title: Topical formulations of novel angiostatic steroids inhibit rabbit corneal neovascularization.
abstract: OBJECTIVE
  To evaluate the antiangiogenic potential of topical ophthalmic formulations of the novel angiostatic steroids AL-3789 and AL-4940, 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 microg 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.
authors.affiliation: Department of Ophthalmology, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: D
authors.initials: D
authors.lastname: BenEzra
authors.forename: B W
authors.initials: BW
authors.lastname: Griffin
authors.forename: G
authors.initials: G
authors.lastname: Maftzir
authors.forename: N A
authors.initials: NA
authors.lastname: Sharif
authors.forename: A F
authors.initials: AF
authors.lastname: Clark
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D005260:Female; D006854:Hydrocortisone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D008070:Lipopolysaccharides; D008297:Male; D009883:Ophthalmic Solutions; D011145:Polyvinyls; D011817:Rabbits; D012486:Salmonella typhimurium
chemical_list: C108423:AL 3789; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D009883:Ophthalmic Solutions; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; C108424:Anecortave; D006854:Hydrocortisone