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Published in: BMC Ophthalmology 1/2015

Open Access 01-12-2015 | Research article

Short-term outcomes of switching anti-VEGF agents in eyes with treatment-resistant wet AMD

Authors: Figen Batioglu, Sibel Demirel, Emin Özmert, Ahmet Abdullayev, Serdar Bilici

Published in: BMC Ophthalmology | Issue 1/2015

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Abstract

Background

To investigate the short-term outcomes of treatment with intravitreal aflibercept in cases with wet age-related macular degeneration (AMD) resistant to ranibizumab.

Methods

The study included patients who had been undergoing follow-up for a minimum of three months at the Ankara University Faculty of Medicine Ophthalmology Department’s Retina Unit with a diagnosis of wet AMD. All cases had received intravitreal aflibercept injection due to the presence of intraretinal/subretinal fluid and pigment epithelial detachment (PED), as detected by optical coherence tomography (OCT), despite having received intravitreal ranibizumab. Medical records of the cases were investigated retrospectively and the demographic data, treatments administered before aflibercept injection, best-corrected visual acuity (BCVA) before and after aflibercept injection, central macular thickness (CMT), and the presence of intraretinal/subretinal fluid and the height and presence of PED were recorded.

Results

A total of 29 eyes from 11 females and 17 males were included in the study. The mean age was 73.89 ± 7.49 (62–92). The average number of intraocular injections administered before aflibercept injection was 11.75 ± 5.73 (6–25). The mean duration of follow-up following aflibercept injection was 4.55 ± 2.14 (3–11) months, with a mean of 3.44 ± 0.73 (3–5) aflibercept injections during this period. The mean BCVA values before and after aflibercept injection were found to be 0.83 and 0.77 LogMAR, respectively. The mean CMT values before and after aflibercept injection were 471.3 (97–1365) and 345.1 (97–585) microns, respectively (p < 0.001). The PED height before and after aflibercept injection was 350.4 ± 151.7 (129–793) and 255.52 ± 156.8 (0–528) microns, respectively (p < 0.05).

Conclusion

Switching to intravitreal aflibercept appears to be an effective treatment modality for patients with AMD who are resistant to ranibizumab. While anatomic success including the effect of reducing the PED height was achieved in the short term following aflibercept injection in all cases, no concomitant increase in visual acuity occurred. This is attributed to the long-term presence of chronic fluid and the development of scar tissue before the treatment.
Literature
1.
go back to reference Boyer DS, Heier JS, Brown DM, et al. A phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology. 2009;116:1731–9.CrossRefPubMed Boyer DS, Heier JS, Brown DM, et al. A phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology. 2009;116:1731–9.CrossRefPubMed
2.
go back to reference Fung AE, Lalwani GA, Rosenfeld PJ, et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol. 2007;143:566–83.CrossRefPubMed Fung AE, Lalwani GA, Rosenfeld PJ, et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol. 2007;143:566–83.CrossRefPubMed
3.
go back to reference Holz FG, Amoaku W, Donate J, et al. Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular agerelated macular degeneration: the SUSTAIN study. Ophthalmology. 2011;118:663–71.CrossRefPubMed Holz FG, Amoaku W, Donate J, et al. Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular agerelated macular degeneration: the SUSTAIN study. Ophthalmology. 2011;118:663–71.CrossRefPubMed
4.
go back to reference Patel RD, Momi RS, Hariprasad SM. Review of ranibizumab trials for neovascular age-related macular degeneration. Semin Ophthalmol. 2011;26:372–9.CrossRefPubMed Patel RD, Momi RS, Hariprasad SM. Review of ranibizumab trials for neovascular age-related macular degeneration. Semin Ophthalmol. 2011;26:372–9.CrossRefPubMed
5.
go back to reference Singer MA, Awh CC, Sadda S, et al. HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology. 2012;119:1175–83.CrossRefPubMed Singer MA, Awh CC, Sadda S, et al. HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology. 2012;119:1175–83.CrossRefPubMed
6.
go back to reference Lalwani GA, Rosenfeld PJ, Fung AE, et al. A variable-dosing regimen with intravitreal ranibizumab for neovascular agerelated macular degeneration: year 2 of the PrONTO Study. Am J Ophthalmol. 2009;148:43–58.CrossRefPubMed Lalwani GA, Rosenfeld PJ, Fung AE, et al. A variable-dosing regimen with intravitreal ranibizumab for neovascular agerelated macular degeneration: year 2 of the PrONTO Study. Am J Ophthalmol. 2009;148:43–58.CrossRefPubMed
7.
go back to reference Rosenfeld PJ, Brown DM, Heier JS, MARINA Study Group, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419–31.CrossRefPubMed Rosenfeld PJ, Brown DM, Heier JS, MARINA Study Group, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419–31.CrossRefPubMed
8.
go back to reference Brown DM, Michels M, Kaiser PK, et al. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR Study. Ophthalmology. 2009;116:57–65.CrossRefPubMed Brown DM, Michels M, Kaiser PK, et al. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR Study. Ophthalmology. 2009;116:57–65.CrossRefPubMed
9.
go back to reference Rofagha S, Bhisitkul RB, Boyer DS, SEVEN-UP Study Group, et al. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology. 2013;120:2292–9.CrossRefPubMed Rofagha S, Bhisitkul RB, Boyer DS, SEVEN-UP Study Group, et al. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology. 2013;120:2292–9.CrossRefPubMed
10.
go back to reference Gasperini JL, Fawzi AA, Khondkaryan A, et al. Bevacizumab and ranibizumab tachyphylaxis in the treatment of choroidal neovascularisation. Br J Ophthalmol. 2012;96(1):14–20.CrossRefPubMed Gasperini JL, Fawzi AA, Khondkaryan A, et al. Bevacizumab and ranibizumab tachyphylaxis in the treatment of choroidal neovascularisation. Br J Ophthalmol. 2012;96(1):14–20.CrossRefPubMed
11.
go back to reference Forooghian F, Cukras C, Meyerle CB, Chew EY, Wong WT. Tachyphylaxis after intravitreal bevacizumab for exudative age-related macular degeneration. Retina. 2009;29(6):723–31.CrossRefPubMedPubMedCentral Forooghian F, Cukras C, Meyerle CB, Chew EY, Wong WT. Tachyphylaxis after intravitreal bevacizumab for exudative age-related macular degeneration. Retina. 2009;29(6):723–31.CrossRefPubMedPubMedCentral
12.
13.
go back to reference Stewart MW, Rosenfeld PJ. Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol. 2008;92:667–8.CrossRefPubMed Stewart MW, Rosenfeld PJ. Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol. 2008;92:667–8.CrossRefPubMed
14.
go back to reference Stewart MW, Rosenfeld PJ, Penha FM, et al. Pharmacokinetic rationale for dosing every 2 weeks versus 4 weeks with intravitreal ranibizumab, bevacizumab, and aflibercept (vascular endothelial growth factor Trap-eye). Retina. 2012;32:434–57.PubMed Stewart MW, Rosenfeld PJ, Penha FM, et al. Pharmacokinetic rationale for dosing every 2 weeks versus 4 weeks with intravitreal ranibizumab, bevacizumab, and aflibercept (vascular endothelial growth factor Trap-eye). Retina. 2012;32:434–57.PubMed
15.
go back to reference Papadopoulos N, Martin J, Ruan Q, et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012;15:171–85.CrossRefPubMedPubMedCentral Papadopoulos N, Martin J, Ruan Q, et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012;15:171–85.CrossRefPubMedPubMedCentral
16.
go back to reference Browning DJ, Kaiser PK, Rosenfeld PJ, Stewart MW. Aflibercept for age-related macular degeneration: a game-changer or quiet addition? Am J Ophthalmol. 2012;154:222–6.CrossRefPubMed Browning DJ, Kaiser PK, Rosenfeld PJ, Stewart MW. Aflibercept for age-related macular degeneration: a game-changer or quiet addition? Am J Ophthalmol. 2012;154:222–6.CrossRefPubMed
17.
go back to reference Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology. 2012;119:2537–48.CrossRefPubMed Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology. 2012;119:2537–48.CrossRefPubMed
18.
go back to reference Ho VY, Yeh S, Olsen TW, et al. term outcomes of aflibercept for neovascular age-related macular degeneration in eyes previously treated with other vascular endothelial growth factor ınhibitors. Am J Ophthalmol. 2013;156(1):23–8.CrossRefPubMedPubMedCentral Ho VY, Yeh S, Olsen TW, et al. term outcomes of aflibercept for neovascular age-related macular degeneration in eyes previously treated with other vascular endothelial growth factor ınhibitors. Am J Ophthalmol. 2013;156(1):23–8.CrossRefPubMedPubMedCentral
19.
go back to reference Binder S. Loss of reactivity in intravitreal anti-VEGF therapy: tachyphylaxis or tolerance? Br J Ophthalmol. 2012;96(1):1–2.CrossRefPubMed Binder S. Loss of reactivity in intravitreal anti-VEGF therapy: tachyphylaxis or tolerance? Br J Ophthalmol. 2012;96(1):1–2.CrossRefPubMed
20.
go back to reference Grossniklaus HE, Ling JX, Wallace TM, et al. Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization. Mol Vis. 2002;8:119–26.PubMed Grossniklaus HE, Ling JX, Wallace TM, et al. Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization. Mol Vis. 2002;8:119–26.PubMed
21.
go back to reference Espinosa-Heidmann DG, Suner IJ, Hernandez P, Monroy D, Csaky KG, Cousins SW. Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci. 2003;44(8):3586–92.CrossRefPubMed Espinosa-Heidmann DG, Suner IJ, Hernandez P, Monroy D, Csaky KG, Cousins SW. Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization. Invest Ophthalmol Vis Sci. 2003;44(8):3586–92.CrossRefPubMed
22.
go back to reference Sakurai E, Anand A, Ambati BK, van Rooijen N, Ambati J. Macrophage depletion inhibits experimental choroidal neovascularization. Invest Ophthalmol Vis Sci. 2003;44(8):3578–85.CrossRefPubMed Sakurai E, Anand A, Ambati BK, van Rooijen N, Ambati J. Macrophage depletion inhibits experimental choroidal neovascularization. Invest Ophthalmol Vis Sci. 2003;44(8):3578–85.CrossRefPubMed
23.
go back to reference Cho H, Shah CP, Weber M, Heier JS. Aflibercept for exudative AMD with persistent fluid on ranibizumab and/or bevacizumab. Br J Ophthalmol. 2013;97(8):1032–5.CrossRefPubMed Cho H, Shah CP, Weber M, Heier JS. Aflibercept for exudative AMD with persistent fluid on ranibizumab and/or bevacizumab. Br J Ophthalmol. 2013;97(8):1032–5.CrossRefPubMed
24.
go back to reference Bakall B, Folk JC, Boldt HC, et al. Aflibercept therapy for exudative age-related macular degeneration resistant to bevacizumab and ranibizumab. Am J Ophthalmol. 2013;156(1):15–22.CrossRefPubMed Bakall B, Folk JC, Boldt HC, et al. Aflibercept therapy for exudative age-related macular degeneration resistant to bevacizumab and ranibizumab. Am J Ophthalmol. 2013;156(1):15–22.CrossRefPubMed
25.
go back to reference Yonekawa Y, Andreoli C, Miller JB, et al. Conversion to aflibercept for chronic refractory or recurrent neovascular age-related macular degeneration. Am J Ophthalmol. 2013;156(1):29–35.CrossRefPubMed Yonekawa Y, Andreoli C, Miller JB, et al. Conversion to aflibercept for chronic refractory or recurrent neovascular age-related macular degeneration. Am J Ophthalmol. 2013;156(1):29–35.CrossRefPubMed
26.
go back to reference Kumar N, Marsiglia M, Mrejen S, et al. 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. 2012;33:1605–12.CrossRef Kumar N, Marsiglia M, Mrejen S, et al. 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. 2012;33:1605–12.CrossRef
27.
go back to reference Hall LB, Zebardast N, Huang JJ and Adelman RA. Aflibercept in the treatment of neovascular age-related Macular degeneration in previously treated patients. J Ocul Pharmacol Ther. DOI: 10.1089/jop.2013.0188 Hall LB, Zebardast N, Huang JJ and Adelman RA. Aflibercept in the treatment of neovascular age-related Macular degeneration in previously treated patients. J Ocul Pharmacol Ther. DOI: 10.1089/jop.2013.0188
28.
go back to reference Heussen FM, Shao Q, Ouyang Y et al. Clinical outcomes after switching treatment from intravitreal ranibizumab to aflibercept in neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol doi:10.1007/s00417-013-2553-7. Heussen FM, Shao Q, Ouyang Y et al. Clinical outcomes after switching treatment from intravitreal ranibizumab to aflibercept in neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol doi:10.1007/s00417-013-2553-7.
29.
go back to reference Hoerster R, Muether PS, Sitnilska V et al. Fibrovascular pigment epithelial detachment is a risk factor for long-term visual decay in neovascular age-related macular degeneretion. Retina. 2014 Jun 14. [Epub ahead of print]. Hoerster R, Muether PS, Sitnilska V et al. Fibrovascular pigment epithelial detachment is a risk factor for long-term visual decay in neovascular age-related macular degeneretion. Retina. 2014 Jun 14. [Epub ahead of print].
30.
go back to reference Inoue M, Arakawa A, Yamane S, Kadonosono K. Variable response of vascularized pigment epithelial detachments to ranibizumab based on lesion subtypes, including polypoidal choroidal vasculopathy. Retina. 2013;33(5):990–7.CrossRefPubMed Inoue M, Arakawa A, Yamane S, Kadonosono K. Variable response of vascularized pigment epithelial detachments to ranibizumab based on lesion subtypes, including polypoidal choroidal vasculopathy. Retina. 2013;33(5):990–7.CrossRefPubMed
Metadata
Title
Short-term outcomes of switching anti-VEGF agents in eyes with treatment-resistant wet AMD
Authors
Figen Batioglu
Sibel Demirel
Emin Özmert
Ahmet Abdullayev
Serdar Bilici
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Ophthalmology / Issue 1/2015
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/s12886-015-0025-z

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