Saccadic variability in patients with Parkinson's disease

Patients with Parkinson's disease (PD) exhibit delayed saccades and saccadic hypometria; Still, the diagnostic yield of saccadic parameters is limited in clinical settings. We hypothesized that, as motor fluctuations, fluctuations would also be documented on saccadic parameters, and these could serve as a feasible interpretative measure for clinical application. This cross-sectional study evaluated a prospectively recruited de novo cohort of 114 patients with PD in South Korea, collected from February 2022 to August 2024. All participants performed horizontal and vertical saccades following a target that alternately appeared on a light bar every 2 s. The mean, standard deviation, and coefficient of variation (CV) of saccadic latency, amplitude, and velocity were analyzed. Dynamic time warping (DTW) was applied to assess the temporal variability of saccadic sequences, including control-deviation DTW (CD-DTW) and population-variability DTW (PV-DTW). The data were compared to those obtained from 70 age- and sex-matched healthy participants. Patients with PD showed a higher CV of saccadic amplitude, both horizontally (p < 0.001) and vertically (p < 0.001), compared with the healthy controls. Latency-, amplitude-, and velocity-based CV and CD-DTW features positively correlated with age and MDS-UPDRS-III. Receiver operating characteristic curve analysis showed that the logistic regression model combining CD-DTW and CV for horizontal saccadic amplitude had the highest discriminatory power (area under the curve of 0.848 [95% confidence interval = 0.777-0.908]; false discovery rate-adjusted q = 0.039). Patients with PD showed a higher saccadic variability than healthy controls, which was correlated with the severity of motor symptoms. Saccadic variability, as well as bradykinesia observed in the extremities, likely reflects the sequence effect of PD. Therefore, saccadic analyses may aid in PD diagnosis and severity assessment.