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H. Ameri, G. Chader, T. Ratanapakorn, N. Rao, S. Sadda, M. Humayun; The Effects of Bevacizumab in VEGF-Injected Rabbit Eyes. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1968.
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To evaluate the effects of intravitreal bevacizumab in blocking exogenous vascular endothelial growth factor (VEGF) in rabbits
30 pigmented rabbits were used. Animals were divided into 5 groups. Group 1 included 10 rabbits; other groups included 5 rabbits each. Group 1 received intravitreal VEGF only, and group 2 received intravitreal bevacizumab only. The remaining 3 groups received intravitreal injection of both VEGF and bevacizumab. In groups 3, 4 and 5, bevacizumab was injected at the same time, at day 2 and at week 1 following VEGF injection, respectively. Follow up evaluations continued for 3-4 weeks and included tonometry, color fundus photography, fundus fluorescein angiography (FA), and optical coherence tomography (OCT). Histological studies included H&E, trichrome and PAS staining.
Intravitreal injection of VEGF was associated with significant changes at day 2, including disc hyperemia, severe vascular and capillary dilatation and tortuousity, marked fluorescein leakage at the optic disc and in the anterior chamber. At week 1, a neovascular membrane had formed over the medullary wing and vascular changes were more pronounced. Fundus exam showed dramatic alterations at week 2: retinal elevation and distortion, reduction in vascular dilatation and tortuousity, abnormal and irregular vascular pattern, significant areas of capillary drop out, and lack of fluorescein leakage at the disc or in the anterior chamber. There was no significant change in retinal appearance beyond week 2. Simultaneous injection of bevacizumab in group 3 was very effective in preventing fluorescein leakage at the disc and in the anterior chamber, and moderately effective in preventing vascular dilatation and tortuousity. Injection of bevacizumab two days after VEGF injection had similar effects but resulted in minimal capillary drop out in two rabbits. Intravitreal injection of bevacizumab one week after VEGF injection resulted in more pronounced changes at week 2 when compared to the control group which received VEGF injection only; the vessels became even narrower than normal and there was more severe capillary drop out.
Intravitreal injection of VEGF in rabbits may result in florid retinal neovascularization within the first week followed by closure of normal capillaries at week 2. Early intravitreal injection of bevacizumab can prevent these effects; whereas, late injection may be associated with more significant closure of normal capillaries. A sudden drop in effective VEGF concentration may be responsible for the closure of the normal capillaries.
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