Part 4 • Infectious Uveitic Conditions

Chapter 14 Ocular Toxoplasmosis

acquired disease, 20 presented with retinal findings; seven of these lesions were in the macular region. A similar epidemic was recently evaluated in Santa Isabel do Ivai in the Parana state of Brazil, where cat feces contaminated drinking water and led to over 600 occurrences of acquired toxoplasmosis (Cristina Muccioli, MD, Claudio Silveira, MD, and Rubens Belfort Jr, MD, personal communication 2005). In one study of 14 patients with postnatally acquired toxoplasmosis who were followed for 4.6 years, recurrent ocular disease occurred in 57%.139 Another outbreak occurred in Coimbatore, India. This was first noted because of a sudden increase in September 2004 of seropositivity in patients coming to an eye clinic.140 In this report by Palanisamy et al., 249 cases were tested and 178 had high titers of both IgG and IgM to the Toxoplasma organism. The majority of the cases came from an area with a single water reservoir, suggesting that contamination was through the municipal water system.

The notion that an unborn child may be ‘protected’ by the mother’s being seropositive at the time of pregnancy has been questioned for years. The group in Brazil141 has reported the case of a woman in whom toxoplasmosis had been diagnosed 20 years earlier and who then delivered a child with toxoplasmosis. Both reactivated and newly acquired disease with genetically different strains or lineages of T. gondii are possible explanations. An excellent review of this whole subject is available to those who read Portuguese.142

Therapy

An initial decision of whether the Toxoplasma-induced lesion needs to be treated must be made. We know that in the immunocompetent person the disease is ultimately selflimited. For us, the decision to treat generally would be based on the following criteria:

•A lesion within the temporal arcade;

•A lesion abutting the optic nerve or threatening a large retinal vessel;

•A lesion that has induced a large degree of hemorrhage;

•A lesion that has induced enough of a vitreal inflammatory response that the vision has dropped below 20/40 in a previously 20/20 eye, or at least has sustained a two-line drop from the visual acuity before the acute infection;

•A relative indication would be the case of multiple recurrences that develop marked vitreal condensation. Here one might be concerned that the continuation of this process might lead to retinal detachment.

Which drug or combination of drugs should one use? Few if any fully powered randomized studies have been published to answer this question completely. Results of a nonrandomized study comparing three therapeutic regimens

– pyrimethamine, sulfadiazine and steroid; clindamycin, sulfadiazine, and steroid; and trimethoprim and sulfamethoxazole – did not show a difference in the duration of the inflammation among therapy arms.143 However, 52% of patients in the group receiving pyrimethamine had a reduction in the size of the retinal inflammatory focus, versus 25% of the untreated group (peripheral lesions). Stanford and colleagues,144 after performing an evidence-based systematic

review of antibiotic therapy for toxoplasmosis, felt that there was lack of evidence to support routine antibiotic treatment for acute ocular disease. A single masked study in Iran compared trimethoprin/suflamethoxazole versus pyrimethamine/sulfadiazine (both groups received oral steroids): 59 patients were randomized and the authors reported no difference in the two groups in terms of retinal lesion quieting and visual acuity. A survey by Holland and Lewis145 asked experts on uveitis how they manage this disease. The 97 respondents do treat, and reported using a total of nine drugs in 25 different regimens. As the first drug combination for the treatment of ocular toxoplasmosis we still use sulfadiazine (1 g orally four times daily) and pyrimethamine (50-mg loading dose and then 25 mg orally twice daily), always given concomitantly with folinic acid 3–5 mg three times per week; this is also the combination most commonly employed by the experts (28%) surveyed by Holland and Lewis. A baseline platelet count followed by weekly counts are obtained for the duration of the folinic acid therapy, which we continue for 1 week after stopping the pyrimethamine. We generally treat immunocompetent patients for 3–4 weeks with this regimen, and judiciously add prednisone to the regimen if the lesion is in the posterior pole or threatening the optic nerve head. Generally we use 20– 40 mg/day of prednisone in the adult patient, beginning 12–24 hours after initiation of the specific antimicrobial therapy. If the macula or optic nerve is threatened we do not hesitate to see the patient frequently, trying to taper the prednisone in such a way that it is stopped before the anti- Toxoplasma therapy is discontinued. It is important to stress that immunosuppressive therapy (prednisone) should never be used alone, but only under the therapeutic cover of the specific antimicrobial therapy, nor do we give it at higher doses for any prolonged period. Periocular injections of corticosteroids are not to be used. Sabates and coworkers146 reported the cases of seven patients in whom the disease was particularly destructive and disseminated, and all were initially treated with corticosteroids alone. We do not use intravitreal steroid injections to treat this disease, our concern being that such high levels in the eye will overcome the antimicrobial effect and lead to reactivation, echoing concerns raised by others.147 Cytotoxic agents do not have a role in the treatment of this infection.

Clindamycin (150–300 mg orally three or four times daily) combined with sulfadiazine has also been shown to be effective in treating this disorder,148,149 and as mentioned earlier has been used intravitreally in pregnant patients,120 but also in those unable to tolerate systemic medication.150 Because the two agents affect unrelated pathways, it may be that the combination could have synergistic effects, although not perhaps as effective as the combination of pyrimethamine and sulfadiazine.151 Although it is a useful approach, the potential for diarrhea and the serious complication of pseudomembranous colitis at worst is problematic. In one study in Germany152 15 of 90 patients treated with clindamycin combined with fluorocortolone had side effects, including diarrhea, allergic exanthem, mild lymphopenia, hepatotoxicity, and gastrointestinal bleeding. The drug was withdrawn in eight patients. Clindamycin has also been given in 50-mg subconjunctival injections, with positive clinical results observed.153 Kishore and associates154 reported treating four patients with 1.0 mg of clindamycin (in 0.1 mL)