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Bevacizumab dosing every 2 weeks for neovascular age-related macular degeneration refractory to monthly dosing

  • Clinical Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose:

To evaluate intravitreal bevacizumab every 2 weeks (biweekly) in refractory neovascular age-related macular degeneration (nAMD).

Study design:

Retrospective study.

Methods:

A retrospective study of consecutive nAMD patients unresponsive to monthly intravitreal anti-vascular endothelial growth factor (VEGF) switched to 3–4 biweekly injections.

Results:

Twenty-seven eyes of patients aged 82.08  ± 6.85 years were included. Prior to the 2-week interval bevacizumab injections, 74.1% (n=20) were treated with both bevacizumab and ranibizumab, 11.1% (3 eyes) also received aflibercept and 14.8% (4 eyes) had received prior treatment of monthly bevacizumab (average number of injections 21.5 ± 6.7). Best corrected visual acuity (BCVA) remained stable between baseline (logMAR 0.72± 0.60) and follow-up (0.76± 0.66) (p=0.41). Mean central macular thickness and macular volume did not change significantly between baseline and follow-up (p=0.35 and p=0.60, respectively). Six eyes (22.2%) showed morphologic anatomic improvements, while 19 eyes (70.4%) were stable and two eyes (7.4%) deteriorated from baseline. Subretinal fluid completely resolved in 3 of the eyes and improved in the other 3 eyes and in this group (22.2%) both central macular thickness (326.2 ± 101.4 versus 297.5 ± 97.2, p=0.002) and macular volume (8.69 ± 1.69 versus 8.22 ± 1.43, p=0.03) were significantly reduced. No adverse events were observed in any of the treated eyes.

Conclusion:

This study demonstrates that biweekly bevacizumab injections are effective in nearly one-quarter of nAMD non-responders with no adverse events reported. Switching earlier, rather than later, to this low cost modality may be of benefit for a portion of non-responders to conventional treatment.

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References

  1. Klein R, Klein BE, Jensen SC, Meuer SM. The five-year incidence and progression of age-related maculopathy: the beaver dam eye study. Ophthalmology. 1997;104:7–21.

    Article  CAS  Google Scholar 

  2. Klein R, Cruickshanks KJ, Nash SD, Krantz EM, Nieto FJ, Huang GH, et al. The prevalence of age-related macular degeneration and associated risk factors. Arch Ophthalmol. 2010;128:750–8.

    Article  CAS  Google Scholar 

  3. Tufail A, Patel PJ, Egan C, Hykin P, da Cruz L, Gregor Z, et al. ABC Trial Investigators. Bevacizumab for neovascular age related macular degeneration (ABC Trial): multicentre randomised double masked study. BMJ. 2010;340:c2459.

    Article  Google Scholar 

  4. Klein R, Klein BE, Jensen SC, Mares-Perlman JA, Cruickshanks KJ, Palta M. Age-related maculopathy in a multiracial United States population: the national health and nutrition examination survey III. Ophthalmology. 1999;106:1056–65.

    Article  CAS  Google Scholar 

  5. Bird AC. Therapeutic targets in age-related macular disease. J Clin Invest. 2010;120:3033–41.

    Article  CAS  Google Scholar 

  6. Kaiser PK, Brown DM, Zhang K, Hudson HL, Holz FG, Shapiro H, et al. Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results. Am J Ophthalmol. 2007;144:850–7.

    Article  CAS  Google Scholar 

  7. Boyer DS, Antoszyk AN, Awh CC, Bhisitkul RB, Shapiro H, Acharya NR. MARINA study Group. Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology. 2007;114:246–52.

    Article  Google Scholar 

  8. Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, et al. ANCHOR study group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432–44.

    Article  CAS  Google Scholar 

  9. Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, et al. MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419–31.

    Article  CAS  Google Scholar 

  10. Comparison of Age-related Macular Degeneration Treatments Trials Research G, Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, Grunwald JE, et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: 2-year results. Ophthalmology. 2012;119:1388–98.

    Article  Google Scholar 

  11. Investigators IS, Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ, Wordsworth S, et al. Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial. Ophthalmology. 2012;119:1399–411.

    Article  Google Scholar 

  12. Falkenstein IA, Cheng L, Morrison VL, Kozak I, Tammewar AM, Freeman WR. Standardized visual acuity results associated with primary versus secondary bevacizumab (avastin) treatment for choroidal neovascularization in age-related macular degeneration. Retina. 2007;27:701–6.

    Article  Google Scholar 

  13. Emerson MV, Lauer AK, Flaxel CJ, Wilson DJ, Francis PJ, Stout JT, et al. Intravitreal bevacizumab (Avastin) treatment of neovascular age-related macular degeneration. Retina. 2007;27:439–44.

    Article  Google Scholar 

  14. El-Mollayess GM, Mahfoud Z, Schakal AR, Salti HI, Jaafar D, Bashshur ZF. Fixed-interval versus OCT-guided variable dosing of intravitreal bevacizumab in the management of neovascular age-related macular degeneration: a 12-month randomized prospective study. Am J Ophthalmol. 2012;153(481–9):e1.

    Google Scholar 

  15. Solomon SD, Lindsley KB, Krzystolik MG, Vedula SS, Hawkins BS. Intravitreal bevacizumab versus ranibizumab for treatment of neovascular age-related macular degeneration: findings from a cochrane systematic review. Ophthalmology. 2016;123(70–7):e1.

    Google Scholar 

  16. Lazzeri S, Ripandelli G, Sartini MS, Parravano M, Varano M, Nardi M, et al. Aflibercept administration in neovascular age-related macular degeneration refractory to previous anti-vascular endothelial growth factor drugs: a critical review and new possible approaches to move forward. Angiogenesis. 2015;18:397–432.

    Article  CAS  Google Scholar 

  17. Otsuji T, Nagai Y, Sho K, Tsumura A, Koike N, Tsuda M, et al. Initial non-responders to ranibizumab in the treatment of age-related macular degeneration (AMD). Clin Ophthalmol. 2013;7:1487–90.

    Article  CAS  Google Scholar 

  18. Krebs I, Schmetterer L, Boltz A, Told R, Vecsei-Marlovits V, Egger S, et al. MANTA Research Group. A randomised double-masked trial comparing the visual outcome after treatment with ranibizumab or bevacizumab in patients with neovascular age-related macular degeneration. Br J Ophthalmol. 2013;97:266–71.

    Article  Google Scholar 

  19. Suzuki M, Nagai N, Izumi-Nagai K, Shinoda H, Koto T, Uchida A, et al. Predictive factors for non-response to intravitreal ranibizumab treatment in age-related macular degeneration. Br J Ophthalmol. 2014;98:1186–91.

    Article  Google Scholar 

  20. Lanzetta P, Mitchell P, Wolf S, Veritti D. Different antivascular endothelial growth factor treatments and regimens and their outcomes in neovascular age-related macular degeneration: a literature review. Br J Ophthalmol. 2013;97:1497–507.

    Article  Google Scholar 

  21. Segal O, Mimouni M, Nemet AY, Segev F, Geffen N, Nesher R. The effects of the frequency of the initial treatment with intravitreal bevacizumab on macular volume and visual acuity. J Ocul Pharmacol Ther. 2015;31:277–81.

    Article  CAS  Google Scholar 

  22. Rosenfeld PJ, Heier JS, Hantsbarger G, Shams N. Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis) for neovascular age-related macular degeneration. Ophthalmology. 2006;113(623):e1.

    Google Scholar 

  23. Stewart MW, Rosenfeld PJ, Penha FM, Wang F, Yehoshua Z, Bueno-Lopez E, et al. Pharmacokinetic rationale for dosing every 2 versus 4 weeks with intravitreal ranibizumab, bevacizumab, and aflibercept (vascular endothelial growth factor Trap-eye). Retina. 2012;32:434–57.

    CAS  PubMed  Google Scholar 

  24. Barikian A, Mahfoud Z, Abdulaal M, Safar A, Bashshur ZF. Induction with intravitreal bevacizumab every 2 weeks in the management of neovascular age-related macular degeneration. Am J Ophthalmol. 2015;159:131–7.

    Article  CAS  Google Scholar 

  25. Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, et al. VIEW 1 and VIEW 2 study groups. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119:2537–48.

    Article  Google Scholar 

  26. Witkin AJ, Rayess N, Garg SJ, Maguire JI, Storey P, Kaiser RS, et al. Alternating bi-weekly intravitreal ranibizumab and bevacizumab for refractory neovascular age-related macular degeneration with pigment epithelial detachment. Semin Ophthalmol. 2017;32(3):309–315.

    Article  Google Scholar 

  27. Simader C, Ritter M, Bolz M, Deak GG, Mayr-Sponer U, Golbaz I, et al. Morphologic parameters relevant for visual outcome during anti-angiogenic therapy of neovascular age-related macular degeneration. Ophthalmology. 2014;121:1237–45.

    Article  Google Scholar 

  28. Amoaku WM, Chakravarthy U, Gale R, Gavin M, Ghanchi F, Gibson J, et al. Defining response to anti-VEGF therapies in neovascular AMD. Eye (Lond). 2015;29:721–31.

    Article  CAS  Google Scholar 

  29. Tozer K, Roller AB, Chong LP, Sadda S, Folk JC, Mahajan VB, et al. Combination therapy for neovascular age-related macular degeneration refractory to anti-vascular endothelial growth factor agents. Ophthalmology. 2013;120:2029–34.

    Article  Google Scholar 

  30. Kim K, Kim ES, Kim Y, Yang JH, Yu SY, Kwak HW. Outcome of intravitreal aflibercept for refractory pigment epithelial detachment with or without subretinal fluid and secondary to age-related macular degeneration. Retina. 2017. https://doi.org/10.1097/iae.0000000000001947.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Curtis LH, Hammill BG, Schulman KA, Cousins SW. Risks of mortality, myocardial infarction, bleeding, and stroke associated with therapies for age-related macular degeneration. Arch Ophthalmol. 2010;128:1273–9.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Ophthalmology, Rambam Health Care Campus, Haifa, Israel

    Michael Mimouni & Igor Vainer

  2. Bruce and Ruth Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    Michael Mimouni

  3. Department of Ophthalmology, Meir Medical Center, Kfar Sava and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Amit Meshi, Tal Koren, Noa Geffen, Arie Y Nemet & Ori Segal

  4. Department of Ophthalmology, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel

    Assaf Gershoni

Authors
  1. Michael Mimouni
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  2. Amit Meshi
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  5. Tal Koren
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  6. Noa Geffen
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  7. Arie Y Nemet
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  8. Ori Segal
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Corresponding author

Correspondence to Ori Segal.

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Conflicts of interest

M. Mimouni, None; A. Meshi, None; I. Vainer, None; A. Gershoni, None; T. Koren, None; N. Geffen, None; A. Y. Nemet, None; O. Segal, None.

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Corresponding author: Ori Segal

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Mimouni, M., Meshi, A., Vainer, I. et al. Bevacizumab dosing every 2 weeks for neovascular age-related macular degeneration refractory to monthly dosing. Jpn J Ophthalmol 62, 652–658 (2018). https://doi.org/10.1007/s10384-018-0619-0

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  • DOI: https://doi.org/10.1007/s10384-018-0619-0

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