OCULAR MELANOMA--DEVELOPMENT OF A PHOTODYNAMIC THERAPY

本研究的长期目标是建立光动力疗法 作为一种安全有效的治疗眼部疾病的临床方法， 肿瘤的 葡萄膜黑色素瘤是最常见的眼内恶性肿瘤， 与高转移率相关。 到目前为止，尽管 治疗，无论是眼球摘除术还是某种形式的放射治疗， 超过四分之一的患者发生转移性疾病。预期寿命 转移瘤患者的生存期一般小于1年。 治疗葡萄膜黑色素瘤的理想替代疗法是 能以最小的眼部发病率根除肿瘤细胞。 光动力疗法（PDT）是一种相对较新的实验性的治疗手段， 治疗那些可以接触到光的肿瘤。 这种方法提供了双重 对肿瘤组织的选择性，这是通过优选的 光敏剂染料保留在肿瘤组织内， 将照明场限制在肿瘤部位。 的潜在 这种选择性靶向肿瘤细胞的方式使得PDT特别适合于 在结构完整性对于 维持重要功能。 眼黑色素瘤应该是一个理想的 候选人的光动力疗法，因为它是很容易可视化，通过 瞳孔扩大，可直接照明。 我们已经建立了色素性脉络膜黑色素瘤的动物模型， 实验室和这个模型，生物分布的各种 将评估荷瘤眼睛中的光敏剂以确定 该光敏剂染料更适合于眼黑色素瘤的PDT。 一旦脉络膜黑色素瘤中光敏剂的保留模式 和周围组织被确定，PDT在 评价色素性脉络膜黑色素瘤的破坏。 黑素瘤- 还将评估反应性抗体增强免疫应答的潜力。 将光敏剂输送到肿瘤部位。 最后，A 光敏剂血管造影将被开发用于检测 光敏剂在眼睛肿瘤轴承。 开发一种有效的光动力疗法， 黑色素瘤细胞更有选择性地可以提高生存率， 眼黑色素瘤患者的视力结果。

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.