Fundus diseases are major causes of visual impairment and blindness worldwide, especially in underdeveloped regions, where the shortage of ophthalmologists hinders timely diagnosis. AI-assisted fundus image analysis has several advantages, such as high accuracy, reduced workload, and improved accessibility, but it requires a large amount of expert-annotated data to build reliable models. To address this dilemma, we propose a general self-supervised machine learning framework that can handle diverse fundus diseases from unlabeled fundus images. Our method's AUC surpasses existing supervised approaches by 15.7%, and even exceeds performance of a single human expert. Furthermore, our model adapts well to various datasets from different regions, races, and heterogeneous image sources or qualities from multiple cameras or devices. Our method offers a label-free general framework to diagnose fundus diseases, which could potentially benefit telehealth programs for early screening of people at risk of vision loss.

Failure to recognize samples from the classes unseen during training is a major limitation of artificial intelligence in the real-world implementation for recognition and classification of retinal anomalies. We established an uncertainty-inspired open-set (UIOS) model, which was trained with fundus images of 9 retinal conditions. Besides assessing the probability of each category, UIOS also calculated an uncertainty score to express its confidence. Our UIOS model with thresholding strategy achieved an F1 score of 99.55%, 97.01% and 91.91% for the internal testing set, external target categories (TC)-JSIEC dataset and TC-unseen testing set, respectively, compared to the F1 score of 92.20%, 80.69% and 64.74% by the standard AI model. Furthermore, UIOS correctly predicted high uncertainty scores, which would prompt the need for a manual check in the datasets of non-target categories retinal diseases, low-quality fundus images, and non-fundus images. UIOS provides a robust method for real-world screening of retinal anomalies.

In ophthalmology, early fundus screening is an economic and effective way to prevent blindness caused by ophthalmic diseases. Clinically, due to the lack of medical resources, manual diagnosis is time-consuming and may delay the condition. With the development of deep learning, some researches on ophthalmic diseases have achieved good results, however, most of them are just based on one disease. During fundus screening, ophthalmologists usually give diagnoses of multi-disease on binocular fundus image, so we release a dataset with 8 diseases to meet the real medical scene, which contains 10,000 fundus images from both eyes of 5,000 patients. We did some benchmark experiments on it through some state-of-the-art deep neural networks. We found simply increasing the scale of network cannot bring good results for multi-disease classification, and a well-structured feature fusion method combines characteristics of multi-disease is needed. Through this work, we hope to advance the research of related fields.