Ocular Toxoplasmosis

Toxoplasma gondii is a ubiquitous intracellular protozoan parasite, acquired most often by ingesting contaminated food or water and less frequently by maternal-fetal transmission. Approximately one-third of the world’s population has been infected by the pathogen – typically without symptoms.1 Ocular involvement has been estimated to occur in approximately 2% of those infected and is associated with a lifelong risk of recurrence and vision loss.2–12 This issue of Ocular Immunology & Inflammation (OII) contains an original article,13 a letter to the editor,14 and a companion editorial with original data,15 each of which addresses important aspects of ocular toxoplasmosis (OT).

Reich et al. report the results of a retrospective clinic-based cohort study of 40 women of childbearing age with OT followed for at least four years in the uveitis center at the University of Heidelberg.13 Of these, 11 (27.5%) completed full-term pregnancy during the follow up period. The remaining 29 patients served as aged-matched controls. Data from six women with OT reported over 30 years ago by Oniki et al16 were added to the pregnancy cohort. Only three recurrences occurred during the pregnant period. Hence, while the mean OT recurrence rate of 0.16 per year during pregnancy was numerically lower than the mean rate of 0.32 per year in the same 17 patients during their non-pregnant period, the observed difference failed to achieve statistical significance (p = 0.088). The mean recurrence rate in the 29 age-matched controls was similar to the mean rate observed in the 17 patients during their non-pregnant period (0.31 vs 0.32 per year, respectively). A similar trend toward a lower mean recurrence rate during pregnancy was recently reported by Braakenbur et al,17 who studied 50 women of childbearing age with OT in a university clinic in Utrecht, the Netherlands, where a total of six of 128 (4.7%) recurrences occurred during pregnancy. Using bivariate, unadjusted analyses, the authors found the annual recurrence rate during the pregnant period to be 17.6% (0.14 vs 0.17/year) to 53.2% (0.22 vs 0.47/year) lower than the rate during the non-pregnant period (both nominal p values < 0.05). Together, the results of these two studies would seem to refute the commonly held believe that rates of recurrence of OT increase during pregnancy.2–12 Of note, the risk of recurrence of OT has been shown to decrease with both increasing duration of disease and increasing time from most recent episode,18^,19 neither of which appear to have been controlled for in the aforementioned studies of recurrence rate during pregnancy. In addition, the studies by Reich et al and by Braakenbur et al were small and retrospective in nature, thereby limiting power and introducing the potential for both bias and confounding. Last, while the overall recurrence rates in the cited studies appear to be similar, it may be that populations exposed to different strains of T. gondii experience different rates of reactivation.20^,21

Yusuf et al.14 described an 81-year-old man who presented with panuveitis associated with a large, confluent area of retinochoroidal atrophy associated with adjacent foci of active retinitis four weeks after uncomplicated cataract surgery. Past medical history was notable for rheumatoid arthritis requiring chronic immunosuppression with 7.5 mg/day of prednisone and 12.5 mg/weekly of methotrexate. Atypical clinical features included the large size of the lesion, the simultaneous presence of multiple active foci, and continued progression of the area of involvement over time. The diagnosis was ultimately confirmed by the presence of T. gondii DNA in the vitreous and clinical improvement in response to antimicrobial therapy, which included two separate injections of intravitreal clindamycin. Both syphilis serologies and testing for the presence of herpes virus DNA or abnormal cells in the vitreous were negative. This report highlights several important aspects of OT. First, while OT tends to present as a single focus of retinitis and typically responses over four to six months with or without antimicrobial therapy, atypical presentations of OT can occur in immunosuppressed patients, including those with HIV/AIDS or who are immunosuppressed for other reasons, such as advanced age or the use of systemic immunosuppression22^,23 - the latter two of which were present in the patient reported by Yusuf et al.14 Second, analysis of intraocular fluids for the presence of T. gondii DNA can be quite useful when considering the possibility of OT, particularly in populations with a high seroprevalence of anti-T. gondii antibodies or when the presentation is atypical.24^,25 Third, intravitreal clindamycin, with or without intravitreal dexamethasone, can play an important role in the treatment of OT, especially when the macula or optic disc are either threatened or involved, or when there is limited response or intolerance to systemic antimicrobial therapy.26–31 And fourth, the recurrence of OT one month after uncomplicated cataract surgery begs the question of whether the surgical procedure itself played any role in causing disease reactivation. Whereas Bosch-Driessen et al observed reactivation of OT following cataract surgery in 5 of 15 eyes (33.3%) – all within four months of survery,32 a more recent analysis by Heringer et al of 69 patients who underwent intraocular sugery reported reactivation in four eyes (5.8%), only one of which occurred within four months of the procedure (1.4%).33 As mentioned above, the most important non-age-related clinical determinants of reactivation risk would appear to be duration of disease and the time from the immediate past episode18^,19 - neither of which were mentioned in the studies of post-operative reactivation. Hence, the relative contribution of intraocular surgery per se to low rate of OT reactivation following such procedures remains unknown – and, in fact, such reactivation events may be coincidental.

Silveira et al.34 and Felix et al.35 have each showed independently that long-term, intermittent treatment with trimethoprim (160 mg)/sulfamethoxazole (800 mg) given once every two to three days reduces the risk of recurrence of OT. Of note, however, ten year follow up data reported by Silvera et al in this issue of OII demonstrated that the protective effect was limited to the treatment period.15 Perhaps, then, both long-term intermittent and perioperative prophylactic treatment with trimethoprim/sulfamethoxazole makes most sense for patients with frequent, severe recurrences, or for those with Zone 1 lesions36 in whom any given recurrence might be associated with a high risk of irreversible vision loss.37–39

Declaration of interest

The authors have no relevant financial conflicts.

Supported in part by The Pacific Vision Foundation (ETC), The San Francisco Retina Foundation (ETC), and Conselho Nacional de Pesquisas (CNPq),Brazil (CM, RB).