The long-term-objective of this study is to establish photodynamic therapy as a safe and effective clinical modality for the treatment of ocular tumors. Uveal melanoma is the most common intraocular malignancy and is associated with a high incidence of metastases. To date, in spite of treatment, whether it is enucleation or some form of radiotherapy, metastatic disease occurs in over a quarter of patients. Life expectancy of patients with metastases is generally less than 1 year. An ideal alternative therapy for the treatment of uveal melanoma is one that would eradicate tumor cells with minimal ocular morbidity. Photodynamic therapy (PDT) is a relatively new and experimental means of treating tumors that are accessible to light. This approach offers dual selectivity for tumor tissue which is accomplished by the preferential retention of photosensitizer dye within the neoplastic tissue and restriction of the field of illumination to the tumor site. The potential of this modality to selectively target tumor cells makes PDT particularly attractive in anatomic regions where structural integrity is crucial for maintenance of vital functions. Ocular melanoma should be an ideal candidate for photodynamic therapy as it is easily visualized through dilated pupils and is accessible to direct illumination. An animal model of pigmented choroidal melanoma has been developed in our laboratory and with this model, biodistribution of various photosensitizers in the tumor-bearing eye will be evaluated to determine which photosensitizer dye is more suitable for PDT of ocular melanoma. Once the retention pattern of photosensitizers within choroidal melanomas and surrounding tissues is determined, the effectiveness of PDT in the destruction of pigmented choroidal melanomas will be evaluated. Melanoma- reactive antibodies will also be assessed for their potential to enhance the delivery of photosensitizers to the tumor site. Lastly, a photosensitizer angiography will be developed for the detection of photosensitizers in tumor-bearing eyes. The development of an effective photodynamic therapy that eradicates melanoma cells more selectively could enhance survival and provide better visual outcome for patients afflicted with ocular melanoma.
