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.


CONCLUSIONS
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 lower doses of bevacizumab might be efficacious.
Hashemian
Mohammad Naser
MN
Farabi Eye Research Center, Department of Ophthalmology, Tehran University of Medical Sciences, Tehran, Iran.
Moghimi
Sasan
S
Kiumehr
Saman
S
Riazi
Mohammad
M
Amoli
Fahime Asadi
FA
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001623:Betamethasone / Q000008:administration & dosage*; D000068258:Bevacizumab; D003228:Conjunctiva / Q000187:drug effects; D003315:Cornea / Q000098:blood supply; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000517:prevention & control*; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000008:administration & dosage*; D007267:Injections; D008297:Male; D009883:Ophthalmic Solutions; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; D009883:Ophthalmic Solutions; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D001623:Betamethasone