First described in detail as a clinical entity by Mooren in 1867.

Mooren’s ulcer is a chronic, painful, peripheral ulcerative keratitis.

More common in males. (M:F = 1.6:1)

Wood and Kaufman classified the disease into 2 groups according to the age of onset.

Unilateral

older patients (fourth decade and older)

limited

More responsive to local surgical and medical therapy.

Bilateral

younger individuals (third decade)

Progressive

resistant to systemic immunosuppression

Pathogenesis

Precise pathophysiological mechanism unknown

autoimmune process: with both cell-mediated and humoral components.

A type III hypersensitivity mechanism has been implicated in the etiopathogenesis of Mooren’s ulcer.

partially purified corneal antigen (Co-Ag).

Neutrophils, lymphocytes &macropages

Ab & complement bound to conjunctival epithelium

PATHOLOGY Mooren’s ulcer is characterized by a progressive,

crescentic, peripheral corneal ulceration that is slightly central to the corneoscleral limbus.

Characteristic extensive, undermined, “overhanging” edge

The histopathology of Mooren's ulcer suggests an immune process.

Involved limbal cornea consisted of three zones.

The superficial stroma vascularized and infiltrated with

plasma cells and lymphocytes. destruction of the collagen

matrix. Epithelium and Bowman's layer

are absent.

The midstroma hyperactivity of fibroblasts disorganization of the collagen lamellae.

The deep stroma heavy macrophage infiltrateDescemet's membrane and the endothelium were

spared

Leading edge of the ulcerHeavy neutrophil infiltrationdissolution of the superficial stromadegranulated neutrophils

The adjacent conjunctiva epithelial hyperplasia and a subconjunctival lymphocytic and plasma cell infiltration.

Clinical features Patients with Mooren’s ulcer will

present with redness, increased lacrimation and photophobia, but pain is typically the outstanding feature.

The pain is excruciating and may seem well out of proportion to the corneal inflammation.

Decreased visual acuity may be secondary to associated iritis, irregular astigmatism due to the peripheral corneal thinning.

The disease may begin as several patchy peripheral stromal infiltrates that then coalesce, commonly in the region of the palpebral fissure.

Generally there is involvement upto

the limbus. The ulcerative process spreads

circumferentially and then centrally to involve the entire cornea eventually.

The anterior 1/3 to 1/2 of the stroma is involved characteristically with a steep overlying central and leading edge.

It is difficult to judge the depth of the involvement unless the lesion is gently probed at the overlying edges.

Adjacent conjunctiva may be inflamed and edematous

iritis is sometimes associated with Mooren’s ulcer.

Hypopyon is rare unless secondary infection is present.

Glaucoma and cataract may complicate the process.

Perforation can occur, especially following minor trauma.

Healing and vascularization occurs slowly with the disease running a chronic course over 4-18 months.

Portions of the ulcer may be quiescent while the remaining

may be active.

Topography demonstrates severe irregular astigmatism and peripheral steepening.

The end stage is a typical scarred, vascularised thinned cornea with the patient experiencing sudden relief from the excruciating pain

Chronic Mooren’s ulcer ultimately results in a central island of hazy stromal tissue with severe peripheral thinning.

DIFFERENTIAL DIAGNOSIS Collagen Vascular Diseases

Rheumatoid ArthritisWegener's GranulomatosisPolyarteritis NodosaSystemic lupus erythematosus

Corneal degenerationsTerrien's DegenerationPellucid Degeneration

OtherStaphylococcal Marginal KeratitisOcular Rosacea

DIAGNOSIS It is a diagnosis of exclusion.

The differential diagnosis is that of peripheral ulcerative keratitis and is extensive.

Infectious aetiologies should be excluded.

Mooren's ulcer is easily distinguished from the non-inflammatory corneal degenerations, in which the epithelium remains intact and pain is absent.

The presence of Mooren's-like ulcer requires an extensive search for occult and potentially lethal systemic diseases.

Investigation includes Total blood count differential count, erythrocyte sedimentation rate,rheumatoid factor, complement fixation, antinuclear antibodies (ANA), antineutrophil cytoplasmic antibody (ANCA), circulating immune complexes, liver function tests, blood urea nitrogen and creatinine, Serum protein electrophoresis, urinalysis, and a chest

roentgenogram.

TREATMENT step-wise approach to the management of

Mooren's ulcer, which is outlined as follows:

1. Topical steroids2. Conjunctival resection3. Systemic immunosuppressives4. Additional surgical procedure5. Rehabilitation

The overall goals of therapy are to arrest the destructive process and to promote healing and reepithelialization of the corneal surface

1. Topical steroids Initial therapy should include intensive topical steroids

Prednisolone 1%, hourly in association with topical cycloplegics and prophylactic antibiotics.

If epithelial healing does not occur within 2 to 3 days, the frequency of topical steroid application can be increased to every half hour.

Once healing occurs, the frequency can be reduced, and tapered slowly over a period of several months.

Such management, especially in unilateral, benign form gives good results.

Oral therapy (60 to 100 mg daily of oral prednisone)

Topical tetracycline or medroxyprogesterone may be used for anticollagenolytic properties of each.

A therapeutic soft contact lens or patching

2. Conjunctival resection

Conjunctiva adjacent to the ulcer contains inflammatory cells that produce antibodies against the cornea and cytokines which amplify the inflammation and recruit additional inflammatory cell.

conjunctival excision to bare sclera extending at least 2 clock hours to either side of the peripheral ulcer, and approximately 4 mm posterior to the corneoscleral limbus and parallel to the ulcer.

The overhanging lip of ulcerating cornea may also be removed.

Tissue adhesive and a therapeutic soft contact lens may be beneficial.

Cryotherapy of limbal conjunctiva may have a similar effect.

3. Systemic immunosuppressives

The most commonly used agents are cyclophosphamide (2 mg/kg/day), methotrexate (7.5 to 15 mg once weekly) and azathioprine (2 mg/kg body weight/day).

The degree of fall in white blood cell count is considered as the most reliable indicator of immunosuppression produced by cyclophosphamide.

Agents such as cyclophosphamide may be effective by suppressing B lymphocytes, which produce autoantibodies and promote immune complex disease.

oral cyclosporin A (10 mg/kg/day) has been successfully used to treat a case of unresponsive bilateral Mooren's ulcer

It work by suppression of the helper T cell population and stimulation of the depressed population of suppressor and cytotoxic T cells present in patients with Mooren's ulcer.

Adverse effects of these, such as anaemia, alopecia, nausea, nephrotoxicity and hepatotoxicity,

local or systemic side effects attributable to topical cyclosporin A were not observed.

4. Additional Surgical Procedures Superficial lamellar keratectomy, has been shown to

arrest the inflammatory process and allow healing.

Application of isobutyl cyanoacrylate, a tissue adhesive, forms a biological barrier between host cornea and the reepithelializing conjunctiva and the immune components it may carry.

Small perforations may be treated with application of tissue adhesive and placement of a soft contact lens to provide comfort and to prevent dislodging of the glue.

When a perforation is too large for tissue adhesive to seal the leak, some type of patch graft will be necessary.

This may range from a small tapered plug of corneal tissue to a penetrating keratoplasty.

In case of larger peripheral perforations, a partial penetrating keratoplasty may be performed.

It should be emphasized that the prognosis of corneal graft in the setting of acute inflammation in patients with Mooren's ulcer is very poor.

5. Rehabilitation Rehabilitative surgical therapy in two stages, namely initial

lamellar tectonic grafting followed by central penetrating keratoplasty may be required in advanced cases.

LKP is the most widely practiced surgery at present.

It removes antigenic targets of the cornea, prevents immunological reactions, reconstructs the anatomical structure, prevents perforation and improves vision.

The principle of lamellar keratoplasty surgery in Mooren’s ulcer is to remove necrotic ulcerative cornea and to reconstruct the anatomical structure of the cornea.

For an ulcer smaller than half circle of the limbus and the central 7-8 mm of the cornea uninvolved crescent shaped lamellar graft can be used.

For an ulcer larger than 2/3 of a circle of the limbus where the central 7-8 mm of cornea is intact, a doughnut shaped lamellar graft is recommended.

Double lamellar grafts (a fresh thin inner graft with corneal endothelial cells is used to repair the perforation, on which another lamellar graft shaped in accordance with the shape of the ulcer is placed) can be used for perforations of the peripheral cornea.

Postoperative use of topical steroids and 1% cyclosporine