Abstract
Objective To determine the natural history of contrast acuity in Friedreich ataxia.
Methods In the Friedreich Ataxia–Clinical Outcome Measures Study, participants (n = 764) underwent binocular high- and low-contrast visual acuity testing at annual study visits. Mixed-effects linear regression was used to model visual acuity as a function of time, with random intercepts and slopes to account for intraindividual correlation of repeated measurements. A time-varying covariate was used to adjust for diabetes, and interaction terms were used to assess for effect modification by GAA repeat length, disease duration, and other variables.
Results Across a median of 4.4 years of follow-up, visual acuity decreased significantly at 100% contrast (−0.37 letters/y, 95% confidence interval [CI]: −0.52 to −0.21), 2.5% contrast (−0.81 letters/year, 95% CI: −0.99 to −0.65), and 1.25% contrast (−1.12 letters/y, 95% CI: −1.29 to −0.96 letters/year). There was a significant interaction between time and GAA repeat length such that the rate of decrease in visual acuity was greater for patients with higher GAA repeat lengths at 2.5% contrast (p = 0.018) and 1.25% contrast (p = 0.043) but not 100% contrast. There was no effect modification by age at onset after adjusting for GAA repeat length.
Conclusions Low-contrast visual acuity decreases linearly over time in Friedreich ataxia, and the rate of decrease is greater at higher GAA repeat lengths. Contrast sensitivity has the potential to serve as a biomarker and surrogate outcome in future studies of Friedreich ataxia.
Glossary
- CI=
- confidence interval;
- FA-COMS=
- Friedreich Ataxia–Clinical Outcome Measures Study;
- FRDA=
- Friedreich ataxia;
- IQR=
- interquartile range
Footnotes
↵* Conducted statistical analysis (academically affiliated).
Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NG.
Supported by a grant from the Friedreich Ataxia Research Alliance.
The Article Processing Charge was funded by the authors.
- Received December 23, 2017.
- Accepted in final form May 22, 2018.
- Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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