Sustained Benefits from Ranibizumab for Central Retinal Vein Occlusion with Macular Edema: 24-Month Results of the CRYSTAL Study

Ophthalmol Retina. 2018 Feb;2(2):134-142. doi: 10.1016/j.oret.2017.05.016. Epub 2017 Sep 9.


Purpose: To assess the efficacy and safety profile of an individualized, stabilization criteria-driven regimen of ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to central retinal vein occlusion (CRVO).

Design: A 24-month, prospective, open-label, single-arm, multicenter study.

Participants: A total of 357 patients.

Methods: Patients received monthly ranibizumab 0.5 mg injections (minimum, 3 injections) until stable visual acuity (VA) was maintained for 3 consecutive months. Thereafter, ranibizumab 0.5 mg injections were administered if monitoring indicated a loss of VA due to disease activity. The primary outcome results have been published previously.

Main secondary outcome measures: Mean change from baseline at months 1 through 24 in best-corrected VA (BCVA) in the overall population and in subgroups categorized according to baseline BCVA, CRVO duration, or presence of macular ischemia.

Results: The baseline mean BCVA was 53.0 letters and baseline mean CRVO duration was 8.9 months (median, 2.4 months). The mean (standard deviation) gain in BCVA from baseline with ranibizumab 0.5 mg at month 24 was 12.1 (18.60) letters (P < 0.0001). Best-corrected VA gains at month 24 were similar in patients with or without baseline macular ischemia (mean change, 11.1 and 12.9 letters, respectively). The mean BCVA gain at month 24 was higher in patients with CRVO duration <3 months (13.2 letters) compared with that in those with CRVO duration >9 months (10.5 letters). Patients with lower baseline BCVA had larger mean BCVA gains at month 24 (≤39 letters; 18.5 letters) than those with higher baseline BCVA (40-59/≥60 letters; 13.9/7.2 letters), although the absolute BCVA values at month 24 were higher in patients with higher baseline BCVA. The mean (standard deviation) and median number of ranibizumab injections up to month 23 were 13.1 (6.39) and 15.0 injections, respectively. No new ocular or nonocular safety events were reported.

Conclusion: An individualized, stabilization criteria-driven dosing regimen of ranibizumab 0.5 mg led to sustained BCVA gains for up to 24 months in patients with CRVO. The presence of macular ischemia at baseline did not influence VA gains. Shorter duration of CRVO at baseline was associated with better VA gains. Safety findings were consistent with those reported in previous ranibizumab studies in patients with CRVO.

Trial registration: NCT01535261.

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
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Fluorescein Angiography
  • Follow-Up Studies
  • Humans
  • Intravitreal Injections
  • Macula Lutea / pathology
  • Macular Edema / diagnosis
  • Macular Edema / drug therapy*
  • Macular Edema / etiology
  • Male
  • Prospective Studies
  • Ranibizumab / administration & dosage*
  • Retinal Vein Occlusion / complications*
  • Retinal Vein Occlusion / diagnosis
  • Retinal Vein Occlusion / drug therapy
  • Time Factors
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Visual Acuity*


  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Ranibizumab

Associated data