Effect of intravitreal bevacizumab injection on aqueous humor cytokine levels in clinically significant macular edema

Ophthalmology. 2009 Jan;116(1):80-6. doi: 10.1016/j.ophtha.2008.09.036.


Purpose: To determine the effect of intravitreal bevacizumab (Avastin, Genentech, Inc., San Francisco, CA) injection on aqueous humor cytokine levels in clinically significant macular edema (CSME).

Design: Retrospective, comparative study.

Participants: Seventeen eyes undergoing intravitreal injection for CSME and 11 eyes undergoing cataract surgery as negative controls. Nine patients with CSME were naïve to intravitreal bevacizumab injection (CSME group 1), and 8 patients previously received 1 intravitreal bevacizumab injection at a mean of 9.6+/-1.4 weeks earlier (CSME group 2).

Methods: Aqueous humor samples were collected before performing intravitreal injection in the CSME group and during cataract surgery in the control group. Aqueous cytokine levels were determined by immunoassay using multianalyte biochip array technology.

Main outcome measures: The concentration of cytokines in the aqueous humor was recorded as a mean (+/- standard deviation) in CSME groups 1 and 2 and the control group. Correlations of aqueous humor cytokine levels were evaluated.

Results: Significantly higher levels of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein (MCP)-1 were noted in patients with CSME compared with controls. Although higher vascular endothelial growth factor (VEGF) levels were noted in CSME group 1 (P = 0.001), a lower level of VEGF was noted after intravitreal bevacizumab injection in CSME group 2 (P = 0.004) compared with the control group. VEGF levels were also lower in CSME group 2 compared with CSME group 1 (P = 0.001). In CSME group 2, a significant negative correlation was observed between VEGF and IL-6 (rho = -0.833, P = 0.01) and VEGF and MCP-1 (rho = -0.736, P = 0.037).

Conclusions: Significantly higher levels of IL-6, IL-8, VEGF, and MCP-1 were noted in the aqueous humor of CSME. However, recurrence of macular edema was noted with significantly lower concentrations of VEGF after a single intravitreal injection of bevacizumab. This suggests the potential importance of IL-6 and MCP-1 in the pathogenesis of CSME.

Financial disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage*
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Aqueous Humor / metabolism*
  • Bevacizumab
  • Chemokine CCL2 / metabolism
  • Cytokines / metabolism*
  • Female
  • Humans
  • Injections
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Macular Edema / drug therapy*
  • Macular Edema / metabolism
  • Male
  • Middle Aged
  • Protein Array Analysis
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism
  • Vitreous Body


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • CCL2 protein, human
  • Chemokine CCL2
  • Cytokines
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab