title: Evaluation of the new photosensitizer Stakel (WST-11) for photodynamic choroidal vessel occlusion in rabbit and rat eyes.
abstract: OBJECTIVE
  To evaluate the photodynamic potential of a new hydrosoluble photosensitizer (WST-11, Stakel; Steba Biotech, Toussus-Le-Noble, France), for use in occlusion of normal choroidal vessels in the rabbit eye and CNV (choroidal neovascularization) in the rat eye.
  
  
  METHODS
  Occlusive and nonocclusive parameters of Stakel and verteporfin photodynamic therapy (PDT) were investigated in pigmented rabbits. Eyes were followed by fluorescein angiography (FA) and histology at various intervals after PDT.
  
  
  RESULTS
  When occlusive parameters (fluence of 50 J/cm(2), 5 mg/kg drug dose and DLI [distance to light illumination] of 1 minute) were used, Stakel PDT was efficient immediately after treatment without associated structural damage of the RPE and retina overlying the treated choroid in the rabbit eye. Two days later, total occlusion of the choriocapillaries was seen in 100% of the treated eyes, along with accompanying histologic structural changes in the overlying retina. When the occlusive parameters (fluence, 100 J/cm2; drug dose, 12 mg/m2; and DLI, 5 minutes) of verteporfin PDT were used, occlusion of the choriocapillaries was observed in 89% of the treated eyes. Histology performed immediately after treatment demonstrated structural damage of the overlying retina and RPE layer. Weaker, nonocclusive Stakel PDT parameters (25 J/cm2, 5 mg/kg, and DLI of 10 minutes) did not induce choriocapillary occlusion or retinal lesions on FA or histology. Weaker, nonocclusive verteporfin PDT parameters (10 J/cm2, 0.2 mg/kg, and DLI of 5 minutes) did not induce choriocapillary occlusion. However, histology of these eyes showed the presence of damage in the retinal and choroidal tissues. Moreover, preliminary results indicate that selective CNV occlusion can be achieved with Stakel PDT in the rat eye.
  
  
  CONCLUSIONS
  Unlike verteporfin PDT, Stakel PDT does not cause direct damage to the RPE cell layer or retina. These observations indicate that Stakel PDT may have a high potential for beneficial therapeutic outcomes in treatment of AMD.
authors.affiliation: Centre de Recherche des Cordeliers, Physiopathology of Ocular Diseases: Therapeutic Innovations, UMR S 872, Université Paris Descartes, Paris, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Berdugo
authors.forename: Riad A
authors.initials: RA
authors.lastname: Bejjani
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Valamanesh
authors.forename: Michele
authors.initials: M
authors.lastname: Savoldelli
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Jeanny
authors.forename: Dominique
authors.initials: D
authors.lastname: Blanc
authors.forename: Herve
authors.initials: H
authors.lastname: Ficheux
authors.forename: Avigdor
authors.initials: A
authors.lastname: Scherz
authors.forename: Yoram
authors.initials: Y
authors.lastname: Salomon
authors.forename: David
authors.initials: D
authors.lastname: BenEzra
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
mesh_terms: D000818:Animals; D001429:Bacteriochlorophylls / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D002829:Choroid / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005451:Fluorescein Angiography; D017075:Laser Coagulation; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000648:ultrastructure; D011166:Porphyrins / Q000627:therapeutic use; D011817:Rabbits; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000187:drug effects / Q000648:ultrastructure; D000077362:Verteporfin
chemical_list: D001429:Bacteriochlorophylls; D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; C503696:padeliporfin