The online version of this article (https://doi.org/10.1186/s12886-018-0688-3) contains supplementary material, which is available to authorized users.
To assess the effect of switching patients previously incompletely treated with ranibizumab (RBZ) to aflibercept (AFL) using a pro re nata (PRN) treatment strategy in neovascular age-related macular degeneration (nvAMD).
A retrospective case series was conducted on patients who had persistent or recurrent intra- and/or sub-retinal fluid treated initially with RBZ and subsequently switched to AFL. The main outcome measures were best corrected visual acuity (BCVA) and central retinal thickness (CRT) measured at different stages of the study. Friedman analysis of variance and Wilcoxon test were used to examine differences in BCVA and CRT.
Two hundred and seven eyes from 182 patients were included. BCVA and CRT improved significantly initially following 3 RBZ injections with a mean gain of 3.7 letters (p < 0.001) and a mean loss of 69 μm (p < 0.001) respectively. Following PRN RBZ therapy and immediately prior to switching to AFL (mean 129 weeks), there was a mean loss of 6.7 letters (p < 0.001) BCVA and a mean gain of 24 μm (p < 0.001) CRT.
AFL loading resulted in a mean improvement of 0.7 letters (p = 0.28) BCVA and 55 μm (p < 0.001) CRT. At final follow-up following AFL PRN therapy (mean 85 weeks), there was a mean loss of 8.9 letters (p < 0.001) BCVA and a mean gain of 12 μm (p < 0.05) CRT.
AFL loading resulted in a significant anatomical improvement but no significant change in visual acuity. However, the benefits of switching were gradually lost over time with AFL PRN dosing despite an increased injection rate when compared with RBZ PRN treatment.
Additional file 1: Supplementary data. Correlated component regression analysis examining the predictors of change in BCVA or CRT at each of the 4 stages of the study. (PDF 38 kb)12886_2018_688_MOESM1_ESM.pdf
Additional file 2: Supplementary data. Subgroup analysis of patients who incompletely responded to RBZ based on the extent of response to RBZ PRN therapy. (PDF 23 kb)12886_2018_688_MOESM2_ESM.pdf
Additional file 3: Supplementary data. Analysis of patients having both eyes treated. (PDF 17 kb)12886_2018_688_MOESM3_ESM.pdf
Gaudreault J, Fei D, Rusit J, Suboc P, Shiu V. Preclinical pharmacokinetics of ranibizumab (rhuFabV2) after a single intravitreal administration. Investig Ophthalmol Vis Sci. 2005;46:726–33. CrossRef
Wykoff CC, Brown DM, Maldonado ME, Croft DE. Aflibercept treatment for patients with exudative age-related macular degeneration who were incomplete responders to multiple ranibizumab injections (TURF trial). Br J Ophthalmol. 2014;98:951 LP–955. CrossRef
Sophie R, Akhtar A, Sepah YJ, Ibrahim M, Bittencourt M, Do DV, et al. Aflibercept: a potent vascular endothelial growth factor antagonist for Neovascular age-related macular degeneration and other retinal vascular diseases. Biol Ther. 2012;2:1–22. CrossRef
Group WC for the UA-RMDEU. The neovascular age-related macular degeneration database: multicenter study of 92 976 ranibizumab injections: report 1: visual acuity manuscript no. 2013-568. Ophthalmology. 2014;121:1092–101. CrossRef
Messenger WB, Campbell JP, Faridi A, Shippey L, Bailey ST, Lauer AK, et al. Injection frequency and anatomic outcomes 1 year following conversion to aflibercept in patients with neovascular age-related macular degeneration. Br J Ophthalmol. 2014;98:1205–7.
Spooner K, Hong T, Wijeyakumar W, Chang AA. Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta analysis. Clinl Ophthalmol. 2017;11:161–77. CrossRef
Davidson MH. Differences Between clinical trial efficacy and real-world effectiveness. Am J Manag Care. 2006;12(15 Suppl):S405–11. PubMed
Eghøj MS, Sørensen TL. Tachyphylaxis during treatment of exudative age-related macular degeneration with ranibizumab. Br J Ophthalmol. 2011;96:21 LP–23. CrossRef
Slean GR, Hemarat K, Khurana RN, Stewart JM. Conversion back to bevacizumab or ranibizumab for recurrent neovascular activity with aflibercept in age-related macular degeneration: a case series. Int J Retin Vitr. 2016;2:2. CrossRef
Homer N, Grewal DS, Mirza RG, Lyon AT, Gill MK. Transitioning to intravitreal aflibercept following a previous treat-and-extend dosing regimen in neovascular age-related macular degeneration: 24-month results. Eye (Lond). 2015;29:1152–5. CrossRef
- Clinical outcomes of switching to aflibercept using a pro re nata treatment regimen in patients with neovascular age-related macular degeneration who incompletely responded to ranibizumab
Peng Yong Sim
Cheng Yi Loo
- BioMed Central