Not Always Toxoplasmosis: Active Retinochoroiditis Presumably Secondary to Herpes in Eyes with Hyperpigmented Retinochoroidal Previous Scars.

PURPOSE: To demonstrate that the presence of active retinochoroiditis in eyes with previous hyperpigmented old retinochoroidal lesions is not exclusive of ocular toxoplasmosis. METHODS: A case series was constructed by reviewing medical records. RESULTS: Four Brazilian patients presenting active posterior uveitis in eyes with previous hyperpigmented old retinochoroidal lesions were identified. Ocular toxoplasmosis was ruled out in all cases. One case had viral etiology confirmed through vitreous PCR (HSV-2 was positive), and the other 3 cases had a presumed diagnosis of herpetic posterior uveitis. CONCLUSION: Focus active retinitis adjacent to an old cicatricial lesion should not be considered pathognomonic of toxoplasmosis and viral etiology must be considered.

Interleukin 17F Gene Polymorphism as a Potential Protective Factor in the Immunopathology of Ocular Toxoplasmosis.

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.

New advances in immune mechanism and treatment during ocular toxoplasmosis.

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-1ß 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.

Systemic and Bilateral Severe Ocular Toxoplasmosis Resembling Autoimmune Phenomena: A Case Report.

PURPOSE: 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. CASE REPORT: 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. CONCLUSION AND IMPORTANCE: 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.

Active toxoplasma chorioretinitis in immunocompromised patients: a case series.

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.

Recurrent acquired ocular toxoplasmosis associated with Kyrieleis plaques and documented allergy to sulfonamide-A treatment proposal for two rare conditions.

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.

Modulation of CXCL10 activity as a therapeutic target of ocular toxoplasmosis in diabetic mice.

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.

The role of age in ocular toxoplasmosis: clinical signs of immunosenescence and inflammaging.

Purpose: This study aimed to investigate the association between age, immune response, and clinical presentation of ocular toxoplasmosis (OT). Design: This was a monocentric, retrospective, observational cohort study. Methods: 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. Results: 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). Conclusion: 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.

Long-Term Low-Dose Pyrimethamine Use for the Prevention of Ocular Toxoplasmosis Recurrences: A Cohort Study.

PURPOSE: To describe the effect of long-term, low-dose pyrimethamine for the prevention of ocular toxoplasmosis (OT) recurrences. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

Prevalence of ocular toxoplasmosis among people living with HIV: a systematic review and meta-analysis.

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.

Macular Punctate Lesions Presenting as a Primary Manifestation of Ocular Toxoplasmosis.

PURPOSE: To study clinical features and outcomes of primary ocular Toxoplasmosis (OT) cases presenting as macular punctate lesions. METHODS: Retrospective review of three cases of OT with positive Toxoplasma serology. RESULTS: We describe three cases presenting as primary OT with no evidence of old retinochoroidal scar in either eye. All the cases had multiple foveal or extrafoveal, punctate, inner/outer, or combined lesions at macula with minimal vitreous reaction. During the first/primary episode, all the lesions resolved with 1. retinal atrophy, thinning (n = 1) or 2. Progressed to limited full-thickness retinitis lesions (n = 2). Recurrence as typical retinochoroiditis was seen in one eye. More than four-fold IgG positivity was seen in all cases while IgM positivity was seen in two cases. CONCLUSIONS: Macular punctate lesions (inner/outer/combination) can be the primary manifestation of ocular toxoplasmosis in the absence of old retinochoroiditis scars in either eye.

Atypical Ocular Toxoplasmosis With Remote Vasculitis and Kyrieleis Plaques.

Retinal vasculitis is common in ocular toxoplasmosis (OT) and typically occurs in the same quadrant as retinochoroiditis. This is a case of atypical ocular toxoplasmosis with remote vasculitis distant from the retinochoroiditis lesion. Examination of the left fundus showed the classic posterior segment finding of "headlight in the fog" in the absence of a chorioretinal scar. Retinal vasculitis was noted in all four quadrants at the periphery far from the retinitis area. A presumptive diagnosis of acute panuveitis secondary to ocular toxoplasmosis was made despite the enzyme-linked immunosorbent assay (ELISA) for Toxoplasmosis antibody being pending. The patient was treated empirically with oral sulfamethoxazole-trimethoprim for eight weeks and received both oral and topical corticosteroids. His symptoms and ocular signs have significantly improved. This case report highlights an atypical remote localization of vasculitis with the classic appearance of retinochoroiditis and vitritis, which is highly due to toxoplasmosis. Early initiation of antibiotic therapy is recommended despite pending serology to ensure a good final visual and ocular outcome.

Surgical management of retinal detachment and macular holes secondary to ocular toxoplasmosis: a systematic review and meta-analysis.

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.

Automated Machine Learning versus Expert-Designed Models in Ocular Toxoplasmosis: Detection and Lesion Localization Using Fundus Images.

PURPOSE: Automated machine learning (AutoML) allows clinicians without coding experience to build their own deep learning (DL) models. This study assesses the performance of AutoML in detecting and localizing ocular toxoplasmosis (OT) lesions in fundus images and compares it to expert-designed models. METHODS: Ophthalmology trainees without coding experience designed AutoML models using 304 labelled fundus images. We designed a binary model to differentiate OT from normal and an object detection model to visually identify OT lesions. RESULTS: The AutoML model had an area under the precision-recall curve (AuPRC) of 0.945, sensitivity of 100%, specificity of 83% and accuracy of 93.5% (vs. 94%, 86% and 91% for the bespoke models). The AutoML object detection model had an AuPRC of 0.600 with a precision of 93.3% and recall of 56%. Using a diversified external validation dataset, our model correctly labeled 15 normal fundus images (100%) and 15 OT fundus images (100%), with a mean confidence score of 0.965 and 0.963, respectively. CONCLUSION: AutoML models created by ophthalmologists without coding experience were comparable or better than expert-designed bespoke models trained on the same dataset. By creatively using AutoML to identify OT lesions on fundus images, our approach brings the whole spectrum of DL model design into the hands of clinicians.

Serous macular detachment in ocular toxoplasmosis: A review.

Ocular toxoplasmosis, a disease of the eye caused by the protozoan parasite Toxoplasma gondii, represents a common cause of posterior uveitis. The Authors review the current Literature regarding the uncommon presentation of ocular toxoplasmosis as macular serous retinal detachment (SRD). It is imperative to keep in mind that inflammatory SRD is a possible presentation of toxoplasmic retinochoroiditis. Underestimation of this clinical scenario and treatment with steroids alone without appropriate antiparasitic drugs, could lead to devastating consequences.

Atypical pattern of ocular toxoplasmosis: recurrent inner foveal toxoplasmic retinitis (rifter).

Failure to recognize the different possible clinical presentations of ocular toxoplasmosis may delay diagnosis and treatment, compromising visual prognosis. The aim of this paper is to describe an atypical pattern of ocular toxoplasmosis, not yet described. Five Brazilian patients, from 4 different referral centers, presented similar atypical pattern of ocular toxoplasmosis characterized by mild vitritis, foveal cavitation involving predominantly all retinal layers associated with adjacent inner retinal necrosis (a necrotizing retinitis with a persisting inner retinal tissue bridge and loss of subjacent retinal layers). The appearance of the OCT image resembling a "rift", led the authors to define this pattern as a Recurrent Inner Foveal Toxoplasmic Retinitis (RIFTER), which can be considered as a new description of an atypical pattern of toxoplasma retinochoroiditis, and clinicians should be aware of it and consider testing for toxoplasmosis in patients with similar findings.

Outcomes of trimethoprim/ sulfamethoxazole treatment for ocular toxoplasmosis in Congolese patients.

BACKGROUND: Ocular toxoplasmosis (OT) is the leading cause of infectious posterior uveitis in several areas worldwide. The combination of Trimethoprim/Sulfamethoxazole (TMP/SMX) has been presented as an attractive alternative to the "classic' treatment therapy (Pyrimethamine/Sulfadiazine). METHODS: A prospective study was carried out between February 2020 and September 2021 in 2 ophthalmic centers in Kinshasa. This study aimed to describe TMP/SMX treatment outcomes for OT in a cohort of immunocompetent Congolese patients. RESULTS: 54 patients were included, with a mean age at presentation of 37.5 ± 13.6 years old and a Male-Female ratio of 1.45:1. Three patients (5.6%) presented a recurrence during the follow-up period. At the end of the follow-up, improvement in VA and resolution of inflammation concerned 75.9% and 77.5% of patients, respectively. Cataracts (3.7%), macular scars (3.7%), and vitreous opacities (3.7%) were the principal causes of non-improvement in VA. Treatment-related adverse events were present in 10 patients (18.5%); gastrointestinal (14.8%) and dermatological (3.7%) adverse events were the most frequent. Dermatological adverse events led to discontinuation of treatment. CONCLUSION: TMP/SMX regimen appears to be a safe and effective treatment for OT in Congolese patients. The low cost and the accessibility of the molecules make this regimen an option for treating OT in resource-limited countries.

Atypical Ocular Toxoplasmosis: Multifocal Segmental Retinal Arteritis (Kyrieleis Arteritis) and Peripheral Choroidal Leision.

A 45-year-old immunocompetent man with a two-week history of unilateral painful red eye was referred to the university hospital for further investigation. High intraocular pressure, corneal edema, large pigmented keratic precipitates, cells and flares in the anterior chamber, patches of iris transillumination with atrophy, multifocal segmental retinal arteritis (SRA) or Kyrieleis arteritis, and peripheral choroidal elevation with overlying vitritis without adjacent old scars were observed. Toxoplasmosis, varicella-zoster virus, herpes simplex, and cytomegalovirus serologies (IgG) were positive. More detailed history-taking revealed that the patient consumed grilled rats in Ghana where rats are eaten more regularly. Toxoplasmosis diagnosis was assumed. The patient was successfully treated according to local guidelines with azithromycin 500 mg/day for five weeks. No recurrence or new lesion was observed during the six-month follow-up period.

Genetic Variations in the Purinergic P2X7 Receptor Are Associated with the Immune Response to Ocular Toxoplasmosis in Colombia.

Ocular toxoplasmosis (OT) is characterized by inflammation within the eye and is the most recognized clinical manifestation of toxoplasmosis. The objective of this study was to identify new single-nucleotide polymorphisms (SNPs) in the P2RX7 gene that may have significance in the immune response to OT in Colombian patients. A case-control study was conducted to investigate the associations between SNPs (rs1718119 and rs2230912) in the P2RX7 gene and OT in 64 Colombian patients with OT and 64 controls. Capillary electrophoresis was used to analyze the amplification products, and in silico algorithms were employed to predict deleterious SNPs. Stability analysis of amino acid changes indicated that both mutations could lead to decreased protein structure stability. A nonsynonymous SNP, Gln460Arg, located in the long cytoplasmic tail of the receptor, showed a significant association with OT (Bonferroni correction (BONF) = 0.029; odds ratio OR = 3.46; confidence interval CI: 1.05 to 11.39), while no significant association between rs1718119 and OT risk was observed. Based on the 3D structure analysis of the P2RX7 protein trimer, it is hypothesized that an increase in the flexibility of the cytoplasmic domain of this receptor could alter its function. This SNP could potentially serve as a biomarker for identifying Colombian patients at risk of OT.

Retinal ferroptosis as a critical mechanism for the induction of retinochoroiditis during ocular toxoplasmosis.

Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer 57Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.