Rituximab appears to cure Mooren’s ulcers in 5 patients

Mooren’s ulcers completely healed in 5 patients treated with rituximab after conventional treatment failed, according to researchers.

“Additional studies should assess the role of this biotherapy in the management of immunological corneal ulcer,” wrote Dr Damien Guindolet from Fondation A. de Rothschild in Paris, France, and colleagues in the British Journal of Ophthalmology.

This case series is the first report the authors could find of rituximab being used for this indication.

A rare corneal ulcerative keratitis, Mooren’s ulcer begins peripherally from the limbus and progresses circumferentially and centrally.

Much about its aetiology remains poorly understood. But researchers believe it involves loss of tolerance to corneal stroma autoantigen by both cellular and humoral components of the immune system.

Discerning two types

Mooren’s ulcers fall into two types: a unilateral peripheral ulcer occurring in elderly Caucasian patients that typically yields to topical steroids, and a bilateral form appearing in young patients-often of African heritage-that requires significant systemic immunosuppression to treat.

The severe inflammation can result in conjunctivalisation or corneal melting and perforation. Corticosteroids are the mainstay of treatment. Conjunctival resection can prevent immune cell infiltration and keratoplasty may be used in cases of severe corneal thinning or perforation, but such surgery is performed with local or systemic immunosuppression.

Cyclophosphamide has been recommended for refractory cases, but the recommendation is based on small case series, and this medication can cause haemorrhagic cystitis, neoplasia, and infertility.

Based on the involvement of humoral immunity in the pathogenesis of Mooren’s ulcer, Guindolet et al. hit upon the idea of treating it with rituximab. A chimeric human and murine anti-CD20 monoclonal antibody, rituximab has treated various autoimmune diseases refractory to conventional treatment, including ulcerative keratitis associated with granulomatosis with polyangiitis.

Diving deeper

Diving deeper

The researchers reported on 5 patients who presented with severe Mooren’s ulcers at the Cornea and External Disorders department of the Rothschild Ophthalmologic Foundation between October 2008 and January 2016.

The patients underwent extensive examinations and workup, including testing for parasitic infections, with patients from endemic areas treated with ivermectin prior to immunosuppressive infusions.

One of the patients had schistosomiasis and another had helminthiasis. A third patient was diagnosed with obsessive-compulsive disorder involving iterative corneal abrasion. A fourth patient had a history of chronic corneal Dellen linked with a prominent filtering bleb.

The patients then underwent hourly administration of local corticosteroids, topical 2% ciclosporin A 3 times a day, systemic immunosuppression, conjunctival resection, and amniotic membrane graft.

Two patients underwent 3 intravenous cyclophosphamide pulses (600 mg/m² weekly) which did not stop their corneas from melting.

Intravenous corticosteroid in 3 to 6 pulses (500 mg/pulse) followed by oral corticosteroid (1 mg/kg/day) also could not stop the ulcers from progressing.

When these 2 patients’ corneas continued thinning after these treatments, they were offered rituximab in the form of 2 infusions of 1,000 mg at 2-week intervals. They healed completely within 15 days.

Seeing this, the clinicians skipped cyclophosphamide and went directly to rituximab in the other 3 patients, and these patients also healed within 15 days.

Patients with corneal keratoplasty also underwent lamellar keratoplasty, receiving rituximab the next day.

Tapering therapy

Tapering therapy

Clinicians gradually tapered the patients’ system of rituximab, with total withdrawal in 2 to 11 months, and also tapered the topical steroids and ciclosporin over 12 months.

Two of the patients relapsed with stromal infiltration and an epithelial defect, 1 at 53 months and 1 at 13 months after the first rituximab infusions. Both underwent another round of 3 intravenous corticosteroid pulses followed by oral corticosteroid, local steroids and local ciclosporin then a new cycle of rituximab.

This treatment led once again to complete healing within 2 weeks, and neither patient had relapsed 11 and 13 months after the last infusion of rituximab.

No patient appeared to suffer any side effects to the rituximab. One patient developed a staphylococcal corneal ulcer 3 months after the lamellar keratoplasty on a loosened suture, but this was successfully treated with local fortified antibiotics and early replacement of the lamellar graft.

A total of 4 eyes in 3 of the patients gained visual acuity following the treatment. Scleral lenses were adapted in the other 2, leading to significant improvement in visual acuity.

Dr Guindolet and colleagues acknowledge that their small case series can hardly be considered definitive proof of the efficacy of rituximab for Mooren’s ulcers. But they point out that a randomised clinical trial would be difficult to achieve.

In the meantime, this experience has altered their approach to the disease, they wrote. “This impressive therapeutic response led us to consider rituximab as a new therapeutic option when cyclophosphamide was previously proposed.”