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.

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.

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.

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.

Object Detectors in the Open Environment: Challenges, Solutions, and Outlook

With the emergence of foundation models, deep learning-based object detectors have shown practical usability in closed set scenarios. However, for real-world tasks, object detectors often operate in open environments, where crucial factors (e.g., data distribution, objective) that influence model learning are often changing. The dynamic and intricate nature of the open environment poses novel and formidable challenges to object detectors. Unfortunately, current research on object detectors in open environments lacks a comprehensive analysis of their distinctive characteristics, challenges, and corresponding solutions, which hinders their secure deployment in critical real-world scenarios. This paper aims to bridge this gap by conducting a comprehensive review and analysis of object detectors in open environments. We initially identified limitations of key structural components within the existing detection pipeline and propose the open environment object detector challenge framework that includes four quadrants (i.e., out-of-domain, out-of-category, robust learning, and incremental learning) based on the dimensions of the data / target changes. For each quadrant of challenges in the proposed framework, we present a detailed description and systematic analysis of the overarching goals and core difficulties, systematically review the corresponding solutions, and benchmark their performance over multiple widely adopted datasets. In addition, we engage in a discussion of open problems and potential avenues for future research. This paper aims to provide a fresh, comprehensive, and systematic understanding of the challenges and solutions associated with open-environment object detectors, thus catalyzing the development of more solid applications in real-world scenarios. A project related to this survey can be found at https://github.com/LiangSiyuan21/OEOD_Survey.

Less is More: Fewer Interpretable Region via Submodular Subset Selection

Image attribution algorithms aim to identify important regions that are highly relevant to model decisions. Although existing attribution solutions can effectively assign importance to target elements, they still face the following challenges: 1) existing attribution methods generate inaccurate small regions thus misleading the direction of correct attribution, and 2) the model cannot produce good attribution results for samples with wrong predictions. To address the above challenges, this paper re-models the above image attribution problem as a submodular subset selection problem, aiming to enhance model interpretability using fewer regions. To address the lack of attention to local regions, we construct a novel submodular function to discover more accurate small interpretation regions. To enhance the attribution effect for all samples, we also impose four different constraints on the selection of sub-regions, i.e., confidence, effectiveness, consistency, and collaboration scores, to assess the importance of various subsets. Moreover, our theoretical analysis substantiates that the proposed function is in fact submodular. Extensive experiments show that the proposed method outperforms SOTA methods on two face datasets (Celeb-A and VGG-Face2) and one fine-grained dataset (CUB-200-2011). For correctly predicted samples, the proposed method improves the Deletion and Insertion scores with an average of 4.9% and 2.5% gain relative to HSIC-Attribution. For incorrectly predicted samples, our method achieves gains of 81.0% and 18.4% compared to the HSIC-Attribution algorithm in the average highest confidence and Insertion score respectively. The code is released at https://github.com/RuoyuChen10/SMDL-Attribution.

mCL-NER: Cross-Lingual Named Entity Recognition via Multi-view Contrastive Learning

Cross-lingual named entity recognition (CrossNER) faces challenges stemming from uneven performance due to the scarcity of multilingual corpora, especially for non-English data. While prior efforts mainly focus on data-driven transfer methods, a significant aspect that has not been fully explored is aligning both semantic and token-level representations across diverse languages. In this paper, we propose Multi-view Contrastive Learning for Cross-lingual Named Entity Recognition (mCL-NER). Specifically, we reframe the CrossNER task into a problem of recognizing relationships between pairs of tokens. This approach taps into the inherent contextual nuances of token-to-token connections within entities, allowing us to align representations across different languages. A multi-view contrastive learning framework is introduced to encompass semantic contrasts between source, codeswitched, and target sentences, as well as contrasts among token-to-token relations. By enforcing agreement within both semantic and relational spaces, we minimize the gap between source sentences and their counterparts of both codeswitched and target sentences. This alignment extends to the relationships between diverse tokens, enhancing the projection of entities across languages. We further augment CrossNER by combining self-training with labeled source data and unlabeled target data. Our experiments on the XTREME benchmark, spanning 40 languages, demonstrate the superiority of mCL-NER over prior data-driven and model-based approaches. It achieves a substantial increase of nearly +2.0 $F_1$ scores across a broad spectrum and establishes itself as the new state-of-the-art performer.