Ophthalmologic findings in a large pedigree of 11778/Haplogroup J Leber hereditary optic neuropathy☆

Abstract 

Purpose

To report the ophthalmologic characteristics of a newly identified seven-generation pedigree of 11778/Haplogroup J Leber hereditary optic neuropathy consisting of 328 living individuals, 111 of whom are maternally related.

Design

Observational population cohort study.

Methods

This prospective study of a large Brazilian Leber hereditary optic neuropathy pedigree was carried out as a field investigation in Brazil. We describe the ophthalmologic findings of 192 eyes from 96 maternally related individuals of this pedigree. Spouses were used as control subjects. We conducted comprehensive neuro-ophthalmologic examinations with psychophysical tests, Humphrey visual fields, and fundus photographs. We also correlated the ophthalmologic findings with the previously published epidemiologic assessment of risk factors.

Results

We examined 76 carriers and 20 affected individuals. The affected individuals showed severe disease with a mean visual acuity of 2.04 logarithm of the minimal angle of resolution and without evidence of recovery. All the affected individuals showed diffuse optic atrophy with a cup-to-disk ratio greater than 0.5 in 55% of cases. Moreover, among Affected individuals, smokers had a poorer visual acuity (P = .002). Among carriers there were several subclinical abnormalities, including microangiopathy, swelling of nerve fibers, and visual field abnormalities that did not correlate with tobacco or alcohol consumption.

Conclusions

Our results demonstrate a significant influence of environmental risk factors, particularly smoking, for developing Leber hereditary optic neuropathy and for the severity of its clinical expression. However, smoking did not correlate with the subclinical abnormalities detected in carriers. Moreover, subclinical abnormalities were equally distributed between gender.