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Year : 2015  |  Volume : 10  |  Issue : 3  |  Page : 295-302

Intravitreal topotecan inhibits laser-induced choroidal neovascularization in a rat model

1 Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
2 Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Correspondence Address:
Mozhgan Rezaei Kanavi
Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, No. 23, Paidarfard Street, Boostan 9 Street, Pasdaran Avenue, Tehran 16666
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2008-322X.170339

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Purpose: A two-phase preclinical study was designed to determine the safe dose of intravitreal topotecan and its inhibitory effect on experimental choroidal neovascularization (CNV) in a rat model. Methods: In phase I, 42 rats were categorized into 6 groups, 5 of which received intravitreal topotecan injections of 0.125 μg, 0.25 μg, 0.5 μg, 0.75 μg, and 1.0 μg/5 μl, respectively; the control group received an injection of normal saline. Ophthalmic examination and electroretinography (ERG) were performed on days 7 and 28, and enucleated globes were processed for histopathology and immunostaining for glial fibrillary acidic protein. In phase II, CNV was induced via laser burns in 20 rats and the animals were divided into 2 groups. One group received topotecan and the other received normal saline intravitreally. Four weeks later, mean scores of fluorescein leakage on fluorescein angiography as well as mean CNV areas on histology sections were compared. Results: In phase I, clinical, ERG and histopathologic results were unremarkable in terms of retinal toxicity in all groups. Based on the results of phase I, a dose of 1 μg/5 μl topotecan was chosen for phase II. Leakage scores obtained from late-phase fluorescein angiography were significantly lower in topotecan-treated than control eyes (P < 0.01) four weeks after induction of CNV. Compared to control eyes, topotecan-treated eyes showed a significantly lower incidence of fibrovascular proliferation (8.7% vs. 96.2%) and significantly smaller areas of CNV (P < 0.01). Conclusion: Intravitreal injection of topotecan at a dose of 1 μg/5 μl is safe and may be a promising treatment for CNV.

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