Systemic Levels of Vascular Endothelial Growth Factor Before and After Intravitreal Injection of Aflibercept or Ranibizumab in Patients With Age-Related Macular Degeneration: A Randomised, Prospective Trial

Acta Ophthalmol. 2015 Mar;93(2):e154-9. doi: 10.1111/aos.12604. Epub 2014 Dec 8.


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

Methods: Thirty-eight patients with exudative AMD were included in this randomised, prospective study. Nineteen patients were randomised to treatment with intravitreal aflibercept (2.0 mg) and 19 to intravitreal ranibizumab (0.5 mg). The concentration of VEGF was measured by ELISA just before the injection, after 7 days and 1 month. Twenty-two age- and sex-matched healthy patients without chorioretinal diseases served as control.

Results: The median baseline plasma VEGF concentration was 61.0 pg/ml in the control group, 43.0 pg/ml in the aflibercept group and 59.0 pg/ml in the ranibizumab group (p=0.127). Seven days after intravitreal injection of aflibercept plasma levels were significantly reduced to values below the minimum detectable dose (MDD) in 17 of 19 patients (89.5%) resulting in a median VEGF concentration of <9 pg/ml (p<0.001). The reduction persisted throughout 1 month with values below the MDD in 5 of 19 patients (26.3%) and a median measurement of 17.0 pg/ml (p<0.001). In patients treated with ranibizumab no significant effects could be observed with a baseline VEGF of 59.0 pg/ml, 54.0 pg/ml at 7 days (p=0.776) and 58.5 pg/ml at 4 weeks of follow-up (p=0.670).

Conclusion: After intravitreal aflibercept injection, the systemic VEGF levels were significantly reduced throughout the observational period of 4 weeks. No significant systemic effects of intravitreal ranibizumab on plasma VEGF were observed.

Keywords: Aflibercept; age-related macular degeneration; ranibizumab; vascular endothelial growth factor (VEGF).

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Intravitreal Injections
  • Male
  • Prospective Studies
  • Ranibizumab
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use*
  • Recombinant Fusion Proteins / therapeutic use*
  • Tomography, Optical Coherence
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / blood*
  • Visual Acuity / physiology
  • Wet Macular Degeneration / blood
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / drug therapy*


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Recombinant Fusion Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor
  • Ranibizumab