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Principal Investigator: Benjamin Y. Xu
Organization: UNIVERSITY OF SOUTHERN CALIFORNIA
Fiscal Year: 2024
Award: $468,430
Funding agency: National Eye Institute
Abstract
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. Some racial groups in the United States are more vulnerable to PACG-related blindness;
Blacks and Hispanics are at 50% and 30% higher risk compared to non-Hispanic Whites. Recent landmark
studies also 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 disparities in disease burden. 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 disparities in angle closure using biometric data from a large multi-racial 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 disparities in angle closure disease and precise tools for delivering
care to patients at risk for PACG. Ultimately, these studies will help clinicians prevent PACG-related vision loss,
mitigate disparities in disease burden, and optimize utilization of healthcare resources.
Terms: <Affect><Aging><Anatomic Sites><Anatomic structures><Anatomy><Anterior><Aqueous Humor><Biometrics><Biometry><Biostatistics><Black Populations><Black group><Black individual><Black people><Blacks><Blindness><Caring><Clinical><Clinical Evaluation><Clinical Testing><Cluster Analyses><Cluster Analysis><Computer software><Confusion><Confusional State><Custom><Data><Decrease disparity><Detection><Diagnosis><Disease><Disease Outcome><Disorder><Disparities><Disparity><Early Intervention><Eye><Eyeball><Glaucoma><Gonioscopy><Health Care Systems><Health Care Utilization><Healthcare Systems><High Prevalence><Hispanic Populations><Hispanic group><Hispanic individual><Hispanic people><Hispanics><Illumination><Image><Image Analyses><Image Analysis><Impairment><Individual><Intraocular Fluid><Intraocular Pressure><Iris><Knowledge><Lighting><Lower disparity><Manuals><Measurement><Mental Confusion><Methodology><Methods><Non-Hispanic><Nonhispanic><Not Hispanic or Latino><Ocular Tension><POAG><Participant><Pathogenesis><Pathologic><Patients><Persons><Physiologic Intraocular Pressure><Play><Population><Practice Guidelines><Prevalence><Primary Angle Closure Glaucoma><Primary Open Angle Glaucoma><Probabilistic Models><Probability Models><Prophylactic treatment><Prophylaxis><Racial Group><Reproducibility><Research><Research Resources><Resources><Risk><Risk Factors><Role><Software><Statistical Methods><Statistical Models><System><Time><Training><United States><Visual><burden of disease><burden of illness><clinical applicability><clinical application><clinical care><clinical risk><clinical significance><clinical test><clinically significant><cohort><computer based prediction><customs><density><design><designing><disease burden><disparity reduction><glaucomatous><health care service use><health care service utilization><healthcare service use><healthcare service utilization><healthcare utilization><high risk><high risk group><high risk individual><high risk people><high risk population><image evaluation><image interpretation><imaging><intra-ocular pressure><mitigate disparity><multi-racial><multiracial><novel><ocular imaging><patient stratification><predictive modeling><prevent><preventing><prospective><racial population><racial subgroup><reduce disparity><reduction in disparity><research clinical testing><response to therapy><response to treatment><risk stratification><social role><statistic methods><statistical linear mixed models><statistical linear models><stratified patient><stratify risk><therapeutic response><therapy response><tool><treatment response><treatment responsiveness><vision loss><visual loss>