The superficial cornea, consisting of Bowman's membrane, epithelium, and the overlying tear film, is prone to insult from external elements like infectious agents, systemic diseases, various deposits from the tear film including iron, calcium, mucous, and immunoglobulins, and epithelial dysplasias and neoplasms.
The response to these insults can be ulcerative and non-ulcerative. The non-ulcerative pathologies can form distinct patterns. The most important of these patterns are plaque, dendriform, vortex, linear, and superficial punctate keratopathy. The patterns, though distinct, are not specific for a single disease entity. One pattern can be produced by multiple etiologies, and multiple patterns can be produced by a single disease entity.
Corneal mucous plaques are a collection of mucus, epithelial cells, lipid, and proteinaceous debris, which are firmly adhered to the underlying corneal epithelium. The mucous plaques can be translucent to opaque, multiple or single, small or large patterns that can involve more than one half the corneal surface.
Any alteration of the corneal surface or tear film composition can lead to mucus plaque formation.
The common causes of mucus plaques are:
Corneal mucous plaques are most commonly seen in patients with keratoconjunctivitis sicca. Keratoconjunctivitis sicca associated with Sjogren syndrome is more common in women than men. The frequency of corneal mucous plaques increases with age; it is seen more commonly in the elderly age group.
Whatever the etiology, two factors are common in mucous plaque formation, altered corneal epithelium, and disturbed tear film mucous. Mucous receptors present on corneal epithelium are involved in the maintenance of tear film. Alteration in these receptors due to various causes, including inflammatory mediators, exposure, infection, and denervation, can lead to the accumulation of mucous.
Mucins are heavy molecular weight glycoproteins formed by sugar (carbohydrate) chains linked to a core protein called apomucin. In patients with dry eye, there is an alteration in the carbohydrate component of mucin in the goblet cells. Also, there is a decrease in sialic acid and GaINAc (N-acetylgalactosamine) in the goblet cells, which result in the formation of mucin, which is less soluble, more viscous, and thus more prone to accumulation.
This increase in viscosity can also occur in cases associated with staphylococcal blepharitis. The bacteria liberate enzymes, which in turn lyse the glycosaminoglycan and mucoprotein components of the mucin.
These changes cause accumulation of viscous mucous and proteinaceous debris over the altered corneal epithelial cells. This material adheres to the deeper epithelial cells and even to the Bowman membrane through the epithelial defects and abnormal intercellular spaces. The overlying material prevents the normal sloughing of the epithelial cells so that the desquamated cells are incorporated in the material, gradually forming an elevated plaque. Chronic plaque enmeshes dust particles, debris, bacteria, and even foreign bodies.
Corneal mucous plaques are a mixture of mucin, sloughed epithelial cells, and proteinaceous and lipoidal cell debris. Mucus strands are present between widened intercellular spaces between adjoining healthy epithelial cells as well as in the gaps between degenerated epithelial cells. The epithelial cells present in the plaque range from nucleated or non-nucleated cells to necrotic cells. Other than mucus and epithelial cells, variable amounts of flocculent proteinaceous and lipoidal material are found enmeshed in the plaque.
History of dryness of mouth, dry skin, joint pains, family history of connective tissue disorders, is often present in cases of sicca associated with systemic diseases. History of skin lesions is present in cases of plaque secondary to herpes zoster keratitis. History of atopy, contact lens wear, or past corneal surgery may be present.
The symptoms are often present before the onset of plaque formation due to the underlying condition. For example, in sicca associated plaque, complaints of dryness and foreign body sensation are present long before the plaque formation.
The symptoms include:
A slit-lamp examination may reveal:
Investigations include office-based tests and special laboratory tests.
Specialized lab tests:
In cases associated with keratoconjunctivitis sicca, blood investigations are needed to diagnose Sjogren syndrome. Although salivary gland biopsy remains the gold standard, an examination of classic SS biomarkers ANA (anti-nuclear antibody), SS-A/Ro and SS-B/La and rheumatoid factor is a non-invasive way for the diagnosis of Sjogren syndrome.
Polymerase chain reaction for herpes zoster DNA may be indicated in delayed onset plaques and pseudodendrites.
Topical mucolytic agents like acetylcysteine 10-20% one to 4 times a day topically dissolve the mucus and loosen the plaque. The plaques can recur after discontinuation of mucolytic drops. N-acetyl-L-cysteine is an amino-acid L-cysteine derivative and is used to reduce the viscosity of mucus in a variety of disorders. It reduces the action of the free sulphydryl group in the disulfide bonds of the mucoproteins, thereby reducing the viscosity.
Artificial tear substitutes, preferably hypotonic type, are indicated along with topical mucolytics, especially in cases associated with dry eye states. Preservative-free tear substitutes are preferable as preservatives such as benzalkonium chloride are epitheliotoxic and can exacerbate the problem.
Topical cyclosporine A and soft corticosteroids such as fluorometholone and loteprednol etabonate are indicated when there is associated inflammation as in keratoconjunctivitis sicca.
Staphylococcal blepharitis is frequently associated with corneal mucus plaques and should be treated with warm compresses, lid hygiene, and antibiotic ointment. Plaques associated with herpes zoster keratitis can be treated with antiviral therapy.
Highly symptomatic plaques can be removed by debridement (scraping or with a cotton bud). After debridement, a soft bandage contact lens can be applied to the cornea.
Excimer laser phototherapeutic keratectomy (PTK) can be useful for the removal of larger plaques, especially those associated with vernal keratoconjunctivitis. PTK uses an excimer laser (193 nm) and works on the principle of photoablation, i.e., it breaks the bonds between molecules. One pulse of laser affects approximately 0.25 microns of the corneal surface so that the underlying normal tissue remains unaffected.
Corneal mucous plaques can be confused with various other surface pathologies, including:
Corneal plaques last from a few days to a few weeks. They can recur anytime if the underlying condition is uncontrolled. Prognosis, in most cases, is guarded. Those with severe disease have a poor quality of life. Dry eyes frequently associated with the plaques cause significant morbidity. With advancing age, the symptoms tend to worsen.
Complications of corneal mucous plaque occur mainly secondary to the underlying conditions. If the plaque is associated with keratoconjunctivitis sicca, the severe dry eye can result in conjunctival scarring, corneal scarring, corneal vascularization, and in rare cases corneal perforation. Prolonged inflammation associated with sicca can also result in symblepharon formation. If the plaque is secondary to herpes zoster keratitis, the patient might have corneal scarring, vascularization, and corneal ulceration. In very young patients with vernal keratoconjunctivitis, if the plaque is untreated, it might lead to corneal scarring and eventually amblyopia.
Patients with corneal mucous plaque associated with keratoconjunctivitis sicca should be referred to a rheumatologist for systemic management. Patients with herpes zoster disease might need dermatologist consultation. Patients with a plaque with vernal keratitis might be suffering from generalized atopy, and should be referred to primary clinician and dermatologist as needed.
Patients should be counseled regarding prolonged time course to symptom relief. The need for strict adherence to the treatment regimen should be stressed. Purposeful discussion regarding the chance of recurrence and need for further intervention may avoid unrealistic expectations of immediate and complete resolution of the disease. The need for regular follow up with all the care providers should be explained if the corneal plaque is associated with systemic disease.
Sjogren syndrome should be suspected in any case of corneal mucous plaque, which is associated with systemic symptoms like dry mouth and dry skin.
In the case of large, bizarrely shaped mucous plaque, the history of herpes zoster should be elicited.
A corneal mucous plaque has a diverse etiology and can present with a diagnostic dilemma. The ophthalmologist is generally the first one involved in the patient's care. An interprofessional team of specialists, including rheumatologists, dermatologists, and primary clinicians, need to be included according to the etiology of the plaque. Nurses play an important role, too, as they can educate the patient about avoiding contact lenses, and warning signs of the associated systemic disease. Pharmacists should ensure that the patient is using proper topical and systemic medication. The pharmacist also prepares the correct concentration of topical acetylcysteine (10 to 20%) as advised by the ophthalmologist.
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