Antivascular Endothelial Growth Factor Dosing and Expected Acuity Outcome at 1 Year

Abstract

Purpose: 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.Methods: 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.Results: 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 = 26.66 + 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.Conclusion: 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.

Real-world Changes in Injection Frequency and Visual Outcomes Over Time in the Treatment of Neovascular Age-related Macular Degeneration

“…Thus, the treatment outcome was relatively better in patients diagnosed in the later period, supporting the ndings of Holz et al 19 and Spaide. 12 In the present study, the number of injections was markedly higher in patients treated using the TAE regimen (mean 10.5) than that in patients treated using the as-needed regimen (mean 5.9). This result is consistent with those of previous studies showing higher injection frequencies for the TAE regimen compared to the as-needed regimen.…”

“…Spaide also recently con rmed the association between higher injection frequency and better visual outcome. 12 The primary nding of the present study was the higher injection frequency in patients diagnosed in the later period. This trend was observed regardless of the MNV type.…”

“…10 The e cacy of the TAE regimen is generally comparable to that of the xed-dosing regimen and superior to that of the as-needed regimen. 11,12 In addition, switching from the as-needed regimen to the TAE regimen leads to improvement or at least stabilization of visual outcome. 13,14 However, the TAE regimen generally requires more frequent injections than those in the as-needed regimen.…”

Association between Retinal Thickness Variability and Visual Acuity Outcome during Maintenance Therapy Using Intravitreal Anti-Vascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration

“…Several studies and treatment guidelines have suggested that proactive treatment strategies such as fixed dosing and treat-and-extend dosing strategies might result in better visual acuity outcomes than PRN dosing when treating patients with nAMD [ 8 , 9 , 10 , 11 , 12 ]. However, a recent systematic review has demonstrated that after adjusting for the number of intravitreal anti-VEGF injections, neither the treatment dosing regimen adopted, nor the anti-VEGF agent used, were significant predictors for visual acuity changes [ 13 ]. Nonetheless, other factors such as age, anatomical status of the retina, including the presence or absence of subretinal and/or intraretinal fluids, optical coherence tomography (OCT) central macular thickness, and macular morphology have been implicated as important prognostic factors in determining visual outcomes [ 14 , 15 , 16 ].…”

Artificial intelligence-based predictions in neovascular age-related macular degeneration

“…This has been attributed to several factors, particularly differences between real-world and clinical trial patient populations and differences in treatment frequency [ 11 ▪ ]. Notably, several studies, including large real-world studies [ 9 , 10 , 11 ▪ , 12 , 13 ▪ , 14 ] and a recent systematic review [ 15 ▪ ], found that dose frequency is a consistent indicator of vision outcomes, with real-world studies reporting average vision gains of zero to three letters with approximately five to seven injections in the first year of treatment.…”