Objective: To evaluate the relationship between longitudinal changes in saccadic hypometria and changes of clinically meaningful outcomes, specifically axial impairment and MDS-UPDRS Part II scores, in patients with Parkinson’s disease participating in the multicenter PALOMA trial.

Background: Reliable measurement of PD progression remains challenging, particularly for axial impairment (e.g., speech impairment, gait disturbance, postural instability, freezing of gait) and activities of daily living. MDS-UPDRS Part II and the axial subscale reflect disability but are limited in detecting longitudinal change. Saccadic hypometria, quantified by the degree to which saccades undershoot targets (ASH), reflects downstream basal ganglia output and can serve as a biomarker of clinical change over time.

Method: PD symptoms were assessed using MDS-UPDRS, and ASH was measured using a software-based platform (NeuraLight) in 3-month intervals during 12 months in the PALOMA multicenter cohort (250 patients, 66.5±9.4 years, 77 females, H&Y≤2, time from diagnosis: 3.2±1,4 years). Linear regression was used to calculate changes over time of ASH, and Pearson’s coefficient for correlations with MDS-UPDRS II and axial symptoms.

Results: At baseline, ASH correlated significantly with axial scores (r=−0.20, p=0.03) and MDS-UPDRS Part II (r= −0.33, p<0.01). Furthermore, changes over time were also correlated: 12-month change in ASH correlated with 12-month change in both axial score (r =−0.20, p=0.04) and in MDS-UPDRS Part II (r=−0.25, p=0.01). Patients with the most ASH decline (top 33%) showed a mean 12-month worsening of 3.71 points in MDS-UPDRS Part II vs. a 2.11 points worsening in the overall PALOMA cohort.

Conclusion: Changes in ASH were significantly associated with progression in both axial impairment and MDS-UPDRS Part II, two clinically meaningful domains of PD disability. This relationship is biologically and clinically plausible, as axial dysfunction strongly contributes to impairment in motor activities of daily living. Concordant associations across these complementary outcomes strengthen the robustness of the findings. Together, these data support ASH as a marker of disease progression and functional decline, reflecting downstream basal ganglia output relevant to the axial and functional manifestations of PD.

References: Gurevich T, Raveh E, Kreitman R, Ben-Ami E. Monitoring Parkinson’s progression: eye movements vs. MDS-UPDRS III [abstract]. Parkinsonism & Related Disorders, Volume 134, 107389.
Ben-Ami E, Raveh E, Harpaz E, Riklin I, Armstrong R, Januario C, Gurevich T, Alcalay R, Mir P, Tosin MHS, Goetz C, Rascol O. Saccadic hypometria to monitor Parkinson’s disease progression: validation across multiple trials. CNS Drugs. Under review; 2026.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/saccadic-hypometria-as-a-biomarker-of-longitudinal-change-in-mds-updrs-part-ii-and-axial-motor-subscores-results-from-the-multicenter-paloma-trial/