Color Vision Defects in Asymptomatic Carriers of the Lebers Hereditary Optic Neuropathy (LHON) MtDNA 11778 Mutation from a Giant Brazilian LHON Pedigree: A Case Control Study

Abstract

Abstract: : Purpose: To determine if asymptomatic carriers from a previously identified giant pedigree of the Leber's Hereditary Optic Neuropathy (LHON) 11778 mtDNA mutation have color vision deficits. Methods: As part of a comprehensive analysis of over 200 members of a giant Brazilian LHON pedigree spanning 7 generations, color vision tests were obtained from 91 members. Color vision was tested one eye at a time using the Farnsworth-Munsell 100 (FM-100) hue color vision test. The test was administered under uniform conditions, taking into account: ambient light levels, daylight color temperature of 6700 kelvins, and neutral uniform background. Tests were scored using the FM-100 MS-excel computer scoring program. Defects were determined and categorized as tritan, deutan, or protan based on computer generated plots and age-adjusted error scores which coincided with Verriest¹ 95% confidence intervals. 55 of the 91 test subjects were LHON mtDNA 11778 J-haplotype mutation carriers, proven by mtDNA analysis. The remaining 36 subjects were age-matched non-blood relatives (off-pedigree), who served as controls. Results: 27 of 55 carriers (49.10%) were shown to have color vision defects in one or both eyes. 13 of the 27 (48%) abnormal tests in the carrier group were tritan defects and the remaining 14 (52%) were deutan defects. 9 of the 27 (33%) abnormals in the carrier group were identified as having bilateral defects. 6 of these were deutan and the remaining 3 tritan dyschromatopsias. Only 6 of the 36 (16.66%) age-matched controls were found the have any type of dyschromatopsia. 5 (83.3%) of these were deutan defects. The remaining 1 was a tritan defect. The difference between the two groups using a Chi-square test with one degree of freedom was statistically significant with a p value less than 0.001. Conclusions: Until now, LHON has always been characterized by a sudden, devastating vision loss. Asymptomatic carriers, those without vision loss, were considered unaffected by the disease. It now appears that asymptomatic carriers of the LHON mutation are affected with color vision defects and may manifest other subtle, yet chronic, changes. ¹Verriest G, Van Laethem J, Uvijls A. A new Assessment of the normal ranges of the Farnsworth-Munsell 100-hue test scores. Am Jour Ophthalmol, 93:635-42, 1982.

Keywords: color vision • neuro-ophthalmology: optic nerve • genetics