Safe Use of Hematoporphyrin Treatment of Ocular Tumors

Lutty, Gerard

Abstract

The current treatment of malignant melanomas of the retina is limited to enucleation, if the neoplasm is diagnosed early. Recent developments in experimental models of ocular tumors suggest that the photosensitization of a hematoporphyrin derivative may be a possible alternative therapy. Hematoporphyrin derivative (HPd) dye has already been used in animals and human subjects for the detection and destruction of malignant tumors. Its use in the eye presents special difficulties. These arise because of the extreme sensitivity of the retina to damage by the combination of dye and light irradiation which produces singlet oxygen. Singlet oxygen is not only toxic to tumor tissue but also to the vascular endothelium.
The aim of this program is to devise a suitable HPD dosage and irradiation level that will destroy tumors without permanently damaging the retina. A possible alternative that we will investigate is generation of singlet oxygen without the use of dyes. This can be accomplished by a 1.06 micron YAG laser, which gives excellent penetration of tissue by longer wavelength emission. A final approach, if all variations of the hematoporphyrin therapy and the YAG laser treatment are found to be not effective or too destructive to the eye, is to investigate other dyes that can be used to generate singlet oxygen. An obvious choice are the cyanine dyes which absorb and fluoresce at long wavelengths. Longer wavelengths will allow deeper penetration of light into the tumors, especially the melanomas, and are safer for the retina. Once it is established which modality is the most effective in eradicating experimental ocular melanomas with minimal damage to the retina, the effect on six human ocular melanomas maintained in cell cultures will be tested. If this effort produces a safe effective therapy for ocular tumors in rabbits, the technique may be effective in treating not only human malignant melanomas but also retinoblastomas.