Superior Limbic Keratoconjunctivitis

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Article initiated by:

Guillermo Mendoza Adam, MD

All contributors:

Brad H. Feldman, M.D., Guillermo Mendoza Adam, MD, Alejandro Rodríguez-García, MD., Vatinee Y. Bunya, MD, MSCE, Colleen Halfpenny, M.D., Augustine Hong, MD, Benjamin B. Bert, MD, FACS

Assigned editor:

Benjamin B. Bert, MD, FACS

Review:

Assigned status Up to Date

 by Benjamin B. Bert, MD, FACS on October 16, 2024.

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Superior Limbic Keratoconjunctivitis

DiseasesDB

31307

ICD-10

H16.2

ICD-9

370.40

Superior limbic keratoconjunctivitis (SLK) of Theodore is a rare chronic inflammatory disease of the superior bulbar conjunctiva, limbus and upper cornea of unknown etiology. This disease has been associated with thyroid dysfunction, keratoconjunctivitis sicca and rheumatoid arthritis. Multiple treatment modalitites have been described but there is not a gold standard.

Disease Entity

ICD-10:

• H16.299 - Other keratoconjunctivitis, unspecified eye
• H16.291 - Other keratoconjunctivitis, right eye
• H16.292 - Other keratoconjunctivitis, left eye
• H16.293 - Other keratoconjunctivitis, bilateral

ICD-9:

• 370.40 - Keratoconjunctivitis, unspecified

Disease

Superior limbic keratoconjunctivitis (SLK) was described by Frederick Theodore in 1963 in a group of patients without evidence of infection, characterized by marked inflammation of the upper tarsal and bulbar conjunctiva, fluorescein staining of the cornea and upper limbus, positive staining with lissamine green or rose bengal of the superior bulbar conjunctiva adjacent to the limbus, proliferation and redundancy of superior limbic conjunctiva, and filament formation in the limbic area and the upper part of the cornea. The age of presentation is around the sixth decade of life, affecting women more often than men (ratio 3:1). A Mexican case series reported a higher frequency of presentation in females, with a female-to-male ratio of 5.4:1. An association between SLK and thyroid dysfunction has been reported in up to of 30% of the patients. An association with ocular graft-versus-host-disease is also established, though the true incidence is unknown. Keratoconjunctivitis sicca has also been reported to be present in 25% of patients.

Etiology and Pathophysiology

The etiology and pathogenesis of the disease is unknown. SLK may represent the final manifestation of a variety of pathophysiological pathways and disease entities. One of the most propagated theories is the one proposed by Wright. This theory suggests that the initial component leading to the development of SLK is a constant friction between the superior bulbar and tarsal conjunctiva caused by excessive laxity. However, like other theories previously proposed, such as infectious, immunogenic and allergic, it lacks of sufficient and convincing evidence to sustain itself as a unique unifying mechanism in the development of the disease.

Histopathological studies of the conjunctiva of SLK affected patients have typically shown keratinization of epithelial cells with dyskeratosis, acanthosis and nuclear balloon degeneration. Furthermore, by microscopic analysis, a stromal infiltration by polymorphonuclear leukocytes, plasma cells, mastocytes and lymphocytes has been reported. Watanabe et al. showed decreased levels of mucin-like glycoprotein on immunofluorescent staining of 9 study eyes with keratinized superior bulbar conjunctival epithelium, and standardization of such levels when compared to normal control subjects after treatment with topical vitamin A or bandage contact lens. Matsuda et al. detected abnormal differentiation and hyperproliferation of the conjunctival epithelium associated with increased expression of cytokeratins 10,13,14 and proliferating cell nuclear antigen. Additionally, the same group showed upregulation of transforming growth factor beta 2 (TGF-β2) and the tenascin 13. Both factors can be induced by mechanical trauma, supporting the theory of microtrauma as the possible origin of SLK.

Diagnosis

Symptoms

The disease is characterized by unilateral or bilateral, insidious foreign body sensation, photophobia, excessive blinking and ocular burning and pain. When prompted, patients can often specifically localize the physical location of their symptoms to the superior aspect of their adnexa. In a case series of 45 patients, most frequent symptoms reported were: foreign body sensation (71.1%), burning sensation (68.9%), pruritus (46.6%) and dry eye sensation (31.1%), among others.

Physical examination

The ophthalmological examination is characterized by micro-papillary reaction in the upper tarsal conjunctiva, redundancy and laxity of the upper bulbar conjunctiva, sectorial conjunctival hyperemia, keratinization and ciliary injection. In some cases, there is noticeable thickening of the superior bulbar conjunctiva which stains positive with fluorescein, rose bengal and lissamine green in a punctate focal pattern. In a case series of 45 patients, 100% had ciliary injection in the upper bulbar conjunctiva, 73.3% showed corneal erosions in the upper quadrants, 68.9% superior tarsal papillae, 22.2% diffuse superficial corneal erosions, 15.5% conjunctival hyperemia, and eyelid edema in 13.33%, among others.

Diagnostic procedures

Careful slit lamp examination of the superior bulbar conjunctival and upper tarsal conjunctiva are paramount. Evaluation of the upper bulbar conjunctiva, looking for foldings, hyperemia, redundancy, and filament formation. Fluorescein and lissamine green, or rose bengal staining can be extremely useful. Schirmer testing can be useful if keratoconjunctivitis sicca is suspected. Examination for thyroid orbitopathy can also be useful.

Laboratory test

Depending on clinical findings, thyroid function tests may be helpful. Additional testing for autoimmune serologic tests like, anti-Ro (SS-A) and anti-La (SS-B) antibodies, and cyclic citrullinated-peptide antibodies can be considered if suspicious for Sjogren's Syndrome or rheumatoid arthritis. Medical evaluation by a rheumatologist or endocrinologist is recommended in case of suspected associated systemic disease.

Differential diagnosis

• Allergic conjunctivitis
• Dry eye syndrome
• Episcleritis
• Floppy eyelid syndrome
• Epidemic keratoconjunctivitis
• Keratoconjunctivitis sicca
• Ocular surface squamous neoplasia
• Thyroid Ophthalmopathy
• Trachoma
• Viral Conjunctivitis

Management

Medical therapy

There is not a gold standard in the treatment of SLK. Many different therapeutic modalities have been reported, including topical steroids, topical tacrolimus, topical rebamipide, topical silver nitrate, therapeutic soft contact lens, scleral lens, lacrimal puncta occlusion, topical vitamin-A, topical cyclosporine-A 0.5%, ketotifen fumarate, autologous serum, cromolyn sodium, lodoxamide tromethamine, botulinum injection in the muscle of Riolan, and supratarsal triamcinolone injection, all of which have shown variable therapeutic responses.

Medical follow up

Partial disease resolution is common. Patients may require chronic medical therapy. A referral to a specialist may be indicated, especially for coexisting systemic pathology.

Surgery

Fraunfelder et al. reported a case series of seven eyes treated with nitrogen liquid cryotherapy applied with double freeze-thaw technique, this technique is safe but retreatments may be necessary in about one third of eyes. Upper conjunctival resection with or without thermal cauterisation and with or without amniotic membrane implantation has variable results in the treatment of SLK . Long-term results are more variable and partial disease resolution and recurrence may require additional medical attention.

Prognosis

Remissions and exacerbations tend to diminish in frequency as age increases.