Inhibition of corneal neovascularization by subconjunctival and topical bevacizumab and sunitinib in a rabbit model

Cornea. 2013 May;32(5):689-95. doi: 10.1097/ICO.0b013e3182801645.

Abstract

Purpose: To compare the effects of subconjunctival injection and topical application of bevacizumab and sunitinib on experimentally induced corneal neovascularization (CNV).

Methods: CNV was induced by sutures in the right eyes of 36 rabbits. After suture removal, the rabbits were divided into 6 groups with 6 rabbits in each group. In groups 1, 2, and 3, the eyes received a subconjunctival injection of 0.1 mL of normal saline, 2.5 mg/0.1 mL of bevacizumab, and 0.25 mg/0.1 mL of sunitinib, respectively, immediately after suture removal. A booster injection of the same agent was repeated 1 week later in each group. In groups 4, 5, and 6, the eyes received topical applications of saline, bevacizumab (5 mg/mL), and sunitinib (0.5 mg/mL), respectively. These solutions were applied twice a day for 2 weeks, starting immediately after suture removal. CNV was analyzed through biomicroscopy and through histological examination using hematoxylin and eosin and CD31 immunohistochemical staining.

Results: On day 14, the mean percentages of areas of CNV in sunitinib-treated eyes were smaller compared with saline-treated or bevacizumab-treated eyes in both the subconjunctival (P = 0.003 and 0.032, respectively) and topical groups (P < 0.001 in both). The topical administration of sunitinib was significantly more effective than the subconjunctival injection of the same drug at 1 week (P = 0.011). Upon histological examination of samples from the topical group, sunitinib-treated eyes showed lower vascularity than saline-treated and bevacizumab-treated eyes (P = 0.036 and 0.046, respectively).

Conclusions: These results suggest that sunitinib is more effective than bevacizumab for the inhibition of CNV. Furthermore, topical administration of sunitinib yields better results than a subconjunctival injection of the same medication.

Publication types

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

MeSH terms

  • Administration, Topical
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bevacizumab
  • Conjunctiva / drug effects
  • Corneal Neovascularization / drug therapy*
  • Corneal Neovascularization / metabolism
  • Corneal Neovascularization / pathology
  • Disease Models, Animal*
  • Female
  • Immunoenzyme Techniques
  • Indoles / therapeutic use*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Pyrroles / therapeutic use*
  • Rabbits
  • Sunitinib
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Indoles
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Pyrroles
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Sunitinib