Detecting Glaucoma Across Multi-ethnic Myopic and Non-Myopic Populations Using an Uncertainty-Aware Vision Transformer: A Multicentre Model Development and Validation Study

Abstract

Background: Artificial intelligence (AI)-based glaucoma detection from colour fundus photographs (CFP) offers scalable screening, but performance may decline on external datasets because of differences in ground-truth definitions, populations, and coexisting conditions such as high myopia (HM). We developed and validated a Vision Transformer-based deep learning (DL) model for glaucoma detection across multi-ethnic cohorts with and without HM. Methods: A ViT-B/16 model with predictive uncertainty estimation was developed using 56,483 CFPs (57.1% with myopia; 14.4% with HM). Glaucoma labels were standardised using clinical, imaging, and perimetry data. The model was validated on 16 independent datasets across three continents, including four datasets with explicit HM labels. Findings: Internal AUROC was 98.7% (95% CI 98.2-99.1%), with sensitivity 94.5% and specificity 97.3%. Across 16 external datasets from eight countries, AUROCs ranged from 86.4% to 99.6%. In HM eyes, internal AUROC was 97.8% (95% CI 96.1-99.2%), with sensitivity 94.8% and specificity 93.7%. External HM AUROCs were 86.5% in the Beijing Eye Study and 93.3%, 91.8%, and 85.5% in hospital-based datasets from Taiwan, Thailand, and South Korea. In an exploratory HM clinical evaluation, the model had higher CFP-only diagnostic accuracy than ophthalmologists and trained graders (92.0% vs 70.0%; p=0.008) and performed comparably to glaucoma specialists using full clinical information. Interpretation: The model showed robust glaucoma detection across myopic and non-myopic multi-ethnic populations and may support AI-assisted screening in settings with high HM prevalence.