Background and Objectives: Open-angle glaucoma subtypes share a structural phenotype but differ in pathophysiology: pseudoexfoliative glaucoma (PXG) involves vascular endothelial dysfunction associated with deposition of exfoliative material, whereas normal-tension glaucoma (NTG) reflects primary vascular dysregulation in the absence of elevated intraocular pressure. We characterized subtype-specific OCT angiography (OCTA) profiles obtained from a 3 × 3 mm macular scan and evaluated their discriminatory power for pairwise subtype classification. Materials and Methods: This was a single-center, cross-sectional study of 304 eyes: 198 glaucomatous eyes—primary open-angle glaucoma (POAG, glaucoma simplex in our clinical nomenclature), n = 102; PXG (glaucoma capsulare), n = 68; NTG (glaucoma sine tensio), n = 28—and 106 healthy controls. The Cirrus HD-OCT 5000 AngioPlex 3 × 3 mm OCTA protocol was used to assess vessel density (VD), perfusion density, foveal avascular zone (FAZ) morphology, ganglion cell complex (GCC), and retinal nerve fiber layer (RNFL) thickness. Analyses included Kruskal–Wallis tests with Bonferroni post hoc correction, ROC analysis with DeLong comparison of combined versus structural-only models, multivariate regression, and an exploratory XGBoost classifier with SHAP-based interpretation. Results: VD Inner and Perfusion Inner were lower in PXG (16.37 ± 3.33%; 0.31 ± 0.05) than in POAG (18.73 ± 3.41%; 0.34 ± 0.05; both p < 0.001); Perfusion Inner was also lower than in NTG (p < 0.05). FAZ Area was largest in NTG (0.27 ± 0.11 mm2) and greater than in PXG (0.19 ± 0.08; p < 0.01); FAZ Circularity differed across subtypes (p < 0.001). Combined OCTA–structural models outperformed structural-only models for POAG vs. PXG (DeLong p = 0.002) and for PXG vs. NTG (AUC = 0.770; p = 0.010). Sector-resolved Spearman analysis revealed subtype-specific coupling: in NTG, VD Inner and Perfusion Inner correlated with the inferior RNFL (r = 0.53 and r = 0.52; both p < 0.01); in PXG, coupling shifted nasally (r = 0.41 and r = 0.46; both p < 0.001). The exploratory XGBoost classifier separated glaucoma from controls with an internal cross-validated AUC of 0.975 ± 0.008 (5-fold CV; not externally validated); FAZ Circularity (mean |SHAP| = 0.418) and FAZ Area (0.411) were the top inter-subtype features, supported by case-level SHAP. RNFL avg and average GCC independently predicted MD across subtypes; in PXG, Perfusion Inner also predicted MD (β = −32.78; p = 0.032). Conclusions: In this single-center, cross-sectional cohort, OCTA revealed subtype-associated macular microvascular profiles that are complementary to structural OCT. Reduced vessel and perfusion density characterized PXG, whereas FAZ enlargement and reduced circularity distinguished NTG and PXG. Vascular–structural coupling was nasal-predominant in PXG and inferior-predominant in NTG. Combined multimodal models outperformed structural-only approaches. Macular perfusion additionally predicted MD in PXG. The XGBoost/SHAP analysis is exploratory; prospective and externally validated studies are required before clinical deployment.
Živković et al. (Tue,) studied this question.