Deborah Brauser

February 28, 2017

ORLANDO — New research suggests that continual eye problems after demyelination isn't reserved for adults with MS only, as youth are also affected.

A prospective comparison study of more than 100 adolescents showed that those with MS had more progressive thinning of the ganglion cell–inner plexiform layer (GCIPL) of the retina than their healthy peers or those who had had a single demyelinating episode.

In addition, girls showed more pronounced retinal nerve fiber layer (RNFL) atrophy than boys, "suggesting a sexual dimorphism in the mechanisms of retinal damage and/or repair," senior author, E. Ann Yeh, MD, Hospital for Sick Children, University of Toronto, Ontario, Canada, told attendees here at Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2017.

Dr E. Ann Yeh

She added that no previous studies to date have examined these issues over time in a pediatric population.

"The take-away is that kids suffer from ongoing degeneration and that, even though they may look very good, it's the beginning of a neurodegenerative process," Dr Yeh told Medscape Medical News.

Measuring Changes Over Time

Dr Yeh, who is also director of the MS and Demyelinating Disorders Clinic at the University of Toronto, reported that past studies using optical coherence tomography (OCT) have shown reduced GCL and RNFL in youth with central nervous system demyelination after they achieve clinical recovery.

However, those studies were cross-sectional and did not measure changes over time.

"We always assumed that children were resilient and better than adults because they bounce back quickly. We've learned over the years that there is neurodegeneration, although they compensate very well," said Dr Yeh.

She added that the investigators wanted to examine effects in the eye because "it really is a window to the brain in the MS population."

The researchers enrolled 106 children between 2012 and 2016. Of these, 24 were healthy (65% girls), 39 had MS (72% girls), and 43 had monophasic acquired demyelinating syndrome (monoADS; 58% girls).

The mean age at optic neuritis (ON) onset was 12.8 and 9.6 years for the latter two groups, respectively, and the mean time from incident demyelination at study entry was 2.1 and 2.4 years.

In addition, the MS, monoADS, and healthy groups had 81, 79, and 29 total OCT scans at various intervals up to about a year of follow-up. Scans that had been obtained less than 15 days or more than 90 days from ON onset were excluded.

Progressive Decline

Results showed that during 1 year, GCIPL thickness decreased in the group of patients with MS (P = .004), with thinning significantly more pronounced for them than for the group with monoADS (PP = .0008).

Although RNFL thickness didn't change significantly over the study time for any of the groups, there was a significantly different trajectory between those with MS and those with monoADS, with thinning more pronounced in the former group (P = .001).

Subgroup analyses showed that greater RNFL thickness was found in the participants who were older at incident demyelination (P = .03), whereas girls had more progressive degeneration of RNFL than boys (–0.5 μ/y; P = .006).

For the finding in girls, "this is something we probably didn't have enough numbers to really parse out and to understand well, especially because we didn't find this relationship in the ganglion cell layer," admitted Dr Yeh.

Finally, there was a decrease in RNFL of 7.2 μm per ON episode (P < .0001) and a decrease in GCIPL of 5.5 μm per episode (P < .0001).

The overall findings show that "there's a progressive decline in GCIPL in kids with MS, suggesting ongoing neurodegenerative changes in the retinal structures of our population," said Dr Yeh.

"For participants with a positive history of ON, the inverse relationship between RNFL or GCIPL thickness and the number of episodes of ON may suggest a loss of integrity secondary to retrograde injury from afferent visual pathway pathology," she added.

Fascinating and Paradoxical

Program chair, Benjamin M. Segal, MD, professor of neurology and director of the MS Center at the University of Michigan Medical School in Ann Arbor, called the study "very interesting" and was especially struck by the sex differences.

Dr Benjamin M. Segal

"I thought that the fact that females had more degeneration than males was fascinating and a little bit paradoxical," said Dr Segal, who was not involved with the study.

"This is certainly something that needs to be followed up."

Dr Segal noted that pediatric MS is relatively rare and that networks of pediatric centers and research have just recently formed over the last few years.

"The ball is beginning to roll and picking up speed. But I think that's why there's been a delay in findings compared with adult-onset MS," he said.

"Optic neuropathy is very common in MS," he added. "Some of these new techniques are a proxy for measuring neurodegeneration and it's much quicker and easier than MRI."

The study was funded by the MS Scientific Research Foundation, the MS Society of Canada, the National MS Society (NMSS), and the Ontario Institutes of Regenerative Medicine (OIRM). Dr Yeh receives research funding from the Guthy-Jackson Charitable Foundation, OIRM, NMSS, the Consortium of MS Centers, Center for Brain and Mental Health, SickKids Foundation, Rare Diseases Foundation, MS Scientific Foundation (Canada), McLaughlin Centre, and Mario Battaglia Foundation. She is also on the neurotoxicity scientific advisory board for Juno and has received speaker's honorarium from Novartis.

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) 2017. Abstract S1.5, P138. Presented February 23, 2017.

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