Corneal Mucous Plaque

Etiology

Any alteration of the corneal surface or tear film composition can lead to mucus plaque formation.

The common causes of mucus plaques are:

• Aqueous tear deficiency as in keratoconjunctivitis sicca[2]    
• Systemic diseases with ocular surface effects as in Sjogren syndrome and rheumatoid arthritis[2]   
• Herpes zoster keratitis[3][4][5][6]           
• Superficial limbic keratoconjunctivitis[2]    
• Vernal keratoconjunctivitis[7]   
• Post corneal surgery eg, laser-assisted in situ keratomileusis (LASIK) and penetrating keratoplasty (PK)[2]  
• Contact lens overwear[8]
• Staphylococcal blepharitis[2]

Epidemiology

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.[2]

Pathophysiology

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.[9][10]

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.[2][6][11]

Histopathology

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.[2]

History and Physical

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.[6][7][8]

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:

• Foreign body sensation
• Blurred vision
• Dryness
• Pain
• Mucoid discharge
• Photophobia and blepharospasm

A slit-lamp examination may reveal:

• Eyelids – Blepharitis, meibomitis
• Conjunctiva – Conjunctivitis, fornix filaments, hyperemia, mucoid discharge, decreased tear film height
• Cornea – The mucous plaque may take the form of thin thread-like material (filament) attached to the corneal epithelium (filamentary keratitis), keratinization, epithelial derangement, corneal scars, decreased corneal sensations, epithelial or stromal edema, epithelial defect, mucus plaque, keratic precipitates
• Others – Mild iritis can be seen in cases associated with herpes zoster keratitis.
• Mucus plaques may vary in size and shape according to the etiology. In dry eye states, the plaques are round and small. In herpes zoster keratitis, they are large and bizarrely shaped known as dendriform plaques. The plaques may be associated with filaments in case of dry eye states.[6]
• The plaques are semi-translucent to opaque, whitish-grey, with a dry surface and present in the horizontal median. The plaques are firmly adhered to the underlying epithelium and leave a raw surface when removed.[2]

Evaluation

Investigations include office-based tests and special laboratory tests.

Office-based tests:

• Schirmer’s test – Values are low in cases associated with keratoconjunctivitis sicca.
• Stains  
  • Fluorescein stains the necrotic epithelial debris and epithelial defects
  • Rose Bengal and Lissamine green stains the plaque vividly
  • Alcian blue and eosin stains the plaque faintly

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.[12][13]

Polymerase chain reaction for herpes zoster DNA may be indicated in delayed onset plaques and pseudodendrites.[6]

Treatment / Management

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.[14]

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.[15] Plaques associated with herpes zoster keratitis can be treated with antiviral therapy.[6]

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.[15][16][17][18](A1)

Differential Diagnosis

Corneal mucous plaques can be confused with various other surface pathologies, including:

• Epithelial dysplasia
• Corneal keloid
• Ocular surface squamous neoplasia
• Band shaped keratopathy
• Spheroidal degeneration
• Salzmann nodular degeneration

Prognosis

Corneal plaques last from a few days to a few weeks. They can recur anytime if the underlying condition is uncontrolled.[6] 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

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.