Anti-VEGF monoclonal antibody-induced regression of corneal neovascularization and inflammation in a rabbit model of herpetic stromal keratitis.
BACKGROUND
To determine the efficacy of bevacizumab (Avastin), an anti-VEGF monoclonal antibody, administrated via subconjunctival injection as a corneal anti-angiogenic treatment.


METHODS
Right corneas of rabbits were infected with herpes simplex virus type 1, KOS strain. On day 13 post-infection (p.i.), animals were treated subconjunctivally (sc) with a single 10-microl dose (25 microg/microl) of bevacizumab (group A) or with the same volume of an isotype monoclonal antibody, as negative control (group B). All animals were observed clinically on days 2, 5, 7, 14, 21, and 28 p.i., and two corneas each day were obtained for histological assessment and viral titration.


RESULTS
Viral replication was observed no longer than 5 days after infection. By day 7 a dense neutrophil invasion of the cornea was detected, which significantly increased while herpetic stromal keratitis progressed in severity. Positive outcomes observed following the treatment with bevacizumab, compared to control, included: (1) Total involution of neovascularization, (2) reduction in disease severity, (3) improved corneal translucency, (4) absence of scarring, (5) preservation of corneal thickness, (6) no neutrophil infiltration of the cornea.


CONCLUSIONS
Subconjunctival administration of bevacizumab induced involution of new vessels, abolished inflammatory response, and resulted in return of corneal function. Furthermore, bevacizumab is a novel approach for the treatment of herpetic stromal keratitis.
Saravia
Mario
M
Laboratory of Investigation in Ophthalmology, Department of Pathology, School of Medicine, University of Buenos Aires, J.E. Uriburu 950, Buenos Aires, Argentina. mario.saravia@gmail.com
Zapata
Gustavo
G
Ferraiolo
Paula
P
Racca
Lourdes
L
Berra
Alejandro
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002921:Cicatrix / Q000517:prevention & control; D003228:Conjunctiva; D003315:Cornea / Q000276:immunology / Q000473:pathology; D003316:Corneal Diseases / Q000517:prevention & control; D016510:Corneal Neovascularization / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D003319:Corneal Stroma / Q000473:pathology / Q000821:virology*; D018450:Disease Progression; D007267:Injections; D016849:Keratitis, Herpetic / Q000473:pathology*; D020556:Neutrophil Infiltration / Q000187:drug effects; D011817:Rabbits; D012074:Remission Induction; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab