Superior limbic keratoconjunctivitis (SLK) is relatively an uncommon chronic disease of superior limbus/cornea, and superior bulbar and tarsal conjunctiva. It affects one or both eyes of middle-aged people, about half the patients have abnormal thyroid function (usually hyperthyroidism). About three percent of patients with thyroid eye disease develop SLK. Women are more commonly affected than men.
Superior limbic keratoconjunctivitis is believed to be due to blink-related trauma between the upper lid and the superior bulbar conjunctiva, precipitated in many cases by tear film insufficiency, and an excess of lax conjunctival tissue. With increased conjunctival movement, there is mechanical damage to the tarsal and bulbar conjunctival surfaces. It results in inflammatory response, leading to increased conjunctival oedema and redundancy, with the creation of a self-perpetuating cycle. It may be analogous to conjunctivochalasis (redundant excess fold of conjunctiva) affecting the lower bulbar conjunctiva.
Superior limbic keratoconjunctivitis has similarities to mechanically induced papillary conjunctivitis and a comparable clinical picture may be seen in:
Between 1954 and 1963, reports by Braley and Alexander (Braley AE, Alexander RC. Superficial punctate keratitis. Arch Ophthalmol, 1953; 50(2):147-154), Thygesson and Kimura (Thygesson P, Kimura SJ: Chronic conjunctivitis. Trans Am Acad Ophthalmol Otolaryngol 1963; 67: 494-517) presented information about a new clinical entity associated with filamentary keratopathy.
Superior limbic keratoconjunctivitis was first fully described by Frederick Theodore in 1963. (Theodore FH. Superior limbic keratoconjunctivitis. Eye Ear Nose Throat Mon 1963; 42: 25-28.). He suggested the term Superior limbic keratoconjunctivitis to describe a series of patients with the following presenting signs:
SLK is probably under-diagnosed because symptoms are typically more severe than signs. The course can be prolonged over years although remission eventually occurs spontaneously.
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The characteristic feature of the symptoms of SLK is its variability with intermittent remissions and exacerbations.
Patients may have ocular (eye) symptoms such as:
The symptoms are often intermittent.
Soft contact lens wear may be associated with features like SLK. It may be attributable to preservatives especially thiomersal. Removal of lens or preservatives is usually curative.
There have been many theories about the aetiology of SLK, but still some uncertainty remains till date.
Possible aetiological theories:
Mechanical trauma is the most popularly assumed theory as aetiology of SLK.
There is constant abnormal movement of the superior bulbar conjunctiva during blinking due to abnormal interaction of the superior tarsal and bulbar conjunctiva. The laxity of bulbar conjunctiva because of congenital origin or due to ageing, predisposes it to get repeatedly traumatised by upper lid as the lid is opened or closed. This abnormality may be due to tight apposition of tarsal conjunctiva against the globe in the setting of:
This theory is supported by strong association of SLK with both thyroid dysfunction and dry eye disease.
There is high expression of transforming growth factor-beta 2 and tenascin, both are known to be affected by mechanical stress and injury.
The mechanical irritation induces abnormal mucous production and this abnormal mucous production is responsible for filament formation.
Alteration in expression of certain cytokeratins (CKs) is found in patients with SLK. There is decreased expression of a marker for non-keratinised stratified squamous epithelium, CK13 along with increased expression of CK10, a marker for keratinisation, which correlates with disease severity. These suggest that an abnormality of differentiation in conjunctival epithelium plays a role in the disease.
Some have suggested a viral cause, but cultures are found to be universally negative.
In some studies, bacterial cultures have been shown to be positive, but mostly for normal ocular flora.
An autoimmune aetiology has also been proposed but this is also less likely due to:
Hyperparathyroidism has also been reported in association with SLK.
A familial association has rarely been reported but is not the norm.
History of contact lens wear, and previous eyelid surgery or trauma should be obtained from the patient.
Even in untreated patients, the natural course of disease is one of episodic intermittent relapses and gradual improvement over several years, with eventual resolution. Most patients have bilateral affection, but asymmetric and unilateral disease does occur. The disease is roughly twice more common in females. It typically presents in fourth or fifth decades of life.
Patients with SLK present with non-specific ocular complaints. Symptoms are usually much more severe if the patient has corneal filaments. Often irritation is mild in the morning but it worsens thereafter. The symptoms can be vague and intermittent and often are mistaken for other ocular surface disease, such as dry eye or blepharitis. SLK patients are often misdiagnosed or are not diagnosed for many years, because superior conjunctiva is frequently not examined or clinical findings are often missed.
A diagnosis of SLK should only be made after a thorough patient history is obtained and physical examination is performed, since diagnosis is based primarily on the clinical findings.
It requires slit-lamp (bio-microscopy) examination by an eye-specialist.
It is advisable in suspected SLK patient to simultaneously elevate both upper lids and look at the superior conjunctiva.
The thickening and hyperaemia of bulbar conjunctiva extends from upper limbus towards the insertion of the superior rectus muscle.
The inferior tarsal conjunctiva is typically normal.
Key to the diagnosis:
Key to the diagnosis of SLK is the examination of superior bulbar conjunctiva by:
Biopsy of superior bulbar conjunctiva generally shows keratinised epithelium as well as cellular infiltration (polymorphonuclear leukocytes, lymphocytes and plasma cells). Along with this, it shows acanthosis, dyskeratosis and balloon degeneration of some nuclei. The demonstration of these features on diagnostic scrapings of the superior bulbar conjunctiva stained with Giemsa, helps in diagnosis of doubtful cases.
Electron microscopy shows abnormal distribution and aggregation of nuclear chromatin, filaments in nuclei, dense accumulations of cytoplasmic filaments that surround nuclei, and formation of multi-lobed nuclei or multi-nucleated inflammatory cells.
Palpebral conjunctiva is normal but polymorphonuclear cells are often present.
Wright (Wright P: Superior limbic keratoconjunctivitis. Trans Ophthalmol Soc UK 92: 555, 1972) has stressed on the goblet cell population in SLK. Superior palpebral conjunctiva shows goblet cell hypertrophy, while bulbar conjunctiva which is thickened and keratinised shows very few goblet cells.
Superior limbic keratoconjunctivitis should be differentiated from the conditions such as:
Management should be carried out under medical supervision.
Initially, topical medical treatment should be attempted.
Hallmark of SLK is redundancy of the superior bulbar conjunctiva. Different methods have been employed to attempt to tighten the redundant superior bulbar conjunctiva.
Tightening procedures for redundant superior bulbar conjunctiva:
Resection of the superior bulbar conjunctiva: Resection of the superior bulbar conjunctiva is used in cases where medical treatment and/or conjunctival tightening are not successful. This technique has been most successful, predictable and usually gives immediate as well as permanent relief of symptoms. This is the preferred and initial surgical treatment. Conjunctival resection alleviates symptoms and results in resolution of squamous metaplasia of conjunctiva. In rare cases, redundant conjunctiva can recur, necessitating further conjunctival resection or application of silver nitrate.
Temporary superior and/or inferior punctal occlusion: Temporary superior and/or inferior punctal occlusion may be done for concomitant lacrimal insufficiency, and it may be combined with instillation of artificial tears.
Management of associated thyroid dysfunction may improve SLK.
In general, prognosis for superior limbic keratoconjunctivitis is excellent. With increasing age, exacerbations tend to diminish in frequency with eventual total resolution, though symptoms may last for years.