title: Evaluation of very high- and very low-dose intravitreal aflibercept in patients with neovascular age-related macular degeneration.
abstract: OBJECTIVE
  To determine bioactivity and duration of effect of intravitreal aflibercept injection (also known as vascular endothelial growth factor Trap-Eye) for neovascular age-related macular degeneration (AMD).
  
  
  METHODS
  In this double-masked, phase 1 study, 28 patients with lesions ≤12 disc areas, ≥50% active choroidal neovascularization (CNV), and best corrected visual acuity (BCVA) ≤20/40 were randomized 1:1 to a single intravitreal injection of aflibercept 0.15 or 4 mg. The primary end point was the change from baseline in central retinal/lesion thickness (CR/LT) at week-8. Secondary outcomes were the change from baseline BCVA, the change in CNV lesion size and area of leakage, and proportion of patients requiring repeat injection at 8 weeks.
  
  
  RESULTS
  Mean percent decrease in CR/LT for the 4-mg and 0.15-mg groups was, respectively, 34.2 versus 13.3 at week 4 (P=0.0065), 23.8 versus 5.9 at week 6 (P=0.0380), and 25.2% versus 11.3% at week 8 (P=0.150). The 4-mg group gained a mean of 4.5 letters in BCVA (6/14 patients gaining ≥10 letters) versus 1.1 letters in 0.15-mg group (1/14 gaining ≥10 letters) at week 8. Fewer patients needed retreatment in the 4-mg group at week 8. No serious adverse event or ocular inflammation was reported in either group.
  
  
  CONCLUSIONS
  Intravitreal aflibercept 4 mg had a safety profile similar to that of the very low dose 0.15 mg, and was well-tolerated. The 4-mg dose significantly reduced foveal thickening at weeks 4 and 6, significantly improved BCVA at weeks 6, and reduced the need for repeat injection after 8 weeks compared with intravitreal aflibercept 0.15 mg in neovascular AMD patients.
authors: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA. qnguyen4@jhmi.edu
authors: Quan Dong
authors: QD
authors: Nguyen
authors: Peter A
authors: PA
authors: Campochiaro
authors: Syed Mahmood
authors: SM
authors: Shah
authors: David J
authors: DJ
authors: Browning
authors: Henry L
authors: HL
authors: Hudson
authors: Peter L
authors: PL
authors: Sonkin
authors: Seenu M
authors: SM
authors: Hariprasad
authors: Peter K
authors: PK
authors: Kaiser
authors: Jason
authors: J
authors: Slakter
authors: Julia A
authors: JA
authors: Haller
authors: Diana V
authors: DV
authors: Do
authors: William
authors: W
authors: Mieler
authors: Karen
authors: K
authors: Chu
authors: Avner
authors: A
authors: Ingerman
authors: Robert
authors: R
authors: Vitti
authors: Alyson J
authors: AJ
authors: Berliner
authors: Jesse
authors: J
authors: Cedarbaum
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005584:Fovea Centralis / Q000187:drug effects / Q000473:pathology; D006801:Humans; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014792:Visual Acuity / Q000187:drug effects*
chemical_list: D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor