Solving the mysterious links between multiple sclerosis, optic neuritis, and vision loss

MULTIPLE SCLEROSIS (MS) is a mysterious disease. Women with this debilitating inflammatory condition can go from feeling fairly healthy one day to struggling to walk the next, as a person’s immune system attacks the myelin sheaths that insulate nerve cells in the brain.

In North America and Northern Europe, MS is the most common cause of optic neuritis (inflammation of the optic nerve), and MS patients often experience visual disturbances since our eyes are connected to the brain via the optic nerve.

One of the most intriguing mysteries to Heather Moss, MD, PhD, associate professor of ophthalmology and neurology, and director of clinical research, is how and why MS affects the eyes in a subset of patients. Not all patients with MS develop optic neuritis, and some of those who have visual disturbances do not show the same clinical signs of optic neuritis as others. When imaging the eyes and brain using common techniques, Moss said she was often unable to account for these differences in vision among her patients.

She teamed up with May Han, MD, a neuro-immunologist and associate professor of neurology and neurological sciences; Lucas Kipp, MD, a neuro-immunologist and clinical assistant professor of neurology and neurological sciences; and Alfredo Dubra, PhD, professor of ophthalmology. Together, the researchers set off to see what they could learn about the different causes of visual disturbance in people with and without MS—and at the same time discover a better way to measure the disease and predict who is at risk for vision loss.

Optic neuritis and MS

Optic neuritis can be one of the earliest signs of MS, emerging before a patient even receives an MS diagnosis.

“Optic neuritis is a condition that causes vision loss in one or both eyes, which is understandably alarming to people and brings them to seek immediate medical care,” Moss said.

For many patients, the inflammation will go away on its own or with the help of corticosteroids, and their vision will return. But for some patients, more doses or additional treatments may be needed. “We want to figure out upfront what type of optic neuritis or eye disease people have, so that we can treat them appropriately, and also understand their long-term disease potential and prognosis,” Moss said. “This can be critical, as if you use aggressive treatments on every patient, and they do not need it, someone may end up with side effects or a complication of treatment, which can itself be devastating.”

MS in the retina

Moss, Dubra and their team used adaptive optics imaging, which employs a highly-focused light and detector system Dubra helped invent, to get the highest-resolution, most detailed images of the backs of the eyes of people with MS. Even though MS is thought to affect the optic nerve behind the eye, they were surprised to find characteristic changes in the patients’ retinas.

“These changes have not yet been associated with MS, so this is really exciting because we might finally answer this clinical question of why some MS patients can’t see as well as others,” Dubra said.

After examining the eyes of a broad cohort of MS patients, the team published a paper in 2021, and received additional funding from the Department of Defense to continue the work. So far, the patients have been studied mere months, but since MS progresses slowly over years and decades, it will be crucial to get more data from the same patients over an extended period to understand how their retinas may change.

Other causes of optic neuritis

Moss has also applied this approach to better understand rare variants of optic neuritis. In 2007, scientists discovered that a small number of patients diagnosed with optic neuritis have a specific biomarker, myelin oligodendrocyte glycoprotein (MOG), that other patients don’t have. Initially, researchers believed that MOG was associated with MS, but they soon found that MOG is found in a completely separate disease process, dubbed myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD).

The disease is so rare that it is hard to study in a way that provides reliable answers. Moss’s lab has since teamed up with collaborators from across the world to amass 64 MOG and 50 MS patients, and are actively working on identifying ways to differentiate MOGAD optic neuritis from other types, and determine optimal treatments.

As Moss and other researchers learn more about the different causes of optic neuritis and the prognosis for each classification, they hope to ultimately design treatments that can improve eyesight and quality of life for every type of patient. “Finally moving towards better understanding of the disease will give us a chance to better and more specifically treat our patients—this is the ultimate goal of delivering precision medicine and precision health,” Moss said.

By KATHRYN SILL

Kathryn Sill is the former web and communications specialist for the Byers Eye Institute in the Department of Ophthalmology, at Stanford University School of Medicine.