To determine the dose–response characteristics of the antivascular endothelial growth factor agents ranibizumab and aflibercept in neovascular age-related macular degeneration using published randomized trials and observational series.
Literature review of published series from 2006 to 2018 as determined from electronic searches of PubMed and the Cochrane Library. Data extracted included treatment strategy, frequency, and first year visual acuity response. Monthly or bimonthly treatment schedules were classified as Fixed, pro re nata studies as PRN, treat and extend as TE, and when no strategy was listed, as Variable.
Of 2062 citations retrieved, 96 were deemed eligible; these 96 citations provided 120 data points of dose frequency versus visual acuity change in Year 1 of treatment. The dose–response curve was nonlinear, but a log transform of the number of injections per year yielded a linear relationship defined by the expression, Letters of Improvement = −6.66 + 15.7*log (number of injections Year 1). After accounting for the number of injections neither the drug used (ranibizumab or aflibercept) nor the strategy used (Fixed, pro re nata, treat and extend, or Variable) were significant predictors of acuity change. As a group, studies using the pro re nata approach had the lowest number of injections and the worst acuity improvements as a treatment strategy.
There seems to be a predictable, mathematically defined relationship between dose frequency and visual acuity change at 1 year in neovascular age-related macular degeneration. The performance of current treatment efforts, as suggested by reported series and Medicare claims data, seems to be substandard.