Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of plasma vascular endothelial growth factor levels after intravitreal injection of ranibizumab and aflibercept for exudative age-related macular degeneration

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

Abstract

Background

To evaluate the plasma vascular endothelial growth factor (VEGF) levels after one intravitreal injection of aflibercept or ranibizumab in patients with exudative age-related macular degeneration (AMD).

Methods

Twenty-four Japanese with exudative AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation were included. Fourteen patients received an intravitreal injection of aflibercept, and ten patients received an intravitreal injection of ranibizumab. Plasma VEGF levels were evaluated within 7 days before the intravitreal injections and 1 day, 1 week, and 1 month after the intravitreal injection.

Results

In the ranibizumab group, the mean plasma VEGF levels were 245.7 ± 233.4 pg/ml before the injection, 246.6 ± 304.8 pg/ml after 1 day, 217.8 ± 212.9 pg/ml after 1 week, and 260.0 ± 290.1 pg/ml after 1 month. The plasma VEGF levels did not decrease significantly in patients in the ranibizumab group at any time point. In the aflibercept group, the mean plasma VEGF levels were 280.0 ± 170.3 pg/ml before the intravitreal injection and 8.2 ± 12.9 pg/ml after 1 day, 9.1 ± 9.1 pg/ml after 1 week, and 41.9 ± 41.4 pg/ml after 1 month (p < 0.0001, vs before injection).

Conclusion

Intravitreally injected aflibercept reduced plasma VEGF over at least 1 month. In contrast, intravitreal injection of ranibizumab did not cause a significant reduction in the plasma VEGF levels.

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. Klein R, Wang Q, Klein BE, Moss SE, Meuer SM (1995) The relationship of age-related maculopathy, cataract, and glaucoma to visual acuity. Invest Ophthalmol Vis Sci 36:182–191

    CAS  PubMed  Google Scholar 

  2. Muñoz B, West SK, Rubin GS, Schein OD, Quigley HA, Bressler SB, Bandeen-Roche K (2000) Causes of blindness and visual impairment in a population of older Americans: the Salisbury Eye Evaluation Study. Arch Ophthalmol 118:819–825

    Article  PubMed  Google Scholar 

  3. Attebo K, Mitchell P, Smith W (1996) Visual acuity and the causes of visual loss in Australia: The Blue Mountains Eye Study. Ophthalmology 103:357–364

    Article  CAS  PubMed  Google Scholar 

  4. Ferris FL 3rd, Fine SL, Hyman L (1984) Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol 102:1640–1642

    Article  PubMed  Google Scholar 

  5. Macular Photocoagulation Study Group (1991) Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 109:1220–1231

    Article  Google Scholar 

  6. Yasuda M, Kiyohara Y, Hata Y, Arakawa S, Yonemoto K, Doi Y, Iida M, Ishibashi T (2009) Nine-year incidence and risk factors for age related macular degeneration in a defined Japanese population: the Hisayama study. Ophthalmology 116:2135–2140

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. Stewart MW, Rosenfeld PJ, Penha FM, Wang F, Yehoshua Z, Bueno-Lopez E, Lopez PF (2012) Pharmacokinetic rationale for dosing every 2 weeks versus 4 weeks with intravitreal ranibizumab, bevacizumab, and aflibercept (vascular endothelial growth factor trap-eye). Retina 32:434–457

    CAS  PubMed  Google Scholar 

  10. Papadopoulos N, Martin J, Ruan Q, Rafique A, Rosconi MP, Shi E, Pyles EA, Yancopoulos GD, Stahl N, Wiegand SJ (2012) Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis 15:171–185

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  Google Scholar 

  12. Carneiro AM, Costa R, Falcão MS, Barthelmes D, Mendonça LS, Fonseca SL, Gonçalves R, Gonçalves C, Falcão-Reis FM, Soares R (2012) Vascular endothelial growth factor plasma levels before and after treatment of neovascular age-related macular degeneration with bevacizumab or ranibizumab. Acta Ophthalmol 90:e25–e30

    Article  CAS  PubMed  Google Scholar 

  13. Zehetner C, Kirchmair R, Huber S, Kralinger MT, Kieselbach GF (2013) Plasma levels of vascular endothelial growth factor before and after intravitreal injection of bevacizumab, ranibizumab and pegaptanib in patients with age-related macular degeneration, and in patients with diabetic macular oedema. Br J Ophthalmol 97:454–459

    Article  PubMed  Google Scholar 

  14. Bird AC, Bressler NM, Bressler SB, Chisholm IH, Coscas G, Davis MD, de Jong PT, Klaver CC, Klein BE, Klein R, Mitchell P, Sarks JP, Sarks SH, Soubrane G, Taylor HR, Vingerling JR: The International ARM Epidemiological Study Group (1995) An international classification and grading system for age-related maculopathy and age-related macular degeneration. Surv Ophthalmol 39:367–374

    Article  CAS  PubMed  Google Scholar 

  15. CATT Research Group, Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ (2011) Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 364:1897–1908

    Article  CAS  PubMed  Google Scholar 

  16. Matsuyama K, Ogata N, Matsuoka M, Wada M, Takahashi K, Nishimura T (2010) Plasma levels of vascular endothelial growth factor and pigment epithelium-derived factor before and after intravitreal injection of bevacizumab. Br J Ophthalmol 94:1215–1218

    Article  CAS  PubMed  Google Scholar 

  17. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342

    Article  CAS  PubMed  Google Scholar 

  18. Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, Griffing S, Bergsland E (2003) Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 21:60–65

    Article  CAS  PubMed  Google Scholar 

  19. Kabbinavar FF, Schulz J, McCleod M, Patel T, Hamm JT, Hecht JR, Mass R, Perrou B, Nelson B, Novotny WF (2005) Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 23:3697–3705

    Article  CAS  PubMed  Google Scholar 

  20. Ranpura V, Hapani S, Chuang J, Wu S (2010) Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis of randomized controlled trials. Acta Oncol 49:287–297

    Article  CAS  PubMed  Google Scholar 

  21. Scappaticci FA, Fehrenbacher L, Cartwright T, Hainsworth JD, Heim W, Berlin J, Kabbinavar F, Novotny W, Sarkar S, Hurwitz H (2005) Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 91:173–180

    Article  CAS  PubMed  Google Scholar 

  22. Hood JD, Meininger CJ, Ziche M, Granger HJ (1998) VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol 274:H1054–H1058

    CAS  PubMed  Google Scholar 

  23. Gordon MS, Cunningham D (2005) Managing patients treated with bevacizumab combination therapy. Oncology 69(Suppl 3):25–33

    Article  CAS  PubMed  Google Scholar 

  24. 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; VIEW 1 and VIEW 2 Study Groups (2012) Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 119:2537–2548

    Article  PubMed  Google Scholar 

  25. Sun C, Klein R, Wong TY (2009) Age-related macular degeneration and risk of coronary heart disease and stroke: the Cardiovascular Health Study. Ophthalmology 116:1913–1919

    Article  PubMed  Google Scholar 

  26. Hu CC, Ho JD, Lin HC (2010) Neovascular age-related macular degeneration and the risk of stroke: a 5-year population-based follow-up study. Stroke 41:613–617

    Article  PubMed  Google Scholar 

  27. Ikram MK, Mitchell P, Klein R, Sharrett AR, Couper DJ, Wong TY (2012) Age-related macular degeneration and long-term risk of stroke subtypes. Stroke 43:1681–1683

    Article  PubMed Central  PubMed  Google Scholar 

  28. Chang AA, Li H, Broadhead GK, Hong T, Schlub TE, Wijeyakumar W, Zhu M (2013) Intravitreal aflibercept for treatment-resistant neovascular age-related macular degeneration. Ophthalmology 121:188–192

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

There was no sponsorship or other support for this study. The authors have no financial conflicts of interest. We had no statistical consultation or assistance.

Conflict of interest

The authors have no proprietary or financial interest in any aspect of this report.

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Toho University Sakura Medical Center, 564-1 Shimoshizu, Chiba, Sakura, 285-8741, Japan

    Izumi Yoshida, Tomoaki Shiba, Hikari Taniguchi, Yuichi Hori & Takatoshi Maeno

  2. Cardiovascular Center, Toho University Sakura Medical Center, Chiba, Japan

    Mao Takahashi

  3. Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Chiba, Japan

    Takeyoshi Murano & Hdieaki Bujo

  4. Department of Pathology, Toho University Sakura Medical Center, Chiba, Japan

    Nobuyuki Hiruta

Authors
  1. Izumi Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomoaki Shiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hikari Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mao Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takeyoshi Murano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nobuyuki Hiruta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuichi Hori
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hdieaki Bujo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Takatoshi Maeno
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tomoaki Shiba.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoshida, I., Shiba, T., Taniguchi, H. et al. Evaluation of plasma vascular endothelial growth factor levels after intravitreal injection of ranibizumab and aflibercept for exudative age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 252, 1483–1489 (2014). https://doi.org/10.1007/s00417-014-2717-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-014-2717-0

Keywords

Search

Navigation