Systemic Safety of Intravitreal Anti-vascular Endothelial Growth Factor Agents in Age-Related Macular Degeneration

Vaidehi S. Dedania; Sophie J. Bakri


Curr Opin Ophthalmol. 2016;27(3):224-243. 

In This Article


Despite the abundance of evidence supporting the efficacy of intravitreal anti-VEGF agents in the treatment of neovascular AMD, there is a lack of data on their safety. Many studies evaluating safety are not powered to detect infrequent events and current data are insufficient for investigating the incidence of adverse events and associated risk factors. For those studies evaluating adverse events as a primary end point, many are small, uncontrolled and retrospective.

Current data suggest intravitreal anti-VEGF agents are safe overall, although this is not conclusive. There may be a trend toward increased risk of overall SAE, ATE, stroke, cardiac failure, and nonocular hemorrhage in treated patients, especially those receiving bevacizumab. Until more definitive data emerge, patients should be considered for treatment on a case-by-case basis.[76] It may be prudent to defer treatment or use ranibizumab or aflibercept in patients with recent stroke (past 3 months). There is a notion that decreasing injection frequency can decrease the risk of nonocular SAE, but this was not supported by the findings in CATT[6,17] and IVAN.[15,16]

As many of the concerns surrounding the systemic safety of intravitreal anti-VEGF agents center on cardiovascular health, it is imperative that patients receiving these medications have regular systemic evaluations. Additionally, a pretreatment risk factor assessment, especially in patients with a history of stroke, may aid in prevention or early recognition of nonocular adverse events.

As the population of patients with neovascular AMD grows, the goal of future of treatment is to deliver optimal visual results with a reasonable safety profile, while decreasing treatment burden and containing costs.