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15.12.2017 | review | Ausgabe 5/2019

Spektrum der Augenheilkunde 5/2019

Systemic side effects after intravitreal administration of antivascular endothelial growth factors for neovascular age-related macular degeneration

A systematic review

Spektrum der Augenheilkunde > Ausgabe 5/2019
Alina Popa-Cherecheanu, Raluca Iancu, Danut Vasile, Ruxandra Pirvulescu, Aida Geamanu, Cristina Coman, George Iancu



Age-related macular degeneration is a chronic and progressive disease of the retina that occurs with increasing frequency with age, representing the leading cause of irreversible blindness in patients over 50 years of age. The loss of visual perception occurs due to neovascular proliferation. Antivascular endothelial growth factors revolutionized the treatment of exudative age-related macular degeneration.

Materials and methods

Our aim was to assess the systemic safety of intravitreal administration of ranibizumab, bevacizumab, or aflibercept in patients with neovascular age-related macular degeneration. The study was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. The primary outcomes included: all-cause death and all serious systemic adverse events. We calculated the incidence of systemic adverse events, relative risk of the outcomes, and 95% confidence intervals.


This review included representative outcome data on 12,292 participants from 24 trials, which included both men and women aged 50 years or older with neovascular age-related macular degeneration. In bevacizumab-treated patients, the most frequent systemic adverse event in our analysis was nonocular hemorrhage. In ranibizumab-treated patients, systemic adverse events were not dose-dependent. The number of systemic adverse events was similar in patients treated with ranibizumab (4.73%) or with aflibercept (4.76%).


This meta-analysis did not find any statistically significant difference regarding the occurrence of death or other serious systemic adverse events such as treatment-emergent hypertension, myocardial infarction, stroke, or nonocular hemorrhage after intravitreal use of antivascular endothelial growth factors.

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