Visual and Anatomic Outcomes in Patients with Diabetic Macular Edema with Limited Initial Anatomic Response to Ranibizumab in RIDE and RISE

Ophthalmology. 2016 Jun;123(6):1345-50. doi: 10.1016/j.ophtha.2016.02.007. Epub 2016 Mar 15.


Purpose: To explore the visual acuity and anatomic outcomes over 24 months of patients with diabetic macular edema (DME) who showed a delayed anatomic response after 3 ranibizumab injections in the RIDE and RISE trials.

Design: Analysis of data from RIDE and RISE, 2 phase III, parallel, randomized, multicenter, double-masked trials ( identifiers, NCT00473382 and NCT00473330).

Participants: Patients with DME (n = 681) who received monthly intravitreal ranibizumab 0.3-mg injections, ranibizumab 0.5-mg injections, or sham injections.

Methods: Patients were separated into 3 groups: delayed responders (ranibizumab-treated patients with ≤10% central foveal thickness [CFT] reduction after 3 injections), immediate responders (ranibizumab-treated patients with >10% CFT reduction after 3 injections), and sham recipients. Central foveal thickness was measured by time-domain optical coherence tomography, best-corrected visual acuity (BCVA) was measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores, and diabetic retinopathy (DR) was measured by the standardized ETDRS severity scale (using fundus photographs).

Main outcome measures: Month-24 CFT, BCVA, and DR severity levels.

Results: In RIDE and RISE, 9% to 10% of ranibizumab-treated eyes were delayed responders. At month 24, delayed responders had less CFT reduction (median, -102 μm) from baseline compared with immediate responders (median, -274 μm; P < 0.0001). Delayed responders gained a median of 10 letters at 24 months, similar to immediate responders (14 letters; P = 0.15). At month 24, DR improvement among the delayed responders (31% and 22% of patients with ≥2- or ≥3-step DR improvement, respectively) was comparable with that among immediate responders (42% and 17%, respectively; P = 0.21 and P = 0.48, respectively).

Conclusions: With continued treatment, at month 24, patients with DME with delayed anatomic response (≤10% CFT reduction) after 3 ranibizumab injections had visual acuity gains and DR improvement similar to those of patients with DME who had immediate anatomic response.

Publication types

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

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / therapeutic use*
  • Diabetic Retinopathy / diagnosis
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / physiopathology
  • Double-Blind Method
  • Female
  • Humans
  • Intravitreal Injections
  • Macular Edema / diagnosis
  • Macular Edema / drug therapy*
  • Macular Edema / physiopathology
  • Male
  • Middle Aged
  • Ranibizumab / administration & dosage
  • Ranibizumab / therapeutic use*
  • Retina / pathology*
  • Tomography, Optical Coherence
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Visual Acuity / physiology*


  • Angiogenesis Inhibitors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Ranibizumab

Associated data