Electrophysiological Evidence of Visual Dysfunction in SCA3: PERG/PVEP as Novel Biomarkers for Ataxia Severity and...

Spinocerebellar ataxia type 3 (SCA3), a rare autosomal dominant neurodegenerative disease, consistently exhibits visual abnormalities. Retinal functional and morphological abnormalities present in SCA3 patients may serve as clinically relevant biomarkers.

The aim of this study was to investigate structure-based functional alterations in SCA3 to identify potential biomarkers.

This study analyzed 98 eyes from 52 SCA3 patients and 130 eyes from 65 controls using pattern visual evoked potentials (PVEP), pattern electroretinography (PERG), and spectral-domain optical coherence tomography (SD-OCT). Electrophysiological parameters and retinal morphological parameters were measured and correlated with clinical variables (age, disease duration, CAG repeats) and scales, including the Scale for the Assessment and Rating of Ataxia (SARA), the International Cooperative Ataxia Rating Scale (ICARS), the Hamilton Depression Scale (HAMD), and the Montreal Cognitive Assessment (MoCA). Statistical analyses employed generalized estimating equations (GEE) for longitudinal data and bootstrapped Spearman's correlation with false discovery rate (FDR) adjustment. Receiver operating characteristic (ROC) curves evaluated diagnostic accuracy for SCA3.

In SCA3 patients, PERG and PVEP amplitudes are markedly reduced with significant prolongation in PVEP latency. Significant thinning was observed in all peripapillary retinal nerve fiber layer (pRNFL) sectors and macular layers. Retinal function and structure significantly correlated with clinical scales (SARA, ICARS, MoCA). Retinal PERG amplitudes and structure showed negative correlations with disease duration. PVEP latency negatively correlated with CAG repeats. Combined retinal functional and structural parameters demonstrated superior diagnostic accuracy in SCA3.

We demonstrate selective retinal functional and structural impairment in SCA3, with visual electrophysiological abnormalities and SD-OCT morphological thinning significantly correlated with clinical phenotypes. Integrated with retinal functional and structural assessments, this approach provides a novel multimodal diagnostic framework and a more sensitive biomarker for SCA3 natural history studies and clinical trials. © 2026 International Parkinson and Movement Disorder Society.