Is there an increased risk of systemic adverse events following intravitreal anti–vascular endothelial growth factor treatments?
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.
Intravitreal anti-VEGF treatments seem to be safe, but caution should be taken especially in older patients regarding haemorrhagic systemic adverse events.
The systemic safety of intravitreal anti–vascular endothelial growth factor (anti-VEGF) medications is still a matter of debate.
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.
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.
Thulliez M, Angoulvant D, Pisella P, Bejan-Angoulvant T. Overview of Systematic Reviews and Meta-analyses on Systemic Adverse Events Associated With Intravitreal Anti–Vascular Endothelial Growth Factor Medication Use. JAMA Ophthalmol. 2018;136(5):557–566. doi:10.1001/jamaophthalmol.2018.0002
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