Retinal OCTA Phenotyping with LLM Reporting for Alzheimer's Disease

Age-related macular degeneration (AMD) is characterized by early micro-vascular alterations that can be captured non-invasively using optical coherence tomography angiography (OCTA), yet most deep learning (DL) models rely on global features and fail to exploit clinically meaningful vascular biomarkers. We introduce an external multiplicative attention framework that incorporates vessel-specific tortuosity maps and vasculature dropout maps derived from arteries, veins, and capillaries. These biomarker maps are generated from vessel segmentations and smoothed across multiple spatial scales to highlight coherent patterns of vascular remodeling and capillary rarefaction. Tortuosity reflects abnormalities in vessel geometry linked to impaired auto-regulation, while dropout maps capture localized perfusion deficits that precede structural retinal damage. The maps are fused with the OCTA projection to guide a deep classifier toward physiologically relevant regions. Arterial tortuosity provided the most consistent discriminative value, while capillary dropout maps performed best among density-based variants, especially at larger smoothing scales. Our proposed method offers interpretable insights aligned with known AMD pathophysiology.

Age-related macular degeneration (AMD) and diabetic macular edema (DME) are leading causes of vision loss, and optical coherence tomography (OCT) is the standard modality for detecting and monitoring the subtle lesions that drive treatment decisions. Most deep-learning segmentation work for OCT is validated only in-domain, leaving generalization to clinical data collected under different acquisition protocols largely untested. This work develops and systematically ablates four lesion-segmentation pipelines -- 2D and 3D variants for AMD and DME -- reaching Dice scores of 0.76 to 0.82 with strong volumetric and surface calibration (r vol, r surf greater than or equal to 0.97 across all four pipelines) on an in-domain validation set. The ablation process establishes a full-volume, calibration-aware adoption standard that catches mechanisms an ordinary slice-level evaluation would keep, and identifies ensemble composition as the most consistent driver of improvement. To test generalization, the models are evaluated on OLIVES, an external clinical cohort with no lesion-level ground truth, using a proxy-metric framework built around biomarker AUROC, central subfield thickness (CST) correlation, and longitudinal concordance. Predictions track clinical biomarkers outside the training distribution, though less strongly than in-domain -- evidence for, not validation of, automated lesion-burden tracking as a clinical tool.

To develop and evaluate deep learning models for automated grading of age-related macular degeneration (AMD) severity using optical coherence tomography (OCT) and OCT angiography (OCTA) data. Two hundred seventy-one participants aged >= 50 years with varying AMD severities. Central macular 6 x 6 mm OCT/OCTA volumes were acquired using a swept-source OCTA system (SOLIX; Visionix/Optovue Inc., CA). AMD severity was graded into four stages (No AMD, Early AMD, Intermediate AMD, and Advanced AMD) according to the AREDS simplified severity scale. Three deep learning models were developed using different input modalities: (1) biomarker maps derived from segmented pathological features, including retinal fluid, drusen, geographic atrophy (GA), and macular neovascularization (MNV); (2) two-dimensional (2D) en face OCT and OCTA projections; and (3) three-dimensional (3D) OCT/OCTA volumes. EfficientNet-based architectures were trained using normalized inputs, data augmentation, and five-fold cross-validation. A total of 2,030 OCT/OCTA volumes from 351 eyes of 271 participants were analyzed. All models demonstrated strong AMD staging performance with substantial agreement with the reference standard (QWK >= 0.83). The biomarker-based model achieved the highest overall performance (QWK = 0.85 +/- 0.03, mean +/- standard deviation) and the best detection of early AMD (F1-score = 0.59 +/- 0.14). The 3D model achieved performance comparable to the 2D OCT/OCTA model (QWK = 0.83 +/- 0.04 vs. 0.83 +/- 0.09), while the 2D OCT/OCTA model showed the highest precision (0.79 +/- 0.06) and most accurately identified eyes without AMD. Deep learning models using OCT/OCTA data can accurately and automatically grade AMD severity. Among the evaluated approaches, the biomarker-based model provided the most balanced performance and showed particular value for early AMD detection.