Vision problems are among the most common MS symptoms, and often serve as the first symptom of the disease. Vision problems can affect a person’s ability to work and perform other activities of daily living. To review what’s currently known, to explore the role of vision as an outcome in clinical trials for new therapies for MS, and to identify areas for future research, a meeting was convened by the International Advisory Committee on Clinical Trials in Multiple Sclerosis (sponsored by the National MS Society and the European Committee on Treatment and Research in MS). More than 60 world-renowned experts in the fields of MS, neuroophthalmology, and clinical trial design met in Dublin Ireland in November 2013 and now publish their conclusions and recommendations in an open-access article (Brain, First published online: 29 November 2014).
The article, by Drs. Laura J. Balcer (New York University), David H. Miller (University College London), Stephen C. Reingold (Scientific and Clinical Review Associates, LLC), and Jeffrey A. Cohen (Cleveland Clinic), provides an extensive review of published research related to vision and MS, and summarizes the meeting’s focus on optimal ways to evaluate visual signs and symptoms in people with MS and their impact on quality of life, developing consensus on how to design clinical trials that incorporate vision-related outcomes, and identifying priorities for future vision research.
New Tools Available: A test called “low-contrast letter acuity” (LCLA) has emerged as a leading candidate to measure visual impairment in MS. This test involves measuring a person’s ability to distinguish grey letters against a white background, whereas standard vision tests use black letters against a white background. LCLA has been shown to correlate with how vision affects quality of life in people with MS.
Another relatively new tool for evaluating vision and its impact on MS is optical coherence tomography. OCT is a non-invasive and painless imaging tool for viewing nerve structures at the back of the eye. It provides a potential window not only to see damage to important structures that support proper vision, but also to give a window into how MS may be impacting the central nervous system more generally. Studies using OCT support the idea that impairments observed on LCLA reflect nerve fiber and cell loss in people with MS.
OCT also is being used to determine damage to nerve cells known as ganglion cells. This damage has been correlated with MS tissue damage in the cortex (outer layer of the brain) on MRI scans.
Window for Repair: The authors discussed the use of visual outcomes in clinical trials, including trials of experimental strategies for protecting or repairing the nervous system. Some studies, including two recent trials involving stem cells, enrolled people with MS who had a history of visual problems to determine if treatment results in repair to that damage.
Assessing visual outcomes in acute optic neuritis – inflammation of the optic nerve that often presents as the first MS symptom – shows promise as a model for screening neuroprotective and repair strategies. The optic nerve is one of the few locations in the central nervous system that can be assessed directly and noninvasively.
Another test discussed was “visual evoked potentials,” which may complement OCT outcomes. “VEPs” measure electrical activity in the brain in response to sensory – in this case visual – input. Participants sit in front of a screen on which an alternating checkerboard pattern is displayed. The readout indicates blocks in nerve impulse conduction, and can provide more information on damage to myelin or nerve fibers.
Future Directions: The authors summarized future needs for vision research in MS, including:
• studies addressing how measuring visual impairment correlates over time with or predicts more general measures of neurologic disability;
• further exploration of blood markers that have been shown to be elevated in people with optic neuritis and other vision problems;
• further studies to evaluate vision and visual outcomes in children with MS, to assess similarities and differences compared to adults;
• studies that correlate objective visual outcomes with patient-reported outcomes so that the latter would be accepted by regulatory agencies for drug development and approval;
• the development of practical methods to assess abnormal eye movements – which are common in MS – in clinical trials.
Potential for Progress: The authors comment that the field of vision research now benefits from a well-organized network of investigators, and that their findings will be important to the development of new MS therapies aiming to restore function. “The capacity for measures of visual function, quality of life, visual pathway structure, and electrophysiology to show not only deterioration but also improvement will be critical in the emerging era of agents that repair and protect the nervous system,” they write.
Finding solutions to address this important symptom can improve the daily life and clinical care of many people who live with MS.
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