title: Efficacy of topical aflibercept versus topical bevacizumab for the prevention of corneal neovascularization in a rat model.
abstract: The aim of this experimental study was to compare the efficacy of topical aflibercept and topical bevacizumab in preventing corneal neovascularization. A chemical burn was created in the right central cornea of male Sprague-Dawley rats, followed immediately by instillation of one drop (25 mg/ml, 20 μl volume) of aflibercept (15 eyes), bevacizumab (14 eyes), or saline (15 eyes). Treatment was repeated twice daily for 7 days. Corneal neovascularization was determined using corneal photographs (ImageJ) on days 1, 4, 7, 10, and histological and immunofluorescence studies, on day 10. Stromal immunoreactivity was evaluated 2 days after injury in 6 rats treated singly with bevacizumab or aflibercept. Corneal neovascularization was observed clinically on day 4 in all groups. In the aflibercept group, the area of neovascularization increased from 7.38 ± 2.23% on day 4 to 21.73 ± 14.59% on day 7 and 31.0 ± 23.61% on day 10. Corresponding values in the bevacizumab group were 6.04% ± 1.81%, 51.27 ± 15.50%, and 54.4 ± 11.33%, and in the control group, 8.99 ± 1.93%, 42.6 ± 19.59%, and 55.15 ± 11.54%. The area of neovascularization was significantly smaller on days 7 and 10 in the aflibercept group than in the control and bevacizumab groups (P < 0.001, all analyses), with no significant differences between the latter two groups (day 7, P = 0.868; day 10, P = 0.213). Clinical findings were compatible with the histological data and supported by immunofluorescence and corneal flat-mount staining. Both drugs demonstrated variable penetration into the corneal stroma. Topical aflibercept effectively inhibits corneal neovascularization in a rat model of chemical burn. These findings may have important therapeutic implications for humans.
authors.affiliation: Department of Ophthalmology, Rabin Medical Center, Petach Tikva 49100, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: rutibd@gmail.com.
authors.forename: Ruti
authors.initials: R
authors.lastname: Sella
authors.affiliation: Department of Ophthalmology, Rabin Medical Center, Petach Tikva 49100, Israel. Electronic address: blorlyga@clalit.org.il.
authors.forename: Orly
authors.initials: O
authors.lastname: Gal-Or
authors.affiliation: Department of Ophthalmology, Rabin Medical Center, Petach Tikva 49100, Israel. Electronic address: eitanli@clalit.org.il.
authors.forename: Eitan
authors.initials: E
authors.lastname: Livny
authors.affiliation: Laboratory of Eye Research, Felsenstein Medical Research Center, Petach Tikva 49100, Israel. Electronic address: morda2@clalit.org.il.
authors.forename: Mor
authors.initials: M
authors.lastname: Dachbash
authors.affiliation: Laboratory of Eye Research, Felsenstein Medical Research Center, Petach Tikva 49100, Israel. Electronic address: yaeln@clalit.org.il.
authors.forename: Yael
authors.initials: Y
authors.lastname: Nisgav
authors.affiliation: Department of Ophthalmology, Rabin Medical Center, Petach Tikva 49100, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; Laboratory of Eye Research, Felsenstein Medical Research Center, Petach Tikva 49100, Israel. Electronic address: dwin@clalit.org.il.
authors.forename: Dov
authors.initials: D
authors.lastname: Weinberger
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; Laboratory of Eye Research, Felsenstein Medical Research Center, Petach Tikva 49100, Israel. Electronic address: livnatami@gmail.com.
authors.forename: Tami
authors.initials: T
authors.lastname: Livnat
authors.affiliation: Department of Ophthalmology, Rabin Medical Center, Petach Tikva 49100, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: iritba2@clalit.org.il.
authors.forename: Irit
authors.initials: I
authors.lastname: Bahar
mesh_terms: D000287:Administration, Topical; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000068258:Bevacizumab / Q000008:administration & dosage / Q000494:pharmacology*; D002057:Burns, Chemical / Q000150:complications / Q000188:drug therapy*; D003228:Conjunctiva / Q000187:drug effects; D065306:Corneal Injuries / Q000150:complications / Q000188:drug therapy*; D016510:Corneal Neovascularization / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005126:Eye Burns / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009883:Ophthalmic Solutions / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D009883:Ophthalmic Solutions; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Aflibercept; Bevacizumab; Chemical burn; Corneal neovascularization; Topical treatment