The effect of bevacizumab on corneal neovascularization in rabbits

Abstract

Purpose: To determine the efficacy of topical application and subconjunctival injection of bevacizumab in the treatment of corneal neovascularization.

Methods: Corneal neovascularization was induced with a silk suture of the corneal stroma in 12 rabbits (24 eyes). One week after suturing, four rabbits were treated with topical bevacizumab at 5 mg/mL (group A) and another four rabbits were treated with topical bevacizumab 10 mg/mL (group B) in the right eyes twice a day for two weeks. A subconjunctival injection of bevacizumab 1.25 mg/mL was done in the right eyes of four rabbits (group C). All of the left eyes (12 eyes) were used as controls. The area of corneal neovascularization was measured after one and two weeks, and the concentration of vascular endothelial growth factor (VEGF) in corneal tissue was measured after two weeks.

Results: The neovascularized area was smaller in all treated groups than in the control group (p<0.001). Upon analysis of the neovascularized area, there was no significant difference between groups A and B. However, the mean neovascularized area of group B was significantly smaller than that of group C after two weeks of treatment (p=0.043). The histologic examination revealed fewer new corneal vessels in all treated groups than the control group. The concentration of VEGF was significantly lower in all treated groups compared to the control group (p<0.01), but no difference was shown between treated groups.

Conclusions: Topical and subconjunctival bevacizumab application may be useful in the treatment of corneal neovascularization and further study is necessary.

Keywords: Bevacizumab; Cornea; Neovascularization.

Fig. 1

Microscopic examination of the neovascularized area in the cornea. (A,B,C) Control group. (D,E,F) Group treated with topical 5 mg/mL bevacizumab. (G,H,I) Group treated with topical 10 mg/mL bevacizumab. (J,K,L) Group treated with subconjunctival bevacizumab 1.25 mg injection. (A,D,G,J) Initial neovascularization of the cornea was observed. One week later, neovascularized areas were quite similar in the control group (B), but markedly regressed in the treated groups (E,H,K). After two weeks, neovascularized areas were somewhat regressed in the control group (C), but significantly lower than that of treated groups (F,I,L).

Fig. 2

Mean area of new vessels in the treated and control groups, and p-value between topically treated groups and group with subconjunctival injection by Mann-Whitney U-test. The group treated with 10 mg/mL bevacizumab eye drops showed a more significant reduction of neovascularization area than the group treated by subconjunctival injection at the second week.

Fig. 3

Light microscopic examination of cornea stained with hematoxylin-eosin. (A) Some new vessels were seen in the stroma of the control group. (B) Some ghost vessels were seen and new vessels were almost regressed in that of groups treated with topical 5 mg/mL bevacizumab. Markedly regressed new vessels were also observed in that of the group treated with topical 10 mg/mL bevacizumab (C) and subconjunctival bevacizumab 1.25 mg injection (D). There were no pathologic changes in the stroma, epithelium, and endothelium of all groups.

Fig. 4

Mean concentration of vascular endothelial growth factor (VEGF) (pg/mL) in the cornea after two weeks treatment. A p-value was estimated by comparing each group with the control group (Mann-Whitney U-test). The treated group showed a reduction of significant concentrations in comparison with the control group.