Validation of microsaccades as a biomarker for disability in multiple sclerosis

Abstract

Purpose : To quantitatively analyze microsaccades, as recorded by the tracking scanning laser ophthalmoscope, to monitor disability in patients with multiple sclerosis (MS).

Methods : We recruited 110 people with MS (diagnosed by 2010 International Panel criteria) from the UCSF MS Center as two sequential cohorts of 50 and 60 subjects. Retinal imaging and eye-tracking was performed with the tracking scanning laser ophthalmoscope (TSLO) using 840 nm light to raster scan the retina. Three, 10-second recordings of fixation, spanning a 5-degree field of view, were acquired for each patient. Patients were instructed to fixate on the upper right-hand corner of the imaging raster. Strip-based, offline analysis of the retinal images was used to extract eye motion at 480 Hz. Microsaccadic metrics of speed, amplitude, quantity of microsaccades, directionality, and overall fixation pattern were analyzed and compared to both Expanded Disability Status Scale (EDSS) scores and Functional System Scores (FSS) for each cohort.

Results : For the 50 people with MS in cohort 1 the mean age was 46.6 (range 24-73) and mean EDSS was 3.45 (range 1-8), and for the 60 people with MS in cohort 2 the mean age was 52.4 (range 24-73) and the mean EDSS was 3.28 (range 0-7). Both Cohort 1 (C1) and Cohort 2 (C2) demonstrated a clear correlation between the number of microsaccades recorded in a 10-second interval and a patient’s EDSS score (C1: p < 0.001, C2: p=0.028). In a multivariable linear regression model combining both cohorts and adjusting for age, average number of microsaccades in a 10-second recording increased by 1.68 for every 1-point increase in EDSS (p<0.001). Microsaccades also correlated with brainstem specific disability (brainstem FSS), for average number of microsaccades for C1 (p=0.0028) and average microsaccadic velocity and amplitude for C2 (p=0.008). Average number of microsaccades also correlated with motor disability in C2 (p=0.049) and a trend in C1 (p=0.05), combined cohort p=0.006.

Conclusions : A greater number of microsaccades, occurring during 10s of fixation, were quantitatively measured using TSLO and correlated with a greater global disability (EDSS), brainstem and motor disability in people with MS. Longitudinal studies in people with MS evaluating change in microsaccadic number and their properties over time are needed in order to evaluate the TSLO as a quantitative biomarker to evaluate disease progression and prognosis.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.