Investigation of Early Stage Cardiovascular-Kidney-Metabolic Syndrome on Retinal Structure and Function Evaluated by Optical Coherence Tomography Angiography

Yunyi Liang¹Congbi Liang¹Jianping Yang¹Wanhua Li¹Runyi Liang¹Kun Li¹Jingfeng Zhang¹Peiqiong Lao¹Junhua Zhu¹Lin An²Zhaohao Liang³Chubin Ou^4*

• ¹The Sixth Affiliated Hospital of South China University of Technology, Foshan, Guangdong Province, China
• ²Hangzhou Dianzi University, Hangzhou, Zhejiang Province, China
• ³Foshan Technology Transfer Center of the Hong Kong University of Science and Technology, Foshan, Guangdong Province, China
• ⁴Guangdong Provincial People's Hospital, Guangzhou, Guangdong Province, China

The retina serves as a noninvasive window to visualize systemic health, with optical coherence tomography angiography (OCTA) enabling simultaneous assessment of retinal structural thickness and vascular density. Suboptimal Cardiovascular-Kidney-Metabolic (CKM) health status, defined by early stage of CKM syndrome may impact retinal neurovascular integrity, yet comprehensive OCTA-based evaluations remain limited and controversial. This study aimed to investigate retinal structural and vascular alterations in early stage CKM using OCTA and explore its potential as a biomarker tool. Methods A cross-sectional study included 2153 participants undergoing OCTA during health checks (2023-2024). Early stage CKM (stage 1-2) is characterized by abnormal levels of glucose, lipid profile, uric acid, or blood pressure. Retinal thickness and vessel density in nine ETDRS grid regions were measured. Univariate and multivariate logistic regression analyses identified associations between early stage CKM and OCTA parameters, adjusting for age and gender.Early stage CKM subjects (n=1,843, 94.5%) showed significantly reduced retinal thickness and vessel density across multiple regions compared to healthy controls (all p < 0.05).Multivariate analysis revealed that outer temporal thickness (OR=0.986, p < 0.001), outer superficial vessel density (OR=1.04, p=0.020), and inner superior vessel density (OR=0.962, p=0.010) were independent predictors of early stage CKM, alongside age and gender. Specific abnormalities, such as hypertension and diabetes, were linked to distinct regional decreases in thickness and density, suggesting dose-dependent impact of glycemic dysregulation on retinal health.Early stage CKM syndrome is associated with subtle retinal structural and vascular alterations detectable by OCTA, particularly in macular layers. OCTA-derived biomarkers, including outer temporal thickness and macular vessel density, may serve as noninvasive tools for evaluating systemic health status, offering promise for early detection of metabolic and cardiovascular risks.