title: Intravitreal Topotecan Inhibits Laser-induced Choroidal Neovascularization in a Rat Model.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Intravitreal injection of topotecan at a dose of 1 μg/5 μl is safe and may be a promising treatment for CNV.
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Gholipour
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mozhgan Rezaei
authors.initials: MR
authors.lastname: Kanavi
authors.affiliation: Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Ahmadieh
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
authors.forename: Seyed Javid
authors.initials: SJ
authors.lastname: Aldavood
authors.affiliation: Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Nourinia
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Bagher
authors.initials: SB
authors.lastname: Hosseini
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Narsis
authors.initials: N
authors.lastname: Daftarian
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ebrahim Mohammad
authors.initials: EM
authors.lastname: Nashtaei
authors.affiliation: Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Adib
authors.initials: A
authors.lastname: Tousi
authors.affiliation: Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Sare
authors.initials: S
authors.lastname: Safi
keywords: Choroidal Neovascularization; Electroretinography; Intravitreal Injection; Topotecan