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Original Investigation
November 19, 2020

Insights From Survival Analyses During 12 Years of Anti–Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration

Author Affiliations
  • 1Moorfields Eye Hospital National Health Service (NHS) Foundation Trust, London, United Kingdom
  • 2University College London Institute of Ophthalmology, London, United Kingdom
  • 3Department of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland
  • 4Eye Clinic of the Cantonal Hospital of Lucerne, Lucerne, Switzerland
  • 5Vienna Institute for Research in Ocular Surgery, A Karl Landsteiner Institute, Hanusch Hospital, Vienna, Austria
  • 6Department of Ophthalmology, University Hospital of Munich, Munich, Germany
  • 7School of Population Health and Environmental Sciences, King’s College London, London, United Kingdom
  • 8Gloucestershire Retinal Research Group, Gloucester, United Kingdom
  • 9National Institute for Health and Research Biomedical Center, Moorfields Eye Hospital, London, United Kingdom
JAMA Ophthalmol. Published online November 19, 2020. doi:10.1001/jamaophthalmol.2020.5044
Key Points

Question  Can the limitations of current visual outcomes reporting standards of retrospective ophthalmology studies be overcome?

Findings  In this cohort study of 7802 patients, those with neovascular age-related macular degeneration beginning antivascular endothelial growth factor therapy were most likely to experience a positive visual outcome within the first 2.0 years after injection that is typically maintained for 1.1 years, with deterioration to poor vision within 8.7 years.

Meaning  Survival analyses can provide long-term prognostic information that may overcome the limitations of current reporting practices and should therefore be considered in analyses of real-world data.

Abstract

Importance  Although multiple imputation models for missing data and the 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, also called real-world outcomes.

Objective  To explore the potential usefulness of survival analysis techniques for retrospective clinical practice visual outcomes.

Design, Setting, and Participants  This retrospective cohort study covered a 12-year observation period at a tertiary eye center. Of 10 744 eyes with neovascular age-related macular degeneration receiving anti–vascular endothelial growth factor (VEGF) therapy between October 28, 2008, and February 1, 2020, 7802 eyes met study criteria (treatment-naive, first-treated eyes starting anti-VEGF therapy). Eyes were excluded from the analysis if they received photodynamic therapy or macular laser, any previous anti-VEGF therapy, treatment with anti-VEGF agents other than ranibizumab or aflibercept, or had an unknown date or visual acuity (VA) value at first injection.

Main Outcomes and Measures  Kaplan-Meier estimates and Cox proportional hazards modeling were used to consider VA reaching an Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 70 (Snellen equivalent, 20/40) or better, duration of VA sustained at or better than 70 (20/40), and VA declining to 35 (20/200) or worse.

Results  A total of 7802 patients (mean [SD] age, 78.7 [8.8] years; 4776 women [61.2%]; and 4785 White [61.3%]) were included in the study. The median time to attaining a VA letter score greater than or equal to 70 (20/40) was 2.0 years (95% CI, 1.87-2.32) after the first anti-VEGF injection. Predictive features were baseline VA (hazard ratio [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, 1.12; 95% CI, 1.10-1.15). Of the 4439 of 7802 patients (57%) attaining this outcome, median time sustained at an ETDRS letter score of 70 (20/40) or better was 1.1 years (95% CI, 1.1-1.2).

Conclusions and Relevance  In this cohort study, patients with neovascular age-related macular degeneration beginning anti-VEGF therapy were more likely to experience positive visual outcomes within the first 2.0 years after treatment, typically maintaining this outcome for 1.1 years but then deteriorating to poor vision within 8.7 years. These findings demonstrate the potential usefulness of the proposed analyses. This data set, combined with the statistical approach for retrospective analyses, may provide long-term prognostic information for patients newly diagnosed with this condition.

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