Oculomotor deficits are common in hereditary ataxia, but disproportionally neglected in clinical ataxia scales and as outcome measures for interventional trials. Quantitative assessment of oculomotor function has become increasingly available and thus applicable in multicenter trials and offers the opportunity to capture severity and progression of oculomotor impairment in a sensitive and reliable manner. In this consensus paper of the Ataxia Global Initiative Working Group On Digital Oculomotor Biomarkers, based on a systematic literature review, we propose harmonized methodology and measurement parameters for the quantitative assessment of oculomotor function in natural-history studies and clinical trials in hereditary ataxia. MEDLINE was searched for articles reporting on oculomotor/vestibular properties in ataxia patients and a study-tailored quality-assessment was performed. One-hundred-and-seventeen articles reporting on subjects with genetically confirmed (n=1134) or suspected hereditary ataxia (n=198), and degenerative ataxias with sporadic presentation (n=480) were included and subject to data extraction. Based on robust discrimination from controls, correlation with disease-severity, sensitivity to change, and feasibility in international multicenter settings as prerequisite for clinical trials, we prioritize a core-set of five eye-movement types: (i) pursuit eye movements, (ii) saccadic eye movements, (iii) fixation, (iv) eccentric gaze holding, and (v) rotational vestibulo-ocular reflex. We provide detailed guidelines for their acquisition, and recommendations on the quantitative parameters to extract. Limitations include low study quality, heterogeneity in patient populations, and lack of longitudinal studies. Standardization of quantitative oculomotor assessments will facilitate their implementation, interpretation, and validation in clinical trials, and ultimately advance our understanding of the evolution of oculomotor network dysfunction in hereditary ataxias.

Balance Disorders and Ataxia Service Royal Victoria Eye and Ear Hospital East Melbourne Melbourne VIC 3002 Australia

Departamento de Medicina Interna Universidade Federal do Rio Grande do Sul Porto Alegre Brazil

Department of Genetics Neurogene National Reference Centre for Rare Diseases Pitié Salpêtrière University Hospital Assistance Publique Hôpitaux de Paris Paris France

Department of Neurology Centre of Hereditary Ataxias 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Neurology Massachusetts General Hospital Harvard Medical School Boston MA USA

Department of Neurology University of Pécs Medical School Pécs Hungary

Department of Neurosciences and Reproductive and Odontostomatological Sciences University of Naples Federico 2 Naples Italy

Department of Otology and Laryngology and Department of Neurology Harvard Medical School Boston MA USA

Faculty of Medicine University of Zurich Zurich Switzerland

German Center for Neurodegenerative Diseases University of Tübingen Tübingen Germany

Institute of Psychiatry and Neurology Warsaw Poland

Neurology Cantonal Hospital of Baden 5404 Baden Switzerland

NeuroMetrology Lab Nuffield Department of Clinical Neurosciences Clinical Neurology Medical Sciences Division University of Oxford Oxford OX3 9DU UK

Nuffield Department of Clinical Neurosciences University of Oxford Oxford UK

Oxford Centre for Genomic Medicine Oxford University Hospitals NHS Trust Oxford UK

Research Division Translational Genomics of Neurodegenerative Diseases Hertie Institute for Clinical Brain Research and Center of Neurology University of Tübingen Tübingen Germany

Roche Pharma Research and Early Development Neuroscience and Rare Diseases Roche Innovation Center Basel Basel Switzerland

Serviço de Genética Médica Centro de Pesquisa Clínica e Experimental Hospital de Clínicas de Porto Alegre Porto Alegre Brazil

Sorbonne Université Institut du Cerveau Paris Brain Institute ICM Inserm U1127 CNRS UMR7225 Paris France

The Florey Institute of Neuroscience and Mental Health Parkville Melbourne VIC 3052 Australia

University of California Los Angeles Los Angeles California USA

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