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

Hemal Mehta; Adnan Tufail; Vincent Daien; Aaron Y Lee; Vuong Nguyen; Mehmet Ozturk; Daniel Barthelmes; Mark C Gillies

doi:10.1016/j.preteyeres.2017.12.002

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

Prog Retin Eye Res. 2018 Jul:65:127-146. doi: 10.1016/j.preteyeres.2017.12.002. Epub 2018 Jan 2.

Authors

Hemal Mehta¹, Adnan Tufail², Vincent Daien³, Aaron Y Lee⁴, Vuong Nguyen⁵, Mehmet Ozturk⁶, Daniel Barthelmes⁷, Mark C Gillies⁸

Affiliations

¹ Macula Research Group, Save Sight Institute, University of Sydney, Sydney, Australia; Royal Free London NHS Foundation Trust, London, UK.
² Moorfields Eye Hospital NHS Foundation Trust and University College London Institute of Ophthalmology, London, UK.
³ Macula Research Group, Save Sight Institute, University of Sydney, Sydney, Australia; University of Montpellier and INSERM 1061, Montpellier, France.
⁴ Department of Ophthalmology, University of Washington, Seattle, USA.
⁵ Macula Research Group, Save Sight Institute, University of Sydney, Sydney, Australia.
⁶ Royal Free London NHS Foundation Trust, London, UK.
⁷ Macula Research Group, Save Sight Institute, University of Sydney, Sydney, Australia; Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁸ Macula Research Group, Save Sight Institute, University of Sydney, Sydney, Australia. Electronic address: mark.gillies@sydney.edu.au.

PMID: 29305324
DOI: 10.1016/j.preteyeres.2017.12.002

Abstract

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.

Keywords: Age-related macular degeneration; Neovascular; Real-world outcomes; Registry; Vascular endothelial growth factor inhibitor.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Angiogenesis Inhibitors / therapeutic use*
Choroidal Neovascularization / drug therapy*
Choroidal Neovascularization / physiopathology
Humans
Intravitreal Injections
Macular Degeneration / drug therapy*
Macular Degeneration / physiopathology
Vascular Endothelial Growth Factor A
Visual Acuity / physiology

Substances

Angiogenesis Inhibitors
Vascular Endothelial Growth Factor A