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Impact of Intravitreal Injection of Bevacizumab (Avastin) on Rabbit's Choroid and Retina

Aim: The aim of the study was to evaluate the impact of intravitreal injection of bevacizumab (Avastin) on chorio-capillaris permeability as well as structure changes in the choroid and the retina of pigmented rabbits. Material and Methods: The study included 10 pigmented rabbits (20 clinically free eyes) ranged in weight between 1.2 and 2 kg (mean 1.7±0.05). The rabbits were subjected to intravitreal injection of 5 mg, 0.1mg Avastin in the right eyes (10eyes), while the left eyes (10eyes) were injected with equal volumes of balanced salt solution. 1 week later, Clinical examination and fundus fluorescein angiography (FFA) were done. Histological examination was performed on specimens of retina & choroid of Avastin & BSS injected eyes of sacrificed rabbits using light microscopy (LM) & transmission electron microscopy (TEM). Results were recorded and compared Results: Post injection clinical examination of the eyes showed no abnormality of cornea, lens, vitreous and fundus. FFA showed remarkable decrease in background chorio-capillaris fluorescence in 7 eyes (70 percent) injected with Avastin as compared with eyes injected with BSS. No change was observed in regards to retinal vasculature, or abnormal dye leak. LM examination: specimens from Avastin group were evaluated in comparison to control eyes Treated eyes exhibited the same microscopic appearance in most specimens (8/10, 80 percent). The chorio-capillaris layer showed elongated, stretched monolayer of capillaries with flat, elongated endothelial cell lining. The laminae showed closely packed RBCs arranged in a monolayer with ribbon like shape. The surrounding interstitial tissue showed stretched, elongated & compact collagen fibers. The RPE cells were tightly adherent to each other with prominent nuclei. The different retinal layers were in concomitance with the control specimens, however mild to moderate disruption of photoreceptor outer segments together with mild vacuolization in the ganglion cell layer were seen. TEM examination of both control and treated specimens confirmed the findings recorded by LM. The endothelial cell limning of the choriocapillaris exhibited reduced fenestrations in between the cells. TEM also highlighted the compact lamellae of collagen fibers. The RPE cells showed remarkable increase in the number of mitochondria and prominent endoplasmic reticulum. Variable sized melanosomes were also seen Conclusion: Though single intravitreal injection of Avastin does not cause appreciable histological changes in rabbit retina and choroid, yet, it imposes definite effect on choriocapillaris permeability as evidenced by FFA and ultra structural changes. Repeated intravitreal injections might alter the hemostasis of the chorio-capillaris RPE complex.