Balk Lisanne J, Cruz-Herranz Andrés, Albrecht Philipp, Arnow Sam, Gelfand Jeffrey M, Tewarie Prejaas, Killestein Joep, Uitdehaag Bernard M J, Petzold Axel, Green Ari J
Department of Neurology, MS Centre, VU University Medical Center, Mailbox 7057, 1007 MB, Amsterdam, The Netherlands.
Department of Neurology, University of California San Francisco, San Francisco, USA.
J Neurol. 2016 Jul;263(7):1323-31. doi: 10.1007/s00415-016-8127-y. Epub 2016 May 3.
The objective of the study was to investigate the timing of central nervous system tissue atrophy in MS by evaluating longitudinal retinal volume changes in a broadly representative cohort with disease duration across the entire arc of disease. In this longitudinal study, 135 patients with MS and 16 healthy reference subjects underwent spectral-domain optical coherence tomography (OCT) at baseline and 2 years later. Following OCT quality control, automated segmentation of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell-inner plexiform layer (mGCIPL) and macular inner nuclear layer (mINL) was performed. Generalized estimation equations were used to analyze longitudinal changes and associations with disease duration and clinical measures. Participants had a median disease duration at baseline of 16.4 years (range 0.1-45.4). Nearly half (44 %) of the MS patients had previously experienced MS-related optic neuritis (MSON) more than 6 months prior. The MS patients demonstrated a significant decrease over 2 years of the pRNFL (-1.1 µm, 95 % CI 1.4-0.7, p < 0.001) and mGCIPL (-1.1 µm, 95 % CI -1.4 to -0.8, p < 0.001). This thinning was most pronounced early in the course of disease. These findings were irrespective of previous episodes of MSON. No consistent pattern of change was observed for the mINL (-0.03 µm, 95 % CI -0.2 to 0.2, p = 0.795). This longitudinal study demonstrated that injury of the innermost retinal layers is found in MS and that this damage occurs most rapidly during the early stages of disease. The attenuation of atrophy with longer disease duration is suggestive of a plateau effect. These findings emphasize the importance of early intervention to prevent such injury.
本研究的目的是通过评估一组具有广泛代表性、涵盖疾病全过程的队列中视网膜体积的纵向变化,来研究多发性硬化症(MS)中枢神经系统组织萎缩的时间。在这项纵向研究中,135例MS患者和16名健康对照者在基线时及2年后接受了光谱域光学相干断层扫描(OCT)。在进行OCT质量控制后,对视乳头周围视网膜神经纤维层(pRNFL)、黄斑神经节细胞 - 内丛状层(mGCIPL)和黄斑内核层(mINL)进行自动分割。使用广义估计方程分析纵向变化以及与疾病持续时间和临床指标的关联。参与者在基线时的疾病持续时间中位数为16.4年(范围0.1 - 45.4年)。近一半(44%)的MS患者在6个月以上曾经历过与MS相关的视神经炎(MSON)。MS患者在2年期间pRNFL(-1.1 µm,95%CI 1.4 - 0.7,p < 0.001)和mGCIPL(-1.1 µm,95%CI -1.4至 -0.8,p < 0.001)显著减少。这种变薄在疾病过程早期最为明显。这些发现与既往MSON发作无关。mINL未观察到一致的变化模式(-0.03 µm,95%CI -0.2至0.2,p = 0.795)。这项纵向研究表明,MS患者存在最内层视网膜层的损伤,且这种损伤在疾病早期发生得最快。随着疾病持续时间延长萎缩减弱提示存在平台效应。这些发现强调了早期干预以预防此类损伤的重要性。