Jin Zi, Wang Xinmin, Lang Ying, Song Yufeng, Zhan Huangxiong, Shama Wuge, Shen Yingying, Zeng Guihua, Zhou Faying, Gao Hongjian, Ye Shuling, Wang Yanjiang, Lu Fan, Shen Meixiao
National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
State Key Laboratory of Ophthalmology, Optometry and Vision Science, Eye Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
Alzheimers Res Ther. 2025 Feb 1;17(1):33. doi: 10.1186/s13195-025-01676-z.
The nature and severity of Alzheimer's disease (AD) pathologies in the retina and brain correspond. However, retinal biomarkers need to be validated in clinical cohorts with confirmed AD biomarkers and optical coherence tomography (OCT). The main objective of this study was to investigate whether retinal metrics measured by OCT aid in the early screening and brain pathology monitoring for confirmed AD.
This was a case-control study. All participants underwent retinal OCT imaging, and neurological examinations, including amyloid-β (Aβ) positron emission tomography. Participants were subdivided into cognitively normal (CN), mild cognitive impairment (MCI), and AD-derived dementia (ADD). Except retinal thickness, we developed the grey level co-occurrence matrix algorithm to extract retinal OCT intensity spatial correlation features (OCT-ISCF), including angular second matrix (ASM), correlation (COR), and homogeneity (HOM), one-way analysis of variance was used to compare the differences in retinal parameters among the groups, and to analyze the correlation with brain Aβ plaques and cognitive scores. The repeatability and robustness of OCT-ISCF were evaluated using experimental and simulation methods.
This study enrolled 82 participants, subdivided into 20 CN, 22 MCI, and 40 ADD. Compared with the CN, the thickness of retinal nerve fiber layer and myoid and ellipsoid zone were significantly thinner (P < 0.05), and ASM, COR, and HOM in several retinal sublayers changed significantly in the ADD (P < 0.05). Notably, the MCI showed significant differences in ASM and COR in the outer segment of photoreceptor compared with the CN (P < 0.05). The changing pattern of OCT-ISCF with interclass correlation coefficients above 0.8 differed from that caused by speckle noise, and was affected by OCT image quality index. Moreover, the retinal OCT-ISCF were more strongly correlated with brain Aβ plaque burden and MoCA scores than retinal thickness. The accuracy using retinal OCT-ISCF (AUC = 0.935, 0.830) was better than that using retinal thickness (AUC = 0.795, 0.705) in detecting ADD and MCI.
The study demonstrates that retinal OCT-ISCF enhance the association and detection efficacy of AD pathology compared to retinal thickness, suggesting retinal OCT-ISCF have the potential to be new biomarkers for AD.
视网膜和大脑中阿尔茨海默病（AD）病理的性质和严重程度相对应。然而，视网膜生物标志物需要在具有确诊AD生物标志物和光学相干断层扫描（OCT）的临床队列中进行验证。本研究的主要目的是调查通过OCT测量的视网膜指标是否有助于确诊AD的早期筛查和脑病理监测。
这是一项病例对照研究。所有参与者均接受了视网膜OCT成像以及包括淀粉样蛋白-β（Aβ）正电子发射断层扫描在内的神经学检查。参与者被分为认知正常（CN）、轻度认知障碍（MCI）和AD源性痴呆（ADD）。除了视网膜厚度，我们开发了灰度共生矩阵算法来提取视网膜OCT强度空间相关特征（OCT-ISCF），包括角二阶矩阵（ASM）、相关性（COR）和同质性（HOM），采用单因素方差分析比较各组之间视网膜参数的差异，并分析其与脑Aβ斑块和认知评分的相关性。使用实验和模拟方法评估OCT-ISCF的重复性和稳健性。
本研究共纳入82名参与者，分为20名CN、22名MCI和40名ADD。与CN相比，ADD组的视网膜神经纤维层、肌样和椭圆体带厚度显著变薄（P < 0.05），ADD组几个视网膜亚层的ASM、COR和HOM发生了显著变化（P < 0.05）。值得注意的是，与CN相比，MCI组在光感受器外段的ASM和COR存在显著差异（P < 0.05）。类内相关系数高于0.8的OCT-ISCF变化模式与散斑噪声引起的不同，且受OCT图像质量指数影响。此外，视网膜OCT-ISCF与脑Aβ斑块负荷和MoCA评分的相关性比视网膜厚度更强。在检测ADD和MCI方面，使用视网膜OCT-ISCF的准确性（AUC = 0.935，0.830）优于使用视网膜厚度的准确性（AUC = 0.795，0.705）。
该研究表明，与视网膜厚度相比，视网膜OCT-ISCF增强了AD病理的关联性和检测效能，提示视网膜OCT-ISCF有可能成为AD的新型生物标志物。
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