Artificial intelligence has shown promise in medical imaging, yet most existing systems lack flexibility, interpretability, and adaptability - challenges especially pronounced in ophthalmology, where diverse imaging modalities are essential. We present EyeAgent, the first agentic AI framework for comprehensive and interpretable clinical decision support in ophthalmology. Using a large language model (DeepSeek-V3) as its central reasoning engine, EyeAgent interprets user queries and dynamically orchestrates 53 validated ophthalmic tools across 23 imaging modalities for diverse tasks including classification, segmentation, detection, image/report generation, and quantitative analysis. Stepwise ablation analysis demonstrated a progressive improvement in diagnostic accuracy, rising from a baseline of 69.71% (using only 5 general tools) to 80.79% when the full suite of 53 specialized tools was integrated. In an expert rating study on 200 real-world clinical cases, EyeAgent achieved 93.7% tool selection accuracy and received expert ratings of more than 88% across accuracy, completeness, safety, reasoning, and interpretability. In human-AI collaboration, EyeAgent matched or exceeded the performance of senior ophthalmologists and, when used as an assistant, improved overall diagnostic accuracy by 18.51% and report quality scores by 19%, with the greatest benefit observed among junior ophthalmologists. These findings establish EyeAgent as a scalable and trustworthy AI framework for ophthalmology and provide a blueprint for modular, multimodal, and clinically aligned next-generation AI systems.

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