Vision impairment affects millions globally, and early detection is critical to preventing irreversible vision loss. Ophthalmology workflows require clinicians to integrate medical images, structured clinical data, and free-text notes to determine disease severity and management, which is time-consuming and burdensome. Recent multimodal large language models (MLLMs) show promise, but existing general and medical MLLMs perform poorly in ophthalmology, and few ophthalmology-specific MLLMs are openly available. We present VOLMO (Versatile and Open Large Models for Ophthalmology), a model-agnostic, data-open framework for developing ophthalmology-specific MLLMs. VOLMO includes three stages: ophthalmology knowledge pretraining on 86,965 image-text pairs from 26,569 articles across 82 journals; domain task fine-tuning on 26,929 annotated instances spanning 12 eye conditions for disease screening and severity classification; and multi-step clinical reasoning on 913 patient case reports for assessment, planning, and follow-up care. Using this framework, we trained a compact 2B-parameter MLLM and compared it with strong baselines, including InternVL-2B, LLaVA-Med-7B, MedGemma-4B, MedGemma-2
Current benchmarks evaluating large language models (LLMs) in ophthalmology are limited in scope and disproportionately prioritise accuracy. We introduce BELO (BEnchmarking LLMs for Ophthalmology), a standardized and comprehensive evaluation benchmark developed through multiple rounds of expert checking by 13 ophthalmologists. BELO assesses ophthalmology-related clinical accuracy and reasoning quality. Using keyword matching and a fine-tuned PubMedBERT model, we curated ophthalmology-specific multiple-choice-questions (MCQs) from diverse medical datasets (BCSC, MedMCQA, MedQA, BioASQ, and PubMedQA). The dataset underwent multiple rounds of expert checking. Duplicate and substandard questions were systematically removed. Ten ophthalmologists refined the explanations of each MCQ's correct answer. This was further adjudicated by three senior ophthalmologists. To illustrate BELO's utility, we evaluated six LLMs (OpenAI o1, o3-mini, GPT-4o, DeepSeek-R1, Llama-3-8B, and Gemini 1.5 Pro) using accuracy, macro-F1, and five text-generation metrics (ROUGE-L, BERTScore, BARTScore, METEOR, and AlignScore). In a further evaluation involving human experts, two ophthalmologists qualitatively revie
Large language models (LLMs) show potential for ophthalmic clinical reasoning, yet individual models risk introducing harm. We evaluated whether multi-agent LLM deliberative councils improve diagnostic performance and mitigate harm compared to individual LLMs. In a comparative cross-sectional study, we assessed 12 individual LLMs and three multi-agent councils on 100 ophthalmology clinical vignettes. Each council comprised four models assembled by type: proprietary flagship, proprietary fast, and open-source. Models independently answered a vignette, anonymously ranked one another's responses, and a designated chair synthesized all responses and peer reviews into a final answer. Councils consistently outperformed pooled individual models across all three tiers. Accuracy improved for proprietary flagship (95.0% vs 90.8%; risk difference [RD]: 4.25 [95% CI: 0.45, 8.05]), proprietary fast (96.0% vs 86.5%; RD: 9.50 [5.31, 13.59]), and open-source councils (91.0% vs 83.2%; RD: 7.75 [4.17, 11.33]). Harm rates declined for proprietary flagship (10.0% vs 22.5%; RD: -12.50 [-16.86, -8.14]), proprietary fast (16.0% vs 31.8%; RD: -15.75 [-21.49, -10.01]), and open-source councils (22.0% vs 38
Question: What is the performance and reasoning ability of OpenAI o1 compared to other large language models in addressing ophthalmology-specific questions? Findings: This study evaluated OpenAI o1 and five LLMs using 6,990 ophthalmological questions from MedMCQA. O1 achieved the highest accuracy (0.88) and macro-F1 score but ranked third in reasoning capabilities based on text-generation metrics. Across subtopics, o1 ranked first in ``Lens'' and ``Glaucoma'' but second to GPT-4o in ``Corneal and External Diseases'', ``Vitreous and Retina'' and ``Oculoplastic and Orbital Diseases''. Subgroup analyses showed o1 performed better on queries with longer ground truth explanations. Meaning: O1's reasoning enhancements may not fully extend to ophthalmology, underscoring the need for domain-specific refinements to optimize performance in specialized fields like ophthalmology.
Recent advances in reasoning-focused large language models (LLMs) mark a shift from general LLMs toward models designed for complex decision-making, a crucial aspect in medicine. However, their performance in specialized domains like ophthalmology remains underexplored. This study comprehensively evaluated and compared the accuracy and reasoning capabilities of four newly developed reasoning-focused LLMs, namely DeepSeek-R1, OpenAI o1, o3-mini, and Gemini 2.0 Flash-Thinking. Each model was assessed using 5,888 multiple-choice ophthalmology exam questions from the MedMCQA dataset in zero-shot setting. Quantitative evaluation included accuracy, Macro-F1, and five text-generation metrics (ROUGE-L, METEOR, BERTScore, BARTScore, and AlignScore), computed against ground-truth reasonings. Average inference time was recorded for a subset of 100 randomly selected questions. Additionally, two board-certified ophthalmologists qualitatively assessed clarity, completeness, and reasoning structure of responses to differential diagnosis questions.O1 (0.902) and DeepSeek-R1 (0.888) achieved the highest accuracy, with o1 also leading in Macro-F1 (0.900). The performance of models across the text-ge
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 p
This paper introduces the modeling of circular data with excess zeros under a longitudinal framework, where the response is a circular variable and the covariates can be both linear and circular in nature. In the literature, various circular-circular and circular-linear regression models have been studied and applied to different real-world problems. However, there are no models for addressing zero-inflated circular observations in the context of longitudinal studies. Motivated by a real case study, a mixed-effects two-stage model based on the projected normal distribution is proposed to handle such issues. The interpretation of the model parameters is discussed and identifiability conditions are derived. A Bayesian methodology based on Gibbs sampling technique is developed for estimating the associated model parameters. Simulation results show that the proposed method outperforms its competitors in various situations. A real dataset on post-operative astigmatism is analyzed to demonstrate the practical implementation of the proposed methodology. The use of the proposed method facilitates effective decision-making for treatment choices and in the follow-up phases.
Vision-threatening eye diseases pose a major global health burden, with timely diagnosis limited by workforce shortages and restricted access to specialized care. While multimodal large language models (MLLMs) show promise for medical image interpretation, advancing MLLMs for ophthalmology is hindered by the lack of comprehensive benchmark datasets suitable for evaluating generative models. We present a large-scale multimodal ophthalmology benchmark comprising 32,633 instances with multi-granular annotations across 12 common ophthalmic conditions and 5 imaging modalities. The dataset integrates imaging, anatomical structures, demographics, and free-text annotations, supporting anatomical structure recognition, disease screening, disease staging, and demographic prediction for bias evaluation. This work extends our preliminary LMOD benchmark with three major enhancements: (1) nearly 50% dataset expansion with substantial enlargement of color fundus photography; (2) broadened task coverage including binary disease diagnosis, multi-class diagnosis, severity classification with international grading standards, and demographic prediction; and (3) systematic evaluation of 24 state-of-the
Purpose: To evaluate the accuracy and reasoning ability of DeepSeek-R1 and three other recently released large language models (LLMs) in bilingual complex ophthalmology cases. Methods: A total of 130 multiple-choice questions (MCQs) related to diagnosis (n = 39) and management (n = 91) were collected from the Chinese ophthalmology senior professional title examination and categorized into six topics. These MCQs were translated into English using DeepSeek-R1. The responses of DeepSeek-R1, Gemini 2.0 Pro, OpenAI o1 and o3-mini were generated under default configurations between February 15 and February 20, 2025. Accuracy was calculated as the proportion of correctly answered questions, with omissions and extra answers considered incorrect. Reasoning ability was evaluated through analyzing reasoning logic and the causes of reasoning error. Results: DeepSeek-R1 demonstrated the highest overall accuracy, achieving 0.862 in Chinese MCQs and 0.808 in English MCQs. Gemini 2.0 Pro, OpenAI o1, and OpenAI o3-mini attained accuracies of 0.715, 0.685, and 0.692 in Chinese MCQs (all P<0.001 compared with DeepSeek-R1), and 0.746 (P=0.115), 0.723 (P=0.027), and 0.577 (P<0.001) in English MCQ
The emergence of artificial intelligence (AI), particularly deep learning (DL), has marked a new era in the realm of ophthalmology, offering transformative potential for the diagnosis and treatment of posterior segment eye diseases. This review explores the cutting-edge applications of DL across a range of ocular conditions, including diabetic retinopathy, glaucoma, age-related macular degeneration, and retinal vessel segmentation. We provide a comprehensive overview of foundational ML techniques and advanced DL architectures, such as CNNs, attention mechanisms, and transformer-based models, highlighting the evolving role of AI in enhancing diagnostic accuracy, optimizing treatment strategies, and improving overall patient care. Additionally, we present key challenges in integrating AI solutions into clinical practice, including ensuring data diversity, improving algorithm transparency, and effectively leveraging multimodal data. This review emphasizes AI's potential to improve disease diagnosis and enhance patient care while stressing the importance of collaborative efforts to overcome these barriers and fully harness AI's impact in advancing eye care.
Medical Large Vision-Language Models (Med-LVLMs) demonstrate significant potential in healthcare, but their reliance on general medical data and coarse-grained global visual understanding limits them in intelligent ophthalmic diagnosis. Currently, intelligent ophthalmic diagnosis faces three major challenges: (i) Data. The lack of deeply annotated, high-quality, multi-modal ophthalmic visual instruction data; (ii) Benchmark. The absence of a comprehensive and systematic benchmark for evaluating diagnostic performance; (iii) Model. The difficulty of adapting holistic visual architectures to fine-grained, region-specific ophthalmic lesion identification. In this paper, we propose the Eyecare Kit, which systematically tackles the aforementioned three key challenges with the tailored dataset, benchmark and model: First, we construct a multi-agent data engine with real-life ophthalmology data to produce Eyecare-100K, a high-quality ophthalmic visual instruction dataset. Subsequently, we design Eyecare-Bench, a benchmark that comprehensively evaluates the overall performance of LVLMs on intelligent ophthalmic diagnosis tasks across multiple dimensions. Finally, we develop the EyecareGPT,
Vision impairment and blindness are a major global health challenge where gaps in the ophthalmology workforce limit access to specialist care. We evaluate AMIE, a medically fine-tuned conversational system based on Gemini with integrated web search and self-critique reasoning, using real-world clinical vignettes that reflect scenarios a general ophthalmologist would be expected to manage. We conducted two complementary evaluations: (1) a human-AI interactive diagnostic reasoning study in which ophthalmologists recorded initial differentials and plans, then reviewed AMIE's structured output and revised their answers; and (2) a masked preference and quality study comparing AMIE's narrative outputs with case author reference answers using a predefined rubric. AMIE showed standalone diagnostic performance comparable to clinicians at baseline. Crucially, after reviewing AMIE's responses, ophthalmologists tended to rank the correct diagnosis higher, reached greater agreement with one another, and enriched their investigation and management plans. Improvements were observed even when AMIE's top choice differed from or underperformed the clinician baseline, consistent with a complementary
Large language models (LLMs) have shown significant promise across various medical applications, with ophthalmology being a notable area of focus. Many ophthalmic tasks have shown substantial improvement through the integration of LLMs. However, before these models can be widely adopted in clinical practice, evaluating their capabilities and identifying their limitations is crucial. To address this research gap and support the real-world application of LLMs, we introduce the OphthBench, a specialized benchmark designed to assess LLM performance within the context of Chinese ophthalmic practices. This benchmark systematically divides a typical ophthalmic clinical workflow into five key scenarios: Education, Triage, Diagnosis, Treatment, and Prognosis. For each scenario, we developed multiple tasks featuring diverse question types, resulting in a comprehensive benchmark comprising 9 tasks and 591 questions. This comprehensive framework allows for a thorough assessment of LLMs' capabilities and provides insights into their practical application in Chinese ophthalmology. Using this benchmark, we conducted extensive experiments and analyzed the results from 39 popular LLMs. Our evaluati
The prevalence of vision-threatening eye diseases is a significant global burden, with many cases remaining undiagnosed or diagnosed too late for effective treatment. Large vision-language models (LVLMs) have the potential to assist in understanding anatomical information, diagnosing eye diseases, and drafting interpretations and follow-up plans, thereby reducing the burden on clinicians and improving access to eye care. However, limited benchmarks are available to assess LVLMs' performance in ophthalmology-specific applications. In this study, we introduce LMOD, a large-scale multimodal ophthalmology benchmark consisting of 21,993 instances across (1) five ophthalmic imaging modalities: optical coherence tomography, color fundus photographs, scanning laser ophthalmoscopy, lens photographs, and surgical scenes; (2) free-text, demographic, and disease biomarker information; and (3) primary ophthalmology-specific applications such as anatomical information understanding, disease diagnosis, and subgroup analysis. In addition, we benchmarked 13 state-of-the-art LVLM representatives from closed-source, open-source, and medical domains. The results demonstrate a significant performance d
Large language models (LLMs) such as GPT-5 integrate advanced reasoning capabilities that may improve performance on complex medical question-answering tasks. For this latest generation of reasoning models, the configurations that maximize both accuracy and cost-efficiency have yet to be established. We evaluated 12 configurations of OpenAI's GPT-5 series (three model tiers across four reasoning effort settings) alongside o1-high, o3-high, and GPT-4o, using 260 closed-access multiple-choice questions from the American Academy of Ophthalmology Basic Clinical Science Course (BCSC) dataset. The primary outcome was multiple-choice accuracy; secondary outcomes included head-to-head ranking via a Bradley-Terry model, rationale quality assessment using a reference-anchored, pairwise LLM-as-a-judge framework, and analysis of accuracy-cost trade-offs using token-based cost estimates. GPT-5-high achieved the highest accuracy (0.965; 95% CI, 0.942-0.985), outperforming all GPT-5-nano variants (P < .001), o1-high (P = .04), and GPT-4o (P < .001), but not o3-high (0.958; 95% CI, 0.931-0.981). GPT-5-high ranked first in both accuracy (1.66x stronger than o3-high) and rationale quality (1.1
Purpose: To assess the alignment of GPT-4-based evaluation to human clinician experts, for the evaluation of responses to ophthalmology-related patient queries generated by fine-tuned LLM chatbots. Methods: 400 ophthalmology questions and paired answers were created by ophthalmologists to represent commonly asked patient questions, divided into fine-tuning (368; 92%), and testing (40; 8%). We find-tuned 5 different LLMs, including LLAMA2-7b, LLAMA2-7b-Chat, LLAMA2-13b, and LLAMA2-13b-Chat. For the testing dataset, additional 8 glaucoma QnA pairs were included. 200 responses to the testing dataset were generated by 5 fine-tuned LLMs for evaluation. A customized clinical evaluation rubric was used to guide GPT-4 evaluation, grounded on clinical accuracy, relevance, patient safety, and ease of understanding. GPT-4 evaluation was then compared against ranking by 5 clinicians for clinical alignment. Results: Among all fine-tuned LLMs, GPT-3.5 scored the highest (87.1%), followed by LLAMA2-13b (80.9%), LLAMA2-13b-chat (75.5%), LLAMA2-7b-Chat (70%) and LLAMA2-7b (68.8%) based on the GPT-4 evaluation. GPT-4 evaluation demonstrated significant agreement with human clinician rankings, with S
IMPORTANCE The response effectiveness of different large language models (LLMs) and various individuals, including medical students, graduate students, and practicing physicians, in pediatric ophthalmology consultations, has not been clearly established yet. OBJECTIVE Design a 100-question exam based on pediatric ophthalmology to evaluate the performance of LLMs in highly specialized scenarios and compare them with the performance of medical students and physicians at different levels. DESIGN, SETTING, AND PARTICIPANTS This survey study assessed three LLMs, namely ChatGPT (GPT-3.5), GPT-4, and PaLM2, were assessed alongside three human cohorts: medical students, postgraduate students, and attending physicians, in their ability to answer questions related to pediatric ophthalmology. It was conducted by administering questionnaires in the form of test papers through the LLM network interface, with the valuable participation of volunteers. MAIN OUTCOMES AND MEASURES Mean scores of LLM and humans on 100 multiple-choice questions, as well as the answer stability, correlation, and response confidence of each LLM. RESULTS GPT-4 performed comparably to attending physicians, while ChatGPT (
We introduce an annotated corpus of 600 ophthalmology notes labeled with detailed spatial and contextual information of ophthalmic entities. We extend our previously proposed frame semantics-based spatial representation schema, Rad-SpatialNet, to represent spatial language in ophthalmology text, resulting in the Eye-SpatialNet schema. The spatially-grounded entities are findings, procedures, and drugs. To accurately capture all spatial details, we add some domain-specific elements in Eye-SpatialNet. The annotated corpus contains 1715 spatial triggers, 7308 findings, 2424 anatomies, and 9914 descriptors. To automatically extract the spatial information, we employ a two-turn question answering approach based on the transformer language model BERT. The results are promising, with F1 scores of 89.31, 74.86, and 88.47 for spatial triggers, Figure, and Ground frame elements, respectively. This is the first work to represent and extract a wide variety of clinical information in ophthalmology. Extracting detailed information can benefit ophthalmology applications and research targeted toward disease progression and screening.
Despite the potential of Large Language Models (LLMs) in medicine, they may generate responses lacking supporting evidence or based on hallucinated evidence. While Retrieval Augment Generation (RAG) is popular to address this issue, few studies implemented and evaluated RAG in downstream domain-specific applications. We developed a RAG pipeline with 70,000 ophthalmology-specific documents that retrieve relevant documents to augment LLMs during inference time. In a case study on long-form consumer health questions, we systematically evaluated the responses including over 500 references of LLMs with and without RAG on 100 questions with 10 healthcare professionals. The evaluation focuses on factuality of evidence, selection and ranking of evidence, attribution of evidence, and answer accuracy and completeness. LLMs without RAG provided 252 references in total. Of which, 45.3% hallucinated, 34.1% consisted of minor errors, and 20.6% were correct. In contrast, LLMs with RAG significantly improved accuracy (54.5% being correct) and reduced error rates (18.8% with minor hallucinations and 26.7% with errors). 62.5% of the top 10 documents retrieved by RAG were selected as the top referenc
Domain specific large language models are increasingly used to support patient education, triage, and clinical decision making in ophthalmology, making rigorous evaluation essential to ensure safety and accuracy. This study evaluated four small medical LLMs Meerkat-7B, BioMistral-7B, OpenBioLLM-8B, and MedLLaMA3-v20 in answering ophthalmology related patient queries and assessed the feasibility of LLM based evaluation against clinician grading. In this cross sectional study, 180 ophthalmology patient queries were answered by each model, generating 2160 responses. Models were selected for parameter sizes under 10 billion to enable resource efficient deployment. Responses were evaluated by three ophthalmologists of differing seniority and by GPT-4-Turbo using the S.C.O.R.E. framework assessing safety, consensus and context, objectivity, reproducibility, and explainability, with ratings assigned on a five point Likert scale. Agreement between LLM and clinician grading was assessed using Spearman rank correlation, Kendall tau statistics, and kernel density estimate analyses. Meerkat-7B achieved the highest performance with mean scores of 3.44 from Senior Consultants, 4.08 from Consulta