Inhibition of Experimental Corneal Neovascularization by Bevacizumab (Avastin) Baskent University, School of Medicine Department of Ophthalmology, Ankara Turkey Yonca A. Akova, MD Veysi Öner, MD Cem Küçükerdönmez, MD The authors acknowledge no financial interest in the subject matter of this presentation

Purpose To evaluate and compare the inhibitory effects of topical high dose, low-dose and subconjunctival bevacizumab (Avastin, Genentech Inc., San Francisco, Ca, USA) on corneal vascularization in a rat model

Methods Corneas of 20 rats (Sprague-Dawley, male) were chemically cauterized with silver nitrate sticks in order to induce neovascularization Animals were divided in four groups Group 1: Control group that received only topical artificial tear twice daily Grup 2: Subconjunctival injection group that received 0.05 ml (1.25mg) of bevacizumab on day 1, 4 and 7 Group 3: Low-dose topical bevacizumab (4 mg/ml) group that received twice daily Group 4: High-dose topical bevacizumab (12.5 mg/ml) group that received twice daily

Methods Digital photographs of the corneas were taken and analyzed using an image analysis software (Pixcavator Image Analyzer, Intelligent Perception,WV, USA) On day 10, all animals were sacrificed and the eyes were enucleated Corneas were excised and examined histopathologically

Control group Group 2Group 3Group 4 Mean percentage of neovascularized corneal area (%) ± ± ± ± p value < 0.01 Results

Control group Topical high-dose bevacizumab group (12.5 mg/ml)

Control groupTopical low-dose bevacizumab group (4 mg/ml)

Subconjunctival bevacizumab group (1.25mg/0,05ml) Control group

Results In histological examination of the excised corneas, treated eyes showed significantly less neovascular areas and number of vessels in group 2,3 and 4 than the control group The differences between control group and treatment groups were found to be statistically significant (p < 0.05 for all) Bevacizumab is able to inhibit corneal angiogenesis, without any difference of this effect with –Changing the route of administration (subconjunctival or topical) –Increasing the dosage (4mg/ml or 12.5mg/ml for topical form)

Control group Topical low-dose bevacizumab group

Discussion Both topical and subconjunctival application of bevacizumab reduces experimental corneal vascularization significantly compared to the control group Clinical use of bevacizumab may have an additional effect in the treatment for corneal neovascularization

NAME: Yonca Aydın Akova, M.D. TITLE: Professor in Ophthalmology DATE AND PLACE OF BIRTH: October 21, 1960, Turkey 1983: Doctor of Medicine, Istanbul University, School of Medicine 1990: Istanbul University, School of Medicine, Department of Ophthalmology 2000: Professor of Ophthalmology, Baskent University, School of Medicine, Department of Ophthalmology, Ankara, Turkey 2002: Chairperson, Baskent University, School of Medicine, Department of Ophthalmology, Ankara, Turkey NAME: Cem Küçükerdönmez, M.D. TITLE: Fellow in Ophthalmology DATE AND PLACE OF BIRTH: October 9, 1975, Turkey 1999: Doctor of Medicine, Hacettepe University, School of Medicine 2003 : Başkent University, School of Medicine, Department of Ophthalmology NAME:, Veysi Öner, M.D. TITLE: Resident in Ophthalmology DATE AND PLACE OF BIRTH: March 01, 1979, Turkey 2002: Doctor of Medicine, Hacettepe University, School of Medicine : Resident, Başkent University, School of Medicine, Department of Ophthalmology, Ankara, Turkey