John A Wells1, Adam R Glassman2, Allison R Ayala3, Lee M Jampol4, Neil M Bressler5, Susan B Bressler5, Alexander J Brucker6, Frederick L Ferris7, G Robert Hampton8, Chirag Jhaveri9, Michele Melia2, Roy W Beck2. 1. Palmetto Retina Center, Columbia, South Carolina. 2. Jaeb Center for Health Research, Tampa, Florida. 3. Jaeb Center for Health Research, Tampa, Florida. Electronic address: drcrstat1@jaeb.org. 4. Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 5. Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. 6. Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania. 7. National Eye Institutes, National Institutes of Health, Bethesda, Maryland. 8. Retina-Vitreous Surgeons of Central New York, PC, Syracuse, New York. 9. Retina Research Center, Austin, Texas.
Abstract
PURPOSE: To provide 2-year results comparing anti-vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen. DESIGN: Randomized clinical trial. PARTICIPANTS: Six hundred sixty participants with visual acuity (VA) impairment from DME. METHODS: Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol-specific follow-up and retreatment regimen. Focal/grid laser photocoagulation was added after 6 months if DME persisted. Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable. MAIN OUTCOME MEASURES: Change in VA, adverse events, and retreatment frequency. RESULTS:Median numbers of injections were 5, 6, and 6 in year 2 and 15, 16, and 15 over 2 years in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P = 0.08). Focal/grid laser photocoagulation was administered in 41%, 64%, and 52%, respectively (aflibercept vs. bevacizumab, P < 0.001; aflibercept vs. ranibizumab, P = 0.04; bevacizumab vs. ranibizumab, P = 0.01). At 2 years, mean VA improved by 12.8, 10.0, and 12.3 letters, respectively. Treatment group differences varied by baseline VA (P = 0.02 for interaction). With worse baseline VA (20/50 to 20/320), mean improvement was 18.1, 13.3, and 16.1 letters, respectively (aflibercept vs. bevacizumab, P = 0.02; aflibercept vs. ranibizumab, P = 0.18; ranibizumab vs. bevacizumab, P = 0.18). With better baseline VA (20/32 to 20/40), mean improvement was 7.8, 6.8, and 8.6 letters, respectively (P > 0.10, for pairwise comparisons). Anti-Platelet Trialists' Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab (global P = 0.047; aflibercept vs. bevacizumab, P = 0.34; aflibercept vs. ranibizumab, P = 0.047; ranibizumab vs. bevacizumab, P = 0.20; global P = 0.09 adjusted for potential confounders). CONCLUSIONS: All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2. Visual acuity outcomes were similar for eyes with better baseline VA. Among eyes with worse baseline VA, aflibercept had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials.
RCT Entities:
PURPOSE: To provide 2-year results comparing anti-vascular endothelial growth factor (VEGF) agents for center-involved diabetic macular edema (DME) using a standardized follow-up and retreatment regimen. DESIGN: Randomized clinical trial. PARTICIPANTS: Six hundred sixty participants with visual acuity (VA) impairment from DME. METHODS: Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol-specific follow-up and retreatment regimen. Focal/grid laser photocoagulation was added after 6 months if DME persisted. Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable. MAIN OUTCOME MEASURES: Change in VA, adverse events, and retreatment frequency. RESULTS: Median numbers of injections were 5, 6, and 6 in year 2 and 15, 16, and 15 over 2 years in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P = 0.08). Focal/grid laser photocoagulation was administered in 41%, 64%, and 52%, respectively (aflibercept vs. bevacizumab, P < 0.001; aflibercept vs. ranibizumab, P = 0.04; bevacizumab vs. ranibizumab, P = 0.01). At 2 years, mean VA improved by 12.8, 10.0, and 12.3 letters, respectively. Treatment group differences varied by baseline VA (P = 0.02 for interaction). With worse baseline VA (20/50 to 20/320), mean improvement was 18.1, 13.3, and 16.1 letters, respectively (aflibercept vs. bevacizumab, P = 0.02; aflibercept vs. ranibizumab, P = 0.18; ranibizumab vs. bevacizumab, P = 0.18). With better baseline VA (20/32 to 20/40), mean improvement was 7.8, 6.8, and 8.6 letters, respectively (P > 0.10, for pairwise comparisons). Anti-Platelet Trialists' Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab (global P = 0.047; aflibercept vs. bevacizumab, P = 0.34; aflibercept vs. ranibizumab, P = 0.047; ranibizumab vs. bevacizumab, P = 0.20; global P = 0.09 adjusted for potential confounders). CONCLUSIONS: All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2. Visual acuity outcomes were similar for eyes with better baseline VA. Among eyes with worse baseline VA, aflibercept had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials.
Authors: Michael J Elman; Lloyd Paul Aiello; Roy W Beck; Neil M Bressler; Susan B Bressler; Allison R Edwards; Frederick L Ferris; Scott M Friedman; Adam R Glassman; Kellee M Miller; Ingrid U Scott; Cynthia R Stockdale; Jennifer K Sun Journal: Ophthalmology Date: 2010-04-28 Impact factor: 12.079
Authors: Daniel F Martin; Maureen G Maguire; Stuart L Fine; Gui-shuang Ying; Glenn J Jaffe; Juan E Grunwald; Cynthia Toth; Maryann Redford; Frederick L Ferris Journal: Ophthalmology Date: 2012-05-01 Impact factor: 12.079
Authors: Quan Dong Nguyen; David M Brown; Dennis M Marcus; David S Boyer; Sunil Patel; Leonard Feiner; Andrea Gibson; Judy Sy; Amy Chen Rundle; J Jill Hopkins; Roman G Rubio; Jason S Ehrlich Journal: Ophthalmology Date: 2012-02-11 Impact factor: 12.079
Authors: John A Wells; Adam R Glassman; Allison R Ayala; Lee M Jampol; Lloyd Paul Aiello; Andrew N Antoszyk; Bambi Arnold-Bush; Carl W Baker; Neil M Bressler; David J Browning; Michael J Elman; Frederick L Ferris; Scott M Friedman; Michele Melia; Dante J Pieramici; Jennifer K Sun; Roy W Beck Journal: N Engl J Med Date: 2015-02-18 Impact factor: 91.245
Authors: David M Brown; Ursula Schmidt-Erfurth; Diana V Do; Frank G Holz; David S Boyer; Edoardo Midena; Jeffrey S Heier; Hiroko Terasaki; Peter K Kaiser; Dennis M Marcus; Quan D Nguyen; Glenn J Jaffe; Jason S Slakter; Christian Simader; Yuhwen Soo; Thomas Schmelter; George D Yancopoulos; Neil Stahl; Robert Vitti; Alyson J Berliner; Oliver Zeitz; Carola Metzig; Jean-François Korobelnik Journal: Ophthalmology Date: 2015-07-18 Impact factor: 12.079
Authors: Usha Chakravarthy; Simon P Harding; Chris A Rogers; Susan M Downes; Andrew J Lotery; Lucy A Culliford; Barnaby C Reeves Journal: Lancet Date: 2013-07-19 Impact factor: 79.321
Authors: Ursula Schmidt-Erfurth; Peter K Kaiser; Jean-François Korobelnik; David M Brown; Victor Chong; Quan Dong Nguyen; Allen C Ho; Yuichiro Ogura; Christian Simader; Glenn J Jaffe; Jason S Slakter; George D Yancopoulos; Neil Stahl; Robert Vitti; Alyson J Berliner; Yuhwen Soo; Majid Anderesi; Olaf Sowade; Oliver Zeitz; Christiane Norenberg; Rupert Sandbrink; Jeffrey S Heier Journal: Ophthalmology Date: 2013-09-29 Impact factor: 12.079
Authors: Neil M Bressler; Wesley T Beaulieu; Adam R Glassman; Kevin J Blinder; Susan B Bressler; Lee M Jampol; Michele Melia; John A Wells Journal: JAMA Ophthalmol Date: 2018-03-01 Impact factor: 7.389
Authors: Neil M Bressler; Wesley T Beaulieu; Maureen G Maguire; Adam R Glassman; Kevin J Blinder; Susan B Bressler; Victor H Gonzalez; Lee M Jampol; Michele Melia; Jennifer K Sun; John A Wells Journal: Am J Ophthalmol Date: 2018-08-02 Impact factor: 5.258