Project Summary The objective of this study, “Diagnostic Innovations in Glaucoma Study (DIGS): Glaucoma and High Myopia”, is to overcome barriers to the detection of open angle glaucoma (OAG) in individuals with high myopia (mypOAG). In 2010, there was an estimated 1.4 billion people worldwide with myopia and the prevalence is rapidly rising to an estimated 4.75 billion by 2050. Moreover, persons with high myopia are 2.5 times more likely to have OAG than those without high myopia. It is unclear why myopia increases the risk of OAG, but it is likely related at least in part to biomechanical factors; longer axial lengths in myopic eyes may result in deformation of the lamina cribrosa, temporal displacement of Bruch's membrane, parapapillary changes and vascular factors; these all lead to increased susceptibility of the optic nerve to OAG damage. Given the higher prevalence of tilted discs and peripapillary atrophy in myopic eyes, the structural and functional tests that usually guide treatment decisions are of diminished value. This proposal will provide essential follow-up to establish best practices for patient-centered detection of OAG progression in the challenging high myopia population. Specifically, this proposal will 1) identify optic nerve head (ONH) 3D morphologic parameters from optical coherence tomography (OCT) scans (segmented and unsegmented) to differentiate between myopia eyes with and without progressive OAG; 2) optimize change detection using novel OCT features (e.g. texture and microvasculature) from wide field of view (WFOV) maps merged from individual ONH and macula scans; and 3) develop novel longitudinal and multimodal deep learning (DL) models to predict OAG progression. Most importantly, we will improve our understanding of the complex temporal relationship between structural, functional and microvascular age- and OAG related changes in a diverse cohort across the range of myopia. Specifically, in Specific Aim 1 (To improve our understanding of the complex relationship between ONH morphology and structural, functional, and microvascular change in the aging and OAG eye), we address several hypotheses related to the characterization of myopic ONH morphology in healthy eyes with and without high myopia. We hypothesize that ONH morphology is predictive of age – and OAG related structural, functional and microvascular changes and that it is predictive of fast progression. In Specific Aim 2 (To improve detection of OAG progression in myopic eyes using WFOV maps, unsegmented 3D volumes, ONH morphology), we address several hypotheses designed to detect and predict OAG progression using novel DL approaches. In Specific Aim 3, we will establish a cloud-based pipeline for data curation and computation that will facilitate secure DL model development and extensive data sharing with the vision research community.