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

Abstract

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.