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Lasers Med Sci (2018) 33:1431–1439 1435 LED (590 nm) on 900 patients [98]. Red light (660 nm) effects were also assessed in aged/photoaged individuals in a split- face single-blinded study by Barolet and collaborators [99]. This study showed that LED therapy is able to reverse colla- gen downregulation and MMP-1 upregulation, suggesting that the use of LED at 660 nm could represent a safe and effective collagen enhancement strategy. Evidence has been also reported indicating the higher efficacy of the combination of different wavelengths in LED therapy than monotherapy [40, 100]. Therefore, the use of blue light coupled with ALA- PDT showed improved elasticity, texture, pigmentation, and complexion of the skin [101–103]. In an in vivo study of 20 subjects [104], Zane and collaborators showed also a statisti- cally significant improvement of skin rejuvenation following treatment with MAL-PDT and red light. The efficacy of this treatment has been also demonstrated in a larger study, involv- ing 94 subjects [105]. LED therapy has also been successfully coupled with LLLT as adjuvant therapy for enhancing existing result from photo rejuvenation treatments [106]. LED therapy in pre-cancerous and cancerous skin lesions Pre-cancerous skin lesions refer to skin lesions with a certain degree of risk of progression to squamous cell carcinoma of the skin [107]. Actinic keratosis (AK) represents the most common pre-cancerous lesion encountered in clinical practice, developing after long-term exposure to the sun. Among dif- ferently available therapies for AK [108], photodynamic ther- apy is going to be an additional option. Therapy PDT has been recognized as effective in the treatment of AK at sites of poor healing or in case of poor response to other topical therapies by therapy guidelines [109, 110]. A randomized intra- individual study of face/scalp AK in 119 patients published by Morton and collaborators [111] compared LED therapy using MAL as photosensitizer to conventional cryotherapy. This study highlights a significantly higher rate of healing after PDT treatment and an equivalent response in non- responder-retreated subjects. Another study reported by Piacquadio and collaborators [112] reported 75% clearance of lesions in 77% of studied patients after treatment with a formulation containing 20% of ALA and blue light. Another randomized study showed the efficacy of narrowband red LED source coupled to BF-200 nano-emulsion [113]. Recent studies compared red light LED-PDT to daylight- PDT [114, 115]. Both studies demonstrated slightly higher clearance and recurrence rates with LED therapy. PDT therapy is also considered a reasonable option for treatment, even though not as first-line, for small and superfi- cial basal cell carcinoma (BCC). Use of red narrowband LED light has also been reported in the treatment of squamous cell carcinoma (SCC) in situ [116]. LED therapy for hair loss disorders The efficacy of PDT for the treatment of hair loss is reported in several published studies [117]. Main reported evidence refers to LLLT as the most used light source [118–120]. In the 2007, FDA approved the first LLLT device (laser, 635 nm) for the treatment of hair loss, in particular for androgenetic alopecia. Following, in 2009, FDA approved similar device (laser, 655 nm) for alopecia, both in men and female. More recently also, LED therapy showed a real efficacy in the field of hair loss, especially thera- pies involving the use of red and infrared wavelengths [121, 122]. Today, both laser and LED devices have FDA approval for hair loss. In two studies reported from Lanzafame and col- laborator [121, 122], 655 nm red light significantly improved hair counts both in men and women with androgenetic alopecia (Fig. 3). A more recent study [40] reported the effect of yellow LED device both on patients with androgenetic alopecia and alopecia areata. The efficacy of LED therapy by visible light has also been recognized as a valid adjuvant therapy in the recal- citrant form of alopecia areata [123]. Nowadays, no PDT studies are available for telogen efflu- vium, although the use of LLLT and especially LED has now entered common practice among dermatologists both in pre- and post-surgical periods. Also, the role of PDT and LED therapy in scarring alopecia should be further studied as a potential adjuvant treatment in the clinical management of cicatricial alopecia. ALA-PDT has been successfully used in the treatment of cutaneous Lichen Planus, as reported by many case reports [124]. PDT may act both on hyperproliferation of cells [125] and also by an immunomod- ulatory effect with increasing CD8+ reaction [126]. This evi- dence coupled with the first data on LP treatment encourages the use of LED therapy also in subjects with cicatricial alope- cia such as Lichen Planopilaris. Limitations section Despite its increasing efficacy and use in medical practice, knowledge on LED therapy remains still limited. Published studies often addressed a small number of patients (n < 20) and are difficult to compare each other since diversity in pa- rameters used. Therefore, as explained above, wavelength, irradiation, power density, and treatment time period can influence clinical outcomes at several degrees. Different devices, from different manufacturers, may present differences in light output and power densities. These limitations pose the need of future larger (patient sample n > 20) and more controlled studies in order to define LED therapy efficacy in different skin conditions, each of one presents specific parameters to be set up.PDF Image | Photodynamic and photobiological effects of (LED) therapy
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