Aflibercept in the treatment of diabetic macular edema: a review and consensus paper



To reach a consensus, among experts, on the role of aflibercept in diabetic macular edema (DME) through literature review.


Two round tables, involving 12 Italian experts, were organized: in the first one, 6 pharmacologic and clinical questions were selected and analyzed by a systematic literature review, using a population, intervention, control, and outcomes framework; in the second one, the nominal group technique was used to discuss relevant evidence related to each question. The consensus was assessed using the 5-point Delphi score.


Agreement on statements was reached on 6/6 questions. The final statements were as follows: 1) High levels of both vascular endothelial growth factor (VEGF) and placental growth factor play an important role in the pathogenesis of DME. 2) The aflibercept pharmacologic profile is notably different from that of other anti-VEGF. 3) Aflibercept significantly improves functional and anatomical outcomes, and rapidly improves best-corrected visual acuity up to its peak; these results remain stable over time. 4) Diabetic macular edema aflibercept treatment requires a 5-monthly injection loading phase. Alternatively, a personalized pro re nata (PRN) regimen based on monthly monitoring and strict retreatment criteria can be used. 5) As an alternative to the bimonthly fixed regimen, in the maintenance phase the treatment schedule may be a PRN regimen with strict retreatment criteria or a treat and extend regimen. 6) No concerns on aflibercept ocular and systemic safety emerged from the literature.


Consensus was reached among experts on how to best treat patients with DME with aflibercept.

Eur J Ophthalmol 2017; 27(6): 627 - 639

Article Type: REVIEW



Teresio Avitabile, Claudio Azzolini, Francesco Bandello, Francesco Boscia, Sandro De Falco, Diego Fornasari, Paolo Lanzetta, Leonardo Mastropasqua, Edoardo Midena, Federico Ricci, Giovanni Staurenghi, Monica Varano

Article History


Financial support: No financial support was received for this submission.
Conflict of interest: Teresio Avitabile receives remuneration for participation on advisory boards of Bayer, Novartis, Sifi, and Allergan. Claudio Azzolini has received research funding. Francesco Bandello is a consultant for or receives remuneration for participation on advisory boards of Alcon, Allergan, Alimera Science, Bayer, Bausch & Lomb, Boehringer-Ingelheim, Farmila Thea, Genentech, Hofmann La Roche, Novagali Pharma, Novartis, Sanofi Aventis, Santen, Sifi, Sooft, Thrombogenics, and Zeiss. Francesco Boscia is a consultant of Bayer, Novartis, Allergan, Alcon, and Pfenex. Sandro De Falco is a consultant of Abbott Diagnostics and receives remuneration for participation on the advisory board of Bayer. Diego Fornasari is a consultant of Angelini, Bayer, Grunenthal, Alfa-Sigma, Teva, and Molteni. Paolo Lanzetta is a consultant of Bayer, Genentech, Novartis, and Roche. Leonardo Mastropasqua and Edoardo Midena have no conflicts of interest. Federico Ricci receives personal honoraria for clinical trials, advisory board participation, meeting participation as speaker, and consultancies: PTV Foundation; research grants; Bayer. Giovanni Staurenghi is a consultant from or receives remuneration for participation on advisory boards of Heidelberg Engineering, Quantel Medical, Carl Zeiss Meditec, Alcon, Allergan, Bayer, Boehringer, Genentech, GSK, Novartis, and Roche; receives grant support from Heidelberg Engineering, Optos, Optovue, Quantel Medical, and Centervue; receives lecture fee from Alcon, Allergan, Bayer, GSK, Novartis, and Roche; and receives patents/royalty from Ocular Instruments. Monica Varano receives remuneration for participation on advisory boards of Bayer, Novartis, Sifi, and Allergan.

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  • G. Rodolico Ophthalmic, Eye Clinic, University of Catania, Catania - Italy
  • Department of Medicine and Surgery, University of Insubria, Varese and Como - Italy
  • Department of Ophthalmology, IRCCS Ospedale San Raffaele, University Vita-Salute, Milan - Italy
  • Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Sassari - Italy
  • Institute of Genetics and Biophysics, CNR, Naples - Italy
  • Department of Medical Biotechnology and Translational Medicine, Università  degli Studi di Milano, Milan - Italy
  • Department of Medical and Biological Sciences, Ophthalmology Unit, University of Udine, Udine - Italy
  • Ophthalmology Clinic, Department of Medicine and Science of Aging, Center of Excellence in Ophthalmology, University G. D’Annunzio, Chieti-Pescara - Italy
  • Department of Ophthalmology, University of Padua, Padua - Italy
  • UOSD Retinal Diseases, Policlinico Tor Vergata, University Tor Vergata, Rome - Italy
  • Ophthalmology Clinic, Department of Biomedical Sciences and Clinics, Luigi Sacco Hospital, University of Milan, Milan - Italy
  • IRCCS G.B. Bietti Foundation for the Study and Research in Ophthalmology, Rome - Italy

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