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.

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.

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; p = 0.044) and GCIPL thickness (–2.74 ± 1.02 μm; 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 μm/y; p = 0.015) and GCIPL (25% faster; –0.35 vs –0.28 μm/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.

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.

血清神经丝轻链 (sNfL) 和光学相干断层扫描 (OCT) 衍生的视网膜测量值（包括视盘周围视网膜神经纤维层 [pRNFL] 和黄斑神经节细胞层/内丛状层 [GCIPL] 厚度）已被提议作为神经变性的生物标志物多发性硬化症 (MS)。然而，评估 MS 中 sNfL 和 OCT 衍生的视网膜测量之间关联的研究是有限的。

在这项纵向、观察性、单中心队列研究的回顾性分析中，使用单分子阵列测量了 MS 患者和健康对照 (HC) 患者的 sNfL 水平。MS 参与者接受连续 OCT 随访，中位随访时间为 4.5 年。排除在基线 OCT 后 6 个月内患有视神经炎 (ON) 或在随访期间出现视神经炎 (ON) 的眼睛。sNfL 的年龄标准截止值是使用 HC 数据得出的，sNfL 大于年龄的第 97.5 个百分位数的 MS 参与者被归类为 sNfL 升高 (sNfL-E)。使用混合效应线性回归模型进行分析，并根据年龄、性别、种族和 ON 病史进行调整。

总共包括 130 名 HC（年龄：42.4 ± 14.2 岁；62% 为女性）和 403 名 MS 患者（年龄：43.1 ± 12.0 岁；78% 为女性）。80 名 MS 参与者 (19.9%) 在基线时存在升高的 sNfL 水平。在基线时，sNfL-E 参与者的 pRNFL（–3.03 ± 1.50 μm； p = 0.044）和 GCIPL 厚度（–2.74 ± 1.02 μm；p = 0.007）适度降低。与参考范围内的 sNfL 相比，NfL-E 参与者的眼睛表现出更快的 pRNFL 纵向变薄（快 45%；–0.74 与 –0.51 μm/y；p = 0.015）和 GCIPL（快 25% ； – 0.35 对比 –0.28 微米/年；p= 0.021）。sNfL 组之间 pRNFL 和 GCIPL 变薄率的显着差异仅在复发缓解型 MS 而非进展型 MS 患者中发现。

升高的基线 sNfL 与复发缓解型 MS 中视网膜神经轴突丢失的加速速率相关，与明显的 ON 无关，但可能较少反映进行性 MS 中的视网膜神经变性。