Influence of Glycosylated Hemoglobin on the Efficacy of Ranibizumab for Diabetic Macular Edema: A Post Hoc Analysis of the RIDE/RISE Trials

Ophthalmology. 2015 Aug;122(8):1573-9. doi: 10.1016/j.ophtha.2015.04.029. Epub 2015 Jun 4.


Purpose: To investigate the influence of glycosylated hemoglobin (HbA1c) on treatment outcomes in patients with diabetic macular edema (DME) receiving intravitreal ranibizumab.

Design: Post hoc analysis of 2 identical phase III clinical trials assessing the efficacy and safety of intravitreal ranibizumab in DME over 36 months (RIDE: NCT00473382/RISE: NCT00473330).

Participants: A total of 483 adults with vision loss from DME treated with ranibizumab were included in this analysis from RIDE/RISE. Participants received monthly intravitreal ranibizumab (0.3 or 0.5 mg).

Main outcome measures: Differences in visual and anatomic outcomes, and diabetic retinopathy (DR) severity score, between subgroups of patients with baseline HbA1c ≤7% versus HbA1c >7% at 36 months.

Results: There were 195 patients in RIDE/RISE who were treated with ranibizumab with a baseline HbA1c ≤7% and 288 patients with a baseline HbA1c >7% included in this analysis. The mean improvement in visual acuity (VA) at 36 months was +13 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in patients with baseline HbA1c ≤7% compared with +11 ETDRS letters in the patients with a baseline HbA1c >7% (P = 0.17). After adjustment for baseline central foveal thickness (CFT) and duration of diabetes, the mean CFT reduction was -268 μm in patients with a baseline HbA1c ≤7% and -269 μm in patients with a baseline HbA1c >7% (P = 0.98; 95% confidence interval, -22.93 to 23.54). The proportion of patients with a ≥2-step improvement in DR severity score was 38% in patients with baseline HbA1c ≤7% compared with 41% in the patients with a baseline HbA1c >7% (P = 0.53). There was no correlation of baseline HbA1c with any visual or anatomic parameter.

Conclusions: The improvement in VA, anatomic reduction of macular edema, and improvement in DR severity score with ranibizumab treatment seem to be independent of baseline HbA1c.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Diabetic Retinopathy / blood
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / physiopathology
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Intravitreal Injections
  • Macular Edema / blood
  • Macular Edema / drug therapy*
  • Macular Edema / physiopathology
  • Male
  • Middle Aged
  • Ranibizumab
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Visual Acuity / physiology


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Glycated Hemoglobin A
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • hemoglobin A1c protein, human
  • Ranibizumab

Associated data