Large vision foundation models have been widely adopted for retinal disease classification without systematic evidence justifying their parameter requirements. In the present work we address two critical questions: First, are large domain-specific foundation models essential, or do compact general-purpose architectures suffice? Second, does specialized retinal pretraining justify its computational cost? To answer this, we benchmark initialization strategies across four retinal imaging classification tasks spanning Optical Coherence Tomography (OCT) and Color Fundus Photography (CFP) modalities: 8-class OCT classification, 3-class diabetic macular edema (DME), 5-class diabetic retinopathy (DR), and 3-class glaucoma (GL) detection. We evaluate 12-13 model configurations per task, including vision transformers (22.8M-86.6M parameters), Swin Transformers (27.6M-28.3M), ConvNeXt (28.6M), and the domain-specific RETFound models (303M), under identical training conditions. Our results challenge prevailing assumptions: First, we demonstrate that pretraining provides universal benefits (5.18-18.41% improvement), scaling with task difficulty. Second, compact architectures (27-29M) dominate Pareto frontiers; SwinV2-tiny achieves top-1 performance on three datasets. Third, RETFound (303M) justifies its computational cost only for challenging DR grading (accuracy of 71.15%), while ImageNet pretraining proves to be sufficient with all other tasks (DME accuracy: 99.24%, OCT accuracy: 97.96%). CFP tasks show larger pretraining accuracy gains (9.13-18.41%) than OCT (5.18%). Thus, the evidence suggests that compact general-purpose models deliver near-optimal performance for most retinal classification tasks; specialized foundation models warranted only for fine-grained discrimination under extreme class imbalance.

Current artificial intelligence models for medical imaging are predominantly single modality and single disease. Attempts to create multimodal and multi-disease models have resulted in inconsistent clinical accuracy. Furthermore, training these models typically requires large, labour-intensive, well-labelled datasets. We developed MerMED-FM, a state-of-the-art multimodal, multi-specialty foundation model trained using self-supervised learning and a memory module. MerMED-FM was trained on 3.3 million medical images from over ten specialties and seven modalities, including computed tomography (CT), chest X-rays (CXR), ultrasound (US), pathology patches, color fundus photography (CFP), optical coherence tomography (OCT) and dermatology images. MerMED-FM was evaluated across multiple diseases and compared against existing foundational models. Strong performance was achieved across all modalities, with AUROCs of 0.988 (OCT); 0.982 (pathology); 0.951 (US); 0.943 (CT); 0.931 (skin); 0.894 (CFP); 0.858 (CXR). MerMED-FM has the potential to be a highly adaptable, versatile, cross-specialty foundation model that enables robust medical imaging interpretation across diverse medical disciplines.

The advent of foundation models (FMs) is transforming medical domain. In ophthalmology, RETFound, a retina-specific FM pre-trained sequentially on 1.4 million natural images and 1.6 million retinal images, has demonstrated high adaptability across clinical applications. Conversely, DINOv2, a general-purpose vision FM pre-trained on 142 million natural images, has shown promise in non-medical domains. However, its applicability to clinical tasks remains underexplored. To address this, we conducted head-to-head evaluations by fine-tuning RETFound and three DINOv2 models (large, base, small) for ocular disease detection and systemic disease prediction tasks, across eight standardized open-source ocular datasets, as well as the Moorfields AlzEye and the UK Biobank datasets. DINOv2-large model outperformed RETFound in detecting diabetic retinopathy (AUROC=0.850-0.952 vs 0.823-0.944, across three datasets, all P<=0.007) and multi-class eye diseases (AUROC=0.892 vs. 0.846, P<0.001). In glaucoma, DINOv2-base model outperformed RETFound (AUROC=0.958 vs 0.940, P<0.001). Conversely, RETFound achieved superior performance over all DINOv2 models in predicting heart failure, myocardial infarction, and ischaemic stroke (AUROC=0.732-0.796 vs 0.663-0.771, all P<0.001). These trends persisted even with 10% of the fine-tuning data. These findings showcase the distinct scenarios where general-purpose and domain-specific FMs excel, highlighting the importance of aligning FM selection with task-specific requirements to optimise clinical performance.

Background: RETFound, a self-supervised, retina-specific foundation model (FM), showed potential in downstream applications. However, its comparative performance with traditional deep learning (DL) models remains incompletely understood. This study aimed to evaluate RETFound against three ImageNet-pretrained supervised DL models (ResNet50, ViT-base, SwinV2) in detecting ocular and systemic diseases. Methods: We fine-tuned/trained RETFound and three DL models on full datasets, 50%, 20%, and fixed sample sizes (400, 200, 100 images, with half comprising disease cases; for each DR severity class, 100 and 50 cases were used. Fine-tuned models were tested internally using the SEED (53,090 images) and APTOS-2019 (3,672 images) datasets and externally validated on population-based (BES, CIEMS, SP2, UKBB) and open-source datasets (ODIR-5k, PAPILA, GAMMA, IDRiD, MESSIDOR-2). Model performance was compared using area under the receiver operating characteristic curve (AUC) and Z-tests with Bonferroni correction (P<0.05/3). Interpretation: Traditional DL models are mostly comparable to RETFound for ocular disease detection with large datasets. However, RETFound is superior in systemic disease detection with smaller datasets. These findings offer valuable insights into the respective merits and limitation of traditional models and FMs.

Integrating deep learning into medical imaging is poised to greatly advance diagnostic methods but it faces challenges with generalizability. Foundation models, based on self-supervised learning, address these issues and improve data efficiency. Natural domain foundation models show promise for medical imaging, but systematic research evaluating domain adaptation, especially using self-supervised learning and parameter-efficient fine-tuning, remains underexplored. Additionally, little research addresses the issue of catastrophic forgetting during fine-tuning of foundation models. We adapted the DINOv2 vision transformer for retinal imaging classification tasks using self-supervised learning and generated two novel foundation models termed DINORET and BE DINORET. Publicly available color fundus photographs were employed for model development and subsequent fine-tuning for diabetic retinopathy staging and glaucoma detection. We introduced block expansion as a novel domain adaptation strategy and assessed the models for catastrophic forgetting. Models were benchmarked to RETFound, a state-of-the-art foundation model in ophthalmology. DINORET and BE DINORET demonstrated competitive performance on retinal imaging tasks, with the block expanded model achieving the highest scores on most datasets. Block expansion successfully mitigated catastrophic forgetting. Our few-shot learning studies indicated that DINORET and BE DINORET outperform RETFound in terms of data-efficiency. This study highlights the potential of adapting natural domain vision models to retinal imaging using self-supervised learning and block expansion. BE DINORET offers robust performance without sacrificing previously acquired capabilities. Our findings suggest that these methods could enable healthcare institutions to develop tailored vision models for their patient populations, enhancing global healthcare inclusivity.

Early detection of eye diseases like glaucoma, macular degeneration, and diabetic retinopathy is crucial for preventing vision loss. While artificial intelligence (AI) foundation models hold significant promise for addressing these challenges, existing ophthalmic foundation models primarily focus on a single modality, whereas diagnosing eye diseases requires multiple modalities. A critical yet often overlooked aspect is harnessing the multi-view information across various modalities for the same patient. Additionally, due to the long-tail nature of ophthalmic diseases, standard fully supervised or unsupervised learning approaches often struggle. Therefore, it is essential to integrate clinical text to capture a broader spectrum of diseases. We propose EyeCLIP, a visual-language foundation model developed using over 2.77 million multi-modal ophthalmology images with partial text data. To fully leverage the large multi-modal unlabeled and labeled data, we introduced a pretraining strategy that combines self-supervised reconstructions, multi-modal image contrastive learning, and image-text contrastive learning to learn a shared representation of multiple modalities. Through evaluation using 14 benchmark datasets, EyeCLIP can be transferred to a wide range of downstream tasks involving ocular and systemic diseases, achieving state-of-the-art performance in disease classification, visual question answering, and cross-modal retrieval. EyeCLIP represents a significant advancement over previous methods, especially showcasing few-shot, even zero-shot capabilities in real-world long-tail scenarios.

In the realm of dermatology, the complexity of diagnosing skin conditions manually necessitates the expertise of dermatologists. Accurate identification of various skin ailments, ranging from cancer to inflammatory diseases, is paramount. However, existing artificial intelligence (AI) models in dermatology face challenges, particularly in accurately diagnosing diseases across diverse skin tones, with a notable performance gap in darker skin. Additionally, the scarcity of publicly available, unbiased datasets hampers the development of inclusive AI diagnostic tools. To tackle the challenges in accurately predicting skin conditions across diverse skin tones, we employ a transfer-learning approach that capitalizes on the rich, transferable knowledge from various image domains. Our method integrates multiple pre-trained models from a wide range of sources, including general and specific medical images, to improve the robustness and inclusiveness of the skin condition predictions. We rigorously evaluated the effectiveness of these models using the Diverse Dermatology Images (DDI) dataset, which uniquely encompasses both underrepresented and common skin tones, making it an ideal benchmark for assessing our approach. Among all methods, Med-ViT emerged as the top performer due to its comprehensive feature representation learned from diverse image sources. To further enhance performance, we conducted domain adaptation using additional skin image datasets such as HAM10000. This adaptation significantly improved model performance across all models.

Optical coherence tomography (OCT) has become critical for diagnosing retinal diseases as it enables 3D images of the retina and optic nerve. OCT acquisition is fast, non-invasive, affordable, and scalable. Due to its broad applicability, massive numbers of OCT images have been accumulated in routine exams, making it possible to train large-scale foundation models that can generalize to various diagnostic tasks using OCT images. Nevertheless, existing foundation models for OCT only consider 2D image slices, overlooking the rich 3D structure. Here, we present OCTCube, a 3D foundation model pre-trained on 26,605 3D OCT volumes encompassing 1.62 million 2D OCT images. OCTCube is developed based on 3D masked autoencoders and exploits FlashAttention to reduce the larger GPU memory usage caused by modeling 3D volumes. OCTCube outperforms 2D models when predicting 8 retinal diseases in both inductive and cross-dataset settings, indicating that utilizing the 3D structure in the model instead of 2D data results in significant improvement. OCTCube further shows superior performance on cross-device prediction and when predicting systemic diseases, such as diabetes and hypertension, further demonstrating its strong generalizability. Finally, we propose a contrastive-self-supervised-learning-based OCT-IR pre-training framework (COIP) for cross-modality analysis on OCT and infrared retinal (IR) images, where the OCT volumes are embedded using OCTCube. We demonstrate that COIP enables accurate alignment between OCT and IR en face images. Collectively, OCTCube, a 3D OCT foundation model, demonstrates significantly better performance against 2D models on 27 out of 29 tasks and comparable performance on the other two tasks, paving the way for AI-based retinal disease diagnosis.

Inability to express the confidence level and detect unseen classes has limited the clinical implementation of artificial intelligence in the real-world. We developed a foundation model with uncertainty estimation (FMUE) to detect 11 retinal conditions on optical coherence tomography (OCT). In the internal test set, FMUE achieved a higher F1 score of 96.76% than two state-of-the-art algorithms, RETFound and UIOS, and got further improvement with thresholding strategy to 98.44%. In the external test sets obtained from other OCT devices, FMUE achieved an accuracy of 88.75% and 92.73% before and after thresholding. Our model is superior to two ophthalmologists with a higher F1 score (95.17% vs. 61.93% &71.72%). Besides, our model correctly predicts high uncertainty scores for samples with ambiguous features, of non-target-category diseases, or with low-quality to prompt manual checks and prevent misdiagnosis. FMUE provides a trustworthy method for automatic retinal anomalies detection in the real-world clinical open set environment.

Artificial intelligence (AI) is vital in ophthalmology, tackling tasks like diagnosis, classification, and visual question answering (VQA). However, existing AI models in this domain often require extensive annotation and are task-specific, limiting their clinical utility. While recent developments have brought about foundation models for ophthalmology, they are limited by the need to train separate weights for each imaging modality, preventing a comprehensive representation of multi-modal features. This highlights the need for versatile foundation models capable of handling various tasks and modalities in ophthalmology. To address this gap, we present EyeFound, a multimodal foundation model for ophthalmic images. Unlike existing models, EyeFound learns generalizable representations from unlabeled multimodal retinal images, enabling efficient model adaptation across multiple applications. Trained on 2.78 million images from 227 hospitals across 11 ophthalmic modalities, EyeFound facilitates generalist representations and diverse multimodal downstream tasks, even for detecting challenging rare diseases. It outperforms previous work RETFound in diagnosing eye diseases, predicting systemic disease incidents, and zero-shot multimodal VQA. EyeFound provides a generalizable solution to improve model performance and lessen the annotation burden on experts, facilitating widespread clinical AI applications for retinal imaging.