Automated Multi-Class Classification of Retinal Pathologies: A Deep Learning Approach to Unified Ophthalmic Screening

<b>Background/Objectives</b>: The prevailing paradigm in ophthalmic AI involves siloed, single-disease models, which fails to address the complexity of differential diagnosis in clinical practice. This study aimed to develop and validate a unified deep learning framework for the automated multi-class classification of a wide spectrum of retinal pathologies from fundus photographs, moving beyond the single-disease paradigm to create a comprehensive screening tool. <b>Methods</b>: A publicly available dataset was manually curated by an ophthalmologist, resulting in 1841 images across nine classes, including Diabetic Retinopathy, Glaucoma, and Healthy retinas. After extensive data augmentation to mitigate class imbalance, three pre-trained CNN architectures (ResNet-152, EfficientNetV2, and a YOLOv11-based classifier) were comparatively evaluated. The models were trained using transfer learning and their performance was assessed on an independent test set using accuracy, macro-averaged F1-score, and Area Under the Curve (AUC). <b>Results</b>: The YOLOv11-based classifier demonstrated superior performance over the other architectures on the validation set. On the final independent test set, it achieved a robust overall accuracy of 0.861 and a macro-averaged F1-score of 0.861. The model yielded a validation set AUC of 0.961, which was statistically superior to both ResNet-152 (<i>p</i> < 0.001) and EfficientNetV2 (<i>p</i> < 0.01) as confirmed by the DeLong test. <b>Conclusions</b>: A unified deep learning framework, leveraging a YOLOv11 backbone, can accurately classify nine distinct retinal conditions from a single fundus photograph. This holistic approach moves beyond the limitations of single-disease algorithms, offering considerable promise as a comprehensive AI-driven screening tool to augment clinical decision-making and enhance diagnostic efficiency in ophthalmology.