Zohar Yehoshua1, Carlos Alexandre de Amorim Garcia Filho2, Renata Portella Nunes1, Giovanni Gregori1, Fernando M Penha2, Andrew A Moshfeghi1, Kang Zhang3, Srinivas Sadda4, William Feuer1, Philip J Rosenfeld5. 1. Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. 2. Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; Department of Ophthalmology, Federal University of Säo Paulo, UNIFESP, São Paulo, Brazil. 3. Institute for Genomic Medicine and Shiley Eye Center, University of California, San Diego, La Jolla, California. 4. Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California. 5. Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. Electronic address: prosenfeld@med.miami.edu.
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 of GA significantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months.
RCT Entities:
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 of GA significantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months.
Authors: Michael L Klein; Frederick L Ferris; Peter J Francis; Anne S Lindblad; Emily Y Chew; Sara C Hamon; Jurg Ott Journal: Ophthalmology Date: 2010-04-09 Impact factor: 12.079
Authors: Peter Hillmen; Neal S Young; Jörg Schubert; Robert A Brodsky; Gerard Socié; Petra Muus; Alexander Röth; Jeffrey Szer; Modupe O Elebute; Ryotaro Nakamura; Paul Browne; Antonio M Risitano; Anita Hill; Hubert Schrezenmeier; Chieh-Lin Fu; Jaroslaw Maciejewski; Scott A Rollins; Christopher F Mojcik; Russell P Rother; Lucio Luzzatto Journal: N Engl J Med Date: 2006-09-21 Impact factor: 91.245
Authors: Dominique C Baas; Lintje Ho; Sarah Ennis; Joanna E Merriam; Michael W T Tanck; André G Uitterlinden; Paulus T V M de Jong; Angela J Cree; Helen L Griffiths; Fernando Rivadeneira; Albert Hofman; Cornelia van Duijn; R Theodore Smith; Gaetano R Barile; Theo G M F Gorgels; Johannes R Vingerling; Caroline C W Klaver; Andrew J Lotery; Rando Allikmets; Arthur A B Bergen Journal: Ophthalmology Date: 2009-12-22 Impact factor: 12.079
Authors: Gregory S Hageman; Lisa S Hancox; Andrew J Taiber; Karen M Gehrs; Don H Anderson; Lincoln V Johnson; Monte J Radeke; David Kavanagh; Anna Richards; John Atkinson; Seppo Meri; Julie Bergeron; Jana Zernant; Joanna Merriam; Bert Gold; Rando Allikmets; Michael Dean Journal: Ann Med Date: 2006 Impact factor: 4.709
Authors: Janet S Sunness; Gary S Rubin; Aimee Broman; Carol A Applegate; Neil M Bressler; Barbara S Hawkins Journal: Ophthalmology Date: 2008-05-16 Impact factor: 12.079
Authors: Hendrik P N Scholl; Monika Fleckenstein; Lars G Fritsche; Steffen Schmitz-Valckenberg; Arno Göbel; Christine Adrion; Christine Herold; Claudia N Keilhauer; Friederike Mackensen; Andreas Mössner; Daniel Pauleikhoff; Andreas W A Weinberger; Ulrich Mansmann; Frank G Holz; Tim Becker; Bernhard H F Weber Journal: PLoS One Date: 2009-10-12 Impact factor: 3.240
Authors: Zhichao Wu; Chi D Luu; Lauren N Ayton; Jonathan K Goh; Lucia M Lucci; William C Hubbard; Jill L Hageman; Gregory S Hageman; Robyn H Guymer Journal: Invest Ophthalmol Vis Sci Date: 2015-02-12 Impact factor: 4.799
Authors: Emma C Zanzottera; Jeffrey D Messinger; Thomas Ach; R Theodore Smith; K Bailey Freund; Christine A Curcio Journal: Invest Ophthalmol Vis Sci Date: 2015-05 Impact factor: 4.799
Authors: Juan E Grunwald; Maxwell Pistilli; Ebenezer Daniel; Gui-Shuang Ying; Wei Pan; Glenn J Jaffe; Cynthia A Toth; Stephanie A Hagstrom; Maureen G Maguire; Daniel F Martin Journal: Ophthalmology Date: 2016-10-27 Impact factor: 12.079