Immune Mediators against Toxoplasma Gondii during Reactivation of Toxoplasmic Retinochoroiditis.

Purpose: The purpose of this article is to analyze possible associations between systemic and ocular cytokine levels and specific clinical ophthalmologic signs from patients with a reactivation of toxoplasmic retinochoroiditis (RTR). Methods: A total of 18 patients with an active RTR episode, 8 patients with inactive scars, and 14 control patients were included in the study. Serum samples and aqueous humor (AH) samples were analyzed for IFN (interferon)-γ, interleukin (IL)-10, and IL-6 levels by ELISA. Inflammation grade, location, and size of the retinochoroidal active lesion, sampling time, and time to resolution were recorded. Results: A significantly negative correlation between AH and serum levels of IFN-γ was detected (p < 0.05). Patients with an AH IFN-γ/IL-10 ratio lower than 1 were associated with the longest time to resolution and/or severe complications. Conclusion: Serum IFN-γ levels may be used as a prognostic marker for both time to resolution and the development of possible severe complications during a given RTR episode.

Cytokine Signatures Associated With Early Onset, Active Lesions and Late Cicatricial Events of Retinochoroidal Commitment in Infants With Congenital Toxoplasmosis.

BACKGROUND: Ocular toxoplasmosis is a prominent and severe condition of high incidence in Brazil. The current study provides new insights into the immunological events that can be associated with retinochoroiditis in the setting of congenital toxoplasmosis in human infants. METHODS: Flow cytometry of intracytoplasmic cytokines in leukocyte subsets following in vitro short-term antigenic recall in infants with congenital T. gondii infection. RESULTS: Our data demonstrates that whereas neutrophils and monocytes from T. gondii-infected infants display a combination of proinflammatory and regulatory cytokine profiles, natural killer cells showed a predominantly proinflammatory profile upon in vitro T. gondii stimulation. The proinflammatory response of CD4(+) and CD8(+) T cells, characterized by the production of interferon γ (IFN-γ) and interleukin 17 in patients with an active retinochoroidal lesion, revealed the presence of IFN-γ and tumor necrosis factor α during early and late immunological events. This specific proinflammatory pattern is associated with early events and active retinochoroidal lesion, whereas a robust monocyte-derived interleukin 10-mediated profile is observed in children with cicatricial ocular lesions. CONCLUSIONS: These findings support the existence of a progressive immunological environment concomitant with the initial, apical, and cicatricial phases in the process of retinochoroidal lesion formation in infants with congenital toxoplasmosis that may be relevant in the establishment of stage-specific clinical management.

Birdshot retinochoroidopathy review.

Birdshot retinochoroidopathy (BSRC) is a distinct type of posterior uveitis originally described in the 1940s. Its characteristics include minimal anterior segment inflammation and diffuse posterior choroidopathy with vitritis and retinal vasculitis. The precise etiology of this disease is yet to be elucidated. However, various treatment modalities have been employed with the ultimate goal of durable remission of this vision threatening intraocular disease. The purpose of this review is not only to emphasize the importance of recognizing BSRC, but also to discuss the new discoveries, immune mediators, current and new therapies, and techniques applied to monitor and accomplish disease remission.

Birdshot retinochoroidopathy review / Revisão sobre retinocoroidopatia do tipo "birdshot"

Birdshot retinochoroidopathy (BSRC) is a distinct type of posterior uveitis originally described in the 1940s. Its characteristics include minimal anterior segment inflammation and diffuse posterior choroidopathy with vitritis and retinal vasculitis. The precise etiology of this disease is yet to be elucidated. However, various treatment modalities have been employed with the ultimate goal of durable remission of this vision threatening intraocular disease. The purpose of this review is not only to emphasize the importance of recognizing BSRC, but also to discuss the new discoveries, immune mediators, current and new therapies, and techniques applied to monitor and accomplish disease remission.

Retinocoroidopatia do tipo "birdshot" é um tipo de uveíte posterior originalmente descrita na década de 1940. Achados característicos incluem inflamação mínima do segmento anterior, retinocoroidopatia difusa associada à vitreíte e vasculite retiniana. A etiologia da doença ainda não foi completamente definida, entretanto várias modalidades de tratamento têm sido utilizadas com o objetivo de atingir a remissão. O objetivo desta revisão é enfatizar não só a importância do reconhecimento da doença como também discutir novas descobertas relacionadas a mediadores imunes, formas de tratamentos e como monitorar a doença.

Incidence of Toxoplasma retinochoroiditis in patients with ankylosing spondylitis after using TNF-α blockers.

TNF-α blockers are associated with reactivation of latent granulomatous infections and almost 6% of the world population has some chorioretinitis (CR) caused by Toxoplasma gondii. Thus, the blockade of TNF-α could reactivate a latent toxoplasmosis infection (LTxI). This study was conducted to evaluate the prevalence and incidence of chronic and active CR related to T. gondii in patients with ankylosing spondylitis (AS). A total of 74 eyes from 37 active AS outpatients starting TNFα blockers were compared with 35 AS patients, matched to age and sex, under conventional therapy in a prospective and controlled trial. All patients underwent serological tests for T. gondii, as well as periodic ophthalmologic examination during 12months. Active CR was defined if a white, focal retinochoroidal lesion with overlying vitreous inflammation had been found. Retinochoroidal lesions with sharp edges, hyperpigmented borders and atrophic center were defined as CR scars. At baseline, no patient had active CR. From the 144 eyes examined, almost 6% had CR scars and only 2.1% had a typical toxoplasmic CR scar and all of them were negative for HLA-B27. During 12months of follow-up, no recurrence or new CR were observed. AS patients using TNF-α blockers do not have a higher risk of acute or chronic CR caused by T. gondii.

Spectral optical coherence tomography findings in patients with ocular toxoplasmosis and active satellite lesions (MINAS Report 1).

PURPOSE: To characterize the active retinochoroiditis lesion observed in patients with the classic clinical presentation of ocular toxoplasmosis (OT) utilizing spectral optical coherence tomography (SOCT). METHODS: Twenty-four patients with OT and satellite lesions underwent standardized ophthalmologic examination and multimodal fundus imaging. The SOCT findings observed at presentation were described. RESULTS: The mean age of the fourteen (58.3%) women and ten (41.7%) men was 27.6 years. The mean LogMAR ETDRS best-corrected visual acuity was 0.58 (Snellen equivalent, 20/80(+1) ). On SOCT evaluation, the posterior hyaloid was diffusely thickened in 23 (95.8%) of 24 eyes, increased hyper-reflective signals in the vitreous were observed in 18 (75.0%), and vitreal spherical hyper-reflective depositions were observed in 12 (50.0%) eyes. In all patients, at the active OT lesion site, the inner retinal layers were abnormally hyper-reflective with full-thickness disorganization of the retinal reflective layers (smudge effect); associated choriocapillaris/choroidal optical shadowing was observed in 22 (91.7%) eyes. The retina was thickened in 22 (91.7%) eyes, the retinal pigment epithelium-Bruch membrane reflective complex was focally increased or contained focal splits in 16 (66.7%) eyes and the choroid appeared thickened in 17 (70.8%) eyes. Disorganization of the outer retinal highly reflective layers adjacent to the active OT lesion was observed in all eyes. CONCLUSION: Full-thickness disorganization of the retinal reflective layers, generally associated with some degree of posterior optical shadowing, was observed in the active OT lesion in all patients. The posterior hyaloid was often thickened and, adjacent to the OT lesion, the outer retina was consistently altered.

Toxoplasma gondii in the peripheral blood of patients with acute and chronic toxoplasmosis.

BACKGROUND AND AIMS: Toxoplasmic retinochoroiditis may recur months or years after the primary infection. Rupture of dormant cysts in the retina is the accepted hypothesis to explain recurrence. Here, the authors present evidence supporting the presence of Toxoplasma gondii in the peripheral blood of immunocompetent patients. METHODS: Direct observation by light microscopy and by immunofluorescence assay was performed, and results were confirmed by PCR amplification of parasite DNA. RESULTS: The authors studied 20 patients from Erechim, Brazil, including acute infected patients, patients with recurrent active toxoplasmic retinochoroiditis, patients with old toxoplasmic retinal scars, and patients with circulating IgG antibodies against T gondii and absence of ocular lesions. Blood samples were analysed, and T gondii was found in the blood of acutely and chronically infected patients regardless of toxoplasmic retinochoroiditis. CONCLUSIONS: The results indicate that the parasite may circulate in the blood of immunocompetent individuals and that parasitaemia could be associated with the reactivation of the ocular disease.

Imunologia da retinocoroidite toxoplásmica / Immunology of the toxoplasmic retinochoroiditis

A infecção pelo Toxoplasma gondii é uma importante causa de doença ocular, tanto em indivíduos imunocomprometidos como em imunocompetentes. A patogênese da destruição retinocoroidiana associada a essa infecção ainda não está totalmente esclarecida. Nesta revisão, discute-se o papel do sistema imune no controle da infecção pelo Toxoplasma, especialmente, no olho.

Toxoplasma gondii infection is an important cause of ocular disease in both immunocompromised and immunocompetent subjects. The pathogenesis of retinochoroidal lesion associated with this infection is not fully understood. In this review, the role of the immune system in the control of Toxoplasma infection, especially in the eye, is discussed.

Toxoplasmose congênita em filho de mãe cronicamente infectada com reativação de retinocoroidite na gestação / Congenital toxoplasmosis from a chronically infected woman with reactivation of retinochoroiditis during pregnancy an underestimated event?

Objetivo: Apresentar um caso raro de toxoplasmose congênita de uma mãe imunocompetente com infecção crônica que teve reativação da doença ocular durante a gestação. Descrição: O recém-nascido estava assintomático no nascimento e foi identificado através de triagem neonatal (IgM anti-Toxoplasma gondii em sangue seco) entre outros 190 bebês com toxoplasmose congênita durante um período de 7 meses. Sua mãe tinha tido um episódio não tratado de reativação de retinocoroidite toxoplásmica durante a gestação, com títulos de IgG estáveis e resultados negativos para IgM. Os resultados de IgM e IgG no soro do recém-nascido e o teste de immunoblotting para IgG foram positivos, e detectou-se lesões retinocoroideanas ativas na periferia da retina. O recém-nascido foi tratado com sulfadiazina, pirimetamina e ácido folínico. Aos 14 meses de vida, a criança permanecia assintomática, com regressão das lesões retinocoroideanas e persistência de IgG. Comentários: É possível que a triagem neonatal sistemática em áreas com alta prevalência de infecção possa identificar esses casos.

Objectives: To report a rare case of congenital toxoplasmosis from an immunocompetent mother with chronic infection who had reactivation of ocular disease during pregnancy. Descriptions:The newborn was asymptomatic at birth and identified by neonatal screening (IgM anti-Toxoplasma gondii in dried blood) among other 190 infants with congenital toxoplasmosis during a 7-month period. His mother had had a non-treated episode of reactivation of toxoplasmic retinochoroiditis during pregnancy, with stable IgG titers and negative IgM results. Results of IgM and IgG in the newborn’s serum, as well as IgG immunoblotting were positive and active retinochoroidal lesions were detected in his peripheral retina. The neonate was treated with sulfadiazine, pyrimethamine and folinic acid. At 14 months of life, the child remained asymptomatic, with regression of retinochoroidal lesions and persistence of IgG. Comments: It is possible that systematic neonatal screening in areas with high prevalence of infection may identify these cases.

[Immunology of the toxoplasmic retinochoroiditis]. / Imunologia da retinocoroidite toxoplásmica.

Toxoplasma gondii infection is an important cause of ocular disease in both immunocompromised and immunocompetent subjects. The pathogenesis of retinochoroidal lesion associated with this infection is not fully understood. In this review, the role of the immune system in the control of Toxoplasma infection, especially in the eye, is discussed.

Congenital toxoplasmosis from a chronically infected woman with reactivation of retinochoroiditis during pregnancy.

OBJECTIVE: To report a rare case of congenital toxoplasmosis from an immunocompetent mother with chronic infection who had reactivation of ocular disease during pregnancy. DESCRIPTION: The newborn was asymptomatic at birth and identified by neonatal screening (IgM anti-Toxoplasma gondii in dried blood) among other 190 infants with congenital toxoplasmosis during a 7-month period. His mother had had a non-treated episode of reactivation of toxoplasmic retinochoroiditis during pregnancy, with stable IgG titers and negative IgM results. Results of IgM and IgG in the newborn's serum, as well as IgG immunoblotting were positive and active retinochoroidal lesions were detected in his peripheral retina. The neonate was treated with sulfadiazine, pyrimethamine and folinic acid. At 14 months of life, the child remained asymptomatic, with regression of retinochoroidal lesions and persistence of IgG. COMMENTS: It is possible that systematic neonatal screening in areas with high prevalence of infection may identify these cases.

The IFN-gamma +874T/A gene polymorphism is associated with retinochoroiditis toxoplasmosis susceptibility.

Toxoplasmosis is a worldwide zoonosis that generally produces an asymptomatic infection. In some cases, however, toxoplasmosis infection can lead to ocular damage. The immune system has a crucial role in both the course of the infection and in the evolution of toxoplasmosis disease. In particular, IFN-gamma plays an important role in resistance to toxoplasmosis. Polymorphisms in genes encoding cytokines have been shown to have an association with susceptibility to parasitic diseases. The aim of this work was to analyse the occurrence of polymorphisms in the gene encoding IFN-gamma (+874T/A) among Toxoplasma gondii seropositive individuals, including those with ocular lesions caused by the parasite, from a rural population of Santa Rita de Cássia, Barra Mansa, state of Rio de Janeiro, Brazil. Further, we verified which of these polymorphisms could be related to susceptibility to the development of ocular toxoplasmosis. This study included 34 individuals with ocular toxoplasmosis (ocular group) and 134 without ocular lesions (control group). The differences between A and T allele distributions were not statistically significant between the two groups. However, we observed that a higher frequency of individuals from the ocular group possessed the A/A genotype, when compared with the control group, suggesting that homozygocity for the A allele could enhance susceptibility to ocular toxoplasmosis in T. gondii infection.

The IFN-γ +874T/A polymorphism is associated with retinochoroiditis toxoplasmosis susceptibility

Toxoplasmosis is a worldwide zoonosis that generally produces an asymptomatic infection. In some cases, however, toxoplasmosis infection can lead to ocular damage. The immune system has a crucial role in both the course of the infection and in the evolution of toxoplasmosis disease. In particular, IFN-γ plays an important role in resistance to toxoplasmosis. Polymorphisms in genes encoding cytokines have been shown to have an association with susceptibility to parasitic diseases. The aim of this work was to analyse the occurrence of polymorphisms in the gene encoding IFN-γ (+874T/A) among Toxoplasma gondii seropositive individuals, including those with ocular lesions caused by the parasite, from a rural population of Santa Rita de Cássia, Barra Mansa, state of Rio de Janeiro, Brazil. Further, we verified which of these polymorphisms could be related to susceptibility to the development of ocular toxoplasmosis. This study included 34 individuals with ocular toxoplasmosis (ocular group) and 134 without ocular lesions (control group). The differences between A and T allele distributions were not statistically significant between the two groups. However, we observed that a higher frequency of individuals from the ocular group possessed the A/A genotype, when compared with the control group, suggesting that homozygocity for the A allele could enhance susceptibility to ocular toxoplasmosis in T. gondii infection.

Toxoplasmosis retinochoroiditis after photodynamic therapy and intravitreal triamcinolone for a supposed choroidal neovascularization: a case report

The purpose is to report a complication after photodynamic therapy (PDT) and intravitreal triamcinolone for a presumed choroidal neovascularization in age-related macular degeneration. Photodynamic therapy and intravitreal triamcinolone were used in an 84-year-old man with choroidal neovascularization in the left eye. Forty-five days after therapy, the patient returned with a severe necrotizing uveitis in the posterior pole and vitritis. Laboratory investigation disclosed a high anti-Toxoplasma IgG titer. Therapy with pyrimethamine, sulfadiazine and folinic acid resulted in total lesion healing although central vision was lost. Intravitreal triamcinolone may have had an influence on the exacerbation of retinochoroiditis in the posterior pole of the patient. Although rare, this complication may not be disregarded in the cases that require intraocular corticosteroids for treatment of several conditions, especially in patients who had previously suffered from toxoplasmosis infection.

O objetivo é relatar complicação após terapia fotodinâmica (PDT) e triancinolona intravítrea para presumida neovascularização de coróide em degeneração macular relacionada à idade. A terapia fotodinâmica e triancinolona intravítrea foram utilizados em paciente de 84 anos, do sexo masculino, com neovascularização de coróide no olho esquerdo. Quarenta e cinco dias após o tratamento, o paciente retornou com grave retinite necrosante do pólo posterior e vitreíte. Investigação laboratorial indicou alto título de IgG anti-Toxoplasma. Tratamento com pirimetamina, sulfadiazina e ácido folínico levaram à total cicatrização da lesão embora a visão central tenha sido comprometida. Conclui-se que a triancinolona intravítrea pode ter influenciado na exacerbação da retinocoroidite no pólo posterior do paciente. Embora rara, esta complicação não pode ser descartada nos casos que necessitem corticóide intra-ocular para tratamento de várias doenças, principalmente em pacientes que tenham tido surtos prévios de toxoplasmose ocular.

Screening by ophthalmoscopy for Toxoplasma retinochoroiditis in Colombia.

PURPOSE: To measure the prevalence of toxoplasmic retinal scars in a young universitary population. DESIGN: Observational cohort study. METHODS: The study was performed at the "Universidad del Quindío," Armenia (Colombia), from November to December 2005. Indirect ocular funduscopy by ophthalmologists was performed in students, teachers, and administrative staff between 18 and 45 years of age without previous ocular pathology. The diagnostic criteria were based on the observation of typical funduscopic lesions and the detection of positive immunoglobulin (Ig) G anti-Toxoplasma antibodies. RESULTS: From a total of 200 people, 12 (6%) had inactive retinochoroidal scars. Two of them had visual acuity of <20/200 and one of 20/70. Enzyme-Linked Immunosorbent Assay (ELISA) IgG and IgM anti-Toxoplasma was performed in nine patients, all of whom were positive for IgG and one for IgM. CONCLUSIONS: A relatively high prevalence of retinochoroidal scars (6%) was detected in a young universitary population in Colombia.

[Toxoplasmic retinochoroiditis reactivated in the puberty]. / Retinocoroiditis toxoplasmósicas reactivadas en la pubertad.

By a clinical-infectious and ophthalmologic examination that includes serologic studies, we found that 17 cases of retinochoroiditis reactivated in the puberty.

Retinocoroiditis toxoplasmósicas reactivadas en la pubertad / Toxoplasmic retinochoroiditis reactivated in the puberty

Mediante el examen clínico infectológico, oftalmológico y serológico se comprobaron 17 casos de retinocoroiditis reactivadas en pacientes en desarrollo puberal. (Au)

Retinocoroidopatia de Birdshot; relato de um caso brasileiro / Birdshot retinochoroidopathy; a brazilian case report

A retinocoroidopatia de Birdshot é uma doença rara em nosso meio, que acomete principalmente mulheres caucasianas, entre a terceira e sexta décadas de vida. Os autores apresentam um caso de paciente do sexo masculino, de 25 anos de idade, com retinocoroidopatia de Birdshot, cujo quadro clínico é bilateral e constitui-se basicamente de discreta reaçäo inflamatória do segmento anterior, vitreíte, "leakage" vascular retiniano e presença de lesöes simétricas, ovaladas e branco-amareladas, evidenciadas à fundoscopia. O objetivo deste trabalho é discutir os aspectos clínicos, eletrofisiológicos, imunológicos e angiofluoresceinográficos da doença, além de relatar o primeiro caso publicado na literatura brasileira