Researchers found that patients with Friedreich’s ataxia (FA) show a gradual reduction in low-contrast visual acuity over time. This decline is more pronounced in those with higher numbers of GAA repeats, a hallmark in FA, and could be a biomarker for future studies.
The study, “Longitudinal analysis of low-contrast acuity in Friedreich ataxia (S18.007),” will be presented at the 2018 American Academy of Neurology (ANN) Annual Meeting on April 23 as part of Session S18, “Movement Disorders: Ataxia and Tremor.”
The AAN meeting is April 21-27 in Los Angeles, and will be covered by Friedreich’s Ataxia News.
FA is caused by inherited defective copies of the FXN gene, which provides instructions to make frataxin, a key protein for the proper functioning of nerve and muscle cells.
Specifically, the FXN gene of Friedreich’s ataxia patients exhibits expansion of a GAA trinucleotide repeat, which leads to reduced levels of frataxin. Nucleotides are the building blocks of genes. Research indicates that the length of the GAA repeat is associated with disease severity and progression.
Patients with FA often have optic neuropathy, which is characterized by damage in the optic nerve. Studies found that reduced sensitivity of low-contrast vision correlates with disease severity. But there was no data from long-term studies.
The scientists used information from the ongoing, multicenter Friedreich Ataxia – Clinical Outcomes Measures Study (FA-COMS) in patients with FA. A total of 764 participants underwent annual high-contrast (100%) and low-contrast (2.5% and 1.25%) visual acuity assessments.
The team also collected data regarding GAA repeat length, FA duration, and other clinical and demographic features.
Results revealed that, over a median 4.4 years of follow-up, visual acuity declined significantly at contrasts of 100%, 2.5%, and 1.25% after accounting for diabetes, which may also lead to optic neuropathy.
Importantly, the data also showed that the decline in visual acuity was greater in patients with a higher number of GAA repeat lengths at 2.5% and 1.25% contrast, but not at 100% contrast. The scientists did not find an association with age of FA onset in the decline of visual acuity after adjusting for GAA repeat length.
The study demonstrates that low-contrast visual acuity gradually declines in Friedreich’s ataxia patients, and that the rate of decline is faster in patients with increased GAA repeat lengths.
“Contrast sensitivity has the potential to serve as a biomarker and surrogate outcome in future studies of [FA],” researchers wrote.