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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
1R03AR051443-01
Application #
6816006
Study Section
Special Emphasis Panel (ZAR1-YZW-A (M1))
Program Officer
Moshell, Alan N
Project Start
2004-07-01
Project End
2007-03-31
Budget Start
2004-07-01
Budget End
2005-03-31
Support Year
1
Fiscal Year
2004
Total Cost
$75,750
Indirect Cost
Name
University of California Irvine
Department
Dermatology
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
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Chen, Jennifer K; Ghasri, Pedram; Aguilar, Guillermo et al. (2012) An overview of clinical and experimental treatment modalities for port wine stains. J Am Acad Dermatol 67:289-304
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Huang, Yu-Chih; Tran, Nadia; Shumaker, Peter R et al. (2009) Blood flow dynamics after laser therapy of port wine stain birthmarks. Lasers Surg Med 41:563-71
Tournas, Joshua A; Lai, Jennifer; Truitt, Anne et al. (2009) Combined benzoporphyrin derivative monoacid ring photodynamic therapy and pulsed dye laser for port wine stain birthmarks. Photodiagnosis Photodyn Ther 6:195-9
Channual, Jennifer; Choi, Bernard; Osann, Kathryn et al. (2008) Vascular effects of photodynamic and pulsed dye laser therapy protocols. Lasers Surg Med 40:644-50
Choi, Bernard; Jia, Wangcun; Channual, Jennifer et al. (2008) The importance of long-term monitoring to evaluate the microvascular response to light-based therapies. J Invest Dermatol 128:485-8
Kelly, Kristen (2007) Current Treatment Options for Port Wine Stain Birthmarks. Photodiagn Photodyn Ther 4:147-148
Smith, Tia K; Choi, Bernard; Ramirez-San-Juan, Julio C et al. (2006) Microvascular blood flow dynamics associated with photodynamic therapy, pulsed dye laser irradiation and combined regimens. Lasers Surg Med 38:532-9

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