ABSTRACT
Photodynamic therapy (PDT) entails the administration of a photosensitizer with its subsequent accumulation in the target tissue and then activation by monochromatic light corresponding to the sensitizer’s absorption profi le (1). Cytotoxic singlet oxygen and free radicals are produced causing irreversible cellular damage. PDT has traditionally been used in the treatment of cancer (2), but the potential for selective destruction of diseased vessels, while sparing normal overlying tissues, coupled with promising clinical effi cacy, resulted in its use for the treatment of age-related macular degeneration (AMD), particularly subfoveal choroidal neovascularization (CNV). PDT’s relative selectivity for CNV is achieved both through photosensitizer retention in choroidal neovascular membranes and through targeted light application. This chapter will provide an overview of the photochemistry of PDT and the clinical trials that have established its clinical effectiveness in the treatment of neovascular AMD.
VASCULAR TARGETING PDT causes direct cellular injury in addition to microvascular damage and nonperfusion within illuminated tissue. Uptake is due to the increased expression of low-density lipoprotein receptors on tumor cells and neovascular endothelium. Porphyrin photosensitization in mammals was studied beginning in 1910 when Hausmann investigated the effects of hematoporphyrin and light in mice (3). The results established the phototoxic capability of porphyrins, and Hausmann concluded that peripheral vasculature was targeted by PDT. In 1963, Castellani and colleagues demonstrated microvasculature to be a crucial target (4). Vascular occlusion following PDT is marked by the release of vasoactive molecules, vasoconstriction, blood cell aggregation, endothelial cell damage, blood fl ow stasis, and hemorrhage. The response is dependent on the sensitizer type, concentration, and the time interval between administration and treatment. Benzoporphyrin derivative monoacid ring A (BPD-MA)-induced PDT resulted in selective destruction of tumor microvasculature in a chondrosarcoma rodent model when compared with the surrounding normal microvasculature (5).
