Inhibition of corneal neovascularization by topical bevacizumab (Anti-VEGF) and Sunitinib (Anti-VEGF and Anti-PDGF) in an animal model.
OBJECTIVE
To evaluate the effects of topically applied bevacizumab and sunitinib on experimentally induced corneal neovascularization.


METHODS
Experimental animal study.


METHODS
Thirty-six New Zealand rabbits were involved. One eye per rabbit was used. Corneal neovascularization was induced by placing 5 silk sutures in the upper cornea. Rabbits were randomized to 1 of 3 groups (12 rabbits each): Group 1 received saline 0.9%, Group 2 bevacizumab 5 mg/mL, and Group 3 sunitinib 0.5 mg/mL. All treatments were administered 3 times daily for 14 days. Photographs were taken on a slit lamp on days 7 and 14, and angiographic photographs were taken on day 14. The area of neovascularization was measured in mm(2), percentage of the total corneal area, and percentage of the corneal surface covered by sutures.


RESULTS
On day 14, corneal neovascularization area in Group 1 (25.92 ± 5.08 mm(2), 18.78% ± 3.5% of corneal surface, 105.59% ± 18.9% of corneal surface with sutures) was larger than in Groups 2 (18.52 ± 7.94 mm(2), 13.67% ± 5.8%, 76.35% ± 33.2%) (1-way analysis of variance, P = .041) and 3 (4.57 ± 2.32 mm(2), 3.40% ± 1.7%, 18.94% ± 9.2%)(P < .001). Neovascularization in Group 2 was larger than in Group 3 (P < .001). Compared to saline, corneal neovascularization was inhibited 28.5% by bevacizumab and 82.3% by sunitinib. Sunitinib settled on the iris.


CONCLUSIONS
Topical administration of both bevacizumab and sunitinib inhibits corneal neovascularization in rabbits. But vascular endothelial growth factor (VEGF) pathway blockade by bevacizumab was not sufficient for a profound inhibition. Blocking both VEGF and platelet-derived growth factor pathways using sunitinib was 3-fold more effective.
Pérez-Santonja
Juan J
JJ
Refractive Surgery and Cornea Unit, Alicante Institute of Ophthalmology/Vissum, Miguel Hernández University School of Medicine, Alicante, Spain. jjpsantonja@coma.es
Campos-Mollo
Ezequiel
E
Lledó-Riquelme
Mariola
M
Javaloy
Jaime
J
Alió
Jorge L
JL
D000287:Administration, Topical; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016510:Corneal Neovascularization / Q000175:diagnosis / Q000517:prevention & control*; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000008:administration & dosage*; D011817:Rabbits; D011897:Random Allocation; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007211:Indoles; D009883:Ophthalmic Solutions; D010982:Platelet-Derived Growth Factor; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000077210:Sunitinib