Subclinical carriers and conversions in leber hereditary optic neuropathy: A prospective psychophysical study

Alfredo A. Sadun, Solange R. Salomao, Adriana Berezovsky, Federico Sadun, Anna Maria DeNegri, Peter A. Quiros, Filipe Chicani, Dora Ventura, Piero Barboni, Jerome Sherman, Erich Sutter, Rubens Belfort, Valerio Carelli

Research output: Contribution to journalArticle

Abstract

Purpose: The authors previously presented the results of their 2001 field investigation to rural Brazil to investigate a 336-member pedigree of Leber hereditary optic neuropathy (LHON). The present work describes the yearly field investigations 2001 to 2005, utilizing a variety of highly sophisticated psychophysical and electrophysiologic procedures, in asymptomatic LHON carriers, some of whom converted to affected status. Methods: Careful, repeated examinations of 75 carriers of homoplasmic 11778 LHON mtDNA J-haplogroup mutants were performed as part of the field investigation of this pedigree. All subjects underwent a detailed neuro-ophthalmologic investigation, including formal visual fields (Humphrey; HVF) and fundus photography. In addition, many subjects underwent rigorous psychophysical examination, including Cambridge Research Systems color vision and contrast sensitivity testing, OCT, GDx, and multifocal visual evoked response (mfVER) and multifocal electroretinogram (mfERG). Two patients followed as nonsymptomatic LHON carriers converted to affected status. Results: Many LHON carriers did, in fact, show subclinical or occult abnormalities. Focal edema was often seen involving the arcuate nerve fiber bundles, and this corresponded with areas of relative paracentral or arcuate scotomas on HVF testing. Compared to controls, LHON carriers had significant losses in color vision affecting mostly the red-green system and reduction in spatial but not temporal contrast sensitivity. The mfVER and mfERG data showed that most carriers had depressed central responses and abnormal interocular asymmetries. Conclusions: In this very large pedigree of 11778 LHON, the carriers frequently showed manifestations of optic nerve impairments. Their occult disease reflected low-grade compromise that waxed and waned. In two cases, these changes led to a crescendo of dramatic impairments that characterize conversion to affected status.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalTransactions of the American Ophthalmological Society
Volume104
Publication statusPublished - 2006

ASJC Scopus subject areas

  • Ophthalmology

Fingerprint Dive into the research topics of 'Subclinical carriers and conversions in leber hereditary optic neuropathy: A prospective psychophysical study'. Together they form a unique fingerprint.

  • Cite this

    Sadun, A. A., Salomao, S. R., Berezovsky, A., Sadun, F., DeNegri, A. M., Quiros, P. A., Chicani, F., Ventura, D., Barboni, P., Sherman, J., Sutter, E., Belfort, R., & Carelli, V. (2006). Subclinical carriers and conversions in leber hereditary optic neuropathy: A prospective psychophysical study. Transactions of the American Ophthalmological Society, 104, 51-59.