The Effect of Long-term Intermittent Trimethoprim/Sulfamethoxazole Treatment on Recurrences of Toxoplasmic Retinochoroiditis: 10 Years of Follow-up

Toxoplasmosis is one of the most common causes of infectious retinitis, accounting for 30–50% of posterior uveitis in Brazil.1 Ocular toxoplasmosis is characterized by episodes of necrotizing retinochoroiditis thought to be caused by both proliferation of live organisms that emerge from tissue cysts and an associated inflammatory reaction. Recurrent toxoplasmic retinochoroiditis can be associated with severe morbidity.2 The current approach to treatment of recurrent toxoplasmic retinochoroiditis involves courses of anti-Toxoplasma gondii therapy, with or without corticosteroids, at the onset of recurrences. No available drug eliminates tissue cysts from the eye and treatment therefore does not prevent recurrences.

We hypothesized that long-term treatment may reduce recurrences and tested this hypothesis in a prospective randomized clinical trial.3 Patients were treated with trimethoprim/sulfamethoxazole. In that study patients received a single tablet of a commercially available combination of trimethoprim (160 mg) and sulfamethoxazole (800 mg; Bactrim F) every 3 days for 20 months. Children were treated with a commercially available liquid suspension of trimethoprim (40 mg/5 mL)/sulfamethoxazole (200 mg/5 mL) at a dose of 0.375 mL/kg orally every 3 days. Patients in the control group received no treatment, the accepted standard of care. Our study demonstrated that trimethoprim/sulfamethoxazole treatment can, however, reduce the rate of recurrent toxoplasmic retinochoroiditis during the period of treatment. Recurrences developed in 4 (6.6%) treated patients and in 15 (23.8%) controls (p = .01).

We wished to evaluate the possible benefit of this regimen even after its discontinuation.

The initial study ended in 2000 and 116 of the 124 original patients were followed from 2000 to 2010 with 59 (50.86%) from the treated group and 57 (49.13%) from the control group. After 10 years the recurrence rate was the same in both groups (22 in each group), suggesting that the prophylactic treatment effect disappears when the treatment is stopped. Thus, long-term intermittent treatment with trimethoprim/sulfamethoxazole can reduce the rate of recurrent toxoplasmic retinochoroiditis only when the patient is being treated.

Long-term therapy may play a role in the management of ocular toxoplasmosis in specific situations. It might be most appropriate for individuals or populations with demonstrated histories of frequent and severe recurrences. It might also be considered for people at greatest risk of vision loss, such as those with retinochoroidal scars adjacent to the fovea, where any reactivation can result in profound vision loss.

Declaration of interest

Dr. Belfort has served on advisory boards or has received grants from Alcon-Novartis, Allergan, Kemin, NovaBay, Ophthalmos, Bayer, and Santen. None of the other authors have financial disclosures.

Supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico and the Fundação de Amparo à Pesquisa do Estado de São Paulo (CNPq/FAPESP; Drs. Silveira, Muccioli, and Belfort) and the Intramural program, NEI, NIH (Dr. Nussenblatt).

Author contributions: Study design (CS, RBJ, RN), data collection: (CS), data management and analysis (CS, RN, RBJ), data interpretation (CS, CM, RN, RBJ), preparation of initial draft, review and approval of manuscript (CS, CM, RN, RBJ).