Change in drusen volume as a novel clinical trial endpoint for the study of complement inhibition in age-related macular degeneration

Ophthalmic Surg Lasers Imaging Retina. 2014 Jan-Feb;45(1):18-31. doi: 10.3928/23258160-20131217-01.


Background and objective: To evaluate the change in drusen volume following treatment with eculizumab, a systemic inhibitor of complement component 5.

Patients and methods: Single-center, prospective, randomized, double-masked clinical trial. Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 26 weeks.

Main outcome measure: 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Complement C5 / antagonists & inhibitors*
  • Double-Blind Method
  • Endpoint Determination*
  • Female
  • Fluorescein Angiography
  • Follow-Up Studies
  • Geographic Atrophy / diagnosis
  • Geographic Atrophy / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Retinal Drusen / drug therapy*
  • Retinal Drusen / pathology*
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Visual Acuity / physiology


  • Antibodies, Monoclonal, Humanized
  • Complement C5
  • eculizumab