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Serum neurofilament levels reflect outer retinal layer changes in multiple sclerosis.

Caspar B Seitz1, Falk Steffen1, Muthuraman Muthuraman1

  • 1Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

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|June 9, 2021
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Summary

Serum neurofilament light chain (sNfL) predicts outer retinal thinning in multiple sclerosis (MS). sNfL levels are a good biomarker for neurodegeneration in the outer plexiform layer (OPL) in early MS patients.

Keywords:
multiple sclerosisneuroimmunologyoptic neuritisoptical coherence tomographyserum neurofilamenttranslation

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Area of Science:

  • Neuroscience
  • Ophthalmology
  • Biomarker Discovery

Background:

  • Serum neurofilament light chain (sNfL) and intra-retinal layers are potential biomarkers for neuro-axonal injury in multiple sclerosis (MS).
  • Neurofilament expression varies across intra-retinal layers, suggesting specific roles in MS pathology.
  • Understanding the interplay between sNfL and retinal layer integrity is crucial for early MS detection and monitoring.

Purpose of the Study:

  • To investigate the association between sNfL levels and specific intra-retinal layer volumes in early MS patients.
  • To determine if sNfL can predict neuro-axonal damage within the retina, particularly the outer plexiform layer (OPL).
  • To explore the utility of sNfL as a biomarker for retinal neurodegeneration in MS.

Main Methods:

  • 156 early MS patients underwent 3D spectral domain macular optical coherence tomography (OCT) and sNfL level assessment.
  • Patients were categorized based on history of optic neuritis (HON vs. NHON).
  • Support vector machine analysis was used to model associations and predict OPL volume changes longitudinally in a subgroup (n=38).

Main Results:

  • Patients with a history of optic neuritis (HON) exhibited significantly thinner outer plexiform layer (OPL) volumes compared to those with no history (NHON).
  • Higher sNfL levels were significantly correlated with thinner OPL volumes in HON patients.
  • Longitudinal analysis confirmed that higher sNfL levels predicted OPL atrophy over 2 years, with 75.7% accuracy in predicting OPL volume via machine learning.

Conclusions:

  • sNfL levels serve as a reliable predictor of future outer retinal thinning in MS patients.
  • The outer plexiform layer (OPL), rich in neurofilaments, represents a key retinal layer where neurodegeneration can be monitored in MS.
  • sNfL and OPL changes offer complementary insights into MS neurodegeneration, potentially enhancing diagnostic and prognostic capabilities.