Fusing Structural Phenotypes with Functional Data for Early Prediction of Primary Angle-Closure Glaucoma Progression.

Purpose: To classify eyes as slow or fast glaucoma progressors in patients with primary angle closure glaucoma (PACG) using an integrated approach combining optic nerve head (ONH) structural features and sector-based visual field (VF) functional parameters. Design: Retrospective longitudinal study. Participants: PACG patients from glaucoma clinics. Methods: PACG patients with ≥5 reliable VF tests over ≥5 years were included. Progression was assessed in Zeiss Forum, with baseline VF within six months of OCT. Fast progression was VFI decline <-2.0% per year; slow progression ≥-2.0% per year. OCT volumes were AI-segmented to extract 31 ONH parameters. The Glaucoma Hemifield Test defined five regions per hemifield, aligned with RNFL distribution. Mean sensitivity per region was combined with structural parameters to train ML classifiers. Multiple models were tested, and SHAP identified key predictors. Main outcome measures: Classification of slow versus fast progressors using combined structural and functional data. Results: We analyzed 451 eyes from 299 patients. Mean VFI progression was -0.92% per year; 369 eyes progressed slowly and 82 rapidly. The Random Forest model combining structural and functional features achieved the best performance (AUC = 0.87±0.02, 2000 Monte Carlo iterations). SHAP identified six key predictors: inferior MRW, inferior and inferior-temporal RNFL thickness, nasal-temporal LC curvature, superior nasal VF sensitivity, and inferior RNFL and GCL+IPL thickness. Models using only structural or functional features performed worse with AUC of 0.82±0.03 and 0.78±0.03, respectively. Conclusions: Combining ONH structural and VF functional parameters significantly improves classification of progression risk in PACG. Inferior ONH features, MRW and RNFL thickness, were the most predictive, highlighting the critical role of ONH morphology in monitoring disease progression.