TY - JOUR
T1 - Association of Serum Neurofilament Light Chain with Inner Retinal Layer Thinning in Multiple Sclerosis
AU - Sotirchos, Elias S.
AU - Vasileiou, Eleni S.
AU - Filippatou, Angeliki G.
AU - Fitzgerald, Kathryn C.
AU - Smith, Matthew D.
AU - Lord, Hannah Noelle
AU - Kalaitzidis, Grigorios
AU - Lambe, Jeffrey
AU - Duval, Anna
AU - Prince, Jerry L.
AU - Mowry, Ellen M.
AU - Saidha, Shiv
AU - Calabresi, Peter A.
N1 - Publisher Copyright:
© American Academy of Neurology.
PY - 2022/8/16
Y1 - 2022/8/16
N2 - Background and ObjectivesSerum 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.MethodsIn 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.ResultsA 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 m; p = 0.044) and GCIPL thickness (-2.74 ± 1.02 m; p = 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 m/y; p = 0.015) and GCIPL (25% faster; -0.35 vs -0.28 m/y; 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.DiscussionElevated 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.
AB - Background and ObjectivesSerum 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.MethodsIn 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.ResultsA 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 m; p = 0.044) and GCIPL thickness (-2.74 ± 1.02 m; p = 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 m/y; p = 0.015) and GCIPL (25% faster; -0.35 vs -0.28 m/y; 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.DiscussionElevated 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.
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U2 - 10.1212/WNL.0000000000200778
DO - 10.1212/WNL.0000000000200778
M3 - Article
C2 - 35618438
AN - SCOPUS:85136216968
SN - 0028-3878
VL - 99
SP - E688-E697
JO - Neurology
JF - Neurology
IS - 7
ER -