title: Comparison of the efficacy of aflibercept, ranibizumab, and bevacizumab in an RPE/choroid organ culture.
abstract: OBJECTIVE
  Anti-VEGF treatment is the therapy of choice in age-related macular degeneration and is also applied in diabetic macular edema or retinal vein occlusion. Recently, aflibercept has been approved for therapeutic use. In this study, we investigate the efficacy of aflibercept in comparison with the VEGF-antagonists ranibizumab and bevacizumab in RPE/choroid organ cultures.
  
  
  METHODS
  RPE/choroid organ cultures were prepared from freshly slaughtered pigs' eyes. Organ cultures were treated with 125 μg/ml aflibercept, ranibizumab, or bevacizumab, and the VEGF content of the supernatant was evaluated over the course of 7 days. Additionally, the minimal concentration of VEGF inhibition was evaluated in organ cultures, measured after 6 h of application.
  
  
  RESULTS
  Aflibercept was able to completely inhibit VEGF detection for 6 h at a minimal concentration of 0.031 μg/ml, in contrast to bevacizumab (3.9 μg/ml) and ranibizumab (0.244 μg/ml). A statistically significant VEGF inhibition compared to control could be found for aflibercept and ranibizumab down to and including 0.031 μg/ml, while bevacizumab was significantly reduced compared to control down to a concentration of 0.244 μg/ml and again at 0.061 μg/ml. Inhibition of VEGF after a single aflibercept application of 125 μg/ml could be found over the course of 7 days, with some VEGF detectable at the 7th day. In contrast, VEGF was detectable after 72 h of ranibizumab treatment and some VEGF could already be found 12 h after bevacizumab treatment.
  
  
  CONCLUSIONS
  In conclusion, aflibercept displays a prolonged VEGF inhibition, confirming its effectiveness but also raising concerns about possible side effects of long-term usage.
authors.affiliation: Department of Ophthalmology, Kiel University Medical Center, Arnold-Heller-Str 3, Kiel, 24105, Germany, aklettner@auge.uni-kiel.de.
authors.forename: Alexa
authors.initials: A
authors.lastname: Klettner
authors.forename: Muhammed
authors.initials: M
authors.lastname: Recber
authors.forename: Johann
authors.initials: J
authors.lastname: Roider
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D002829:Choroid / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D009924:Organ Culture Techniques; D000069579:Ranibizumab; D040262:Receptors, Vascular Endothelial Growth Factor / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab