Developing and validating an explainable clinlabomics-based machine-learning model for screening primary angle-closure glaucoma in the context of PPPM.

Background: Primary angle-closure glaucoma (PACG) is a common cause of blindness. Early screening is critical to prevent vision loss, yet current methods rely on specialized ophthalmic imaging, which are resource-intensive and reactive, detecting structural damage only after symptom onset. Therefore, we propose a novel clinlabomics-based machine learning prediction model as a screening tool to stratify individuals at high risk for glaucoma, enabling targeted ophthalmic evaluations, preventing progression of optic nerve damage, and facilitating personalized, long-term monitoring in alignment with the principles of predictive, preventive, and personalized medicine (PPPM/3PM).

Methods: This is a multicenter, retrospective study. We retrieved clinical laboratory data from digital medical records between April 2016 and April 2021 in the Eye and ENT Hospital of Fudan University as a discovery set, consisting of 949 normal subjects and 1152 PACG patients. The internal validation was conducted on the dataset of 646 normal subjects and 657 PACG patients from June 2021 to October 2024, also from the Eye and ENT Hospital of Fudan University; the external validation was performed on a dataset of 246 normal subjects and 136 PACG patients from March 2023 to June 2024, from Shanghai Xuhui Central Hospital and Wanbei Coal Electric Group General Hospital. Based on whether there was optic nerve damage, patients were categorized into early PACG patients, namely primary angle closure(PAC) patients, and non-early PACG. Specifically, in the internal validation cohort of 657 PACG patients, 160 were PAC. In the external validation cohort of 136 PACG patients, 41 were PAC. With the inclusion of 50 features, 12 machine learning models were selected and compared to develop the screening model. The feature reduction was performed by SHAP model and Delong test, and the final model was explained by SHAP method. The evaluation parameters of the models include AUC, AUCPR, sensitivity, specificity, and accuracy.

Results: A total of 1841 normal subjects and 1945 PACG patients were included in the study. Among the 12 machine learning models, 4 models, LGBM (AUC = 0.92), XGB (AUC = 0.92), Ada (AUC = 0.91), and GB (AUC = 0.91), performed better than others (P > 0.05). After feature reduction based on feature importance ranking, a final LGBM model of accurate screening PACG ability with six features including TT, PDW, MCV, APTT, TC, and PT was developed, achieving AUC of 0.91, AUCPR of 0.94, sensitivity of 0.89, specificity of 0.79, PPV of 0.84, NPV of 0.85, accuracy of 0.84, and F1 score of 0.86. This final model maintained strong performance in internal validation (AUC = 0.87, accuracy = 0.83, F1 score = 0.85) and external validation (AUC = 0.85, accuracy = 0.89, F1 score = 0.84). The screening efficacy of the final model for PAC was also assessed, where the ROC was 0.85 in the internal validation and 0.84 in the external validation. To enhance its practical application and dissemination, the final model was transformed into an accessible web application.

Conclusion: This study establishes a clinically applicable clinlabomics-based model that implements PPPM principles for glaucoma management through routine blood parameters. Our predictive model enables early identification of high-risk PACG patients, while also facilitating cost-effective population screening and personalized risk assessment through explainable artificial intelligence. The current study demonstrates that routine blood parameters serve as critical indicators for glaucoma risk stratification, predictive diagnosis, and targeted intervention. Consequently, this innovative screening approach provides an essential tool for optimizing clinical outcomes in high-risk populations and improving glaucoma care accessibility, particularly in underserved communities with limited ophthalmic resources.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-025-00419-2.