The effects of subconjunctival bevacizumab, ranibizumab, and aflibercept on corneal neovascularization

Hum Exp Toxicol. 2022 Jan-Dec:41:9603271221084674. doi: 10.1177/09603271221084674.

Abstract

Purpose: To investigate the effects of subconjunctival bevacizumab, ranibizumab, and aflibercept in an experimental corneal neovascularization model.

Materials and methods: The eyes of 24 rats were chemically cauterized and randomly divided into four groups: bevacizumab group (0.05 mL/1.25 mg bevacizumab), ranibizumab group (0.05 mL/0.5 mg ranibizumab), aflibercept group (0.05 mL/1.25 mg aflibercept), and control group (0.05 mL saline solution). Plasma vascular endothelial growth factor (VEGF) levels were among the major measurement outcomes to assess corneal neovascularization. The collected plasmas were analyzed using the SIGMA RAB0511 Rat VEGF Elisa kit. The PCR technique and VEGF amplification procedures were used for molecular analysis. Each cornea was removed and histologically examined on day 21. Corneal images were evaluated by image analyzer software.

Results: In the post-injection period, the number of major corneal arteries decreased significantly in the injection groups when compared to the control group (p = 0.037), but no statistically significant differences were noted among the injection groups (p > 0.05). The aflibercept group had the lowest area of neovascularization. Immunohistochemical staining revealed substantially lower VEGF percentages in neovascularized arteries of the injection groups than the control group (p = 0.015). In TUNEL staining, the mean TUNEL value (number/1hpf) was substantially greater in the control group than in the injection groups, but the mean TUNEL values were similar between the injection groups (p = 0.019, p > 0.05, respectively). No statistically significant differences were observed between the groups in terms of corneal surface area with increased cellularity, edema, and inflammation (p = 0.263). The mean plasma VEGF concentration in the control group was statistically greater than those in the injection groups (p = 0.001).

Conclusion: Subconjunctival bevacizumab, ranibizumab, and aflibercept crossed the blood and seemed to be effective in inhibiting corneal neovascularization without causing epitheliopathy in an experimental rat model compared to the controls. However, no significant results were noted between these three anti-VEGF molecules.

Keywords: Corneal neovascularization; TUNEL staining; immunohistochemical examination; subconjunctival injection; vascular endothelial growth factor.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Bevacizumab / pharmacology
  • Bevacizumab / therapeutic use
  • Corneal Neovascularization* / drug therapy
  • Corneal Neovascularization* / metabolism
  • Corneal Neovascularization* / pathology
  • Disease Models, Animal
  • Ranibizumab* / pharmacology
  • Ranibizumab* / therapeutic use
  • Rats
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A / metabolism

Substances

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