Systemic Complement Inhibition with Eculizumab for Geographic Atrophy in Age-Related Macular Degeneration

Purpose: To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD).Design: Prospective, double-masked, randomized clinical trial.Participants: Patients with GA measuring from 1.25 to 18 mm(2) based on spectral-domain optical coherence tomography imaging.Methods: Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. in the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. the placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and low-luminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores.Main Outcome Measures: Change in area of GA at 26 weeks.Results: Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. for the 30 study eyes, mean square root of GA area measurements +/-standard deviation at baseline were 2.55+/-0.94 and 2.02+/-0.74 mm in the eculizumab and placebo groups, respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19+/-0.12 and 0.18+/-0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37+/-0.22 mm in the eculizumab-treated eyes and by a mean of 0.37+/-0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified.Conclusions: Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate ofGAsignificantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months. (C) 2014 by the American Academy of Ophthalmology.Alexion PharmaceuticalsMacula Vision Research FoundationCarl Zeiss Meditec, Inc., Dublin, CaliforniaResearch to Prevent Blindness, Inc., New York, New YorkNational Eye Institute, National Institutes of Health, Bethesda, MarylandDepartment of Defense, Washington, DCJerome A. Yavitz Charitable FoundationEmma Clyde Hodge Memorial FoundationFlorman Family Foundation, Inc.Gemcon Family FoundationUniv Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USAUniversidade Federal de São Paulo, UNIFESP, Dept Ophthalmol, São Paulo, BrazilUniv Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USAUniv Calif San Diego, Shiley Eye Ctr, La Jolla, CA 92093 USAUniv So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USAUniversidade Federal de São Paulo, UNIFESP, Dept Ophthalmol, São Paulo, BrazilNational Eye Institute, National Institutes of Health, Bethesda, Maryland: P30 EY014801Department of Defense, Washington, DC: W81XWH-09-10675Web of Scienc