Refined Four-Layer Peripapillary OCTA Enables Layer-Specific Localization of Microvascular Alterations in Retinal Vein Occlusion

Purpose: To evaluate whether refined four-layer anatomical stratification of the peripapillary microvasculature improves anatomical localization, optical coherence tomography angiography (OCTA)-based discriminative performance, and functional interpretation in newly diagnosed, treatment-naïve retinal vein occlusion (RVO). Methods: This cross-sectional study included 186 eyes (72 RVO-affected, 72 fellow, and 42 healthy eyes). Peripapillary microvasculature was quantified across three hierarchical dimensions: global (Dim 1), two-layer (Dim 2), and a refined four-layer model (Dim 3: RPC, SVP, ICP, and DCP). Microvascular metrics, including vessel density (VD), fractal dimension (FD), perfusion area (PA), vessel length density (VLD), and vessel diameter index (VDI), were quantified. Discriminative performance was assessed with area under the curve (AUC) and AIC, whereas functional associations with visual acuity (BCVA) were evaluated using regression analysis. Results: Standardized disease contrasts for VD were -0.57 in the global inner retina, -0.83 in the conventional deep vascular complex (DVC), and -0.79 in the DCP. Corresponding FD contrasts were -0.07, -0.39, and -0.39, respectively, indicating that DCP isolation did not increase standardized disease contrast beyond the conventional DVC. However, refined four-layer stratification improved anatomical localization of deep-layer abnormalities and enhanced OCTA-based discriminative performance (AUC: VD, 0.636 to 0.826; FD, 0.603 to 0.807; both P < 0.05). FD-based models showed stronger associations with BCVA (adjusted R², 0.021 to 0.211), with DCP-related metrics contributing substantially to model performance. Conclusions: Refined four-layer peripapillary OCTA enables more specific localization of layer-related abnormalities in RVO. Although DCP isolation did not increase standardized disease contrast beyond the conventional DVC, DCP-resolved metrics, particularly FD, may provide complementary information regarding vascular network organization and visual function. Translational Relevance: Plexus-resolved peripapillary OCTA may support more anatomically specific characterization of RVO-related microvascular abnormalities and provide a methodological framework for future longitudinal and externally validated studies.