A Digital Measure of Eye Movements During Reading Sensitively Captures Oculomotor and Speech Dysfunction, Early Changes, and Disease Progression in Ataxias.
Brandon Oubre, Faye Yang, Anna C Luddy, Rohin Manohar, Nancy N Soja, Christopher D Stephen, Jeremy D Schmahmann, Divya Kulkarni, Lawrence White, Siddharth Patel, Anoopum S Gupta
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引用次数: 0
Abstract
Objective: Sensitive behavioral measures are needed for clinical trials in ataxias and other neurodegenerative diseases. We hypothesized that quantitative analysis of eye movements during a natural multi-component task (passage reading) could produce a measure capable of capturing subclinical signs and disease progression.
Methods: Binocular gaze sampled at 1000 hertz (Hz) was collected from 102 individuals with ataxia (including 36 spinocerebellar ataxias, 12 Friedreich's ataxia, and 5 multiple system atrophy) and 70 healthy controls. Longitudinal data were available for 26 participants with ataxia in the ongoing Neurobooth natural history study. The Reading Eye Abnormality Digital (READ) score was developed by training a regression model to aggregate saccade and fixation kinematics.
Results: Mean displacement of fixations, the number and frequency of saccades, and the proportion of regressive saccades were related to oculomotor dysfunction, speech dysfunction, and overall ataxia severity. The READ score was reliable (intraclass correlation coefficient [ICC] = 0.96, p < 0.001) and correlated with Brief Ataxia Rating Scale (BARS) total score (r = 0.82, p < 0.001), oculomotor (r = 0.52, p < 0.001), and speech (r = 0.73, p < 0.001) subscores, and patient reports of function including patient-reported outcome measures (PROM)-Ataxia (r = 0.51, p < 0.001) and the Dysarthria Impact Scale (DIS; r = 0.53, p < 0.001). The READ score detected subclinical oculomotor (area under the curve [AUC] = 0.69, p = 0.02) and speech signs (AUC = 0.72, p < 0.001) and disease progression (d = 0.36, p = 0.03). The BARS total did not reach statistical significance in capturing progression between study visits in this cohort (d = 0.27, p = 0.08).
Interpretation: Digital measures of eye movements are a promising approach for sensitively measuring ataxia in clinical trials (including early-stage disease) and may have utility in other neurodegenerative diseases affecting speech or ocular control. ANN NEUROL 2025.
期刊介绍：
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
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