Two-Year Efficacy of Ranibizumab Plus Laser-Induced Chorioretinal Anastomosis vs Ranibizumab Monotherapy for Central Retinal Vein Occlusion: A Randomized Clinical Trial

JAMA Ophthalmol. 2018 Dec 1;136(12):1391-1397. doi: 10.1001/jamaophthalmol.2018.4973.


Importance: Adding a laser-induced chorioretinal anastomosis (L-CRA) to current treatments for central retinal vein occlusion (CRVO) may improve outcomes and lessen therapy burdens.

Objective: To determine the 2-year efficacy of intravitreal ranibizumab with an L-CRA vs ranibizumab alone for patients with macular edema caused by CRVO.

Design, setting, and participants: In this randomized clinical trial conducted at a single university clinic from March 2012 to June 2015, 58 participants with macular edema caused by CRVO were randomized 1:1 to either an L-CRA or sham procedure at baseline. All participants received monthly intravitreal injections of ranibizumab, 0.5 mg. Data were analyzed from April 2017 to September 2017.

Interventions: Random assignment to L-CRA plus monthly injections of intravitreal ranibizumab, 0.5 mg, (combination group; n = 29) or to a sham L-CRA procedure plus monthly injections of intravitreal ranibizumab, 0.5 mg, (ranibizumab alone group; n = 29) for 6 months. From month 7 to month 24, participants were evaluated monthly and received an injection of ranibizumab if a loss of 5 or more letters of best-corrected visual acuity (BCVA) on ETDRS chart from previous highest score occurred or if there was evidence of residual macular edema on optical coherence tomography.

Main outcomes and measures: Mean number of injections from month 7 to month 24, change in BCVA, and change in central subfield thickness (CST).

Results: Of the 58 included participants, 38 (66%) were men, and the mean (SD) age was 68.6 (11.8) years; participants had a mean (SD) BCVA of 57.09 (11.87) ETDRS letters (Snellen equivalent, 20/73) and a mean (SD) CST of 738.36 (175.54) μm. A successful L-CRA was created in 24 of 29 participants (83%) in the combination group. The mean number of injections from month 7 to month 24 was 3.2 (95% CI, 2.5-3.8) in the combination group and 7.1 (95% CI, 6.0-8.0) in the ranibizumab alone group. The ratio of the number of injections in the combination group compared with the ranibizumab alone group was 0.46 (95% CI, 0.36-0.61; P < .001). Mixed-effects regression modeling showed a difference in mean BCVA at 2 years between the combination and ranibizumab alone groups (combination, 70.3 letters [Snellen equivalent, 20/40]; ranibizumab alone, 61.6 letters [Snellen equivalent, 20/60]; difference, 8.8 letters; 95% CI, 0.2-17.3; P = .05). There was also a difference in CST at 2 years between the combination and ranibizumab alone groups (mean CST: combination, 303.6 μm; ranibizumab alone, 394.5 μm; difference, 90.9 μm; 95% CI, 24.3-157.5; P = .01). Four participants (14%) in the combination group required a vitrectomy for early macular traction or vitreous hemorrhage.

Conclusions and relevance: For macular edema caused by CRVO, an L-CRA significantly reduced the number of ranibizumab injections required.

Trial registration: Identifier: ACTRN12612000004864.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anastomosis, Surgical / methods
  • Angiogenesis Inhibitors / administration & dosage
  • Choroid / surgery*
  • Female
  • Fluorescein Angiography
  • Follow-Up Studies
  • Fundus Oculi
  • Humans
  • Intravitreal Injections
  • Laser Therapy / methods*
  • Male
  • Prospective Studies
  • Ranibizumab / administration & dosage*
  • Retinal Vein Occlusion / diagnosis
  • Retinal Vein Occlusion / therapy*
  • Retinal Vessels / surgery*
  • 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

  • ANZCTR/ACTRN12612000004864