Top

Graefe's Archive for Clinical and Experimental Ophthalmology

Published in:

Open Access 01-08-2020 | Macular Degeneration | Retinal Disorders

Beneficial switch from aflibercept to ranibizumab for the treatment of refractory neovascular age-related macular degeneration

Authors: Liza-Marie Marquis, Irmela Mantel

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 8/2020

Abstract

Purpose

The aim of this study was to evaluate the effects of switching to ranibizumab in patients with neovascular age-related macular degeneration (nAMD) refractory to aflibercept treatment and to identify predictive factors for switch response.

Methods

A retrospective chart review was conducted including 32 eyes from 26 patients with refractory nAMD, who switched from monthly intravitreal aflibercept treatment (≥ 6 months) to ranibizumab. Outcome measures included changes in visual acuity (VA), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and central retinal thickness (CRT), evaluated at 6 months before switch (T1), at the time of switch (T2), and 3 months post-switch (T3).

Results

There was an increase in CRT from T1 to T2, which decreased after switch from T2 to T3. Regression analysis of the changes per month observed between time points showed significant differences in PED height (p = 0.02), SRF (p = 0.01), and neuroretinal thickness as a measure for IRF (p = 0.03). No significant change was found for VA. Predictive factors for better switch response included an exacerbation between T1 and T2, thicker measurements at T2, male sex, shorter treatment duration before switch, and fewer preceding injections. No association with preceding switch was found.

Conclusion

Patients with nAMD refractory to aflibercept benefit from switching to ranibizumab, particularly those whose condition worsened prior to the switch. This may be explained by drug tolerance to aflibercept. Our findings may facilitate making appropriate treatment decisions, potentially improving patient outcomes.

Klaver CCW, Wolfs RCW, Vingerling JR, Hofman A, de Jong PTVM (1998) Age-specific prevalence and causes of blindness and visual impairment in an older population: the Rotterdam study. Arch Ophthalmol 116:653–658. https://doi.org/10.1001/archopht.116.5.653 CrossRefPubMed

The Eye Diseases Prevalence Research Group* (2004) Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 122:477–485. https://doi.org/10.1001/archopht.122.4.477 CrossRef

Heier JS, Brown DM, Chong V et al (2012) Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 119:2537–2548. https://doi.org/10.1016/j.ophtha.2012.09.006 CrossRefPubMed

Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431. https://doi.org/10.1056/NEJMoa054481 CrossRefPubMed

Papadopoulos N, Martin J, Ruan Q, Rafique A, Rosconi MP, Shi E, Pyles EA, Yancopoulos GD, Stahl N, Wiegand SJ (2012) Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF trap, ranibizumab and bevacizumab. Angiogenesis 15:171–185. https://doi.org/10.1007/s10456-011-9249-6 CrossRefPubMedPubMedCentral

Stewart M (2012) Clinical and differential utility of VEGF inhibitors in wet age-related macular degeneration: focus on aflibercept. Clin Ophthalmol 6:1175–1186. https://doi.org/10.2147/OPTH.S33372 CrossRefPubMedPubMedCentral

Stewart MW, Rosenfeld PJ (2008) Predicted biological activity of intravitreal VEGF trap. Br J Ophthalmol 92:667. https://doi.org/10.1136/bjo.2007.134874 CrossRefPubMed

Yang S, Zhao J, Sun X (2016) Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review. Drug Des Devel Ther 10:1857–1867. https://doi.org/10.2147/DDDT.S97653 CrossRefPubMedPubMedCentral

Dirani A, Mantel I (2018) Ranibizumab treatment history as predictor of the switch-response to aflibercept: evidence for drug tolerance. Clin Ophthalmol 12:593–600. https://doi.org/10.2147/OPTH.S160367 CrossRefPubMedPubMedCentral

10.

Arcinue CA, Ma F, Barteselli G, Sharpsten L, Gomez ML, Freeman WR (2015) One-year outcomes of aflibercept in recurrent or persistent neovascular age-related macular degeneration. Am J Ophthalmol 159:426–436.e2. https://doi.org/10.1016/j.ajo.2014.11.022 CrossRefPubMed

11.

de Massougnes S, Dirani A, Ambresin A, Decugis D, Marchionno L, Mantel I (2016) Pigment epithelial detachment response to aflibercept in neovascular age-related macular degeneration refractory to ranibizumab: time course and drug effects. Retina 36:881–888. https://doi.org/10.1097/IAE.0000000000000813 CrossRefPubMed

12.

Ho VY, Yeh S, Olsen TW, Bergstrom CS, Yan J, Cribbs BE, Hubbard GB (2013) Short-term outcomes of aflibercept for neovascular age-related macular degeneration in eyes previously treated with other vascular endothelial growth factor inhibitors. Am J Ophthalmol 156:23–28.e2. https://doi.org/10.1016/j.ajo.2013.02.009 CrossRefPubMedPubMedCentral

13.

Kumar N, Marsiglia M, Mrejen S, Fung AT, Slakter J, Sorenson J, Freund KB (2013) Visual and anatomical outcomes of intravitreal aflibercept in eyes with persistent subfoveal fluid despite previous treatments with ranibizumab in patients with neovascular age-related macular degeneration. Retina 33:1605–1612. https://doi.org/10.1097/IAE.0b013e31828e8551 CrossRefPubMed

14.

Bakall B, Folk JC, Boldt HC, Sohn EH, Stone EM, Russell SR, Mahajan VB (2013) Aflibercept therapy for exudative age-related macular degeneration resistant to bevacizumab and ranibizumab. Am J Ophthalmol 156:15–22.e1. https://doi.org/10.1016/j.ajo.2013.02.017 CrossRefPubMed

15.

Chang AA, Li H, Broadhead GK, Hong T, Schlub TE, Wijeyakumar W, Zhu M (2014) Intravitreal aflibercept for treatment-resistant neovascular age-related macular degeneration. Ophthalmology 121:188–192. https://doi.org/10.1016/j.ophtha.2013.08.035 CrossRefPubMed

16.

Fassnacht-Riederle H, Becker M, Graf N, Michels S (2014) Effect of aflibercept in insufficient responders to prior anti-VEGF therapy in neovascular AMD. Graefes Arch Clin Exp Ophthalmol 252:1705–1709. https://doi.org/10.1007/s00417-014-2589-3 CrossRefPubMedPubMedCentral

17.

Griffin DR, Richmond PP, Olson JC (2014) Intravitreal aflibercept outcomes in patients with persistent macular exudate previously treated with bevacizumab and/or ranibizumab for neovascular age-related macular degeneration. J Ophthalmol 2014:1–6. https://doi.org/10.1155/2014/497178 CrossRef

18.

Despreaux R, Cohen SY, Semoun O, Zambrowski O, Jung C, Oubraham H, Souied EH (2016) Short-term results of switchback from aflibercept to ranibizumab in neovascular age-related macular degeneration in clinical practice. Graefes Arch Clin Exp Ophthalmol 254:639–644. https://doi.org/10.1007/s00417-015-3084-1 CrossRefPubMed

19.

Gale RP, Pearce I, Eter N et al (2019) Anatomical and functional outcomes following switching from aflibercept to ranibizumab in neovascular age-related macular degeneration in Europe: SAFARI study. Br J Ophthalmol 2019:314251. https://doi.org/10.1136/bjophthalmol-2019-314251 CrossRef

20.

Slean GR, Hemarat K, Khurana RN, Stewart JM (2016) Conversion back to bevacizumab or ranibizumab for recurrent neovascular activity with aflibercept in age-related macular degeneration: a case series. Int J Retina Vitreous 2:2. https://doi.org/10.1186/s40942-016-0028-9 CrossRefPubMedPubMedCentral

21.

Parvin P, Zola M, Dirani A, Ambresin A, Mantel I (2017) Two-year outcome of an observe-and-plan regimen for neovascular age-related macular degeneration treated with aflibercept. Graefes Arch Clin Exp Ophthalmol 255:2127–2134. https://doi.org/10.1007/s00417-017-3762-2 CrossRefPubMedPubMedCentral

22.

Gianniou C, Dirani A, Ferrini W, Marchionno L, Decugis D, Deli A, Ambresin A, Mantel I (2015) Two-year outcome of an observe-and-plan regimen for neovascular age-related macular degeneration: how to alleviate the clinical burden with maintained functional results. Eye 29:342–349. https://doi.org/10.1038/eye.2014.258 CrossRefPubMed

23.

Mantel I, Niderprim S-A, Gianniou C, Deli A, Ambresin A (2014) Reducing the clinical burden of ranibizumab treatment for neovascular age-related macular degeneration using an individually planned regimen. Br J Ophthalmol 98:1192–1196. https://doi.org/10.1136/bjophthalmol-2013-304556 CrossRefPubMedPubMedCentral

24.

Hara C, Wakabayashi T, Fukushima Y, Sayanagi K, Kawasaki R, Sato S, Sakaguchi H, Nishida K (2019) Tachyphylaxis during treatment of exudative age-related macular degeneration with aflibercept. Graefes Arch Clin Exp Ophthalmol 257:2559–2569. https://doi.org/10.1007/s00417-019-04456-2 CrossRefPubMed

25.

Binder S (2012) Loss of reactivity in intravitreal anti-VEGF therapy: tachyphylaxis or tolerance? Br J Ophthalmol 96:1–2. https://doi.org/10.1136/bjophthalmol-2011-301236 CrossRefPubMed

26.

Simader C, Ritter M, Bolz M, Deák GG, Mayr-Sponer U, Golbaz I, Kundi M, Schmidt-Erfurth UM (2014) Morphologic parameters relevant for visual outcome during anti-angiogenic therapy of neovascular age-related macular degeneration. Ophthalmology 121:1237–1245. https://doi.org/10.1016/j.ophtha.2013.12.029 CrossRefPubMed

Title: Beneficial switch from aflibercept to ranibizumab for the treatment of refractory neovascular age-related macular degeneration
Authors: Liza-Marie Marquis
Irmela Mantel
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Keywords: Macular Degeneration
Aflibercept
Ranibizumab
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 8/2020
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-020-04730-8

At a glance: The STEP trials

Springer Medicine

Beneficial switch from aflibercept to ranibizumab for the treatment of refractory neovascular age-related macular degeneration

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 8/2020

Characteristic distribution of microaneurysms and capillary dropouts in diabetic macular edema

Intraocular pressure increases during dynamic resistance training exercises according to the exercise phase in healthy young adults

Effect of image averaging on optical coherence tomography angiography data in eyes with branch retinal vein occlusion

FFP3, FFP2, N95, surgical masks and respirators: what should we be wearing for ophthalmic surgery in the COVID-19 pandemic?

Quantitative analysis of retinal and choriocapillary vascular density of multiple evanescent white dot syndrome by optical coherence tomography angiography

The long-term effect of human immunodeficiency virus infection on retinal microvasculature and the ganglion cell–inner plexiform layer: an OCT angiography study