Ocular toxoplasmosis (OT) is an intraocular infection caused by the parasite Toxoplasma gondii. OT is manifested as retinal choroiditis and is the most common infectious cause of posterior uveitis. Invasion of the retina by T. gondii leads to disruption of the blood-ocular barrier and promotes the migration of immune cells to the ocular tissues. Cytokines such as IFN-γ and IL-1β are effective for controlling parasite growth, but excessive inflammatory responses can cause damage to the host. In this review, we will discuss in detail the latest advances in the immunopathology and treatment of OT.

Ocular toxoplasmosis (OT) is characterised by intraocular inflammation due to Toxoplasma gondii infection. Studies have found that interleukin 17 (IL-17) plays a central role in the pathology of OT. However, nucleotide variability in IL17 and interleukin 17 receptor (IL17R) genes has not been characterised in OT. As cytokine gene polymorphisms may influence the expression of these molecules, the aim of this study was to verify whether IL17A (rs2275913), IL17F (rs763780), IL17RA (rs4819554) and IL17RC (rs708567) polymorphisms are associated with OT in a Brazilian population. This study enrolled 214 patients seropositive for T. gondii (110 with OT and 104 without) and 107 controls. Polymorphisms were identified by PCR-restriction fragment length polymorphism analysis, validated by DNA sequencing with chi-square and multivariate analyses being used to assess possible associations between polymorphisms and OT. Logistic regression under the dominant model revealed a protection factor against OT of the C mutant allele of the IL17F (rs763780) polymorphism. The T/C-C/C genotypes were significantly more common in patients without OT compared to those with OT (p value = 0.0066) and controls (p value = 0.014). Findings from this study suggest that the IL17F polymorphism may have an influence in the immunopathology of OT in Brazilian individuals.

Toxoplasma chorioretinitis (TC) can exhibit atypical features in immunocompromised patients including bilaterality, extensive spread, multifocal presentation, large areas of retinal necrosis without adjacent retinal scarring, and diffuse necrotizing retinitis resembling the viral retinitis that may cause confusion in the differential diagnosis. The aim of this study was to present the clinical features of four eyes of three immunocompromised patients with active toxoplasma chorioretinitis. Two of the patients were female and one, male. Two patients had hematological malignancies and the remaining patient was under adalimumab treatment for ankylosing spondylitis. Visual complaints began 10 days to four months prior to TC diagnosis. All four eyes had mild-to-moderate anterior chamber cells together with severe vitritis on slit-lamp examination while there were solitary chorioretinitis lesions on fundoscopy. Despite all patients were negative for anti-toxoplasma immunoglobulin M, all were positive for immunoglobulin G. All three patients were successfully treated with a combined treatment of systemic and intravitreal anti-toxoplasmic drugs. Clinicians should be cautious for the possible toxoplasma chorioretinitis besides the other infectious entities when a new uveitis episode is detected in an immunosuppressed patient in order to avoid misdiagnosis and thereby wrong treatment.

The aim of this study was to describe a case of a patient with ocular toxoplasmosis, which has resulted in Kyrieleis plaques formation (segmental periarteritis associated with severe inflammation) and later follow-up and alternative treatment due to documented allergy to sulfonamide. A 33-year-old Brazilian woman diagnosed with acute toxoplasmosis, initially treated with sulfonamide, developed a critical cutaneous rash. Cotrimoxazole was changed to clindamycin and pyrimethamine, and prednisone was started. The medication was maintained for 45 days. Four months later, she developed retinal lesions suggestive of toxoplasmosis with Kyrieleis plaques in the upper temporal vessels. Pyrimethamine, clindamycin, and prednisone were initiated until healing. She presented reactivation months later, and a suppressive treatment with pyrimethamine was instituted for one year. This is the first report to use the combination of clindamycin with pyrimethamine in the treatment and recurrence prophylaxis for OT in a documented allergy to sulfonamide.

UNASSIGNED: To present an atypical case of severe bilateral ocular toxoplasmosis with systemic involvement that initially mimicked an autoimmune etiology, posing challenges to its diagnosis and treatment.
UNASSIGNED: A 39-year-old immunocompetent male was admitted to the hospital due to a presumed pulmonary thromboembolism concomitant with an abrupt onset of vision loss. Initial differential diagnoses included antiphospholipid syndrome and systemic lupus erythematosus, prompting the administration of corticosteroid pulses and rituximab. Despite observing a partial systemic response, there was no improvement in visual acuity. Subsequent aqueous humor polymerase chain reaction confirmed Toxoplasma gondii infection, leading to the introduction of oral antibiotic therapy. The patient\'s condition showed a partially favorable response; however, the treatment could not reverse the permanent retinal damage.
UNASSIGNED: This case underscores the importance of ruling out an infectious etiology in all cases of uveitis. Additionally, it alerts clinicians to the possibility that elevated positive autoantibodies may result from a severe inflammatory reaction caused by pathogens rather than an autoimmune or autoinflammatory disease, particularly in instances of poor treatment response or atypical clinical presentation.

Aim: To determine the prevalence of ocular toxoplasmosis among people living with HIV through a systematic review and meta-analysis. Materials & methods: A literature search was conducted, estimating pooled prevalence and performing quality assessment, outlier, influential and meta-regression analyses. Results: Twenty-nine studies were included in the analysis, revealing that the rate of ocular toxoplasmosis among people living with HIV was 0.37% (95% CI: 0.2-0.6). Substantial heterogeneity was observed among the studies. Despite analyzing continuous variables, including year of publication, proportion of males, mean age and proportion of patients receiving antiretroviral therapy, no statistically significant associations were found. Conclusion: This study provides an overview of the prevalence of ocular toxoplasmosis in people living with HIV, emphasizing the need for further research to uncover factors contributing to its development.
This study looked at how common ocular toxoplasmosis, a type of parasitic infection, is among people living with HIV. We did this by reviewing other studies, combining their results and evaluating the quality of each study. We also looked for any unusual findings and other factors that might affect the prevalence of ocular toxoplasmosis. After analyzing 29 studies, we found that approximately 0.37% of people living with HIV had ocular toxoplasmosis, ranging from 0.2% to 0.6%. There was a significant variation in the results among the studies. Our study provides an overview of the prevalence of ocular toxoplasmosis in people living with HIV, highlighting the need for further research to identify the factors contributing to its development.

UNASSIGNED: This study aimed to investigate the association between age, immune response, and clinical presentation of ocular toxoplasmosis (OT).
UNASSIGNED: This was a monocentric, retrospective, observational cohort study.
UNASSIGNED: A review of the medical records of patients with active OT at the Uveitis Center, Charité Universitätsmedizin, was conducted. Baseline parameters included age at presentation, visual acuity, intraocular pressure (IOP), size and location of active lesions, inflammatory activity, antibody index (AI), and complications of intraocular inflammation. The data were presented as the mean ± standard deviation (SD). The level of significance was set at a p-value of <0.05.
UNASSIGNED: Between 1998 and 2019, 290 patients with active OT were diagnosed at our tertiary reference center. The mean age of the participants was 37.7 ± 17.1 years, 53.8% of them were female individuals, and 195 patients (70.9%) showed recurrent disease. Older age was associated with lower baseline visual acuity (p = 0.043), poor visual outcome (p = 0.019), increased inflammatory activity (p < 0.005), and larger retinal lesions (p < 0.005). Older patients presented a lower AI (<35 years: 45.1 ± 82.7, median: 12.1; ≥35 years: 18.6 ± 50.5, median: 5.8; p = 0.046), confirmed by a decrease in AI with increasing age (R2 = 0.045; p = 0.024). Finally, AI was correlated with lesion size (multiple linear regression analysis: p = 0.043). Macular involvement (24.3% of patients) was positively correlated with complications (macular/peripapillary edema and retinal detachment, p < 0.005) and poor visual outcome (p < 0.005) and was negatively correlated with inflammatory activity (p < 0.005).
UNASSIGNED: We found a strong and clinically relevant impact of age on the clinical presentation and course of OT. While an unspecific inflammatory response increased with age, the specific, local humoral immune response declined. These findings are well in line with the concept of immunosenescence and inflammaging in uveitis.

UNASSIGNED: To describe the effect of long-term, low-dose pyrimethamine for the prevention of ocular toxoplasmosis (OT) recurrences.
UNASSIGNED: Sixty-three consecutive patients with inactive ocular toxoplasmosis and positive toxoplasma IgG serology were included. Pyrimethamine (25 mg) + folinic acid (15 mg) were administered every other day (three times weekly) for 12 months. Eighteen patients received the treatment for an additional six months as part of an extension study.
UNASSIGNED: Thirty-eight patients (60.3%, n = 63) were female; 38 (60.3%) had a previous history of recurrence and 37 (58.7%) had active OT within the preceding 12 months. Three (4.8%) patients had unilateral recurrences at 8, 12 and 18 months after starting intermittent pyrimethamine treatment. Five patients (7.9%) were discontinued due to hematological, renal and hepatic changes. Treatment was considered successful in 42 patients (84%).
UNASSIGNED: Long-term, low-dose pyrimethamine can be considered as a treatment option for the prevention of ocular toxoplasmosis recurrence in selected patients, with only a few, mild and reversible systemic adverse events.

Ocular toxoplasmosis is likely the most common cause of infectious posterior uveitis worldwide. CXCL10 chemokine has an important role in the maintenance of the T-cell response and the control of Toxoplasma gondii in the eye during chronic infection. Drugs that can modulate the chemokine activity could be effective against the parasite. In this work, CXCL10 local retinal expression was investigated in a diabetic mouse model with ocular toxoplasmosis for the first time. In addition, the efficacy of naphthoquinones and quinolones was compared to spiramycin (SP) in treating the infection and modulating the chemokine expression. Our results revealed that chloroquine (CQ) achieved the best results regarding the reduction of cerebral cyst burden (84.36%), improving the retinal histopathological changes, cellular infiltrates, and vasculitis significantly (P < 0.005), and balancing the strong CXCL10 expression caused by the infection. Buparvaquone-treated mice showed a significant percentage of reduction of brain cysts (76.25%), moderate improvement of histopathology, and mild to moderate CXCL10 expression. While SP showed the least efficacy against the parasite in the eye in the form of mild improvement of histopathological changes and downregulation of retinal chemokine expression with the least reduction rate of cerebral parasitic burden (57%). In conclusion, Optimal control of pathogens probably needs a balanced immune response with an optimum expression of chemokines. So, targeting the modulation of retinal CXCL10 may eventually be beneficial in the management of ocular toxoplasmosis plus its potential to act as a marker for predictive local immunological response during the infection.

BACKGROUND: Toxoplasma gondii causes ocular toxoplasmosis (OT), involving inflammation, scarring, and retinal complications. The OT complications were retinal detachment (RD), and retinal breakage (RB). Surgical interventions like scleral buckling (SB) and vitrectomy are common. Limited understanding exists of the safety and efficacy of surgical management of RD/RB secondary to OT. Another complication is toxoplasmosis-related macular holes (tMH), with sparse evidence on surgical outcomes. This meta-analysis aims to clarify clinical characteristics, and surgical results, and enhance understanding of RD, RB, and MH secondary to OT.
METHODS: PubMed, Cochrane, Embase and Web of Science database were queried for retrospective studies, case series and case reports that provided information on RD, RB and MH associated with OT and reported the outcomes of: (1) Retinal reattachment of RD/RB and tMH closure; (2) Best-corrected visual acuity (BCVA) improvement; and (3) Complications. Heterogeneity was examined with I2 statistics. A random-effects model was used for outcomes with high heterogeneity. Statistical analysis was performed using the software R (version 4.2.3, R Foundation for Statistical Computing, Vienna, Austria).
RESULTS: Fourteen final studies, comprising a total of 96 patients were analyzed, 81 with RD or RB and 15 with tMH. Overall, surgical management was associated with several advantages: a high rate of retinal reattachment of RD/RB of 97% (95% Confidence Interval [CI] 92-100%; I2 = 0%), retinal reattachment of just RD of 96% (95% CI 89-100%; I2 = 30%) and tMH closure 97% (95% CI 87-100; I2 = 12%). There were significant differences in BCVA after surgeries in studies of RD/RB (MD 0.60; 95% CI 0.35-0.65; I2 = 20%) and MH (MD 0.67; 95% CI 0.50-0.84; I2 = 0%). The overall complication rate associated with surgical procedures in RD/RB secondary to OT was confirmed to be 25%.
CONCLUSIONS: The systematic review and meta-analysis showed that the treatment approaches currently in use are effective, with a remarkable rate of retinal reattachment of RD/RB, tMH closure, and substantial improvements in visual acuity. More randomized, long-term studies on disease and surgical factors can provide valuable insights into their impact on anatomical and visual outcomes.