Recovery of plasma vascular endothelial growth factor concentrations during aflibercept loading phase and after the transition to bimonthly treatment for neovascular age-related macular degeneration

Br J Ophthalmol. 2015 Dec;99(12):1610-3. doi: 10.1136/bjophthalmol-2015-306781. Epub 2015 May 12.


Aims: To provide data on plasma vascular endothelial growth factor (VEGF) concentration during three consecutive monthly intravitreal aflibercept injections and after transition to bimonthly treatment in patients with neovascular age-related macular degeneration (nAMD).

Methods: Sixteen consecutive treatment-naïve Caucasian patients with nAMD were included in the study. The treatment consisted of one intravitreal aflibercept (2 mg) injection every 28 days for three consecutive months followed by a fourth injection 8 weeks later. VEGF plasma concentrations were measured with Luminex on day 0 (baseline, prior to first injection); days 1, 6 and 27 (prior to second injection); day 55 (prior to third injection) and days 97 and 111 (after third injection).

Results: Baseline plasma VEGF concentration was 59.6±13.3 pg/mL. Aflibercept decreased plasma VEGF concentration to 32.5±3 pg/mL on day 1 (p<0.0001) and 34.7±6.3 pg/mL on day 6 (p<0.0001). On day 27, the VEGF plasma level increased to 50.6±6.5 pg/mL (p=0.009) and on day 55 to 52.8±8.8 pg/mL (p=0.027). There was no statistically significant difference between mean plasma VEGF concentrations on days 27 and 55 (p=0.139). Plasma VEGF concentration recovered completely 6 weeks after the third injection, reaching 57.9±9.6 pg/mL on day 97 (p=0.600) and 59.5±11.6 pg/mL on day 111 (p=0.987).

Conclusions: Intravitreal aflibercept decreases plasma VEGF concentration mostly in the first week after treatment. Despite repeated monthly intravitreal injections, there was a monthly increase in plasma VEGF values to near baseline levels, with complete recovery 6 weeks after the third injection.

Trial registration number: Identifier no. NCT02125864.

Keywords: Degeneration; Macula; Neovascularisation; Retina; Treatment Medical.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / therapeutic use
  • Drug Administration Schedule
  • Female
  • Fluorescein Angiography
  • Humans
  • Intravitreal Injections
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, Vascular Endothelial Growth Factor / administration & dosage*
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / therapeutic use
  • Retina / pathology
  • Tomography, Optical Coherence
  • Vascular Endothelial Growth Factor A / blood*
  • Visual Acuity / physiology
  • Wet Macular Degeneration / blood
  • Wet Macular Degeneration / drug therapy*


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

Associated data