Evaluation of the New Photosensitizer Stakel (WST-11) for Photodynamic Choroidal Vessel Occlusion in Rabbit and Rat Eyes

• Published in: Investigative ophthalmology & visual science 2008-04, Vol.49 (4), p.1633-1644
• Main Authors: Berdugo, Marianne, Bejjani, Riad A, Valamanesh, Fatemeh, Savoldelli, Michele, Jeanny, Jean-Claude, Blanc, Dominique, Ficheux, Herve, Scherz, Avigdor, Salomon, Yoram, BenEzra, David, Behar-Cohen, Francine
• Format: Article
• Language: English
• Subjects: Animals; Bacteriochlorophylls - pharmacokinetics; Bacteriochlorophylls - therapeutic use; Bacteriochlorophylls - toxicity; Biological and medical sciences; Choroid - drug effects; Choroidal Neovascularization - drug therapy; Choroidal Neovascularization - etiology; Choroidal Neovascularization - pathology; Disease Models, Animal; Drug Evaluation, Preclinical; Eye and associated structures. Visual pathways and centers. Vision; Fluorescein Angiography; Fundamental and applied biological sciences. Psychology; Laser Coagulation; Medical sciences; Ophthalmology; Photochemotherapy; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - therapeutic use; Photosensitizing Agents - toxicity; Pigment Epithelium of Eye - drug effects; Pigment Epithelium of Eye - ultrastructure; Porphyrins - therapeutic use; Rabbits; Rats; Rats, Inbred BN; Retina - drug effects; Retina - ultrastructure; Vertebrates: nervous system and sense organs; Verteporfin
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.07-0767

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. 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. 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. 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.