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High-frequency aflibercept injections in persistent neovascular age-related macular degeneration

  • Retinal Disorders
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

An Erratum to this article was published on 19 May 2017

Abstract

Purpose

To report the 1-year outcomes of every-4-weeks (Q4W) as-needed aflibercept treatment in resistant neovascular age-related macular degeneration (nAMD) patients who had been treated and failed prior bevacizumab or ranibizumab injections, and who also responded poorly to every-8-weeks (Q8W) aflibercept treatment.

Methods

Forty-three eyes of 39 patients with persistent nAMD despite monthly bevacizumab and/or ranibizumab injections and who were switched to Q8W 2-mg aflibercept injections, but showed persistence of fluid were included. Patients were treated with as-needed Q4W aflibercept injections with monthly monitoring. Maximum retinal thickness (MRT), central macular thickness (CMT), maximum pigment epithelial detachment height (PED) and best-corrected visual acuity (BCVA) were assessed and compared to baseline when high-frequency aflibercept was initiated.

Results

A mean of 8 (interquartile range, 4–11) Q4W injections were given during the follow-up. MRT and CMT significantly decreased at all follow-up visits (p < 0.05); however, there was no significant change in maximum PED height (p > 0.05) at any visit. Mean BCVA was 0.38 ± 0.28 (logMAR) (≈20/63, Snellen) at baseline, and 0.4 ± 0.34 (logMAR) (≈20/76, Snellen) at 1 year (p = 0.76). Seventy-two percent of eyes maintained a final BCVA of 20/63 or better. Twelve eyes (28 %) had some subretinal scar tissue formation and 5 eyes (11.6 %) had evidence of atrophy at 1 year.

Conclusion

A stepwise algorithm with Q4W as-needed aflibercept treatment led to anatomic improvement in previously treated eyes which failed other therapies, including aflibercept every 8 weeks. Lack of visual improvement may be due to a ceiling effect as our eyes generally had good visual acuity.

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References

  1. Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, Martin DF, Maguire MG, Fine SL et al (2012) Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology 119:1388–1398

    Article  Google Scholar 

  2. Chin-Yee D, Eck T, Fowler S, Hardi A, Apte RS (2015) A systematic review of as needed versus treat and extend ranibizumab or bevacizumab treatment regimens for neovascular age-related macular degeneration. Br J Ophthalmol. doi:10.1136/-306987

    PubMed  Google Scholar 

  3. Rayess N, Houston SK 3rd, Gupta OP, Ho AC, Regillo CD (2015) Treatment outcomes after 3 years in neovascular age-related macular degeneration using a treat-and-extend regimen. Am J Ophthalmol 159:3–8

    Article  PubMed  Google Scholar 

  4. 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

    Article  CAS  PubMed  Google Scholar 

  5. Yonekawa Y, Andreoli C, Miller JB (2013) Conversion to aflibercept for chronic refractory or recurrent neovascular age-related macular degeneration. Am J Ophthalmol 156:29–35

    Article  CAS  PubMed  Google Scholar 

  6. Bakall B, Folk JC, Boldt HC et al (2013) Aflibercept therapy for exudative age-related macular degeneration resistant to bevacizumab and ranibizumab. Am J Ophthalmol 156:15–22

    Article  CAS  PubMed  Google Scholar 

  7. Cho H, Shah CP, Weber M, Heier JS (2013) Aflibercept for exudative AMD with persistent fluid on ranibizumab and/or bevacizumab. Br J Ophthalmol 97:1032–1035

    Article  PubMed  Google Scholar 

  8. Kumar N, Marsiglia M, Mrejen S et al (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

    Article  CAS  PubMed  Google Scholar 

  9. Ho VY, Yeh S, Olsen TW et al (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Heier JS, Brown DM, Chong V et al (2012) Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 119:2537–2548

    Article  PubMed  Google Scholar 

  11. Muftuoglu IK, Arcinue CA, Tsai FT et al (2016) Long term results of as needed aflibercept treatment in persistent neovascular macular degeneration. Am J Ophthalmol 167:1–9

    Article  CAS  PubMed  Google Scholar 

  12. Dirani A, Ambresin A, Marchionno L, Decugis D, Mantel I (2015) Factors influencing the treatment response of pigment epithelium detachment in age-related macular degeneration. Am J Ophthalmol 160:732–738

    Article  PubMed  Google Scholar 

  13. Broadhead GK, Hong T, Zhu M, Li H, Schlub TE, Wijeyakumar W, Chang AA (2015) Response of pigment epithelial detachments to intravitreal aflibercept among patients with treatment-resistant neovascular age-related macular degeneration. Retina 35:975–981

    Article  CAS  PubMed  Google Scholar 

  14. Zweifel SA, Engelbert M, Laud K et al (2009) Outer retinal tubulation: a novel optical coherence tomography finding. Arch Ophthalmol 127:1596–1602

    Article  PubMed  Google Scholar 

  15. Duker JS, Kaiser PK, Binder S et al (2013) The International Vitreomacular Traction Study Group classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology 120:2611–2619

    Article  PubMed  Google Scholar 

  16. Chhablani JK, Kim JS, Cheng L, Kozak I, Freeman W (2012) External limiting membrane as a predictor of visual improvement in diabetic macular edema after pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol 250:1415–1420

    Article  PubMed  Google Scholar 

  17. Stewart MW, Rosenfeld PJ (2008) Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol 92:667–668

    Article  CAS  PubMed  Google Scholar 

  18. Brown DM, Chen E, Mariani A, Major JC Jr, SAVE Study Group (2013) Super-dose anti-VEGF (SAVE) trial: 2.0 mg intravitreal ranibizumab for recalcitrant neovascular macular degeneration-primary end point. Ophthalmology 120:349–354

    Article  PubMed  Google Scholar 

  19. Wykoff CC, Brown DM, Maldonado ME, Croft DE (2014) Aflibercept treatment for patients with exudative age-related macular degeneration who were incomplete responders to multiple ranibizumab injections (TURF trial). Br J Ophthalmol 98:951–955

    Article  PubMed  PubMed Central  Google Scholar 

  20. Lee JE, Shin JP, Kim HW et al (2016) Efficacy of fixed-dosing aflibercept for treating polypoidal choroidal vasculopathy: 1-year results of the VAULT study. Graefes Arch Clin Exp Ophthalmol. doi:10.1007/s00417-016-3489-5

    Google Scholar 

  21. Ho AC, Busbee BG, Regillo CD, Wieland MR, Van Everen SA, Li Z, Rubio RG, Lai P, HARBOR Study Group (2014) Twenty-four-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology 121:2181–2192

    Article  PubMed  Google Scholar 

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Author information

Author notes

  1. Frank F. Tsai

    Present address: Sharp Rees-Stealy Medical Group Division of Ophthalmology, San Diego, CA, USA

Authors and Affiliations

  1. Department of Ophthalmology, Jacobs Retina Center at the Shiley Eye Institute, University of California San Diego, La Jolla, CA, USA

    Ilkay Kilic Muftuoglu, Frank F. Tsai, Raouf Gaber, Mostafa Alam, Amit Meshi & William R. Freeman

  2. Department of Ophthalmology, Istanbul Training and Research Hospital, Istanbul, Turkey

    Ilkay Kilic Muftuoglu

  3. Jacobs Retina Center at the Shiley Eye Institute, University of California San Diego, 94093 Campus Point Drive, La Jolla, CA, 92037, USA

    William R. Freeman

Authors
  1. Ilkay Kilic Muftuoglu
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  2. Frank F. Tsai
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  3. Raouf Gaber
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  4. Mostafa Alam
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  6. William R. Freeman
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Corresponding author

Correspondence to William R. Freeman.

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Funding

This work was supported in part by an unrestricted grant from the Research to Prevent Blindness organization (NY, USA) to the Department of Ophthalmology, Jacobs Retina Center, University of California San Diego (WRF) and the Scientific and Technological Research Council of Turkey (IKM; 2219/2015/2). The funding organizations had no role in the design or conduct of this research.

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s00417-017-3691-0.

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Muftuoglu, I.K., Tsai, F.F., Gaber, R. et al. High-frequency aflibercept injections in persistent neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 255, 709–717 (2017). https://doi.org/10.1007/s00417-016-3547-z

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  • DOI: https://doi.org/10.1007/s00417-016-3547-z

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