Superior limbic keratoconjunctivitis
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.
- H16.299 - Other keratoconjunctivitis, unspecified eye
- H16.291 - Other keratoconjunctivitis, right eye
- H16.292 - Other keratoconjunctivitis, left eye
- H16.293 - Other keratoconjunctivitis, bilateral
- 370.40 - Keratoconjunctivitis, unspecified
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. 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. One of the most accepted 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, which has been suggested to be involved in the interaction of the epithelium and mucin of the conjunctiva, and standardization of such levels after successful treatment of the disease. 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 probable origin of SLK.
The disease is characterized by unilateral or bilateral, insidious foreign body sensation, photophobia, excessive blinking and ocular burning and pain. 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.
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 and ciliary injection. In some cases, there is noticeable thickening of the superior bulbar conjunctiva which stains positive with fluorescein and vital pigments such as, 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.
Careful slit lamp examination of the upper tarsal conjunctiva looking for papillary reaction. Evaluation of the upper bulbar conjunctiva, looking for foldings, hyperemia, redundancy, and filament formation. Fluorescein and lissamine green, or rose bengal staining. Schirmer test. Rule out dysthyroid orbitopathy.
Thyroid function tests, autoimmune serologic tests like, anti-Ro (SS-A) and anti-La (SS-B) antibodies, and cyclic citrullinated-peptide antibodies, depending on the symptoms and clinical findings. Medical evaluation by a rheumatologist or endocrinologist is recommended in case of suspected associated systemic disease.
- Allergic conjunctivitis
- Dry eye syndrome
- Floppy eyelid syndrome
- Epidemic keratoconjunctivitis
- Keratoconjunctivitis sicca
- Ocular surface squamous neoplasia
- Thyroid Ophthalmopathy
- Viral Conjunctivitis
There is not a gold standard in the treatment of SLK. Many different therapeutic modalities have been reported, including topical silver nitrate, therapeutic soft contact 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
Treat exacerbations, refer to specialist in case of coexisting systemic pathology.
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 been reported to have satisfactory results in the treatment of SLK of Theodore.
Remissions and exacerbations tend to diminish in frequency as age increases.
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