The study, “Peripapillary retinal nerve fibre layer thickness in Friedreich’s ataxia: a biomarker for trials?” was published in the journal Brain.
FA is a rare, genetic, progressive disease that affects the nerves and muscles. Initially, patients notice an unusual loss of balance that gradually progresses to a complete loss of control of body movements, a medical condition known as ataxia.
The disease is caused by the repetition of three nucleotides — the building blocks of DNA — one guanine (G) and two adenines (A), in the first intron (a region of the gene that does not encode for a protein) of the FXN gene.
“Many clinical trials have been carried out in patients with FA though none have shown efficacy in modifying disease progression. Therefore there is a pressing need to identify more sensitive biomarkers that are able to capture disease progression in an objective, quantifiable manner,” the investigators wrote.
Abnormalities in the control of eye movements and optic neuropathy (any type of damage to the optic nerve that may compromise eyesight) are also common among FA patients.
In a previous study involving a large group of FA patients, researchers found a possible relationship between the disease and the thinning of the layer of nerve cells forming the eye retina, called the retinal nerve fiber layer (RNFL).
In this study, these researchers sought to validate this observation by showing that RNFL thickness was correlated with FA severity and quality of life in the same group of patients.
To do so, they assessed disease severity using the Scale for Assessment and Rating of Ataxia (SARA) and patients’ quality of life using the Activities of Daily Living Questionnaire (ADLQ) from the Friedreich’s Ataxia Rating Scale (FARS).
The study enrolled 52 FA patients who completed a battery of neurological tests, as well as the ADLQ. RNFL thickness was measured using a special optical coherence tomography (OCT) imaging device.
Results showed the RNFL thickness of the participants ranged from 39.1 to 104.2 micrometers, with a mean value of 76.3 micrometers.
Correlation analyses identified a positive correlation between RNFL thickness and patients’ age at symptom onset, as well as a negative correlation among RNFL thickness, the number of GAA repeats, and disease duration, “demonstrating that the earlier the age at onset, the larger the GAA [repeats] and the longer the disease duration, the thinner the RFNL,” according to the researchers.
Moreover, analyses also found a negative correlation between RNFL thickness and the SARA and ADLQ scores, indicating that patients’ neurological function and quality of life both decline as the RNFL becomes thinner.
“To summarize, the results from this study show that OCT measurements of RNFL thickness have the potential to become a robust and objective biomarker for future treatment trials in FA,” the researchers wrote.
“Future work will focus on exploring the possibility that RNLF thickness in FA will change with the progression of the disease, therefore a longitudinal study is required. If a prospective study proves positive, OCT of the RNFL will be the first quantifiable biomarker that is readily available and cost-effective, thus suitable for multi-centric trials in FA,” they added.