Retinal optical coherence tomography intensity spatial correlation features as new biomarkers for confirmed Alzheimer's disease

Background 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. Methods 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. Results 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. Conclusions 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. This project has been registered in the Chinese Clinical Trials Registry (registration number: ChiCTR2000040786; registration date: 2020-12-10).