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.

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. Keywords: Ophthalmic Visual Question Answering, Large Language Models, Multimodal Image Interpretation, Report Generation, Generative Artificial Intelligence Introduction Accurate diagnosis of ophthalmic diseases often relies on the comprehensive analysis of multimodal ophthalmic images, including color fundus photographs (CFP), optical coherence tomography (OCT), fundus fluorescein angiography (FFA), scanning laser ophthalmoscopy (SLO), anterior segment photographs and corneal topography, etc.

Ophthalmic images and derivatives such as the retinal nerve fiber layer (RNFL) thickness map are crucial for detecting and monitoring ophthalmic diseases (e.g., glaucoma). For computer-aided diagnosis of eye diseases, the key technique is to automatically extract meaningful features from ophthalmic images that can reveal the biomarkers (e.g., RNFL thinning patterns) linked to functional vision loss. However, representation learning from ophthalmic images that links structural retinal damage with human vision loss is non-trivial mostly due to large anatomical variations between patients. The task becomes even more challenging in the presence of image artifacts, which are common due to issues with image acquisition and automated segmentation. In this paper, we propose an artifact-tolerant unsupervised learning framework termed EyeLearn for learning representations of ophthalmic images. EyeLearn has an artifact correction module to learn representations that can best predict artifact-free ophthalmic images. In addition, EyeLearn adopts a clustering-guided contrastive learning strategy to explicitly capture the intra- and inter-image affinities. During training, images are dynamically organized in clusters to form contrastive samples in which images in the same or different clusters are encouraged to learn similar or dissimilar representations, respectively. To evaluate EyeLearn, we use the learned representations for visual field prediction and glaucoma detection using a real-world ophthalmic image dataset of glaucoma patients. Extensive experiments and comparisons with state-of-the-art methods verified the effectiveness of EyeLearn for learning optimal feature representations from ophthalmic images.

Deep hashing methods have been proved to be effective for the large-scale medical image search assisting reference-based diagnosis for clinicians. However, when the salient region plays a maximal discriminative role in ophthalmic image, existing deep hashing methods do not fully exploit the learning ability of the deep network to capture the features of salient regions pointedly. The different grades or classes of ophthalmic images may be share similar overall performance but have subtle differences that can be differentiated by mining salient regions. To address this issue, we propose a novel end-to-end network, named Attention-based Saliency Hashing (ASH), for learning compact hash-code to represent ophthalmic images. ASH embeds a spatial-attention module to focus more on the representation of salient regions and highlights their essential role in differentiating ophthalmic images. Benefiting from the spatial-attention module, the information of salient regions can be mapped into the hash-code for similarity calculation. In the training stage, we input the image pairs to share the weights of the network, and a pairwise loss is designed to maximize the discriminability of the hash-code. In the retrieval stage, ASH obtains the hash-code by inputting an image with an end-to-end manner, then the hash-code is used to similarity calculation to return the most similar images. Extensive experiments on two different modalities of ophthalmic image datasets demonstrate that the proposed ASH can further improve the retrieval performance compared to the state-of-the-art deep hashing methods due to the huge contributions of the spatial-attention module.