COMBINED PHOTODYNAMIC AND PULSED DYE LASER TREATMENT OF PORT WINE STAINS

光动力和脉冲染料激光相结合处理波特酒污渍

• 批准号: 7606644
• 负责人: KRISTEN M KELLY
• 金额: $ 0.74万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606644
• 关键词: Adult; Age related macular degeneration; Appearance; Area; Argon; Back; Blood Vessels; Blood capillaries; Blood flow; Caliber; Canada; Caring; Chemicals; Chin; Cicatrix; Clinical; Clinical Management; Complex; Computer Retrieval of Information on Scientific Projects Database; Computers; Coupled; Cutaneous; Depth; Dermatology; Dermis; Dyes; Esthetic Surgery; Evaluation; Excision; Face; Fiber; Fiber Optics; Flowmetry; Funding; Goals; Grant; Human; Image; In Situ; Injury; Institution; Laser-Doppler Flowmetry; Lasers; Lesion; Light; Low-Level Laser Therapy; Measurement; Measures; Methods; Optical Coherence Tomography; Optics; Output; Pan Genus; Patients; Perfusion; Philadelphia; Photochemotherapy; Photosensitivity; Photosensitizing Agents; Physiologic pulse; Port-Wine Stain; Principal Investigator; Process; Protocols documentation; Publications; Pulse taking; Pump; Quebec; Raven; Reactive Oxygen Species; Research; Research Personnel; Research Proposals; Resolution; Resources; Risk; Safety; Signal Transduction; Singlet Oxygen; Skin; Source; Standards of Weights and Measures; Tissues; United States; United States Food and Drug Administration; United States National Institutes of Health; Update; Verteporfin; Yang; absorption; capillary; clinically relevant; day; experience; improved; instrument; irradiation; malformation; response; time use; tomography

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Port wine stains (PWS) are congenital vascular malformations of the skin present in 1.5 million patients in the United States. The pulsed dye laser (PDL) is the standard of care for treatment of these lesions and by selectively targeting tissue vasculature, lightens these lesions in some PWS patients. However, few patients (< 10%) achieve complete blanching of their lesion and multiple treatments (5 -30 or more) are generally required (1). One primary factor limiting PWS lesion blanching for many patients is the limited ability of the PDL to remove small (less than 20 m diameter) superficial vessels, which contribute significantly to the clinical appearance of these birthmarks (2). Another highly effective method for selectively targeting tissue vasculature is photodynamic therapy (PDT), which utilizes a chemical photosensitizer and light to generate singlet oxygen radicals (3). PDT using red light and vascular specific photosensitizers has been implemented in a few small trials for PWS treatment (4,5,6). Impressive lesion lightening was noted; however, mild scarring also occurred in some cases as a result of total and deep vascular destruction induced by the use of long wavelength red light. Further, patients experienced prolonged photosensitivity (30 days). In the last few years, a new, vascular specific photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), has been developed and approved by the Food and Drug Administration for treatment of age-related macular degeneration and other ocular indications using an absorption band at 690 m. BPD-MA has an additional absorption peak at 576 nm (yellow light) and is rapidly metabolized, limiting the photosensitivity period in humans to 5 days or less. We plan to use BPD-MA and yellow light to treat PWS birthmarks. This photosensitizer and wavelength combination will limit vascular injury to the most superficial 1mm of the dermis. In order to provide an additional margin of safety, we will use sub-threshold PDT treatment to create an initial vascular injury and then use the PDL (wavelength = 585 nm) to induce photothermal effects, resulting in removal of vessels in the targeted superficial 1 mm region of the dermis. We will use optical Doppler flowmetry (ODT; see description below) to determine when the initial injury has occurred and initial irradiation should be stopped. ODT combines laser Doppler flowmetry with optical coherence tomography to obtain high resolution (10 microns) images of blood flow in human skin in-situ and on-line. The utility of ODT for documenting the change of PWS blood flow in response to therapy has been demonstrated (7). We developed an ODT instrument, which uses a fiber optic Michelson interferometer with an AFC Inc. (Quebec, Canada) superluminescent diode (SLD) at a wavelength of 850 nm as the light source. The output power is 5 mW. Light backscattered from the skin is coupled back into the fiber and forms interference fringes at the photodetector. The digitized fringe signal is then processed by a computer to generate conventional ODT images from complex analytic continuation of the interference fringes. ODT measurements pose NO RISK to subjects. Use of the ODT instrument is similar to shining a flashlight on the skin and measuring the backscattered light. The exact same ODT instrument is approved for evaluations in protocol 96-200. Dr. Stuart Nelson is the principal investigator for 96-200 and a co-investigator in the current protocol. Our goal is to safely achieve maximum clinically relevant PWS vessel destruction utilizing the combined approach of sub-threshold photodynamic together with standard photothermal destruction. The central hypothesis of this research proposal is that combined sub-threshold photodynamic and pulsed dye laser therapy can be used to safely achieve improved PWS lesion lightening as compared to either sub-threshold photodynamic therapy or pulsed dye laser therapy alone. For this PILOT STUDY, we will treat small areas of non-facial PWS in adults and compare the results of our combined PDT/PDL approach to standard pulsed dye laser treatment alone and sub-threshold PDT alone. 1. Kelly, K.M., Nelson, J.S. An update on the clinical management of port wine stains, Lasers Med Sci 2000; 15,220-226. 2. Edstom, D.W., Hedblad, M-A., Ros, A-M. Flashlamp pulsed dye laser and argon-pumped dye laser in the treatment of port-wine stains: a clinical and histological comparison. Br J Derm 2002; 146:285-289. 3. Nelson, J.S., McCullough, J.L., Berns, M.W. Principles and applications of Photodynamic Therapy in dermatology. In: Arndt K.A., Dover J.E., Olbricht S.A. (eds.), Lasers in Cutaneous and Aesthetic Surgery. Philadelphia, PA: Lippincott-Raven, 1997;349-382. 4. Jiang, L., Gu, Y., Li, X., Zhao, X., Li, J., Wang, K., Liang, J., Pan, Y., Zhang, Y. Changes of skin perfusion after photodynamic therapy for port wine stain. Chin Med J 1998;111:136-138. 5. Lin, X.X., Wang, W., Wu, S.F., Yang, C., Chang, T.S. Treatment of capillary vascular malformation (port-wine stains) with photochemotherapy. Plast Reconstr Surg. 1997;99:1826-1830. 6. Kimel, S., Svaasand, L.O., Kelly, K.M., Nelson, J.S. Synergistic photodynamic and photothermal treatment of port wine stains. Submitted for publication Lasers Surg Med. 7. Nelson J.S., Kelly K.M., Zhao Y., Chen Z. Imaging blood flow in human port wine stain in-situ and In real-time using optical doppler tomography. Arch Dermatol 2001;137: 741-744.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 港口葡萄酒污渍（PWS）是美国150万患者的皮肤的先天性血管畸形。 脉冲染料激光器（PDL）是治疗这些病变的护理标准，通过选择性靶向组织脉管系统，在某些PWS患者中减轻了这些病变。 但是，很少有患者（<10％）获得病变的完全毛病，通常需要多种治疗（5-30或更多）（1）。 对于许多患者来说，限制PWS病变的一个主要因素是PDL去除小（小于20 m）浅表血管的能力有限，这对这些胎记的临床表现产生了显着贡献（2）。 选择性靶向组织脉管系统的另一种高效方法是光动力疗法（PDT），它利用化学光敏剂和光产生单重氧自由基（3）。 使用红光和血管特异性光敏剂的PDT已在一些小型PWS治疗中实施（4,5,6）。 注意到了令人印象深刻的病变照明。然而，在某些情况下，由于使用长波长红光引起的全部和深血管破坏而导致轻度疤痕。 此外，患者经历了长时间的光敏性（30天）。 在过去的几年中，食品和药物管理局已经开发和批准了一种新的，血管特异性的光敏剂，苯并甲磷脂衍生物单拟足环A（BPD-MA），用于治疗与年龄相关的黄斑变性和其他眼睛的适应症带690 m。 BPD-MA在576 nm（黄光）处具有额外的吸收峰值，并迅速代谢，将人类的光敏性周期限制为5天或更短。 我们计划使用BPD-MA和黄光来治疗PWS胎记。 这种光敏剂和波长组合将限制真皮最浅1mm的血管损伤。 为了提供额外的安全余量，我们将使用亚阈值PDT治疗来产生初始血管损伤，然后使用PDL（波长= 585 nm）诱导光热效应，从而导致靶向表面浅表1真皮的MM区域。 我们将使用光学多普勒流量计（ODT；请参见下面的描述）来确定何时发生初始损伤，并应停止初始辐射。 ODT将激光多普勒流量指定与光学相干断层扫描相结合，以获得高分辨率（10微米）在原位和在线的人皮肤中的血液流动图像。 已经证明了ODT记录PWS血流变化而响应治疗的变化的效用（7）。 我们开发了一种ODT仪器，该仪器在AFC Inc.（加拿大魁北克）使用光纤米歇尔森干涉仪上，以850 nm的波长作为光源。 输出功率为5 mW。 从皮肤反向散射的光耦合回纤维，并在光电探测器处形成干扰条纹。 然后，计算机处理数字化的条纹信号，以从干扰条纹的复杂分析延续中生成常规的ODT图像。 ODT测量对受试者没有风险。 ODT仪器的使用类似于在皮肤上闪耀手电筒并测量反向散射的光线。完全相同的ODT仪器已被批准在协议96-200中进行评估。 斯图尔特·尼尔森（Stuart Nelson）博士是96-200的首席研究员，也是当前协议中的共同研究员。 我们的目标是利用亚阈值光动力学的联合方法以及标准的光热破坏，安全实现最大临床相关的PWS血管破坏。 这项研究提案的中心假设是，与单独的阈值光动力疗法或单独的脉冲染料激光疗法相比，可以使用亚阈值光动力和脉冲染料激光疗法来安全地实现改善的PWS病变降低。 在这项试验研究中，我们将在成人中对非种族PW的小面积进行处理，并将我们合并的PDT/PDL方法的结果与单独的标准脉冲染料激光治疗和单独的亚阈值PDT进行比较。 1。Kelly，K.M.，Nelson，J.S。港口葡萄污渍临床管理的最新动态，Lasers Med Sci 2000； 15,220-226。 2。D.W.Edstom，Hedblad，M-A。，Ros，A-M。 闪光灯脉冲染料激光和氩气染料激光在港口染色的处理中：一种临床和组织学比较。 Br J Derm 2002; 146：285-289。 3。Nelson，J.S。，McCullough，J.L.，Berns，M.W。光动力疗法在皮肤病学中的原理和应用。在：Arndt K.A.，Dover J.E.，Olbricht S.A.（编辑），皮肤和美学手术的激光。宾夕法尼亚州费城：Lippincott-Raven，1997年； 349-382。 4。Jiang，L.，Gu，Y.，Li，X.，Zhao，X.，Li，J.，Wang，K.，Liang，J.，Pan，Y.，Zhang，Y.光动力疗法用于港口葡萄酒污渍。 Chin Med J 1998; 111：136-138。 5。Lin，X.X.，Wang，W.，Wu，S.F.，Yang，C.，Chang，T.S。用光化学疗法处理毛细血管血管畸形（港口污渍）。塑料重合手术。 1997; 99：1826-1830。 6. Kimel，S.，Svaasand，L.O.，Kelly，K.M.，Nelson，J.S。 港口葡萄酒污渍的协同光动力和光热处理。 已提交出版激光手术。 7。NelsonJ.S.，Kelly K.M.，Zhao Y.，Chen Z.使用光学多普勒层析成像实时的人类港口葡萄酒染色中的血流。 Arch Dermatol 2001; 137：741-744。