Authors: Yan Lin, Ziheng Wang, Shuang Chen, Amir Atapour-Abarghouei, Stephen McGough
Abstract
Medical image classifiers are often trained within one source population, yet clinical deployment requires robustness to patients whose appearance, acquisition style, and disease prevalence differ from the source cohort. Existing fairness and robustness methods often require group supervision or treat appearance variation as an undifferentiated nuisance, which is insufficient when population-correlated low-level cues and lesion evidence share edge and texture structure. We study a strict source-only cross-population setting, where external populations are unseen during optimization, validation, scheduling, hyperparameter and model selection. We propose RED-Sphere, a plug-and-play robustness framework for image classification under unseen population shifts. It estimates shortcut-sensitive nuisance responses with an edge and feature energy prior, attenuates dominant responses through residual soft gating, regularizes masked nuisance views with counterfactual-inspired consistency and separation losses, and predicts labels with normalized spherical prototypes. It favours angular semantic evidence over source-correlated activation magnitude while preserving lesion structure. Although demonstrated on 2D Scanning Laser Ophthalmoscopy (SLO) fundus classification for Age-Related Macular Degeneration (AMD) and Diabetic Retinopathy (DR), RED-Sphere is not tied to retinal anatomy: the same principle can be adapted with modality-specific nuisance priors wherever appearance shortcuts and semantic evidence are entangled. Under a strict White-only Harvard-FairVision protocol, RED-Sphere improves held-out macro-F1 across all 20 task and backbone comparisons, with average gains of 1.28 and 2.98 F1 points on AMD and DR. Gains in AUC and PR-AUC, visual diagnostics, ablations, and sensitivity analyses further support stronger external semantic alignment and more stable angular disease geometry.
Artificial intelligence (AI) shows remarkable potential in medical imaging diagnostics, yet most current models require retraining when applied across different clinical settings, limiting their scalability. We developed GlobeReady, a deployment-oriented platform powered by the RetiGlobe foun- dation model and local feature augmentation. RetiGlobe was pretrained in two stages: 1) self-supervised learning using DINOv2 on 38 million synthetic ophthalmic images, and 2) contrastive learning using CLIP on 475,845 real image-text pairs spanning diverse ethnicities, imaging devices, and geographic regions worldwide. We evaluate GlobeReady on 488,448 ophthalmic images, including color fundus photographs (CFPs) and optical coherence tomography scans, from multi-centres in China, Singapore, Vietnam and the UK. Prospective testing included usability assessment with 31 ophthalmologists. Exploratory analyses evaluated domain generalisability, Bayesian uncertainty quantification, out-of-distribution (OOD) detection, and feature-based case retrieval.
Foundation models are used to extract transferable representations from large amounts of unlabeled data, typically via self-supervised learning (SSL). However, many of these models rely on architectures that offer limited interpretability, a critical issue in high-stakes domains such as medical imaging. We propose \model, a foundation model that is interpretable-by-design via a BagNet backbone whose small receptive fields generate class evidence maps that are faithful to the model's decision-making process. Additionally, \model{} incorporates a 2D projection layer during pretraining that enables direct visualization of the representation space, providing a dataset-level view of the learned structure including meaningful clinical clusters as well as potential spurious correlations. We trained \model{} on over 800,000 color fundus photographs from various sources to learn generalizable representations for different downstream tasks. Our model achieves performance comparable to RETFound, which has 16× more parameters, while providing interpretable predictions on out-of-distribution data. These results suggest that large-scale SSL pretraining paired with inherent interpretability can lead to robust representations for retinal imaging. Code and pretrained models are available at \href{https://anonymous.4open.science/r/dual-ifm-3D5A/README.md}{www.anonymous.4open.science/dual-IFM}.
Samuel Ofosu Mensah, Camila Roa, Kerol Djoumessi +1
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.