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

A systematic review

Systemische Nebenwirkungen nach intravitrealer Verabreichung von Anti-VEGF-Faktoren bei neovaskulärer altersbedingter Makuladegeneration

Eine systematische Übersicht

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Summary

Background

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.

Results

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%).

Conclusion

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.

Zusammenfassung

Hintergrund

Die altersbedingte Makuladegeneration ist eine chronische und progressive Erkrankung der Netzhaut, die mit zunehmendem Alter gehäuft auftritt und die wichtigste Ursache für irreversible Blindheit bei Patienten über 50 Jahre darstellt. Zum Verlust der Sehfähigkeit bei der exsudativen Form der Erkrankung kommt es durch neovaskuläre Proliferation. Gegen vaskuläres endotheliales Wachstum wirkende Substanzen („anti-vascular endothelial growth factors“, Anti-VEGF-Faktoren) haben die Behandlung der exsudativen altersbedingte Makuladegeneration revolutioniert.

Material und Methoden

Das Ziel der vorliegenden Analyse war es, die systemische Sicherheit der intravitrealen Verabreichung von Ranibizumab, Bevacizumab und Aflibercept bei Patienten mit neovaskulärer altersbedingter Makuladegeneration zu untersuchen. Die Studie wurde nach der Checkliste „preferred reporting items for systematic reviews and meta-analyses“ (PRISMA) durchgeführt und dokumentiert. Primäre Zielvariablen waren Gesamtmortalität und alle schweren systemischen Nebenwirkungen. Es wurden die Inzidenz systemischer Nebenwirkungen, das relative Risiko und die 95%-Konfidenzintervalle berechnet. Die vorliegende Übersichtsarbeit enthält repräsentative Daten von 12.292 weiblichen und männlichen Teilnehmern über 50 Jahre, die an 24 Studien teilgenommen haben.

Ergebnisse

Zwischen der Inzidenz (4–5%) von systemischen Nebenwirkungen bei Ranibizumab (4,73%) und Aflibercept (4,76%) gab es keinen signifikanten Unterschied. Bei mit Bevacizumab behandelten Patienten bestand die häufigste systemische Nebenwirkung in der vorliegenden Studie in einer nichtokulären Blutung. Bei mit Ranibizumab behandelten Patienten wurde keine Dosisabhängigkeit hinsichtlich des Auftretens systemischer Nebenwirkungen festgestellt.

Schlussfolgerung

Die vorliegende Metaanalyse zeigt keinen signifikanten Unterschied in Bezug auf die Inzidenz von Todesfällen oder anderen schwerwiegenden Nebenwirkungen wie therapiebedingte Hypertension, Myokardinfarkt, Schlaganfall oder nichtokuläre Blutung nach intravitrealer Verabreichung verschiedener Anti-VEGF-Substanzen.

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Authors and Affiliations

  1. Carol Davila University of Medicine and Pharmacy, Tineretului Bvd 51, 040341, Bucharest, Romania

    Alina Popa-Cherecheanu, Raluca Iancu, Danut Vasile, Ruxandra Pirvulescu, Aida Geamanu, Cristina Coman & George Iancu

  2. Ophthalmology Department, Emergency University Hospital, Bucharest, Romania

    Alina Popa-Cherecheanu, Raluca Iancu, Ruxandra Pirvulescu & Aida Geamanu

  3. Surgery Department, Emergency University Hospital, Bucharest, Romania

    Danut Vasile

  4. Obstetrics and Gynecology Department, Filantropia Clinical Hospital, Bucharest, Romania

    George Iancu

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A. Popa Cherecheanu, R. Iancu, D. Vasile, R. Pirvulescu, A. Geamanu, C. Coman, and G. Iancu declare that they have no competing interests.

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Popa-Cherecheanu, A., Iancu, R., Vasile, D. et al. Systemic side effects after intravitreal administration of antivascular endothelial growth factors for neovascular age-related macular degeneration. Spektrum Augenheilkd. 33, 110–116 (2019). https://doi.org/10.1007/s00717-017-0384-3

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