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.

Keywords

Multiple sclerosis biomarkers prognosis fixational eye motion microsaccades retinal eye-tracking

Get full access to this article

View all access options for this article.

References

Wallin

Culpepper

Campbell

, et al. The prevalence of MS in the United States: A population-based estimate using health claims data. Neurology 2019; 92(10): e1029–e1140.

Dutta

Trapp

BD.

Mechanisms of neuronal dysfunction and degeneration in multiple sclerosis. Prog Neurobiol 2011; 93(1): 1–12.

Disanto

Barro

Benkert

, et al. Serum neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Ann Neurol 2017; 81(6): 857–870.

Noyes

Weinstock-Guttman

Impact of diagnosis and early treatment on the course of multiple sclerosis. Am J Manag Care 2013; 19(Suppl. 17): S321–S331.

Sorensen

Frederiksen

Bronnum-Hansen

, et al. Optic neuritis as onset manifestation of multiple sclerosis: A nationwide, long-term survey. Neurology 1999; 53(3): 473–478.

Leibowitz

Alter

Optic nerve involvement and diplopia as initial manifestations of multiple sclerosis. Acta Neurol Scand 1968; 44(1): 70–80.

Tilikete

Jasse

Vukusic

, et al. Persistent ocular motor manifestations and related visual consequences in multiple sclerosis. Ann N Y Acad Sci 2011; 1233: 327–334.

Graves

Balcer

LJ.

Eye disorders in patients with multiple sclerosis: Natural history and management. Clin Ophthalmol 2010; 4: 1409–1422.

Serra

Derwenskus

Downey

, et al. Role of eye movement examination and subjective visual vertical in clinical evaluation of multiple sclerosis. J Neurol 2003; 250(5): 569–575.

10.

Downey

Stahl

Bhidayasiri

, et al. Saccadic and vestibular abnormalities in multiple sclerosis: Sensitive clinical signs of brainstem and cerebellar involvement. Ann N Y Acad Sci 2002; 956: 438–440.

11.

Derwenskus

Rucker

Serra

, et al. Abnormal eye movements predict disability in MS: Two-year follow-up. Ann N Y Acad Sci 2005; 1039: 521–523.

12.

Niestroy

Rucker

Leigh

RJ.

Neuro-ophthalmologic aspects of multiple sclerosis: Using eye movements as a clinical and experimental tool. Clin Ophthalmol 2007; 1(3): 267–272.

13.

Mallery

Poolman

Thurtell

, et al. Visual fixation instability in multiple sclerosis measured using SLO-OCT. Invest Ophthalmol Vis Sci 2018; 59(1): 196–201.

14.

Nij Bijvank

Petzold

Coric

, et al. Quantification of visual fixation in multiple sclerosis. Invest Ophthalmol Vis Sci 2019; 60(5): 1372–1383.

15.

Polman

Reingold

Banwell

, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69(2): 292–302.

16.

Belza

Miyawaki

Liu

, et al. The Multidimensional Assessment of Fatigue scale: A 25-year review and evaluation. Arthritis Rheumatol 2015; 67: 3077–3078.

17.

Sheehy

Yang

Arathorn

, et al. High-speed, image-based eye tracking with a scanning laser ophthalmoscope. Biomed Opt Express 2012; 3(10): 2611–2622.

18.

Mulligan

Recovery of motion parameters from distortions in scanned images. In: Proceedings of the image registration workshop (NASA Publication #CP-1998-206853), Greenbelt, MD, 20–21 November 1997, pp. 281–292. Moffett Field, CA: NASA Ames Research Center.

19.

Stevenson

Roorda

Kumar

. Eye tracking with the adaptive optics scanning laser ophthalmoscope. In: Proceedings of the 2010 symposium on eye-tracking research & applications, Austin, TX, 22–24 April 2010, pp. 195–198. New York: ACM.

20.

Cherici

Kuang

Poletti

, et al. Precision of sustained fixation in trained and untrained observers. J Vis 2012; 12(6): 31.

21.

Okuda

Mowry

Beheshtian

, et al. Incidental MRI anomalies suggestive of multiple sclerosis: The radiologically isolated syndrome. Neurology 2009; 72(9): 800–805.

22.

Zuber

Stark

Cook

Microsaccades and the velocity-amplitude relationship for saccadic eye movements. Science 1965; 150(3702): 1459–1460.

23.

Otero-Millan

Troncoso

Macknik

, et al. Saccades and microsaccades during visual fixation, exploration, and search: Foundations for a common saccadic generator. J Vis 2008; 8(14,21): 1–18.

24.

Engbert

Kliegl

Microsaccades uncover the orientation of covert attention. Vision Res 2003; 43(9): 1035–1045.

25.

Walker

Tian

Shan

, et al. Enhancement of the bias component of downbeat nystagmus after lesions of the nodulus and uvula. Ann N Y Acad Sci 2009; 1164: 482–485.

26.

Choi

Park

Kim

, et al. Paraneoplastic downbeat nystagmus associated with cerebellar hypermetabolism especially in the nodulus. J Neurol Sci 2014; 343(1–2): 187–191.

27.

Waxman

SG.

Axonal conduction and injury in multiple sclerosis: The role of sodium channels. Nat Rev Neurosci 2006; 7(12): 932–941.

28.

Sheehy

Beaudry-Richard

Bensinger

, et al. Methods to assess ocular motor dysfunction in multiple sclerosis. J Neuroophthalmol 2018; 38(4): 488–493.

29.

Choe

Blake

Lee

S-H.

Pupil size dynamics during fixation impact the accuracy and precision of video-based gaze estimation. Vision Res 2015; 118: 48–59.

30.

Drewes

Zhu

, et al. Smaller is better: Drift in gaze measurements due to pupil dynamics. PLoS ONE 2014; 9(10): e111197.

31.

Drewes

Masson

Montagnini

Shifts in reported gaze position due to changes in pupil size: Ground truth and compensation. In: Proceedings of the symposium on eye tracking research and applications, Santa Barbara, CA, 28–30 March 2012. New York: ACM.

32.

McCamy

Najafian Jazi

Otero-Millan

, et al. The effects of fixation target size and luminance on microsaccades and square-wave jerks. PeerJ 2013; 1: e9.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.38 MB