How Do I Treat a Patient With Ocular Toxoplasmosis?
Toxoplasma gondii is the most common cause of retinal infections in otherwise healthy individuals, and it can cause severe, blinding disease in those with immunodeficiency states. Diagnosis is usually based on the typical appearance of a focal necrotizing lesion (Figure 26-1), often arising from the border of a pre-existing retinochoroidal scar, as recurrent disease (Figure 26-2). A substantial proportion of the general population is infected with T. gondii; therefore, serum antibody tests are usually of little diagnostic utility. I believe that it is appropriate to treat suspected lesions without laboratory confirmation (as might be obtained with PCR testing of vitreous humor specimens).
Figure 26-1. A large retinochor-oidal lesion in the left macula of an immunocompetent adult with postnatally acquired Toxoplasma gondii infection. (Reprinted with permission of Holland GN. Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and management. Am J Ophthalmol. 2004;137:1-17, with permission from Elsevier.)
Figure 26-2. Recurrent toxoplasmic retinochoroiditis in an immunocompetent adult patient. There is a “satellite lesion” associated with pre-existing retinochoroidal scars and a mild overlying vitreous inflammatory reaction. (Reprinted with permission of Holland GN. Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and management. Am J Ophthalmol. 2004;137:1-17, with permission from Elsevier.)
My choice of therapy for active disease depends primarily on the immune status of the patient. For the majority (those with normal host defenses), I treat with a combination of antimicrobial agents and corticosteroids, despite the fact that the value of such therapy has never been shown in well-designed clinical trials.1 Most clinicians agree that treatment does have some beneficial effects, but lack of confirming evidence for any given treatment has resulted in a variety of drugs being used2 (the fact that treatment efficacy has never been proven may simply reflect a lack of appropriate studies). By tradition, I still use “classic therapy” (pyrimethamine with folinic acid to reduce the risk of drug-associated side effects, sulfadiazine, and prednisone). Another, more convenient combination of a dihydrofolate reductase inhibitor and sulfonamide that is gaining increased popularity is trimethoprim/sulfamethoxazole (Bactrim, Septra). It is thought to be useful, despite animal studies showing it to be less effective than pyrimethamine/sulfadiazine. In patients who are allergic to sulfonamides, I use atovaquone as an alternative to pyrimethamine/sulfadiazine. Drug doses are listed in Table 26-1. With severe disease, I have occasionally added a fourth drug (clindamycin, the combination known as “quadruple therapy”2), although I am not convinced that it is more effective to do so.
I suspect that corticosteroids are the most important component of treatment for recurrent lesions in most otherwise healthy patients. It is likely that parasites reproduce for only brief periods of time and may already be encysted again in an inactive form by the time antimicrobials are taken. Corticosteroids limit the damaging effect of inflammation, but corticosteroids alone can lead to exacerbation of infection if active parasites are still present; antimicrobials protect against such proliferation. I wrote about many of these concepts in a comprehensive review, published elsewhere.3
Patients often have an anterior chamber cellular reaction, with redness and elevated intraocular pressure, at the onset of an active retinal lesion. Also by tradition, I treat those cases with a topical corticosteroid, but the risk of complications (eg, posterior synechiae) is small, and these reactions seem to resolve with systemic treatment alone. Elevated intraocular pressure will resolve without glaucoma medications.
With regard to duration of treatment, I continue drug therapy until lesion borders begin to “harden” and become more distinct (generally by 4 to 6 weeks), at which time I will rapidly taper and discontinue corticosteroids. I stop antimicrobials completely after corticosteroids have been stopped (antimicrobials should never be “tapered”). Vitreous haze may persist for months, but I do not consider it alone as an indication for continued treatment.
The goal of treatment is to hasten resolution, but because disease is self-limited with normal immune defenses, it is probably appropriate to observe some lesions without treatment, especially if they are small, in the peripheral retina, and without substantial vitreous haze. In that situation, I generally discuss the option of observation with patients, letting them decide whether to start treatment based on its potential risks, benefits, and expense. Patients who are observed without treatment should be followed closely; I reconsider treatment if vitreous haze increases and vision changes. Observation is an appropriate strategy for pregnant women with recurrent disease (a situation in which there is little potential for fetal damage because of pre-existing maternal antibodies). For pregnant women with newly acquired T. gondii infection, or with retinal lesions that are vision-threatening, choice of drug therapies should be made in conjunction with the patient’s obstetrician and an infectious disease specialist.2
There is less doubt about the need for treatment of toxoplasmic retinochoroiditis in immunodeficient patients (eg, people with AIDS or those on immunosuppressive drug therapy). Without treatment, lesions will continue to enlarge, suggesting persistent parasite activity. Disease in elderly individuals may behave in a similar manner, probably because of waning host defenses. In such cases, I treat with antimicrobials alone. With persistent immunodeficiency, chronic therapy may be necessary. Options include trimethoprim/sulfamethoxazole or atovaquone; usually, one drug is sufficient.
In selected immunocompetent patients, I also administer long-term treatment as secondary prophylaxis to prevent recurrences. I do so based on a study undertaken in Brazil, in which trimethoprim/sulfamethoxazole, given every 3 days over a 20-month period, reduced the risk of recurrences.4 I offer secondary prophylaxis to patients with histories of frequent recurrences or with lesions that would be immediately vision threatening with recurrence (eg, parafoveal lesions). If treatment is tolerated medically, I continue it for at least 2 years (when risk of recurrence is highest); however, some of my patients have elected to continue treatment for years. Regimens and alternatives were shown in Table 26-1.
1. Stanford MR, See SE, Jones LV, Gilbert RE. Antibiotics for toxoplasmic retinochoroiditis: an evidence-based systematic review. Ophthalmology. 2003;110:926-931.
2. Holland GN, Lewis KG. An update on current practices in the management of ocular toxoplasmosis. Am J Ophthalmol. 2002;134:102-114.
3. Holland GN. Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and management. Am J Ophthalmol. 2004;137:1-17.
4. Silveira C, Belfort R Jr, Muccioli C, et al. The effect of long-term intermittent trimethoprim/sulfamethoxazole treatment on recurrences of toxoplasmic retinochoroiditis. Am J Ophthalmol. 2002;134:41-46.