Retinal structural changes in Parkinson’s disease: differences in pRNFL thickness between GBA1-associated and idiopathic cases

Introduction: In recent years, retinal structural changes have attracted considerable attention as a potential biomarker of neurodegeneration in Parkinson’s disease (PD). Several studies have reported a reduced Retinal Nerve Fiber Layer (pRNFL) thickness in patients with PD compared with age-matched controls. However, potential retinal differences between “idiopathic” PD and GBA1-associated PD (GBA-PD) remain largely unexplored. Methods: In this single-center observational study, we enrolled 59 PD patients: 32 GBA-PD and 27 non-mutated (NM-PD). A comprehensive clinical assessment included MoCA, MDS-UPDRS and Hoehn-Yahr. Spectral-domain OCT measured pRNFL thickness at 3.5, 4.1 and 4.7 mm diameters across six sectors. Statistical analysis assessed intergroup differences and associations with clinical variables. Results: NM-PD exhibited significantly thinner temporal sectors compared to GBA-PD (p<0.05, Mann-Whitney U test). In NM-PD, positive correlations emerged between temporal-superior pRNFL and MoCA scores, in line with previous studies, and, more surprisingly, between nasal-inferior sector and MDS-UPDRS part-IV. No robust associations with clinical variables were found in GBA-PD. Conclusions: This study demonstrates differences in retinal thickness between GBA-PD and NM-PD. In particular, a lower pRNFL in NM-PD may be the product of a different pathophysiological mechanism. Moreover, sector-specific retinal thickness showed correlations to cognitive impairment and motor complications in NM-PD. These observations provide novel insights into genotype-specific mechanisms of neurodegeneration in PD and suggest that retinal imaging may offer a window into both cognitive and motor complications. Further longitudinal studies, including healthy controls and expanded retinal layer analyses, are needed to confirm and expand these findings.