Background: Abnormalities of eye movements occur early in the disease course of Huntington's disease, often preceding clinical motor diagnosis. The increasing availability of digital eye tracking tools indicate a potential role for eye movements as biomarkers of prognosis and progression in Huntington's disease, yet the optimal set of oculomotor tasks to measure is currently unknown.
Methods: We explored the clinical progression of the six oculomotor items of the Unified Huntington's Disease Rating Scale in data from the Enroll-HD (N = 4,775) and PREDICT-HD (N = 969) observational studies and their association with time to clinical motor diagnosis and functional decline in time-dependent survival models.
Results: Vertical eye movements were affected in larger proportions of participants before motor diagnosis than horizontal eye movements. Stepwise Cox proportional hazard regression analyses identified saccade velocity, vertical smooth pursuit, and horizontal saccade initiation as independently significant predictors of progression to motor manifest disease and functional decline.
Conclusion: Oculomotor progression follows a distinct pattern in early Huntington's disease, which should be kept in mind when developing digital eye tracking paradigms to be used as biomarkers in future observational studies and clinical trials.
Keywords: Enroll-HD; Huntington's disease; biomarker; eye movements; prognosis.
Copyright © 2026 Kaddoura, Dalbro, van Walsem and Pihlstrøm.