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REVIEW TABLE 4. Improvement in wrinkle severity, treated vs. covered side of the face ACCESSOR GROUP 1 (830nm ALONE) GROUP 2 (633nm ALONE) GROUP 3 (830nm AND 633nm) GROUP 4 (SHAM CONTROL) TREATED COVERED TREATED COVERED TREATED COVERED TREATED COVERED Assessor 1, mean (SD) 2.38 (0.65) 0.29 (0.63) 2.06 (0.78) 0.33 (0.75) 2.41 (0.72) 0.32 (0.82) 0.33 (0.70) 0.20 (0.65) Assessor 2, mean (SD) 2.57 (0.66) 0.14 (0.64) 2.17 (0.76) 0.28 (0.65) 2.45 (0.66) 0.36 (0.71) 0.13 (0.62) 0.07 (0.57) From Lee et al 200740 which lasted approximately 10 to 14 days. After that time, all subjects showed excellent cosmetic results. The most common adverse event (100%) was stinging and burning pain during and after irradiation with a mean (SD) pain score of 6.95 (1.73). No patient discontinued treatment due to discomfort. AESTHETIC APPLICATIONS Skin rejuvenation. LEDs have also been used to improve the appearance of photoaged skin. In contrast with thermal-based skin-tightening devices, such as radiofrequency and focused ultrasound,35 LEDs do not produce thermal injury. The skin-rejuvenating effects of LED systems are produced by a mechanism known as photobiomodulation.36,37 This nonthermal process involves exciting endogenous chromophores to elicit photophysical and photochemical events. Photobiomodulation stimulates fibroblast proliferation, collagen synthesis, growth factors, and extracellular matrix production by activating cellular mitochondrial respiratory pathways. The result is lifting and tightening lax skin and the reduction of rhytids. One small, controlled study (N=23) demonstrated the effectiveness of a 633nm (96 J/ cm2) LED light when administered as 20-minute treatments three times weekly for three weeks.38 Subjects had not received any aesthetic treatments within the previous six months before initiation of the study treatment. Improvements included reduction in fine lines and wrinkles and softer, smoother skin. No adverse events were reported. Another small controlled study (N=31) demonstrated the effectiveness of combining a 633nm (126J/cm2) LED and a 830nm (66J/cm2) for treating periorbital wrinkles.39 Exclusion criteria included laser treatment or other ablative or nonablative cosmetic intervention within the previous six months, including injectables or fillers, a history of laser treatment or trauma to the test site, and Fitzpatrick Skin Type VI. Subjects were irradiated with the 830nm LED for 20 minutes on Days 1, 3, 5, 15, 22, and 29 and with the 633nm LED for 20 minutes on Days 8, 10, and 12. Most subjects achieved softening of periorbital wrinkles, improvement in photoaging scores, and improvements in softness, smoothness, and firmness of their skin. Mild erythema was reported by eight subjects. Based on these promising results, the following randomized, double-blind, controlled study was designed to assess the efficacy of 830nm and 633nm LEDs, alone or together, for facial rejuvenation.40 Exclusion criteria included a history of photosensitivity or recent use of photosensitizing drugs including systemic retinoids or recent use of topical retinoic acid; recent skin disease, operation, trauma, or systemic disease that could affect the skin status; or aesthetic procedures, such as botulinum toxin, dermal filler, laser resurfacing, chemical peels, dermabrasion, or nonablative rejuvenation treatments within the three years on enrollment previous to the trial. Subjects with facial wrinkles (N=76) were randomized to receive treatment with a quasi-monochromatic 830nm (126J/cm2) LED alone (Group 1, n=28), 633nm (66J/cm2) LED alone (Group 2, n=28), 830nm, 633nm LEDs sequentially (Group 3, n=28) on one side of the face, or sham treatment (Group 4, n=28) on the other side of the face. Treatments were performed twice weekly for four weeks with a 3- to 4-day interval between sessions. Digital images of both periorbital areas of each subject were obtained at baseline, Week 3 during treatment, and two, four, and eight, and 12 weeks post-treatment. Profilometric evaluation using silicon imprints was performed on the outer canthus of both periorbital areas at baseline and at two, four, eight, and 12 weeks post-treatment. Objective measurements of the melanin level were performed before and after each treatment session, and measurements of the skin elasticity were performed at baseline, Weeks 2, 3, and 4 during treatment, and at Weeks 2, 4, 8, and 12 post-treatment. There were 4 to 6 subjects in each group who volunteered for punch biopsies for tissue assays. Assessment scales were used to assess clinical improvement and subject satisfaction. There was a significant decrease in mean wrinkle severity among subjects in Groups 1, 2, and 3 and a significant decrease in melanin in Group 2. At the final assessment, the proportion of improved subjects in Group 1 (95.2%), Group 2 (72.3%), and Group 3 (95.5%) were much greater than sham-treated subjects (13.3%). Investigator assessments in overall wrinkle severity are summarized in Table 4. The highest mean scores were in Groups 1 and 3. Group 4 results demonstrate sham treatment produced no effect. Tissue assay results showed increased collagen throughout the entire dermis in Groups 1, 2, and 3 and particularly in the perifollicular areas and the papillary and upper reticular dermis. Collagen bundles were more packed and well-organized and the thickness of each bundle appeared greater than before treatment. Microscopic examination revealed the presence of highly activated fibroblasts in the active treatment groups and an increase in the size and number of collagen and elastic fibers. Fibroblasts appeared enlarged with numerous dilated endoplasmic reticula, surrounded by abundant thick collagen bundles and normal-structured elastic fibers. Photodynamic rejuvenation with 5-aminolevulinic acid (5-ALA). The objective of this two-part pilot study was to 1) evaluate the optimum dose and tolerance of 5-ALA when used with a 633nm LED light in healthy volunteers compared to a placebo cream and 2) determine whether ALA-PDT treatments improve the signs of aging skin.41 Subjects with normal forearm skin and Glogau Scale II photodamage were enrolled (N=6). Subjects had no inflammatory skin conditions in the areas to be treated, JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY February 2018 • Volume 11 • Number 2 25PDF Image | Phototherapy with Light Emitting Diodes treating for dermatology
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