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Hamid Ahmadieh, Mohammad Ali Gholipour, Seyed Javad Aldavood, Ramin Nourinia, Mozhgan Rezaei Kanavi; Intravitreal Topotecan Inhibits Laser Induced Choroidal Neovascularization in a Rat Model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1962.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the safe dose of intravitreal topotecan and its inhibitory effect on laser induced choroidal neovascular membrane (CNV) in a rat model.
In phase I , 35 rats were assigned into 5 treatment groups. Each group received serial intravitreal injection of topotecan with specific concentrations (0.125 µg, 0.25µg, 0.5µg, 0.75µg and 1.0µg per 5 µl) in one eye and no injection in the fellow eye (control). In addition, 7 other rats were assigned into a 6th group as a double control and received 5µl of intravitreal normal saline in one eye. All eyes underwent ophthalmic and ERG examinations on days 7, 14 and 28 following the injections. After the last examination, rats were sacrificed and the enucleated globes were processed for light microscopic examination. Immunohistochemical staining for glial fibrillary acidic protein (GFAP) was performed in addition to the routine hematoxylin and eosin. In phase II, CNV was induced by laser photocoagulation in the treatment and control groups; twenty normal rats received infrared diode-laser photocoagulation in their right eyes (8 lesions per eye). Immediately thereafter, eyes in the treatment group (n=10) received 1 µg/5µl of intravitreal topotecan whereas the control eyes (n=10) received 5µl of intravitreal normal saline. Four weeks later, rats were euthanized after fluorescein angiography (FA), and the enucleated globes were fixed in 10% formalin solution. Serial sections of each laser induced lesion were examined under light microscopy.
Ophthalmic and histopathologic examinations in the first phase of the study revealed no abnormality in the topotecan-treated and control eyes; GFAP immunoreactivity was also unremarkable. There was no significant difference between the topotecan-injected and control eyes (p>0.05) in terms of ERG responses. Based on phase I results , 1µg/5µl of intravitreal topotecan was chosen as the treatment dose for the second phase. FA leakage scores were significantly lower in the topotecan-treated eyes compared to the controls (p<0.01). Eyes which received topotecan had a significantly lower incidence of fibrovascular proliferation (8.7% vs 96.2%), and the average area of CNV membrane was smaller in these eyes compared to the controls (p<0.01).
The results of this experimental study show that intravitreal injection of topotecan may have an inhibitory effect on choroidal neovascularization.
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