title: Aflibercept in wet AMD: specific role and optimal use.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) is a naturally occurring glycoprotein in the body that acts as a growth factor for endothelial cells. It regulates angiogenesis, enhances vascular permeability, and plays a major role in wet age-related macular degeneration. The consistent association between choroidal neovascularization and increased VEGF expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of this disorder. Blockade of VEGF activity is currently the most effective strategy for arresting choroidal angiogenesis and reducing vascular permeability, which is frequently the main cause of visual acuity deterioration. In recent years, a number of other molecules have been developed to increase the efficacy and to prolong the durability of the anti-VEGF effect. Aflibercept (EYLEA®; Regeneron Pharmaceutical Inc and Bayer), also named VEGF Trap-eye, is the most recent member of the anti-VEGF armamentarium that was approved by the US Food and Drug Administration in November 2011. Because of its high binding affinity and long duration of action, this drug is considered to be a promising clinically proven anti-VEGF agent for the treatment of wet maculopathy.
  
  
  OBJECTIVE
  This article reviews the current literature and clinical trial data regarding the efficacy and the pharmacological properties of VEGF-Trap eye and describes the possible advantages of its use over the currently used "older" anti-VEGF drugs.
  
  
  METHODS
  For this review, a search of PubMed from January 1989 to May 2013 was performed using the following terms (or combination of terms): vascular endothelial growth factors, VEGF, age-related macular degeneration, VEGF-Trap eye in wet AMD, VEGF-Trap eye in diabetic retinopathy, VEGF-Trap eye in retinal vein occlusions, aflibercept. Studies were limited to those published in English.
  
  
  CONCLUSIONS
  Two Phase III clinical trials, VEGF Trap-eye Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2, comparing VEGF Trap-eye to ranibizumab demonstrated the noninferiority of this novel compound. The clinical equivalence of this compound against ranibizumab is maintained even when the injections are administered at 8-week intervals, which indicates the potential to reduce the risk of monthly intravitreal injections and the burden of monthly monitoring.
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Specialties and Public Health, Ophthalmology Clinic, University of Brescia, Piazzale Spedali Civili 1, Brescia, Italy. semeraro@med.unibs.it
authors.forename: F
authors.initials: F
authors.lastname: Semeraro
authors.forename: F
authors.initials: F
authors.lastname: Morescalchi
authors.forename: S
authors.initials: S
authors.lastname: Duse
authors.forename: F
authors.initials: F
authors.lastname: Parmeggiani
authors.forename: E
authors.initials: E
authors.lastname: Gambicorti
authors.forename: C
authors.initials: C
authors.lastname: Costagliola
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D020256:Choroidal Neovascularization / Q000188:drug therapy / Q000473:pathology; D002986:Clinical Trials as Topic; D006801:Humans; D058449:Intravitreal Injections; D000069579:Ranibizumab; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab
keywords: AMD; VEGF; VEGF inhibition; VEGF-Trap eye; aflibercept; neovascularization