Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy.

PURPOSE: To conduct systematic epidemiologic, neuro-ophthalmologic, psychophysical, and mitochondrial DNA (mtDNA) genetic examinations on a newly identified pedigree with Leber hereditary optic neuropathy (LHON). DESIGN: Observational population cohort study. METHODS: A prospective investigation of an entire Brazilian LHON family. SETTING: A field investigation by an international team conducted in a remote part of Brazil. STUDY POPULATION: We evaluated 265 (both eyes) of the 328 living family members of this LHON pedigree. Only members of this pedigree were studied. Those entering the pedigree as spouses were used as controls. OBSERVATION PROCEDURES: We conducted epidemiologic interviews emphasizing possible environmental risk factors, comprehensive neuro-ophthalmologic examinations, psychophysical tests, Humphrey visual field studies, fundus photography, and blood testing for mitochondrial genetic analysis. RESULTS: We reconstructed a seven-generation maternal lineage descended from a common ancestor dating to the 1870s. All maternally related family members were invariably homoplasmic 11778 with a haplogroup J mtDNA, 33 being affected, of which 22 are still living. With each subsequent generation, there was a progressive decrease of penetrance, and only males were affected in the last two generations. A significant exposure (greater than 95% confidence intervals) to a variety of environmental risk factors characterized the affected individuals, with smoking as the most common (P <.01). Both affected and carriers (95% confidence intervals) presented with a significantly lower incidence of hypertension and high cholesterol compared with the control group (P <.05). CONCLUSIONS: Almost 95% of a 328-living-member pedigree with LHON 11778/J haplogroup was comprehensively studied. Our initial results indicate the strong influence of environmental risk factors. The remarkably reduced incidence of cardiovascular risk in the maternal lineage is discussed. Further genetic analysis may reveal a role for the nuclear genome.

Validação clínica de teste psicofísico computadorizado para avaliação de visão de cores e sensibilidade ao contraste / Clinical validation of a computadorized psychophysical teste for color vision and contrats sensitivity

Objetivo: Avaliar a confiabilidade do teste computadorizado Two Docs para determinação da visão de cores e sensibilidade ao contraste em indivíduos adultos normais. Métodos: Trinta voluntários normais, com idades variando de 20 a 30 anos (média de 23,3 anos) foram submetidos ao TwoDocs Test para determinação de sua sensibillidade ao contraste e classificação de sua visão de cores. Seus resultados foram comparados com os dados obtidos pelas tabelas de Pelli-Robson e Farnsworth-Munsell 100 cores. Resultados: O teste TwoDocs mostrou total concordância com os resultados da sensibilidade ao contraste obtidos com a tabela de Pelli-Robson. Os testes para determinação da visão de cores não concordaram em seus resultados pois a avaliação dessa função visual por meio do teste TwoDocs foi superestimada tendo como base os resultados apresentados pelo teste Farnsworth-Munsell.

Purpose: To determine the reliability of TwoDocs computerized test for the evaluation of color vision and contrast sensitivity in normal adults. Methods: Thirty normal volunteers aged from 20 to 30 years (mean 23.3 years) had their color vision and contrast sensitivity tested by a new computerized test (TwoDocs test). Informed consent was obtained from all participants before testing. Inclusion criteria were: absence of visual complaints, absence of previous ophthalmic surgery, absence of family history of ophthalmologic diseases, best corrected visual acuity for near and distance of 20/20. Tests with the Farnsworth-Munsell 100-hue (FM-100) test for color vision assessment and the Pelli-Robson chart for contrast sensitivity measurement were also performed on the same visit, and both were considered gold standards for clinical validation. Results: The results of contrast sensitivity obtained with the Pelli-Robson chart and TwoDocs test showed agreement of 100%. Color vision results obtained with the TwoDocs test showed a strong trend to overestimate color vision classification when compared with FM-100. Conclusion: The new computerized psychophysical TwoDocs test showed a high sensitivity and specificity for contrast sensitivity measurement and can be a useful clinical tool in ophthalmology practice for this visual task. Color vision classification obtained with the TwoDocs test showed a low specificity when compared with FM-100. One possible reason for this overestimation is the computer monitor used to generate the color pattern. Additional studies in patients with disorders in color vision should be done for understanding the usefulness of this method better in clinical color vision assessment.