Serum neurofilament levels correlate with retinal nerve fiber layer thinning in multiple sclerosis

Abstract

Background: Serum neurofilament light chain (sNfL) levels and peripapillary retinal nerve fiber layer (pRNFL) are both emerging biomarkers of neuro-axonal damage in multiple sclerosis (MS). However, data on the relation between sNfL and pRNFL are scarce.

Objective: We aimed to determine the relation of sNfL levels with pRNFL thinning in a large cohort of relapsing-remitting (RR) MS patients.

Methods: We identified 80 patients from a prospective, 3-year observational study on retinal changes in RRMS with annual blood samples available. sNfL levels were measured using single-molecule array (Simoa^TM) assay. Annualized loss of pRNFL (aLpRNFL) was determined by individual linear regression models. Correlations between single and repeated sNfL levels and aLpRNFL were analyzed using multivariate linear regression and mixed-effect models.

Results: After correction for sex, age, and baseline sNfL, an sNfL increase of 10 pg/mL was associated with an aLpRNFL of -0.7 µm (95% confidence interval (CI): (-1.3, -0.2), p < 0.001). Patients with ⩾2 sNfL measurements >75th percentile displayed higher aLpRNFL (2.2 µm, standard deviation (SD) 0.6) compared to patients with no sNfL measure >75th percentile (0.4 µm, SD 0.2, p < 0.001). Between 15% and 20% of the aLpRNFL variance could be predicted from sNfL levels.

Conclusion: sNfL levels contribute to the prediction of retinal thinning in patients with RRMS, strengthening its value as a biomarker of neuro-axonal damage.

Keywords: Multiple sclerosis; biomarker; neurofilament; optical coherence tomography; peripapillary retinal nerve fiber layer.