Clinical Studies:
DRCR Protocol W
Citation: Maturi RK, Glassman AR, Josic K, et al. Effect of Intravitreous Anti-Vascular Endothelial Growth Factor vs Sham Treatment for Prevention of Vision-Threatening Complications of Diabetic Retinopathy: The Protocol W Randomized Clinical Trial. JAMA Ophthalmol. Published online March 30, 2021. doi:10.1001/jamaophthalmol.2021.0606
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Objective
To determine the efficacy of aflibercept versus sham in preventing progression to PDR or DME in eyes with moderate to severe NPDR without DME.
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STUDY DESIGN
Double-masked, randomized, prospective clinical trial.
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DURATION
24 Months
With Yoshihiro Yonekawa, MD; Ajay Kuriyan, MD; Anton Orlin, MD; and Paula Pecen, MD
STUDY SUBJECTS
- Adult patients with type 1 or 2 diabetes mellitus with moderate to severe NDPR (DRSS 43-59) with no DME on OCT or NV on FA
- VA >79 ETDRS letters (20/25 or better)
- Previous treatment for DME or DR within 12 months
- Previous PRP
Major inclusion criteria:
Major exclusion criteria:
RANDOMIZATION SCHEME AND INTERVENTIONS
Randomized 1:1 to
(a) aflibercept 2 mg 1, 2, and 4 months, and then every 4 months for 2 years unless DRSS was less than 35 (mild NPDR)
(b) sham injections
Retreatment criteria with aflibercept for both groups if developed DME with 10% increase in CST from baseline along with 10 letter decrease in VA or 5-9 letter loss for 2 consecutive visits or if developed high-risk PDR. PRP was performed if aflibercept therapy failed.
RESULTS (52 months)
Study population
- 200 patients in aflibercept arm, 199 in sham arm
- 17% with moderate NPDR, 32% with moderately severe NPDR DRSS 47A, 27% moderately severe DRSS 47B-D, and 24% severe NPDR
Treatment effect on DR and DME
- For the development of DME with vision loss or PDR, hazard ratio (HR) comparing aflibercept to sham was 0.32 (p < 0.001)
- Probability of developing DME with vision loss or PDR within 2 years was 16.3% with aflibercept and 43.5% with sham (p < 0.001)
- HR for DME alone was 0.36 (p = 0.002), HR for PDR alone was 0.34 (p <0.001)
- Probability of developing DME was 4.1% with aflibercept and 14.8% with sham at 2 years
- Probability of developing PDR was 13.5% with aflibercept and 33.2% with sham at 2 years
- Probability of developing high risk PDR was 2.4% with aflibercept and 8.9% with sham at 2 years
Visual acuity end-points
- No difference in visual acuity was found
- The mean change in VA at 2 years was -0.9 letters with aflibercept and -2.0 letters for sham
- 75% of aflibercept eyes and 72% of sham eyes were 20/20 or better at 2 years
- VA loss of 10 or more letters at 2 years occurred in 6.9% of aflibercept eyes and 8.4% of sham eyes
Adverse events
- 3 cases of endophthalmitis in the aflibercept cohort
- No difference in cardiovascular or cerebrovascular adverse events
CONCLUSIONS
- Aflibercept decreased the rates of progression to DME with vision loss and PDR in eyes with moderate to severe NPDR at 2 years, but did not have an effect on visual acuity