TY - JOUR
T1 - Change in Drusen volume as a novel clinical trial endpoint for the study of complement inhibition in age-related macular degeneration
AU - De Amorim Garcia Filho, Carlos Alexandre
AU - Yehoshua, Zohar
AU - Gregori, Giovanni
AU - Nunes, Renata Portella
AU - Penha, Fernando M.
AU - Moshfeghi, Andrew A.
AU - Zhang, Kang
AU - Feuer, William
AU - Rosenfeld, Philip J.
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
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U2 - 10.3928/23258160-20131217-01
DO - 10.3928/23258160-20131217-01
M3 - Article
C2 - 24354307
AN - SCOPUS:84902317208
VL - 45
SP - 18
EP - 31
JO - Ophthalmic Surgery and Lasers
JF - Ophthalmic Surgery and Lasers
SN - 2325-8160
IS - 1
ER -