Multimodal large language models in ophthalmology: Diagnostic accuracy and the risk of metadata-induced confirmation bias
Abstract
• GPT-5.2 demonstrated superior and more robust performance in binarized diabetic retinopathy referral tasks compared to GPT-4 and Gemini 3. • Gemini 3 exhibited significant vulnerability to "textual confirmation bias," leading to changes in clinical recommendations in over 50% of cases when presented with conflicting metadata. • All multimodal LLMs exhibited degenerate predictive behavior on glaucoma tasks, with near-zero Kappa scores indicating a lack of true discriminative ability for spatial nerve assessment. • GPT-4 and GPT-5.2 displayed "vision-dominant" stability, maintaining initial visual interpretations even when faced with contradictory clinical narratives. • Native multimodal integration enables direct pixel-level processing, yet LLMs currently serve better as integrative clinical assistants than as standalone diagnostic tools. To evaluate the diagnostic capability of state-of-the-art multimodal Large Language Models (LLMs) in autonomous interpretation of raw image input (fundus photographs) and to assess their susceptibility to "textual confirmation bias" when integrated with real or synthetic clinical metadata. Retrospective diagnostic validation study. A cohort of 265 retinal fundus images was sampled from the Brazilian Ophthalmological Dataset (mBRSET), representing a diverse distribution of diabetic retinopathy stages and suspected glaucoma cases. Three LLMs (GPT-4, GPT-5.2, and Gemini 3) were evaluated via native multimodal integration. Each model was tested under three multimodal input conditions:(1) Image-Only Multimodal Input, (2) Metadata-Enhanced Multimodal Input, and (3) Synthetic Metadata Multimodal Input. Primary tasks included ICDR severity grading, binary DR referral, and an increased Vertical Cup-to-Disc Ratio (VCDR > 0.6). Metrics included accuracy, Cohen’s kappa, and macro F1-score. GPT-5.2 emerged as the top performer for DR tasks, achieving the highest ICDR accuracy (72.2%) and DR referral kappa (0.51). In contrast, all models demonstrated degenerate prediction behavior for glaucoma referral proxy, with moderate accuracy (76.3%) but near-zero kappa scores (
Fields of Study & Subjects
Artificial Intelligence in Healthcare and Education
Machine Learning in Healthcare
Multimodal Machine Learning Applications
Publication details
- Journal / source
- AJO International
- Publisher
- Elsevier BV
- Volume
- 3
- Issue
- 2
- Pages
- 100253–100253
- Publication date
- 2 April 2026
- Language
- EN