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Progressive Multiple Sclerosis Is Associated with Faster and Specific Retinal Layer Atrophy.

Elias S Sotirchos1, Natalia Gonzalez Caldito1, Angeliki Filippatou1

  • 1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Annals of Neurology
|April 15, 2020
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Progressive multiple sclerosis (PMS) shows faster retinal atrophy than normal aging or relapsing-remitting MS. Inner nuclear and outer nuclear layers may serve as novel biomarkers for PMS neurodegeneration.

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Area of Science:

  • Ophthalmology and Neurology
  • Neuroscience and Neurodegeneration
  • Biomarker Discovery

Background:

  • Therapeutic development for progressive multiple sclerosis (PMS) is hindered by the absence of reliable biomarkers for monitoring neurodegeneration.
  • Optical coherence tomography (OCT)-derived retinal measures are potential biomarkers, but their utility in PMS requires further investigation.
  • It remains unclear if retinal atrophy in PMS is distinct from normal aging or relapsing-remitting multiple sclerosis (RRMS).

Purpose of the Study:

  • To investigate whether retinal atrophy in PMS differs from normal aging and RRMS.
  • To determine if retinal measures can serve as biomarkers for neurodegeneration in PMS.
  • To assess the impact of aging on retinal layer thinning in multiple sclerosis (MS).

Main Methods:

  • Serial OCT scans were performed on 178 RRMS, 186 PMS, and 66 control participants over a median follow-up of 3.7 years.
  • Rates of thinning in the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell + inner plexiform layer (GCIPL), inner nuclear layer (INL), and outer nuclear layer (ONL) were analyzed.
  • Statistical analyses were conducted to compare thinning rates between groups and assess the influence of age and disease-modifying therapies (DMTs).

Main Results:

  • Retinal atrophy, specifically thinning of the pRNFL and GCIPL, accelerated with age in all participants.
  • Progressive multiple sclerosis (PMS) exhibited significantly faster pRNFL and GCIPL thinning compared to RRMS, independent of age.
  • Inner nuclear layer (INL) and outer nuclear layer (ONL) thinning were independently faster in PMS compared to controls and RRMS, and this effect was not observed between RRMS and controls.
  • Unlike in RRMS, DMTs did not influence the rates of retinal layer atrophy in PMS.

Conclusions:

  • Progressive multiple sclerosis (PMS) is characterized by accelerated retinal atrophy that is independent of age.
  • Inner nuclear layer (INL) and outer nuclear layer (ONL) thinning represent potential novel biomarkers for neurodegeneration in PMS.
  • These novel biomarkers in PMS appear unaffected by conventional disease-modifying therapies (DMTs), suggesting a distinct disease mechanism.
  • Clinical trials using OCT outcomes in MS should account for the effects of aging on retinal layer atrophy rates.