Topical formulations of novel angiostatic steroids inhibit rabbit corneal neovascularization

David BenEzra, Brenda W. Griffin, Genia Maftzir, Najam A. Sharif, Abbot Clark

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Purpose. To evaluate the antiangiogenic potential of topical ophthalmic formulations of the novel angiostatic steroids AL-3789 and AL-940, using a rabbit model of corneal neovascularization. Methods. Neovascularization was induced in the rabbit cornea by surgical implantation of a standard ethylene vinyl acetate copolymer (Elvax-40) pellet containing 1 μg lipopolysaccharide. Coded formulations of the control vehicle or the following test agents were administered in prevention and intervention treatment protocols: 1% formulations of AL-3789, AL-4940, and cortisol acetate as a positive drug control. Three doses of AL-3789 (0.01%, 0.1%, and 1%) were also evaluated in a prevention treatment protocol. Corneal responses were monitored throughout a 2-week treatment period, and 1 week after the last treatment dose. Observations included quantitative measurement of the area of new blood vessel growth and qualitative assessment of cellular infiltrate and edema. All treatments and observations were performed in a double-masked manner. Results. All tested formulations, except the vehicle and the 0.01% AL-3789 preparation, significantly inhibited corneal neovascularization and other lipopolysaccharide-induced responses in the various treatment protocols employed. AL-4940, the free alcohol form of AL- 3789, was slightly less effective than cortisol acetate or AL-3789. The extent of inhibition of the angiogenic response by the 1% and 0.1% AL-3789 suspensions ranged from 76% to 100% 1 week after the last treatment. Conclusions. The antiangiogenic steroid AL-3789 may be a therapeutically useful angiostatic agent for corneal neovascularization and potentially could be effective in other ocular neovascular diseases.

Original languageEnglish
Pages (from-to)1954-1962
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number10
StatePublished - 1 Sep 1997

Keywords

  • AL-3789 ophthalmic formulation
  • Angiostatic steroid
  • Lipopolysaccharide
  • Neovascularization inhibitor
  • Rabbit corneal neovascularization

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