title: Change in drusen volume as a novel clinical trial endpoint for the study of complement inhibition in age-related macular degeneration.
abstract: OBJECTIVE
  To evaluate the change in drusen volume following treatment with eculizumab, a systemic inhibitor of complement component 5.
  
  
  METHODS
  Single-center, prospective, randomized, double-masked clinical trial. Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 26 weeks.
  
  
  METHODS
  decrease in drusen volume of at least 50% at 26-week follow-up.
  
  
  RESULTS
  Mean drusen cube root volumes were 0.49 mm and 0.47 mm (P = .64) at baseline and 0.51 mm and 0.42 mm (P = .17) at 26 weeks in the eculizumab and placebo groups, respectively. In the placebo group, one eye had a decrease in drusen volume of at least 50% and two eyes developed neovascularization through 26 weeks.
  
  
  CONCLUSIONS
  Systemic complement inhibition with eculizumab did not significantly reduce drusen volume. Drusen growth was dependent on the number of complement at-risk alleles. Future trials should consider the use of a composite clinical trial endpoint in which efficacy is defined by the treatment’s ability to prevent drusen growth, neovascularization, and the formation of geographic atrophy over 1 year.
authors.forename: Carlos Alexandre de Amorim
authors.initials: CA
authors.lastname: Garcia Filho
authors.forename: Zohar
authors.initials: Z
authors.lastname: Yehoshua
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gregori
authors.forename: Renata Portella
authors.initials: RP
authors.lastname: Nunes
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Penha
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Moshfeghi
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
authors.forename: William
authors.initials: W
authors.lastname: Feuer
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenfeld
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003182:Complement C5 / Q000037:antagonists & inhibitors*; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D057092:Geographic Atrophy / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015593:Retinal Drusen / Q000188:drug therapy* / Q000473:pathology*; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D014792:Visual Acuity / Q000502:physiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; C481642:eculizumab