Objective: To perform an in-depth characterization of eye movement abnormalities in Parkinson’s disease (PD) and non-manifesting carriers of GBA1 pathogenic variants.

Background: Eye movement abnormalities are important biomarkers for movement disorders. Variants in the beta-glucocerebrosidase gene (GBA1) represent one of the most common genetic risk factors of PD. Bi-allelic variants of GBA1 cause Gaucher disease (GD). Slow saccades, horizontal more than vertical, are the typical hallmark of GD type 3, a neuropathic form of GD. In PD, reductions in saccade amplitude and velocity in self-paced voluntary saccades are reported, while standard reflexive saccades tend to be normal. There is limited understanding of eye movement abnormalities in genetic forms of PD.

Method: We collected demographic and clinical information (including rating scales for motor and non-motor symptoms) of a clinical cohort, and recorded horizontal (h) and vertical (v) prosaccades, gap and overlap saccades, self-paced saccades (SPS), and smooth pursuit through Infrared video-oculography (EyeLink 1000 Plus, SR Research). Data were analyzed off-line using custom Matlab software.

Results: We assessed n=80 individuals: 16 with GBA1-PD (GBA-PD), 34 with PD no GBA1 variants (iPD), 8 non-manifesting GBA1 carriers (GBA-CTRL), and 22 non-affected individuals without GBA1 variants (CTRL). Group differences occurred predominantly in the SPS paradigm. hSPS frequency was reduced in GBA-PD compared to iPD (1.6 ±1 vs 2.7±0.7, p=0.0013). h and vSPS amplitude (h 14.7± 5.7 vs 22±5, p=0.006; v 10.6±2.1 vs 13.3± 3.8, p=0.03) and hSPS frequency (1.9±0.9 vs 2.7± 1, p=0.04) were reduced in GBA-PD compared to GBA-CTRL. In GBA-CTRL, there was a significant correlation between both reduced vSPS amplitude and reduced peak velocity to increased Hoehn and Yahr (HY) scale (p=0.02, p=0.01), and between UPDRS part III (p=0.04, p=0.05) and UPDRS total score (p=0.05, p=0.04). No correlations were found in GBA-PD. There were no group differences in other eye movement parameters.

Conclusion: Eye tracking showed distinct features in SPS performance between PD and CTRL groups with and without GBA1 variants. We did not identify any of the characteristic features of GD type 3 in the GBA1 groups (GBA-PD and GBA-CTRL), suggesting a different underlying pathology. The identified parameters should be tested in larger cohorts to assess biomarker validity for GBA-PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/eye-movement-abnormalities-in-gba1-related-parkinsons-disease-and-non-manifesting-gba1-carriers/