Association of Serum Neurofilament Light Chain With Inner Retinal Layer Thinning in Multiple Sclerosis

Abstract

Objective:Serum neurofilament light chain (sNfL) and optical coherence tomography (OCT)-derived retinal measures (including peri-papillary 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.Methods:In this retrospective analysis of a longitudinal, observational, single-center cohort study, sNfL levels were measured in people with MS and healthy controls (HC) using Single Molecule Array (SIMOA). MS participants 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 cut-offs 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.Results:130 healthy controls (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 MS participants (19.9%). At baseline, sNfL-E participants had modestly lower pRNFL (-3.03±1.50μm; p=0.044) and GCIPL thickness (-2.74±1.02μm; p=0.007). As compared to those with sNfL within the reference range, eyes from NfL-E participants exhibited faster longitudinal thinning of the pRNFL (45% faster; -0.74μm/year vs -0.51μm/year; p=0.015) and GCIPL (25% faster; -0.35μm/year vs -0.28μm/year; p=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.Conclusions:Elevated baseline sNfL is associated with accelerated rates of retinal neuro-axonal loss in relapsing-remitting MS, independent of overt ON, but may be less reflective of retinal neurodegeneration in progressive MS.

Optical Coherence Tomography in Chronic Relapsing Inflammatory Optic Neuropathy, Neuromyelitis Optica and Multiple Sclerosis: A Comparative Study

“…Furthermore, we did not take into consideration various lifestyle factors, such as race, obesity, sleep duration and quality, and smoking that might interfere with the interpretation of our findings, as they can potentially affect the retinal structure and contribute to RNFL thinning [ 10 , 11 , 12 ]. Moreover, we have not studied any correlations with visual outcomes or serum neurofilament light chain levels that previous reports showed positive correlation with accelerated rates of neuro-axonal loss association in RRMS±ON [ 34 ]. These limitations necessitate cautious interpretation of our results and emphasize the need for longitudinal multicenter OCT studies on a larger number of patients to help shed more light on the OCT differences among these potentially disabling diseases.…”

Serum neurofilament light chain and cognition decline in US elderly: A cross‐sectional study

“…This immunoassay is based on direct AE chemiluminescence detection, employing one antibody and solid‐phase magnetic bead capture with another antibody. Researchers have established that this assay highly compares to the traditional single‐molecule array (Simoa; Quanterix) assay 34,35 . Furthermore, other pertinent research investigations 36–38 have employed it.…”

A narrative review of neuro-ophthalmologic disease in African Americans and Hispanics with multiple sclerosis

“…37 Indeed, neurosensory retinal loss measured in a variety of ways is accelerated in those who identify as African American relative to Caucasian, primarily within the inner retina. 27 In addition, macular volume loss correlates well with global brain volume loss, serum neurofilament light chain levels, 50,51 as well as with visual function, including low contrast visual acuity. [52][53][54] Taken cumulatively, there are data to suggest the cross-sectional volume of the macula has significant prognosis value, with lower macular volumes being predictive of an increased risk of disability accumulation at 10 years, regardless of optic neuritis.…”