Leveraging Visual Outcome Measures to Advance Therapy Development in Neuroimmunologic Disorders
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Abstract
The visual system offers unparalleled precision in the assessment of neuroaxonal damage. With the majority of patients with multiple sclerosis (MS) experiencing afferent and efferent visual dysfunction, outcome measures capturing these deficits provide insight into neuroaxonal injury, even in those with minimal disability. Ideal for use in clinical trials, visual measures are generally inexpensive, accessible, and reproducible. Quantification of visual acuity, visual fields, visual quality of life, and electrophysiologic parameters allows assessment of function, whereas optical coherence tomography (OCT) provides reliable measures of the structural integrity of the anterior afferent visual pathway. The technology of oculomotor biometrics continues to advance, and discrete measures of fixation, smooth pursuit, and saccadic eye movement abnormalities are ready for inclusion in future trials of MS progression. Visual outcomes allow tracking of neuroaxonal injury and aid in distinguishing MS from diseases such as neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody–associated diseases (MOGAD). OCT has also provided unique insights into pathophysiology, including the identification of foveal pitting in NMOSD, possibly from damage to Müller cells, which carry an abundance of aquaporin-4 channels. For some study designs, the cost-benefit ratio favors visual outcomes over more expensive MRI outcomes. With the next frontier of therapeutics focused on remyelination and neuroprotection, visual outcomes are likely to take center stage. As an international community of collaborative, committed, vision scientists, this review by the International MS Visual System Consortium (IMSVISUAL) outlines the quality standards, informatics, and framework needed to routinely incorporate vision outcomes into MS and NMOSD trials.
Glossary
- AQP4=
- aquaporin-4;
- CS=
- contrast sensitivity;
- EDSS=
- Expanded Disability Status Scale;
- EDTRS=
- Early Treatment Diabetic Retinopathy Study;
- ERGs=
- Electroretinograms;
- GCIPL=
- ganglion cell + inner plexiform layer;
- GCL=
- ganglion cell layer;
- HCVA=
- High-contrast visual acuity;
- IMSVISUAL=
- International MS Visual System Consortium;
- INL=
- inner nuclear layer;
- ISCEV=
- International Society for Clinical Electrophysiology of Vision;
- LCLA=
- low-contrast letter acuity;
- LGN=
- lateral geniculate nucleus;
- MD=
- mean deviation;
- MOGAD=
- myelin oligodendrocyte glycoprotein antibody–associated disease;
- MSFC=
- MS Functional Composite;
- NEI-VFQ=
- National Eye Institute Visual Function Questionnaire;
- NMOSDs=
- neuromyelitis optica spectrum disorders;
- OCT=
- optical coherence tomography;
- ON=
- optic neuritis;
- ONH=
- optic nerve head;
- ONL=
- outer nuclear layer;
- OPL=
- outer plexiform layer;
- ONTT=
- optic neuritis treatment trial;
- OR=
- optic radiation;
- OT=
- optic tract;
- QoL=
- quality of life;
- RGC=
- Retinal ganglion cells;
- RNFL=
- retinal nerve fiber layer;
- VEPs=
- Visual Evoked Potentials
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by the authors.
IMSVISUAL coinvestigators are listed in the appendix at the end of the article.
- Received February 15, 2021.
- Accepted in final form November 4, 2021.
- Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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- Abstract
- Glossary
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- Afferent Visual Function Measures
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- Efferent Visual System and Oculometrics
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- Study Funding
- Disclosure
- Appendix 1 Authors
- Appendix 2 Coinvestigators
- Footnotes
- References
- Figures & Data
- Info & Disclosures
Dr. Sevil Yaşar and Dr. Behnam Sabayan
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