title: Retinal vein cannulation with prolonged infusion of tissue plasminogen activator (t-PA) for the treatment of experimental retinal vein occlusion in dogs.
abstract: OBJECTIVE
  To evaluate the feasibility, safety, and efficacy of local thrombolytic agents directly injected into occluded retinal veins in an experimental animal model.
  
  
  METHODS
  Experimental animal study.
  
  
  METHODS
  This experimental study was performed in two phases. In phase 1, 15 enucleated porcine eyes and 8 in vivo canine eyes were used for the development of the instrumentation and surgical technique required for retinal vein cannulation with prolonged intravascular infusion. In phase 2 of this study, experimental branch retinal vein occlusion was photo-chemically created using an intravenous injection of rose bengal followed by diode laser photocoagulation in eight eyes of eight dogs. Four eyes were treated by retinal vein cannulation and an injection of tissue plasminogen activator (t-PA) using a specifically designed microcatheter, while the remaining four eyes were untreated (control group). The total amount of t-PA injected intravenously ranged from 400 to 1000 mug, infused over a period ranging from 25 to 45 minutes with a mean pressure of 40 psi, resulting in a mean injection flow rate of 0.05 ml/min. The dogs underwent clinical examination, fluorescein angiography, and histologic examination. Main outcome measures were: Achievement of prolonged intravascular infusion of t-PA, changes in fundus appearance, fluorescein angiography, and histology.
  
  
  RESULTS
  A microcatheter instrument and a surgical technique for retinal vein cannulation with prolonged intravascular infusion were developed. Cannulation and t-PA infusion for a period of at least 30 minutes was achieved in all four treated eyes with experimental branch retinal vein occlusion. No complications were recorded in all treated eyes. One week and 1 month postoperatively, treated eyes exhibited marked decreases in retinal hemorrhages, retinal vein dilation, and tortuosity, whereas nontreated eyes exhibited persistence of these findings. Fluorescein angiography demonstrated improved circulatory flow in treated relative to nontreated eyes. Histologic analysis confirmed the presence of thrombi in nontreated eyes only.
  
  
  CONCLUSIONS
  Retinal vein cannulation with prolonged intravascular injection of t-PA is feasible and safe, and this may offer a new treatment option for retinal vein occlusion.
authors.affiliation: Doheny Retina Institute, Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Mohamed K
authors.initials: MK
authors.lastname: Tameesh
authors.forename: Rohit R
authors.initials: RR
authors.lastname: Lakhanpal
authors.forename: Gildo Y
authors.initials: GY
authors.lastname: Fujii
authors.forename: Michael
authors.initials: M
authors.lastname: Javaheri
authors.forename: Terry H
authors.initials: TH
authors.lastname: Shelley
authors.forename: Sam
authors.initials: S
authors.lastname: D'Anna
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Barnes
authors.forename: Eyal
authors.initials: E
authors.lastname: Margalit
authors.forename: Michel
authors.initials: M
authors.lastname: Farah
authors.forename: Eugene
authors.initials: E
authors.lastname: De Juan
authors.forename: Mark S
authors.initials: MS
authors.lastname: Humayun
mesh_terms: D000818:Animals; D002406:Catheterization, Peripheral / Q000379:methods*; D004195:Disease Models, Animal; D004285:Dogs; D005240:Feasibility Studies; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D005451:Fluorescein Angiography; D007262:Infusions, Intravenous; D012169:Retinal Vein / Q000187:drug effects*; D012170:Retinal Vein Occlusion / Q000188:drug therapy*; D012449:Safety; D013552:Swine; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator