The systemic antiangiogenic effect of intravitreal aflibercept injection in a mouse model of retinopathy of prematurity

FASEB J. 2021 Mar;35(3):e21390. doi: 10.1096/fj.202002414R.


Retinopathy of prematurity (ROP) is a leading cause of childhood blindness and intravitreal anti-vascular endothelial growth factor (VEGF) injection is becoming a first-line choice for treatment of ROP. However, there is a major concern that intravitreally injected anti-VEGF agents could escape from the eye into the systemic circulation and impair systemic development. Moreover, escaped anti-VEGF agents could have an effect on the retina of the fellow eye. In this study, we investigated the hematogenous effect of a single intravitreal anti-VEGF injection in a mouse model of ROP. Here, we showed that single intravitreal aflibercept injection to one eye can affect body weight gain, the fellow eye, and renal vessels, although no apparent effect was observed in brain vessels. Furthermore, this hematogenous effect was dose-dependent. Our results provide very important insights into the clinical use of anti-VEGF agents for ROP treatment.

Keywords: anti-vascular endothelial growth factor; fellow eye; hematogenous effect; retinopathy of prematurity; systemic effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Animals
  • Dose-Response Relationship, Drug
  • Intravitreal Injections
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Vascular Endothelial Growth Factor / administration & dosage*
  • Receptors, Vascular Endothelial Growth Factor / blood
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / blood
  • Retinopathy of Prematurity / drug therapy*
  • Vascular Endothelial Growth Factor A / blood
  • Weight Gain / drug effects


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