Skip to main content
SpringerLink
Log in

Aflibercept: A Review of Its Use in Diabetic Macular Oedema

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Aflibercept (Eylea®) is an anti-vascular endothelial growth factor agent indicated for intravitreal use in the treatment of diabetic macular oedema. In patients with diabetic macular oedema, significantly greater improvements from baseline to week 52 in visual acuity were seen with intravitreal aflibercept versus macular laser photocoagulation in the phase III VISTA-DME and VIVID-DME trials, and versus intravitreal bevacizumab or ranibizumab in those with worse visual acuity at baseline (i.e. Early Treatment Diabetic Retinopathy Study letter score of <69) in the phase III PROTOCOL-T trial. Intravitreal aflibercept was generally well tolerated in patients with diabetic macular oedema. In conclusion, intravitreal aflibercept is an important new treatment for diabetic macular oedema.

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

Similar content being viewed by others

References

  1. Aiello LP. Angiogenic pathways in diabetic retinopathy. N Engl J Med. 2005;353(8):839–41.

    Article  CAS  PubMed  Google Scholar 

  2. Klein BEK. Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiol. 2007;14(4):179–83.

    Article  PubMed  Google Scholar 

  3. Singh A, Stewart JM. Pathophysiology of diabetic macular edema. Int Ophthalmol Clin. 2009;49(2):1–11.

    Article  PubMed  Google Scholar 

  4. Virgili G, Parravano M, Menchini F, et al. Anti-vascular endothelial growth factor for diabetic macular oedema. Cochrane Database Syst Rev. 2014;10:CD007419.

    PubMed  Google Scholar 

  5. Stewart MW. The expanding role of vascular endothelial growth factor inhibitors in ophthalmology. Mayo Clin Proc. 2012;87(1):77–88.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Simó R, Sundstrom JM, Antonetti DA. Ocular anti-VEGF therapy for diabetic retinopathy: the role of VEGF in the pathogenesis of diabetic retinopathy. Diabetes Care. 2014;37(4):893–9.

    Article  PubMed  Google Scholar 

  7. Carmeliet P, Moons L, Luttun A, et al. Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med. 2001;7(5):575–83.

    Article  CAS  PubMed  Google Scholar 

  8. European Medicines Agency. Eylea (aflibercept): EU summary of product characteristics. 2015. http://www.ema.europa.eu/. Accessed 1 May 2015.

  9. Regeneron Pharmaceuticals Inc. EYLEA® (aflibercept): US prescribing information. 2015. http://www.eylea.us/. Accessed 1 May 2015.

  10. Frampton JE. Aflibercept for intravitreal injection: in neovascular age-related macular degeneration. Drugs Aging. 2012;29(10):839–46.

    Article  CAS  PubMed  Google Scholar 

  11. Yang LPH, McKeage K. Intravitreal aflibercept (Eylea®): a review of its use in patients with macular oedema secondary to central retinal vein occlusion. Drugs Aging. 2014;31(5):395–404.

    Article  CAS  PubMed  Google Scholar 

  12. Holash J, Davis S, Papadopoulos N, et al. VEGF-trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA. 2002;99(17):11393–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. 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(2):171–85.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Stewart MW, Rosenfeld PJ. Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol. 2008;92(5):667–8.

    Article  CAS  PubMed  Google Scholar 

  15. Deissler HL, Lang GK, Lang GE. Capacity of aflibercept to counteract VEGF-stimulated abnormal behavior of retinal microvascular endothelial cells. Exp Eye Res. 2014;122(Suppl C):20–31.

    Article  CAS  PubMed  Google Scholar 

  16. Ammar DA, Mandava N, Kahook MY. The effects of aflibercept on the viability and metabolism of ocular cells in vitro. Retina. 2013;33(5):1056–61.

    Article  CAS  PubMed  Google Scholar 

  17. Schnichels S, Hagemann U, Januschowski K, et al. Comparative toxicity and proliferation testing of aflibercept, bevacizumab and ranibizumab on different ocular cells. Br J Ophthalmol. 2013;97(7):917–23.

    Article  PubMed  Google Scholar 

  18. Malik D, Tarek M, Caceres del Carpio J, et al. Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture. Br J Ophthalmol. 2014;98(Suppl 1):i11–6.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Saishin Y, Saishin Y, Takahashi K, et al. VEGF-TRAPR1R2 suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier. J Cell Physiol. 2003;195(2):241–8.

    Article  CAS  PubMed  Google Scholar 

  20. Do DV, Nguyen QD, Shah SM, et al. An exploratory study of the safety, tolerability and bioactivity of a single intravitreal injection of vascular endothelial growth factor Trap-Eye in patients with diabetic macular oedema. Br J Ophthalmol. 2009;93(2):144–9.

    Article  CAS  PubMed  Google Scholar 

  21. Do DV, Schmidt-Erfurth U, Gonzalez VH, et al. The DA VINCI study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema. Ophthalmology. 2011;118(9):1819–26.

    Article  PubMed  Google Scholar 

  22. Do DV, Nguyen QD, Boyer D, et al. One-year outcomes of the DA VINCI study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology. 2012;119(8):1658–65.

    Article  PubMed  Google Scholar 

  23. Korobelnik J-F, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014;121(11):2247–54.

    Article  PubMed  Google Scholar 

  24. The Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372(13):1260–1.

    Article  Google Scholar 

  25. Gonzalez VH, Boyer DS, Schmidt-Erfurth U, et al. Microperimetric assessment of retinal sensitivity in eyes with diabetic macular edema from a phase 2 study of intravitreal aflibercept. Retina. 2015;35(4):687–94.

    Article  CAS  PubMed  Google Scholar 

  26. Stewart MW. Aflibercept ophthalmic solution: drug development and clinical uses. Clin Investig. 2013;3(11):1045–56.

    Article  CAS  Google Scholar 

  27. Christoforidis JB, Williams MM, Kothandaraman S, et al. Pharmacokinetic properties of intravitreal I-124-aflibercept in a rabbit model using PET/CT. Curr Eye Res. 2012;37(12):1171–4.

    Article  CAS  PubMed  Google Scholar 

  28. Stewart MW. What are the half-lives of ranbizumab and aflibercept (VEGF Trap-eye) in human eyes? Calculations with a mathematical model. Eye Rep. 2011;1(1):e5.

    Article  Google Scholar 

  29. Varano M, for the VIVID-DME/VISTA-DME Study Investigators. Evaluation of the efficacy and safety of intravitreal aflibercept in patients with diabetic macular edema: 100-week results from the VIVID-DME and VISTA-DME studies [poster]. In: 6th World Congress on Controversies in Ophthamology. 2015.

  30. McAllister I, Holz F, Metzig C. Time course of visual acuity changes with intravitreal aflibercept (IVT-AFL) or macular laser photocoagulation in patients with diabetic macular edema (DME): outcomes from the VIVID-DME and VISTA-DME clinical trials [abstract no. 0504]. Clin Exp Ophthalmol. 2014;42(Suppl 1):13.

    Google Scholar 

  31. Metzig C. Diabetic macular oedema and diabetic retinopathy: treatment outcomes with aflibercept do not depend on systemic diabetes control [abstract no. 54]. Diabetologia. 2014;57(Suppl 1):S29.

    Google Scholar 

  32. Lorenz K. Evaluation of intravitreal aflibercept for treatment of diabetic macular edema: visual acuity subgroups in VIVID-DME and VISTA-DME [abstract no. 5054]. In: AVRO 2014 Annual Meeting. 2014.

  33. Hahn P, Chung MM, Flynn HW Jr, et al. Postmarketing analysis of aflibercept-related sterile intraocular inflammation. JAMA Ophthalmol. 2015;133(4):421–6.

    Article  PubMed  Google Scholar 

  34. Fine HF, Roth DB, Shah SP, et al. Frequency and characteristics of intraocular inflammation after aflibercept injection. Retina. 2015;35(4):681–6.

    Article  CAS  PubMed  Google Scholar 

  35. Rodriguez M, Storey P, Do DV. Anti-VEGF therapy for the management of diabetic macular edema. Curr Ophthalmol Rep. 2013;1(3):122–7.

    Article  Google Scholar 

  36. American Diabetes Association. Standards of medical care in diabetes: 2015. Diabetes Care. 2015;38(Suppl 1):S1–93.

    Google Scholar 

  37. European Medicines Agency. Lucentis (ranibizumab): EU summary of product characteristics. 2014. http://www.ema.europa.eu/. Accessed 1 May 2015.

  38. Genentech Inc. Lucentis (ranibizumab): US prescribing information. 2015. http://www.lucentis.com/. Accessed 1 May 2015.

  39. Wykoff CC, Hariprasad SM. Comparing aflibercept, bevacizumab, and ranibizumab for DME: analysis of DRCR Protocol T. Ophthalmic Surg Lasers Imaging Retina. 2015;46(3):302–5.

    Article  PubMed  Google Scholar 

  40. Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119(4):789–801.

    Article  PubMed  Google Scholar 

  41. Michaelides M, Kaines A, Hamilton RD, et al. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology. 2010;117(6):1078–86.e2.

    Article  PubMed  Google Scholar 

  42. Falavarjani KG, Nguyen QD. Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature. Eye (Basingstoke). 2013;27(7):787–94.

    Google Scholar 

  43. Schwartz SG, Flynn HW, Scott IU. Emerging drugs for diabetic macular edema. Expert Opin Emerg Drugs. 2014;19(3):397–405.

    Article  CAS  PubMed  Google Scholar 

  44. O’Malley PG. Comparative effectiveness of anti-growth factor therapies for diabetic macular edema: summary of primary findings and conclusions. Arch Intern Med. 2012;172(13):1014–5.

    PubMed  Google Scholar 

  45. Martin DF, Maguire MG. Treatment choice for diabetic macular edema. N Engl J Med. 2015;372(13):1260–1.

    Article  CAS  PubMed  Google Scholar 

  46. Terasaki H. Efficacy and safety of intravitreal aflibercept injection for diabetic macular edema in Japanese patients: analysis of the VIVID-DME, VISTA-DME, and VIVID-Japan studies [abstract no. FP-FR-20]. In: World Ophthalmology Congress 2014. 2014.

Download references

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit. Gillian Keating is a salaried employee of Adis/Springer.

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay 0754, Auckland, New Zealand

    Gillian M. Keating

Authors
  1. Gillian M. Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gillian M. Keating.

Additional information

The manuscript was reviewed by: D. S. Boyer, Retina-Vitreous Associates Medical Group, Los Angeles, CA, USA; M. W. Stewart, Department of Ophthalmology, Mayo Clinic, Jacksonville, FL, USA; F. Viola, Ophthalmological Unit, Ca’ Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Keating, G.M. Aflibercept: A Review of Its Use in Diabetic Macular Oedema. Drugs 75, 1153–1160 (2015). https://doi.org/10.1007/s40265-015-0421-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-015-0421-y

Keywords

Search

Navigation