Systemic Factors Associated with Long-Term Glaucoma Progression – 10-year follow-up results based on electronic medical records

Abstract Glaucoma is a multifactorial disease where various systemic features are involved in the progression of the disease. Based on initial systemic profiles in electronic medical records (EMRs), this study aimed to develop a model predicting factors of long-term rapid retinal nerve fiber layer (RNFL) thinning over 5 years in 505 patients with primary open-angle glaucoma. Eyes with faster or slower RNFL thinning were stratified using a decision-tree model, and systemic and ophthalmic data were incorporated into the models based on random forest and permutation methods, with the models interpreted by Shapley additive explanation plots (SHAP). According to decision tree, higher lymphocyte ratio (> 34.65%) was the most important systemic variable discriminating faster or slower RNFL thinning. Higher mean corpuscular hemoglobin (> 32.05 pg) and alkaline phosphatase (> 88.0 IU/L) concentrations were distinguishing factors in the eyes with lymphocyte ratios > 34.65% and < 34.65%, respectively. SHAP demonstrated larger baseline RNFL thickness, greater fluctuation of intraocular pressure (IOP), and higher maximum IOP as strongest ophthalmic factors, while higher lymphocyte ratio and higher platelet counts as strongest systemic factors associated with faster RNFL thinning. Machine learning-based modeling identified several systemic factors as well as previously acknowledged ophthalmic risk factors associated with long-term rapid RNFL thinning.