Clinical Trials in Medical Retina

Article initiated by:

Francesc March de Ribot, MD, PhD

All authors and contributors:

Leo A. Kim, MD, PhD, Koushik Tripathy, MD (AIIMS), FRCS (Glasgow), Francesc March de Ribot, MD, PhD

Assigned editor:

Koushik Tripathy, MD (AIIMS), FRCS (Glasgow)

Review:

Assigned status Update Pending

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DRCR protocols

Protocol W 2021

Objectives

The goal was to determine the efficacy of intravitreous aflibercept injections compared to sham in preventing potentially vision-threatening complications in eyes with moderate to severe NPDR. The role of anti-VEGF in managing NPDR without center-involved diabetic macular edema (CI-DME) has not been established.

Design

Clinical trial, eyes with moderate to severe NPDR without CI-DME were randomized to receive 2.0 mg aflibercept or sham. Treatment was given at baseline; 1, 2, and 4 months; and every 4 months through 2 years. Between 2 and 4 years, treatment was deferred if the eye had mild NPDR or better. Aflibercept was administered in both groups if CI-DME with vision loss (≥10 letters at 1 visit or 5-9 letters at 2 consecutive visits) or high-risk proliferative diabetic retinopathy (PDR) developed.

Main outcomes measures

Development of CI-DME with vision loss or PDR.

Results

From 2016 to 2020, 328 participants (399 eyes) with moderate to severe NPDR without CI-DME were randomized to aflibercept injections (n = 200) or sham (n = 199). The 2-year cumulative probability of developing CI-DME with vision loss or PDR was 16.3% with aflibercept vs. 43.5% with sham. The 2-year cumulative probability of developing PDR was 13.5% in the aflibercept group vs. 33.2% in the sham, and the 2-year cumulative probability of developing CI-DME with vision loss was 4.1% in the aflibercept group vs. 14.8% in the sham group. The mean (SD) change in VA from baseline to 2 years was not significant, -0.9 (5.8) letters with aflibercept and -2.0 (6.1) letters with sham.

Limitations

20% loss of follow-up.

Conclusions

Eyes with moderate to severe NPDR treatment with periodic aflibercept decreased the development of PDR or vision-reducing CI-DME. However, through 2 years, preventive aflibercept did not confer VA benefit compared with observation plus treatment with aflibercept only after development of PDR or vision-reducing CI-DME.

Pearls for clinical practice

Eyes with moderate to severe NPDR can be observed and treated if required.