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

Abstract

IMPORTANCEAlthough 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 PARTICIPANTSThis 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 MEASURESKaplan-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 RELEVANCEIn 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.

Predictors of Visual Acuity After Treatment of Neovascular Age-Related Macular Degeneration – Current Perspectives

“…In real world studies, the relationship between age and visual outcome is not as consistent ( Table 2 ). Though associations are found in larger observational cohorts, 28 , 29 , 50 suggesting this is due to smaller sample sizes and larger patient variations in combination with its relatively small effect size.…”

“…In real world studies, the relationship between age and visual outcome is not as consistent (Table 2). Though associations are found in larger observational cohorts, 28,29,50 suggesting this is due to smaller sample sizes and larger patient variations in combination with its relatively small effect size. The effect of age may be influenced by other factors, with Yamashiro et al 51 finding that age was associated with 12-month VA changes in typical nAMD patients, but not for those presenting with the polypoidal choroidal vasculopathy (PCV) variant of AMD.…”

“…As data from real-world studies suggest that patients receive fewer injections than those studied in clinical trials, the benefit seen from a TREX regime likely comes from its proactive nature, as a higher number of injections are also associated with better visual outcomes. 28 , 37 , 50 , 118 …”

“…27 While it appears that anti-VEGF treatment is more effective in eyes with poorer VA, patients presenting with better initial VA are more likely to have better final VA. A large retrospective analysis from the Moorfields Eye Hospital (MEH) database reported a 43% increase in likelihood for achieving and maintaining a VA of 20/40 for every 5-letter increase in VA at baseline. 28 Meanwhile, data from the Swedish Macular Register revealed that eyes with initial VA >60 letters (20/63) had only a 20% risk of having low VA (≤60 letters) after 1 or 2 years of treatment, compared to 60% in eyes with low initial VA. 29 This relationship has also been observed in several longterm studies, [30][31][32][33][34][35] suggesting that the larger visual gains in those with worse initial VA are not enough to overcome a good starting VA despite continuous treatment. As those with worse initial VA are also more likely to respond negatively to treatment, low baseline VA may be an indicator for worse disease severity as there may be underlying pathology not treatable by anti-VEGF, such as atrophy, scarring or other anatomical changes not controlled for in multivariate analysis.…”

Ocular Therapeutics and Molecular Delivery Strategies for Neovascular Age-Related Macular Degeneration (nAMD)

“…A 12-year clinical cohort study on the patients with Ranibizumab and Aflibercept concluded that the visual outcomes positive within the first 2.0 years after treatment. However, within 8.7 years the visual outcome downgraded to poor vision [ 78 ].…”