Change in diabetic retinopathy through 2 years secondary analysis of a randomized clinical trial comparing aflibercept, bevacizumab, and ranibizumab

Susan B. Bressler, Danni Liu, Adam R. Glassman, Barbara A. Blodi, Alessandro A. Castellarin, Lee M. Jampol, Paul L. Kaufman, Michele Melia, Harinderjit Singh, John A. Wells

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


IMPORTANCE: Anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) favorably affects diabetic retinopathy (DR) improvement and worsening. It is unknown whether these effects differ across anti-VEGF agents. OBJECTIVE: To compare changes in DR severity during aflibercept, bevacizumab, or ranibizumab treatment for DME. DESIGN, SETTING, AND PARTICIPANTS: Preplanned secondary analysis of data from a comparative effectiveness trial for center-involved DME was conducted in 650 participants receiving aflibercept, bevacizumab, or ranibizumab. Retinopathy improvement and worsening were determined during 2 years of treatment. Participants were randomized in 2012 through 2013, and the trial concluded on September 23, 2015. INTERVENTIONS: Random assignment to aflibercept, 2.0 mg; bevacizumab, 1.25 mg; ranibizumab, 0.3 mg, up to every 4 weeks through 2 years following a retreatment protocol. MAIN OUTCOMES AND MEASURES: Percentages with retinopathy improvement at 1 and 2 years and cumulative probabilities for retinopathy worsening through 2-year without adjustment for multiple outcomes. RESULTS: A total of 650 participants (495 [76.2%] nonproliferative DR [NPDR], 155 proliferative DR [PDR]) were analyzed; 302 (46.5%) were women and mean (SD) age was 61 (10) years; 425 (65.4%) were white. At 1 year, among423 NPDR eyes, 44 of 141 (31.2%) treated with aflibercept, 29 of 131 (22.1%) with bevacizumab, and 57 of 151 (37.7%) with ranibizumab had improvement of DR severity (adjusted difference: 11.7%; 95% CI, 2.9% to 20.6%; P =.004 for aflibercept vs bevacizumab; 8.9%; 95% CI, 1.7% to 16.1%; P =.01 for ranibizumab vs bevacizumab; and 2.9%; 95% CI, -5.7% to 11.4%; P=.51 for aflibercept vs ranibizumab). At 2 years, 33 eyes (24.8%) in the aflibercept group, 25 eyes (22.1%) in the bevacizumab group, and 40 eyes (31.0%) in the ranibizumab group had DRimprovement; no treatment group differences were identified. For 93 eyes with PDRat baseline, 1-year improvement rates were 75.9% for aflibercept, 31.4% for bevacizumab, and 55.2% for ranibizumab (adjusted difference: 50.4%; 95% CI, 26.8% to 74.0%; P <.001 for aflibercept vs bevacizumab; 20.4%; 95%CI,-3.1% to 440%; P=.09 for ranibizumab vs bevacizumab; and 30.0%; 95% CI, 4.4% to 55.6%; P =.02 for aflibercept vs ranibizumab). These rates and treatment group differences appeared to be maintained at 2 years. Despite the reduced numbers of injections in the second year, 66 (59.5%) of NPDR and 28 (70.0%) of PDR eyes that manifested improvement at 1 year maintained improvement at 2 years. Two-year cumulative rates for retinopathy worsening ranged from 7.1% to 10.2% and 17.2% to 26.4% among anti-VEGF groups for NPDR and PDR eyes, respectively. No statistically significant treatment differences were noted. CONCLUSIONS AND RELEVANCE: At 1 and 2 years, eyes with NPDR receivinganti-VEGF treatment for DME may experience improvement in DR severity. Less improvement was demonstrated with bevacizumab at 1 year than with aflibercept or ranibizumab. Aflibercept was associated with more improvement at 1 and 2 years in the smaller subgroup of participants with PDR at baseline. All 3 anti-VEGF treatments were associated with low rates of DR worsening. These data provide additional outcomes that might be considered when choosingan anti-VEGF agent to treat DME.

Original languageEnglish (US)
Pages (from-to)558-568
Number of pages11
JournalJAMA ophthalmology
Issue number6
StatePublished - Jun 2017

ASJC Scopus subject areas

  • Ophthalmology


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