The natural history of OPA1-related autosomal dominant optic atrophy.
OBJECTIVE
Autosomal dominant optic atrophy (ADOA) is a genetically heterogenous disease. However, a large proportion of this disease is accounted for by mutations in OPA1. The aim of this longitudinal study was to investigate disease progression in Australian ADOA patients with confirmed OPA1 mutations.


METHODS
Probands with characteristic clinical findings of ADOA were screened for OPA1 mutations, and relatives of identified mutation carriers were invited to participate. Disease progression was determined by sequential examination or using historical records over a mean of 9.6 (range 1-42) years.


RESULTS
OPA1 mutation carriers (n = 158) were identified in 11 ADOA pedigrees. Sixty-nine mutation carriers were available for longitudinal follow-up. Using the right eye as the default, best-corrected visual acuity (BCVAR) remained unchanged (defined as visual acuity at or within one line of original measurement) in 43 patients (62%). BCVAR worsened by 2 lines in 13 patients (19%). BCVAR deteriorated by more than 2 lines in six patients (9%). Ten per cent of patients had an improvement in visual acuity. Mean time to follow-up was 9.6 years with the mean visual acuity being 6/18 for both the initial and subsequent measurements. There was no statistical significance in the rate of BCVAR loss across different OPA1 mutations (p = 0.55).


CONCLUSIONS
OPA1-related ADOA generally progresses slowly and functional visual acuity is usually maintained. Longitudinal disease studies are important to enable appropriate counselling of patients. This study enables a better understanding of the natural history of ADOA.
Cohn
A C
AC
Centre for Eye Research Australia, University of Melbourne, Department of Ophthalmology, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.
Toomes
C
C
Hewitt
A W
AW
Kearns
L S
LS
Inglehearn
C F
CF
Craig
J E
JE
Mackey
D A
DA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D002648:Child; D018450:Disease Progression; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D014644:Genetic Variation; D020180:Heteroduplex Analysis / Q000379:methods; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics* / Q000503:physiopathology; D009898:Optic Disk / Q000503:physiopathology; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational / Q000502:physiology; D014792:Visual Acuity
D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human