Therapeutic alternatives for the treatment of ocular toxoplasmosis

Ocular toxoplasmosis is caused by Toxoplasma gondii, inducing retinochoroiditis. It is the leading cause of infectiousposterior uveitis worldwide. Its treatment is based on oral drug administration. However, the blood–ocular barriersystems make the penetration of therapeutic drug concentrations within the eye difficult, limiting the effectiveness oftreatments. In this context, ocular drug delivery systems represent therapeutic alternative for the treatment of oculartoxoplasmosis. In this study, a review of clinical manifestations, diagnosis, treatment, and perspectives regardingthe treatment of ocular toxoplasmosis was conducted. A search was carried out on ScienceDirect, Scopus, Webof Science, PubMed, and SciELO, and the following keywords were used: toxoplasmosis, ocular toxoplasmosis,toxoplasmic retinochoroiditis, and congenital toxoplasmosis; and Boolean operators, associated with other keywords,such as epidemiology, ocular toxoplasmosis diagnosis, ocular toxoplasmosis treatment, and ocular toxoplasmosisperspectives, were applied. In conclusion, ocular toxoplasmosis still lacks effective treatment. Therefore, it is essentialto develop new molecules and/or new drug delivery systems capable of releasing therapeutic doses of anti-Toxoplasmadrugs directly in the posterior segment of the eye, for an extended period, since complications resulting from thedisease may shorten the productive life of individuals and may even lead to blindness

Intravitreal Clindamycin Injection for Toxoplasmic Retinochoroiditis

PURPOSE: To present cases of toxoplasmic retinochoroiditis (TRC) treated successfully with intravitreal clindamycin injection. CASE SUMMARY: (Case 1) A 41-year-old man presented with blurred left eye vision for several months. The patient had a large chorioretinal scar with infiltrations at the boundaries, and fluorescein angiography (FA) showed active retinochoroiditis. Antitoxoplasmosis (antiTX) immunoglobulin G (IgG) was positive, and the patient was started on antiTX medication. Despite several weeks of treatment with maximum doses of antiTx, the TRC progressed and visual acuity worsened. Pars plana vitrectomy (PPV) with intravitreal clindamycin injection (1.0 mg/0.1 ml) was performed, and an additional injection was given 4 weeks later. Six weeks after the second injection, TRC wascompletely resolved with 20/20 vision. (Case 2) A 67-year-old man presented with decreased left eye vision for 1 year. Fundus examinations showed vitreous opacity and epiretinal membranes. The FA revealed retinochoroiditis and the antiTX IgG titer was elevated. The presumed diagnosis was TRC, and oral medications of trimethoprim-sulfamethoxazole, clindamycin, and prednisolone was administered. Inflammation began to improve however, as the patient was not tolerating systemic antiTx medications, an intravitreal injection of clindamycin (1.0 mg/0.1 ml) was administered with PPV. The patientdiscontinued oral medication after surgery, and the inflammation resolved 5 weeks later. CONCLUSIONS: Intravitreal clindamycin injections may be an additional treatment option for TRC in patients who are unable to tolerate systemic therapy or whose disease progresses despite systemic therapy.

Candidate gene analysis of ocular toxoplasmosis in Brazil: evidence for a role for toll-like receptor 9 (TLR9)

Toxoplasma gondii infection is an important mediator of ocular disease in Brazil more frequently than reported from elsewhere. Infection and pathology are characterized by a strong proinflammatory response which in mice is triggered by interaction of the parasite with the toll-like receptor (TLR)/MyD88 pathway. A powerful way to identify the role of TLRs in humans is to determine whether polymorphisms at these loci influence susceptibility to T. gondii-mediated pathologies. Here we report on a small family-based study (60 families; 68 affected offspring) undertaken in Brazil which was powered for large effect sizes using single nucleotide polymorphisms with minor alleles frequencies > 0.3. Of markers in TLR2, TLR5 and TLR9 that met these criteria, we found an association Family Based Association Tests [(FBAT) Z score = 4.232; p = 1.5 x 10-5; p corrected = 1.2 x 10-4] between the C allele (frequency = 0.424; odds ratio = 7; 95 percent confidence interval 1.6-30.8) of rs352140 at TLR9 and toxoplasmic retinochoroiditis in Brazil. This supports the hypothesis that direct interaction between T. gondii and TLR9 may trigger proinflammatory responses that lead to severe pathologies such as the ocular disease that is associated with this infection in Brazil.

Bilateral Toxoplasma Retinochoroiditis Simulating Cytomegalovirus Retinitis in an Allogeneic Bone Marrow Transplant Patient

A 36-year old female with acute myelogenous leukemia presented with a sudden decrease in vision one month following bone marrow transplantation (BMT). She had been taking multiple immunosuppressants to treat her recently-developed graft-versus-host-disease (GVHD). Visual acuity was 20/60 in her right eye and 20/25 in her left. Ophthalmic examination revealed mild inflammatory reaction in both the anterior chamber and the vitreous of both eyes, as well as densely opaque yellow-white infiltrates with well-demarcated borders in the posterior retina of both eyes. She was originally diagnosed as CMV retinitis, but treatment with ganciclovir failed to improve her ocular condition. Subsequent work-up, including serology and brain MRI, led to a diagnosis of combined ocular and cerebral toxoplasmosis. After 6 weeks of antiparasitic therapy, her retinal lesions became inactive and her cerebral lesions improved. Immunosuppressed patients with necrotizing retinochoroiditis should be suspected of having toxoplasmosis. Accurate differentiation between this condition and CMV, and early intervention with the appropriate treatment may be critical to preserve the best vision.