Effect of intravitreal bevacizumab on macular thickness: exploring serum and vitreous proangiogenic biomarkers in patients with diabetic macular edema

Turk J Med Sci. 2018 Aug 16;48(4):833-839. doi: 10.3906/sag-1802-212.

Abstract

Background/aim: This study evaluates diabetic macular-edema (DME) patients for the effect of intravitreal bevacizumab (IVB) injection on macular thickness and proangiogenic biomarkers in serum and vitreous.

Materials and methods: Forty DME patients were analyzed for macular thickness (MT). Twelve proangiogenic biomarkers in serum and vitreous were analyzed before and after IVB.

Results: Significant decrease in MT with vitreal vascular endothelial growth factor-A (VEGF-A) was observed as expected after IVB, while serum VEGF-A did not follow a decreasing trend in contrast to VEGF-C, which decreased both in serum and vitreous. Other vitreal factors like bone morphogenetic protein-9 (BMP9) and fibroblast growth factor (FGF) were also significantly decreased, while endothelial growth factor (EGF) increased following IVB. Before IVB, significant negative correlations were vitreous BMP9 with serum FGF, vitreous human growth factor (HGF) and interleukin-8 (IL-8) with serum endothelin, and vitreous and serum FGF and serum placental growth factor (PLGF) with EGF. After IVB, negative correlations in serum vs. vitreous were found for both HGF and PLGF with BMP9, and angiopoietin with FGF. Cube average thickness was negatively correlated with serum FGF and positively correlated with vitreous PLGF and endothelin.

Conclusion: Vascular endothelial growth factors are not the only factors that cause macular edema in diabetic patients. The effect of IVB on different proangiogenic biomarkers indicated a complex interplay of other factors in DME.

Keywords: Bevacizumab; central macular thickness; angiogenic factors; vascular endothelial growth factor; placental growth factor.

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Angiopoietins / metabolism
  • Bevacizumab / administration & dosage
  • Bevacizumab / pharmacology*
  • Bevacizumab / therapeutic use
  • Biomarkers / metabolism
  • Diabetic Retinopathy / complications*
  • Diabetic Retinopathy / drug therapy
  • Endothelins / metabolism
  • Epidermal Growth Factor / metabolism
  • Female
  • Fibroblast Growth Factors / metabolism
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Interleukin-8 / metabolism
  • Intravitreal Injections
  • Macula Lutea / drug effects*
  • Macula Lutea / pathology
  • Macular Edema / drug therapy
  • Macular Edema / pathology*
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / drug therapy
  • Placenta Growth Factor / blood
  • Vascular Endothelial Growth Factor A / metabolism
  • Vitreous Body / drug effects*
  • Vitreous Body / metabolism

Substances

  • Angiogenesis Inhibitors
  • Angiopoietins
  • Biomarkers
  • Endothelins
  • HGF protein, human
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • PGF protein, human
  • Vascular Endothelial Growth Factor A
  • Placenta Growth Factor
  • Bevacizumab
  • Fibroblast Growth Factors
  • Epidermal Growth Factor
  • Hepatocyte Growth Factor