Long-term outcomes of treat-and-extend ranibizumab with and without navigated laser for diabetic macular oedema: TREX-DME 3-year results

Br J Ophthalmol. 2021 Feb;105(2):253-257. doi: 10.1136/bjophthalmol-2020-316176. Epub 2020 Apr 17.


Background/aims: To evaluate the long-term effects of treat-and-extend dosing of ranibizumab with and without navigated focal laser for diabetic macular oedema (DME).

Methods: This is a multicentre, randomised clinical trial where 150 eyes were randomised into three cohorts; Monthly (n=30), TReat and EXtend without macular laser photocoagulation (TREX; n=60), and treat and extend with angiography-GuIded macular LAser photocoagulation (GILA; n=60). During the first 2 years, eyes either received ranibizumab 0.3 mg every 4 weeks or underwent treat-and-extend ranibizumab with or without angiography-guided laser therapy. In the third year, all eyes were treated as needed with ranibizumab for >5 letters vision loss or if the central retinal thickness (CRT) was >325 µm, and all eyes were eligible to receive focal laser.

Results: 109 eyes (73%) completed the 3-year end-point. At week 156, mean best-corrected visual acuity (BCVA) and CRT improved by 6.9, 9.7, 9.5 letters (p=0.60) and 129, 138, 165 µm (p=0.39), in the Monthly, TREX and GILA cohorts, respectively. These improvements were reached prior to week 104 and no significant changes occurred from week 104 to week 156 (BCVA: p=0.34; CRT: p=0.36). The mean number of injections in the third year was 3.0, 3.1, and 2.4 in the Monthly, TREX and GILA cohorts, respectively (p=0.56). 86 eyes (79%) required at least one ranibizumab injection in the third year.

Conclusion: The improvements achieved after 2 years of treat-and-extend ranibizumab for DME were maintained in the third year with a mean of 3 intravitreal injections.

Trial registration number: FDA IND 119146, NCT01934556.

Keywords: retina; treatment lasers; treatment medical.

Publication types

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

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / therapeutic use*
  • Combined Modality Therapy
  • Diabetic Retinopathy / drug therapy
  • Diabetic Retinopathy / physiopathology
  • Diabetic Retinopathy / surgery
  • Diabetic Retinopathy / therapy*
  • Female
  • Fluorescein Angiography
  • Follow-Up Studies
  • Humans
  • Intravitreal Injections
  • Laser Coagulation*
  • Macular Edema / drug therapy
  • Macular Edema / physiopathology
  • Macular Edema / surgery
  • Macular Edema / therapy*
  • Male
  • Middle Aged
  • Ranibizumab / administration & dosage
  • Ranibizumab / therapeutic use*
  • Surgery, Computer-Assisted
  • Tomography, Optical Coherence
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Visual Acuity / physiology


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

Associated data

  • ClinicalTrials.gov/NCT01934556