Clinical characteristics, visual acuity outcomes, and factors associated with loss of vision among patients with active ocular toxoplasmosis: A retrospective study in a Thai tertiary center.

BACKGROUND: Ocular toxoplasmosis (OT) is the most common cause of infectious uveitis worldwide, including Thailand. This study describes the clinical presentation, visual acuity (VA) outcomes, and factors associated with VA loss in patients with active OT following antiparasitic treatment. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective chart review of patients with active OT treated with antiparasitic drugs between 2010 and 2020 was performed. Outcome measures included clinical characteristics, interval VA, and predictive factors associated with loss of VA ≤ 20/50 at 6 months post-treatment. Ninety-two patients (95 eyes) were enrolled. The median follow-up time was 10.9 months (IQR 4.9-31.8 months). The median age at presentation was 35.9 years, 51% were male, and 92.4% had unilateral OT. Eleven patients (12%) were immunocompromised (HIV infection, eight patients; receiving immunosuppressive agents, three patients). Patients mainly presented with primary retinitis without previous scar (62%), posterior pole lesion (56%), and lesion size of ≤ 2-disc area (75%). Immunocompromised patients showed a significantly larger size of retinitis than immunocompetent patients. Oral trimethoprim/sulfamethoxazole monotherapy was the primary short-term antiparasitic drug prescribed (85%). At the final visit, 21% of all affected eyes suffered VA ≤ 20/200. The cumulative incidence of recurrent OT at three years was 33.9% (95% CI, 19.7%-54.2%). Immunocompromised patients [adjusted odds ratio (aOR) 4.9, p = 0.041], macular lesion (aOR 5.4, p = 0.032), and initial VA ≤ 20/200 (aOR 9.1, p = 0.014) were predictive of having VA ≤ 20/50 at 6 months post-treatment. CONCLUSIONS: Ocular toxoplasmosis mainly presents as unilateral primary retinitis within the posterior pole. Severe VA loss was observed in one-fifth of eyes following treatment with lesion resolution. Immunocompromised patients, eyes with macular lesions, and poor initial VA were associated with poor VA outcomes.

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.

Unilateral Toxoplasma retinochoroiditis with frosted branch angiitis: a multimodal imaging study.

A woman in her late 30s presented with sudden diminution of vision, redness and pain in the right eye (OD) of 10 days' duration. Best corrected visual acuity (BCVA) was 20/160 in OD and 20/20 in the left eye (OS). Anterior segment of OD showed keratic precipitates, flare 3+, cells 2+ and a festooned pupil. Vitreous haze and cells were seen in OD. Frosted branch angiitis (FBA) was seen in all quadrants in OD and old Toxoplasma scar was seen in both eyes. Serum toxoplasma immunoglobulin G (IgG) was positive and IgM negative, and PCR of an aqueous humour sample was negative for Toxoplasma She was diagnosed with toxoplasa retinochoroiditis in OD and treated with intravitreal clindamycin injections, oral anti-Toxoplasma antibiotics and steroids. Three months later, her BCVA in OD was 20/40 with resolving inflammation. She presented 2 months later with a new focus of retinochoroiditis without FBA and an old Toxoplasma scar.

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.

Atypical acquired toxoplasmosis.

A 33-year-old male presented with unilateral painless vision loss with a history of sub-tenon steroid for the same. The fundus showed an elevated focus of retinochoroiditis with vitritis. On investigating for the cause, polymerase chain reaction test on the anterior chamber tap was found to be positive for Toxoplasma. Such confusing and atypical cases usually produce a clinical dilemma and should be managed in a stepwise manner. Ancillary investigations usually provide a clue to the clinician and should be performed without any hesitation.

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.

Toxoplasmosis outbreak in São Paulo, Brazil: Epidemiology and visual outcome.

PURPOSE: To describe a 2019 acute toxoplasmosis outbreak in the city of São Paulo, Brazil, and to evaluate the laboratory serological profile for toxoplasmosis for three consecutive years. The ophthalmological manifestations of the patients involved in the outbreak were also studied. METHODS: A cross-sectional descriptive study of a toxoplasmosis outbreak in São Paulo, Brazil, between February and May 2019. Epidemiological data were described, as were the observed ocular manifestations. As part of this study the number of patients with positive IgM toxoplasmosis serology was obtained from a large laboratory network (DASA) for three consecutive years, including the year of the outbreak (2018, 2019, 2020). RESULTS: Eighty-three individuals were identified in the outbreak and two clusters were studied. The clinical picture of at least 77% of the patients, the epidemiological analysis, and the short incubation period (5-8 days) suggested contamination by oocysts. Serological laboratory data analysis revealed an increase of positive toxoplasmosis IgM in 2019 of 73% compared to the previous year. Ophthalmological examination revealed that at least 4.8% of the patients developed toxoplasmic retinochoroiditis, none of whom had been treated during the acute systemic disease. CONCLUSION: Our findings indicate vegetable contamination as the possible source of this outbreak, a high prevalence of toxoplasmosis in São Paulo during the outbreak period, and a drop in the number of tests during the COVID-19 pandemic. Retinochoroiditis was observed in at least 4.8% of the cases. We confirm the need to implement effective means for the prevention, diagnosis, and treatment of the disease. This may involve raising awareness among the population of the importance of vegetable hygiene, and improved quality control of food and water.

Long-term Ocular Outcomes in Congenital Toxoplasmosis Treated Perinatally.

BACKGROUND: Congenital toxoplasmosis (CT) can be accompanied by serious organ manifestations, particularly retinochoroiditis, and may occur throughout life. We aimed to monitor long-term ocular prognosis in a large French cohort of patients with CT and its changes over time in the context of mandatory prenatal screening (since 1992) and incidence decrease since 2008. METHODS: Patients with CT diagnosed between 1987 and 2021 were prospectively included and followed for up to 35 years. The effect of the period of conception on the risk of first retinochoroiditis has been tested using a flexible extension of the Cox model. Incidence rates of retinochoroiditis were estimated. RESULTS: A total of 646 infected live born children were followed for a median of 12 years (range, 0.5-35); 187 patients (29%) had at least 1 ocular lesion (first at a median age of 5 years; range, 0-26 years) with peaks at 7 and 12 years. Early maternal infection and the presence of nonocular signs at birth were associated with a higher risk of retinochoroiditis, whereas delayed diagnosis of CT (after birth versus before or at birth) was associated with a lower risk (13% decrease for each additional month after birth; P = .01). A period effect for the risk of developing retinochoroiditis in patients born after 2008 was not detected. CONCLUSIONS: Despite prenatal screening and prolonged perinatal treatment, retinochoroiditis is not a rare event in French patients with CT and can occur well into adulthood, with peak incidences at 7 and 12 years of age. It rarely causes severe damage but warrants regular follow-up into adulthood.

An alternative method to establish an early acute ocular toxoplasmosis model for experimental tests.

PURPOSE: To provide a simple alternative acute ocular toxoplasmosis model with great reproducibility for experimental tests that demand monitoring of the ocular lesion. METHODS: ME49-wt and ME49-GFP tachyzoites from cell culture were used to infect male C57BL6 mice by intraperitoneal injection. B1 expression by real-time polymerase chain reaction (qPCR) assay was used to detect the presence of T. gondii in ocular tissue at the beginning of the infection. Fluorescence microscopy and histopathology analysis were carried out to assess the evolution of the acute infection up to 20 days in both eyes of infected mice. RESULTS: All mice infected with the 104 tachyzoites showed B1 expression in the retina of both eyes, in the RPE (retinal pigment epithelium), and choroid structures, after 5 days of infection. Tachyzoites of the ME49-GFP strain were easily detected by fluorescence microscopy in the retina tissue of mice after 5 days post-infection. After 20 days, mice inflammatory cell infiltrates and a disorganized morphology of the retinal laminar architecture were observed. CONCLUSION: Infection of C57BL6 mice via intraperitoneal with 104 tachyzoites of the ME49-GFP strain from cell culture is a suitable model for acute ocular toxoplasmosis. This model has great reproducibility in establishing the ocular lesion since day 5 post-infection. This model can be suitable for experimental tests of chemotherapy and the investigation of the role of the immune response on the development of uveitis.

Comparison of immunological and molecular methods for laboratory diagnosis of ocular toxoplasmosis in blood, serum and tears in Brazil.

Ocular toxoplasmosis (OT) is caused by protozoan T. gondii. Ophthalmological examination is considered the gold standard for OT diagnosis, and laboratory tests are used for diagnostic confirmation. However, these tests can present different results, which change depending on their basis, on sample type and on patients' clinical alteration. Thus, the aim of the present study is to assess immunodiagnostic and molecular techniques applied in blood, serum and tear fluid to diagnose T. gondii infection in patients seen at an Ophthalmology Clinic. In total, 160 patients were included in the study, 40 of them had OT with active lesions (G1); 40 had OT with healed lesions (G2), 40 had non-toxoplasmic uveitis (G3) and 40 had no ocular alterations (G4). Serum samples were subjected to Immunoenzymatic Assay (ELISA) and to Indirect Immunofluorescence Reaction (IFAT) to search for anti-T. gondii IgM and IgG. Tear fluid samples were analyzed through ELISA for IgA research. All blood and tear fluid samples were subjected to conventional polymerase chain reaction (cPCR) and in a Nested PCR model for T. gondii DNA amplification with targets B1, GRA7 and REP 529. IgG and IgM anti-T. gondii was detected in serum samples from 106 and 15 patients, respectively, when combining ELISA and IFAT results. Anti-T.gondii IgA antibodies were detected in 9.2% of the tear material. Nested PCR with GRA7 target showed higher positivity in blood samples (24.4%); Nested PCR with B1 target showed a higher frequency of positivity in tears (15%). Biological samples of patients with active lesions showed the highest positivity frequencies in all immunodiagnostic assays, as well as in most PCR models. The present results highlighted the need of associating techniques with different fundamentals to confirm OT diagnosis. Furthermore, further tear fluid analyses should be performed to validate this biological material as lesser invasive alternative for the more accurate OT diagnosis.

Considerations in the management of ocular toxoplasmosis in pregnancy: a review of literature.

Ocular toxoplasmosis is the most common cause of infectious posterior uveitis. Available literature is still conflicting regarding the incidence of recurrence during pregnancy as various calculations were employed in the different published studies. Although earlier reports have suggested a difference in presentation and an increase in severity during pregnancy, newer studies appear to show otherwise. Further diagnostic testing, including serologic and intraocular fluid sampling, may be indicated to increase the diagnostic accuracy in this special population of patients. The management of ocular toxoplasmosis during pregnancy is challenging as the foetus is additionally considered in the choice of treatment. Traditionally preferred anti-toxoplasmosis regimens containing antifolate drugs, such as pyrimethamine and trimethoprim-sulfamethoxazole, cannot be used routinely in pregnant patients, especially during the first trimester. This review includes literature on alternative treatments for ocular toxoplasmosis during pregnancy, including spiramycin and intravitreal treatment options.

Metagenomic analysis of the ocular toxoplasmosis in children uveitis from Fayoum governorate, Egypt.

Granulomatous anterior uveitis with single or numerous gelatinous nodules was found in children living in rural Egypt. All ocular diseases were originally thought to be water-born and related to digenic flukes. The current study sought to learn more about the causes of anterior granulomatous uveitis in Egyptian youngsters who used to swim in rural water canals. 50 children with eye lesions that had not responded to medical treatment were recruited. Four samples were surgically extracted and examined using real-time PCR, transmission electron microscopy (TEM), and shotgun metagenomic sequencing (SMS). Toxoplasma gondii was detected free within the syncytium's distal section, while the proximal part exhibited active synthesis of a presumably extra-polymeric material, possibly released by the microbial population. Toxoplasma gondii was found in 30 samples. Serologically, distinct anti-Toxoplasma antibodies were not found in 91.6% of patients. SMS showed that the T. gondii ME 49 strain had the greatest percentage (29-25%) in all samples within an Acinetobacter-containing microbial community. These findings suggested that these bacteria entered the body via the exterior route rather than the circulatory route. The lack of genetic evidence for subsequent parasite stages invalidates the prior findings about the assumed trematode stage.

Crystalline Retinopathy Following Intravitreal Clindamycin.

This case report describes a 74-year-old woman who developed a crystalline retinopathy following intravitreal injection of clindamycin. The patient presented with ocular toxoplasmosis in the left eye but was allergic to sulfa medications, so she was treated with intravitreal clindamycin. Subsequently, fine refractile yellow-white crystals were observed on examination of the left macula. Optical coherence tomography localized the crystals to the posterior hyaloid. Intravitreal clindamycin should be considered in the differential diagnosis of crystalline retinopathy. [Ophthalmic Surg Lasers Imaging Retina 2024;55:168-170.].

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.

Ocular toxoplasmosis following anti-tumour necrosis factor-α therapy combined with oral methotrexate therapy: A case report and review of literature.

Purpose: To report a case of ocular toxoplasmosis following long-term treatment with adalimumab and review the literature on ocular toxoplasmosis following anti-Tumour necrosis factor-α therapy. Method: A retrospective chart review of A 21-year-old male who developed retinochoroiditis in his left eye following adalimumab therapy combined with oral methotrexate. Result: A known patient of juvenile idiopathic arthritis (JIA) on adalimumab and oral methotrexate for the last four years presented to us with a blurring of vision for the last 15 days. Fundus examination of the left eye revealed severe vitritis and two patches of retinochoroiditis in the inferior part of the fundus. Subsequent investigations confirmed it to be a case of toxoplasma retinochoroiditis, and he responded to anti-toxoplasma treatment. A review of literature on a similar topic revealed five such cases, and the index case was the first such report in patients with JIA. Conclusion: The index case highlights the importance of early recognition and management of opportunistic infections in patients receiving biologicals.

Fundus topographical distribution patterns of ocular toxoplasmosis.

BACKGROUND: To establish topographic maps and determine fundus distribution patterns of ocular toxoplasmosis (OT) lesions. METHODS: In this retrospective study, patients who presented with OT to ophthalmology clinics from four countries (Argentina, Turkey, UK, USA) were included. Size, shape and location of primary (1°)/recurrent (2°) and active/inactive lesions were converted into a two-dimensional retinal chart by a retinal drawing software. A final contour map of the merged image charts was then created using a custom Matlab programme. Descriptive analyses were performed. RESULTS: 984 lesions in 514 eyes of 464 subjects (53% women) were included. Mean area of all 1° and 2° lesions was 5.96±12.26 and 5.21±12.77 mm2, respectively. For the subset group lesions (eyes with both 1° and 2° lesions), 1° lesions were significantly larger than 2° lesions (5.52±6.04 mm2 vs 4.09±8.90 mm2, p=0.038). Mean distances from foveola to 1° and 2° lesion centres were 6336±4267 and 5763±3491 µm, respectively. The majority of lesions were found in temporal quadrant (p<0.001). Maximum overlap of all lesions was at 278 µm inferotemporal to foveola. CONCLUSION: The 1° lesions were larger than 2° lesions. The 2° lesions were not significantly closer to fovea than 1° lesions. Temporal quadrant and macular region were found to be densely affected underlining the vision threatening nature of the disease.

Bacillary layer detachment as an inflammatory biomarker in toxoplasmosis retinochoroiditis: serial evolution on optical coherence tomography.

We describe the clinical course and serial evolution of bacillary layer detachment (BALAD) on optical coherence tomography (OCT) in toxoplasmosis retinochoroiditis and its importance as an inflammatory biomarker. Colour fundus photography and swept-source OCT of the BALAD were done at the time of presentation and subsequently at 1 week, 2 weeks, 4 weeks and at 11 weeks. Treatment involved oral trimethoprim (160 mg) + sulphamethoxazole (800 mg) two times per day, started at presentation for 2 months. Oral prednisolone was started after 1 week at a dose of 50 mg a day and tapered weekly over the next 5 weeks. The BALAD initially increased after starting treatment with trimethoprim-sulphamethoxazole and regressed within 1 week after initiation of oral prednisolone. Best corrected visual acuity improved to 20/40 from 20/160 at presentation (Snellen equivalent). This suggests that BALAD is an indicator of an acute inflammatory event and the accumulated fluid is secondary to retinal and choroidal inflammation.

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.