Statistical analysis
Based on the VIEW studies [Although both the pro re nata and T&E treatment approaches include 3 initial monthly injections, not all patients in the RAINBOW study received these initial injections (defined here as the first 3 injections received within 45–90 days after the first injection in month 0 for a total of ≥ 4 injections within the first 90 days). Therefore, patients were retrospectively divided into 3 cohorts depending on their treatment pattern during the first 12 months of treatment. Specifically, the regular cohort comprised patients who received the 3 initial monthly (− 1/ + 2 weeks) IVT-AFL injections followed by IVT-AFL injections every 2 months (− 3/ + 4 weeks). The 2 irregular cohorts included patients who received IVT-AFL injections every < 2 or > 2 months over the first 12 months, with or without the 3 initial monthly (− 1/ + 2 weeks) injections.All data collected up to month 48 were analyzed for the overall FAS. Data from the FAS population were analyzed on an intent-to-treat basis and included data after any switch from IVT-AFL to another treatment. To analyze data during treatment with IVT-AFL specifically, an additional exploratory analysis was conducted in a population defined as the “FAS before switch;” in this population, data were included until the switch and considered missing after the switch. Outcomes at 4 years are reported here for the overall FAS population, the FAS before switch population, and for patients in the FAS stratified by treatment pattern during the first year.Statistical analyses were explorative and descriptive; the study did not aim to confirm or reject predefined hypotheses. Continuous variables were described by absolute values and as changes from baseline per analysis time point. All data reported here are for patients with assessments at each of the indicated timepoints, and none of the results are based on a last observation carried forward (LOCF) analysis or any other method of imputation. A mixed model for repeated measures was used to estimate the change in BCVA over time in the FAS before switch population (fixed effects: baseline BCVA and time). In addition, several robustness analyses were performed on the FAS (data not reported here). These analyses included imputation of missing data by replacement with the patient’s last observed value (i.e., using the LOCF approach), imputation of missing data by replacement with the median value of the population, and smoothing imputation. Statistical analyses were performed by use of the SAS software package, release 9.4 (SAS Institute Inc., Cary, NC, USA).