Evaluation of photodynamically induced damage to healthy eye tissues of rabbits using the second-generation photosensitizers bacteriochlorin a and mTHPC

摘要

Abstract: Immediate illumination after sensitizer administration is currently often applied in PDT-trials in ophthalmology. The extent of possible damage to healthy ocular tissue after i.v. administration of the photosensitizers bacteriochlorin a (BCA) or mesa (tetrahydroxyphenyl) chlorin (mTHPC) and subsequent illumination with light of the appropriate wavelength and dose was assessed in rabbit eyes. Both hydrophobic drugs were formulated in 30% polyethylene glycol, 20% ethanol and 50% water to obtain an iv injectable suspension. Rabbits destined for BCA-PDT received a single dose of 10 mg/kg.bw. Rabbits destined for mTHPC-PDT received a dose of 0.3 mg/kg.bw. BCA- treated animals were illuminated immediately and 1, 2 and three hours after administration of the dye with an experimental Philips laser diode (760 nm, c.w., 100 mW/cm$+2$/, 100 J). To illuminate the eyes of the mTHPC- treated animals a Krypton laser was used (648 nm, c.w., 100 mW/cm$+2$/, 20 J). Illumination of these animals was performed immediately, 24, 48 and 72 hours after administration of the dye. BCA or mTHPC without illumination or illumination without administration of a sensitizing dye did not affect normal ocular tissues as judged by histology. Illumination of the entire eye of BCA-treated animals, immediately after administration of the dye caused a lesion in the macula area with a diameter of 3 mm. At the lesion side the photoreceptors were destroyed, ganglion cells were swollen and the sclera was affected. No skin photosensitivity was observed at anytime. Skin photosensitivity was observed in animals treated with mTHPC. Illumination caused swollen eyelids in all animals except when performed immediately after dye administration. !14