Clinical Studies:
DRCR.net Protocol V
Citations: Baker CW, Glassman AR, Beaulieu WT, et al. Effect of Initial Management With Aflibercept vs Laser Photocoagulation vs Observation on Vision Loss Among Patients With Diabetic Macular Edema Involving the Center of the Macula and Good Visual Acuity: A Randomized Clinical Trial. JAMA. 2019;321(19):1880–1894. doi:10.1001/jama.2019.5790
Key Points
- Protocol V was a double-blind, randomized clinical trial enrolling Type 1 or Type 2 diabetic eyes with central involving macular edema and good vision (20/25 or better)
- There was no significant difference in eyes initially managed with aflibercept, laser, or observation and given aflibercept only if vision worsened, suggesting that observation without treatment unless vision worsens is a reasonable strategy
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Objective
To compare vision loss at 2 years among eyes with center involving macular edema and vision of 20/25 or better when initially managed with aflibercept, laser photocoagulation, or observation.
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STUDY DESIGN
Phase 3, multicenter, randomized, double-masked, treatment-controlled trial
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Duration
2 years
STUDY SUBJECTS
- Adults with type 1 or type 2 diabetes with one study eye with center-involved diabetic macular edema and visual acuity of 20/25 or better
- Eyes with type 1 or type 2 diabetes with central involving DME and VA 20/25 or better
Major inclusion criteria:
- Any prior intraocular surgery, recent or impending need for PRP, any condition that might impede improvement of visual acuity with resolution of macular edema
Major exclusion criteria:
Randomization scheme and interventions:
- Adults with type 1 or type 2 diabetes with 1 study eye with CI-DME and visual acuity of 20/25 or better. Study eyes were randomly assigned 1:1:1:
- 2.0 mg of aflibercept
- Continued injections if visual acuity or OCT central subfield thickness (CST) was improving or worsening (defined as ≥5-letter visual acuity or ≥10% CST change) from either of the last two 4-week visits
- focal/grid laser photocoagulation
- observation.
- Aflibercept injections were initiated for eyes in the laser photocoagulation and observation groups if visual acuity decreased from baseline by at least 10 letters (≥2 lines on an eye chart) at any visit or by 5 to 9 letters (1-2 lines) at 2 consecutive visits
Results:
Study Population:
- 702 participants were randomly assigned to initial management with aflibercept (n=226), laser photocoagulation (n=240), or observation (n=236)
- Study completion 92%; similar across groups
Injections Performed
- In aflibercept group, mean number of injections over 2 years was 8 (interquartile range 6-11). 13 eyes (6%) required laser photocoagulation.
- In laser photocoagulation group, 60 eyes (25%) required injections. In eyes receiving injections, the median was 7.
- In observation group, 80 eyes (34%) required injections. In eyes receiving injections, the median was 9.
Primary outcome (% eyes with >5-letter visual acuity decrease at 2 years)- no significant difference
- Aflibercept: 16%
- Laser photocoagulation: 17%
- Observation: 19%
Mean change in visual acuity letter score (secondary outcome)- no significant difference
- Aflibercept: 0.9 (SD 6.4)
- Laser photocoagulation: 0.1 (SD 6.3)
- Observation: -0.4 (SD 6.3)
Change in retinal thickening (central subfield thickness)- no significant difference
- Aflibercept: -48 μm (SD 65)
- Laser photocoagulation: -41 μm (SD 75)
- Observation: -42 μm (SD 75)
Adverse Events:
- No cases of endophthalmitis among 4872 injections
- Similar rates of MI, stroke, CVA, all-cause mortality between groups
CONCLUSIONS
- Among eyes with center involving DME and good visual acuity, there was no significant difference in vision loss at 2 years if eyes were initially managed with aflibercept, laser photocoagulation, or observation. Observation without treatment unless visual acuity worsens may be a reasonable strategy for these eyes.