eMedicine Specialties > Ophthalmology > Cornea

Keratoconjunctivitis, Superior Limbic

James H Oakman Jr, MD, Partner, Southern Eye Center, Augusta, Georgia

Updated: Nov 6, 2008

Introduction

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.
  • 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.
• Morphological or functional changes in superior conjunctival apposition to the globe following upper eyelid procedures may induce SLK.⁵

Differential Diagnoses

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.

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.

Lodoxamide tromethamine 0.1% (Alomide)

Mast cell stabilizer with reported efficacy in the treatment of SLK.

Dosing

Adult

1 gtt qid for 10 d to affected eye(s)

Pediatric

<2 years: Not established
>2 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Often experience transient burning or stinging from instillation of medication; soft contact lens wearers should refrain from using while under treatment

Cromolyn sodium 4% (Crolom, Intal)

Mast cell stabilizer with reported efficacy in the treatment of SLK.

Dosing

Adult

1 gtt q3-4h until symptoms improve (approximately 1 mo); then, taper dosage to maintain control of symptoms

Pediatric

<5 years: Not established
>5 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Soft contact lens wearers should refrain from using lenses while under this treatment; do not use in severe renal or hepatic impairment; symptoms may reoccur when withdrawing drug

Cauterizing agents

Topical application for treatment of keratinized conjunctiva

Silver nitrate solution

An application to anesthetized conjunctiva usually relieves symptoms of SLK for 4-6 weeks. Then, the treatment can be repeated safely.

Dosing

Adult

0.5-1% solution: Make fresh each day for use and discard afterwards; apply to anesthetized upper tarsus, which then is allowed to fall back into place over affected palpebral conjunctiva; irrigation with sterile saline after 1 min follows this application

Pediatric

Administer as in adults

Interactions

Decreases effects of sulfacetamide preparations

Contraindications

Documented hypersensitivity; broken skin or cuts

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use silver nitrate sticks; not for internal use

Immunomodulators

These agents modulate key factors of the immune system.

Cyclosporine A, 0.05% topical (Restasis)

Used to relieve dry eyes caused by suppressed tear production secondary to ocular inflammation. Thought to act as partial immunomodulator. Exact mechanism of action is not known.

Dosing

Adult

Instill 1 gtt in each eye q6h

Pediatric

<16 years: Not established
>16 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; ocular infection

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Herpes keratitis; do not administer while wearing contact lenses; may cause ocular burning, conjunctival hyperemia, ocular discharge, excessive tearing, eye pain, foreign body sensation, pruritus, stinging, or blurred vision

Follow-up

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.

Inpatient & Outpatient Medications

• 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

• The 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 will help to allay their fear of the unknown and also will help them to cope with the often prolonged symptoms of this entity.

Miscellaneous

Medicolegal 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

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Keywords

superior limbic keratoconjunctivitis, SLK, superior limbic filamentary keratoconjunctivitis

Contributor Information and Disclosures

Author

James H Oakman Jr, MD, Partner, Southern Eye Center, Augusta, Georgia
James H Oakman Jr, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Georgia Medical Society, Georgia Society of General Surgeons, and Georgia Society of Ophthalmology
Disclosure: Nothing to disclose.

Medical Editor

Stephen D Plager, MD, FACS, Chief, Department of Ophthalmology, Dominican Hospital; Assistant Clinical Professor, Department of Ophthalmology, Stanford University Hospital
Stephen D Plager, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and California Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Co-Chairman of the Cornea Service, Co-Chairman of Refractive Surgery Department, Wills Eye Institute
Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, International Society of Refractive Surgery, and Pan-American Association of Ophthalmology
Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; Inspire Honoraria Speaking and teaching; RPS Ownership interest Other; Vistakon Honoraria Speaking and teaching

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

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