皮肤光动力疗法的研究进展

随着皮肤光动力治疗（PDT）技术的发展和不断成熟,光动力三要素中光敏剂、光源方面都有了新的发展,研发了透皮性更好的氨基酮戊酸（ALA）凝胶和贴片制剂;光源上除了传统的激光或二极管红光,“日光PDT”因其光谱的可行性和便捷的治疗方式在欧美国家得到普遍关注;PDT疗法的适应证也有新的拓展,如部分皮肤肿瘤及皮肤区域癌化（field cancerization）的防治等。PDT与其他物理方法的联合也取得了较为满意的疗效……     

光动力治疗中疼痛管理研究进展

局部光动力疗法是一种高效、安全、无创的治疗方法,对于皮肤科领域的多种疾病具有良好的疗效,如,光线性角化病、尖锐湿疣、痤疮等。制约光动力疗法普及的主要原因是在治疗过程中产生的疼痛,有些患者因无法耐受需要暂停甚至终止治疗。目前,对于PDT疼痛的控制研究已经取得了一些进展。影响PDT疼痛的因素有个体特征、皮损特征和治疗参数如光源、光敏剂等。用于控制PDT疼痛的方法有局部降温、口服镇痛药、二步照射法、表面麻醉、注射麻醉、吸入性麻醉、经皮神经电刺激、催眠等。     

皮肤病的光动力诊断与治疗

随着光动力治疗(photodynamic therapy,PDT)技术的发展和成熟,光敏剂、光源方面都相继有新产品或新方案推出,其在皮肤病诊断中的应用和适应症的拓展已有很大进展。PDT不但用于皮肤肿瘤和增生性皮肤病的治疗,而且对荧光诊断、预防皮肤肿瘤、皮肤光老化、痤疮、以及局部微生物感染等炎症性皮肤病治疗方面均有研究报告,本文对近年来皮肤局部光动力诊断与治疗的研究进展作简要概述。     

光动力治疗宫颈湿疣合并宫颈上皮内瘤变一例

光动力疗法（photodynamic therapy,PDT）是一种通过光敏剂和激光结合的治疗方法,主要用于肿瘤、癌前病变和尖锐湿疣等,损伤小,属于非侵入性治疗手段。我们采用以635 nm半导体激光治疗光源的PDT治疗宫颈上皮内瘤变1例,疗效满意,报道如下……     

光动力疗法在皮肤科的应用

光动力疗法（photodynamic therapy,PDT）是应用光动力效应的原理、联合使用光敏剂及相应光源选择性破坏靶组织的一种非侵袭性的全新治疗技术,它能特效针对靶组织,并且同一时期可以多次重复治疗而不累积毒性,其独特的优势以及良好的耐受性使它在皮肤科中的应用日益受到关注。     

光动力学疗法对豚鼠光老化治疗作用的研究

目的探讨5-氨基酮戊酸(ALA)联合强脉冲光(IPL)的光动力学疗法(PDT)对豚鼠光老化模型的影响,并摸索合适的5-ALA治疗浓度。方法以模拟日光光源(SSR)建立豚鼠光老化模型,10%、20%5-ALA联合IPL治疗,每3周一次,共3次。观察真皮细胞外基质(胶原纤维、弹力纤维)的改变。结果豚鼠以亚红斑量SSR照射13周,光照部位真皮浅层出现了典型的光化性弹力纤维变性损害。经10%5-ALA联合IPL治疗后,上述改变明显改善,而20%5-ALA联合IPL可进一步加重损伤。结论光动力疗法对光老化有一定改善作用,选择合适的5-ALA治疗浓度很重要。     

增强光动力治疗肿瘤的应用研究进展

 光动力疗法（PDT）是一种相对较新且有前景的肿瘤治疗方法，主要是通过光敏剂、氧及光源之间的相互作用而产生单线态氧及活性氧簇，从而选择性地杀伤肿瘤细胞。PDT治疗肿瘤适应症较为广泛，有较高的肿瘤选择性和极低的耐药性，且毒副作用较低，在临床上得到广泛的应用，但存在如光源及光敏剂的穿透深度较弱，光敏剂局部生物利用度不高等缺点。本文对近年来针对光敏剂、光源的改良以及PDT联合药物治疗、PDT介导的肿瘤疫苗几个方面进行文献综述，探讨未来PDT治疗肿瘤的新方向。     

光动力疗法治疗皮肤癌及癌前病变

光动力疗法(photodynamic therapy,PDT)是近年来用于皮肤癌治疗的一项新兴技术,可有效用于光线性角化病、原位鳞癌、基底细胞癌等皮肤肿瘤的治疗,尤其适用于那些不能耐受手术、面积广泛或多发性皮损。在恢复时间、耐受性和美容效果上具有优势,可作为上述情况的一线治疗手段。PDT对乳房外Paget's病、侵袭性鳞癌、皮肤T细胞淋巴瘤和黑素瘤的治疗以及皮肤癌的预防有一定应用价值,其疗效尚待探索。照光过程中的疼痛是亟待解决的主要不良反应。文中对光动力疗法在皮肤癌及癌前病变中的临床应用进展进行了综述。     

光动力学疗法在病毒感染性皮肤病治疗中的应用

光动力学疗法（photodynamictherapy,PDT）是一种新型的治疗方法,随着光动力学技术及光敏剂的发展,光动力学疗法作为新型抗病毒的治疗方法受到关注,并取得一定进展。该文就PDT治疗某些病毒感染性皮肤痫的机制和应用进展作一综述。     

光动力疗法的应用研究现状

光动力疗法治疗恶性肿瘤是近二十年兴起的并不断发展的新技术，PDT是一种很有发展前途的局部疗法，研究重点主要是阐明PDT杀伤肿瘤细胞的作用机制和开发更新型的光敏剂，近年来PDT对正常组织器官的效应更是引起部分学者的重视，本文将分别从PDT作用机制，光敏剂的作用及其在临床皮肤治疗研究等方面的广泛应用前景，进行总结。     

Photodynamic therapy in dermatology

Application of non-ionising radiation with or without photosensitizers is rather common in dermatology. Though the method itself was described in ancient times, its routine use in medicine based on scientific research started in the second half of the 20th century. Light can be used in three different patterns: phototherapy (UV-A or UV-B light), photochemotherapy (combination of psoralens with UV-A light) and photodynamic therapy (combination of photosensitizers with UV- and/or visible light). The following article deals with the photodynamic therapy or PDT. Using PDT implies the understanding of light dosimetry and calculation of light dose using different light sources and photosensitizers. The number of PDT sensitisers under investigation is rapidly increasing. The PDT itself, being a relatively new modality, quickly spreads its list of applications covering new indications in different areas of medicine. Though the main part of this list is made up of dermatological conditions, the use of PDT in other disciplines is also discussed to make dermatologists familiar with different aspects of the issue. PDT, like any treatment modality, has its benefits and adverse effects. The future of PDT is closely related to teamwork in physical, biochemical and clinical research which could provide better understanding of underlying mechanisms and help to create protocols for higher therapeutic efficacy.     

Guidelines for topical photodynamic therapy: report of a workshop of the British Photodermatology Group

Topical photodynamic therapy (PDT) is effective in the treatment of certain non-melanoma skin cancers and is under evaluation in other dermatoses. Its development has been enhanced by a low rate of adverse events and good cosmesis. 5-Aminolaevulinic acid (ALA) is the main agent used, converted within cells into the photosensitizer protoporphyrin IX, with surface illumination then triggering the photodynamic reaction. Despite the relative simplicity of the technique, accurate dosimetry in PDT is complicated by multiple variables in drug formulation, delivery and duration of application, in addition to light-specific parameters. Several non-coherent and coherent light sources are effective in PDT. Optimal disease-specific irradiance, wavelength and total dose characteristics have yet to be established, and are compounded by difficulties comparing light sources. The carcinogenic risk of ALA-PDT appears to be low. Current evidence indicates topical PDT to be effective in actinic keratoses on the face and scalp, Bowen's disease and superficial basal cell carcinomas (BCCs). PDT may prove advantageous where size, site or number of lesions limits the efficacy and/or acceptability of conventional therapies. Topical ALA-PDT alone is a relatively poor option for both nodular BCCs and squamous cell carcinomas. Experience of the modality in other skin diseases remains limited; areas where there is potential benefit include viral warts, acne, psoriasis and cutaneous T-cell lymphoma. A recent British Photodermatology Group workshop considered published evidence on topical PDT in order to establish guidelines to promote the efficacy and safety of this increasingly practised treatment modality.     

Laser-mediated photodynamic therapy

Photodynamic therapy (PDT) has evolved since its inception at the beginning of the 20th century, when it was defined as an oxygen-dependent reaction between a photosensitizing dye and light. Photosensitizers and light sources have since been continually optimized for distinct applications and tissues. Systemic porphyrins, such as hematoporphyrin, were the first photosensitizers to be used, mostly to treat tumors. The first light sources used were broad-band, noncoherent lights, such as quartz, xenon, tungsten, or halogen lamps. The wavelengths of light chosen were based upon the absorption spectrum of porphyrins: blue because the largest peak is at 400 nm (the Soret band) and red because of its greater penetration depth but lesser absorption at 650 nm (a Q band). Systemic photosensitizers caused prolonged photosensitivity, and broad-band light sources had limitations and side effects. The development of topical photosensitizers, such as 5-aminolevulinic acid, and the advent of lasers in recent years have advanced PDT for cutaneous use. In the 1990s, red lasers were applied to PDT because of their increased skin penetration despite lesser absorption by porphyrins. Broad-band blue light and red light have been studied extensively, the former achieving Food and Drug Administration approval in combination with topical aminolevulinic acid for the treatment of actinic keratosis in 1997. These lasers and light sources caused significant side effects, such as discomfort, erythema, crusting, blistering, and dyspigmentation. The recent application of the long-pulsed pulsed dye laser (595 nm) after topical aminolevulinic acid greatly minimized side effects without compromising efficacy. Long-pulsed pulsed dye laser-mediated PDT has since been shown to be effective in treatment of actinic keratosis, actinic cheilitis, sebaceous hyperplasia, lichen sclerosus, and, most recently, acne vulgaris. Finally, intense pulsed light sources have been introduced to PDT for the treatment of photodamage and acne, offering advantages of versatility in wavelengths and applications.     

Treatment of photoaging with topical aminolevulinic acid and light

Photodynamic therapy (PDT) has been used for several years for the treatment of actinic keratoses and prevention of invasive nonmelanoma cancers. More recently, increasing physician expertise with the topical sensitizers and light sources employed in PDT has led to expanded applications, including its use for improvement of the visible signs of photoaging. Aesthetic treatment of photoaged skin with brief application of topical 5-aminolevulinic acid followed by well-tolerated light sources, such as intense pulsed light or pulsed-dye laser, can enhance the effectiveness of nonablative laser treatment without increasing adverse effects or downtime.     

Photodynamic Therapy in Dermatology – an Update 2008

Photodynamic therapy (PDT) is used for the prevention and treatment of non‐melanoma skin cancer. Until recently, clinically approved indications have been restricted to actinic keratoses, nodular and superficial basal cell carcinoma, and – since 2006 – Bowen disease. However, the range of indications has been expanding continuously. PDT is also used for the treatment of non‐malignant conditions such as acne vulgaris and leishmaniasis, as well as for treating premature skin aging due to sun exposure. Here, PDT is used for the stimulation of immunomodulatory effects in contrast to the induction of necrosis and apoptosis as produced in the treatment of skin tumors. The porphyrin precursor 5‐aminolevulinic acid (ALA) or its methyl ester (MAL, so far the only approved formulation in Europe) is applied topically as photosensitizer to exclude systemic reactions. Possible light sources include lasers as well as incoherent light sources; irradiation with incoherent light sources is cheaper and more appropriate for large treatment areas. The main advantages of PDT in comparison to other treatment modalities are its excellent cosmetic results and its high remission rates despite low invasiveness.This article provides up‐to‐date information about PDT with focus on recently published studies.     

Photodynamic therapy: a review of the literature and image documentation

Photodynamic therapy (PDT) consists of a chemical reaction activated by light energy that is used to selectively destroy tissue. The reaction requires a photosensitizer in the target tissue, a light source and oxygen. The most extensively studied photosensitizing agents for PDT are 5-aminolevulinic acid for the treatment of actinic keratosis and methyl-aminolevulinate, which has been approved for the treatment of actinic keratosis, basal cell carcinoma and Bowen's disease. The light sources used in photodynamic therapy should emit light at wavelengths within the absorption spectrum of the photosensitizer used in PDT treatment. Light emitting diode (LED) lamps are indicated for the photodynamic treatment of nonmelanoma skin cancer. PDT should be considered as a therapeutic option, particularly in the case of patients with superficial, multiple or disseminated lesions and for immunosuppressed patients. More recently, PDT has been indicated for a wide range of dermatological conditions such as photo-damaged skin, acne, hidradenitis, scleroderma, psoriasis, warts and leishmaniosis, among others. This article provides an extensive review of photodynamic therapy, its mechanisms, indications and results.     

Topical aminolaevulinic acid- and aminolaevulinic acid methyl ester-based photodynamic therapy with red and violet light: influence of wavelength on pain and erythema

Background Photodynamic therapy (PDT) is based on the combination of an exogenously administered precursor of photosensitizer [protoporphyrin IX (PpIX)] synthesis and exposure to light. Choosing the optimal wavelength is important. Red light penetrates deeper into tissue, while violet light is more efficient in activating PpIX but does not penetrate so deeply. Objectives We studied PpIX formation and the PDT effect after application to human skin of creams containing aminolaevulinic acid (ALA) and aminolaevulinic acid methyl ester (MAL). The aim of the study was to investigate whether the wavelength of the light used has an influence on pain sensations during topical PDT with the different prodrugs. Methods ALA cream (10%) and MAL cream (10%) were topically applied on the skin of 10 healthy volunteers. After 24 h the application site was exposed to 8 mW cm⁻² violet laser or to 100 mW cm⁻² red laser light. The erythema index was monitored up to 24 h after light exposure. For the first time the pain during topical ALA‐ and MAL‐PDT was assessed by measuring the time taken for pain to occur. Also, for the first time, the intensities of the light sources were calibrated so as to have the same relative quantum efficiency. Results The pain sensation during ALA‐PDT with red light came 22 s sooner than during ALA‐PDT with violet light, which is statistically significant (P < 0·05). Moreover, ALA‐PDT with red light gave stronger and more persistent erythema than ALA‐PDT with violet light. ALA induced about three times more PpIX than MAL. No statistically significant differences were found for erythema, or for the time for pain to occur, in the case of MAL‐PDT with red vs. violet light. Conclusions Topical ALA‐PDT with violet light allows longer exposure times before pain is induced and gives less erythema as compared with topical ALA‐PDT with red light.     

Photodynamic therapy with BF‐200 ALA for the treatment of actinic keratosis: results of a prospective,randomized, double‐blind,placebo‐controlled phase III study

Background Photodynamic therapy (PDT) with 5‐aminolaevulinic acid (ALA) provides a therapeutic option for the treatment of actinic keratosis (AK). Different strategies are applied to overcome the chemical instability of ALA in solution and to improve skin penetration. A new stable nanoemulsion‐based ALA formulation, BF‐200 ALA, is currently in clinical development for PDT of AK. Objectives To evaluate the efficacy and safety of PDT of AK with BF‐200 ALA. Methods The study was performed as a randomized, multicentre, double‐blind, placebo‐controlled, interindividual, two‐armed trial with BF‐200 ALA and placebo. A total of 122 patients with four to eight mild to moderate AK lesions on the face and/or the bald scalp were included in eight German study centres. The efficacy of BF‐200 ALA after one and two PDT treatments was evaluated. BF‐200 ALA was used in combination with two different light sources under illumination conditions defined by European competent authorities. Results PDT with BF‐200 ALA was superior to placebo PDT with respect to patient complete clearance rate (per‐protocol group: 64% vs. 11%; P < 0·0001) and lesion complete clearance rate (per‐protocol group: 81% vs. 22%) after the last PDT treatment. Statistically significant differences in the patient and lesion complete clearance rates and adverse effect profiles were observed for the two light sources, Aktilite^® CL128 and PhotoDyn^® 750, at both time points of assessment. The patient and lesion complete clearance rates after illumination with the Aktilite^® CL128 were 96% and 99%, respectively. Conclusions BF‐200 ALA is a very effective new formulation for the treatment of AK with PDT. Marked differences between the efficacies and adverse effects were observed for the different light sources used. Thus, PDT efficacy is dependent both on the drug and on the characteristics of the light source and the illumination conditions used.     

Photodynamic therapy for skin rejuvenation: review and summary of the literature – results of a consensus conference of an expert group for aesthetic photodynamic therapy

Skin rejuvenating effects of photodynamic therapy (PDT) for photoaged skin has been well‐documented in several clinical trials. Different photosensitizers (5‐aminolevulinic acid, methyl aminolevulinate) and diverse light sources (light‐emitting diodes, lasers, intense pulsed light) have been used with promising results. An improvement of lentigines, skin roughness, fine lines and sallow complexion has been achieved with PDT. These clinically evident effects are at least in part due to histologically proven increase of collagen and decrease of elastotic material in the dermis. Effective improvement of photoaged skin, simultaneous treatment and possibly also prevention of actinic keratoses, the possibility of repeated treatments and, in contrast to other procedures, limited and calculable side effects make PDT a promising procedure for skin rejuvenation.     

Evidence-based review of photodynamic therapy in the treatment of acne

Background

Photodynamic therapy (PDT) has been used for acne, however, the efficacy and safety need to be determined.

Objective

To assess the effects and safety of PDT for acne using an evidence-based approach.

Methods

Randomized controlled trials (RCTs) on the treatment of acne with PDT were identified by searching PubMed, CNKI and the Cochrane Library.

Results

A total of 14 RCTs involving 492 patients were included. Photosensitizers included aminolevulinic acid (ALA), methylaminolevulinate (MAL), and indole-3-acetic acid (IAA). Light sources included red light, pulsed dye laser (PDL), intense pulsed light (IPL), long-pulsed dye laser (LPDL) and green light. The PDT protocols, including ALA + red light, ALA + PDL, ALA + IPL, MAL + red light, and MAL + LPDL, all showed great efficacy on inflammatory lesions. ALA + red light also had effects on non-inflammatory lesions and sebum secretion. ALA + IPL and IAA + green light significantly decreased sebum secretion. Triple treatment protocols showed great improvement on inflammatory and non-inflammatory lesions. Increasing ALA concentration, ALA incubation time, PDT sessions, dose of light source or using occlusion for photosensitizers, or a combination of other treatments with PDT may achieve greater efficacy. The common side effects of PDT were tolerable and transient.

Conclusion

Limited evidence indicates that PDT shows good efficacy in the treatment of acne with acceptable side effects. ALA + red light was shown to be the optimal choice. However, more RCTs are needed to determine the types and concentrations of photosensitizers and light sources, and the duration of light activation and incubation.