Skip to main content

Advertisement

SpringerLink
Log in

Long-term switching between ranibizumab and aflibercept in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

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

Abstract

Purpose

To investigate the rate and timing of switching between ranibizumab and aflibercept and to evaluate the difference in the switching rates among the different subtypes of neovascularization.

Methods

This retrospective study included 386 patients (386 eyes) who had been diagnosed with neovascular age-related macular degeneration (AMD) or polypoidal choroidal vasculopathy (PCV) and treated with ranibizumab (ranibizumab group, n = 260) or aflibercept (aflibercept group, n = 126). The rate and timing of switching from ranibizumab to aflibercept or vice versa were evaluated. Within the ranibizumab and the aflibercept groups, the switching rates were compared among the 3 subtypes of neovascularization: PCV, type 1 or 2 neovascularization, and type 3 neovascularization.

Results

During the mean 44.9 ± 15.9 months of follow-up period, switching rate was significantly higher in the ranibizumab group (28.8%, 75 patients) than in the aflibercept group (9.5%, 12 patients) (P < 0.001). No difference was observed in the mean duration between the diagnosis and switching among the ranibizumab (18.7 ± 14.6 months) and the aflibercept groups (14.8 ± 14.5 months) (P = 0.379). In the ranibizumab group, the switching rate was markedly higher in PCV (39.6%) than in type 1 or 2 neovascularization (17.6%) or in type 3 neovascularization (13.3%) (P < 0.001). In the aflibercept group, there was no significant difference in the switching rates among the subtypes of neovascularization (P = 0.811).

Conclusions

Although the timings of switching were similar, switching rate was higher in patients undergoing ranibizumab therapy than in those undergoing aflibercept therapy. The switching rate was especially higher in PCV patients undergoing ranibizumab therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. 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

    CAS  PubMed  Google Scholar 

  2. Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444

    CAS  PubMed  Google Scholar 

  3. Fung AE, Lalwani GA, Rosenfeld PJ, Dubovy SR, Michels S, Feuer WJ, Puliafito CA, Davis JL, Flynn HW Jr, Esquiabro M (2007) An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol 143:566–583

    CAS  PubMed  Google Scholar 

  4. Gupta OP, Shienbaum G, Patel AH, Fecarotta C, Kaiser RS, Regillo CD (2010) A treat and extend regimen using ranibizumab for neovascular age-related macular degeneration clinical and economic impact. Ophthalmology 117:2134–2140

    PubMed  Google Scholar 

  5. Cho M, Barbazetto IA, Freund KB (2009) Refractory neovascular age-related macular degeneration secondary to polypoidal choroidal vasculopathy. Am J Ophthalmol 148:70–78 e71

    PubMed  Google Scholar 

  6. Stangos AN, Gandhi JS, Nair-Sahni J, Heimann H, Pournaras CJ, Harding SP (2010) Polypoidal choroidal vasculopathy masquerading as neovascular age-related macular degeneration refractory to ranibizumab. Am J Ophthalmol 150:666–673

    CAS  PubMed  Google Scholar 

  7. Hatz K, Prunte C (2014) Polypoidal choroidal vasculopathy in Caucasian patients with presumed neovascular age-related macular degeneration and poor ranibizumab response. Br J Ophthalmol 98:188–194

    PubMed  Google Scholar 

  8. Eghoj MS, Sorensen TL (2012) Tachyphylaxis during treatment of exudative age-related macular degeneration with ranibizumab. Br J Ophthalmol 96:21–23

    PubMed  Google Scholar 

  9. Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U (2012) Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 119:2537–2548

    PubMed  Google Scholar 

  10. Browning DJ, Kaiser PK, Rosenfeld PJ, Stewart MW (2012) Aflibercept for age-related macular degeneration: a game-changer or quiet addition? Am J Ophthalmol 154:222–226

    CAS  PubMed  Google Scholar 

  11. 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 e11

    CAS  PubMed  Google Scholar 

  12. Yonekawa Y, Andreoli C, Miller JB, Loewenstein JI, Sobrin L, Eliott D, Vavvas DG, Miller JW, Kim IK (2013) Conversion to aflibercept for chronic refractory or recurrent neovascular age-related macular degeneration. Am J Ophthalmol 156:29–35 e22

    CAS  PubMed  Google Scholar 

  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

    CAS  PubMed  Google Scholar 

  14. Heussen FM, Shao Q, Ouyang Y, Joussen AM, Muller B (2014) Clinical outcomes after switching treatment from intravitreal ranibizumab to aflibercept in neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 252:909–915

    CAS  PubMed  Google Scholar 

  15. Empeslidis T, Storey M, Giannopoulos T, Konidaris V, Tranos PG, Panagiotou ES, Voudouragkaki IC, Konstas AG (2019) How successful is switching from bevacizumab or ranibizumab to aflibercept in age-related macular degeneration? A systematic overview. Adv Ther 36:1532–1548

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Mantel I, Gillies MC, Souied EH (2018) Switching between ranibizumab and aflibercept for the treatment of neovascular age-related macular degeneration. Surv Ophthalmol 63:638–645

    PubMed  Google Scholar 

  17. Gale RP, Pearce I, Eter N, Ghanchi F, Holz FG, Schmitz-Valckenberg S, Balaskas K, Burton BJL, Downes SM, Eleftheriadis H, George S, Gilmour D, Hamilton R, Lotery AJ, Patel N, Prakash P, Santiago C, Thomas S, Varma D, Walters G, Williams M, Wolf A, Zakri RH, Igwe F, Ayan F (2019) Anatomical and functional outcomes following switching from aflibercept to ranibizumab in neovascular age-related macular degeneration in Europe: SAFARI study. Br J Ophthalmol. https://doi.org/10.1136/bjophthalmol-2019-314251

  18. Laude A, Cackett PD, Vithana EN, Yeo IY, Wong D, Koh AH, Wong TY, Aung T (2010) Polypoidal choroidal vasculopathy and neovascular age-related macular degeneration: same or different disease? Prog Retin Eye Res 29:19–29

    PubMed  Google Scholar 

  19. Spaide RF (2019) New proposal for the pathophysiology of type 3 neovascularization as based on multimodal imaging findings. Retina 39:1451–1464

    CAS  PubMed  Google Scholar 

  20. Tsai ASH, Cheung N, Gan ATL, Jaffe GJ, Sivaprasad S, Wong TY, Cheung CMG (2017) Retinal angiomatous proliferation. Surv Ophthalmol 62:462–492

    PubMed  Google Scholar 

  21. Nagiel A, Sarraf D, Sadda SR, Spaide RF, Jung JJ, Bhavsar KV, Ameri H, Querques G, Freund KB (2015) Type 3 neovascularization: evolution, association with pigment epithelial detachment, and treatment response as revealed by spectral domain optical coherence tomography. Retina 35:638–647

    PubMed  Google Scholar 

  22. Chakravarthy U, Bezlyak V, Sagkriotis A, Griner R, Skelly A, Boyer DS, Milnes F (2019) Effectiveness of continued ranibizumab therapy in neovascular age-related macular degeneration versus switch to aflibercept: real world evidence. Ophthalmol Retina 3:8–15 e11

    PubMed  Google Scholar 

  23. Barthelmes D, Nguyen V, Walton R, Gillies MC, Daien V (2018) A pharmacoepidemiologic study of ranibizumab and aflibercept use 2013-2016. The fight retinal blindness! Project. Graefes Arch Clin Exp Ophthalmol 256:1839–1846

    CAS  PubMed  Google Scholar 

  24. Dansingani KK, Gal-Or O, Sadda SR, Yannuzzi LA, Freund KB (2018) Understanding aneurysmal type 1 neovascularization (polypoidal choroidal vasculopathy): a lesson in the taxonomy of 'expanded spectra' - a review. Clin Exp Ophthalmol 46:189–200

    PubMed  Google Scholar 

  25. Yannuzzi LA, Sorenson J, Spaide RF, Lipson B (1990) Idiopathic polypoidal choroidal vasculopathy (IPCV). Retina 10:1–8

    CAS  PubMed  Google Scholar 

  26. Spaide RF, Yannuzzi LA, Slakter JS, Sorenson J, Orlach DA (1995) Indocyanine green videoangiography of idiopathic polypoidal choroidal vasculopathy. Retina 15:100–110

    CAS  PubMed  Google Scholar 

  27. Wong CW, Yanagi Y, Lee WK, Ogura Y, Yeo I, Wong TY, Cheung CMG (2016) Age-related macular degeneration and polypoidal choroidal vasculopathy in Asians. Prog Retin Eye Res 53:107–139

    PubMed  Google Scholar 

  28. Yadav S, Parry DG, Beare NAV, Pearce IA (2017) Polypoidal choroidal vasculopathy: a common type of neovascular age-related macular degeneration in Caucasians. Br J Ophthalmol 101:1377–1380

    PubMed  Google Scholar 

  29. Oishi A, Kojima H, Mandai M, Honda S, Matsuoka T, Oh H, Kita M, Nagai T, Fujihara M, Bessho N, Uenishi M, Kurimoto Y, Negi A (2013) Comparison of the effect of ranibizumab and verteporfin for polypoidal choroidal vasculopathy: 12-month LAPTOP study results. Am J Ophthalmol 156:644–651

    CAS  PubMed  Google Scholar 

  30. Inoue M, Arakawa A, Yamane S, Kadonosono K (2013) Long-term outcome of intravitreal ranibizumab treatment, compared with photodynamic therapy, in patients with polypoidal choroidal vasculopathy. Eye (Lond) 27:1013–1020 quiz 1021

    CAS  Google Scholar 

  31. Kokame GT, deCarlo TE, Kaneko KN, Omizo JN, Lian R (2019) Anti-vascular endothelial growth factor resistance in exudative macular degeneration and polypoidal choroidal vasculopathy. Ophthalmol Retina 3:744–752

    PubMed  Google Scholar 

  32. Miura M, Iwasaki T, Goto H (2013) Intravitreal aflibercept for polypoidal choroidal vasculopathy after developing ranibizumab tachyphylaxis. Clin Ophthalmol 7:1591–1595

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Saito M, Kano M, Itagaki K, Oguchi Y, Sekiryu T (2014) Switching to intravitreal aflibercept injection for polypoidal choroidal vasculopathy refractory to ranibizumab. Retina 34:2192–2201

    CAS  PubMed  Google Scholar 

  34. Kawashima Y, Oishi A, Tsujikawa A, Yamashiro K, Miyake M, Ueda-Arakawa N, Yoshikawa M, Takahashi A, Yoshimura N (2015) Effects of aflibercept for ranibizumab-resistant neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Graefes Arch Clin Exp Ophthalmol 253:1471–1477

    CAS  PubMed  Google Scholar 

  35. Saito M, Kano M, Itagaki K, Ise S, Imaizumi K, Sekiryu T (2016) Subfoveal choroidal thickness in polypoidal choroidal vasculopathy after switching to intravitreal aflibercept injection. Jpn J Ophthalmol 60:35–41

    CAS  PubMed  Google Scholar 

  36. Gillies MC, Hunyor AP, Arnold JJ, Guymer RH, Wolf S, Ng P, Pecheur FL, McAllister IL (2019) Effect of ranibizumab and aflibercept on best-corrected visual acuity in treat-and-extend for neovascular age-related macular degeneration: a randomized clinical trial. JAMA Ophthalmol 137:372–379

    PubMed  PubMed Central  Google Scholar 

  37. Cho HJ, Kim KM, Kim HS, Han JI, Kim CG, Lee TG, Kim JW (2016) Intravitreal aflibercept and ranibizumab injections for polypoidal choroidal vasculopathy. Am J Ophthalmol 165:1–6

    CAS  PubMed  Google Scholar 

  38. Barthelmes D, Campain A, Nguyen P, Arnold JJ, McAllister IL, Simpson JM, Hunyor AP, Guymer R, Essex RW, Morlet N, Gillies MC (2016) Effects of switching from ranibizumab to aflibercept in eyes with exudative age-related macular degeneration. Br J Ophthalmol 100:1640–1645

    PubMed  PubMed Central  Google Scholar 

  39. Prenner JL, Halperin LS, Rycroft C, Hogue S, Williams Liu Z, Seibert R (2015) Disease burden in the treatment of age-related macular degeneration: findings from a time-and-motion study. Am J Ophthalmol 160:725–731 e721

    PubMed  Google Scholar 

  40. Mueller S, Agostini H, Ehlken C, Bauer-Steinhusen U, Hasanbasic Z, Wilke T (2016) Patient preferences in the treatment of neovascular age-related macular degeneration: a discrete choice experiment. Ophthalmology 123:876–883

    PubMed  Google Scholar 

  41. Markham A (2019) Brolucizumab: first approval. Drugs 79:1997–2000

    PubMed  Google Scholar 

  42. Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, Gomes AV, Warburton J, Weichselberger A, Holz FG (2020) HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 127:72–84

    PubMed  Google Scholar 

Download references

Funding

Kim’s Eye Hospital (Seoul, South Korea) provided funding for English editing support. The sponsor had no role in the design or conduct of this research.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Kim’s Eye Hospital, #156 Youngdeungpo-dong 4ga, Youngdeungpo-gu, Seoul, 150-034, South Korea

    Jae Hui Kim, Jong Woo Kim, Chul Gu Kim & Dong Won Lee

Authors
  1. Jae Hui Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jong Woo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chul Gu Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dong Won Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jae Hui Kim.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the institutional review board of Kim’s Eye Hospital (Seoul, South Korea). This study was conducted in accordance with the tenets of the Declaration of Helsinki.

Informed consent

Informed consent was not obtained in this study. Identifying information about participants was not presented in this study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, J.H., Kim, J.W., Kim, C.G. et al. Long-term switching between ranibizumab and aflibercept in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Graefes Arch Clin Exp Ophthalmol 258, 1677–1685 (2020). https://doi.org/10.1007/s00417-020-04710-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-020-04710-y

Keywords

Search

Navigation