Fundus2Globe: Generative AI-Driven 3D Digital Twins for Personalized Myopia Management

Myopia, projected to affect 50% population globally by 2050, is a leading cause of vision loss. Eyes with pathological myopia exhibit distinctive shape distributions, which are closely linked to the progression of vision-threatening complications. Recent understanding of eye-shape-based biomarkers requires magnetic resonance imaging (MRI), however, it is costly and unrealistic in routine ophthalmology clinics. We present Fundus2Globe, the first AI framework that synthesizes patient-specific 3D eye globes from ubiquitous 2D color fundus photographs (CFPs) and routine metadata (axial length, spherical equivalent), bypassing MRI dependency. By integrating a 3D morphable eye model (encoding biomechanical shape priors) with a latent diffusion model, our approach achieves submillimeter accuracy in reconstructing posterior ocular anatomy efficiently. Fundus2Globe uniquely quantifies how vision-threatening lesions (e.g., staphylomas) in CFPs correlate with MRI-validated 3D shape abnormalities, enabling clinicians to simulate posterior segment changes in response to refractive shifts. External validation demonstrates its robust generation performance, ensuring fairness across underrepresented groups. By transforming 2D fundus imaging into 3D digital replicas of ocular structures, Fundus2Globe is a gateway for precision ophthalmology, laying the foundation for AI-driven, personalized myopia management.

FFA Sora, video generation as fundus fluorescein angiography simulator

Fundus fluorescein angiography (FFA) is critical for diagnosing retinal vascular diseases, but beginners often struggle with image interpretation. This study develops FFA Sora, a text-to-video model that converts FFA reports into dynamic videos via a Wavelet-Flow Variational Autoencoder (WF-VAE) and a diffusion transformer (DiT). Trained on an anonymized dataset, FFA Sora accurately simulates disease features from the input text, as confirmed by objective metrics: Frechet Video Distance (FVD) = 329.78, Learned Perceptual Image Patch Similarity (LPIPS) = 0.48, and Visual-question-answering Score (VQAScore) = 0.61. Specific evaluations showed acceptable alignment between the generated videos and textual prompts, with BERTScore of 0.35. Additionally, the model demonstrated strong privacy-preserving performance in retrieval evaluations, achieving an average Recall@K of 0.073. Human assessments indicated satisfactory visual quality, with an average score of 1.570(scale: 1 = best, 5 = worst). This model addresses privacy concerns associated with sharing large-scale FFA data and enhances medical education.

Interpreting Object-level Foundation Models via Visual Precision Search

Advances in multimodal pre-training have propelled object-level foundation models, such as Grounding DINO and Florence-2, in tasks like visual grounding and object detection. However, interpreting these models\' decisions has grown increasingly challenging. Existing interpretable attribution methods for object-level task interpretation have notable limitations: (1) gradient-based methods lack precise localization due to visual-textual fusion in foundation models, and (2) perturbation-based methods produce noisy saliency maps, limiting fine-grained interpretability. To address these, we propose a Visual Precision Search method that generates accurate attribution maps with fewer regions. Our method bypasses internal model parameters to overcome attribution issues from multimodal fusion, dividing inputs into sparse sub-regions and using consistency and collaboration scores to accurately identify critical decision-making regions. We also conducted a theoretical analysis of the boundary guarantees and scope of applicability of our method. Experiments on RefCOCO, MS COCO, and LVIS show our approach enhances object-level task interpretability over SOTA for Grounding DINO and Florence-2 across various evaluation metrics, with faithfulness gains of 23.7\%, 31.6\%, and 20.1\% on MS COCO, LVIS, and RefCOCO for Grounding DINO, and 102.9\% and 66.9\% on MS COCO and RefCOCO for Florence-2. Additionally, our method can interpret failures in visual grounding and object detection tasks, surpassing existing methods across multiple evaluation metrics. The code will be released at \url{https://github.com/RuoyuChen10/VPS}.

EyeDiff: text-to-image diffusion model improves rare eye disease diagnosis

The rising prevalence of vision-threatening retinal diseases poses a significant burden on the global healthcare systems. Deep learning (DL) offers a promising solution for automatic disease screening but demands substantial data. Collecting and labeling large volumes of ophthalmic images across various modalities encounters several real-world challenges, especially for rare diseases. Here, we introduce EyeDiff, a text-to-image model designed to generate multimodal ophthalmic images from natural language prompts and evaluate its applicability in diagnosing common and rare diseases. EyeDiff is trained on eight large-scale datasets using the advanced latent diffusion model, covering 14 ophthalmic image modalities and over 80 ocular diseases, and is adapted to ten multi-country external datasets. The generated images accurately capture essential lesional characteristics, achieving high alignment with text prompts as evaluated by objective metrics and human experts. Furthermore, integrating generated images significantly enhances the accuracy of detecting minority classes and rare eye diseases, surpassing traditional oversampling methods in addressing data imbalance. EyeDiff effectively tackles the issue of data imbalance and insufficiency typically encountered in rare diseases and addresses the challenges of collecting large-scale annotated images, offering a transformative solution to enhance the development of expert-level diseases diagnosis models in ophthalmic field.

Visual Question Answering in Ophthalmology: A Progressive and Practical Perspective

Accurate diagnosis of ophthalmic diseases relies heavily on the interpretation of multimodal ophthalmic images, a process often time-consuming and expertise-dependent. Visual Question Answering (VQA) presents a potential interdisciplinary solution by merging computer vision and natural language processing to comprehend and respond to queries about medical images. This review article explores the recent advancements and future prospects of VQA in ophthalmology from both theoretical and practical perspectives, aiming to provide eye care professionals with a deeper understanding and tools for leveraging the underlying models. Additionally, we discuss the promising trend of large language models (LLM) in enhancing various components of the VQA framework to adapt to multimodal ophthalmic tasks. Despite the promising outlook, ophthalmic VQA still faces several challenges, including the scarcity of annotated multimodal image datasets, the necessity of comprehensive and unified evaluation methods, and the obstacles to achieving effective real-world applications. This article highlights these challenges and clarifies future directions for advancing ophthalmic VQA with LLMs. The development of LLM-based ophthalmic VQA systems calls for collaborative efforts between medical professionals and AI experts to overcome existing obstacles and advance the diagnosis and care of eye diseases.

Fundus to Fluorescein Angiography Video Generation as a Retinal Generative Foundation Model

Fundus fluorescein angiography (FFA) is crucial for diagnosing and monitoring retinal vascular issues but is limited by its invasive nature and restricted accessibility compared to color fundus (CF) imaging. Existing methods that convert CF images to FFA are confined to static image generation, missing the dynamic lesional changes. We introduce Fundus2Video, an autoregressive generative adversarial network (GAN) model that generates dynamic FFA videos from single CF images. Fundus2Video excels in video generation, achieving an FVD of 1497.12 and a PSNR of 11.77. Clinical experts have validated the fidelity of the generated videos. Additionally, the model's generator demonstrates remarkable downstream transferability across ten external public datasets, including blood vessel segmentation, retinal disease diagnosis, systemic disease prediction, and multimodal retrieval, showcasing impressive zero-shot and few-shot capabilities. These findings position Fundus2Video as a powerful, non-invasive alternative to FFA exams and a versatile retinal generative foundation model that captures both static and temporal retinal features, enabling the representation of complex inter-modality relationships.

Fundus2Video: Cross-Modal Angiography Video Generation from Static Fundus Photography with Clinical Knowledge Guidance

Fundus Fluorescein Angiography (FFA) is a critical tool for assessing retinal vascular dynamics and aiding in the diagnosis of eye diseases. However, its invasive nature and less accessibility compared to Color Fundus (CF) images pose significant challenges. Current CF to FFA translation methods are limited to static generation. In this work, we pioneer dynamic FFA video generation from static CF images. We introduce an autoregressive GAN for smooth, memory-saving frame-by-frame FFA synthesis. To enhance the focus on dynamic lesion changes in FFA regions, we design a knowledge mask based on clinical experience. Leveraging this mask, our approach integrates innovative knowledge mask-guided techniques, including knowledge-boosted attention, knowledge-aware discriminators, and mask-enhanced patchNCE loss, aimed at refining generation in critical areas and addressing the pixel misalignment challenge. Our method achieves the best FVD of 1503.21 and PSNR of 11.81 compared to other common video generation approaches. Human assessment by an ophthalmologist confirms its high generation quality. Notably, our knowledge mask surpasses supervised lesion segmentation masks, offering a promising non-invasive alternative to traditional FFA for research and clinical applications. The code is available at https://github.com/Michi-3000/Fundus2Video.

UWF-RI2FA: Generating Multi-frame Ultrawide-field Fluorescein Angiography from Ultrawide-field Retinal Imaging Improves Diabetic Retinopathy Stratification

Ultrawide-field fluorescein angiography (UWF-FA) facilitates diabetic retinopathy (DR) detection by providing a clear visualization of peripheral retinal lesions. However, the intravenous dye injection with potential risks hamper its application. We aim to acquire dye-free UWF-FA images from noninvasive UWF retinal imaging (UWF-RI) using generative artificial intelligence (GenAI) and evaluate its effectiveness in DR screening. A total of 18,321 UWF-FA images of different phases were registered with corresponding UWF-RI images and fed into a generative adversarial networks (GAN)-based model for training. The quality of generated UWF-FA images was evaluated through quantitative metrics and human evaluation. The DeepDRiD dataset was used to externally assess the contribution of generated UWF-FA images to DR classification, using area under the receiver operating characteristic curve (AUROC) as outcome metrics. The generated early, mid, and late phase UWF-FA images achieved high authenticity, with multi-scale similarity scores ranging from 0.70 to 0.91 and qualitative visual scores ranging from 1.64 to 1.98 (1=real UWF-FA quality). In fifty randomly selected images, 56% to 76% of the generated images were difficult to distinguish from real images in the Turing test. Moreover, adding these generated UWF-FA images for DR classification significantly increased the AUROC from 0.869 to 0.904 compared to the baseline model using UWF-RI images (P < .001). The model successfully generates realistic multi-frame UWF-FA images for enhancing DR stratification without intravenous dye injection.

Generating Multi-frame Ultrawide-field Fluorescein Angiography from Ultrawide-field Color Imaging Improves Diabetic Retinopathy Stratification

Ultrawide-field fluorescein angiography (UWF-FA) facilitates diabetic retinopathy (DR) detection by providing a clear visualization of peripheral retinal lesions. However, the intravenous dye injection with potential risks hamper its application. We aim to acquire dye-free UWF-FA images from noninvasive UWF color fundus (UWF-CF) images using generative artificial intelligence (GenAI) and evaluate its effectiveness in DR screening. A total of 18,321 UWF-FA images of different phases were registered with corresponding UWF-CF images and fed into a generative adversarial networks (GAN)-based model for training. The quality of generated UWF-FA images was evaluated through quantitative metrics and human evaluation. The DeepDRiD dataset was used to externally assess the contribution of generated UWF-FA images to DR classification, using area under the receiver operating characteristic curve (AUROC) as outcome metrics. The generated early, mid, and late phase UWF-FA images achieved high authenticity, with multi-scale similarity scores ranging from 0.70 to 0.91 and qualitative visual scores ranging from 1.64 to 1.98 (1=real UWF-FA quality). In fifty randomly selected images, 56% to 76% of the generated images were difficult to distinguish from real images in the Turing test. Moreover, adding these generated UWF-FA images for DR classification significantly increased the AUROC from 0.869 to 0.904 compared to the baseline model using UWF-CF images (P < .001). The model successfully generates realistic multi-frame UWF-FA images without intravenous dye injection. The generated UWF-FA enhanced DR stratification.

Choroidal Vessel Segmentation on Indocyanine Green Angiography Images via Human-in-the-Loop Labeling

Human-in-the-loop (HITL) strategy has been recently introduced into the field of medical image processing. Indocyanine green angiography (ICGA) stands as a well-established examination for visualizing choroidal vasculature and detecting chorioretinal diseases. However, the intricate nature of choroidal vascular networks makes large-scale manual segmentation of ICGA images challenging. Thus, the study aims to develop a high-precision choroidal vessel segmentation model with limited labor using HITL framework. We utilized a multi-source ICGA dataset, including 55 degree view and ultra-widefield ICGA (UWF-ICGA) images for model development. The choroidal vessel network was pre-segmented by a pre-trained vessel segmentation model, and then manually modified by two ophthalmologists. Choroidal vascular diameter, density, complexity, tortuosity, and branching angle were automatically quantified based on the segmentation. We finally conducted four cycles of HITL. One hundred and fifty 55 degree view ICGA images were used for the first three cycles (50 images per cycle), and twenty UWF-ICGA images for the last cycle. The average time needed to manually correct a pre-segmented ICGA image per cycle reduced from 20 minutes to 1 minute. High segmentation accuracy has been achieved on both 55 degree view ICGA and UWF-ICGA images. Additionally, the multi-dimensional choroidal vascular parameters were significantly associated with various chorioretinal diseases. Our study not only demonstrated the feasibility of the HITL strategy in improving segmentation performance with reduced manual labeling, but also innovatively introduced several risk predictors for choroidal abnormalities.