Multimodal Analysis of the Visual Pathways in Friedreich's Ataxia Reveals Novel Biomarkers

Abstract

A BS TRACT: Background: Optic neuropathy is a near ubiquitous feature of Friedreich's ataxia (FRDA). Previous studies have examined varying aspects of the anterior and posterior visual pathways but none so far have comprehensively evaluated the heterogeneity of degeneration across different areas of the retina, changes to the macula layers and combined these with volumetric MRI studies of the visual cortex and frataxin level. Methods: We investigated 62 genetically confirmed FRDA patients using an integrated approach as part of an observational cohort study. We included measurement of frataxin protein levels, clinical evaluation of visual and

Autosomal recessive cerebellar ataxias: a diagnostic classification approach according to ocular features

“…More recently, a correlation between the peripapillary RNFL and the Scale for Assessment and Rating of Ataxia (SARA) used to quantify disability was demonstrated by Parkinson et al (2018) and Rojas et al (2021) . Another significant correlation has been found between thinning of the RNFL and frataxin protein levels, leading authors to suggest the use of these two measures as biomarkers in future clinical trial design ( Thomas-Black et al, 2023 ).…”

Preparing for Disease‐Modification Trials in Degenerative Cerebellar Ataxias: Which Endpoints to Choose?

“…In the third paper of this ataxia series, Thomas‐Black and colleagues advocate the application of optical coherence tomography (OCT) to quantify and monitor peripapillary retinal nerve fiber layer (pRNFL) thickness in future FRDA trials 8 . They examined the anterior and posterior visual pathways of 62 individuals with FRDA using OCT and volumetric brain MRI and explored relationships with clinical measures of disease severity, GAA1 repeat length, and frataxin protein levels in leukocytes.…”

“…This issue of Movement Disorders features a series of articles on dominantly inherited SCAs, MSA-C, SAOA, and Friedreich ataxia (FRDA) that share this important outcome theme. [5][6][7][8]…”

“…Delineating and predicting natural disease evolution with clinical rating scales, patient‐reported outcomes, observer‐independent metrics, (infratentorial) MRI measures, and biofluid markers constitutes an essential prerequisite for conducting meaningful disease‐modification trials. This issue of Movement Disorders features a series of articles on dominantly inherited SCAs, MSA‐C, SAOA, and Friedreich ataxia (FRDA) that share this important outcome theme 5‐8 …”