Top

Graefe's Archive for Clinical and Experimental Ophthalmology

Published in:

01-09-2014 | Medical Ophthalmology

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

Authors: Izumi Yoshida, Tomoaki Shiba, Hikari Taniguchi, Mao Takahashi, Takeyoshi Murano, Nobuyuki Hiruta, Yuichi Hori, Hdieaki Bujo, Takatoshi Maeno

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 9/2014

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.

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 36:182–191PubMed

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 118:819–825PubMedCrossRef

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

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

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

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 116:2135–2140PubMedCrossRef

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

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

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 32:434–457PubMed

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 15:171–185PubMedCentralPubMedCrossRef

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:e5CrossRef

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–e30PubMedCrossRef

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 97:454–459PubMedCrossRef

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 39:367–374PubMedCrossRef

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 364:1897–1908PubMedCrossRef

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 94:1215–1218PubMedCrossRef

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 350:2335–2342PubMedCrossRef

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 21:60–65PubMedCrossRef

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 23:3697–3705PubMedCrossRef

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 49:287–297PubMedCrossRef

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 91:173–180PubMedCrossRef

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–H1058PubMed

23.

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

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 119:2537–2548PubMedCrossRef

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 116:1913–1919PubMedCrossRef

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 41:613–617PubMedCrossRef

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 43:1681–1683PubMedCentralPubMedCrossRef

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 121:188–192PubMedCrossRef

29.

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

Title: Evaluation of plasma vascular endothelial growth factor levels after intravitreal injection of ranibizumab and aflibercept for exudative age-related macular degeneration
Authors: Izumi Yoshida
Tomoaki Shiba
Hikari Taniguchi
Mao Takahashi
Takeyoshi Murano
Nobuyuki Hiruta
Yuichi Hori
Hdieaki Bujo
Takatoshi Maeno
Publication date: 01-09-2014
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 9/2014
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-014-2717-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 9/2014

Macular ganglion cell–inner plexiform layer thinning in patients with visual field defect that respects the vertical meridian

MiR-9 regulates the post-transcriptional level of VEGF165a by targeting SRPK-1 in ARPE-19 cells

Total IgE and eotaxin (CCL11) contents in tears of patients suffering from seasonal allergic conjunctivitis

Proton beam therapy for presumed and confirmed iris melanomas: a review of 36 cases

Calculating the predicted retinal thickness from spectral domain and time domain optical coherence tomography – comparison of different methods

Trans-conjunctival aqueous humor outflow in glaucomatous patients treated with prostaglandin analogues: an in vivo confocal microscopy study