Noncoding variants alter GATA2 expression in rhombomere 4 motor neurons and cause dominant hereditary congenital facial paresis.

Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.

Retinal layers and symptoms and inflammation in schizophrenia.

Schizophrenia is a neurodevelopmental disorder that affects brain structure and function. The retina, as well as the brain, consists of neuronal and glial cells packed in layers. Cortical volume and brain thickness are associated with inflammatory biomarkers, however, no study has been performed associating inflammatory biomarkers and retina in schizophrenia. our study aims to compare the retinal macular thickness and volume and peripapillary thickness in patients with schizophrenia and controls, and associate it to symptoms of schizophrenia, to interleukin-6 (IL-6) and C Reactive Protein (CRP) levels. Optical coherence tomography was performed to assess retinal layer thickness and volume, and CRP and IL-6 levels were measured in patients with schizophrenia and controls. Positive, negative, and general symptoms of schizophrenia were measured with the Positive and Negative Syndrome Scale (PANSS). A linear regression controlling for confounding factors was performed. 70 subjects were included, 35 patients, and 35 controls matched for sex and age. Patients with schizophrenia presented a significantly lower macular volume (p < 0.05) and thickness (< 0.05) than controls. PANSS positive, general and total scores were associated with retinal nerve fiber layer (RNFL) thickness (p < 0.05). There was no association between inflammatory markers (CRP and IL-6) levels and the retinal layer. A reduction in macular volume and thickness was found in patients with schizophrenia. The severity of schizophrenia symptoms was associated with RNFL thickness. CRP and IL-6 are not associated with retinal thickness/volume in schizophrenia or controls.

Preliminary characterization of a novel form of progressive retinal atrophy in the German Spitz dog associated with a frameshift mutation in GUCY2D.

OBJECTIVE: To describe the clinical, preliminary electroretinographic and optical coherence tomography features of a newly identified form of progressive retinal atrophy (PRA) in German Spitzes, and identify the causal gene mutation. ANIMALS: Thirty-three client-owned German Spitz dogs were included. PROCEDURES: All animals underwent a full ophthalmic examination, including vision testing. In addition, fundus photography, ERG, and OCT were performed. A DNA-marker-based association analysis was performed to screen potential candidate genes and the whole genomes of four animals were sequenced. RESULTS: Initial fundus changes were pale papilla and mild vascular attenuation. Oscillatory nystagmus was noted in 14 of 16 clinically affected puppies. Vision was impaired under both scotopic and photopic conditions. Rod-mediated ERGs were unrecordable in all affected dogs tested, reduced cone-mediated responses were present in one animal at 3 months of age and unrecordable in the other affected animals tested. Multiple small retinal bullae were observed in three clinically affected animals (two with confirmed genetic diagnosis). OCT showed that despite loss of function, retinal structure was initially well-preserved, although a slight retinal thinning developed in older animals with the ventral retina being more severely affected. Pedigree analysis supported an autosomal recessive inheritance. A mutation was identified in GUCY2D, which segregated with the disease (NM_001003207.1:c.1598_1599insT; p.(Ser534GlufsTer20)). Human subjects with GUCY2D mutations typically show an initial disconnect between loss of function and loss of structure, a feature recapitulated in the affected dogs in this study. CONCLUSION: We identified early-onset PRA in the German Spitz associated with a frameshift mutation in GUCY2D.

New Insights on the Regulatory Gene Network Disturbed in Central Areolar Choroidal Dystrophy-Beyond Classical Gene Candidates.

Central areolar choroidal dystrophy (CACD) is a rare hereditary disease that mainly affects the macula, resulting in progressive and usually profound visual loss. Being part of congenital retinal dystrophies, it may have an autosomal dominant or recessive inheritance and, until now, has no effective treatment. Given the shortage of genotypic information about the disease, this work systematically reviews the literature for CACD-causing genes. Three independent researchers selected 33 articles after carefully searching and filtering the Scielo, Pubmed, Lilacs, Web of Science, Scopus, and Embase databases. Mutations of six genes (PRPH2, GUCA1A, GUCY2D, CDHR1, ABCA4, and TTLL5) are implicated in the monogenic dominant inheritance of CACD. They are functionally related to photoreceptors (either in the phototransduction process, as in the case of GUCY2D, or the recovery of retinal photodegradation in photoreceptors for GUCA1A, or the formation and maintenance of specific structures within photoreceptors for PRPH2). The identified genetic variants do not explain all observed clinical features, calling for further whole-genome and functional studies for this disease. A network analysis with the CACD-related genes identified in the systematic review resulted in the identification of another 20 genes that may influence CACD onset and symptoms. Furthermore, an enrichment analysis allowed the identification of 13 transcription factors and 4 long noncoding RNAs interacting with the products of the previously mentioned genes. If mutated or dysregulated, they may be directly involved in CACD development and related disorders. More than half of the genes identified by bioinformatic tools do not appear in commercial gene panels, calling for more studies about their role in the maintenance of the retina and phototransduction process, as well as for a timely update of these gene panels.

Novel OPN1LW/OPN1MW Exon 3 Haplotype-Associated Splicing Defect in Patients with X-Linked Cone Dysfunction.

Certain combinations of common variants in exon 3 of OPN1LW and OPN1MW, the genes encoding the apo-protein of the long- and middle-wavelength sensitive cone photoreceptor visual pigments in humans, induce splicing defects and have been associated with dyschromatopsia and cone dysfunction syndromes. Here we report the identification of a novel exon 3 haplotype, G-C-G-A-T-T-G-G (referring to nucleotide variants at cDNA positions c.453, c.457, c.465, c.511, c.513, c.521, c.532, and c.538) deduced to encode a pigment with the amino acid residues L-I-V-V-A at positions p.153, p.171, p.174, p.178, and p.180, in OPN1LW or OPN1MW or both in a series of seven patients from four families with cone dysfunction. Applying minigene assays for all observed exon 3 haplotypes in the patients, we demonstrated that the novel exon 3 haplotype L-I-V-V-A induces a strong but incomplete splicing defect with 3-5% of residual correctly spliced transcripts. Minigene splicing outcomes were similar in HEK293 cells and the human retinoblastoma cell line WERI-Rb1, the latter retaining a cone photoreceptor expression profile including endogenous OPN1LW and OPN1MW gene expression. Patients carrying the novel L-I-V-V-A haplotype presented with a mild form of Blue Cone Monochromacy or Bornholm Eye Disease-like phenotype with reduced visual acuity, reduced cone electroretinography responses, red-green color vision defects, and frequently with severe myopia.

Clinical and electroretinographic profile of 27 patients with Stargardt disease treated at a hospital in Brazil.

PURPOSE: Stargardt disease is the most common type of juvenile-onset macular dystrophy. It is bilateral and symmetrical in appearance, affects the macula, and its main characteristic is the loss of central vision that starts in the first or second decade of life. The purpose of this study was to describe the profile of the patients evaluated at the Complexo Hospital de Clínicas da Universidade Federal do Paraná, as well as describe the electroretinographic findings with the full-field electroretinogram in these patients. METHODS: An observational, retrospective study was performed by analysis of records and electroretinographic examinations of 27 patients with Stargardt disease and fundus flavimaculatus who were treated at the Complexo Hospital de Clínicas da Universidade Federal do Paraná's Department of Ocular Electrophysiology and Neuro-Ophthalmology between 1997 and 2014. The patients included in this study presented clinical features, fundus examination and/or electroretinographic findings compatible with Stargardt disease. RESULTS: The visual acuity in the best eye varied from 0 to 1.6 logMAR (20/20 to 20/800) with an average of 0.89 ± 0.42 logMAR. The age at onset of symptoms varied from since birth to 36 years old (average 19.2 ± 9.2) with the majority of patients having symptom onset in the first or second decade of life. The mean time from the disease's first symptoms until the diagnosis was 7.3 years. In the fundus examination, every patient presented some kind of abnormality. In the electroretinogram analysis, the majority of patients had results that differed from those of sample controls, i.e., reduced amplitude and increased implicit time in the photopic and scotopic phases. CONCLUSIONS: The visual acuity and the age at symptoms onset in this study were compatible with the natural history of this dystrophy. The typical fundus appearance of Stargardt disease and altered electroretinogram were more frequent because of the delay until diagnosis. New prospective studies are necessary to evaluate these patients based on emergent technologies.

Neurosyphilis and ocular syphilis clinical and cerebrospinal fluid characteristics: a case series.

BACKGROUND: During the first decade of this century, a significant increase in the incidence of syphilis was documented. OBJECTIVE: To study clinical and laboratory characteristics of central nervous system and ocular syphilis. METHODS: A retrospective case series of 13 patients with a clinical and laboratory diagnosis of neurosyphilis and/or ocular syphilis who had been admitted to the Neurology and Neuro-ophthalmology Service of the Hospital de Clínicas, Federal University of Paraná. RESULTS: Nine patients had a diagnosis of neurosyphilis and two of them also had ocular syphilis. Four patients had a diagnosis of ocular syphilis alone. Among the patients with a diagnosis of neurosyphilis, six had symptomatic syphilitic meningitis, of whom one manifested as cranial nerve palsy alone, one as cranial nerve palsy plus ocular syphilis, two as transverse myelitis (syphilitic meningomyelitis), one as meningitis worsening the patient's myasthenia gravis symptoms and one as meningitis plus ocular syphilis. Additionally, we diagnosed three patients with meningovascular neurosyphilis. In the univariate analysis, patients without ocular syphilis showed greater levels of total protein and white blood cells in the cerebrospinal fluid than patients with ocular syphilis. CONCLUSION: This Brazilian case series of patients with neurosyphilis and ocular syphilis highlights the wide variability of this disease. A high degree of diagnostic suspicion is necessary when facing neurological and ocular symptoms for rapid diagnosis and appropriate management of patients.

Neurosyphilis and ocular syphilis clinical and cerebrospinal fluid characteristics: a case series / Características clínicas e liqúoricas de pacientes com neurossífilis e sífilis ocular: uma série de casos

ABSTRACT Background During the first decade of this century, a significant increase in the incidence of syphilis was documented. Objective To study clinical and laboratory characteristics of central nervous system and ocular syphilis. Methods A retrospective case series of 13 patients with a clinical and laboratory diagnosis of neurosyphilis and/or ocular syphilis who had been admitted to the Neurology and Neuro-ophthalmology Service of the Hospital de Clínicas, Federal University of Paraná. Results Nine patients had a diagnosis of neurosyphilis and two of them also had ocular syphilis. Four patients had a diagnosis of ocular syphilis alone. Among the patients with a diagnosis of neurosyphilis, six had symptomatic syphilitic meningitis, of whom one manifested as cranial nerve palsy alone, one as cranial nerve palsy plus ocular syphilis, two as transverse myelitis (syphilitic meningomyelitis), one as meningitis worsening the patient's myasthenia gravis symptoms and one as meningitis plus ocular syphilis. Additionally, we diagnosed three patients with meningovascular neurosyphilis. In the univariate analysis, patients without ocular syphilis showed greater levels of total protein and white blood cells in the cerebrospinal fluid than patients with ocular syphilis. Conclusion This Brazilian case series of patients with neurosyphilis and ocular syphilis highlights the wide variability of this disease. A high degree of diagnostic suspicion is necessary when facing neurological and ocular symptoms for rapid diagnosis and appropriate management of patients.

RESUMO Introdução Na primeira década deste século observou-se um aumento significativo da incidência de sífilis no mundo. Objetivo Estudar características clínicas e laboratoriais da sífilis no Sistema Nervoso Central e da sífilis ocular. Métodos Estudou-se, retrospectivamente, uma série de treze casos com diagnóstico clínico e laboratorial de neurossífilis e/ou sífilis ocular, admitidos aos Serviços de Neurologia ou Neuroftalmologia do Hospital de Clínicas da Universidade Federal do Paraná. Resultados Nove pacientes tiveram diagnóstico de neurosífilis e dois destes apresentaram concomitantemente sífilis ocular. Quatro pacientes tiveram somente o diagnóstico de sífilis ocular. Dos pacientes com diagnóstico de neurosífilis, seis apresentaram meningite sifilítica sintomática, dentre os quais um se apresentou com paralisia isolada de par craniano, um com paralisia de par craniano associada sífilis ocular, dois com mielite transversa (manifestação de meningomielite), um com meningite que agravou sintomas de Miastenia Gravis e um com meningite isolada associada a sífilis ocular. Houve 3 casos de neurosífilis meningovascular. Na análise univariada, pacientes sem manifestações oculares de sífilis apresentaram maiores níveis proteína total e leucócitos do que os pacientes com sífilis ocular. Conclusão Essa série brasileira de casos de pacientes com neurosífilis e sífilis ocular destaca a alta variabilidade clínica desta doença. Alto grau de suspeição diagnóstica é necessário quando em frente a sintomas neurológicos e oculares para rápido diagnóstico e adequado manejo dos pacientes.

Different Cerebellar Ataxia Phenotypes Associated with Mutations of the PNPLA6 Gene in Brazilian Patients with Recessive Ataxias.

Autosomal recessive cerebellar ataxias (ARCAs) represent a heterogeneous group of inherited disorders. The association of early-onset cerebellar ataxia with hypogonadotropic hypogonadism is related to two syndromes, known as Gordon Holmes syndrome (GHS-ataxia and pyramidal signs with hypogonadotropic hypogonadism) and Boucher-Neuhäuser syndrome (BNS-ataxia with chorioretinal dystrophy). Mutations in the PNPLA6 gene have been identified as the cause of hereditary spastic paraplegia and complex forms of ataxia associated with retinal and endocrine manifestations. We reported two Brazilian patients with sporadic, progressive cerebellar ataxia, associated with hypogonadotropic hypogonadism, in whom the GHS and BNS were confirmed by the demonstration of compound heterozygote mutations in the PNPLA6 gene. Genetic analysis of the patient 1 revealed compound heterozygous mutations, one allele in exon 34 and the other allele in exon 29. Genetic exam of the patient 2 also demonstrated compound heterozygous mutations. Three were novel mutations. The missense mutation c.3373G> A, found in the BNS patient, was previously related to Oliver-McFarlane syndrome. These different mutations in this gene suggest a complex phenotype associated disease spectrum.

Characterization of a novel form of progressive retinal atrophy in Whippet dogs: a clinical, electroretinographic, and breeding study.

OBJECTIVE: To describe a form of progressive retinal atrophy (PRA) in Whippets including clinical, electroretinographic, optical coherence tomographic changes and pedigree analysis. ANIMALS STUDIED: Client-owned Whippet dogs (n = 51) living in Brazil. PROCEDURES: All animals were submitted for routine ophthalmic screening for presumed inherited ocular disease, which included the following: visual tests, such as obstacle course tests, in scotopic and photopic conditions, cotton ball test, dazzle reflex, ocular fundus evaluation by indirect ophthalmoscopy followed by fundus photography. Additionally, electroretinography (ERG) and optical coherence tomography (OCT) were performed in 24 and four dogs, respectively. RESULTS: Sixteen dogs were diagnosed with PRA. Vision deficits in dim light were detected in dogs examined at a young age associated with nystagmus. Funduscopic changes included the development of multifocal retinal bullae from 6 months of age. Retinal thinning became apparent later, at which time the bullae were no longer detected. OCT examination of selected young dogs revealed that the retinal bullae were due to separation between photoreceptors and the retinal pigment epithelium, and of dogs with more advanced disease confirmed the development of retinal thinning. Electroretinography in young dogs revealed a negative ERG due to a lack of b-wave in both scotopic and photopic recordings. With progression, the ERG became unrecordable. Pedigree analysis suggested an autosomal recessive mode of inheritance. CONCLUSION: The retinal dystrophy reported here in Whippet dogs has a unique phenotype of an initial lack of ERG b-wave, development of retinal bullae then a progressive generalized retinal degeneration.

Epidemiological profile of age-related macular degeneration patients in Federal University of Parana, Brazil / Perfil epidemiológico da degeneração macular relacionada à idade na Universidade Federal do Paraná, Brasil

ABSTRACT Objective: To evaluate the profile and severity of age-related macular degeneration (AMD) in ophthalmology ambulatory of Federal University of Parana in Curitiba, Parana, Brazil. Methods: This was a cross-sectional study with data collected among the 6155 outpatients ophthalmic appointments (november 2011 to november 2013). In this 6155 patients, a total of 346 patients had retinal diseases and were screened by two retinal specialists for signs of AMD. If present, they were submitted to a protocol including a new ophthalmic evaluation comprising visual acuity, tonometry, biomicroscopy, dilated fundus examination and optical coherence tomography (OCT). Results: A total of 6155 patients underwent ophthalmologic evaluation for several reasons. Three hundred and forty six patients had retinal diseases (incidence of 5.6%) and 68 of these (incidence of 19.6% in retinal patients) had AMD. The mean age of all patients was 53 years and in retinal patients was 60 years. In AMD patients mean age was 73 years. Ethnicity, body-mass index (BMI) and smoking habits were evaluated in the 68 patients diagnosed with AMD (34 exudative and 34 non-exudative) but none of those parameters were statistically significant comparing exudative and non-exudative forms. Conclusion: Most of the patients were European descendants. A higher proportion of advanced cases of AMD comparing with literature was found (50% of exudative form). Regarding ethnicity, iris color, smoking habit and BMI, there was no difference comparing exudative and non-exudative forms. These results may be compared to available AMD studies, since there is little information about AMD in Brazil.

RESUMO Objetivo: Avaliar o perfil epidemiológico e severidade da degeneração macular relacionada à idade (DMRI) no ambulatório de oftalmologia da Universidade Federal do Paraná (UFPR) em Curitiba, Paraná, Brasil. Métodos: Estudo transversal com dados coletados referentes as 6155 consultas oftalmológicas realizadas no período de novembro de 2011 a novembro de 2013. Destes, 346 pacientes possuíam doenças retinianas e foram avaliados por dois especialistas em retina à procura de sinais de DMRI. Os confirmados foram submetidos a um protocolo compreendendo acuidade visual, tonometria, biomicroscopia, oftalmoscopia indireta sob midríase e tomografia de coerência óptica (OCT). Resultados: Um total de 6155 pacientes foram submetidos à consulta oftalmológica na UFPR. Trezentos e quarenta e seis pacientes apresentaram doenças retinianas (incidência de 5.6%) e 68 destes (incidência de 19.6% dos pacientes com doenças de retina) apresentaram DMRI. A média de idade dos pacientes do ambulatório geral foi de 53 anos e em pacientes com doenças de retina foi de 60 anos. Pacientes com DMRI tinham em média 73 anos. Etnia, cor da íris, índice de massa corpórea (IMC) e tabagismo foram avaliados nos 68 pacientes diagnosticados com DMRI (34 exsudativa e 34 não exsudativa), mas nenhum dos parâmetros foram estatisticamente significantes. Conclusão: A maioria dos pacientes eram de origem europeia. Comparando com a literatura, uma maior proporção de casos avançados de DMRI (50% de forma exsudativa) foi encontrada. Em relação à etnia, tabagismo e IMC, não houve diferença entre pacientes com forma exsudativa e não exsudativa. Estes resultados podem ser comparados com estudos disponíveis, considerando a pouca informação referente a DMRI existente no Brasil.

Síndrome dos cabelos anágenos frouxos associada à distrofia macular: descrição de uma família / Loose anagen hair syndrome associated with macular dystrophy: a family description

Descreve-se uma família com síndrome dos cabelos anágenos frouxos (SCAF) associada à distrofia macular. Foram descritos os achados dermatológicos, oftalmológicos e de microscopia óptica e eletrônica de varredura de 11 indivíduos. Dois apresentaram SCAF, sem qualquer alteração ocular. Dos quatro indivíduos com alteração ocular, duas irmãs apresentaram SCAF e dispersões pigmentares em pólo posterior da retina, com coloboma da mácula. Em dois irmãos encontraram-se as mesmas características da SCAF e fundo de olho com dispersões pigmentares em pólo posterior, sem coloboma. Os achados sugerem que essa associação seja uma nova entidade nosológica dentro das displasias ectodérmicas.

Distrofia retiniana com onda rápida escotópica (DRORE) associada à síndrome dos cabelos anágenos frouxos (SCAF). Parte II: genética / Scotopic fast wave retinal dystrophy (SFWRD) associated with loose anagen hair syndrome (LAHS). Part II: genetics

OBJETIVOS: Propor complementação da atual classificação do eletrorretinograma (ERG) com a inclusão deste novo tipo de onda, discutir os possíveis mecanismos para a distrofia retiniana com onda rápida escotópica (DRORE) associada à síndrome dos cabelos anágenos frouxos (SCAF) e análise do heredograma da família estudada. MÉTODO: Foram descritos na parte I deste trabalho. RESULTADOS: A análise do heredograma da família demonstrou tratar-se de herança autossômica recessiva com expressão parcial no heterozigoto; outros resultados foram descritos na parte I deste trabalho. CONCLUSÕES: Por se tratar do primeiro relato na literatura, os achados descritos sugerem fortemente que a distrofia retiniana com onda rápida escotópica associada à síndrome dos cabelos anágenos frouxos pode ser uma nova entidade nosológica. Neste trabalho propomos uma classificação inédita de todas as distrofias maculares e degenerações retinianas associadas a distúrbios capilares no grupo B das displasias ectodérmicas.

Distrofia retiniana com onda rápida escotópica (DRORE) associada à síndrome dos cabelos anágenos frouxos (SCAF). Parte I: Achados oftalmológicos / Scotopic fast wave retinal dystrophy (SFWRD) associated with loose anagen hair syndrome (LAHS). Part I: ophthalmological findings

OBJETIVOS: Descrever os achados oftalmológicos de nova distrofia macular associada à síndrome dos cabelos anágenos frouxos (SCAF). MÉTODOS: Uma família de onze pacientes, quatro deles afetados ocularmente, foram examinados. Sete pacientes foram submetidos aos seguintes exames: avaliação oftalmológica completa, teste de cores, ecografia, angiografia, campo visual, topografia de papila, eletro-oculograma (EOG), eletrorretinograma (ERG), testes laboratoriais e exame dermatológico, teste de suor, microscopia óptica (MO) e microscopia eletrônica de varredura (MEV) dos fios de cabelo. Em quatro pacientes, filhos dos afetados, realizamos somente exame oftalmológico, microscopia óptica e microscopia eletrônica de varredura dos fios de cabelo. RESULTADOS: Dos quatro pacientes afetados, em duas irmãs encontramos no fundo de olho dispersões pigmentares em pólo posterior da retina, com coloboma macular. Em dois de seus irmãos foram encontradas as mesmas alterações oculares, com maior pigmentação e coloração amarelada em área macular e ausência de coloboma. Os resultados do eletro-oculograma e eletrorretinograma estavam dentro dos limites de normalidade em três pacientes sem alterações oculares; por outro lado, o eletro-oculograma foi subnormal e o eletrorretinograma foi subnormal com tempo de culminação diminuído (rápido) na fase escotópica dos pacientes com a distrofia macular, sugerindo que a alteração dessa distrofia se encontra em nível do epitélio pigmentado da retina. Devido a esse comportamento peculiar do tempo de culminação, este achado pode ser considerado como fundamental para o diagnóstico desta distrofia. A denominação sugerida é de distrofia retiniana com onda rápida escotópica (DRORE). A microscopia óptica e microscopia eletrônica de varredura dos fios de cabelo confirmaram a síndrome dos cabelos anágenos frouxos. CONCLUSÕES: Descrevemos os achados da distrofia retiniana com onda rápida escotópica associada à síndrome dos cabelos anágenos frouxos, distrofia cujos achados fundoscópicos são diferentes entre homens e mulheres e com traçado eletrorretinográfico característico.

Influência da idade e da adaptação precoce ao claro, na normatização do eletrorretinograma de campo total em sujeitos normais / Influence of age and the precocious light adaptation, in the standardization of the full-field electroretinogram in normal subjects

Estudar a influência da idade, da adaptação precoce ao claro na fase fotópica e comparar se há diferença entre os olhos e entre os sexos nas diferentes etapas do eletrorretinograma (ERG) padronizado por faixa etária. Tese apresentada ao Setor de Ciências da Saúde da Universidade Federal do Paraná, como parte dos requisitos para obtenção de grau de Mestre em Clínica Cirúrgica. Foram avaliados 40 pacientes com exame oftalmológico normal, separados por sexo e estratificados por faixa etária de 8-65 anos (intervalo de 20 anos). A fim de se proceder à normatização do ERG, utilizou-se o sistema EPIC 2000 (LKC), com modificação do protocolo padrão recomendado pelo ISCEV (International Society for Clinical Electrophysiology of Vision). Os olhos foram adaptados ao claro por 1 minuto ao invés de 10 minutos que é o preconizado pelo ISCEV. Houve grande correlação entre os olhos (r= 0,92 para a amplitude e r= 0,89 para o tempo de culminação) e diferenças significativas a 5por cento no teste t nas seguintes respostas do ERG, separados por faixa etária: 1) diminuição da ampluitude da onda escotópica b, onda a e b (resposta máxima) com a idade; 2) aumento do tempo de culminação (ms) da onda b (resposta máxima), fotópico b e flicker até os 60 anos. Houve diminuição da amplitude e o tempo de culminação foi similar ao de pacientes adaptados ao claro por dez minutos. Não houve diferenças significativas na análise de variância (ANOVA) em quaisquer respostas, sem separação for faixas etárias e na média entre os sexos. No presente trabalho foi demonstrado que sexo e idade do paciente têm influência sobre o ERG, estas variáveis devem ser consideradas para a normatização do ERG, para comparação com pacientes anormais. A adaptação precoce ao claro por 1 minuto tem vantagens em relação aos 10 minutos, por encurtar e facilitar a realização do exame em pacientes com fotofobia e em crianças sob sedação.

Neurorretinite associada à ceratite intersticial: relato do primeiro caso de doença de Lyme no Estado do Paraná / Neuroretinitis associated with interstitial Keratitis: the first case report of Lyme disease in the State of Paraná

Objetivo: Descrever o primeiro caso da doença Lyme (DL com manifestação predominantemente ocular no Paraná. Local: Departamento de Oftalmologia da Faculdade de Medicina da Universidade Federal do Paraná - Brasil. Método: Relato de caso de uma paciente, com 31 anos, que inicialmente apresentou baixa acuidade visual e presença de papiledema bilateral; inicialmente disgnosticado como neurite óptica de causa desmielinizante. Resultados: Exame oftalmológico revelou a presença de neurorretinite bilateral associada a ceratite intersticial de ambas as córneas. Exames laboratoriais posteriores, com a presença de sorologia positiva para anticorpos IgM anti-Borrelia burgdorferi, confirmaram o diagnóstico da DL. Conclusões: A paciente, após o tratamento com ceftriaxona e doxiciclina, apresentou melhora da acuidade visual e diminuição da ceratite intersticial. Por se tratar de entidade desconhecida no Paraná e que, se diagnosticada precocemente possui tratamento com antibióticos, urge que a classe médica realize precocemente o diagnóstico, possibilitando assim ajudar os pacientes. A associação entre neurorretinite e ceratite intersticial nessa paciente constitui, até o presente momento, o primeiro caso no Brasil. Os principais diagnósticos diferenciais com a DL, o quadro clínico e a metodologia para se realizar o seu diagnóstico são discutidos.

Fístula carótido-cavernosa indireta com presença de nódulo subcutâneo pulsátil em pálpebra - relato de um caso com apresentação atípica / Indirect carotid cavernous fistula with a pulsatile subcutaneous nodule on the eyelid - a case report with an atypical manifestation

Objetivo: Relatar os achados oftalmológicos e de imagens de uma paciente que apresentava sinais discretos de fístula carótido-cavernosa (FCC) indireta à direita, discutindo os principais sinais oculares e a importância do exame oftalmológico minucioso, com ausculta da órbita e exoftalmometria para o diagnóstico precoce desta doença. Local: Serviço de Oftalmologia do Hospital de Clínicas da Universidade Federal do Paraná. Método: Relato de caso e discussão das manifestações oculares de um caso atípico de FCC. Resultados: A paciente apresentava, no exame oftalmológico, pressão intra-ocular elevada (pulsátil), discreta congestão conjuntival, sopro orbitário sugestivos de FCC em olho direito (OD) e a presença de nódulo subcutâneo pulsátil, palpável em pálpebra superior do OD em topografia de vasos supra-orbitários, não descrita anteriormente na literatura. Exames de imagem não-invasivos (ecografia ocular, ecografia da órbita com doppler colorido e angiorresonância magnética com contraste) confirmaram o diagnóstico. O estudo angiográfico revelou FCC indireta de baixo fluxo do tipo C, segundo a classificação de Barrow. Conclusão: A FCC indireta ou dural de baixo fluxo geralmente é pouco sintomática e de difícil diagnóstico. As manifestações oculares costumam ser discretas e podem passar despercebidas. Neste caso, a paciente não apresentava proptose evidente no exame externo e mostrava discreta hiperemia conjuntival no OD. Como as manifestações oftalmológicas das FCC indiretas são pouco evidentes, para se chegar ao diagnóstico são necessários uma anamnese cuidadosa e um exame oftalmológico minucioso, incluindo ausculta orbitária com estetoscópio e exoftalmometria. Devido ao risco de perda visual relacionado à FCC, o oftalmologista deve valorizar queixas como hiperemia ocular associada a cefaléia e zumbido, bem como a presença de nódulo subcutâneo pulsátil em pálpebra, para se diagnosticar precocemente esta doença.

Descriçäo de nova distrofia macular associada à síndrome dos cabelos anágenos frouxos / Description of new macular dystrophy associated with loose anagen hair syndrome

Objetivos: Descrever os achados oftalmológicos, dermatológicos e de microscopia óptica (MO) e microscopia etrônica de varredura (MEV) de nova distrofia macular associada à síndrome dos cabelos anágenos frouxos (SCAF). Métodos: Uma família de sete pacientes, quatro deles afetados, foi examinada. Os pacientes foram submetidos ao exame oftalmológico completo, teste de cores (Ishihara e Farnsworth D-15), ecografia, angiografia, exames laboratoriais e dermatológico, teste do suor, microscopia óptica e microscopia eletrônica de varredura dos fios de cabelo. Resultados: Em duas irmäs afetadas encontramos no fundo de olho dispersöes pigmentares em pólo posterior da retina, com estafiloma da mácula. Em dois irmäos foram encontradas as mesmas dispersöes pigmentares em pólo posterior, com maior pigmentaçäo e coloraçäo amarelada em área macular e sem estafiloma. A avaliaçäo na microscopia óptica e microscopia eletrônica de varredura dos indivíduos afetados confirmou a SCAR Em uma mulher e em um homem näo afetados todos os exames foram normais, exceto que na MO e MEV encontramos algumas semelhanças com os indivíduos afetados. Quanto ao modo de herança, o heredograma é compatível com herança autossômica recessiva com expressäo parcial no heterozigoto. Conclusöes: Há somente um relato na literatura internacional da associaçäo de SCAF e coloboma ocular. Neste trabalho descrevemos os achados de nova distrofia macular associada à síndrome dos cabelos anágenos frouxos, distrofia cujos achados fundoscópicos säo diferentes entre homens e mulheres. Por se tratar do primeiro relato na literatura, os achados descritos sugerem fortemente que esta associaçäo pode ser parte de uma nova entidade nosológica.