Prevention and Treatment of Corneal Neovascularization: Comparison of Different Doses of Subconjunctival Bevacizumab with Corticosteroid in Experimental Rats

Background: To evaluate and compare the effect of different doses of subconjunctival bevacizumab with betamethasone on the development of corneal major new vessels in a rat model of corneal chemical injury. Methods: The right eyes of 100 male Sprague-Dawley rats were randomly divided into 10 experimental groups (n = 10 per group). Chemical cauterization of the cornea was performed by using silver nitrate/potassium nitrate sticks. Immediately following corneal cauterization, the animals in groups 1–5 received subconjunctival injections of 0.02 ml of normal saline (control A), betamethasone LA (6 mg/ml) and different doses of bevacizumab (1, 5 and 25 mg/ml), respectively. In another experiment, the animals in groups 6–10 received subconjunctival injections of 0.02 ml of normal saline (control B), betamethasone LA (6 mg/ml) and different doses of bevacizumab (1, 5 and 25 mg/ml), respectively, 7 days following corneal cauterization. The numbers of major thick-walled vessels originating from the limbus reaching the corneal scar were counted 7 days after corneal cauterization in groups 1–5 and 14 days after corneal cauterization in groups 6–10. Results: The number of major vessels in groups 1–5 was 19.63 ± 3.77, 17.25 ± 5.33, 16.10 ± 5.02, 12.89 ± 2.70 and 12.36 ± 4.45 when assessed 7 days after corneal cauterization, respectively. Administration of betamethasone in group 2 had no significant effect on the corneal major vessel count compared to control A. The number of major vessels in groups 4 and 5 (bevacizumab 5 and 25 mg/ml) was significantly lower than that of group 1 (p < 0.01, Student’s t test). The number of vessels in groups 6–10 was 12.55 ± 5.64, 11.30 ± 9.33, 5.50 ± 6.34, 2.73 ± 4.73 and 2.67 ± 3.77 when assessed 14 days after corneal cauterization, respectively. Subconjunctival administration of betamethasone 7 days after corneal cauterization did not reduce the amount of corneal major vessels compared to control B. Administration of 0.02 ml of bevacizumab in doses of 1, 5 and 25 mg/ml 7 days after corneal cauterization significantly reduced the amount of major vessels compared to group 6 (p = 0.01, p < 0.01 and p < 0.01, respectively). There was no significant difference in percent area of corneal scar between different groups. Conclusion: Single subconjunctival injection of bevacizumab is efficacious in the prevention of formation as well as regression of major vessels compared to betamethasone in this rat model of corneal neovascularization. Even