Computerized analysis of the eye vasculature in a mass dataset of digital fundus images: the example of age, sex and primary open-angle glaucoma

Objective: To develop and validate an automated end-to-end methodology for analyzing retinal vasculature in large datasets of digital fundus images (DFIs), aiming to assess the influence of demographic and clinical factors on retinal microvasculature. Design: This study employs a retrospective cohort design to achieve its objectives. Participants: The research utilized a substantial dataset consisting of 115,237 digital fundus images obtained from individuals undergoing routine eye examinations. There was no inclusion of a separate control group in this study. Methods: The proposed methodology integrates multiple stages: initial image quality assessment, detection of the optic disc, definition of the region of interest surrounding the optic disc, automated segmentation of retinal arterioles and venules, and the engineering of digital biomarkers representing vasculature characteristics. To analyze the impact of demographic variables (age, sex) and clinical factors (disc size, primary open-angle glaucoma [POAG]), statistical analyses were performed using linear mixed-effects models. Main Outcome Measures: The primary outcomes measured were changes in the retinal vascular geometry. Special attention was given to evaluating the independent effects of age, sex, disc size, and POAG on the newly engineered microvasculature biomarkers. Results: The analysis revealed significant independent similarities in retinal vascular geometry alterations associated with both advanced age and POAG. These findings suggest a potential mechanism of accelerated vascular aging in patients with POAG. Conclusions: This novel methodology allows for the comprehensive and quantitative analysis of retinal vasculature, facilitating the investigation of its correlations with specific diseases. By enabling the reproducible analysis of extensive datasets, this approach provides valuable insights into the state of retinal vascular health and its broader implications for cardiovascular and ocular health. The software developed through this research will be made publicly available upon publication, offering a critical tool for ongoing and future studies in retinal vasculature.