Angiographic and histologic effects of fundus photodynamic therapy with a hydrophilic sensitizer (mono-L-aspartyl chlorin e6).
OBJECTIVE
To demonstrate the efficacy of the photosensitizer mono-L-aspartyl chlorin e6 (NPe6) in closing choroidal vessels at low energy levels, that tissue uptake and clearance are rapid, and that low concentrations of drug are needed to achieve clinical effects.


METHODS
Experimental animal study.


METHODS
Pigmented rabbits and Japanese monkeys were used in this study.


METHODS
Using a modified 664-nm diode laser, the fundi of pigmented rabbits and Japanese monkeys were irradiated after intravenous administration of NPe6 (2-100 mg/kg). Time from injection to irradiation varied from 5 to 15 minutes, and duration of exposure varied from 1 to 10 seconds. Power output at the corneal surface was either 3.6 or 5.9 mW. Animals were examined by indirect ophthalmoscopy and fluorescein angiography at 2 hours and 7 days after treatment. After enucleation 7 days after treatment, specimens were prepared for light and electron microscopy.


METHODS
Angiographic evidence of occlusion and histopathologic evidence of retinal damage.


RESULTS
Both clinical and histopathologic examination demonstrated effects on the choroidal vasculature and the retinal pigment epithelium, including necrosis of endothelial cells and occlusion in choroidal vessels, particularly within the choriocapillaris, at low energy levels. Overlying neurosensory retina was minimally affected. Fluorescein angiography of lesions treated with 2 mg/kg and laser fluence of 2.3 to 7.5 J/cm2 showed a normal appearance 2 hours after treatment, which changed to early hypofluorescent and later hyperfluorescent lesions 7 days after treatment. In contrast, those animals receiving the 10-mg/kg dose and laser fluence of 0.46 to 0.75 J/cm2 showed marked hypofluorescence of choroidal lesions and occlusion of retinal vessels 7 days after treatment.


CONCLUSIONS
Effective occlusion of normal choroidal vessels was achieved at 2 mg/kg using 2.3 to 7.5 J/cm2 or at 10 mg/kg using 0.46 to 0.75 J/cm2 with minimal injury to overlying neurosensory retina.
Department of Ophthalmology, Saitama Medical School, Iruma, Japan.
K
K
Mori
S
S
Yoneya
M
M
Ohta
A
A
Sano
K
K
Anzai
G A
GA
Peyman
D M
DM
Moshfeghi
D000818:Animals; D002829:Choroid / Q000098:blood supply* / Q000187:drug effects / Q000648:ultrastructure; D005451:Fluorescein Angiography / Q000187:drug effects*; D005654:Fundus Oculi; D007275:Injections, Intravenous; D007834:Lasers; D008251:Macaca; D009887:Ophthalmoscopy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000648:ultrastructure*; D011166:Porphyrins / Q000494:pharmacology*; D011817:Rabbits; D015356:Retinal Artery Occlusion / Q000139:chemically induced / Q000473:pathology*; D012170:Retinal Vein Occlusion / Q000139:chemically induced / Q000473:pathology*
D017319:Photosensitizing Agents; D011166:Porphyrins; C053434:Talaporfin