Background
Superior limbic keratoconjunctivitis (SLK) 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] Contemporaneously, this condition was given its name, superior limbic keratoconjunctivitis (SLK), by Theodore. Five years later, Tenzel and Corwin each reported an association between thyroid abnormalities and SLK. [2, 3] A mimicking disorder has been encountered in soft contact lens (SCL) wearers, typically with exposure to thimerosal-preserved solutions. [4, 5]
In the United States, the frequency of superior limbic keratoconjunctivitis has been reported to be 3% in a cohort of ophthalmopathy patients with Graves disease, but it is much lower in the general population. Although no racial predilection exists, middle-aged people (range, 40-80 years) and women are predominantly affected. [6]
In general, the prognosis of superior limbic keratoconjunctivitis is excellent, with remission as the natural history and eventual total resolution, although symptoms may last for years.
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Etiology and Pathophysiology
The cause of superior limbic keratoconjunctivitis (SLK) is unknown, but inflammatory changes from mechanical soft tissue microtrauma are the final common pathway. [7] This condition also is associated with thyroid dysfunction but has been known to develop in association with scarring of the palpebral conjunctiva in euthyroid patients.
Other potential risk factors for development of superior limbic keratoconjunctivitis include prolonged eyelid closure with associated hypoxia or reduced tear volume, as well as morphologic or functional changes in superior conjunctival apposition to the globe following upper eyelid procedures. [8]
Superior limbic keratoconjunctivitis is believed to be present secondary to superior bulbar conjunctiva laxity, which induces inflammatory changes from mechanical soft-tissue microtrauma. [9] In settings in which the physiologic 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 superior limbic keratoconjunctivitis lends credence to microtrauma being of most significance to the development of superior limbic keratoconjunctivitis.
Dry eye disease also is associated with SLK, as it can exacerbate the repetitive microtrauma between the tarsal and superior palpebral conjunctiva. [7] Studies have shown that secondary dry eye conditions, specifically the ocular form of chronic graft-versus-host disease (cGVHD), also predispose to SLK. Ocular cGVHD, similar to other forms of autoimmune-mediated ocular surface disease, creates inflammatory damage to the lacrimal glands, meibomian glands, cornea, and conjunctiva. [10] These damages increase frictional forces between conjunctival surfaces and consequently create repetitive microtrauma, leading to SLK-like inflammation.
Pathophysiology
It is speculated that SLK may be a mast cell–related disorder, as an increased number of mast cells is found in the subepithelial stroma of patients with SLK. [11] Mechanisms involving promotion of mast cell migration and activation in this disease are unclear, but recent research found an overexpression of stem cell factor (SCF) and thymic stromal lymphopoietin (TSLP) in the conjunctival epithelium of patients with SLK. Thus, it is possible that these factors are involved in promoting mast cell migration and activation, contributing to the pathogenesis of SLK. [12] Immunochemistry analysis also has shown a higher COX-2 expression in patients with SLK compared with normal conjunctiva. [13]
Epidemiology
Superior limbic keratoconjunctivitis is more common in women than in men, by a ratio of 3:1. It also is more common in middle-aged individuals (~60 years).
It has no radical predilection.
People with thyroid dysfunction and keratoconjunctivitis sicca are at an increased risk.
Prognosis
In general, the prognosis of superior limbic keratoconjunctivitis is good, with remission as the natural history and eventual total resolution, although symptoms may last for years.
