Photodynamic therapy of intraocular tumors: examination of hematoporphyrin derivative distribution and long-term damage in rabbit ocular tissue

Abstract

Studies were performed to determine the distribution of hematoporphyrin derivative (HPD) in ocular structures and to characterize long-term damage associated with ocular HPD photodynamic therapy. Pigmented rabbits with an amelanotic melanoma heterotransplanted to the iris were used to obtain quantitative tissue levels of HPD as well as to document HPD localization by fluorescence microscopy. HPD was administered i.v., and tissue concentrations of HPD were determined by spectrofluorometry following porphyrin extraction. Vascular structures such as the tumor, iris, and choroid-retina as well as the aqueous fluid from eyes containing tumors demonstrated rapid HPD localization. The sclera had minimal HPD uptake, and the drug was not detected in avascular structures such as the lens or cornea. HPD was cleared from all ocular structures except the tumor and choroid-retina by 24 h following injection. Fluorescence microscopy data indicate that HPD remained in the avascular photoreceptor cell outer segments of the retina. Long-term damage was documented in rabbits which received HPD photodynamic therapy to a 1-sq cm area of retina via transpupillary light delivery. Acute damage to the exposed area of retina (in the form of a chorioretinal scar) could be induced. This damage was permanent but not progressive. Lens opacities were not observed, and the cornea, aqueous, and vitreous remained clear on all test eyes. The results from these studies suggest that HPD photodynamic therapy may provide a selective and safe approach to the treatment of ocular tumors.