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 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 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 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 sicca4 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

Papillary

Red 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 thyroxine (T4), thyroid-

stimulating 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 cells, 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 keratinized

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 intraoperatively 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 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.

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 variable 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 is 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 swelling 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 green 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 increased 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% cromolyn 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 CL-

SLK 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)