Predictors of limited early response to anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration with machine learning feature importance

PURPOSE: Patients with neovascular age-related macular degeneration (nAMD) have varying responses to anti-vascular endothelial growth factor injections. Limited early response (LER) after three monthly loading doses is associated with poor long-term vision outcomes. This study predicts LER in nAMD and uses feature importance analysis to explain how baseline variables influence predicted LER risk. METHODS: Baseline age, best visual acuity (BVA), central subfield thickness (CST), and baseline and 3 months intraretinal fluid (IRF) and subretinal fluid (SRF) for 286 eyes were collected in a retrospective clinical chart review. At month 3, LER was defined as the presence of fluid, while early response (ER) was the absence thereof. Decision tree classification and feature importance methods determined the influence of baseline age, BVA, CST, IRF, and SRF, on predicted LER risk. RESULTS: One hundred and sixty-seven eyes were LERs and 119 were ERs. The algorithm achieved area under the curve = 0.66 in predicting LER. Baseline SRF was most important for predicting LER while age, BVA, CST, and IRF were somewhat less important. Nonlinear trends were observed between baseline variables and predicted LER risk. Zones of increased predicted LER risk were identified, including age <74 years, and CST <290 or >350 μm, IRF >750 nL, and SRF >150 nL. CONCLUSION: These findings explain baseline variable importance for predicting LER and show SRF to be the most important. The nonlinear impact of baseline variables on predicted risk is shown, increasing understanding of LER and aiding clinicians in assessing personalized LER risk.