The different effects of early and late bevacizumab (Avastin) injection on inhibiting corneal neovascularization and conjunctivalization in rabbit limbal insufficiency.
OBJECTIVE
To compare the effects of early, mid, and late subconjunctival injection of bevacizumab on corneal neovascularization (NV) and conjunctivalization in a rabbit limbal insufficiency model.


METHODS
Limbal insufficiency was created surgically, and subconjunctival injections of 2.5 mg bevacizumab twice weekly for 1 month were started immediately (early group), 1 week (mid group), and 1 month after injury (late group). The corneal epithelial alterations, stromal opacity, centricity, extent, and PICS (percentage of involved corneal surface) of the corneal NV were evaluated. The expression of cytokeratins K3, K4, K12, K13, and MUC5 by the corneal surface cells was examined by immunohistochemistry.


RESULTS
Bevacizumab significantly inhibited corneal NV in the early and mid, but not the late, treatment groups at 4 weeks after treatment (PICS: P < 0.01 in the early group, P < 0.01 in the mid group, and P > 0.05 in the late group). Early and mid treatment produced significant inhibition of corneal alteration (P < 0.01 in the early group and P = 0.03 in the mid group) and stromal opacity (P < 0.01 in the early group and P = 0.02 in the mid group) at 4 months after treatment but not in the late group. The immunohistochemistry of cytokeratin on the corneal surface cells at 1 month after treatment was K3(+), K4(-), K12(+), K13(-), and MUC5(-) in the early group; K3(+), K4(+), K12(+), K13(+), and MUC5(-) in the mid group; and K3(+), K4(+), K12(-), K13(+), and MUC5(+) in the late treatment group.


CONCLUSIONS
Early and mid bevacizumab injection inhibited corneal NV, epithelial alteration, and stromal opacity in limbal insufficiency, but late treatment did not. Early treatment with bevacizumab seems to be clinically beneficial in the management of limbal injury such as chemical burn.
Lin
Chung-Tien
CT
Department of Veterinary Medicine, College of Bio-Resource and Agriculture, National Taiwan University, Taipei, Taiwan.
Hu
Fung-Rong
FR
Kuo
Kuang-Tzu
KT
Chen
Yan-Ming
YM
Chu
Hsiao-Sang
HS
Lin
Ying-Han
YH
Chen
Wei-Li
WL
D016475:3T3 Cells; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002460:Cell Line; D003114:Colony-Forming Units Assay; D003228:Conjunctiva / Q000187:drug effects* / Q000473:pathology; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003319:Corneal Stroma / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000378:metabolism / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D007267:Injections; D007633:Keratins / Q000378:metabolism; D016850:Limbus Corneae / Q000473:pathology*; D051379:Mice; D008856:Microscopy, Fluorescence; D055257:Mucin-5B / Q000378:metabolism; D010641:Phenotype; D011817:Rabbits; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014945:Wound Healing
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D055257:Mucin-5B; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D007633:Keratins