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With Yoshihiro Yonekawa, MD; Ajay Kuriyan, MD; Anton Orlin, MD; and Paula Pecen, MD

STUDY SUBJECTS

Major inclusion criteria:

• 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)



Major exclusion criteria:

• Previous treatment for DME or DR within 12 months
• Previous PRP

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