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High-dose short-term chlorambucil effective for sympathetic ophthalmia

Article

High-dose short-term chlorambucil therapy for sympathetic ophthalmia is effective and allows discontinuation of systemic steroids. The cost of the drug is lower compared with other alkylating agents, according to Laura Echandi, MD, of the Uveitis Department, Hospital Juan Fernandez, Buenos Aires.

High-dose short-term chlorambucil therapy for sympathetic ophthalmia is effective and allows discontinuation of systemic steroids. The cost of the drug is lower compared with other alkylating agents, according to Laura Echandi, MD, of the Uveitis Department, Hospital Juan Fernandez, Buenos Aires.

"Chlorambucil is an alkylating immunosuppressive drug that has been used in ophthalmology since 1970 and has been successful in treating various forms of noninfectious forms of uveitis," Dr. Echandi said. "The high-dose short-term regimen was introduced to treat patients with severe and chronic disease for efficacy and to reduce the systemic side effects; low doses that were increased weekly over the short term were used to achieve bone marrow suppression and control intraocular inflammation. The toxic effects of chlorambucil develop more slowly compared with other alkylating agents; the late serious side effects include malignancy (acute leukemia or lymphoma), male infertility, teratogenicity, myelofibrosis, or pulmonary fibrosis."

The authors conducted a retrospective review of the clinical records of eight patients with sympathetic ophthalmia. Chlorambucil was administered in daily doses that were increased weekly to achieve bone marrow suppression. Steroids were tapered simultaneously.

No leukemia developed in patients treated less than 6 months or with a total daily dose of 1.5 grams. The initial dose was 2 mg daily orally with an increase of 2 mg each weekly until the white blood cell count was below 2,400/mm³ or the platelet count was below 10,000/mm³. When bone marrow suppression occurred, chlorambucil was stopped.

"After the therapy ended, all patients had remission of ocular inflammation; the median follow-up was 32 months (range, 9 months to 5.8 years). The total average dose was 1.9 grams (range, 1.1 to 2.9 grams), Dr. Echandi reported. One patient required platelet transfusion and antibiotics for oral mycosis. Vomiting and nausea were the most frequent side effects of the chlorambucil.

"This short-term high-dose chlorambucil therapy seems to be very highly effective to cure this chronic severe intraocular inflammation and also allows discontinuation of systemic corticosteroids," Dr. Echandi said. "It is important to begin therapy with a low dose (2 mg daily) to provide a margin of safety for idiosyncratic acute bone marrow depression and to perform complete blood cell counts weekly. Chlorambucil is a good alternative treatment choice because the total cost is lower compared with other immunosuppressive drugs that need longer treatment and allows the potential to suspend the use of systemic corticosteroids."

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