Patients diagnosed with exudative neovascular age-related macular degeneration are commonly treated with anti-vascular endothelial growth factor (anti-VEGF) agents. However, response to treatment is heterogeneous, without a clinical explanation. Predicting suboptimal response at baseline will enable more efficient clinical trial designs for novel, future interventions and facilitate individualised therapies. In this multicentre study, we trained a multi-modal artificial intelligence (AI) system to identify suboptimal responders to the loading-phase of the anti-VEGF agent aflibercept from baseline characteristics. We collected clinical features and optical coherence tomography scans from 1720 eyes of 1612 patients between 2019 and 2021. We evaluated our AI system as a patient selection method by emulating hypothetical clinical trials of different sizes based on our test set. Our method detected up to 57.6% more suboptimal responders than random selection, and up to 24.2% more than any alternative selection criteria tested. Applying this method to the entry process of candidates into randomised controlled trials may contribute to the success of such trials and further inform personalised care.