DRCR Protocol I

Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Two-year results of a randomized trial. Diabetic Retinopathy Vitrectomy Study report 2. The Diabetic Retinopathy Vitrectomy Study Research Group. Arch Ophthalmol. 1985 Nov;103(11):1644-52.

*Elman MJ, Ayala A, Bressler NM, Browning D, Flaxel CJ, Glassman AR, et al.; Diabetic Retinopathy Clinical Research Network. Intravitreal Ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results. Ophthalmology. 2015 Feb;122(2):375–81.

*NOTE: This summary focuses on the year 1 report from 2010. However, the results from the 5 year report are also included in this summary, denoted by “*NOTE” followed by text in italics.

Other reports (not summarized here):

Elman MJ, Bressler NM, Qin H, et al. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):609-14.

Elman MJ, Qin H, Glassman AR, et al. Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred Laser Treatment Three-Year Randomized Trial Results. Ophthalmology 2012 Nov;119(11):2312-2318.

Key Points

• The DRCR.net Protocol I was a multicenter randomized clinical trial that compared intravitreal sham injection + prompt laser vs. intravitreal ranibizumab 0.5 mg + prompt laser vs. intravitreal ranibizumab 0.5.mg + deferred (after 6 months) laser vs. intravitreal triamcinolone 4 mg + prompt laser for diabetic macular edema.
• At one year, compared with the sham/prompt focal laser and the triamcinolone/prompt focal laser group, the intravitreal ranibizumab with prompt or deferred laser focal groups showed better visual acuity scores from baseline.
• *NOTE: A 2-year extension study randomized patients who made it to the 3 year time point to ranibizumab every 4 weeks and prompt or deferred (after 6 months) laser.
  • Of those that completed the 5-year total follow up, the ranibizumab/deferred laser group showed equivalent mean change in visual acuity scores from baseline than the ranibizumab/prompt laser group.
  • The proportion of eyes with ≥10 and ≥15 letters of improvement was greater in the ranibizumab/deferred laser group compared with the ranibizumab/prompt laser group.

  Objective

  STUDY DESIGN

  Duration

  STUDY SUBJECTS

  Major inclusion criteria:

  Major exclusion criteria:

  RANDOMIZATION SCHEME AND INTERVENTIONS

  • Each eye could be randomized as a unique study eye.
  • Baseline treatment assigned by block randomization
  • Sham injection + focal laser within 3-10 days of injection
    • Monthly sham for 3 months then PRN
    • -PRN 2nd laser at 3 mos if previous laser incomplete
    • Monthly ranibizumab for 3 months, then PRN
    • PRN 2nd laser at 3 mos if previous laser incomplete
    • Monthly ranibizumab for 3 months, then PRN
    • Triamcinolone ever 4 mos
    • Monthly sham other months
    • At 6 mos, all groups at MD discretion to re-treat with another
    • Monthly follow up with assigned injection for 3 months, then prn.
    • Retreatment criteria for PRN: monthly evaluation and treatment if ≥ 5 letter decrease in vision or disease activity on OCT (IRF, SRF, sub-RPE fluid)
    • Sham given every 4 months with possibility for ranbizumab other months.
    • Triamcinolone every 4 months with sham injection other months.

    RESULTS (1 year)

    Study population

    • 616 eyes from 594 patients randomized, 308 early vitrectomy, 308 deferred vitrectomy
    • 854 study eyes of 691 participants
    • 94-96% study completion across all groups at 1 year
      • Note: this drops to 80% in the year 3 follow up, and 75% in the 5 year follow up.

      Visual acuity end-points

      • At 1 year: Mean change in visual acuity (letter score) from baseline was significantly greater in the ranbizumab + laser groups:
        • +3 in the sham/prompt laser group
        • +9 in the ranibizumab/prompt laser group
        • +9 in the ranibizumab/deferred laser group
        • +4 in the triamcinolone/prompt laser group
        • 15% in the sham/prompt laser group
        • 30% in the ranibizumab/prompt laser group
        • 28% in the ranibizumab/deferred laser group
        • 21% in the triamcinolone/prompt laser group
        • +7.2 letters in the prompt laser group
        • +9.8 letters in the deferred laser group
        • 27% in the ranibizumab/prompt laser
        • 38% in the ranibizumab/deferred laser

        Anatomic end-points:

        • At 1 year: Reduction in mean central subfield thickness in the triamcinolone/prompt laser group (-90 um) was similar to both ranibizumab groups (-112/-111 um) and greater than in the sham/prompt laser group (-79 um).
        • *NOTE: At 5 years: Reduction in mean central subfield thickness was similar in the ranibizumab/prompt laser (-167 um) and ranibizumab/deferred laser (-165 um) groups.

        Number of injections

        • At 1 year: median number of injections was:
          • 11 in the sham/prompt laser group
          • 8 in the ranibizumab/prompt laser group
          • 9 in the ranibizumab/deferred laser group
          • 8 in the triamcinolone/prompt laser group
          • 13 in the ranibizumab/prompt laser group
          • 17 in the ranibizumab deferred laser groups.

          Adverse events at 1 year

          • There were no systemic adverse events.
          • Injection-related endophthalmitis was rare (2 cases, both in the ranibizumab groups).
          • The number of patients with IOP elevations and needing cataract surgery during the study time period was higher in the triamcinolone group, compared with the other groups.

          CONCLUSIONS

          • Protocol I demonstrated that ranibizumab with either prompt or deferred laser results in better visual outcomes compared with sham/prompt laser or triamcinolone/prompt laser.
          • *NOTE: The 5 year extension study suggested that ranibizumab with deferred laser may result in greater long term visual improvement compared with ranibizumab with prompt laser, but that the injection burden may be less with ranibizumab/prompt laser.