Department of Neurosciences (J.S.G.), University of California, San Diego; Experimental and Clinical Research Center (F.C.O., F.P.), Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin & NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Department of neuroscience (A.V.D.W.), Central Clinical School, Monash University, Melbourne, Australia; NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation (S.C.), UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, United Kingdom; Department of Neurology (E.S.S., S.S., S.D.N.), Johns Hopkins University School of Medicine, Baltimore, MD; Rigshospitalet (J.F.), Denmark; Department of Neurology (P.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany; Division of Neurology, Department of Pediatrics (E.A.Y.), Division of Neuroscience and Mental Health, Hospital for Sick Children, Hospital for Sick Children Research Institute, and University of Toronto, Toronto, Canada.
Neurol Neuroimmunol Neuroinflamm. 2021 Dec 26;9(2). doi: 10.1212/NXI.0000000000001126. Print 2022 Mar.
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.
视觉系统在评估神经轴突损伤方面具有无与伦比的精确性。大多数多发性硬化症 (MS) 患者都存在传入和传出视觉功能障碍，因此，能够捕捉这些缺陷的结果测量指标可深入了解神经轴突损伤，即使在那些仅有轻微残疾的患者中也是如此。视觉测量指标非常适合用于临床试验，因为它们通常价格低廉、易于获取且具有可重复性。评估视力、视野、视觉生活质量和电生理参数等功能的量化指标，同时光学相干断层扫描 (OCT) 可提供可靠的前向传入视觉通路结构完整性的测量指标。眼动生物计量学技术不断进步，注视、平滑追踪和眼跳运动异常等离散测量指标已经准备好纳入未来的 MS 进展临床试验中。视觉结果可以跟踪神经轴突损伤，并有助于将 MS 与视神经脊髓炎谱系疾病 (NMOSD) 或髓鞘少突胶质细胞糖蛋白抗体相关疾病 (MOGAD) 等疾病区分开来。OCT 还为病理生理学提供了独特的见解，包括在 NMOSD 中识别出黄斑区小凹，这可能是由于 Müller 细胞受损所致，这些细胞富含水通道蛋白-4 通道。对于某些研究设计，视觉结果的成本效益比优于更昂贵的 MRI 结果。随着下一个治疗重点聚焦于髓鞘再生和神经保护，视觉结果可能会占据中心舞台。作为一个具有协作精神和承诺的国际视觉科学家社区，国际多发性硬化症视觉系统联合会 (IMSVISUAL) 的这篇综述概述了将视觉结果常规纳入 MS 和 NMOSD 临床试验所需的质量标准、信息学和框架。
