Pang Chunyang, Li Yaojia, Jiang Wenhua, Xie Haobo, Cao Wen, Yu Huan, Lin Zhiyang, Cheng Yifan, Fan Dongsheng, Deng Binbin
Department of Rehabilitation Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR. China.
Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR. China.
PLoS Med. 2025 Jun 25;22(6):e1004545. doi: 10.1371/journal.pmed.1004545. eCollection 2025 Jun.
Biomarkers are widely recognized as crucial breakthroughs in tackling amyotrophic lateral sclerosis (ALS). Among them, retina markers may hold promise due to the close retina-brain connection and non-invasive, portable detection methods. Thus, using optical coherence tomography (OCT), we investigated the link between baseline cell-level retinal features and future ALS risk.
Participants from the UK Biobank underwent OCT scans to assess retinal layers, macula, and optic disc parameters. Follow-up commenced two years after the baseline period (2006-2010), during which ALS cases were identified using International Classification of Diseases (ICD) codes from medical and assessment records. Cox proportional hazards models were applied to examine the relationship between retinal markers and incident ALS. Over a median follow-up of 14.11 years, 70 ALS cases occurred among 53,824 participants (incidence 10.58 per 100,000 person-years). Most participants were White (94.6%), 44.8% male, with a median age of 58 years. After adjusting for demographics and comorbidities affecting the retina, a standard deviation (SD) decrease of 15.19 µm in photoreceptor layer (PRL) thickness was associated with a 19% (95% confidence interval [7, 29]; p = 0.002) increased risk of ALS, while a SD increase of 26.11 µm in retinal pigment epithelium (RPE) thickness corresponded to a 20% (95% CI [7, 34]; p = 0.002) higher risk. Sensitivity analyses excluding follow-ups of less than 4 and 6 years yielded consistent results. Subgroup analyses showed these findings were more pronounced in smokers. The main limitation of this study is its single time point observational design.
A thinner PRL and thicker RPE may precede the clinical diagnosis of ALS, offering potential clues for early diagnosis and insights into the disease's pathogenesis.
生物标志物被广泛认为是攻克肌萎缩侧索硬化症（ALS）的关键突破。其中，视网膜标志物因其与大脑紧密的视网膜 - 脑连接以及非侵入性、便携的检测方法而可能具有前景。因此，我们使用光学相干断层扫描（OCT）研究了基线细胞水平的视网膜特征与未来患ALS风险之间的联系。
来自英国生物银行的参与者接受了OCT扫描，以评估视网膜层、黄斑和视盘参数。随访在基线期（2006 - 2010年）两年后开始，在此期间，使用来自医疗和评估记录的国际疾病分类（ICD）代码识别ALS病例。应用Cox比例风险模型来检验视网膜标志物与新发ALS之间的关系。在中位随访14.11年期间，53824名参与者中有70例发生ALS（发病率为每10万人年10.58例）。大多数参与者为白人（94.6%），男性占44.8%，中位年龄为58岁。在调整了影响视网膜的人口统计学和合并症因素后，光感受器层（PRL）厚度标准差（SD）下降15.19 µm与ALS风险增加19%（95%置信区间[7, 29]；p = 0.002）相关，而视网膜色素上皮（RPE）厚度标准差增加26.11 µm则对应于风险高20%（95% CI [7, 34]；p = 0.002）。排除随访时间少于4年和6年的敏感性分析得出了一致的结果。亚组分析表明，这些发现在吸烟者中更为明显。本研究的主要局限性在于其单时间点观察性设计。
较薄的PRL和较厚的RPE可能在ALS临床诊断之前出现，为早期诊断提供了潜在线索，并有助于深入了解该疾病的发病机制。
