Vision and Vision-related Outcome Measures in Multiple Sclerosis

Laura J. Balcer; David H. Miller; Stephen C. Reingold; Jeffrey A. Cohen


Brain. 2015;138(1):11-27. 

In This Article

Abstract and Introduction


Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis.


Historically, multiple sclerosis clinical trials have lacked sensitive, vision-specific outcome measures. Low-contrast letter acuity (LCLA) has emerged as the leading candidate to measure visual impairment in multiple sclerosis. It correlates with vision-specific quality of life measures, providing information on clinical meaningfulness, and with the structural integrity of the retina measured by optical coherence tomography (OCT). Together, these factors have led to rapid accumulation of knowledge about visual impairment in optic neuritis and multiple sclerosis. The additional availability of MRI to provide further structural information and electrophysiological measures [visual-evoked potentials (VEPs) and electroretinography] make the afferent visual pathway a useful model system to elucidate inflammatory and neurodegenerative mechanisms in the CNS and to test novel agents for neuroprotection and repair in multiple sclerosis (Frohman et al., 2008a, b).

An international group of over 60 investigators in multiple sclerosis, neuro-ophthalmology, clinical trial design, and evaluation of clinical outcome measures from Europe, North America, Asia, and Australia met on 21–23 November 2013 in Dublin, Ireland (see Supplementary material for a list of attendees). This meeting was convened by the International Advisory Committee on Clinical Trials in Multiple Sclerosis and sponsored by the European Committee on Treatment and Research in Multiple Sclerosis (ECTRIMS) and the US National Multiple Sclerosis Society. Overriding goals were to review the state of the field of vision in multiple sclerosis and to identify areas for future research. The discussions focused on evaluating visual manifestations in multiple sclerosis and their impact on those with the disease, providing information to physicians for incorporating vision assessment into multiple sclerosis clinical practice, developing consensus on the design and administrative structure of multicentre multiple sclerosis clinical trials incorporating visual outcomes, and identifying priorities for vision research in multiple sclerosis.

This review is based on discussions at that meeting and a comprehensive search of the literature (PubMed search of English language publications, using search terms 'vision', 'visual outcomes', 'specific visual measures', and 'multiple sclerosis'). We summarize the evolution of the role of vision assessment in multiple sclerosis and provide principles that help us understand the importance of vision as a model for outcomes assessment in the next generation of therapeutic trials.