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S. Saati, R. N. Agrawal, S. Louie, G. J. Chader, M. S. Humayun; Effect of Multiple Injections of Small Divided Doses vs Single Injection of Intravitreal Bevacizumab on Retinal Neovascular Model in Rabbits. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2981.
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To compare the effects of multiple injections of small divided doses (0.15 mg) of intravitreal bevacizumab vs. a single injection (1.25 mg) using a retinal neovascular model in rabbits.
We assigned 12 pigmented rabbits to four groups of three each. All rabbits received an intravitreal injection of vascular endothelial growth factor (VEGF, 10 µg) on the first day. Group A received an intravitreal loading dose of bevacizumab (0.5 mg) on day 3, followed by five smaller injections (0.15 mg), one every third day. Those in group B and C received a single intravitreal injection of bevacizumab (1.25 mg) on day 3, followed by five injections of sham (0.1 ml of balanced salt solution), one every third day in group C. Group D received only intravitreal VEGF. Follow-up examinations were performed for 26 days.
Intravitreal injection of VEGF was invariably associated with vascular dilatation, tortuosity, and fluorescein leakage at the optic disc and medullary wings by day 3 in all groups. In groups A and B, vascular changes decreased substantially in the first 3 days after the loading dose or single bevacizumab injection, respectively, and continued to show gradual regression during each follow-up interval. No statistically significant differences were found between the changes in optical coherence tomography measurements of mean retinal thicknesses in groups A and B at the medullary wings and below the optic disc, respectively (p =0.46; p =0.56). In group C, the extra sham injections did not cause any further significant inflammatory reaction. In group D, vascular changes decreased slowly as compared to the other groups after day 3. Also, vascular dilatation and tortuosity were present until the last day of study. The differences in retinal thickness between group D and other groups were statistically significant on day 6 (p = 0.0003) and day 12 (p = 0.03).
Frequent smaller doses of bevacizumab can control VEGF-induced vascular changes as well as the currently utilized model of single monthly large injections. Since smaller distributed doses reduce the dose-dependent and cumulative side effects of bevacizumab, these results led us to conclude injections of more frequent smaller doses could be accomplished by an ocular drug delivery device that our group has developed. Further studies with larger groups and longer follow up are needed to study the long-term effects.
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