Schmidt Mathias Falck, Pihl-Jensen Gorm, Torm Marie Elise Wistrup, Passali Moschoula, Larsen Michael, Frederiksen Jette Lautrup
Department of Neurology, Clinic of Optic Neuritis, The Danish Multiple Sclerosis Center (DMSC), Rigshospitalet and University of Copenhagen, Valdemar Hansens Vej 13, 2600, Glostrup, Denmark.
Department of Neurology, Clinic of Optic Neuritis, The Danish Multiple Sclerosis Center (DMSC), Rigshospitalet and University of Copenhagen, Valdemar Hansens Vej 13, 2600, Glostrup, Denmark.
Mult Scler Relat Disord. 2023 Apr;72:104617. doi: 10.1016/j.msard.2023.104617. Epub 2023 Mar 12.
Hyperreflective granular elements with a transient presence in the retina can be detected non-invasively by optical coherence tomography (OCT). Such foci or dots may represent aggregates of activated microglia. However, in multiple sclerosis an increased number of hyperreflective foci has so far not been demonstrated in the intrinsically hyporeflective and avascular outer nuclear layer of the retina where there are no fixed elements in healthy eyes. Therefore, the present study intended to investigate the presence of hyperreflective foci in the outer nuclear layer in patients with relapsing- remitting multiple sclerosis (RRMS) by using a high-resolution OCT scanning protocol.
This cross-sectional exploratory study examined 88 eyes in 44 RRMS patients and 106 eyes in 53 age- and sex-matched healthy subjects. None of the patients had any sign of retinal disease. All patients and healthy subjects each underwent one session of spectral domain OCT imaging. A total of 23,200 B-scans extracted from 8 × 8 mm blocks of linear B-scans at 60 μm intervals were analysed for hyperreflective foci in the outer nuclear layer of the retina. Analyses were made of the total block scan and a circular 6-mm diameter fovea-centered field in each eye. Multivariate logistic regression analysis was used to assess associations between parameters.
Hyperreflective foci were observed in 31 out of 44 (70.5 %) multiple sclerosis patients compared to 1 out of 53 (1.8%) healthy subjects (p < 0.0001). From analyses of the total block scans, the median number of hyperreflective foci in the outer nuclear layer was 1 (range 0-13) in patients and 0 (range 0-2) in healthy subjects (p < 0.0001). In total, 66.2% of all hyperreflective foci were located within 6 mm of the center of the macula. There was no detectable association between the presence of hyperreflective foci and retinal nerve fiber layer or ganglion cell layer thickness.
Hyperreflective granular foci in the avascular outer nuclear layer of the retina seen by OCT were almost completely absent in healthy subjects, whereas they were found, albeit at low density, in the majority of patients with RRMS. Hyperreflective foci can be repeatedly examined by non-invasive means and without pupil dilation, which opens a new field of investigation of infiltrating elements in an unmyelinated part of the central nervous system.
视网膜中存在的具有短暂性的高反射颗粒状成分可通过光学相干断层扫描（OCT）进行无创检测。此类病灶或小点可能代表活化小胶质细胞的聚集体。然而，在多发性硬化症中，迄今为止尚未在视网膜固有的低反射且无血管的外核层中证实高反射病灶数量增加，而在健康眼中该层并无固定成分。因此，本研究旨在通过使用高分辨率OCT扫描方案，调查复发缓解型多发性硬化症（RRMS）患者外核层中高反射病灶的存在情况。
这项横断面探索性研究检查了44例RRMS患者的88只眼以及53名年龄和性别匹配的健康受试者的106只眼。所有患者均无视网膜疾病迹象。所有患者和健康受试者均接受了一次光谱域OCT成像检查。从以60μm间隔的线性B扫描的8×8mm块中提取的总共23,200次B扫描，用于分析视网膜外核层中的高反射病灶。对每只眼睛的整个块扫描以及以黄斑中心为中心的直径6mm的圆形区域进行分析。采用多变量逻辑回归分析来评估参数之间的关联。
44例（70.5%）多发性硬化症患者中观察到高反射病灶，而53名（1.8%）健康受试者中仅1例观察到（p<0.0001）。通过对整个块扫描的分析，患者外核层高反射病灶的中位数为1（范围0 - 13），健康受试者为0（范围0 - 2）（p<0.0001）。总体而言，所有高反射病灶的66.2%位于黄斑中心6mm范围内。高反射病灶的存在与视网膜神经纤维层或神经节细胞层厚度之间未发现可检测到的关联。
OCT所见视网膜无血管外核层中的高反射颗粒状病灶在健康受试者中几乎完全不存在，而在大多数RRMS患者中虽以低密度存在但仍可发现。高反射病灶可通过无创方式且无需散瞳反复检查，这为中枢神经系统无髓鞘部分浸润成分的研究开辟了一个新领域。
