Progressive MS Linked to Faster Retinal Atrophy, Study Shows

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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People with progressive forms of multiple sclerosis (MS) have faster and disease-modifying therapy (DMT)-resistant retinal atrophy (thinning), compared to those with relapsing-remitting MS (RRMS), a study shows.

Data also highlighted that the thickness of deeper layers of the retina could be used as potential biomarkers of neurodegeneration in people with progressive MS and the potential use of optical coherence tomography (OCT), a non-invasive technique, to monitor such changes in clinical trials and clinical practice.

The study, “Progressive Multiple Sclerosis Is Associated with Faster and Specific Retinal Layer Atrophy,” was published in the journal Annals of Neurology.

Thinning of external and deeper retinal layers has been associated with reductions in brain volume and other measures of disease activity and progression in MS patients.

As a result, retinal changes have been proposed as biomarkers to monitor neurodegeneration in MS. Changes in the thickness of retinal layers can be assessed through a rapid, non-invasive, high-resolution method — OCT.

Moreover, some data suggest there may be differences in retinal atrophy across the various stages of MS. However, the particular retinal features of people with progressive forms of MS — primary progressive MS (PPMS) and secondary progressive MS (SPMS) — remain largely uncharacterized.

A team of researchers at Johns Hopkins University School of Medicine, in Baltimore, Maryland, set out to assess retinal layer atrophy in progressive MS patients and whether it is different from that seen in RRMS patients.

The team also evaluated the contribution of normal aging-related changes to retinal thinning in MS patients and the therapeutic effects of conventional DMT treatment in retinal layers.

The study included 178 RRMS patients, 126 people with SPMS, 60 PPMS patients, and 66 healthy individuals with similar age range (18–65 years) and sex ratio (roughly 70% female) to a typical group of MS patients.

MS patients had no signs of optic neuritis within the six months prior to initial assessment. All participants underwent OCT — to measure changes in two external and two deeper retinal layers — every six to 12 months and were followed for a median of 3.7 years. Data from the first OCT assessment showed that all studied retinal layers were significantly thinner in people with SPMS and PPMS, compared with RRMS patients and healthy individuals.There were no significant differences in retinal layer thickness between SPMS and PPMS patients, so a combination of both was often used in further analyses as a group of progressive MS patients.In addition, all four groups of participants showed significant atrophy in all studied retinal layers over time.Compared with healthy individuals, MS patients showed significantly faster atrophy of the external retinal layers up to their 50–60s. From that point forward, these rates of retinal thinning in MS patients were similar to those expected with normal aging.

Further analysis found that people with progressive MS had significantly faster thinning of all four retinal layers than RRMS patients, regardless of age. The thinning rates of deeper retinal layers were significantly faster in progressive MS patients than in healthy participants, independent of age.

“Our study provides evidence that age impacts rates of retinal layer thinning in [healthy individuals] and MS [patients], and that PMS [progressive MS] is associated with faster retinal atrophy, independently of the effects of aging,” the researchers wrote.

When looking at the effects of DMTs in retinal atrophy, the team classified patients as untreated, treated with “lower” efficacy DMTs  — interferon beta and glatiramer acetate (sold as CopaxoneGlatopa and other generics) — or treated with “higher” efficacy DMTs — Tysabri (natalizumab), rituximab, and Zinbryta (daclizumab).

Results showed that DMTs had no significant effects on retinal layer thickness among people with progressive forms of MS, while RRMS patients treated with “higher” efficacy DMTs had significantly slower retinal thinning than those on “lower” DMTs.

Overall, the team concluded that progressive MS “is associated with faster retinal atrophy independent of age,” and that the atrophy of deeper retinal layers (inner and outer nuclear layers) “appear to predominate in the progressive phases of MS and seem to be unaffected by anti-inflammatory DMTs … and may accordingly represent novel biomarkers of neurodegeneration in PMS.”

The researchers emphasized that these findings may help design clinical trials testing investigational neuroprotective MS therapies, including OCT measures as clinical outcomes and considering aging-related retinal changes.

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