Hematoporphyrin derivative photoradiation therapy for the treatment of intraocular tumors: examination of acute normal ocular tissue toxicity

Preclinical studies designed to define potential side effects resulting from the use of hematoporphyrin derivative (HPD) photoradiation therapy (PRT) as a modality for treating intraocular tumors have been performed. Pigmented rabbits were used to evaluate acute normal ocular tissue toxicity following single HPD PRT treatments in which the light was directed through the pupil and onto a 1-sq cm area of the retina. The treatment procedure consisted of the i.v. administration of HPD (1 to 10 mg/kg) followed 48 hr later by a 15-min exposure of localized red light [635 +/- 5 nm; 40 to 400 milliwatts/sq cm] generated by a free running rhodamine B dye laser pumped by a 5-watt argon laser. Toxicity to normal retinal tissue was documented using fundus photography, fluorescein angiography, and histological examination. The results of this study demonstrated that ocular damage in the form of retinal edema, detachment, and necrosis could be induced by clinically relevant doses of HPD PRT. The area of retinal damage was limited to the treatment field in all but the highest doses of HPD PRT. The histological results were in agreement with the visual observations in that abrupt and demarcated transition areas between injured and normal-appearing retina were observed. Care will have to be used in the delivery of light to the treatment field if HPD PRT is to be utilized for treatment of intraocular tumors.