Photodynamic and Photothermal Port Wine Stain Treatment

描述(申请人提供)：葡萄酒渍(PWS)是一种先天性的进行性皮肤血管畸形，发生在大约0.7%的新生儿中，具有潜在的破坏性心理并发症，在某些情况下还会造成严重的身体影响。目前的治疗方法实现了这些皮损中不到10%的完全漂白，通常需要多种治疗(5-30或更多)。我们打算结合光动力(PDT)和脉冲染料激光(PDL)疗法(PDT+PDL)，在不损伤周围皮肤的情况下，实现对临床上最相关的PWS血管的永久性破坏。我们将使用血管特异性光敏剂，苯并卟啉衍生单酸环A(BPD)和连续波(CW)黄色光，将PDT效应限制在皮肤表面下最浅的1.0 mm处。PDT期间将使用光学多普勒层析成像(ODT)监测血管血流。当注意到血流量减少或给予100J/cm2的光剂量后，将停止CW照射。这种方法将限制对靶血管的血管损伤的深度和程度，并防止皮肤坏死，这将导致完全的血管破坏。PDT后，立即或在短时间间隔后，进行PDL照射，以完成浅表血管的破坏，而不会损伤周围皮肤。 使用鸡绒毛膜尿囊膜的初步实验证实，与单独使用任何一种方法相比，PDT+PDL PWS血管破坏的效果更好。这项建议包括一项协议，以证实PDT+PDL在大鼠背侧皮瓣窗模型中的优越疗效。使用相同的动物模型，还将评估使用BPD和黄光进行PDT的血管损伤阈值以及PDT+PDL血管治疗的最佳治疗参数。最后，我们将在综合临床试验中确定PDT+PDL PWS治疗的有效性和安全性。这项建议中的研究结果有望导致新的和创新的技术的发展，这将提供一种更有效、最重要的是更安全的方法来去除PWS胎记。

DESCRIPTION (provided by applicant): Port wine stains (PWS) are congenital, progressive vascular malformations of the skin that occur in approximately 0.7% of neonates and have potentially devastating psychological complications and, in some cases, serious physical effects as well. Current therapies achieve complete blanching of less than 10% of these lesions and multiple treatments (5 -30 or more) are generally required. We intend to combine photodynamic (PDT) and pulsed dye laser (PDL) therapies (PDT + PDL) to achieve permanent destruction of the most clinically relevant PWS blood vessels without injury to the surrounding skin. We will use a vascular specific photosensitizer, benzoporphyrin derivitive monoacid ring A (BPD), and continuous wave (CW) yellow light to confine PDT effects to the most superficial 1.0 mm below the skin surface. Vascular flow will be monitored during PDT using optical Doppler tomography (ODT). CW irradiation will be stopped when a reduction in blood flow is noted or after a light dose of 100 J/cm2 has been delivered. This approach will limit the depth and extent of vascular injury to the targeted vessels and prevent skin necrosis, which would result from total vascular destruction. PDT will be followed immediately, or after a brief time interval, by PDL irradiation to complete superficial vessel destruction without injury to the surrounding skin. Initial experiments using a chick chorioallantoic membrane confirmed the superior efficacy of PDT + PDL PWS vessel destruction as compared to either modality alone. This proposal includes a protocol to confirm the superior efficacy of PDT + PDL using a rat dorsal skin flap window model. The threshold of vascular lesion damage for PDT using BPD and yellow light and optimal treatment parameters for PDT + PDL vascular therapy will also be evaluated using the same animal model. Finally, we will determine the efficacy and safety of PDT + PDL PWS therapy in comprehensive clinical trials. The results of the studies in this proposal are expected to lead to the development of novel and innovative technology which will provide a more effective and, most importantly, safer method for removal of PWS birthmarks.