Association of Serum Neurofilament Light Chain With Inner Retinal Layer Thinning in Multiple Sclerosis
Elias S. Sotirchos, Eleni S. Vasileiou, Angeliki Filippatou, Kathryn C. Fitzgerald, Matthew D. Smith, Hannah‐Noelle Lord, Grigorios Kalaitzidis, Jeffrey Lambe, Anna DuVal, Jerry L. Prince, Ellen M. Mowry, Shiv Saidha, Peter A. Calabresi
Abstract
<h3>Background and Objectives</h3> Serum neurofilament light chain (sNfL) and optical coherence tomography (OCT)–derived retinal measures (including peripapillary retinal nerve fiber layer [pRNFL] and macular ganglion cell layer/inner plexiform layer [GCIPL] thickness) have been proposed as biomarkers of neurodegeneration in multiple sclerosis (MS). However, studies evaluating the associations between sNfL and OCT-derived retinal measures in MS are limited. <h3>Methods</h3> In this retrospective analysis of a longitudinal, observational, single-center cohort study, sNfL levels were measured in people with MS and healthy controls (HCs) using single molecule array. Participants with MS were followed with serial OCT for a median follow-up of 4.5 years. Eyes with optic neuritis (ON) within 6 months of baseline OCT or ON during follow-up were excluded. Age-normative cutoffs of sNfL were derived using the HC data, and MS participants with sNfL greater than the 97.5th percentile for age were classified as having elevated sNfL (sNfL-E). Analyses were performed with mixed-effects linear regression models and adjusted for age, sex, race, and history of ON. <h3>Results</h3> A total of 130 HCs (age: 42.4 ± 14.2 years; 62% female) and 403 people with MS (age: 43.1 ± 12.0 years; 78% female) were included. Elevated sNfL levels were present at baseline in 80 participants with MS (19.9%). At baseline, sNfL-E participants had modestly lower pRNFL (−3.03 ± 1.50 μm; <i>p</i> = 0.044) and GCIPL thickness (−2.74 ± 1.02 μm; <i>p</i> = 0.007). As compared with those with sNfL within the reference range, eyes from NfL-E participants exhibited faster longitudinal thinning of the pRNFL (45% faster; −0.74 vs −0.51 μm/y; <i>p</i> = 0.015) and GCIPL (25% faster; −0.35 vs −0.28 μm/y; <i>p</i> = 0.021). Significant differences in rates of pRNFL and GCIPL thinning between sNfL groups were found only in those with relapsing-remitting MS but not progressive MS. <h3>Discussion</h3> Elevated baseline sNfL is associated with accelerated rates of retinal neuroaxonal loss in relapsing-remitting MS, independent of overt ON, but may be less reflective of retinal neurodegeneration in progressive MS.