title: Systemic toxicology and laser safety of laser targeted angiography with heat sensitive liposomes.
abstract: Angiography is currently limited by its lack of local and tissue specificity. The dye rapidly fills both the retinal and choroidal vessels and leaks out of the vessels thus hampering visualization of small vascular beds such as occult choroidal neovascularization. We have developed a method of laser targeted delivery based on encapsulating the dye in heat sensitive liposomes, administering the liposomes intravenously and causing them to release their content by noninvasively warming the target tissue with a laser pulse delivered through the pupil. The local release yields a bright fluorescent bolus which selectively highlights retinal or choroidal vessels. A preliminary investigation of the potential side effects of the method is presented. In rats the systemic toxicity of carboxyfluorescein-entrapped liposomes was compared with that of the free dye. No significant difference was found between the two. Non-human primates exposed to repeated laser targeted angiography were monitored over time and no significant side effects were observed. The safety of the laser exposures was assessed by conventional fluorescein angiography and histopathology. Choroidal laser targeted angiography was achieved without damage. Retinal laser targeted angiography was accompanied by mild and local damage in an area remote from the fovea. The study indicates that laser targeted choroidal angiography can be performed safely and holds promise for diseases such as age related macular degeneration with occult choroidal neovascularization. Further improvements are needed to ensure that no side effects accompany retinal laser targeted angiography.
authors.affiliation: Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: S
authors.initials: S
authors.lastname: Asrani
authors.forename: S
authors.initials: S
authors.lastname: D'Anna
authors.forename: H
authors.initials: H
authors.lastname: Alkan-Onyuksel
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Goodman
authors.forename: R
authors.initials: R
authors.lastname: Zeimer
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier / Q000187:drug effects; D002196:Capillaries / Q000033:anatomy & histology / Q000293:injuries; D002829:Choroid / Q000098:blood supply / Q000293:injuries; D004337:Drug Carriers; D005451:Fluorescein Angiography / Q000379:methods*; D005452:Fluoresceins / Q000008:administration & dosage* / Q000633:toxicity*; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000633:toxicity; D006358:Hot Temperature; D007834:Lasers / Q000009:adverse effects; D008081:Liposomes; D008297:Male; D010215:Papio; D051381:Rats; D017207:Rats, Sprague-Dawley; D012171:Retinal Vessels / Q000033:anatomy & histology / Q000293:injuries
chemical_list: D004337:Drug Carriers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008081:Liposomes; C024098:6-carboxyfluorescein