One eye of each participant was randomly assigned in a 1:1:1 ratio to be injected with aflibercept (at a dose of 2.0 mg), bevacizumab (1.25 mg), or ranibizumab (0.3 mg). Randomization was performed at the DRCR.net study website, in permuted blocks and with stratification according to study site and visual acuity in the study eye. Each batch of repackaged bevacizumab underwent sterility, purity, and potency testing before use (Table S2 in the Supplementary Appendix ). When the other (nonstudy) eye required anti-VEGF treatment (129 participants in the aflibercept group [58%], 122 participants in the bevacizumab group [56%], and 121 participants in the ranibizumab group [56%]), the agent that was used was the same as that used for the study eye.
For each agent, the injection volume was 0.05 ml. Injections were performed with the use of topical anesthetic (70% of injections), subconjunctival anesthetic (7%), or both (23%). A sterile lid speculum was used, and povidone–iodine was applied to the injection site. The use of preinjection or postinjection antibiotics was at the investigator’s discretion. Details of the injection procedure are available athttp://drcrnet.jaeb.org/ViewPage.aspx?PageName=Investig_Info .
The primary outcome was assessed at the 1-year visit, with follow-up through 2 years. Only data through 1 year are reported here. During the first year, follow-up visits occurred every 4 weeks (±1 week). At baseline and each follow-up visit, certified personnel measured the best corrected visual acuity using the Electronic Early Treatment of Diabetic Retinopathy Study Visual Acuity Test19 (link) and performed a dilated ocular examination and spectral or time-domain OCT (97% and 3% of scans, respectively). OCT values were converted to time-domain–equivalent values for analysis and reporting.20 (link) Baseline and 1-year OCT scans were graded at the Duke Reading Center (Duke University). Any untoward medical occurrence, regardless of whether the event was considered to be related to treatment, was reported as an adverse event and coded according to the Medical Dictionary for Regulatory Activities (MedDRA). Hospital-discharge summaries were reviewed at the coordinating center.
Study participants, reading-center graders, and the medical monitor who reviewed all adverse events were unaware of the treatment-group assignments. Visual-acuity and OCT technicians were unaware of the treatment-group assignments at the 1-year visit. Investigators and study coordinators were aware of the treatment-group assignments.
For each agent, the injection volume was 0.05 ml. Injections were performed with the use of topical anesthetic (70% of injections), subconjunctival anesthetic (7%), or both (23%). A sterile lid speculum was used, and povidone–iodine was applied to the injection site. The use of preinjection or postinjection antibiotics was at the investigator’s discretion. Details of the injection procedure are available at
The primary outcome was assessed at the 1-year visit, with follow-up through 2 years. Only data through 1 year are reported here. During the first year, follow-up visits occurred every 4 weeks (±1 week). At baseline and each follow-up visit, certified personnel measured the best corrected visual acuity using the Electronic Early Treatment of Diabetic Retinopathy Study Visual Acuity Test19 (link) and performed a dilated ocular examination and spectral or time-domain OCT (97% and 3% of scans, respectively). OCT values were converted to time-domain–equivalent values for analysis and reporting.20 (link) Baseline and 1-year OCT scans were graded at the Duke Reading Center (Duke University). Any untoward medical occurrence, regardless of whether the event was considered to be related to treatment, was reported as an adverse event and coded according to the Medical Dictionary for Regulatory Activities (MedDRA). Hospital-discharge summaries were reviewed at the coordinating center.
Study participants, reading-center graders, and the medical monitor who reviewed all adverse events were unaware of the treatment-group assignments. Visual-acuity and OCT technicians were unaware of the treatment-group assignments at the 1-year visit. Investigators and study coordinators were aware of the treatment-group assignments.
