medRxiv (Medicine)
2026-06-19
DOI: HASH:ca45b6227d704655138fe1a2f0586478
Purpose: To evaluate the performance of secure cloud-based large language models (LLMs) in extracting glaucoma diagnosis, type, and severity from free-text clinical notes in the electronic health record (EHR). Design: Retrospective chart review analysis. Participants: 1,250 subjects from the Bascom Palmer Ophthalmic Repository. Methods: Clinical notes of glaucoma-related encounters between 2014 and 2024 were extracted from the Bascom Palmer Ophthalmic Repository. Two fellowship-trained glaucoma specialists annotated clinical notes for glaucoma presence, type, and severity at the eye level. The dataset was split into development (10%), validation (10%), and test (80%) sets. Development and validation sets were used for prompt engineering and refinement, and the held-out test set was used for evaluation. Five LLMs (Claude Opus 4.6, DeepSeek-V3.2, GPT-5.2, Grok 4.1, and Qwen3.6-35B-A3B) were accessed via Azure AI Foundry within HIPAA-compliant containers. Model performance was assessed using standard metrics. Clinician-entered ICD-10 codes were also compared with adjudicated labels. Main Outcome Measures: Gwet AC1, accuracy, sensitivity, specificity, and F1-score. Results: Inter-grader agreement was high for glaucoma detection (Gwet AC1= 0.930 (95% CI: 0.917-0.945), type classification (Gwet AC1= 0.917 (95% CI: 0.904-0.930), and severity staging (Gwet AC1= 0.901 (95% CI: 0.884-0.916). For glaucoma diagnosis, LLMs demonstrated high overall accuracy, with Claude achieving 97.5%, DeepSeek 96.0%, GPT 96.2%, Grok 94.4%, and Qwen 95.5%. F1 scores for glaucoma detection ranged from 95.4% to 98.9% across models. For glaucoma type classification, accuracies were 97.1%, 94.2%, 94.2%, 94.0%, and 94.4% for Claude, DeepSeek, GPT, Grok, and Qwen, respectively. F1 scores for the most prevalent type (POAG) ranged from 96.3% to 98.9%. For severity staging, accuracies were 95.0%, 94.8%, 94.5%, 94.0%, and 95.2%, respectively, with F1 scores ranging from 89.7% to 96.3% across severity categories and models. ICD-10 codes demonstrated substantially lower performance for type and severity staging, with overall accuracies of 89.2% and 58.5%, respectively. Conclusions: Secure cloud-based LLMs accurately extracted glaucoma diagnosis, type, and severity information from free-text ophthalmology notes, achieving performance approaching expert clinician adjudication while substantially outperforming ICD-based phenotyping approaches, particularly for disease severity classification. These findings demonstrate the potential of LLMs to transform unstructured clinical documentation into scalable, research-ready phenotypic data for large-scale glaucoma cohort development and EHR-based ophthalmic research.