PDT to monkey CNV with ATX-S10(Na): inappropriateness of early laser irradiation for selective occlusion.
OBJECTIVE
There is controversy about which mode of laser irradiation, early irradiation with low-dose photosensitizer or late irradiation with high-dose, benefits the selective occlusion of choroidal neovascularization (CNV) in photodynamic therapy (PDT). In this study, using an amphiphilic photosensitizer, 13,17-bis (1-carboxypropionyl) carbamoylethyl-8-etheny-2-hydroxy-3-hydroxyiminoethylidene-2,7,12,18-tetraethyl porphyrin sodium (ATX-S10(Na); Photochemical Inc., Okayama, Japan), photodynamic and adverse effects of early irradiation on CNV-bearing monkey eyes were investigated.


METHODS
Experimentally induced CNV lesions and normal retina were irradiated with a diode laser (670-nm wavelength) at a dose of 1 to 90 J/cm(2) at 1 to 19 minutes after intravenous injection of 2 mg/kg body weight of ATX-S10(Na). Vascular occlusion and CNV recurrence were evaluated by fluorescein and indocyanine green angiography and histologic analysis, until 4 weeks after irradiation.


RESULTS
Of 45 different conditions, 23 did not induce CNV closure, 20 provided both CNV occlusion and retinal vessel damage, and 2 achieved selective CNV occlusion without retinal vascular injury. Recurrence of CNV was induced in 19 of 22 CNV-occluding conditions. ATX-S10(Na) angiography showed that dyes were similarly distributed between normal vessels and CNV at early time periods after injection, whereas they were preferentially accumulated in CNV after 30 minutes.


CONCLUSIONS
In PDT with ATX-S10(Na), irradiation within 20 minutes of dye injection failed to induce selective CNV occlusion, probably because there is no significant difference in the biodistribution of dye between CNV and retinal vessels. It also caused frequent CNV recurrence after extensive inflammation in the irradiated retina.
Obana
A
A
Department of Ophthalmology and Visual Sciences, Osaka City University Graduate School of Medicine, Japan. akira-kun@med.osaka-u.ac.jp
Gohto
Y
Y
Kaneda
K
K
Nakajima
S
S
Miki
T
T
D000818:Animals; D002829:Choroid / Q000098:blood supply / Q000473:pathology; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D005451:Fluorescein Angiography; D007208:Indocyanine Green; D007275:Injections, Intravenous; D007834:Lasers / Q000009:adverse effects; D008252:Macaca fascicularis; D023421:Models, Animal; D009887:Ophthalmoscopy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011166:Porphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012008:Recurrence; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
C117772:ATX S10Na(II); D017319:Photosensitizing Agents; D011166:Porphyrins; D007208:Indocyanine Green