Figure 1. Study Selection, Randomization, and Flow of Participants’ Eyes.

Protocol-specified visits occurred at baseline (randomization) and at target periods of 1 month (± 2-wk range), 2 months (± 1-wk range), 4 months (± 8-wk range); then every 4 months (± 12-wk range for annual visits; ± 8-wk range otherwise) through 4 years (range, −12 weeks to +24 weeks).

^aOf the 328 participants who were randomized, 71 bilateral participants (30 females and 41 males) had 1 eye randomized to receive afibercept and 1 eye randomized to receive sham.

^bThe 137 patients’ eyes that completed the 4-year visit indicates 68.5% of the 200 randomized (74.9% excluding 17 patients who died).

^cThe 134 patients’ eyes that completed the 4-year visit indicates 67.3% of the 199 randomized (73.2% excluding 16 patients who died).

^dDeaths exclude 1 participant (1 study eye) in the aflibercept group who completed a visit in the 4-year visit window but died before completing the designated 4-year study visit.

^eThe primary analysis of the key outcomes included all randomized participants using all available follow-up time for the anatomical outcome (time to development of proliferative diabetic retinopathy or center-involved diabetic macula edema) and multiple imputation for missing data of the visual acuity outcome (change in visual acuity from baseline to 4 years).

^fThe per-protocol analysis included eyes that were at least 80% adherent with protocol injections (aflibercept or sham) prior to the event or censoring time (for the primary anatomical outcome) and prior to the 4-year visit (for the primary visual acuity outcome). The compete-case analysis for the primary visual acuity outcome included all eyes that completed the 4-year visit.