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Review
March 22, 2018

Overview of Systematic Reviews and Meta-analyses on Systemic Adverse Events Associated With Intravitreal Anti–Vascular Endothelial Growth Factor Medication Use

Author Affiliations
  • 1Ophthalmology Department, Centre Hospitalier Régional Universitaire, Bretonneau Hospital, Tours, France
  • 2Cardiology Department, Centre Hospitalier Régional Universitaire Trousseau Hospital, Tours, France
  • 3Unit EA4245, University Francois Rabelais, Tours, France
  • 4Department of Pharmacology, Centre Hospitalier Régional Universitaire Tours, France
  • 5Unité Mixte de Recherche 7292, Centre Nationnal de la Recherche Scientifique, Tours, France
  • 6Génétique, Immunothérapie, Chimie et Cancer, Department of Medical Research, University François-Rabelais, Tours, France
JAMA Ophthalmol. Published online March 22, 2018. doi:10.1001/jamaophthalmol.2018.0002
Key Points

Question  Is there an increased risk of systemic adverse events following intravitreal anti–vascular endothelial growth factor treatments?

Findings  No increased risks were identified in patients receiving the treatments compared with controls. This overview of meta-analyses reviews suggest that anti-VEGF treatments do not increase the risk of systemic adverse events, but caution might be taken in older patients with age-related macular degeneration who may be at higher risk of haemorrhagic events when receiving ranibizumab.

Meaning  Intravitreal anti-VEGF treatments seem to be safe, but caution should be taken especially in older patients regarding haemorrhagic systemic adverse events.

Abstract

Importance  The systemic safety of intravitreal anti–vascular endothelial growth factor (anti-VEGF) medications is still a matter of debate.

Objective  This overview of systematic reviews evaluates systemic adverse events associated with intravitreal anti-VEGF treatments in patients with neovascular age-related macular degeneration, diabetic macular edema, or retinal vein occlusion.

Design, Evidence, and Reporting  This systematic search of PubMed and the Cochrane Central Register of Controlled Trials database includes meta-analyses and systematic reviews. We describe the summary measures of association between anti-VEGF treatments and outcomes reported in each systematic review.

Main Outcomes and Measures  The quality of the systematic reviews was assessed with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and A Measurement Tool to Assess Systematic Reviews (AMSTAR) checklist, version 1.

Findings  We retrieved 21 systematic reviews published between January 1, 2011, and June 30, 2016. Of these, 11 analyzed systemic adverse events as the primary outcome. The median (interquartile range) PRISMA and AMSTAR scores were 23 of 27 (15-27) and 8 of 11 (5-11), respectively, but 5 reviews (25%) scored below 20 and 7, respectively. All reviews used an objective scale to assess methodological risk of bias in their included studies, the Cochrane Risk of Bias Tool being the most commonly used (16 reviews [76%]). Anti-VEGF treatments did not increase the risk of systemic adverse events when compared with control regimens; similarly, there was no increase in systematic adverse events when treatment was given on a monthly schedule vs an as-needed regimen. Compared with ranibizumab, bevacizumab did not appear to be associated with an increase in the risk of systemic adverse events in the most recent and exhaustive reviews. Compared with control treatments, ranibizumab may be associated with an increase in the risk of nonocular hemorrhage in patients with age-related macular degeneration.

Conclusions and Relevance  This overview of reviews and meta-analyses suggest that anti-VEGF treatments do not increase the risk of systemic adverse events, but that caution might be advisable in older patients with age-related macular degeneration who may be at higher risk of hemorrhagic events when receiving ranibizumab.

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