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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 葡萄酒色斑 (PWS) 是一种先天性皮肤血管畸形，在美国有 150 万患者存在。 脉冲染料激光 (PDL) 是治疗这些病变的标准护理方法，通过选择性地靶向组织脉管系统，可以减轻一些 PWS 患者的这些病变。 然而，很少有患者 (< 10%) 的病变完全变白，通常需要多次治疗（5 -30 次或更多）(1)。 对于许多患者来说，限制 PWS 病变变白的一个主要因素是 PDL 去除小（直径小于 20 m）浅表血管的能力有限，而这对这些胎记的临床表现有很大影响 (2)。 另一种选择性靶向组织脉管系统的高效方法是光动力疗法 (PDT)，它利用化学光敏剂和光产生单线态氧自由基 (3)。 使用红光和血管特异性光敏剂的 PDT 已在一些 PWS 治疗的小型试验中实施 (4,5,6)。 注意到令人印象深刻的病变减轻；然而，在某些情况下，由于使用长波长红光引起的全面和深层血管破坏，也会出现轻微的疤痕。 此外，患者会经历长时间的光过敏（30 天）。 过去几年，美国食品和药物管理局开发并批准了一种新型血管特异性光敏剂苯并卟啉衍生物单酸环 A (BPD-MA)，用于使用 690 m 吸收带治疗年龄相关性黄斑变性和其他眼部适应症。 BPD-MA 在 576 nm（黄光）处有一个额外的吸收峰，并且代谢迅速，将人体的光敏期限制在 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血管损伤限制在真皮最表层 1 毫米内。 为了提供额外的安全边际，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，从而去除目标真皮表层 1 mm 区域的血管。 我们将使用光学多普勒血流计（ODT；参见下面的描述）来确定何时发生初始损伤以及应停止初始照射。 ODT 将激光多普勒血流测量与光学相干断层扫描相结合，可现场和在线获得人体皮肤血流的高分辨率（10 微米）图像。 ODT 在记录治疗后 PWS 血流变化方面的实用性已得到证实 (7)。 我们开发了一种ODT仪器，它使用光纤迈克尔逊干涉仪和AFC Inc.（加拿大魁北克省）波长850 nm的超发光二极管（SLD）作为光源。 输出功率为5毫瓦。 从皮肤反向散射的光耦合回光纤并在光电探测器处形成干涉条纹。 然后，数字化的条纹信号由计算机处理，根据干涉条纹的复杂分析延续生成传统的 ODT 图像。 ODT 测量对受试者不构成风险。 ODT 仪器的使用类似于用手电筒照射皮肤并测量反向散射光。完全相同的 ODT 仪器被批准用于协议 96-200 中的评估。 Stuart Nelson 博士是 96-200 的首席研究员，也是当前方案的联合研究员。 我们的目标是利用亚阈值光动力与标准光热破坏相结合的方法，安全地实现最大程度的临床相关 PWS 血管破坏。 本研究提案的中心假设是，与单独使用亚阈值光动力疗法或脉冲染料激光疗法相比，联合使用亚阈值光动力疗法和脉冲染料激光疗法可安全地实现改善的 PWS 病变减轻。 在这项试点研究中，我们将治疗成人非面部 PWS 的小区域，并将我们的 PDT/PDL 组合方法与单独使用标准脉冲染料激光治疗和单独使用亚阈值 PDT 的结果进行比较。 1. 凯利，K.M.，纳尔逊，J.S.鲜红斑痣临床管理的最新进展，Lasers Med Sci 2000； 15,220-226。 2. Edstom, D.W.、Hedblad, M-A.、Ros, A-M. 闪光灯脉冲染料激光和氩泵染料激光治疗鲜红斑痣：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。见：Arndt K.A.、Dover J.E.、Olbricht S.A.（编辑），皮肤和美容手术中的激光。宾夕法尼亚州费城：Lippincott-Raven，1997；349-382。 4.江丽，顾Y.，李X.，赵X.，李J.，王K.，梁J.，潘Y.，张Y.，鲜红斑痣光动力治疗后皮肤灌注的变化。中医药杂志1998；111：136-138。 5. 林X.X.、王W.、吴S.F.、杨C.、张T.S.用光化疗治疗毛细血管畸形（鲜红斑痣）。塑料重建外科。 1997；99：1826-1830。 6. Kimel, S.、Svaasand, L.O.、Kelly, K.M.、Nelson, J.S. 葡萄酒色斑的协同光动力和光热处理。 已提交出版《激光外科医学》。 7. Nelson J.S.、Kelly K.M.、Zhao Y.、Chen Z. 使用光学多普勒断层扫描对人体葡萄酒色斑中的血流进行原位和实时成像。 Arch Dermatol 2001；137：741-744。