title: Inhibitory effects of regorafenib, a multiple tyrosine kinase inhibitor, on corneal neovascularization.
abstract: OBJECTIVE
  To evaluate the inhibitory effects of regorafenib (BAY 73-4506), a multikinase inhibitor, on corneal neovascularization (NV).
  
  
  METHODS
  Thirty adult male Sprague-Dawley rats weighing 250-300 g, were used. Corneal NV was induced by NaOH in the left eyes of each rat. Following the establishment of alkali burn, the animals were randomized into five groups according to topical treatment. Group 1 (n = 6) received 0.9% NaCl, Group 2 (n = 6) received dimethyl sulfoxide, Group 3 (n = 6) received regorafenib 1 mg/mL, Group 4 (n =6) received bevacizumab 5 mg/mL and Group 5 (n = 6) received 0.1% dexamethasone phosphate. On the 7d, the corneal surface covered with neovascular vessels was measured on photographs as the percentage of the cornea's total area using computer-imaging analysis. The corneas obtained from rats were semiquantitatively evaluated for caspase-3 and vascular endothelial growth factor by immunostaining.
  
  
  RESULTS
  A statistically significant difference in the percent area of corneal NV was found among the groups (P <0.001). Although the Group 5 had the smallest percent area of corneal NV, there was no difference among Groups 3, 4 and 5 (P >0.005). There was a statistically significant difference among the groups in apoptotic cell density (P = 0.002). The staining intensity of vascular endothelial growth factor in the epithelial and endothelial layers of cornea was significantly different among the groups (P <0.05). The staining intensity of epithelial and endothelial vascular endothelial growth factor was significantly weaker in Groups 3, 4 and 5 than in Groups 1 and 2.
  
  
  CONCLUSIONS
  Topical administration of regorafenib 1 mg/mL is partly effective for preventing alkali-induced corneal NV in rats.
authors.affiliation: Department of Ophthalmology, Duzce University Medical Faculty, Duzce 81160, Turkey.
authors.forename: Halil Ibrahim
authors.initials: HI
authors.lastname: Onder
authors.affiliation: Department of Ophthalmology, Abant Izzet Baysal University Medical School, Bolu 14280, Turkey.
authors.forename: Mesut
authors.initials: M
authors.lastname: Erdurmus
authors.affiliation: Ophthalmology Clinic, Izzet Baysal State Hospital, Bolu 14000, Turkey.
authors.forename: Yasin Yücel
authors.initials: YY
authors.lastname: Bucak
authors.affiliation: Ophthalmology Clinic, Izzet Baysal State Hospital, Bolu 14000, Turkey.
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Simavli
authors.affiliation: Department of Pathology, Duzce University Medical Faculty, Duzce 81160, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Oktay
authors.affiliation: Department of Ophthalmology, Abant Izzet Baysal University Medical School, Bolu 14280, Turkey.
authors.forename: Ahmet Sahap
authors.initials: AS
authors.lastname: Kukner
keywords: corneal neovascularization; regorafenib; tyrosine kinase inhibitor