Positive Effect of Anti-VEGF Therapy for nAMD Most Likely in First 2 Years of Treatment

Survival analyses may help overcome the limitations of current reporting practices.

Neovascular age-related macular degeneration (nAMD) patients undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy are most likely to experience positive visual outcomes within the first 2 years after treatment, according to a study published in JAMA Ophthalmology. Researchers employed survival analyses techniques to uncover long-term prognostic information in an effort to overcome the limitations of current reporting practices. This technique should be considered in analyses of real-world data, the investigation concludes.

Long-term, clinically significant outcomes of VEGF inhibitors used to reduce macular neovascularization activity have been uncertain, according to the researchers. In this cohort study, investigators sought to overcome limitations of current visual outcome reporting standards. 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, these approaches typically can’t be applied to visual outcomes from retrospective analyses of clinical practice settings (“real-world outcomes”), according to the research team.

This retrospective study covered a 12-year observation period at a tertiary eye center in the United Kingdom. Of the 10,744 eyes with nAMD receiving anti–VEGF therapy at the center, 7802 eyes (mean [SD] age, 78.7 [8.8] years; 4776 female [61.2%]; and 4785 White [61.3%]) met study criteria. Patients 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. VA was defined as reaching an Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 70 (Snellen equivalent, 20/40) or better.

The analysis revealed that patients with nAMD treated with anti-VEGF therapy were more likely to experience positive visual outcomes within the first 2 years after starting treatment. Outcomes were typically maintained for 1.1 years, with deterioration to poor vision within 8.7 years. Specifically, the median time to attaining a VA letter score greater than or equal to 70 (20/40) was 2 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 4,439 of 7,802 patients (57%) attaining this outcome, the median time sustained at an ETDRS letter score of 70 (20/40) or better was 1.1 years (95%CI, 1.1-1.2).

The team’s findings suggest that early detection of nAMD and early initiation of anti-VEGF therapy were key factors in optimizing the likelihood of positive outcomes. This data set combined with the statistical approach for retrospective analyses, they assert, may provide long-term prognostic information for patients newly diagnosed with this condition.

The investigators acknowledge a few limitations of the study, including an assumption that censored patients have the same chance of experiencing an event as those still under observation. The nature of missing data means that this assumption and the underlying reason for the missing data can never be tested. Another assumption is that time of study enrollment is assumed not to affect event probabilities. In addition, limitations in observational studies of real-world clinical data, including variability of patients, management, follow-up, and outcome measurement are commonly recognized, according to the researchers. 

Disclosure: Several study authors declared affiliations with the pharmaceutical and device manufacturing industries. Please see the original reference for a full list of authors’ disclosures.


Fu DJ, Keenan TD, Faes L, et al. Insights from survival analyses during 12 years of anti–vascular endothelial growth factor therapy for neovascular age-related macular degeneration. JAMA Ophthalmol. Published online November 19, 2020. doi: 10.1001/jamaophthalmol.2020.5044