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S.Y. Lee et al. / Journal of Photochemistry and Photobiology B: Biology 88 (2007) 51–67 61 Fig. 7. Transmission electromicroscopic findings showed activated fibro- blasts with numerous dilated endoplasmic reticula surrounded by abun- dant collagen fibers in the treatment groups (x 8,000). [10–24,38]. A proper amount and penetration depth of the controlled photothermal damage is considered to be vital for effective induction of collagen synthesis [23, 24,39]. The use of LEDs for skin rejuvenation is unique in that it does not produce any thermal damage. Instead of photothermal damaging, it induces a photobiomodulative reaction [25–29]. Photobiomodulation is considered to stimulate fibroblast proliferation, collagen synthesis, growth factors and extracellular matrix production and enhances cutaneous microcirculation through activating the mitochondrial respiratory system of the cells [25–36]. The beneficial effects of a new generation of powerful and quasimonochromatic LEDs were first reported by Whelan et al. [30–32], who have demonstrated that 670 nm LED treatment up-regulated tissue regeneration genes and accel- erated wound closure by stimulating cell activities. Rapid development of both LED-based devices and their applica- tion has now enabled LED therapy to be used for skin rejuvenation by utilizing its effectiveness in inducing photo- biomodulation. Some clinical studies have shown the effi- cacy of 590nm pulsed LEDs in improving photoaged skin through increasing collagen precursors [27]. The clini- cal efficacy of 633 nm and 830 nm LEDs for skin rejuvena- tion has also been reported in some articles [28,29]. However, well-designed clinical studies have been very sparse, which have used split-face exposures performed in a randomized, double-blinded, placebo-controlled trial with repeated and quantitative measures of response [12]. The mechanism of action of LED phototherapy in skin rejuvenation has also not yet been investigated vigorously. In the present study, we tried to determine the clinical effi- cacy of LED phototherapy for skin rejuvenation through an objective methodology utilizing a controlled, double- blinded and hemi-face model. We also investigated the his- tological and ultrastructural changes and alterations in the primary cytokines and enzymes that are known to be affected by other nonablative rejuvenation procedures. The use of profilometry and other instrumental measure- ments enabled us to obtain objective data of the clinical efficacy, which were not observer-dependent and made it possible to compare the therapeutic effects between differ- ent treatment parameters. The results revealed a statistically significant improve- ment in the representative values of wrinkle severity and skin elasticity between baseline and 3 months after treatment completion in the treatment groups, with skin elasticity first tending to show an apparent improvement in treatment week 3. Both sets of values exhibited continued improvement, even during progressive treatment-free follow up assess- ments. This improvement was not observed in the control group, with a statistically significant difference in the per- centage improvements between the control group and the treatment groups. In addition, the within-patient compari- son between the treated and the covered sides in the same individual revealed a statistically significant improvement in wrinkles and skin elasticity only in the treated side, whereas no such changes were noted in the covered side. This ‘double comparison’ methodology allowed us to confirm the improvements in severity of wrinkles and skin elasticity after LED phototherapy in a more objective fashion. Another important reason we set an additional control group in a split-face study was to avoid the bias which might be caused by the possible influence of a paracrine, or a bystander effect. It has been suggested that, in light therapy, photons may stimulate cells to release cytokines [17,30–36,40]. We took the possibility into account that paracrine or bystander signaling agents, such as cytokines or growth factors, might diffuse into the dermis or circulate through the dermal vasculature from the treated side to the non-treated side. In such case of negation of the hemiface model, where any existing difference between the treated and covered sides would become indistinguishable, com- parison between the treatment groups and the sham irradi- ated control group would give another tool for assessment of the therapeutic efficacy. The subjects in the three treatment groups expressed sat- isfaction with LED phototherapy as the follow-up period progressed. They reported overall improvements in the skin tone, texture, firmness and tightness as well as the severity of wrinkles. On the contrary, most of the patients in the control group could not find any perceptible advantages, even by the final assessment session. The dissatisfaction of patients in the control group resulted in the highest drop-out rate among all of the study groups. The investiga- tors’ assessments showed a good correlation with the sub- jects’ assessments (Table 4). The specimens for histological and ultrastructural evaluations were obtained two weeks post-treatment, because the changes in the dermal matrix is known to become prominent 10-20 days after a rejuvenation procedure [20,41]. On the other hand, biochemical responses such as cytokine release are known to be acutely induced by the rejuvenation therapy and last for several hours to a few days [7,20,42,43].PDF Image | LED phototherapy for skin rejuvenation
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