Real-world outcomes in patients with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor inhibitors

Clinical trials identified intravitreal vascular endothelial growth factor inhibitors (anti-VEGF agents) have the potential to stabilise or even improve visual acuity outcomes in neovascular age-related macular degeneration (AMD), a sight-threatening disease. Real-world evidence allows us to assess whether results from randomised controlled trials can be applied to the general population. We describe the development of global registries, in particular the Fight Retinal Blindness! registry that originated in Australia, the United Kingdom AMD Electronic Medical Records User Group and the IRIS registry in the USA. Real-world observations relating to efficacy, safety and resource utilisation of intravitreal anti-VEGF therapy for neovascular AMD are then summarised. Novel observations that would have been challenging to identify in a clinical trial setting are then highlighted, including the risk of late disease reactivation, outcomes in second versus first treated eyes, and the increased risk of posterior capsular rupture during cataract surgery in patients who have received intravitreal anti-VEGF therapy. We conclude by exploring future directions in the field. This includes the development of a global consensus on real-world outcome measures to allow greater comparison of results. Real-world neovascular AMD outcome registries can be linked with other databases to determine systemic safety or genetic predictors of treatment efficacy. Machine learning offers opportunities to extract useful insights from “Big Data” often collected in these registries. Real-world registries could be used by drug regulatory authorities and industry as an alternative to more costly and time-consuming phase 4 clinical trials, potentially allowing medication costs to be based on outcomes achieved.