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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29EY010975-05
Application #
2711133
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1994-09-01
Project End
2000-08-31
Budget Start
1998-09-01
Budget End
2000-08-31
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
02114
Krause, Matthias H J; Xiong, Jing; Gragoudas, Evangelos S et al. (2003) Treatment of experimental choroidal melanoma with an Nd:yttrium-lanthanum-fluoride laser at 1047 nm. Arch Ophthalmol 121:357-63
Krause, Matthias; Kwong, Kenneth K; Xiong, Jing et al. (2002) MRI of blood volume and cellular uptake of superparamagnetic iron in an animal model of choroidal melanoma. Ophthalmic Res 34:241-50
Pineda 2nd, R; Theodossiadis, P G; Gonzalez, V H et al. (1998) Establishment of a rabbit model of extrascleral extension of ocular melanoma. Retina 18:368-72
Kim, R Y; Hu, L K; Flotte, T J et al. (1997) Digital angiography of experimental choroidal melanomas using benzoporphyrin derivative. Am J Ophthalmol 123:810-6
Young, L H; Howard, M A; Hu, L K et al. (1996) Photodynamic therapy of pigmented choroidal melanomas using a liposomal preparation of benzoporphyrin derivative. Arch Ophthalmol 114:186-92
Kim, R Y; Hu, L K; Foster, B S et al. (1996) Photodynamic therapy of pigmented choroidal melanomas of greater than 3-mm thickness. Ophthalmology 103:2029-36