala objektif : Pada keadaan yang ringan ditemukan peradangan kapiler dan hipertrofi papil pada bagian tengah konjungtiva tarsus superior. Konjungtiva tarsus inferior tak ada kelainan. Injeksi konjungtiva pada episklera ditemukan pada konjungtiva bulbi. Pada konjungtiva bulbi yang terkena terdapat bendungan, penebalan dan hipertrofi daerah limbus. Pada keadaan yang berat terlihat seolah-olah ada pembentukan lengkung limbus yang baru. Dapat dijumpai pewarnaan pungtata kornea pada pemeriksaan dengan zat warna dan dapat ditemukan filamen-filamen pada kornea (1/3 bagian atas). Dapat terjadi remisi spontan dan keadaan patologik yang terjadi dapat menghilang hanya dalam satu hari. Kebanyakan penderita mengalami rekurens dan remisi tanpa menimbulkan parut, lamanya bervariasi 1 sampai 10 tahun. Gejala satu mata lebih berat dari yang lain. Jarang yang unilateral.(8,10)
DIAGNOSIS BANDING
Conjunctivitis allergic
Conjunctivitis bacterial
Conjunctivitis Giant Papillary
Conjunctivitis viral
Dry eye syndrome
Episcleritis
Floppy eyelid syndrome
Keratoconjunctivitis epidemic
Keratoconjunctivitis sicca
Red eye evaluation
Sebaceous gland carcinoma
Thyroid ophthalmopathy
Trachoma(5)
TERAPI MEDIKAMENTOSA
Pengobatan yang tepat belum ada, karena penyebabnya belum jelas. Dapat diberikan pengobatan secara simtomatik berupa tetes mata dekongestan, zinc sulfat, metil selulosa, polivinil alkohol, kortikosteroid atau antibiotik. Pada waktu akut dapat juga diberikan AgNO3 0,5%-1% yang diusapkan pada konjungtiva tarsus superior, pemberian tekanan, dan memperbesar diameter pemakaian lensa kontak, retinoic acid topical 0,1% dan siklosporin. Injeksi triamsinolon pada tarsal superior dapat mengurangi gejala dan tanda dari konjungtivitis limbus superior dan merupakan teerapi adjuvant. Lebih dari 50% penderita keratokonjungtivitis limbus superior bisa menjadi keratokonjungtivitis sika dan terdapat masa yang padat di pungtum bagian atas setelah pengobatan keratokonjungtivitis limbus superior. PEMBEDAHAN
Reseksi
limbus
atau
reseksi
konjungtiva
bulbi
bagian
atas
dengan
menggunakan zat warna rose bengal, kauterisasi konjungtiva bulbi bagian atas. KONSULTASI
Diagnostik yang tepat dari fungsi tiroid melibatkan ahli endokrinologi sebagai ahli konsultasi. (5,8,9,10,)
PROGNOSIS Prognosis umumnya baik dan pada kasus-kasus yang telah sembuh, biasanya tidak dijumpai gangguan penglihatan dan gejala sisa. (8,10)
Definition: SLK is a bilateral chronic recurrent inflammatory lesion located in the superior
bulbar
and
tarsal
conjunctiva.
Etiology: SLK is often associated with thyroid dysfunction. One theory is that lid retraction results in rubbing of the tarsus and bulbar conjunctiva producing inflammation. Epidemiology:
Most
common
in
adult
women
20-70
years
old.
Clinical: A bilateral and localized process confined to the superior limbal area and tarsus from the 10-2 o'clock position. Thickening of the conjunctiva accompanies dilated blood vessels and erythema of the conjunctiva. Both Rose Bengal and fluorescein stain in this region. Clinically these cases are often associated with dysthyroid eye disease that features lid retraction. In general thyroid function tests are
recommended
in
patients
that
present
with
these
findings.
Histopathology: Click to enlarge photo.
Superior limbic keratoconjunctivitis has been described as having keratinization of the epithelium (see the keratohyaline granules and anucleate squamous cells here) , acanthosis (notice the thickening to the far right),
and cellular infiltration with lymphocytes, plasma cells and ballooning degeneration (see central cystic space with degeneration of epithelial cells and exocytosis of lymphocytes). In addition in this photo there is a chronic perivascular inflammatory infiltrate. Treatment: SLK often spontaneously resolves but may recur for 10 years. Some treatments that have been used include bandage contact lenses, punctal occlusion, topical cyclosporin A (0.5%), topical application of autologous serum, thermo and chemical cauterization of the area affected , and resection of the conjunctiva. (1)
GAMBAR (2)
GAMBAR (3)
The
conjunctiva
The conjunctiva is a mucous membrane that performs the task of attaching the eyeball to the orbit and lids. It permits a certain degree of rotation of the eyeball in the orbit (the hole in the skull intended for the eyeball). The conjunctiva lines the lids and also covers the surface of the eyeball. The part of the conjuctiva that lines the lids is called the palpebral portion and the part that covers the white of the eyeball is called the bulbar conjunctiva. The other parts of the conjuctiva include two loose recesses, known as the upper and lower fornices. They are also known as conjunctival sacs and are located between the bulbar and the palpebral conjunctiva. It is possible for the eyelids and eyeballs to move only because of the looseness of the conjunctiva at these points. If you’ve been to an ophthalmologist or had the experience of having eye drops put in your eyes. The eye drops are put inside the lower fornice. This is done by pulling the outer lid away from the globe. The drops are retained in this cavity for a short while, which is enough for the liquid to diffuse through the cornea and act on the internal structure of the eye. (3) The typical patient with superior limbic keratoconjunctivitis (SLK) is a woman aged between 20 and 60 years of age with chronic red and irritable eyes.1 Although both eyes are usually
affected, the condition maybe asymmetrical.1 After episodes of exacerbation and remission it usually resolves. The patient may also have abnormal thyroid function.2 SLK has been treated with silver nitrate or thermal cauterisation of the superior bulbar conjunctiva, pressure patching, and large diameter bandage contact lenses (BCL), topical trans-retinoic acid 0.1%, and recession or resection of the superior bulbar conjunctiva .1, 3 Over 50% of patients with SLK are said to have keratoconjunctivitis sicca 4 and recently upper punctal plugs have been used to treat SLK .5 We report two cases in which a unilateral BCL wear ameliorated the symptoms of bilateral SLK and a possible explanation is discussed. (4)
Differential Diagnoses Conjunctivitis, Allergic
Keratoconjunctivitis, Epidemic
Conjunctivitis, Bacterial
Keratoconjunctivitis, Sicca
Conjunctivitis, Giant Papillar yRed Eye Evaluation Conjunctivitis, Viral
Sebaceous Gland Carcinoma
Dry Eye Syndrome
Thyroid Ophthalmopathy
Episcleritis
Trachoma
Floppy Eyelid Syndrome
Other Problems to Be Considered Filamentary keratopathy
Workup Laboratory Studies
Thyroid evaluation - Thyroid-stimulating hormone, free th yroxine (T4), thyroidstimulating immunoglobulin, or thyroid-stimulating hormone – binding inhibitory immunoglobulin
Schirmer test, measurement of tear lake, and tear breakup time evaluating for dry eye syndrome, which is often present with SLK
Histologic Findings Surgical specimens taken from patients with SLK who had not received treatment with silver nitrate demonstrate abnormal limbic epithelium with keratinized epithelial cells with dyskeratosis and acanthosis and balloon degeneration of some nuclei. The intracellular accumulation of glycogen in the epithelial cells of tissue sections of the bulbar conjunctiva has been documented. The conjunctival stroma demonstrates edema without significant inflammatory cellular infiltrate. In specimens obtained after silver nitrate treatment, significant numbers of inflammatory cells, including plasma cell s, neutrophils, and lymphocytes, also are found in the epithelium and stroma. Immunohistochemical pathologic examination of the abnormal conjunctiva in SLK demonstrates a lack of the typical mosaic pattern of the epithelium in the resulting keratiniz ed cells before undergoing treatment and up-regulation of transforming growth factor-beta 2 and tenascin. In separate studies, increased expression of proliferating cell nuclear antigens and altered expression of cytokines, as well as the presence of involucrin, were shown. (5A)
Treatment Medical Care Several approaches are used by practitioners to speed the recovery of patients toward the resolution of symptoms. Pressure patching, placement of a bandage contact lens (primarily or as an adjunct), silver nitrate solution application, mast cell stabilizers, vitamin A preparations, and cyclosporine A6 have been used with moderate success. Supratarsal triamcinolone injection has had reported success in mitigating signs and symptoms and may be helpful as an adjunctive therapy.7 As these approaches usually offer only temporary mitigation of symptoms, more definitive treatments often are required.
Surgical Care Surgical resection of the involved conjunctiva as delineated intraoperativel y by the use of rose bengal staining removes the affected tissue. Folds of superfluous conjunctiva are eliminated, adhesions with underlying Tenon capsule and episclera develop, which may be augmented by transplantation of cryopreserved amniotic membrane with fibrin glue,8 and
keratinized epithelium is replaced by normal ingrowth.9,10 Thermocautery accomplishes 2 of these treatment objectives. Autologous serum application has been shown to be beneficial as an alternative therapy in a small case series.11 Superior lacrimal punctal occlusion and bandage contact lens application have been advocated but are not widely used.
Consultations Appropriate investigations into thyroid function may involve an endocrinologist consultation.
Medication Both mast cell stabilizers and vitamin A preparations have been used with moderate success. However, these approaches usually offer only temporary mitigation of symptoms, and more definitive treatments often are required. Preservative-free artificial tears also may be helpful. Recently, topical cyclosporine A has been shown to provide symptom relief and to improve the signs of SLK; however, maintenance therapy is required for continued benefit .12
Mast cell stabilizers Long-term inhibition of inflammation. Inhibits type 1 immediate hypersensitivity reaction. (5B)
Background This disorder is characterized as an inflammation of the superior bulbar conjunctiva with predominant involvement of the superior limbus, an adjacent epithelial keratitis, and a papillary hypertrophy of the upper tarsal conjunctiva. In 1963, Thygeson and Kimura described it as a chronic, localized, filamentary conjunctivitis.1 It was given its name, superior limbic keratoconjunctivitis (SLK), by Theodore, contemporaneously. Five years later, Tenzel and Corwin reported an association with thyroid abnormalities and SLK .2,3 A mimicking disorder has been encountered in soft contact lens wearers, typically with exposure to thimerosal-preserved solutions.
Pathophysiology
SLK is believed to be present secondary to superior bulbar conjunctiva laxity, which induces inflammatory changes from mechanical soft tissue microtrauma.4 In settings where the physiological tolerance of mechanical forces on the delicate ocular surface is exceeded, chronic inflammation results in thickening of the conjunctiva and keratinization, which is then cyclical in perpetuating the inflammation. Eventually, a filamentar y response may be induced on the affected cornea. Factors inducing conjunctiva laxity include thyroid eye disease, tight upper eyelids, and prominent globes. Immunochemical histopathologic examination of the abnormal conjunctiva in SLK lends credence to microtrauma being of most significance to the development of SLK.
Frequency United States
The frequency of SLK has been found to be 3% in a cohort of Graves ophthalmopathy patients, but it is much lower in the general population. International
The international frequency is unknown.
Mortality/Morbidity The natural history of the disorder is remission and eventual total resolution but only after a prolonged clinical course.
Race No racial predilection exists.
Sex Women are predominantly affected.
Age
Typically, middle-aged people are affected; however, this entity has been reported to occur in patients aged 4-81 years.
Clinical History
Patients present with complaints of burning and irritation of the affected eye. o
Some patients may present with redness. Upgaze may elicit these symptoms.
o
Typically, usage of moisturizing medications only provides minimal relief.
o
Symptoms remit and exacerbate and are var iable in degree, but no diurnal pattern to the worsening of symptoms exists.
In most cases, the condition is present bilaterally, although one eye may be more symptomatic.
Patients with filaments are usually extremely symptomatic.
Commonly, a history of thyroid dysfunction i s elicited upon questioning. The natural history of SLK is prolonged, with gradual clearing.
Patients often have numerous eye specialists for their symptoms. Unless the doctors have specifically examined the upper bulbar conjunctivae or everted the upper eyelids, they may have missed the diagnosis.
Physical
Marked inflammation of the upper lid tarsal conjunctiva, adjacent inflammation of the upper bulbar conjunctiva, and punctate rose bengal staining of the cornea at the upper limbus are signs of SLK.
The conjunctiva extending from the upper limbus to the insertion of the superior rectus muscle also demonstrates thickening, hyperemia, and typical rose bengal staining. It stands out in stark contrast to the normal appearance of the inferior conjunctiva and cornea.
Approximately one third of patients present with filaments on the upper cornea or along the superior limbus.
Causes
The cause of SLK is unknown, but inflammatory changes from mechanical soft tissue microtrauma are the final common pathway.
SLK is associated with thyroid dysfunction.
SLK has also developed in association with scarring of the palpebral conjunctiva in euthyroid patients.
Prolonged eyelid closure with associated hypoxia or reduced tear volume may be a risk factor for SLK development.
Morphological or functional changes in superior conjunctival apposition to the globe following upper eyelid procedures may induce SLK.
(5C)
Signs and Symptoms Individuals presenting with SLK typically report symptoms of ocular discomfort, including burning, foreign body sensation, or non-descript pain. Additionally, patients may complain of photophobia and excessive tearing. Gross clinical signs often include mild lid s welling and pseudoptosis as well as blepharospasm. Visual acuity is usually not affected. Inspection of the ocular surface in SLK reveals a sectoral inflammation and injection of the superior bulbar conjunctiva. The limbal margin of the cornea may be inflamed as well. Eversion of the upper lid reveals a uniform papillary hypertrophy along the tarsus, which may be mild to marked. Vital dye staining is standard in SLK, with patients displaying punctate epithelial disruption of the affected region; this is evident with both sodium fluorescein dye as well as rose bengal or lissamine gr een solutions. Filaments are encountered within the precorneal tear film in roughly half of all patients with SLK. The condition is typically bilateral but often asymmetric. In most instances, the diagnosis of SLK is based solely upon the characteristic presentation. The only known laboratory confirmation is the presence of keratinized epithelial cells from scrapings of the affected superior bulbar conjunctivae.
Pathophysiology The exact etiology and pathogenesis of SLK remains unclear. Infectious agents such as bacteria, viruses, fungi, and other intracellular parasites appear to be unrelated to this condition. An autoimmune etiology has been considered, based upon the pattern of the disorder (i.e., exacerbations and remissions), the female predominance, and an association with thyroid disease and other autoimmune diseases. The most widely accepted theory regarding the pathogenesis of SLK is that it results from mechanical irritation of the superior limbal region, as loose conjunctival tissue rubs against the limbus during blinking. Factors such as tight lids, prominent globes, and thyroid disease have been offered as potential instigators of this reaction. A newer theory regarding the etiology of SLK implicates a local tear deficiency to the superior keratoconjunctiva. Researchers have proposed that this deficiency results in significantly reduced levels of vital tear-based nutrients to the affected region, as well as i ncreased mechanical friction from the superior lid.
Management SLK is a chronic, recurrent and sometimes recalcitrant disorder. While no treatment has yet been shown to be
100 percent effective, many modalities have been employed successfully. The treatment of choice for most practitioners has been 0.5 to 1.0% silver nitrate solution, applied topically to the superior bulbar and tarsal conjunctivae. This treatment chemically cauterizes the irregular tissue, promoting regrowth of new, healthy epithelium. Unfortunately, recurrences have been known to occur after using silver nitrate, and retreatments are common. Pressure patching has been employed for severely symptomatic cases of SLK, as well as the use of subsequent bandage hydrogel lenses to alleviate the mechanical irritation. Thermal cauterization as well as surgical recession or resection of the superior bulbar conjunctiva has also been employed as treatment modalities for SLK. The use of topical preparations, including vitamin A eyedrops, 4% crom olyn sodium solution, and Alomide (0.1% lodoxamide tromethamine solution, Alcon) have also been somewhat effective in managing SLK. Most recently, lacrimal punctal occlusion therapy has been advocated for this disorder.
Clinical Pearls
In managing this disorder, topical agents should be employed in the early stages of all mild and moderate presentations; thermocautery, chemocautery, and surgical resection should be employed only when less invasive means have failed.
Lacrimal occlusion therapy may prove to be a viable option for SLK; while additional research is needed in this area, recent studies have shown great potential.
SLK of Theodore should not be confused with contact lens -induced SLK (CL-SLK), a condition that is occasionally observed in young, otherwise healthy hydrogel lens wearers. An association with thimerosal-preserved solutions has been seen in some of these patients. The typical presentation of CLSLK consists of increasing contact lens intolerance, superior tarsal and bulbar injection, and significant superior corneal staining with stromal hazing. Corneal involvement may be noted as far inferiorly as the superior pupillary margin. Treatment for CL-SLK consists of temporarily discontinuing contact lens wear, along with the liberal use of preservative-free ocular lubricants. Upon resolution, contact lens wear may be resumed with a fresh pair of lenses, however all thimerosal-preserved solutions should be terminated. In more severe or recurrent cases, patients may need to be refit with RGP materials.
Refer all patients presenting with SLK for a systemic workup, including a serologic thyroid panel. A 1995 study demonstrated a 65 percent correlation between SLK and systemic thyroid disease. Other disorders such as rheumatoid arthritis and Sjögren’s syndrome may also have similar associations.
Other reports in this section
Allergic Conjunctivitis &Vernal Keratoconjunctivitis
Viral Conjunctivitis
Bacterial Conjunctivitis
Chlamydial & Gonococcal Conjunctivitis
Conjunctival Laceration
Episcleritis
Scleritis
Pingueculitis
Pterygium
Superior Limbic Keratoconjunctivitis (SLK of Theodore)
Toxic Conjunctivitis
Conjunctivitis with Pseudomembrane
Giant Papillary Conjunctivitis (6)
Superior limbic keratoconjunctivitis is an ocular surface disease characterized by
episodes of recurrent inflammation of the superior cornea and limbus, as well as of the superior tarsal and bulbar conjunctiva.
Even though the pathophysiology remains unclear, it is thought that mechanical trauma from tight upper lids or loose redundant conjunctiva could lead to the disruption of normal epithelium. This mechanical hypothesis is supported by the increased lid apposition of exophthalmic thyroid patients, who are known to have an increased incidence of superior limbic keratoconjunctivitis.
Patients present with red eye, burning, tearing, foreign body sensation, mild photophobia. Inflammation and thickening of the conjunctiva is observed, espedially at the limbus.
Lubrication is an effective treatment for this pathology. (7)
