Insights from survival analyses during 12 years of anti-VEGF therapy for neovascular age-related macular degeneration

Importance: While multiple imputation models for missing data and use of
mixed effects models generally provide better outcome estimates than using
only observed data or last observation carried forward in clinical trials,
such approaches usually cannot be applied to visual outcomes from
retrospective analyses of clinical practice settings, so-called real-world
outcomes. Objective: To explore potential utility of survival analysis
techniques for retrospective clinical practice visual outcomes. Design:
Retrospective cohort study with 12-year observation period. Setting: A
tertiary eye center. Participants: Of 10,744 eyes with neovascular AMD
receiving anti-VEGF therapy between October 2008 and February 2020, 7802
eyes met study criteria (treatment-naïve, first-treated eyes starting
anti-VEGF therapy). Main outcome measures: Kaplan-Meier estimates and Cox
proportional hazards modelling were used to consider: VA reaching ETDRS
(Early Treatment Diabetic Retinopathy Study) letter score 70 (Snellen
equivalent 20/40) or better; duration VA sustained at or better than 70
(20/40); and VA declining to 35 (20/200) or worse. Results: The median
time to attaining VA letter score ≥ 70 (20/40) was 2.0 years (95% CI 1.87
- 2.32) after the first anti-VEGF injection. Predictive features were
baseline VA (HR 1.43 per 5 ETDRS letter score or 1 line [95% CI 1.40 -
1.46]), baseline age (HR 0.88 per 5 years [95% CI 0.86 - 0.90]), and
injection number (HR 1.123 [95% CI 1.101 - 1.15]). Of the 56% attaining
this outcome, median time sustained at 70 (20/40) or better was 1.1 years
(95% CI 1.1 - 1.2). Conclusions and relevance: Survival analysis
potentially addresses key limitations of retrospective clinical practice
(real-world) data by accounting for variable observation time-points and
follow-up durations. Modelling with multiple covariates reveals factors
that may help inform the likely visual trajectory of an individual. We
demonstrate the utility of our proposed analyses by showing that patients
with neovascular AMD beginning anti-VEGF therapy are more likely to
experience positive visual outcomes within the first 2.9 years, typically
maintaining this for 1.1 years, but then deteriorating to poor vision
within 8.7 years. We believe that this dataset, combined with our
statistical approach for retrospective analyses, may provide long-term
prognostic information for patients newly diagnosed with this condition.