Fixational microsaccades: A quantitative and objective measure of disability in multiple sclerosis

Abstract

Background: Objective tools for prognosis and disease progression monitoring in multiple sclerosis (MS) are lacking. The visuomotor system could be used to track motor dysfunction at the micron scale through the monitoring of fixational microsaccades. Aims: The aim of this study was to evaluate whether microsaccades are correlated with standard MS disability metrics and to assess whether these methods play a predictive role in MS disability. Method: We used a custom-built retinal eye tracker, the tracking scanning laser ophthalmoscope (TSLO), to record fixation in 111 participants with MS and 100 unaffected controls. Results: In MS participants, a greater number of microsaccades showed significant association with higher Expanded Disability Status Scale score (EDSS, p < 0.001), nine-hole peg test (non-dominant: p = 0.006), Symbol Digit Modalities Test (SMDT, p = 0.014), and Functional Systems Scores (FSS) including brainstem ( p = 0.005), cerebellar ( p = 0.011), and pyramidal ( p = 0.009). Both brainstem FSS and patient-reported fatigue showed significant associations with microsaccade number, amplitude, and peak acceleration. Participants with MS showed a statistically different average number ( p = 0.020), peak vertical acceleration ( p = 0.003), and vertical amplitude ( p < 0.001) versus controls. Logistic regression models for MS disability were created using TSLO microsaccade metrics and paraclinical tests with ⩾80% accuracy. Conclusion: Microsaccades provide objective measurements of MS disability level and disease worsening.

High-resolution, ultrafast, wide-field retinal eye-tracking for enhanced quantification of fixational and saccadic motion

“…Results shown in Fig. 10 are in good agreement with the previously published results using different instrumentation [2,35]. Notably, our tracking system extends the range of detectable magnitudes of microsaccades and increases the accuracy of their measurement.…”

“…The performance of the system is critically dependent on an adequate choice of reference frame, itself subject to distortion by motion artifacts [33,34]. More significantly, a stationary reference frame sets the upper limit for the range of measurable eye displacements to the spatial extent of the reference frame and limits the detectable velocities to tens of degrees/s [25,30,35].…”

“…Increased fixation instability and altered kinematic saccadic parameters are known quantitative biomarkers of multiple sclerosis [47,48]. In a recent clinical study, microsaccades have been shown to provide objective measurements of multiple sclerosis disability level and disease worsening [35]. Oculomotor abnormalities are therefore a sensitive biomarker for diagnosis and disease progression forecast [49].…”

Can stability of visual fixation be a measure for disability in multiple sclerosis?

“…The list seems exhaustive, but the group from University of California, San Francisco (UCSF) presents a paper which implies that problems with stability of visual fixation as characterized by quantification of microsaccades may eventually be added. 1 What are microsaccades? One of the phenomena listed above is a well known party trick, visual fading.…”

“…The Green lab from UCSF developed a novel approach to monocular recording and quantification of microsaccades, a custom-built retinal eye-tracker. 1 However, the reader should be aware that commercially available instruments of binocular recording such as video-oculography (e.g. EyeLink 1000, SR research) compare at the same level of search-coil techniques when it comes to microsaccades' detection.…”