Al-Nosairy Khaldoon O, Duscha Alexander, Buhr Henrike, Lipp Antonia, Desel Christiane, Hegelmaier Tobias, Thieme Hagen, Haghikia Aiden, Hoffmann Michael B
Department of Ophthalmology, University Hospital Magdeburg, Magdeburg, Germany.
Department of Neurology, University Hospital Magdeburg, Magdeburg, Germany.
Front Integr Neurosci. 2023 Apr 17;17:1158148. doi: 10.3389/fnint.2023.1158148. eCollection 2023.
The retina, a window into the brain, allows for the investigation of many disease-associated inflammatory and neurodegenerative changes affecting the central nervous system (CNS). Multiple sclerosis (MS), an autoimmune disease targeting the CNS, typically impacts on the visual system including the retina. Hence, we aimed to establish innovative functional retinal measures of MS-related damage, e.g., spatially resolved non-invasive retinal electrophysiology, backed by established morphological retinal imaging markers, i.e., optical coherence tomography (OCT).
20 healthy controls (HC) and 37 people with MS [17 without history of optic neuritis (NON) and 20 with (HON) history of optic neuritis] were included. In this work, we differentially assessed photoreceptor/bipolar cells (distal retina) and retinal ganglion cell (RGC, proximal retina) function besides structural assessment (OCT). We compared two multifocal electroretinography-based approaches, i.e., the multifocal pattern electroretinogram (mfPERG) and the multifocal electroretinogram to record photopic negative response (mfERG ). Structural assessment utilized peripapillary retinal nerve fiber layer thickness (pRNFL) and macular scans to calculate outer nuclear thickness (ONL) and macular ganglion cell inner plexiform layer thickness (GCIPL). One eye was randomly selected per subject.
In NON, photoreceptor/bipolar cell layer had dysfunctional responses evidenced by reduced mfERG -N1 peak time of the summed response, but preserved structural integrity. Further, both NON and HON demonstrated abnormal RGC responses as evidenced by the photopic negative response of mfERG (mfPhNR) and mfPERG indices ( < 0.05). Structurally, only HON had thinned retina at the level of RGCs in the macula (GCIPL, < 0.01) and the peripapillary area (pRNFL, < 0.01). All three modalities showed good performance to differentiate MS-related damage from HC, 71-81% area under curve.
In conclusion, while structural damage was evident mainly for HON, functional measures were the only retinal read-outs of MS-related retinal damage that were independent of optic neuritis, observed for NON. These results indicate retinal MS-related inflammatory processes in the retina prior to optic neuritis. They highlight the importance of retinal electrophysiology in MS diagnostics and its potential as a sensitive biomarker for follow-up in innovative interventions.
视网膜是大脑的一扇窗口，可用于研究许多影响中枢神经系统（CNS）的与疾病相关的炎症和神经退行性变化。多发性硬化症（MS）是一种针对中枢神经系统的自身免疫性疾病，通常会影响包括视网膜在内的视觉系统。因此，我们旨在建立与MS相关损伤的创新性视网膜功能检测方法，例如空间分辨的非侵入性视网膜电生理学，并以既定的视网膜形态学成像标记物即光学相干断层扫描（OCT）为后盾。
纳入20名健康对照者（HC）和37名MS患者[17名无视神经炎（NON）病史者和20名有视神经炎（HON）病史者]。在这项研究中，除了结构评估（OCT）外，我们还分别评估了光感受器/双极细胞（视网膜远端）和视网膜神经节细胞（RGC，视网膜近端）的功能。我们比较了两种基于多焦视网膜电图的方法，即多焦图形视网膜电图（mfPERG）和用于记录明视负反应的多焦视网膜电图（mfERG ）。结构评估利用视乳头周围视网膜神经纤维层厚度（pRNFL）和黄斑扫描来计算外核层厚度（ONL）和黄斑神经节细胞内丛状层厚度（GCIPL）。每位受试者随机选择一只眼睛。
在NON组中，光感受器/双极细胞层存在功能障碍反应，表现为总和反应的mfERG -N1峰时间缩短，但结构完整性得以保留。此外，NON组和HON组均表现出异常的RGC反应，mfERG 的明视负反应（mfPhNR）和mfPERG指数可证明这一点（<0.05）。在结构上，只有HON组在黄斑区（GCIPL，<0.01）和视乳头周围区域（pRNFL，<0.01）的RGC水平上视网膜变薄。所有这三种检测方法在区分MS相关损伤与HC方面均表现良好，曲线下面积为71-81%。
总之，虽然结构损伤主要在HON组中明显，但功能检测是MS相关视网膜损伤的唯一视网膜检测指标，且与视神经炎无关，在NON组中也观察到了这一点。这些结果表明在视神经炎之前视网膜中存在与MS相关的炎症过程。它们突出了视网膜电生理学在MS诊断中的重要性及其作为创新干预措施随访的敏感生物标志物的潜力。
