Optical coherence tomography angiography (OCTA) is a noninvasive imaging technique used to visualize retinal blood flow and identify changes in vascular density and enlargement or distortion of the foveal avascular zone (FAZ), which are indicators of various eye diseases. Although several automated FAZ detection and segmentation algorithms have been developed for use with OCTA, their performance can vary significantly due to differences in data accessibility of OCTA in different retinal pathologies, and differences in image quality in different subjects and/or different OCTA devices. For example, data from subjects with direct macular damage, such as in age-related macular degeneration (AMD), are more readily available in eye clinics, while data on macular damage due to systemic diseases like Alzheimer’s disease are often less accessible; data from healthy subjects may have better OCTA quality than subjects with ophthalmic pathologies. Typically, segmentation algorithms make use of convolutional neural networks and, more recently, vision transformers, which make use of both long-range context and fine-grained detail. However, transformers are known to be data-hungry, and may overfit small datasets, such as those common for FAZ segmentation in OCTA, to which there is limited access in clinical practice. To improve model generalization in low-data or imbalanced settings, we propose a multi-condition transformer-based architecture that uses four teacher encoders to distill knowledge into a shared base model, enabling the transfer of learned features across multiple datasets. These include intra-modality distillation using OCTA datasets from four ocular conditions: healthy aging eyes, Alzheimer’s disease, AMD, and diabetic retinopathy; and inter-modality distillation incorporating color fundus photographs of subjects undergoing laser photocoagulation therapy. Our multi-condition model achieved a mean Dice Index of 83.8% with pretraining, outperforming single-condition models (mean of 83.1%) across all conditions. Pretraining on color fundus photocoagulation images improved the average Dice Index by a small margin on all conditions except AMD (1.1% on single-condition models, and 0.1% on multi-condition models). Our architecture demonstrates potential for broader applications in detecting and analyzing ophthalmic and systemic diseases across diverse imaging datasets and settings.

Stargardt disease is the most common form of juvenile-onset macular dystrophy. Spectral-domain optical coherence tomography (SD-OCT) imaging provides an opportunity to directly measure changes to retinal layers due to Stargardt atrophy. Generally, atrophy segmentation and prediction can be conducted using mean intensity feature maps generated from the relevant retinal layers. In this paper, we report an approach using advanced OCT-derived features to augment and enhance data beyond the commonly used mean intensity features for enhanced prediction of Stargardt atrophy with an ensemble deep learning neural network. With all the relevant retinal layers, this neural network architecture achieves a median Dice coefficient of 0.830 for six-month predictions and 0.828 for twelve-month predictions, showing a significant improvement over a neural network using only mean intensity, which achieved Dice coefficients of 0.744 and 0.762 for six-month and twelve-month predictions, respectively. When using feature maps generated from different layers of the retina, significant differences in performance were observed. This study shows promising results for using multiple OCT-derived features beyond intensity for assessing the prognosis of Stargardt disease and quantifying the rate of progression.

The diagnosis of primary open-angle glaucoma (POAG) progression based on structural imaging such as color fundus photos (CFPs) is challenging due to the limited number of early biomarkers, as commonly determined by clinicians, and the inherent variability in optic nerve heads (ONHs) between individuals. Moreover, while visual function is the main concern for glaucoma patients, and the ability to infer future visual outcome from imaging will benefit patients by early intervention, there is currently no available tool for this. To detect glaucoma progression from ocular hypertension both structurally and functionally, and identify potential objective early biomarkers associated with progression, we developed and evaluated deep convolutional long short-term memory (CNN-LSTM) neural network models using longitudinal CFPs from the Ocular Hypertension Treatment Study (OHTS). Patients were categorized into four diagnostic groups for model input: healthy, POAG with optic disc changes, POAG with visual field (VF) changes, and POAG with both optic disc and VF changes. Gradient-weighted class activation mapping (Grad-CAM) was employed for the post hoc visualization of image features, which may be associated with the objective POAG biomarkers (rather than the biomarkers determined by clinicians). The CNN-LSTM models for the detection of POAG progression achieved promising performance results both for the structural and functional models, with an area under curve (AUC) performance of 0.894 for the disc-only group, 0.911 for the VF-only group, and 0.939 for the disc and VF group. The model demonstrated high precision (0.984) and F1-score (0.963) in the both-changes group (disc + VF). Our preliminary investigation for early POAG biomarkers with Grad-CAM feature visualization signified that retinal vasculature could serve as an early and objective biomarker for POAG progression, complementing the traditionally used optic disc features and improving clinical workflows.

Stargardt atrophy and geographic atrophy (GA) represent pivotal endpoints in FDA-approved clinical trials. Predicting atrophy progression is crucial for evaluating drug efficacy. Fundus autofluorescence (FAF), the standard 2D imaging modality in these trials, has limitations in patient comfort. In contrast, spectral-domain optical coherence tomography (SD-OCT), a 3D imaging modality, is more patient friendly but suffers from lower image quality. This study has two primary objectives: (1) develop an efficient predictive modeling for the generation of future FAF images and prediction of future Stargardt atrophic (as well as GA) regions and (2) develop an efficient predictive modeling with advanced 3D OCT features at ellipsoid zone (EZ) for the comparative performance in the generation of future enface EZ maps and prediction of future Stargardt atrophic regions on OCT as on FAF. To achieve these goals, we propose two deep neural networks (termed ReConNet and ReConNet-Ensemble) with recurrent learning units (long short-term memory, LSTM) integrating with a convolutional neural network (CNN) encoder–decoder architecture and concurrent learning units integrated by ensemble/multiple recurrent learning channels. The ReConNet, which incorporates LSTM connections with CNN, is developed for the first goal on longitudinal FAF. The ReConNet-Ensemble, which incorporates multiple recurrent learning channels based on enhanced EZ enface maps to capture higher-order inherent OCT EZ features, is developed for the second goal on longitudinal OCT. Using FAF images at months 0, 6, and 12 to predict atrophy at month 18, the ReConNet achieved mean (±standard deviation, SD) and median Dice coefficients of 0.895 (±0.086) and 0.922 for Stargardt atrophy and 0.864 (±0.113) and 0.893 for GA. Using SD-OCT images at months 0 and 6 to predict atrophy at month 12, the ReConNet-Ensemble achieved mean and median Dice coefficients of 0.882 (±0.101) and 0.906 for Stargardt atrophy. The prediction performance on OCT images is comparably good to that on FAF. These results underscore the potential of SD-OCT for efficient and practical assessment of atrophy progression in clinical trials and retina clinics, complementing or surpassing the widely used FAF imaging technique.

Age-related macular degeneration (AMD) is the leading cause of central vision loss in aging populations. Geographic atrophy (GA) is the advanced, non-neovascular form of AMD. Predicting the longitudinal progression of GA remains a critical challenge in ophthalmic clinical practice and clinical trial design. Forecasting the trajectory of GA is complicated by highly variable growth rates and the inherent scarcity of long-term, high-quality imaging data. To address these challenges, we introduce the Sliding Window Attention U-Net (SWAU-Net), a hybrid architecture that integrates Transformer-based temporal modeling of GA growth with precise spatial modeling of GA location with a U-Net convolutional neural network (CNN). To ensure generalization in the low-data regime, SWAU-Net embeds explicit temporal and geometric consistency priors via a weight-shared Sliding Window Attention core and feature-level regularization that preserves sparse, high-frequency lesion boundaries across frames. Experimental results demonstrate that these structural constraints prevent the model from overfitting to imaging noise, achieving a Growth Mask Dice Similarity Coefficient (DSC) of 0.66 (representing the spatial overlap between the predicted and ground truth lesion expansion regions), a significant improvement over unregularized Transformer and standard recurrent baseline models. Our framework provides a robust tool for predicting GA lesion trajectories, potentially supporting more efficient clinical trial designs and personalized patient monitoring.