Photodynamic therapy of age-related macular degeneration: History and principles

We briefly review the history and principles of photodynamic therapy (PDT), especially as it is applied to choroidal neovascularization (CNV) in age-related macular degeneration (AMD). After a brief general history of PDT, we discuss the relationship between the physicochemical structure and photodynamic activity of the second-generation photosensitizers, such as those in current clinical use. We then discuss the basic photophysics of photosensitizer molecules, and describe the initial chemical reactions induced by activated sensitizers. We outline a novel method for screening photosensitizers to be used in treating CNV, as well as the complex biomolecular pathways modulated by PDT-induced oxidative stress and the vascular effects of PDT in solid tumors. The paper closes with a discussion of how all this information might be used to improve the selectivity and efficacy of clinically useful photosensitizers.