Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study

Br J Ophthalmol. 2016 Jun;100(6):787-95. doi: 10.1136/bjophthalmol-2015-307249. Epub 2015 Oct 9.


Aims: To demonstrate non-inferiority of ranibizumab treat-and-extend (T&E) with/without laser to ranibizumab pro re nata (PRN) for best-corrected visual acuity (BCVA) in patients with diabetic macular oedema (DMO).

Methods: A 24-month single-masked study with patients randomised 1:1:1 to T&E+laser (n=121), T&E (n=128) or PRN (control; n=123). All patients received monthly injections until BCVA stabilisation. The investigator decided on re-treatment in the PRN and treatment-interval adaptations in the T&E groups based on loss of BCVA stability due to DMO activity. Likewise, laser treatment was at investigator's discretion. Collectively, these features reflect a real-life scenario. Endpoints included mean average change in BCVA from baseline to months 1-12 (primary), mean BCVA change from baseline to months 12 and 24, treatment exposure and safety profile.

Results: Both T&E regimens were non-inferior to PRN based on mean average BCVA change from baseline to months 1-12 (T&E+laser: +5.9 and T&E: +6.1 vs PRN: +6.2 letters; both p<0.0001). Mean BCVA change at month 24 was similar across groups (+8.3, +6.5 and +8.1 letters, respectively). The mean number of injections was 12.4 and 12.8 in the T&E+laser and T&E groups and 10.7 in the PRN group. The T&E regimens showed 46% reduction in the number of clinic visits. Over 70% of patients maintained their BCVA, with treatment intervals of ≥2 months over 24 months. Safety profile was consistent with that described in the product information.

Conclusions: T&E is a feasible treatment option for patients with DMO, with a potential to reduce treatment burden. Slightly more injections were required versus PRN, likely due to the specifics of the T&E regimen applied here.

Trial registration number: NCT01171976.

Keywords: Clinical Trial; Macula; Treatment Lasers; Treatment Medical; Vision.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Diabetic Retinopathy / complications*
  • Diabetic Retinopathy / diagnosis
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Intravitreal Injections
  • Macula Lutea / diagnostic imaging*
  • Macular Edema / diagnosis
  • Macular Edema / drug therapy*
  • Macular Edema / etiology
  • Male
  • Middle Aged
  • Ranibizumab / administration & dosage*
  • Retrospective Studies
  • Single-Blind Method
  • 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

  • ClinicalTrials.gov/NCT01171976