and 1 mg of dexamethasone (in 0.1 mL) given intravitreally. In three of the patients systemic medications were continued. A favorable response was seen within 2 weeks. All patients needed three to four injections. As mentioned earlier, the question of which therapeutic combination is more effective in treating the acute disease and preventing recurrences has not been evaluated in a randomized study. It was initially thought that clindamycin might prevent recurrences, but this has not been the case (RJ Belfort, personal communication, 1992).

There is now evidence to suggest that treating congenitally acquired disease does have a positive therapeutic effect, though one could wish it were even more effective. In a cohort of 25 children diagnosed with congental toxoplasmosis, who were not treated during their first year of life and who had an average followup of 5.7 years, 18 (72%) had at least one new lesion, with 13 of them having lesions in their macula.155 Indeed, new lesions were noted after the first decade of life in some. This is in contrast to 132 children with congental toxoplasmosis who were treated with anti- Toxoplasma medication (pyrimethamine, sulfadiazine, and leucovorin) during the first year: 34 (31%) developed new eye lesions, with 15 (14%) being in the macula.156 McLeod and coworkers157 have reported the overall neurologic longterm effects of therapy for 1 year (with sulfadiazine and pyrimethamine) in children with congenital toxoplasmosis. Those with no substantial neurologic damage all had normal cognitive, neurologic and auditory outcomes. For those with significant neurologic damage early in their life, the results are not as positive.

A trimethoprim/sulfamethoxazole combination has been used by some clinicians. In principle this would inhibit the synthesis of tetrahydrofolic acid, as does pyrimethamine. This combination of trimethoprim/sulfamethoxazole was evaluated in the treatment of toxoplasmosis by Opremcak and colleagues,158 who found that in all 16 patients studied active retinochoroiditis resolved and vision improved. Two patients had drug allergies. In a recent study in Brazil159 124 patients with a history of ocular toxoplasmosis were randomly assigned either to receive intermittent trimethoprim/ sulfamethoxazole (Bactrim) therapy or to be observed. Over a 20-month period of follow-up there was a significant reduction in ocular attacks in the trimethoprim/sulfameth- oxazole-treated group.

Another drug used with positive results in the treatment of toxoplasmosis is atovaquone (Mepron). Of great potential interest is its ability to kill Toxoplasma cysts in vitro,160 and others have shown that atovaquone reduced the number of cerebral cysts in a Syrian gold hamster model.161 If this action were true in humans, it would be conceivable that one therapeutic course with this agent could prevent recurrences, assuming adequate levels of the drug were available to resolve the infection completely. Atovaquone is a quinolone derivative first developed because of its antimalarial properties. It has been used most extensively in the treatment of CNS toxoplasmosis, with reasonably good results.162 We reported its use in the treatment of ocular toxoplasmosis in a patient with AIDS who was unable to continue more standard therapy, with a very good therapeutic response.163 Anecdotal reports do not seem to support the notion that recurrences can be eliminated with atovaquone.164 However, in a study of immunocompetent patients, therapy with

Therapy

atovaquone 750 mg four times daily for 3 months combined with 40 mg of prednisone in 17 patients resulted in a positive therapeutic outcome.165

Empiric observations in the immunoincompetent host (e.g., patients with AIDS) have shown that the disease will be arrested only with therapy and will reactivate once the therapy has been stopped. Allergies to drugs as well as other side effects always complicated the therapeutic approach. With the cellular response so important for host defense, before the availability of highly active antiretroviral therapy (HAART), long-term anti-Toxoplasma therapy was needed. However, it is not yet clear how HAART alters this treatment approach in patients with AIDS.

Additional therapeutic approaches

Cryotherapy of peripheral lesions that cause enough vitreal inflammatory activity to affect vision can also be considered. However, excessive cryotherapy applied to these ‘hot’ eyes could potentially induce unwanted and excessive vitreous condensation and membrane formation, ultimately pulling on the retina and causing retinal detachment. Photocoagulation has also been advocated by some as a means to treat toxoplasmosis. Ghartey and Brockhurst166 described their experience in treating five eyes with toxoplasmic lesions unresponsive to antimicrobial therapy and corticosteroids. Photocoagulation treatment was thought to benefit four eyes, with healing of the lesion after a few weeks. Others have suggested that such treatment could reactivate dormant cysts, leading to a renewal of ocular disease.

Therapies addressing choroidal neovascularization have been evaluated in the treatment of this complication secondary to ocular toxoplasmosis. PDT167, 168 and avastin injections169,170 have been used by several, with the results (albeit in a small number of patients) that the CNV seems amenable to these therapies. There is one caveat: one report recounted a patient who received PDT and an intraocular steroid injection and returned 45 days later with a necrotizing retinitis and high IgG toxoplamosis titers.171 Laser therapy in the case reported above of multiple CNV lesions in one eye resulted in recurrence of the lesions.57

Vitrectomy and lensectomy can be performed on these eyes to remove vitreous and lens opacities that affect vision.172 Significant vitreous condensations can form in eyes having a history of multiple episodes of inflammation due to toxoplasmosis. In patients with toxoplasmosis who are undergoing vitrectomy, we usually begin antimicrobial therapy before surgery and continue it postoperatively. Prophylaxis is also suggested for cataract extraction.50 The rationale for this approach is the concern that the nonspecific inflammation induced by the vitrectomy might initiate an inflammatory episode of toxoplasmosis. We would not use periocular steroid injection after the procedure, but will give steroids by mouth if indicated.

Case 14-1

A 28-year-old white man was first seen at the National Eye Institute in March 1981. He was complaining of a reduction in vision with floaters in the left eye for over 1 week. The vision in his right eye was 20/20 and in the left 20/25. The anterior chambers were quiet. There was 1+ haze in the vitreous of the

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