Prospective Evaluation Of Unaffected Carriers Belonging To A Large Lhon Family From Brazil: Results From Five Years Of Follow Up

Abstract

Purpose: : To report on the comprehensive ophthalmological evaluation of unaffected carriers from the previously reported large Brazilian (SOA–BR) family followed for five consecutive years.

Methods: : Since 2001 we have evaluated and systematically re–examined about 285 individuals of the 328 living members belonging to the Brazilian SOA–BR LHON pedigree carrying the homoplasmic 11778/haplogrop J mtDNA. Unaffected carriers underwent yearly serial comprehensive neuro–ophthalmological examinations; Humphrey visual field studies (HVF), GDx analysis, fundus photography, OCT analysis, psychophysical tests of color vision and contrast sensitivity were also performed. Fundus examination was judged abnormal when temporal pallor (TP) or the combination of NFL swelling and microangiopathy (S+M) were observed at fundus examination and fundus pictures in at least two out of three yearly consecutive examinations.

Results: : Eighty–two (82) unaffected maternally related individuals were prospectively followed. Two (2) subjects that were classified as unaffected in 2001 converted to affected status during the follow up. Twenty–one (21) individuals showed fundus abnormalities consisting on S+M, 1 patient showed combination of S+M and TP, 3 subjects had TP. Abnormalities in HVF, GDX, OCT, color vision or contrast sensitivities were also identified and correlated in several subjects.

Conclusions: : Subclinical findings are common in unaffected LHON individuals and may precede conversion to affected status. Further follow–up studies of this large LHON family may provide clues to identify subjects at higher risk for developing visual loss.

Keywords: neuro-ophthalmology: optic nerve • mitochondria • genetics