AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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. 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. A mimicking disorder has been encountered in soft contact lens wearers, typically with exposure to thimerosal-preserved solutions.

Pathophysiology

It is believed that SLK is present secondary to superior bulbar conjunctiva laxity, which induces 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 then is 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

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

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Patients present with complaints of burning and irritation of the affected eye.
• • Some patients may present with redness. Upgaze may elicit these symptoms.
  • Typically, usage of moisturizing medications only provides minimal relief.
  • 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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Filamentary keratopathy

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab 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.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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, and vitamin A preparations have been used with moderate success. 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, and keratinized epithelium is replaced by normal ingrowth. 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. 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

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.

Drug Category: Mast cell stabilizers

Long-term inhibition of inflammation. Inhibits type 1 immediate hypersensitivity reaction.

Drug Category: Cauterizing agents

Topical application for treatment of keratinized conjunctiva

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Patients should receive follow-up care for recurrences of symptoms after treatment of SLK, and they require careful examinations for the development of thyroid ophthalmopathy.

In/Out Patient Meds

• A 10-day course of lodoxamide, 4 times per day, has been shown in a series of 3 patients to mitigate the symptoms of SLK. Again, this is not considered definitive treatment by most.

Complications

• No specific complications from the disease are recognized; since the natural history of the entity is complete, eventual resolution occurs.
• Inappropriate use of silver nitrate sticks, which should never be used in the eyes, as opposed to preparations of topical silver nitrate solution, results in a severe caustic injury to the affected part of the eye where applied.
• Surgical resection of the conjunctiva has the usual complication profile of any surgical procedure, and special care should be taken to avoid involvement of the superior rectus muscle in the dissection.

Prognosis

• Prognosis is excellent, although symptoms may last for years.

Patient Education

• Discussing the disease process with patients is important because it will improve compliance with treatment modalities. It also will help to allay the patient's fear of the unknown and help them to cope with the often prolonged symptoms of this entity.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Inappropriate use of silver nitrate sticks, which should never be used in the eyes, as opposed to preparations of topical silver nitrate solution, has reportedly resulted in litigation.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Albert DM, Jakobiec FA. Superior Limbic Keratoconjunctivitis. In: Principles and Practice of Ophthalmology. Vol. 1. 1994: 265.
• Bartley GB. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc. 1994;92:477-588. [Medline].
• Baum JL. The Castroviejo Lecture. Prolonged eyelid closure is a risk to the cornea. Cornea. Nov 1997;16(6):602-11. [Medline].
• Cher I. Clinical features of superior limbic keratoconjunctivitis in Australia. A probable association with thyrotoxicosis. Arch Ophthalmol. Nov 1969;82(5):580-6. [Medline].
• Cher I. Blink-related microtrauma: when the ocular surface harms itself. Clin Experiment Ophthalmol. Jun 2003;31(3):183-90. [Medline].
• Cher I. Superior limbic keratoconjunctivitis: multifactorial mechanical pathogenesis. Clin Experiment Ophthalmol. Jun 2000;28(3):181-4. [Medline].
• Collin B. The fine structure of nuclear changes in Superior Limbic Keratoconjunctivitis. Invest Ophthalmol. 1978;17:79.
• Condon GP, Brownstein S, Codere F. Sebaceous carcinoma of the eyelid masquerading as superior limbic keratoconjunctivitis. Arch Ophthalmol. Oct 1985;103(10):1525-9. [Medline].
• Confino J, Brown SI. Treatment of superior limbic keratoconjunctivitis with topical cromolyn sodium. Ann Ophthalmol. Apr 1987;19(4):129-31. [Medline].
• Corwin ME. Superior limbic keratoconjunctivitis. Am J Ophthalmol. Aug 1968;66(2):338-40. [Medline].
• Donshik PC, Collin HB, Foster CS, et al. Conjunctival resection treatment and ultrastructural histopathology of superior limbic keratoconjunctivitis. Am J Ophthalmol. Jan 1978;85(1):101-10. [Medline].
• Goto E, Shimmura S, Shimazaki J, Tsubota K. Treatment of superior limbic keratoconjunctivitis by application of autologous serum. Cornea. Nov 2001;20(8):807-10. [Medline].
• Grutzmacher RD, Foster RS, Feiler LS. Lodoxamide tromethamine treatment for superior limbic keratoconjunctivitis. Am J Ophthalmol. Sep 1995;120(3):400-2. [Medline].
• Kadrmas EF, Bartley GB. Superior limbic keratoconjunctivitis. A prognostic sign for severe Graves ophthalmopathy. Ophthalmology. Oct 1995;102(10):1472-5. [Medline].
• Kaufman HB, McDonald MB, Barron BA, Waltman SR. Superior limbic keratoconjunctivitis. In: Maguen, Nesburn, eds. The Cornea. 1988;1:653-4.
• Matsuda A, Tagawa Y, Matsuda H. Cytokeratin and proliferative cell nuclear antigen expression in superior limbic keratoconjunctivitis. Curr Eye Res. Oct 1996;15(10):1033-8. [Medline].
• Matsuda A, Tagawa Y, Matsuda H. TGF-beta2, tenascin, and integrin beta1 expression in superior limbic keratoconjunctivitis. Jpn J Ophthalmol. Jul-Aug 1999;43(4):251-6. [Medline].
• Mondino BJ, Zaidman GW, Salamon SW. Use of pressure patching and soft contact lenses in superior limbic keratoconjunctivitis. Arch Ophthalmol. Dec 1982;100(12):1932-4. [Medline].
• Nelson JD. Superior limbic keratoconjunctivitis (SLK). Eye. 1989;3 ( Pt 2):180-9. [Medline].
• Ohashi Y, Watanabe H, Kinoshita S, et al. Vitamin A eyedrops for superior limbic keratoconjunctivitis. Am J Ophthalmol. May 15 1988;105(5):523-7. [Medline].
• Passons GA, Wood TO. Conjunctival resection for superior limbic keratoconjunctivitis. Ophthalmology. Aug 1984;91(8):966-8. [Medline].
• Raber IM. Superior limbic keratoconjunctivitis in association with scarring of the superior tarsal conjunctiva. Cornea. May 1996;15(3):312-6. [Medline].
• Saika S, Minamide A, Tanaka T. Expression of involucrin by ocular surface epithelia of patients with benign and malignant disorders. Curr Eye Res. Nov 2000;21(5):877-85. [Medline].
• Sendele DD, Kenyon KR, Mobilia EF, et al. Superior limbic keratoconjunctivitis in contact lens wearers. Ophthalmology. Jun 1983;90(6):616-22. [Medline].
• Smolin G, Thoft RA. Superior limbic keratoconjunctivitis. In: Ostler HB, ed. The Cornea. 2nd ed. 1987;1:296-9.
• Stenson S. Superior limbic keratoconjunctivitis associated with soft contact lens wear. Arch Ophthalmol. Mar 1983;101(3):402-4. [Medline].
• Tai MC, Cosar CB, Cohen EJ, et al. The clinical efficacy of silicone punctal plug therapy. Cornea. Mar 2002;21(2):135-9. [Medline].
• Tenzel RR. Comments on superior limbic filamentous keratitis: II. Arch Ophthalmol. Apr 1968;79(4):508. [Medline].
• Theodore FH. Further observations on superior limbic keratoconjunctivitis. Trans Am Acad Ophthalmol Otolaryngol. Mar-Apr 1967;71(2):341-51. [Medline].
• Theodore FH, Ferry AP. Superior limbic keratoconjunctivitis. Clinical and pathological correlations. Arch Ophthalmol. Oct 1970;84(4):481-4. [Medline].
• Theodore FH. The Collected Letters of the International Correspondence Society of Ophthalmology. 1961;6:1989.
• Thygeson P, Kimura SJ. Chronic Conjunctivitis. Trans Am Acad Ophthalmol. 1963;67:494.
• Udell IJ, Kenyon KR, Sawa M, Dohlman CH. Treatment of superior limbic keratoconjunctivitis by thermocauterization of the superior bulbar conjunctiva. Ophthalmology. Feb 1986;93(2):162-6. [Medline].
• Watanabe H, Maeda N, Kiritoshi A, et al. Expression of a mucin-like glycoprotein produced by ocular surface epithelium in normal and keratinized cells. Am J Ophthalmol. Dec 1997;124(6):751-7. [Medline].
• Watson S, Tullo AB, Carley F. Treatment of superior limbic keratoconjunctivitis with a unilateral bandage contact lens. Br J Ophthalmol. Apr 2002;86(4):485-6. [Medline].
• Wilson FM 2nd, Ostler HB. Superior limbic keratoconjunctivitis. Int Ophthalmol Clin. Winter 1986;26(4):99-112. [Medline].
• Wright P. Superior limbic keratoconjunctivitis. Trans Ophthalmol Soc U K. 1972;92:555-60. [Medline].
• Yang HY, Fujishima H, Toda I, et al. Lacrimal punctal occlusion for the treatment of superior limbic keratoconjunctivitis. Am J Ophthalmol. Jul 1997;124(1):80-7. [Medline].
• Yanoff M, Fine BS. Superior Limbic Keratoconjunctivitis. In: Ocular Pathology. 4th ed. 1996;1:240.

Article Last Updated: Apr 5, 2006