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.

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.

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.

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.

Elevated interleukin-10 levels in patients with ocular toxoplasmosis.

In elderly patients, ocular toxoplasmosis is one of the most common etiologies of uveitis, which should be differentially diagnosed from ocular lymphoma, another common pathology of uveitis in older adults. The high level of interleukin (IL)-10 and an IL-10/IL-6 ratio higher than 1 (>1.0) are helpful parameters to diagnose ocular lymphoma. In this study, we used aqueous humor samples to detect 4 cases of ocular toxoplasmosis in patients with high levels of IL-10 and an IL-10/IL-6 ratio higher than 1. Our results show that ocular toxoplasmosis may be associated with increased cytokine levels in aqueous humor.

Acquired Ocular Toxoplasmosis: a Case Report and Review of the Literature.

BACKGROUND: Toxoplasmosis is a zoonotic illness caused by Toxoplasma gondii. Ocular infection frequently manifests as acute necrotizing retinal chorioretinitis. In this paper, we describe a case of retinal chorioretinitis caused by Toxoplasma gondii infection, as well as the most recent diagnostic and treatment techniques. METHODS: Serum and vitreous fluid were collected and analyzed, and PCR for Toxoplasma gondii DNA, ELISA for Toxoplasma gondii IgG and Goldmann-Witmer coefficient, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and fundus autofluorescence were done (FAF). RESULTS: Toxoplasma gondii DNA (-), serum and vitreous IgG from Toxoplasma gondii (+) cells, and the Goldmann-Witmer coefficient of Toxoplasma gondii were all considerably enhanced, indicating Toxoplasma gondii infection. Antiparasitic infection in combination with an anti-inflammatory glucocorticoid were given, laser treatment of the fundus was provided, and the patient's condition has been stable with no indication of recurrence to date following conclusion of therapy. CONCLUSIONS: Toxoplasma gondii can infect the whole retina, causing variable degrees of visual impairment; thus, rapid diagnosis and tailored therapy are necessary to enhance prognosis and reduce disease recurrence.

Toxoplasmic maculopathy with bacillary layer detachment in a pediatric patient.

We report the case of a 14-year-old girl with ocular toxoplasmosis presenting with severe panuveitis with anterior segment involvement, moderate vitreous haze, focal retinochoroiditis, extensive retinal periphlebitis, and macular bacillary layer detachment. Toxoplasmosis treatment was complicated by Stevens-Johnson syndrome, which developed 8 days after starting trimethoprim-sulfamethoxazole.

Current practice in the management of ocular toxoplasmosis.

BACKGROUND: Ocular toxoplasmosis is common across all regions of the world. Understanding of the epidemiology and approach to diagnosis and treatment have evolved recently. In November 2020, an international group of uveitis-specialised ophthalmologists formed the International Ocular Toxoplasmosis Study Group to define current practice. METHODS: 192 Study Group members from 48 countries completed a 36-item survey on clinical features, use of investigations, indications for treatment, systemic and intravitreal treatment with antiparasitic drugs and corticosteroids, and approach to follow-up and preventive therapy. RESULTS: For 77.1% of members, unilateral retinochoroiditis adjacent to a pigmented scar accounted for over 60% of presentations, but diverse atypical presentations were also reported. Common complications included persistent vitreous opacities, epiretinal membrane, cataract, and ocular hypertension or glaucoma. Most members used clinical examination with (56.8%) or without (35.9%) serology to diagnose typical disease but relied on intraocular fluid testing-usually PCR-in atypical cases (68.8%). 66.1% of members treated all non-pregnant patients, while 33.9% treated selected patients. Oral trimethoprim-sulfamethoxazole was first-line therapy for 66.7% of members, and 60.9% had experience using intravitreal clindamycin. Corticosteroid drugs were administered systemically by 97.4%; 24.7% also injected corticosteroid intravitreally, almost always in combination with an antimicrobial drug (72.3%). The majority of members followed up all (60.4%) or selected (35.9%) patients after resolution of acute disease, and prophylaxis against recurrence with trimethoprim-sulfamethoxazole was prescribed to selected patients by 69.8%. CONCLUSION: Our report presents a current management approach for ocular toxoplasmosis, as practised by a large international group of uveitis-specialised ophthalmologists.

A new look into uveitis in Colombia: changes in distribution patterns and clinical characteristics over the last 25 years.

PURPOSE: To describe the distribution patterns and clinical characteristics of patients diagnosed with uveitis at a specialized uveitis center in Bogotá, Colombia, from 2013 to 2021 and compare these patterns with the previously reported between 1996 and 2006. METHODS: We performed an observational descriptive cross-sectional study systematically reviewing clinical records of patients attending between 2013 and 2021. Data were analyzed and compared with previous reports. RESULTS: Of the 489 patients with uveitis, 310 were females (63.4%). The mean age of onset was 38.7, with a range between 1 and 83 years. Bilateral (52.8%), anterior (45.8%), non-granulomatous (90.8%), and recurrent (47.6%) were the most common types of uveitis found in our population sample. The most common cause of uveitis in this study was idiopathic, followed by toxoplasmosis and HLA-B27 + associated uveitis, which differs from the previous Colombian study where ocular toxoplasmosis was the most frequent cause. This highlights a significant shift from infectious etiologies to more immune-mediated processes as the cause of uveitis in Colombia nowadays. CONCLUSION: The results of this study provide a comparison between the clinical patterns of presentation of uveitis from 1996 to 2006 and the patterns observed from 2013 to 2021, enhancing awareness about the changing dynamics of uveitis in Colombia to guide a better understanding of the diagnosis, classification, and correlation with other systemic conditions of the disease.

[Diagnostics and treatment of ocular toxoplasmosis : Results of a survey]. / Diagnostik und Behandlung der okulären Toxoplasmose : Ergebnisse einer Umfrage.

BACKGROUND: Ocular toxoplasmosis (OT) is the most common infectious cause of posterior uveitis. This survey aimed to evaluate the current diagnostic and therapeutic approach to OT in Germany. MATERIAL AND METHODS: A detailed questionnaire with specific patient examples was sent in July 2021 to the members of the Uveitis Section of the German Ophthalmological Society (DOG) and the Retinological Society (RG). RESULTS: The questionnaire was answered by 53 (29 RG and 24 DOG) ophthalmologists. Of the respondents 16 (30%) work in private practice, 18 (34%) in a clinical facility and 19 (36%) in university hospital, 9 (17%) colleagues see < 50, 28 (53%) 50-200 and 16 (30%) more than 200 uveitis patients per year. The clinical results are still the gold standard (87%) for the diagnosis of OT and in cases of first manifestation 60% are supported by serological antibody investigations, while 10 out of 53 (19%) ophthalmologists rely on the clinical presentation only. An IgM test is requested by 25 (47%) respondents, 6 expected an increase in IgG titer (11%) and 1 the detection of specific IgA antibodies (2%). The majority (n = 28, 53%) of ophthalmologists would aim at confirming the diagnosis by an anterior chamber puncture, from which 20 (38%) prefer PCR, 3 (6%) determination of Goldmann-Witmer coefficients (GW) and 5 (9%) a combination of both methods. Clindamycin was most frequently used for treatment (n = 21, 40%), followed by pyrimethamine/sulfadiazine (n = 17, 32%) and trimethoprime + sulfamethoxazole (TMP/SMX) (n = 10, 19%); the latter was also used (n = 40, 75%) for secondary prophylaxis. CONCLUSION: The results show that apart from the clinical results as the gold standard for the diagnosis, there is no uniform approach to diagnosis and treatment of OT. The high request rate for serum IgM antibodies indicates a widespread uncertainty about the importance of serological findings. This should be viewed critically, given the continued high seroprevalence in Germany.