title: Prevention of experimental choroidal neovascularization and resolution of active lesions by VEGF trap in nonhuman primates.
abstract: OBJECTIVE
  To evaluate the efficacy of systemic and intravitreous administration of VEGF Trap (aflibercept) in a nonhuman primate model of choroidal neovascularization (CNV).
  
  
  METHODS
  VEGF Trap treatment on laser-induced CNV was evaluated in 48 adult cynomolgus monkeys. In the prevention arms of the study, VEGF Trap was administered by intravenous injection (3 or 10 mg/kg weekly) or intravitreous injection (50, 250, or 500 μg/eye every 2 weeks) beginning before laser injury. In the treatment arm, a single intravitreous injection (500 μg) was given 2 weeks following laser injury. Laser-induced lesions were scored from grade 1 (no hyperfluorescence) to grade 4 (clinically relevant leakage). Representative lesions were evaluated histologically.
  
  
  RESULTS
  Grade 4 leakage developed at 32.4% and 45.4% of the laser sites in animals receiving intravitreous or intravenous administration of placebo at 2 weeks following laser injury, respectively. In contrast, the development of grade 4 lesions was completely or nearly completely prevented in all groups receiving intravenous or intravitreous injections of VEGF Trap. A single intravitreous injection of VEGF Trap (500 μg) administered following the development of CNV reduced the frequency of grade 4 lesions from 44.4% to 0% within 14 days of treatment. Intravitreous VEGF Trap was well tolerated with either no or only mild ocular inflammation. Histological evaluation showed decreased scores for morphologic features of tissue proliferation in the VEGF Trap prevention groups.
  
  
  CONCLUSIONS
  VEGF Trap prevented the development of clinically relevant CNV leakage when administered at the lowest doses tested. Moreover, a single intravitreous injection induced inhibition of active CNV leakage.
  
  
  CONCLUSIONS
  The animal model used in this study has an established track record as a predictor of pharmacologic efficacy of antineovascular drugs in humans having the neovascular, or wet, form of age-related macular degeneration.
authors.affiliation: Comparative Ophthalmic Research Laboratories, Madison, Wisconsin, USA. tmnork@wisc.edu
authors.forename: T Michael
authors.initials: TM
authors.lastname: Nork
authors.forename: Richard R
authors.initials: RR
authors.lastname: Dubielzig
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Christian
authors.forename: Paul E
authors.initials: PE
authors.lastname: Miller
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Miller
authors.forename: Jingtai
authors.initials: J
authors.lastname: Cao
authors.forename: Edward P
authors.initials: EP
authors.lastname: Zimmer
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Wiegand
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000517:prevention & control*; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D058449:Intravitreal Injections; D017075:Laser Coagulation; D008252:Macaca fascicularis; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D012160:Retina / Q000473:pathology
chemical_list: D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor