Clinical Evaluation and Risk Stratification of Angle Closure Disease Using Quantitative OCT - Glaucoma is the leading cause of irreversible blindness worldwide. Angle closure, which impairs aqueous humor outflow and leads to elevated intraocular pressure (IOP), is the primary cause of 23 million or nearly one third of all glaucoma cases. Primary angle closure glaucoma (PACG) is three-fold more visually damaging than primary open angle glaucoma (POAG), afflicting 6 million people with blindness. While most cases of PACG are preventable with early intervention, current practice paradigms are severely limited in predicting which patients with early angle closure, termed narrow angles, will develop PACG. Among key barriers hindering the care of at-risk patients is reliance on gonioscopy, the current clinical standard for detecting angle closure. Gonioscopy is subjective, qualitative, expertise-dependent, time-intensive, and uncomfortable. These limitations contribute to underperformance of gonioscopy by clinicians, delayed detection of PACG, and blindness in a quarter of diagnosed cases. Recent landmark studies show that current disease definitions based on gonioscopy are weakly predictive of which patients will develop PACG; over 100 “at-risk” patients require treatment to prevent a single case of PACG. This limitation leads to poorly defined practice guidelines and confusion among clinicians regarding prophylactic treatment for PACG, which, unlike POAG, is largely preventable. Therefore, there is an urgent need for a more convenient and precise clinical tool to prevent PACG-related blindness and mitigate the burden of disease. Anterior segment OCT (AS-OCT) is a non-contact, reproducible, quantitative alternative to gonioscopy for evaluating the angle. Our research group have been pioneers in clinical applications of AS-OCT for angle closure. We showed AS-OCT measurements are predictive of elevated IOP, disease course, and treatment response, whereas gonioscopy is not. More recently, we developed custom software to automate quantitative analysis of AS-OCT images, thereby removing the barrier of manual analysis and unlocking the full potential of AS-OCT for clinical care and scientific research. In this proposal, we seize the momentum of recent research findings and methodological advances to shift practice paradigms and establish quantitative AS-OCT as the new clinical standard for evaluating and risk-stratifying patients for PACG. Specifically, we will: 1) elucidate the anatomical basis of angle closure using biometric data from a large, hospital-based cohort; 2) establish quantitative OCT-based definitions of narrow angles based on 3-year risk of elevated IOP and PACG; 3) identify novel dynamic biometric risk factors to predict disease outcomes. Our proposed studies will address urgent needs by clinicians for fundamental knowledge about in angle closure mechanisms and precise tools for delivering care to patients at risk for PACG. Ultimately, these studies will help clinicians prevent PACG-related vision loss, mitigate disease burden, and optimize utilization of healthcare resources.
