Fundus fluorescein angiography (FFA) is critical for assessing retinal vascular abnormalities, but its acquisition is invasive and not always feasible. In contrast, color fundus photography (CFP) is non-invasive and widely accessible, which has motivated studies on CFP-to-FFA synthesis. However, prior works rely solely on CFP surface texture, fundamentally limiting the ability to reconstruct functional vascular information and subtle pathological changes. To address this, we propose a novel framework that synthesizes FFA from CFP with structural guidance provided by optical coherence tomography (OCT). We construct a multi-modal retinal imaging dataset with paired CFP, FFA, and OCT from 3,676 patient eyes--the first tri-modally aligned dataset in retinal imaging. To bridge the spatial gap between OCT and fundus modalities, we propose a Spatially Aligned Cross-Modal Fusion (SACMF) module that projects depth-resolved OCT features onto the fundus plane and injects them into the CFP encoder via adaptive layer normalization. Beyond feature fusion, we further introduce Token-wise Cross-Modality Alignment (TCMA), a token-level contrastive learning strategy that explicitly aligns CFP and FFA representations at corresponding spatial positions. Our method achieves superior synthesis performance compared to state-of-the-art methods. Moreover, extensive experiments demonstrate that the FFA images synthesized by our approach bring greater improvements in downstream disease diagnosis performance than existing methods, highlighting the clinical potential of our approach as a non-invasive decision-support tool in routine workflows. The code is available at https://github.com/while-plus/OCT-guide-FFA-Syn.
Color fundus photography (CFP) is the mainstay of large-scale retinal screening, but its diagnostic capacity is limited by the lack of depth-resolved structure, which optical coherence tomography (OCT) provides yet is less accessible at population scale. We present EyeMVP, a cross-modal retinal foundation model that uses paired CFP--OCT pretraining to learn OCT-informed CFP representations while requiring only CFP at inference. Pretrained on 674,893 same-eye same-day CFP--OCT triples from 112,642 patients across eight hospitals, EyeMVP uses cross-modal masked reconstruction to enrich CFP features with OCT-associated supervision, and combines source-constrained cross-attention with CFP-derived structural masks to accommodate the non-aligned geometry of en-face CFP and cross-sectional OCT. Across 15 dataset-level settings spanning classification and segmentation, under both full-data and few-shot regimes, EyeMVP performs on par with or better than representative retinal foundation models, with consistent gains on macular and optic-nerve tasks; it attains AUROCs of 0.923 for macular edema and 0.867 for myopic macular schisis, two conditions poorly resolved in CFP. In an exploratory reader study, EyeMVP surpasses junior and intermediate ophthalmologists but not seniors on macular edema, while exceeding all groups on myopic macular schisis. These results indicate that cross-modal reconstruction can enrich CFP representations with OCT-associated supervision, offering a practical route to stronger CFP-based screening.
Diabetic retinopathy (DR) is a leading cause of vision impairment worldwide, highlighting the need for accurate and accessible screening tools. Optical Coherence Tomography (OCT) provides high-resolution structural information of the retina, whereas OCT angiography (OCTA) offers complementary vascular information that is highly relevant for DR diagnosis. In this study, we propose a cross-modal fusion of OCT B-scans with single-channel en face OCTA using a bidirectional cross-modal attention network for automated DR classification. Two independent datasets, OCT500 and UIC, comprising 730 subjects in total, were utilized to evaluate performance under within-dataset, combined-dataset, and cross-dataset generalization settings. A ConvNeXt V2 model trained solely on OCT images served as the unimodal baseline. In addition to ground-truth (GT) OCTA, we explored the use of translated (TR) OCTA generated from OCT scans, eliminating the requirement for dedicated OCTA hardware. Experimental results demonstrate that cross-modal fusion consistently outperforms unimodal OCT classification across all evaluation scenarios. Fusion with GT OCTA improved classification accuracy and discriminative performance, while TR OCTA achieved comparable or superior results in most settings. Furthermore, TR OCTA improved sensitivity and cross-dataset generalization, indicating enhanced robustness to domain shifts. These findings demonstrate that attention-based OCT-OCTA en face fusion provides clinically meaningful improvements for DR detection and suggest that computationally generated OCTA can serve as a practical, low-cost alternative to hardware-acquired OCTA, enabling broader deployment of high-performance retinal screening systems in resource-limited clinical environments.
Rashadul Hasan Badhon, Atalie Carina Thompson, Jennifer I. Lim +2
Color Fundus Photography (CFP) is a primary non-invasive imaging modality for large-scale screening of ophthalmic and systemic diseases. Existing surveys mainly summarize task-specific algorithms, datasets, or preprocessing techniques independently, lacking a unified perspective on their co-evolution with modern artificial intelligence. This review provides an integrated overview of CFP AI through the interplay of dataset evolution, preprocessing paradigms, and modeling frameworks. We show that CFP datasets have evolved from small single-center collections with task-specific labels to large multi-center resources featuring multimodal pairings and longitudinal clinical records. Preprocessing has progressed from conventional image enhancement to neural data-engineering pipelines, hardware-aware token optimization, and self-supervised imputation for incomplete electronic health records (EHRs). Meanwhile, modeling has advanced from convolutional neural networks (CNNs) to vision foundation models, state space models (SSMs), and multimodal expert architectures. At the multimodal frontier, CFP is increasingly integrated with EHRs and longitudinal patient information, enabling more comprehensive clinical reasoning beyond isolated image analysis. We conclude that future progress depends on the collaborative optimization of datasets, preprocessing, and multimodal modeling, providing a roadmap toward robust clinical deployment, improved cross-domain generalization, and resource-efficient edge intelligence.