Identifying Predictors of Anti-VEGF Treatment Response in Patients with Neovascular Age-Related Macular Degeneration through Discriminant and Principal Component Analysis.

OBJECTIVE: AURA was an observational study that monitored visual acuity outcomes following ranibizumab use in neovascular age-related macular degeneration patients over 2 years. The aim of this analysis was to identify factors that were predictive of visual acuity outcomes in AURA. METHODS: The correlation between the baseline characteristics, the use of resources and the visual acuity outcomes in AURA was explored using principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA). The response variables analysed were mean change in visual acuity over 2 years (analysed via PCA) and no decline in visual acuity at 2 years compared with baseline (analysed via PLS-DA). RESULTS: The AURA dataset comprised 2,227 patients and 132 variables. Using PCA and PLS-DA, we found that the number of ranibizumab injections, clinic and monitoring visits, number of optical coherence tomography scans and ophthalmoscopies correlated with a change in visual acuity at Years 1 and 2, and are therefore key drivers of treatment success. CONCLUSION: This is a novel approach to graphically explore relationships between multiple correlated covariates and outcomes in real-life ophthalmology studies. It identified a number of variables that are positively linked with treatment outcomes.

A noninterventional study to monitor patients with diabetic macular oedema starting treatment with ranibizumab (POLARIS).

PURPOSE: Antivascular endothelial growth factor agents are increasingly used in diabetic macular oedema (DME); however, there are few studies exploring their use in DME in real-world settings. METHODS: POLARIS was a noninterventional, multicentre study to monitor 12-month outcomes in patients starting ranibizumab treatment in routine practices. The primary outcome was mean change in visual acuity (VA) from baseline to month 12 (last observation carried forward approach). Other outcomes included mean change in central retinal thickness (CRT) and resource utilization. Visual acuity (VA) outcomes were also stratified by country, baseline visual acuity score (VAS), sex, age and injection frequency. RESULTS: Outcomes were analysed from all treated patients (n = 804) and from first-year completers (patients who had a visual acuity assessment at 12 months; n = 568). The mean (SD) baseline VAS was 59.4 (15.9) letters, and the mean change in visual acuity was 4.4 letters (95% confidence interval: 3.3-5.4) at month 12 (study eye; first-year completers). The mean number of injections (study eye) was 4.9, and the mean number of all visits (any eye) was 10 (58% were injection visits) over 12 months (first-year completers). The mean (SD) baseline CRT was 410.6 (128.8) µm, and the mean change in CRT was -115.2 µm at month 12 (study eye; first-year completers). Visual acuity (VA) outcomes were generally comparable across most countries and subgroups and were greatest in patients with the lowest baseline VAS (≤60 letters). CONCLUSION: POLARIS showed that real-world outcomes in DME patients starting treatment with ranibizumab were lower than those observed in clinical studies, in spite of extensive monitoring.

Key drivers of visual acuity gains in neovascular age-related macular degeneration in real life: findings from the AURA study.

BACKGROUND/AIMS: To identify predictive markers for the outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD). METHODS: AURA was a retrospective, observational, multicentre study that monitored the 2-year outcomes following intravitreal ranibizumab treatment in patients with nAMD. Using stepwise regression analysis, we evaluated the association between visual acuity outcomes, baseline characteristics and resource utilisation in order to determine which variables are significantly linked to outcomes in AURA. We also examined the relationship between visual acuity outcomes and number of injections received. RESULTS: Analyses were performed using data from year 1 (n=1695) and year 2 completers (n=1184). Logistic analysis showed that baseline visual acuity score, age at start of therapy, number of ophthalmoscopies and optical coherence tomography (OCT) (combined) and number of injections (ranibizumab) were significant (p<0.05) prognostic factors for vision maintenance (loss <15 letters) or vision gain (≥15 letters). Patients who received >7 injections (in 1 year) or >14 injections (over 2 years) gained more letters and demonstrated greater vision maintenance (loss of <15 letters) than patients who received fewer injections. There was a significant (p<0.05) association between number of injections and national reimbursement schemes and OCT. CONCLUSIONS: A number of factors that are predictive of treatment outcomes in a real-life setting were identified. Notably, the decline of treatment benefits may be linked to number of injections and a failure to visit clinicians and receive OCT as required. These findings may be helpful in guiding ophthalmologist treatment decisions under limited time and financial constraints. TRIAL REGISTRATION NUMBER: NCT01447043.