Outer retinal layer changes are associated with serum neurofilament levels

Outer retinal layer changes are associated with serum neurofilament levels in multiple sclerosis

Serum neurofilament levels were a good predictor of future outer retinal layer thinning in multiple sclerosis (MS)

Monitoring the neuroinflammatory and chronic neurodegenerative component of multiple sclerosis (MS) pathology is crucial for individualized patient treatment decisions and development of new treatment paradigms. These pathological changes can be assessed by magnetic resonance imaging (MRI) of the brain, but also regionally by optical coherence tomography (OCT) of the eye. OCT is a valuable technique to study tissue alterations within the central nervous system (CNS). The visual system offers a unique and easily accessible window into the CNS of MS patients, allowing researchers to monitor inflammatory activity within the retina and to measure neuro-axonal loss of intra-retinal layers by OCT on a microscopic scale. The strength of the visual system as a marker of MS disease activity or progression lays in the fact that it is frequently and early affected in MS patients.

Besides this imaging marker with good spatial resolution, serum neurofilament light chain (sNfL) is an emerging fluid biomarker of neuro-axonal injury primarily independent of the underlying cause. Taken together, the value of sNfL in monitoring and predicting disease evolution in MS and its association with clinical and structural MRI markers of activity confirms the usefulness of this measure as a serum biomarker.

A recently published study investigated the association of both markers in early MS, having identified that neurofilament has a distinct immunohistochemical expression pattern among intra-retinal layers. Three-dimensional (3D) spectral domain macular optical coherence tomography scans and sNfL levels were investigated in 156 early MS patients (female/male: 109/47, mean age: 33.3 ± 9.5 years, mean disease duration: 2.0 ± 3.3 years). Out of the whole cohort, 110 patients had no history of optic neuritis (NHON) and 46 patients had a previous history of optic neuritis (HON). In addition, a subgroup of patients (n = 38) was studied longitudinally over 2 years. Support vector machine analysis was applied to test a regression model for significant changes.

In these cohort, HON patients had a thinner outer plexiform layer (OPL) of retinal layer volume compared to NHON patients (B = −0.016, SE = 0.006, p = 0.013). Higher sNfL levels were significantly associated with thinner OPL volumes in HON patients (B = −6.734, SE = 2.514, p = 0.011). This finding was corroborated in the longitudinal subanalysis by the association of higher sNfL levels with OPL atrophy (B = 5.974, SE = 2.420, p = 0.019). sNfL levels were 75.7% accurate at predicting OPL volume in the supervised machine learning.

In conclusion, sNfL levels were a good predictor of future outer retinal thinning in MS. Changes within the neurofilament-rich OPL could be considered as an additional retinal marker linked to MS neurodegeneration.

Source: Seitz CB, Steffen F, Muthuraman M, et al. Serum neurofilament levels reflect outer retinal layer changes in multiple sclerosis. Therapeutic Advances in Neurological Disorders. January 2021. doi:10.1177/17562864211003478