Inhibition of Experimental Corneal Neovascularization by Bevacizumab (Avastin)

Baskent University, School of Medicine Department of Ophthalmology, Ankara Turkey

Yonca A. Akova, MDVeysi Öner, MDCem 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 2 Group 3 Group 4

Mean percentage of neovascularized corneal area (%)

63.32

± 13.10

30.22

± 15.73

26.76

± 10.23

25.52

± 12.45

p value < 0.01 < 0.01 < 0.01

Results

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

Control group Topical 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 OphthalmologyDATE AND PLACE OF BIRTH: March 01, 1979, Turkey2002: Doctor of Medicine, Hacettepe University, School of Medicine2003-2008 : Resident, Başkent University, School of Medicine, Department of Ophthalmology, Ankara, Turkey