Clinical and imaging characteristics of outer retinal folds in eyes with retinitis

Purpose: To describe clinical and imaging characteristics of the outer retinal folds (ORF) in cases of retinitis, retinochoroiditis, and chorioretinitis. Methods: Retrospective review of retinitis cases with presence of ORFs either at presentation or during follow up. Results: ORFs were seen adjacent to retinitis lesions in 16 eyes of 14 cases (retinitis post-febrile illness n = 10, toxoplasma retinochoroiditis n = 2, fungal chorioretinitis n = 2) either at presentation (n = 2) or during follow up (n = 14). Optical coherence tomography (OCT) appearance was outer retinal vertical stout lesions involving ellipsoid, external limiting membrane, and outer nuclear layer. All the cases had a presence of past or concurrent subretinal fluid and/or subretinal hyperreflective material when ORF was seen. ORF resolved with variable outer retinal atrophy over a mean period of 2.86 months. Conclusion: ORF is observed in cases of retinitis with subretinal fluid either at presentation or during resolution. It is not specific to any etiological disease. Differentiation of this sign from vertical outer retinal stripes in viral retinitis on OCT is important to avoid misinterpretation.

Therapeutic alternatives for the treatment of ocular toxoplasmosis

Ocular toxoplasmosis is caused by Toxoplasma gondii, inducing retinochoroiditis. It is the leading cause of infectiousposterior uveitis worldwide. Its treatment is based on oral drug administration. However, the blood–ocular barriersystems make the penetration of therapeutic drug concentrations within the eye difficult, limiting the effectiveness oftreatments. In this context, ocular drug delivery systems represent therapeutic alternative for the treatment of oculartoxoplasmosis. In this study, a review of clinical manifestations, diagnosis, treatment, and perspectives regardingthe treatment of ocular toxoplasmosis was conducted. A search was carried out on ScienceDirect, Scopus, Webof Science, PubMed, and SciELO, and the following keywords were used: toxoplasmosis, ocular toxoplasmosis,toxoplasmic retinochoroiditis, and congenital toxoplasmosis; and Boolean operators, associated with other keywords,such as epidemiology, ocular toxoplasmosis diagnosis, ocular toxoplasmosis treatment, and ocular toxoplasmosisperspectives, were applied. In conclusion, ocular toxoplasmosis still lacks effective treatment. Therefore, it is essentialto develop new molecules and/or new drug delivery systems capable of releasing therapeutic doses of anti-Toxoplasmadrugs directly in the posterior segment of the eye, for an extended period, since complications resulting from thedisease may shorten the productive life of individuals and may even lead to blindness

Toxoplasmosis ocular en Colombia: 10 años de aportes investigativos / Ocular toxoplasmosis in Colombia: 10 years of research contributions

Objetivo: Describir aportes investigativos en Toxoplasmosis ocular, realizados en Colombia. Método: Revisión narrativa de la literatura entre 2007 y 2017 en Toxoplasmosis Ocular (TO) en Colombia, sobre aspectos relacionados con el parásito y con el hospedero. Se incluyeron las revisiones publicadas, así como todos los artículos originales relacionados con diversos temas: epidemiológicos, inmunológicos, clínicos, diagnósticos y terapéuticos a través de PubMed usando los términos MeSH, con la siguiente sintaxis: "(((Colombia[Affiliation]) OR colombia[MeSHTerms]) OR south america[MeSH Terms]) AND "toxoplasmosis, ocular"[MeSH Terms] AND ("2007/01/01"[PDAT] : "2017/12/31"[PDAT]). Adicionalmente se realizaron búsquedas manuales. Resultados: En la búsqueda de la literatura con los términos MESH mencionados, se encontraron 36 artículos, distribuidos en el territorio con 10 en Colombia y 26 en el resto de Suramérica. Se encontraron diferencias importantes relacionadas con el parásito y con el hospedero, al comparar Colombia con el mundo. Las cepas en Colombia son más virulentas (Tipo I/III y atípicas). Se encontró una alta prevalencia de títulos positivos y desarrollo de TO en el país, presentándose el agua y los productos cárnicos como uno de los principales medios de contagio. Se determinó la importancia de péptidos que activan la respuesta inmune humoral en pacientes. Se encontraron diferencias significativas en la severidad clínica (tamaño de las lesiones, grado de inflamación, compromiso macular, compromiso bilateral y recurrencias, siendo mayores para los pacientes colombianos) relacionada con la respuesta inflamatoria producida en el hospedero, asociada con una disminución de los niveles intraoculares de IFN-γ /IL-17 y un aumento de IL-6/Il-13. En los pacientes colombianos el citoquinoma ocular está relacionado con las características clínicas, presentando una respuestaTh 2 relacionada con un compromiso severo ocular. Conclusión: Los aportes investigativos que Colombia ha realizado en TO, han sido de importancia mundial, permitiendo conocer más acerca del tipo de parásito, la epidemiología, la presentación clínica y la respuesta inmune.

Purpose: To describe research contributions in ocular toxoplasmosis performed in Colombia. Method: We conducted a narrative review of the literature on ocular toxoplasmosis (OT) in Colombia between 2007 and 2017 on aspects related to the parasite and to the host. Published reviews were included, as well as all the original articles related to various topics: epidemiological, immunological, clinical, diagnostic and therapeutic through PubMed using the MeSH terms, with the following syntax: "(((Colombia [Affi liation]) OR colombia [MeSH Terms]) OR south america [MeSH Terms]) AND "toxoplasmosis, ocular" [MeSH Terms] AND ("2007/01/01" [PDAT]: "2017/12/31" [PDAT]). Hand searches were also conducted. Results: In the literature search with the MESH terms, 36 articles were found, distributed in the territory with 10 in Colombia and 26 in the rest of South America. Important diff erences were found in the relationship between the parasite and the host when comparing Colombia with the rest of the world. The strains in Colombia are more virulent (Type I / III and atypical) and we found a high prevalence of positive titers and development of OT in the country, with water and meat products as one of the main means of contagion. The importance of peptides that triggered the humoral immune response in patients was determined. Significant differences were found in the clinical severity (with Colombian patients experiencing a greater size of lesions, degree of infl ammation, macular involvement, bilateral involvement, and recurrences) related to the infl ammatory response produced in the host, associated with a decrease in intraocular levels of IFN-γ / IL-17 and an increase of IL-6 / Il-13. In Colombian patients, ocular cytokinome is related to clinical features, presenting a Th 2 response related to severe ocular involvement. Conclusion: Research contributions of OT in Colombia have been of global importance, allowing to know more about the type of parasite, the epidemiology, the clinical presentation, the immune response.

Diagnóstico y tratamiento inicial de la uveítis por médicos no oftalmólogos / Diagnosis and treatment of uveitis by non-ophthalmologist physicians

Resumen Objetivos: Describir los principales signos y síntomas, así como el tratamiento inicial de un paciente con diagnóstico de uveítis con el propósito de evitar retardo en la remisión y el inicio del manejo oportuno de esta patología. Métodos: Se realizó una revisión sistemática de la literatura en la cual se identificaron los principales signos y síntomas que deben ser tenidos en cuenta para sospechar el diagnóstico de uveítis y su tratamiento indicado. Se llevó a cabo una búsqueda en PubMed durante el periodo del 2010-2015, se eligieron 439 artículos, los cuales fueron sometidos a dos procesos de filtrado manual, eligiendo por un grupo de investigadores los resúmenes que respondieran nuestra pregunta de investigación. Posteriormente un grupo de oftalmólogos expertos y médicos con experiencia en oftalmología realizaron una segunda revisión. Resultados: Posterior al primer proceso de filtrado se obtuvieron 73 artículos que se sometieron a un segundo proceso de selección donde se obtuvieron 30 artículos. De la selección final de artículos: seis fueron estudios observacionales o ensayos clínicos; los artículos restantes fueron revisiones de la literatura. Los estudios observacionales y ensayos clínicos aleatorizados se evaluaron con la herramienta GRADE siendo la mayoría de evidencia alta. Se hizo una revisión de los treinta artículos seleccionados, por parte de nuestros investigadores, dando como resultado recomendaciones para el diagnóstico y tratamiento de la uveítis para el personal médico no oftalmólogo. Conclusiones: Existen un conjunto de signos y síntomas que pueden hacer sospechar al médico no oftalmólogo el diagnóstico de uveítis. Ante un paciente que presenta dolor ocular asociado a disminución de la agudeza visual, fotofobia, ojo rojo sin secreción conjuntival, miosis pupilar, depósitos retroquératicos y hallazgos al fondo de ojo como vitreitis o coriorretinitis se debe sospechar una uveítis. El manejo precoz de la uveítis anterior no infecciosa puede ser instaurado por el médico no oftalmólogo con corticoides tópicos, sin embargo, en caso de uveítis intermedia y posterior es importante remitir al oftalmólogo cuanto antes. Proponemos un algoritmo para ayudar al diagnóstico de la uveítis y recomendaciones para su manejo inicial.

Abstract Objective: The purpose of this study was to describe the main diagnostic features and the initial management of uveitis, in order to avoid delays in the treatment and the remission to the ophthalmologist. Methods: A systematic review of the literature, which identified the main signs and symptoms and initial treatment for patients with uveitis, was done. A search of the literature published through 2010-2015 was performed using PubMed database. Four hundred and thirty nine eligible articles underwent a selection process in which titles, abstracts and full texts were reviewed, obtaining thirty final articles. Results: Thirty articles were reviewed, six were observational studies and clinical trials; 24 articles were reviews or case reports. The observational studies and clinical trials were rated with the Grading of Recommendations Assessment (GRADE) tool. After the grading tree of the articles were of high level of evidence. Conclusions: In a patient with ocular pain related to decreased visual acuity, photophobia, red eye without secretion, miosis, keratic precipitates, and vitritis or chorioretinitis the healthcare provider should rule out the diagnosis of uveitis. A non-ophthalmologist physician can start the initial management of an anterior uveitis and then refer the patient to the ophthalmologist as soon as possible. If the diagnosis is an infectious anterior uveitis, intermediate uveitis or posterior uveitis the patient should be derived to the ophthalmologist immediately.

Serum levels of neurotrophic factors in active toxoplasmic retinochoroiditis

Abstract Toxoplasmic retinochoroiditis (TR) is the most common identifiable cause of posterior uveitis in Brazil. Response to treatment and clinical presentation may vary significantly. We assessed serum levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin (NT)-3, and NT-4/5 in patients with active TR, before and after TR treatment. Methods: Twenty patients with active lesion and 15 healthy controls were enrolled in the study. Serum concentration of neurotrophic factors was determined by enzyme-linked immunosorbent assay. Results: BDNF levels were significantly higher in patients before treatment when compared with controls (p = 0.0015). There was no significant difference in pro-BDNF, NGF, GDNF, NT-3, and NT-4/5 levels between TR patients and controls. Treatment did not affect the levels of these factors. Conclusion: BDNF may be released in the context of the active TR inflammatory response.

Propriedades psicométricas do Children's Visual Function Questionnaire adaptado para avaliação de qualidade de vida relacionada à visão de crianças com toxoplasmose congênita / Psychometric properties of the Children's Visual Function Questionnaire adapted to assess vision-related quality of life in children with congenital toxoplasmosis

Introdução: A elevada prevalência da toxoplasmose congênita (TC) no Brasil, verificada também no estado de Minas Gerais, associada ao maior comprometimento ocular observado nas crianças brasileiras comparadas às europeias; e a evolução de muitos desses indivíduos para a baixa visão (BV), nos remetem à necessidade de compreender o impacto da perda visual na qualidade de vida em uma coorte de crianças infectadas identificadas no período neonatal e tratadas com antiparasitários durante o primeiro ano de vida. Objetivo: Adaptar o questionário Children's Visual Function Questionnaire (CVFQ) à realidade sociocultural de crianças brasileiras com toxoplasmose congênita e investigar as propriedades psicométricas para mensuração da qualidade de vida (QV) relacionada à visão nesses pacientes; descrever as lesões retinocoroideanas observadas em uma coorte de crianças pré-escolares com TC em Minas Gerais; avaliar quantitativamente o déficit visual e investigar sua correlação com a pontuação na percepção da QV relacionada à perda visual (CVFQ7-BR-toxo). Método: Estudo epidemiológico transversal aninhado, em uma coorte de 142 crianças acompanhadas prospectivamente nos Serviços de Infectologia Pediátrica e Oftalmologia do Hospital das Clínicas da UFMG. Questionários foram aplicados aos pais e cuidadores para avaliar a percepção sobre a QV de suas crianças com TC e para verificar a situação socioeconômica das famílias. Oftalmologistas do setor de uveite avaliaram a retina das crianças e descreveram as lesões de retinocoroidite quanto à localização, número de lesões, tamanho e lateralidade. No setor de baixa visão, oftalmologistas avaliaram a acuidade visual. Foram usadas técnicas de estatística multivariada para avaliar as propriedades psicométricas da escala de QV e testes de Kruskal Wallis e Mann Whitney para a comparação dos escores medianos da escala de QV em crianças com visão normal, perda visual leve e baixa visão. O estudo foi aprovado pelo Comitê de Ética em Pesquisa da UFMG. Resultado: Adaptações no CVFQ versão brasileira deram origem ao CVFQ7-BR-toxo, questionário para avaliar a percepção de pais/cuidadores sobre qualidade de vida relacionada a baixa visão de crianças com toxoplasmose congênita pré-escolares. Na análise fatorial exploratória o resultado do teste Kaiser-Meyer-Olkin Measure of Sampling Adequacy (KMO) foi de 0,74, indicando boa adequabilidade do modelo fatorial. Seis componentes (fatores) extraídos correspondem a 46,3% da variância total explicada, e são compostos por itens com coeficiente de saturação (carga fatorial) maior ou igual a 0,45. Pela descrição, estrutura de variabilidade, e interpretação do agrupamento dos itens do questionário CVFQ adaptado (CVFQ7-BR-toxo) identificaram-se seis subescalas: saúde geral; capacidade visual; desempenho visual/visão funcional; comportamento social e pessoal, impacto na família e tratamento. A homogeneidade das medidas para o construto QV no CVFQ adaptado foi avaliada pela consistência interna das subescalas. As subescalas Desempenho visual - visão funcional e o Impacto na família se mostraram adequadas, com coeficiente alfa de Cronbach de 0,75 e 0,77 respectivamente. As subescalas comportamento pessoal e social e, tratamento apresentaram valores de alfa de Cronbach menores que 0,7 (0,68 e 0,61 respectivamente). A correlação entre as subescalas e a escala global foram todas significativas (p-valor <0,001) variando de 0,42 a 0,75. As correlações item-escala globais foram significativas (p-valor <0,01) e maiores do que 0,20, sendo estes valores considerados aceitáveis. Verificou-se a validade discriminante do instrumento pelas diferenças significativas (p<0,005) na comparação das escalas do CVFQ7-BR-toxo para escores relatados pelo pai/cuidador de crianças com e sem baixa visão. A validação convergente foi verificada pela correlação (r=0,58; p<0,001) entre o escores globais do CVFQ7-BR-toxo e do PedsQL, com resultado moderado. Para análise dos exames clínicos oftalmológicos, das 142 crianças, duas foram excluídas por não terem realizado todos os exames. Das 140 crianças, 87,1% (121/139) apresentaram pelo menos uma lesão de retinocoroidite e, dentre elas, 20,7% (25/121) foram diagnosticadas com baixa visão (BV). A retinocoroidite esteve presente em ambos os olhos de 81,0% (98/121) das crianças com lesões, sendo que 25,5% (25/98) destas tinham BV. Lesão macular (foveal e/ou extrafoveal) em ambos os olhos ocorreu em 43,9% (43/98) das crianças e 51,2% (22/43) destas apresentaram BV. Pelo menos 50% das crianças com BV apresentaram lesões com tamanho médio superior a 3,0 diâmetros de disco óptico (DD). Ausência de lesão ocorreu em apenas 12,9% (18/140) das crianças. Na percepção dos pais cuidadores (CVFQ7-BR-toxo) das crianças diagnosticadas com BV, os escores medianos foram menores nas dimensões capacidade visual (p=0,002), desempenho funcional/visão funcional (p=0,002), impacto na família (p=0,001) e na QV global (p=0,009) quando comparados às crianças com perda visual leve e com visão normal. Conclusão: As propriedades psicométricas do CVFQ7-BR-toxo se mostraram adequadas quanto à validade do construto QV. O instrumento foi capaz de registrar o impacto no comprometimento da visão funcional e na família de crianças com toxoplasmose congênita. Na avaliação oftalmológica dessa população foram observadas lesões retinocoroideanas de maior gravidade, por serem em sua maioria maculares, múltiplas, bilaterais, resultando em comprometimento da função visual e menor acuidade visual. Na percepção dos pais e cuidadores sobre a QV relacionada a baixa visão, estas crianças apresentaram pior capacidade visual, pior desempenho funcional / visão funcional, com maior impacto nas suas famílias e piora da qualidade de vida global. Esses resultados podem subsidiar políticas para melhor controle e prevenção da toxoplasmose congênita.

Introduction: The high prevalence of congenital toxoplasmosis (CT) in Brazil, in addition to the high burden of ocular involvement in infected individuals, evolving to low vision (LV) in many of them, highlights the importance of assessing their quality of life (QOL). Objective:To adapt the Children's Visual Function Questionnaire (CVFQ) to the sociocultural reality of Brazilian children with CT, and to investigate the psychometric properties to measure vision-related quality of life (QOL) for these patients; to characterize retinochoroidal changes in a cohort of preschool children with CT in Minas Gerais; to quantitatively evaluate the visual deficit and to investigate its correlation with QOL perception scores (CVFQ7-BR-toxo instrument).Methods: Cross-sectional epidemiological study with nested cohort of 142 children prospectively followed at the Pediatric Infectious Disease and Ophthalmology Services of Hospital das Clínicas da Universidade Federal de Minas GeraisQuestionnaires were applied to parents and carers to evaluate QOL perception of their children with CT and to characterize the socioeconomic status of their families. Number, location, size and laterality of retinochoroidal lesions were recorded. Best-corrected visual acuity was also assessed. Multivariate statistical techniques were used to evaluate psychometric qualities of QOL scale. Kruskal Wallis and Mann Whitney test were employed for comparison of median scores of the QOL scale in children with normal visual, mild vision loss and low vision. Results: Adaptations in the CVFQ-Brazilian version originated the CVFQ7-BR-toxo, a questionnaire to evaluate perception of parents/carers about vision-related QOL of preschool children with CT. In the exploratory factor analysis, result of KaiserMeyer-Olkin Measure of Sampling Adequacy test (KMO) was 0.74, indicating good suitability of the factor model.Six extracted components (factors) explained 46.3% of total variance, consisting of items with saturation coefficient (factor load) ≥ 0.45. Six subscales were identified after description, variability structure and interpretation of grouping of items of CVFQ7-BR-toxo: Overall Health; Visual Acuity; Visual Performance/Functional Vision; Individual and Social Behavior, Impact on Family, and Treatment. Homogeneity of measures for the QOL construct in the adapted CVFQ was evaluated by internal consistency of the subscales: Subscales Visual Performance/Functional Vision and Impact on Family showed to be adequate, with Cronbach's alpha of 0.75 and 0.77 respectively.Subscales Individual and Social Behavior and Treatment showed Cronbach's alpha coefficient smaller than 0.7 (0.68 and 0.61 respectively). The correlations between subscales and the global scale were all statistically significant (p-value <0.001) ranging from 0.42 to 0.75. The global item-scale correlations were also significant (p-value <0.01) and greater than 0.20, with these values being considered acceptable. Discriminant validity of the instrument by significant differences (p <0.005) was verified in the comparison of CVFQ7-BR-toxo scales to the scores reported by the parent/carers of children with and without low vision.The convergent validity was verified by the moderate correlation (r = 0.58; p <0.001) between the overall scores CVFQ7- BR-toxo and PedsQL. For the analysis of the clinical examinations of the 142 children, two were excluded because they did not have all the exams. Of the 140 children, 87.1% (121/139) had at least one retinochoroidal lesion. Among them, 20.7% (25/121) were diagnosed with LV. Retinochoroiditis was found in both eyes in 81.0% (98/121), and 25.5% (25/98) of these had LV. Macular (foveal and/or extrafoveal) lesions in both eyes occurred in 43.9% (43/98); 51.2% (22/43) of these children had low LV. At least 50% of children with LV presented retinochoroidal lesions with an average size > 3 optic disc diameter. Absence of retinochoroidal lesions was recorded in only 12.9% (18/140) of children. In the perception of carers parents (CVFQ7-BR-toxo) of children diagnosed with LV, median scores were lower for visual ability dimensions (p = 0.002), functional performance- visual function (p = 0.002), impact on family (p = 0.001) and overall QOL (p = 0.009) when compared to those of children with mild visual loss and with normal vision. Conclusion: CVFQ7-BR-toxo psychometric properties were appropriate concerning the validity of the QOL construct. The questionnaire was able to register the impact of visual disability on families of children with CT. Retinochoroiditis, was more severe, with frequent multiple, bilateral and macular lesions, resulting in impaired visual function. According to QOL perception of parents and carers, children with LV presented worse scores for visual capacity, functional performance/functional vison, with greater impact on their families and decreased overall quality of life. These results can support policies for better control and prevention of CT.

Ocular toxoplasmosis with positive polymerase chain reaction in peripheral blood ­ report of two cases, São Paulo State, Brazil / Toxoplasmose ocular com reação em cadeia da polimerase positiva em sangue periférico ­ relato de dois casos, estado de São Paulo, Brasil

Aims: To describe the use of polymerase chain reaction (PCR) in peripheral blood and demonstrate its importance in the clinical follow-up of patients with ocular toxoplasmosis. Case description: Two immunocompetent patients were clinically diagnosed with acute ocular toxoplasmosis. The routine clinical evaluation consisted of fundus examination using binocular indirect ophthalmoscopy, color fundus photography, fluorescein angiography, and spectral domain optical coherence tomography. The serological diagnosis was made by enzyme-linked immunosorbent assay (ELISA) and confirmed by enzyme-linked fluorescent assay (ELFA). The molecular diagnosis was made by PCR in peripheral blood using the B1 gene of Toxoplasma gondii as marker. The younger patient was male, had previous lesion in the right eye, complained of low visual acuity in the left eye and was under treatment. The older patient was male, had retinal detachment, and presented with sudden loss of acuity in the right eye. The fundus examination revealed chorioretinal scar in the left eye. IgG was reactive, IgM was non-reactive, and PCR was positive in the peripheral blood of both patients. New blood samples were collected for serological and molecular monitoring and PCR remained positive in both cases. Six weeks after treatment with oral sulfadiazine and pyrimethamine, the PCR yielded negative results. Conclusion: The results show that T. gondii antigens may be found in peripheral blood during ocular reactivations and that PCR may be a good tool for the follow-up of patients with ocular toxoplasmosis.

Objetivos: Descrever o uso da reação em cadeia da polimerase (PCR) no sangue periférico e demonstrar sua importância no acompanhamento clínico de pacientes com toxoplasmose ocular. Descrição dos casos: Dois pacientes imunocompetentes foram clinicamente diagnosticados com toxoplasmose ocular aguda. Rotineiramente, a avaliação clínica foi feita por fundoscopia com o uso de oftalmoscópio binocular indireto, retinografia colorida, angiografia fluorescente e tomografia de coerência óptica espectral. A sorologia foi realizada por ensaio imunoenzimático (ELISA) e confirmada por ensaio imunoenzimático fluorescente ELFA (IgG, IgM). O diagnóstico molecular foi realizado por PCR em sangue periférico usando o gene B1 de Toxoplasma gondii como marcador. O paciente mais jovem era do sexo masculino, apresentava lesão prévia no olho direito, queixa de baixa acuidade visual no olho esquerdo e estava sob tratamento. O paciente mais velho era do sexo masculino, apresentava descolamento de retina e súbita diminuição de visão no olho direito. A fundoscopia revelou cicatriz coriorretiniana no olho esquerdo. Ambos os pacientes tinham IgG reagente, IgM não reagente e PCR positivo em sangue periférico. Novas amostras de sangue foram coletadas para monitoramento sorológico e molecular e a PCR permaneceu positiva em ambos os casos. Seis semanas após o início do tratamento com sulfadiazina e pirimetamina oral, os resultados do PCR tornaram-se negativos. Conclusões: Os resultados mostram que antígenos de T. gondii podem ser encontrados em sangue periférico durante as reativações oculares e que a PCR parece ser uma boa ferramenta para o acompanhamento de pacientes com toxoplasmose ocular.

Reactivation of Ocular Toxoplasmosis – A Case Report

Ocular toxoplasmosis is the commonest cause of posterior uveitis and is usually the result of an acquired infection caused by the protozoan Toxoplasma gondii,here we present report of case of spontaneous reactivation of toxoplasmosis in a 14-yr old girl. with reactivation o oocular toxoplasmosis.

Single nucleotide polymorphisms in the interferon gamma gene are associated with distinct types of retinochoroidal scar lesions presumably caused by Toxoplasma gondii infection

The association of single nucleotide polymorphisms (SNPs) in the interferon (IFN)-γ gene ( IFNG ) with different types of retinal scar lesions presumably caused by toxoplasmosis were investigated in a cross-sectional population-based genetic study. Ten SNPs were investigated and after Bonferroni correction, only the associations between SNPs rs2069718 and rs3181035 with retinal/retinochoroidal scar lesions type A (most severe scar lesions) and C (least severe scar lesions), respectively, remained significant. The associations of two different IFNG SNPs with two different types of retinal lesions attributable to toxoplasmosis support the hypothesis that different inflammatory mechanisms underlie the development of these lesions. The in vitro analysis of IFN-γ secretion by peripheral blood mononuclear cells stimulated with Toxoplasma gondii antigens was also investigated. The association between SNP rs2069718 and type A scar lesions revealed that differential IFN-γ levels are correlated with distinct genotypes. However, no correlation was observed with IFN-γ secretion levels and the SNP rs3181035 , which was significantly associated with type C scar lesions. Our findings strongly suggest that immunogenetic studies of individuals with congenital or postnatally acquired infection are needed to better understand the role of IFN-γ and its polymorphisms in the pathogenesis of ocular toxoplasmosis.

Epidemiologia de la toxoplasmosis ocular en pacientes del Instituto Nacional de Oftalmología del Perú, 2003-2007 / Ocular toxoplasmosis epidemiology in patients of National Institute Ophthalmology of Peru, 2003-2007

Objetivo: Describir las características clínico epidemiológicas de la Toxoplasmosis ocular activa, enpacientes del Servicio de Úvea del Instituto Nacional de Oftalmología (INO), desde el 2003 hasta el 2007. Materiales y Métodos: Estudio descriptivo retrospectivo, en el que se utilizaron 1498 historiasclínicas de pacientes del servicio de Úvea del Instituto Nacional de Oftalmología desde enero del 2003hasta octubre del 2007. Se obtuvieron 210 historias con diagnóstico de Toxoplasmosis ocular, siendo excluidos del estudio 109 pacientes por presentar: 16 IgG toxoplasma negativo, 46 sin coriorretinitis exudativa activa, 45 sin IgG toxoplasma y dos con opacidad vítrea intensa. La ceguera legal fue definida como la mejor agudeza visual corregida en el ojo afectado, menor o igual a 20/200. Se utilizaron comovariables: la edad, sexo, lugar de nacimiento y procedencia, características clínicas, tiempo de seguimiento, tiempo de inactivación de la lesión, complicaciones y agudeza visual final. Resultados: De 99 pacientes(102 ojos), el 55,56% fueron del sexo masculino. El grupo etario mayormente comprometido fueel de 21-30 años (31,31%). El 96,97% presentó lesión unilateral. La localización más frecuente fue la perifé-rica (61,90%). La complicación más frecuente: lesiones maculares (23,53%). El 7,07% de pacientes fue VIH(+), sin diferencias en la presentación clínica con respecto a los otros pacientes. Conclusiones: Lafrecuencia de Toxoplasmosis Ocular fue de 14,02%, inferior a los reportes mundiales (22,5%), lapresentación clínica-epidemiológica fue similar a la descrita en la literatura, mayormente en nacidos enel interior del país, en la tercera década de la vida, afección ocular unilateral y localización periférica de lalesión retinal. (AU)

Objective: To describe clinical - epidemiological characteristics of the ocular active toxoplasmosis, in patients of Uvea's Service of the National Institute of Ophthalmology, from 2003 to 2007. Materials and Methods: Retrospective descriptive study, which used 1498 patient records Uveal Service National Eye Institute from January 2003 to October 2007 as an information source. Were 210 patients obtained with diagnosis of ocular toxoplasmosis. Were 109 patients excluded: 16 IgG toxoplasma negative, 46 without exudative chorioretinitis activate, 45 without IgG toxoplasma, 02 with intense vitreous opacity. Legal blindness was definite to the best visual keenness corrected in the affected, minor eye or like 20/200. Variables were used as age, sex, place of birth and origin, clinical characteristics, time of follow-up, time of unactivation of the injury, complications and visual final keenness. Results: From 99 patients (102 eyes), 55.56 %. The age group mainly damaged was from 21 to 30 years old (31.31 %). 96.97 % showed unilateral injury. The most frequent location: peripheral (61.90 %).The most frequent complication: cataract (8.82 %). 7.07 % were HIV (+), without differences in the clinical presentation regarding the other patients. Conclusions: The predominance of the ocular Toxoplasmosis was 14.02 %, lower than the world reports (22.5 %).The clinical - epidemiologic presentation was similar to that described in the documentation, where the unilateral ocular condition and the peripheral location of the retinal injury affected to those born inside the country (Lima-Callao), in the third decade of the life. (AU)

Genetic polymorphism for IFNγ +874T/A in patients with acute toxoplasmosis / Polimorfismo genético para IFNγ +874T/A em pacientes com toxoplasmose aguda

INTRODUCTION: A single nucleotide polymorphism (SNP) in the gene encoding gamma interferon influences its production and is associated with severity of infectious diseases. This study aimed to evaluate the association of IFNγ+874T/A SNP with duration of disease, morbidity, and development of retinochoroiditis in acute toxoplasmosis. METHODS: A case-control study was conducted among 30 patients and 90 controls. RESULTS: Although statistical associations were not confirmed, A-allele was more common among retinochoroiditis cases and prolonged illness, while T-allele was more frequent in severe disease. CONCLUSIONS: Despite few cases, the results could indicate a relation between IFNγ+874T/A single nucleotide polymorphism and clinical manifestations of toxoplasmosis.

INTRODUÇÃO: Um polimorfismo de nucleotideo único (SNP) no gene codificante para interferon gama influencia a sua produção e pode estar associado à gravidade de diversas doenças infecciosas. O objetivo deste estudo foi avaliar a associação entre SNP para IFNγ+874T/A com a duração da doença, a morbidade e o desenvolvimento de retinocoroidite na toxoplasmose aguda. MÉTODOS: Estudo de caso-controle incluindo 30 pacientes e 90 controles. RESULTADOS: Apesar da ausência de associação estatística, o alelo A foi mais comum entre os casos com retinocoroidite e doença prolongada e o alelo T nas formas mais severas. CONCLUSÕES: Os dados encontrados sugerem uma relação entre o polimorfismo de base única em IFNγ+874T/A com a morbidade e com o desenvolvimento de retinocoroidite por toxoplasmose.

Caracterización clínica y serológica de la toxoplasmosis ocular activa / Clinical and serological characterization of active ocular toxoplasmosis

Objetivo: Describir las características clínicas y serológicas de un grupo de pacientes afectados de toxoplasmosis ocular activa. Método: Estudio observacional, descriptivo, de corte transversal realizado en 54 ojos de igual número de pacientes con diagnóstico de toxoplasmosis ocular. Se les realizó un examen oftalmológico completo y se determinó los niveles de anticuerpos Ig G anti-toxoplasma en suero por inmunofluorescencia indirecta. Resultados: Las edades de 16 a 45 años y el sexo masculino predominaron en los pacientes estudiados. El 100 % presentó retinocoroiditis acompañada de vitritis de variable intensidad. Predominaron en 51,9 % las lesiones recurrentes. La afectación visual moderada fue más frecuente (46,3 %), constituyó la zona I de retina el área mayormente afectada (53,7 %). La Ig G fue positiva en el 88,9 % de los pacientes, hubo un predominio de la dilución 1/32 (38,9 %). Las complicaciones más frecuentes fueron: membrana epirretinal (7,41 %), opacidades vítreas (5,56 %) y glaucoma secundario (5,56 %). Conclusiones: Las características epidemiológicas de los pacientes coincidieron con lo descrito en la literatura. El grado de afectación visual estuvo relacionado con la localización de las lesiones. Prevaleció la serpositividad a la Ig G para toxoplasma a diluciones bajas.

Objective: To report the clinical and serological features of active ocular toxoplasmosis in a group of patients. Methods: A cross-sectional observational and descriptive study was conducted in 54 eyes from an equal number of patients, with a diagnosis of active ocular toxoplasmosis. A complete ophthalmologic exam was performed; and indirect immunofluorescence was applied to estimate the anti-toxoplasma IgG antibodies levels in peripheral serum. Results: Male patients and 16-45 y age group prevailed. All of the patients presented with retinochoroiditis along with vitreous haze of variable density. Recurrent lesions prevailed in 51.9% of cases. Mild visual impairment was more common (46.3%,), being the retinal zone I the most compromised(53.7 %). Ig G was positive in 88.9% of patients; 1/32 dilution prevailed (38.9 %). The most frequent ocular complications were epiretinal membrane (7. 41 %), vitreous opacities (5.56 %) and secondary glaucoma (5.56 %). Conclusion: In this study, the epidemiological characteristics of patients were similar to those described in literature. The level of visual impairment was related with the location of lesions, whereas IgG positivity to toxoplasma at low dilutions predominated.

Fulminant toxoplasmic retino-choroiditis following intravitreal triamcinolone administration.

We report two cases of fulminant toxoplasmic retinochoroiditis following intravitreal triamcinolone acetonide (IVTA) administration. Case 1: A 42-year-old female received IVTA for presumed non-infectious panuveitis. Within 2 months, she developed diffuse macular retinochoroiditis with optic disc edema. Upon starting anti-toxoplasmic therapy (ATT), her intraocular inflammation resolved with catastrophic damage to the disc and macula. Case 2: A 30-year-old male received IVTA for presumed reactivation of previously scarred toxoplasmic retinochoroiditis. Despite simultaneous ATT, within 6 weeks, he developed extensive, multifocal macular retinochoroiditis. He continued to require ATT for 18 months and later underwent vitrectomy with silicone oil placement for severe epiretinal proliferation. Aqueous tap polymerase chain reactions were found positive for Toxoplasma gondii in both cases. In conclusion, IVTA administration can lead to fulminant toxoplasmic retinochoroiditis even when used with appropriate ATT. Extreme caution should be exercised while administering depot corticosteroids in eyes with panuveitis of unknown origin.

Intravitreal Clindamycin Injection for Toxoplasmic Retinochoroiditis

PURPOSE: To present cases of toxoplasmic retinochoroiditis (TRC) treated successfully with intravitreal clindamycin injection. CASE SUMMARY: (Case 1) A 41-year-old man presented with blurred left eye vision for several months. The patient had a large chorioretinal scar with infiltrations at the boundaries, and fluorescein angiography (FA) showed active retinochoroiditis. Antitoxoplasmosis (antiTX) immunoglobulin G (IgG) was positive, and the patient was started on antiTX medication. Despite several weeks of treatment with maximum doses of antiTx, the TRC progressed and visual acuity worsened. Pars plana vitrectomy (PPV) with intravitreal clindamycin injection (1.0 mg/0.1 ml) was performed, and an additional injection was given 4 weeks later. Six weeks after the second injection, TRC wascompletely resolved with 20/20 vision. (Case 2) A 67-year-old man presented with decreased left eye vision for 1 year. Fundus examinations showed vitreous opacity and epiretinal membranes. The FA revealed retinochoroiditis and the antiTX IgG titer was elevated. The presumed diagnosis was TRC, and oral medications of trimethoprim-sulfamethoxazole, clindamycin, and prednisolone was administered. Inflammation began to improve however, as the patient was not tolerating systemic antiTx medications, an intravitreal injection of clindamycin (1.0 mg/0.1 ml) was administered with PPV. The patientdiscontinued oral medication after surgery, and the inflammation resolved 5 weeks later. CONCLUSIONS: Intravitreal clindamycin injections may be an additional treatment option for TRC in patients who are unable to tolerate systemic therapy or whose disease progresses despite systemic therapy.

A Case of Ocular Toxoplasmosis Imaged with Spectral Domain Optical Coherence Tomography

A 54-year-old man presented with blurred central vision in the right eye of two weeks' duration. On presentation, visual acuity was 40 / 50 in the right eye and fundus examination showed a whitish-yellow inflammatory lesion near an atrophic, pigmented retinochoroidal scar located in the superotemporal quadrant. Serologic assessment was negative for IgM, but serum IgG to toxoplasma was elevated. Spectral domain optical coherence tomography (SD-OCT) revealed increased reflectivity from the inner retinal layer, retinal thickening, and choroidal shadowing while focal posterior hyaloid thickening and detachment were observed in the new lesion. He was treated with trimethoprim/sulfamethoxazole, clindamycin, and prednisone. SD-OCT is helpful for definitively differentiating ocular toxoplasmosis from other retinal diseases.

Achados oculares em crianças com toxoplasmose congênita / Ocular findings in children with congenital toxoplasmosis

OBJETIVO: Conhecer as lesões oculares mais frequentes encontradas em crianças expostas à toxoplasmose congênita. MÉTODOS: Trata-se de um estudo retrospectivo, a partir de uma coorte histórica, de abordagem quantitativa. Foram avaliadas crianças encaminhadas de um serviço de infectologia pediátrica e inseridas apenas aquelas com diagnóstico confirmado de toxoplasmose congênita. A avaliação oftalmológica incluiu o mapeamento de retina sequencial, sob dilatação pupilar. RESULTADOS: Das 58 crianças presumivelmente expostas ao risco de doença durante a gestação, 20 apresentaram lesões oftalmológicas ao longo do primeiro ano de vida (34 olhos). Destas, 12 estavam assintomáticas ao nascimento. Estrabismo foi registrado em 14 crianças (70 por cento). Em uma criança observou-se ptose palpebral e em outra diminuição da fenda palpebral (microftalmia). Retinocoroidite foi a complicação mais frequente, presente em todas as 20 crianças. Sete crianças apresentaram alterações unilaterais (35 por cento) e 13 crianças apresentaram alterações bilaterais (65 por cento), prevalecendo a localização no polo posterior e mácula. CONCLUSÃO: Retinocoroidite e estrabismo destacaram-se como importantes sequelas da toxoplasmose congênita.

PURPOSE: This study aimed to know the most common ocular findings in children with congenital toxoplasmosis. METHODS: This is a retrospective study carried out from a historical cohort, with a quantitative approach. We evaluated children referred to a pediatric infectious disease service and included only those with confirmed diagnosis of congenital toxoplasmosis. The ophthalmologic evaluation included regular fundus examination under pupil dilation. RESULTS: Of 58 children presumably exposed to risk of the disease during the pregnancy, 20 had ocular lesions during the first year of life (34 eyes). Of these, 12 were asymptomatic at birth. Strabismus was noted in 14 children (70 percent). In one child there was ptosis, and another had decrease in the palpebral fissure (microphthalmia). Retinochoroiditis was the most common complication, present in all 20 children. Seven children (35 percent) showed unilateral changes and 13 children showed bilateral changes (65 percent), with emphasis on the location in the posterior pole and macula. CONCLUSION: Retinochoroiditis and strabismus were outstanding as important sequelae of congenital toxoplasmosis.

Comportamiento clínico-epidemiológico de la toxoplasmosis ocular / Clinical-epidemiological behavior of ocular toxoplasmosis

OBJETIVO: Determinar aspectos clínico-epidemiológicos en pacientes con diagnóstico de toxoplasmosis ocular, que asistieron a la consulta de oftalmología del Policlínico de Guanajay, durante el año 2008. MÉTODOS: Fue realizado un estudio observacional, descriptivo, longitudinal y prospectivo, donde se analizaron las variables edad, sexo, presencia de animales domésticos, hábitos alimentarios, signos y síntomas, número de lesiones, localización, actividad, ojo afectado y complicaciones. Fueron atendidos 11 pacientes en consulta con el diagnóstico de toxoplasmosis ocular. RESULTADOS: Predominaron las edades comprendidas entre 30 y 44 años, con 36,3 por ciento. Tenían animales domésticos el 72,2 por ciento de los pacientes y el 81,8 por ciento presentaban hábitos no adecuados de alimentación. Predominó la visión borrosa (72,7 por ciento). La retinocoroiditis se presentó en el 72,7 por ciento de los pacientes. De ellos, 54,5 por ciento tenían un daño severo. Predominaron las lesiones inactivas con 72,7 por ciento y las lesiones únicas (90,9 por ciento). El 45,4 por ciento tuvo una localización macular y el 36,3 por ciento perimacular. Las complicaciones que se presentaron fueron el déficit visual y la catarata. CONCLUSIÓN: La toxoplasmosis ocular predomina en el sexo masculino y es más frecuente en regiones de bajas condiciones de salud pública e inadecuados hábitos alimenticios. Dentro de los factores de riesgo se encuentra la presencia de animales domésticos, sobre todo los felinos. La visión borrosa y la retinocoroiditis son referidos por los pacientes. Generalmente cursa con algún grado de afectación visual, y es severa en el mayor número de los pacientes. Las lesiones inactivas, únicas y con localización macular, y el déficit visual y la catarata son complicaciones predominantes en estos casos

OBJECTIVE: To determine the clinical-epidemiological features in patients diagnosed with ocular toxoplasmosis seen in the Ophthalmology consultation of the Guanajay municipality polyclinic during 2008. METHODS: A prospective, longitudinal, descriptive and observational study was conducted to analyze the following variables: age, sex, and presence of domestic animals, food habits, signs and symptoms, number of lesions, location, activity, involved eye and complications. In consultation 11 patients were seen diagnosed with ocular toxoplasmosis. RESULTS: There was predominance of ages between 30 and 44 years for a 36.3 percent. The 71.2 percent of patients had domestic animals and the 81.8 percent had no appropriate feeding habits. Also, there was predominance of blurred vision (72.7 percent). Retinochoroiditis was present in the 72.7 percent of patients. From them, the 54.5 percent had a severe damage. There were many inactive lesions with a 72.7 percent and unique lesions (90.9 percent) The 45.4 percent had a macular location and the 36.3 percent a perimacular one. Complications present were a visual deficit and cataract. CONCLUSION: Ocular toxoplasmosis is more predominant in male sex and is more frequent in regions with poor conditions of public health and inappropriate food habits. Included in factors is the presence of domestic animals, mainly the cats. The blurred vision and retinochoroiditis are referred by patients. In general, it has some degree of visual involvement and it is severe in most of patients. The unique inactive lesions and with macular location as well as the visual deficit and cataract are complications predominant in these cases

Clinical Features of Ocular Toxoplasmosis in Korean Patients

We report here the records of 10 consecutive Korean patients (10 eyes) with ocular toxoplasmosis which showed the typical clinical manifestations with seropositivity for Toxoplasma gondii specific IgG antibodies by micro-ELISA between 2006 and 2010. Nine patients were males and 1 was female; their age was 50.5+/-13.8 years. The most common accompanying signs were vitritis (100%), anterior uveitis (70%), and scattered white deposit (80%). Pre-existing retinochoroidal scar was found in 1 (10%) patient. All patients received antiparasitic chemotherapy and systemic corticosteroid treatment, which resolved the presenting attack and recovered the visual acuity better than initial one in 9 patients and worse in 1. Optic atrophy, cataract, and retinal neovascularization were observed during the follow-up period and recurrence was detected in 3 eyes (30%) 6 to 20 months after the initial attack. In Korea, although rarely detected and reported, ocular toxoplasmosis needs more attention in clinical field of retinal diseases.

Candidate gene analysis of ocular toxoplasmosis in Brazil: evidence for a role for toll-like receptor 9 (TLR9)

Toxoplasma gondii infection is an important mediator of ocular disease in Brazil more frequently than reported from elsewhere. Infection and pathology are characterized by a strong proinflammatory response which in mice is triggered by interaction of the parasite with the toll-like receptor (TLR)/MyD88 pathway. A powerful way to identify the role of TLRs in humans is to determine whether polymorphisms at these loci influence susceptibility to T. gondii-mediated pathologies. Here we report on a small family-based study (60 families; 68 affected offspring) undertaken in Brazil which was powered for large effect sizes using single nucleotide polymorphisms with minor alleles frequencies > 0.3. Of markers in TLR2, TLR5 and TLR9 that met these criteria, we found an association Family Based Association Tests [(FBAT) Z score = 4.232; p = 1.5 x 10-5; p corrected = 1.2 x 10-4] between the C allele (frequency = 0.424; odds ratio = 7; 95 percent confidence interval 1.6-30.8) of rs352140 at TLR9 and toxoplasmic retinochoroiditis in Brazil. This supports the hypothesis that direct interaction between T. gondii and TLR9 may trigger proinflammatory responses that lead to severe pathologies such as the ocular disease that is associated with this infection in Brazil.