Phthalocyanine mediated photodynamic thrombosis of experimental corneal neovascularization: Effect of phthalocyanine dose and irradiation onset time on vascular occlusion rate

Abstract

The aim of this study was to evaluate the possible influence of phthalocyanine dose and of time interval between phthalocyanine injection and irradiation commencement on the rate of experimental corneal neovascularization photodynamic thrombosis in albino rabbits. New corneal vessels were irradiated with a diode laser (670 nm, 2 mW) after the intravenous injection of chloroaluminum sulfonated phthalocyanine. Different animals were irradiated either 5 min after the injection of different phthalocyanine doses (3, 6, 8, 12, or 14 mg/kg), or at different times (5 min, 24 h, or 58 h) after a standard phthalocyanine dose (3 mg/kg) injection. Irradiation time necessary for vascular occlusion was recorded. Decrease of phthalocyanine dose as well as delay of irradiation onset resulted in a statistically significant increase of irradiation time. Electron and light histological examination revealed platelet thrombi inside irradiated corneal new vessels. Damage in the vascular endothelial cell membrane and in intercellular contact structure was noted, leading to disorganization of the endothelial cells layer and death of most endothelial cells. These results indicate that both early commencement of irradiation after phthalocyanine injection and phthalocyanine dose increase accelerate the rate of phthalocyanine mediated corneal neovascularization photodynamic thrombosis. Thrombosis seems to result from photochemically induced vascular endothelial cell damage.

Application of femtosecond ultrashort pulse laser to photodynamic therapy mediated by indocyanine green

“…15 Thirty one albino rabbits weighing 2-2.5 kg were used. Corneal neovascularisation was induced in one eye of each animal using an intracorneal suturing technique as previously described.…”

Treatment Parameters for Selective Occlusion of Experimental Corneal Neovascularization by Photodynamic Therapy using a Water Soluble Photosensitizer, ATX-S10(Na)

“…Some authors recommend starting laser irradiation directly after dye injection (Tsilimbaris et al, 1994), and others recommend during some time after dye injection, in which the dye has been allowed to accumulate in new vessels and is signi®-cantly greater in these vessels than in the surrounding normal tissue. Schmidt-Erfurth et al (1995) showed by spectrophotometry that BPD accumulated in CoNV 60±90 min after dye injection and suggested that PDT to occlude CoNV be started 1 hr after injection of liposomal BPD.…”

“…Some kinds of second-generation photosensitizers, such as chloro-aluminum sulfonated phthalocyanine (CASPc) (Pallikaris et al, 1993;Tsilimbaris et al, 1994), benzoporphyrin derivative (BPD) (Schmidt-Erfurth et al, 1995), and tin ethyl etiopurpurin (SnET2) (Soliman et al, 1997;Primbs et al, 1998) Group, 1999;Thomas et al, 2000). A new photosensitizer, ATX-S10(Na), which is a synthetic chlorin derivative, is one of the second-generation photosensitizers, sharing with them the advantages of rapid elimination from the body (Nakajima et al, 1998).…”

Selective occlusion of choroidal neovascularization by photodynamic therapy with a water-soluble photosensitizer, ATX-S10

“…Different optimal time periods for laser irradiation have been reported for other dyes. For PDT using chloro-aluminum sulfonated phthalocyanine, the optimal time was immediately after dye injection [14]. For BPD, the optimal was suggested to be 1-2 h after dye injec- tion in an investigation of corneal neovascularization [18] and 20-50 min in other CNV investigations [19,20].…”

“…Photodynamic therapy (PDT), in which intravenous administration of a photosensitizer is followed by laser irradiation at the absorption peak of the photosensitizer, theoretically can destroy vascular endothelial cells [4] and induce thrombosis with subsequent regression of the new vessels, without any direct injury to surrounding normal tissue [5,6]. Many photosensitizers have been examined for the treatment of ocular neovascularization [7][8][9][10][11][12][13][14][15][16][17][18][19][20], but only benzoporphyrin derivative monoacid (BPD) [21] and tin ethyl etiopurpurin (SnET2) [22], which belong to the so-called class of second-generation photosensitizers, are presently under clinical trials and have been evaluated to be effective for treatment of this condition. Although hematoporphyrin derivatives (HPDs) have occlusive effects on ocular neovascularization and have been approved for clinical use in patients with certain kinds of cancer [7][8][9], they have the disadvantage of exhibiting long retention times in the body and correspondingly high residual phototoxicity to the skin.…”