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

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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

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Leber's Hereditary Optic Atrophy
Prospective Studies
Pedigree
Scotoma
Color Vision
Contrast Sensitivity
Visual Evoked Potentials
Photography
Optic Nerve
Visual Fields
Mitochondrial DNA
Nerve Fibers
Brazil
Edema

ASJC Scopus subject areas

  • Ophthalmology

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Subclinical carriers and conversions in leber hereditary optic neuropathy : A prospective psychophysical study. / Sadun, Alfredo A.; Salomao, Solange R.; Berezovsky, Adriana; Sadun, Federico; DeNegri, Anna Maria; Quiros, Peter A.; Chicani, Filipe; Ventura, Dora; Barboni, Piero; Sherman, Jerome; Sutter, Erich; Belfort, Rubens; Carelli, Valerio.

In: Transactions of the American Ophthalmological Society, Vol. 104, 2006, p. 51-59.

Research output: Contribution to journalArticle

Sadun, AA, Salomao, SR, Berezovsky, A, Sadun, F, DeNegri, AM, Quiros, PA, 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, vol. 104, pp. 51-59.
Sadun, Alfredo A. ; Salomao, Solange R. ; Berezovsky, Adriana ; Sadun, Federico ; DeNegri, Anna Maria ; Quiros, Peter A. ; Chicani, Filipe ; Ventura, Dora ; Barboni, Piero ; Sherman, Jerome ; Sutter, Erich ; Belfort, Rubens ; Carelli, Valerio. / Subclinical carriers and conversions in leber hereditary optic neuropathy : A prospective psychophysical study. In: Transactions of the American Ophthalmological Society. 2006 ; Vol. 104. pp. 51-59.
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AU - Salomao, Solange R.

AU - Berezovsky, Adriana

AU - Sadun, Federico

AU - DeNegri, Anna Maria

AU - Quiros, Peter A.

AU - Chicani, Filipe

AU - Ventura, Dora

AU - Barboni, Piero

AU - Sherman, Jerome

AU - Sutter, Erich

AU - Belfort, Rubens

AU - Carelli, Valerio

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N2 - 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.

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