Thinning of Retinal Nerve Cells Tied to Severity of Friedreich’s Ataxia
Frataxin protein levels correlate with thickness of these fibers in eye, study finds
Among people with Friedreich’s ataxia, thinner layers of nerve cells at the retina — the light-sensing cells located at the back of the eye — are associated with more severe disease and lower frataxin protein levels, a study reported.
Results suggest that measuring the thickness of these retinal nerves could be a useful and low-cost marker for clinical trials.
“The data presented in this study furthers what is currently known about the retina and its connections in [Friedreich’s ataxia]. Our data highlight new biomarkers for exploration in clinical trials and reveal novel findings about the visual pathway” in patients, the researchers wrote.
The study, “Multimodal Analysis of the Visual Pathways in Friedreich’s Ataxia Reveals Novel Biomarkers,” was published in the journal Movement Disorders.
Retinal nerve fiber thickness, frataxin levels may be useful trial markers
Friedreich’s ataxia is caused by mutations that results in low levels of the protein frataxin. Although issues with vision and eye anatomy have been reported in the disease, the relationship between changes in eye structure and clinical manifestations of Friedreich’s ataxia remain incompletely understood.
Researchers at University College London performed a battery of detailed eye exams to learn more.
Their study recruited 62 people with Friedreich’s ataxia at two U.K. sites. Among the patients, 58% were female, and the median age was 31.9. Just under half (44.4%) of the patients wore glasses to help them see.
Eye analyses showed that the retinal nerve fiber layer (RNFL) — the layer of nerve cells at the back of the eyeball, which transmit visual data from the eyes to processing centers in the brain — was significantly thinner in patients than a control group without the disease. Reduced volume also was seen in some areas of the macula, the round area at the center of the retina that is responsible for central vision.
Notably, patients with a thinner RNFL tended to perform significantly worse on the Goldmann visual field test, an assessment of the total area in which objects can be seen as the eyes are focused on a central point.
In statistical analyses, a thinner RNFL significantly associated with a younger age at symptom onset, longer disease duration, and lower levels of frataxin. Low frataxin levels also independently associated with a younger age at disease onset.
“In this study we provide evidence that the fundamental cause of Friedreich’s ataxia, and therefore key target engagement biomarker, the frataxin protein level correlates with the RNFL,” the researchers wrote.
Since the retinal nerve fiber layer can be measured at low cost, this finding “has obvious implications for future clinical trials, especially given the fact that there are compounds, and indeed gene therapy approaches, with the aim of augmenting frataxin levels now progressing towards phase II/III trials,” they added.
Results also showed that a thinner RNFL was associated with more severe disease, as measured with the Scale for Assessment and Rating of Ataxia (SARA) and other standardized tests.
Given the association between frataxin levels and disease severity, the researchers proposed that “the RNFL may be an informative imaging biomarker in future [Friedreich’s ataxia] clinical trials.”
Future studies into how these measures change over time will be crucial in determining their suitability as trial biomarkers, the team concluded.