To investigate eye movement abnormalities in patients with PD and heterozygous GBA variants compared to non-carrier PD.

Mono- and bi-allelic variants of GBA represent the major genetic risk factor for PD, although with reduced penetrance. Biomarkers for phenoconversion in GBA-carriers are not available. Bi-allelic GBA variants cause Gaucher disease (GD). A subtype of GD (GD3) have characteristic slowing of horizontal saccades. Systematic analysis of eye movement in het GBA-carriers has not been previously reported.

We enrolled 18 participants with PD and het GBA variants (PD/GBA) and 35 participants with no GBA variants (PD). Demographic information and clinical rating scales were collected (Unified Parkinson’s disease Rating Scale –UPDRS, Montreal Cognitive Assessment -MOCA, Hoehn and Yahr -HY). Binocular eye movements were recorded with infrared video-oculography (EyeLink 1000 Plus, SR Research). Horizontal and vertical pro-saccades and self-paced saccades were recorded; eye movement data were analyzed off-line using custom Matlab software.

Mean age and age-of-onset were lower in PD/GBA compared to PD, consistent with previous literature, with no significant difference of disease duration. PD/GBA showed significantly lower horizontal self-paced saccade frequency (1.95hz and 2.69hz respectively, t=-3.3, p=.0016) while horizontal saccades were slower in PD compared to PD/GBA. GBA status significantly correlated with horizontal self-paced frequency (-0.44, p=.0016). A significant correlation was found across all patients (0.28, p=.045) between UPDRS total score and horizontal prosaccade latency, and a nearly significant correlation (0.24, p=.094) with horizontal self-paced saccade frequency. Correlation between HY and horizontal self-paced saccade frequency also approached significance (r=0.26, p=.077). No significant correlations were found between UPDRS part 3 or MOCA and eye movement metrics.

PD/GBA participants had specific eye movement abnormalities compared to non-carrier PD. Interestingly, we did not observe slow horizontal saccades in PD/GBA, as hypothesized based on GD3 phenotype. Ongoing analysis will include comparison with controls participants and non-manifesting GBA carriers.