Changes in Saccadic Hypometria over Time to Monitor Parkinson's Disease Progression

Eye movement biomarkers are emerging as promising tools for monitoring neurodegenerative diseases in clinical trials. Saccadic hypometria, the reduced saccade amplitude leading to undershooting visual targets, is a recognized feature of Parkinson's disease (PD), correlated with motor symptoms severity in cross-sectional studies. However, its use as a biomarker to monitor disease progression has not been studied.

The aim was to assess the sensitivity and reproducibility of saccadic hypometria as a biomarker of PD progression.

The amplitude of saccadic hypometria (ASH) was measured in two cohorts: a single-center cohort (SCC) (30 PD patients, 50 healthy controls) followed by a multicenter cohort (MCC) (250 PD patients, 91 healthy controls across 4 sites). Assessments occurred every 3 months over 9 months using a software-based platform (NeuraLight). Motor symptoms were assessed with the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III. ASH and MDS-UPDRS changes were analyzed using individual slopes of change and compared between groups.

ASH significantly declined over time in PD patients compared to controls in both cohorts (SCC: -  1.96 ± 4.14% vs. 0.33 ± 1.75%, P < 0.01; MCC: - 1.05 ± 3.09% vs. 0.54 ± 1.85%, P < 0.001), and these changes were consistent across MCC sites. MDS-UPDRS III scores remained unchanged over the same period in the SCC, and changes were highly variable across MCC sites, resulting in a non-statistically significant change over time.

ASH progressively worsened in PD patients over 9 months, even when standard clinical scales showed no significant change. These findings support ASH as a sensitive, objective, and quantitative biomarker for monitoring PD progression.