Toward Reliable Diabetic Retinopathy Screening.

Diabetic retinopathy (DR) grading requires reliable five-grade severity assessment under substantial acquisition variability and cross-dataset distribution shift. We propose PRISM-DR, a multi-objective five-grade DR grading framework trained under a gradient-partitioned strategy. The architecture is organized as a feedforward pipeline: a data-driven preprocessing stage followed by a ConvNeXtV2-Base backbone, a Recurrent BiFPN neck for multi-scale feature fusion, a Frequency-Aware Fusion module, a lightweight multi-scale reasoning transformer, dual classification heads with gradient-isolated pathways (categorical and ordinal), and a prototype memory module for embedding regularization. The CORAL ordinal head operates through a dedicated projection layer and is gradient-isolated from the backbone; the backbone is shaped by the cross-entropy, prototype contrastive, and view-consistency objectives, which carry indirect ordinal signal through severity-weighted class penalties and grade-indexed cluster regularization. The model is trained in a multi-crop setting with a phased loss curriculum designed for severely imbalanced DR datasets. Evaluated across six datasets under Fixed-Source, Multi-Target (FSMT) protocols, PRISM-DR trained on EyePACS + DDR achieves QWK of 0.835 on IDRiD, 0.865 on APTOS2019, and 0.720 on Messidor-2, with in-domain QWK = 0.920 and AUC-PR = 0.941 on EyePACS, outperforming RETFound, RETFound-Green, and MedGemma-4B in AUC-PR across all evaluated datasets. Quantitative interpretability evaluation against 755 expert-annotated lesion images yields 8.0× Energy Ratio Enrichment and a FAF gate retention ratio of 4.4× inside lesion regions, confirming that anatomically plausible spatial priors emerge from grade-level supervision alone, without pixel-level annotation. PRISM-DR establishes a superior accuracy-robustness-capacity trade-off for scalable, automated DR screening.