Treatment Of Photodamaged Skin Research Articles

665 Matrix metalloproteinase 2 is a potential mediator of retinoid efficacy in photoaging

Considered the gold standard in the treatment of photodamaged skin, tretinoin (retinoic acid) is thought to restore collagen in sun-damaged skin through the induction of pro-collagen I and suppression of matrix metalloproteinases (MMPs) which degrade collagen, particularly MMP1, MMP3, and MMP9. The clinical efficacy of tretinoin therapy, however, is often limited by local adverse effects, such as burning, itching, or peeling. Cosmeceutical formulations containing precursors of tretinoin have been marketed to provide similar efficacy as tretinoin while minimizing toxicity.

Photodynamic therapy for correction of involutive facial skin changes

Background.The appearance of the skin is of high social importance, largely determining the behavior and self-confidence of a person. The relevance of methods for the correction of involutive skin changes is growing every year. One modern treatment for photodamaged skin is photodynamic therapy.
 Objective:the study evaluated the effectiveness of photodynamic therapy using chlorin E6 as a photosensitizer for the correction of involutive changes in the skin of the face compared to using only light exposure.
 Methods.The study involved patients aged 4060 years with signs of involutive changes in the skin of the face. In group 1 (n=36), patients underwent therapy using only light coherent radiation. In group 2 (n=35), patients underwent PDT using light coherent radiation.
 Results.According to the results of elastometry, corneometry, assessment of transepidermal water loss, ultrasound examination of the skin in group2, more positive indicators were obtained than in group1. When assessing safety, the results in groups 1 and2 are comparable.
 Conclusions.The method of photodynamic therapy using chlorin E6 can be recommended for course use in wide clinical practice.

Abstract B20: Fractional laser exposure can stimulate systemic anti-tumor immune response

Abstract Background: Ablative fractional photothermolysis (aFP) using a CO2 laser generates multiple small diameter tissue lesions within the irradiation field. AFP is commonly used for a wide variety of dermatological indications, including treatment of photodamaged skin and dyschromia, drug delivery and modification of scars due to acne, surgical procedure and burns. In this study we explore the utility of aFP for treating oncological indications, including induction of local tumor regression or inducing anti-tumor immunity which is in marked contrast to current indications of aFP. Methodology/Principal Findings: Six-week-old female BALB/c mice were inoculated intradermally on the left leg with murine colon carcinoma cell line (CT26.CL25) which expressed a tumor antigen, beta-galactosidase (beta-gal). At day eight, when tumors reached a diameter of approximately 5–7 mm, the tumor site was irradiated with a fractional CO2 laser (100 mJ pulse energy, 5% laser density (surface coverage), 300 Hz pulse frequency). Tumor-free mice after FP treatment for 90 days were rechallenged with CT26.CL25 tumor cells on the opposite leg. To determine the mechanism of this tumor protection BALB/c Nu/Nu mice lacking lymphocytes mediated immunity were subjected to the same protocol. FP treated tumors grew significantly slower as compared to untreated controls (p<0.005). Complete remission after a single FP treatment was observed in 6 of 13 CT26.CL25 tumor-bearing mice (47%) in treated group, but one of 13 mice in the control group (p<0.05). All 6 mice survived for an additional 60 days with no detectable tumors after rechallenge test. The FP-treated group using BALB/c Nu/Nu nude mice showed a delay in tumor growth. But tumors then grew progressively, as in the control group, suggesting a requirement for lymphocyte-mediated adaptive immunity for long term tumor eradication. Flow cytometric analysis of the FP-treated tumors showed less infiltrating regulatory T lymphocytes in the tumor at 7 day after FP treatment in CT26.CL25 tumor-bearing mice. CD8 T lymphocytes from drainage lymph node of survival mice in treated group showed more cytotoxicity than control group. Adoptive transfer experiment using CD8 T lymphocytes from drainage lymph node of survival mice in treated group to BALB/c Nu/Nu nude mice showed a delay in tumor growth comparing with control group. Conclusion: We have demonstrated that ablative fractional photothermolysis is able to induce systemic anti-tumor adaptive immunity preventing tumor recurrence in a murine colon carcinoma in a mouse model. This study has demonstrated a potential role of FP treatments in oncology and further studies should be performed. Although FP treatments of oncological applications hold promise and should further be investigated, at present time FP is not be performed as clinical care for tumors. Citation Format: Masayoshi Kawakubo, Dieter Manstein. Fractional laser exposure can stimulate systemic anti-tumor immune response. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B20.

Transepidermal drug delivery in daylight photodynamic therapy in the treatment of photodamaged skin: a pilot study

Transepidermal drug delivery in daylight photodynamic therapy in the treatment of photodamaged skin: a pilot study

All-trans retinoic acid is an effective inhibitor of hyaluronate synthesis in a human dermal equivalent

All-trans retinoic acid (ATRA) is known to have beneficial effects on skin. It has been used extensively for the treatment of photodamaged skin. To assess the effects of all-trans retinoic acid on the dermis, specifically its effect on hyaluronate (hyaluronic acid, HA) synthesis and inhibition, tissue-engineered human dermal equivalents were prepared in the presence of varying concentrations of ATRA using the method of "self-assembly". A substantial extracellular matrix was formed at the end of the culture period. The extracellular matrices of these dermal constructs were characterized and compared to the construct prepared in the absence of ATRA (Normal). Inhibition of hyaluronate was observed in constructs prepared in the presence of varying concentrations of all-trans retinoic acid. Chondroitin sulfate synthesis was unaffected up to 1μM ATRA. Collagen synthesis was enhanced at lower concentrations of ATRA (250 and 500nM) and inhibited at higher concentrations of ATRA. Differential gene array experiments were performed comparing the construct grown in the presence of 500nM ATRA to one grown in the absence of ATRA, to obtain preliminary information regarding the gene(s) involved in HA inhibition using a GLYCOv4 gene chip. These preliminary experiments demonstrated the differential expression of 127 genes and suggest that down-regulation of five key enzymes in the HA biosynthetic pathway may be involved in this inhibitory process.

Fractional ablative LASER versus fractional ablative and coagulative LASER for treatment of photodamaged skin in arms and forearms

Fractional ablative LASER versus fractional ablative and coagulative LASER for treatment of photodamaged skin in arms and forearms

The clinical efficacy of cosmeceutical application of liquid crystalline nanostructured dispersions of alpha lipoic acid as anti-wrinkle

Topical 5% alpha lipoic acid (ALA) has shown efficacy in treatment of photo-damaged skin. The aim of this work was to evaluate the potential of poloxamer (P407) gel as a vehicle for the novel lipid base particulate system (cubosome dispersions) of ALA. Cubosome dispersions were formulated by two different approaches, emulsification of glyceryl monoolein (GMO) and poloxamer (P407) in water followed by ultrasonication, and the dilution method using a hydrotrope. Three different concentrations of GMO were used to formulate the cubosome dispersions using the first method, 5% (D1), 10% (D2) and 15% w/w (D3). In the second technique an isotropic liquid was produced by combining GMO with ethanol, and this isotropic liquid was then diluted with a P407 solution (D4). The dispersions were characterized by zeta potential, light scattering techniques, optical and transmission electron microscopy, encapsulation efficiency and in vitro drug release. Results showed that D4 was not a uniform dispersion and that D1, D2 and D3 were uniform dispersions, in which by increasing the GMO content in the dispersion, the size of the cubosomes decreased, zeta potential became more negative, encapsulation efficiency increased up to 86.48% and the drug release rate was slower. P407 gels were prepared using the cold method. Two concentrations of P407 gel were fabricated, 20 and 30% w/w. P407 gels were loaded with either ALA or dispersions containing ALA cubosomes. P407 gels were characterized by critical gelation temperature, rheological measurements and in vitro drug release studies. Results suggested that by increasing P407 concentration, the gelation temperature decreases and viscosity increases. Drug release in both cases was found to follow the Higuchi square root model. Gel loaded with ALA cubosomes provided a significantly lower release rate than the gel loaded with the un-encapsulated ALA. A double blinded placebo controlled clinical study was conducted, aiming to evaluate the efficacy as an anti-wrinkle agent and volunteer’s satisfaction upon application of topical 30% P407 gel loaded with ALA cubosomes. Results indicated reduction in facial lines, almost complete resolution of fine lines in the periorbital region and upper lip area and overall improvement in skin color and texture in most volunteers. There were no instances of irritation, peeling or other apparent adverse side effects.

Complications of Carbon Dioxide Laser Resurfacing

The carbon dioxide laser has been shown to be an effective tool in the treatment of photodamaged skin since its introduction over 20 years ago. Scars, premalignant, and malignant skin lesions of the face have all been treated successfully with the carbon dioxide laser. While improvements in laser technology have facilitated the use of the carbon dioxide laser in the oral and maxillofacial surgery office, there is a paucity of literature describing the incidence of postoperative complications following laser resurfacing in the OMS literature. Previous studies have reported a relatively common occurrence of bacterial infections, viral infections, and inflammatory reactions in the early postoperative period, and scarring and facial pigment changes in the long term, as well as—rarely—iatrogenic damage during treatment. A retrospective study of 110 patients, who underwent laser resurfacing with a carbon dioxide laser between 1999 and 2013, examined the rates of complications after treatment. Complications were separated into early (within one week) and late (one to three weeks post-procedure), and categorized by complication subtype (eg infectious, inflammatory, etc). Additionally, laser settings, Fitzpatrick skin type, immunocompromising conditions (diabetes, AIDS, etc), postoperative pain, and smoking history were all assessed. The results of this study indicate a 3% early complication rate consisting of herpes zoster and bacterial dermatologic infections. There was an 8% late complication rate, including mostly minor dermatologic sequelae such as milia/acneiform lesions and contact dermatitis and one late HSV outbreak. All complications quickly and fully resolved with proper intervention. Despite the high rates of postoperative hypoand hyperpigmentation found in many studies, we found a much lower incidence in ours. This is most likely due to our selection criteria for laser treatment, which includes patients only with Fitzpatrick skin types I, II and III, who are less likely to suffer these complications than patients with darker skin. This study will help clinicians understand and anticipate complications that are most likely to follow carbon dioxide laser resurfacing, and plan to treat these adverse outcomes appropriately. Furthermore, our confirmation of low rates of serious complications should encourage

Is the Magnitude of Maxillomandibular Advancement Correlated With Long-Term Changes in the Apnea-Hypopnea Index in Patients With Obstructive Sleep Apnea?

The carbon dioxide laser has been shown to be an effective tool in the treatment of photodamaged skin since its introduction over 20 years ago. Scars, premalignant, and malignant skin lesions of the face have all been treatedsuccessfullywith thecarbondioxidelaser. While improvements in laser technology have facilitated the use of the carbon dioxide laser in the oral and maxillofacialsurgeryoffice,thereisapaucityof literaturedescribing the incidence of postoperative complications following laser resurfacing in the OMS literature. Previous studies have reported a relatively common occurrence of bacterial infections, viral infections, and inflammatory reactions in the early postoperative period, and scarring and facial pigment changes in the long term, as well as—rarely—iatrogenic damage during treatment. A retrospective study of 110 patients, who underwent laser resurfacing with a carbon dioxide laser between 1999 and 2013, examined the rates of complications after treatment. Complications were separated into early (within one week) and late (one to three weeks post-procedure), and categorized by complication subtype (eg infectious, inflammatory, etc). Additionally, laser settings, Fitzpatrick skin type, immunocompromising conditions (diabetes, AIDS, etc), postoperative pain, and smoking history were all assessed. The results of this study indicate a 3% early complication rate consisting of herpes zoster and bacterial dermatologic infections. There was an 8% late complication rate, including mostly minor dermatologic sequelae such as milia/acneiform lesions and contact dermatitis and one late HSV outbreak. All complications quickly and fully resolved with proper intervention. Despite the high rates of postoperative hypo- and hyperpigmentation found in many studies, we found a much lower incidence in ours. This is most likely due to our selection criteria for laser treatment, which includes patients only with Fitzpatrick skin types I, II and III, who are less likely to suffer these complications than patients with darker skin. This study will help clinicians understand and anticipate complications that are most likely to follow carbon dioxide laser resurfacing, and plan to treat these adverse outcomes appropriately. Furthermore, our confirmation of low rates of serious complications should encourage

Adverse events of non-ablative fractional laser photothermolysis: a retrospective study of 856 treatments in 362 patients

Background: Non-ablative fractional laser photothermolysis (NAFP) has been used effectively in the treatment of photodamaged skin and scars, with short post-operative recovery times; but, studies evaluating its adverse events and complication rates in Asian population have been limited. Objective: To determine the frequency and range of adverse events associated with NAFP treatment in Korean patients. Materials and methods: We retrospectively evaluated the outcomes of 754 1550-nm erbium-doped and 102 1927-nm thulium fiber fractional laser treatments in patients with skin phototypes III–IV treated at a single center. Adverse events were identified and tabulated, as were patient demographics and laser parameters. Results: From 856 treatments, there were 43 adverse events (5.0%), the most frequent being prolonged erythema (1.8%), post-inflammatory hyperpigmentation (1.1%) and aggravation of melasma (0.9%). Less frequently observed adverse events included herpes simplex outbreak (0.6%) and acneiform eruption (0.2%). There were no reports of long-term adverse events. Conclusion: Non-ablative fractional laser skin treatment has a relatively low complication rate. The adverse events found were temporary and did not result in long-term or severe sequelae such as hypertrophic scarring, atrophic scarring or permanent pigmentary alteration.

Squamous Cell Carcinoma Developing after CO2 Laser Resurfacing

Skin resurfacing with the carbon dioxide (CO(2)) laser is currently a popular means of improving rhytides and scars and has been reported useful in the treatment for photodamaged skin, including precancerous and benign skin lesions, as well as superficial benign pigmented lesions. We describe a 68-year-old man who developed rapid squamous cell carcinoma (SCC) on the resurfaced areas 3 weeks following CO(2) laser resurfacing. Rapid occurrence of SCC should be considered a rare complication, and we recommend carefully considering CO(2) laser resurfacing after excision of an SCC and surveying any cancer recurrences. We report a rare complication of CO(2) laser resurfacing. This report suggests that additional work in this area is warranted.

Assessment of safety and efficacy of a bipolar fractionated radiofrequency device in the treatment of photodamaged skin

Background: A number of devices are available for skin rejuvenation and conventional devices include both ablative and non-ablative lasers. More recently, bipolar fractionated radiofrequency (RF) devices have been introduced. Objective: To evaluate the safety and efficacy of a novel 144 pin high density tip bipolar fractionated radiofrequency (RF) device for skin rejuvenation in Fitzpatrick skin types I-IV. Methods and materials: This single-center, prospective, study enrolled 25 female between the ages of 35–60 years, with mild to moderate wrinkling based on the Fitzpatrick Wrinkle Scale. The subjects were of Fitzpatrick skin types I-IV. Each subject underwent 3 full-face treatments with a 144 pin fractional bipolar RF device at 30-day intervals. All subjects underwent clinical evaluations during the study period to evaluate for any adverse events. Subsequently, all subjects were evaluated for improvement in rhytides, dyschromias and skin texture based on photographic evaluation by blinded investigators at 6 months following the final RF treatment. Results: A statistically significant improvement in rhytides, dyschromias and texture was noted. Adverse events were limited to mild erythema and swelling. Post-inflammatory pigmentary changes were not observed in any subjects. Conclusion: The novel 144 pin high density tip bipolar fractionated RF device is both safe and effective for facial skin rejuvenation in Fitzpatrick skin types I-IV.

Influence of chemical peeling on the skin stress response system

Skin stress response system (SSRS) involves corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC)-derived peptides, such as adrenocorticotropic hormone (ACTH), a-melanocyte-stimulating hormone (MSH) and b-endorphin that are locally generated in response to locally provided stressors or proinflammatory cytokines. This system would restrict tissue damage and restore local homoeostasis. Trichloroacetic acid (TCA) is one of the most widely used peeling agents and applied for cosmetic treatment of photodamaged skin. However, the biological mechanism responsible for TCA peeling has yet to be fully determined. While our investigation focused on the inflammation and wound healing pathways, in the recent study, we have examined involvement of the SSRS as the third pathway. Mostly depending on our findings that TCA peeling activates the SSRS by inducing the POMC expression of keratinocytes in the CRH-independent manner, together with the results reported by other researchers, we can say that the biological effect of POMC seems to be responsible for the TCA-induced epidermal SSRS activation.

Combined superficial & deep fractional skin treatment for photodamaged skin—a prospective clinical trial

Background and objectives. Deep microthermal zones targeted by Fractional CO2 lasers stimulate fibroblast activity, whereas superficial microthermal zones target the epidermal layer pigment. The new combination modality enables targeting both deep and superficial disorders. The study is designed to evaluate the improvement in photodamage and determine downtime. Materials and methods. This IRB approved study was aimed to evaluate histology phenotype of combined deep and superficial skin resurfacing. A 120-micron, focused CO2 laser beam was used to create both deep and superficial fractional skin resurfacing using ultrapulse and continuous wave laser modes, respectively. Fifteen patients (skin types II–V) underwent combined treatment and returned for assessment at 1 week, 1 and 3 months to evaluate the clinical outcome. Additional histological analysis of human tissue was performed to elucidate the combined impact on tissue. Results. Pre-clinical histologies demonstrated the ability to achieve fractional discrete 1.3-mm-diameter spots of superficial ablation with a uniform shallow and narrow area of coagulation while maintaining the deep, fractional 120-micron-ablation spot capabilities. Histologies of the human tissue confirmed the ability to control both superficial and deep fractional treatment using a single handpiece. Pigmentation was greatly reduced at the 1 month follow-up with significant textural improvement. No unexpected AEs or SAEs were reported. Conclusion. The new modality enables combined superficial and deep fractional impact and improvements that are demonstrated at both the phenotype and tissue level.

Lesion dimensions following ablative fractional laser treatment in non-melanoma skin cancer and premalignant lesions

Non-melanoma skin cancer (NMSC), which comprises basal cell carcinomas (BCC) and squamous cell carcinomas (SCC), is the most common human cancer with an estimated incidence of more than one million new cancers per year alone in the USA [1–5]. SCC may be preceded by precursor lesions such as actinic keratoses (AK) and SCC in situ (Bowen’s disease), whereas BCCs are regarded as invasive tumours from the beginning. The incidence of the premalignant lesions is even higher with a reported prevalence of AK at 15.4% in men over 40 years of age in a UK population [5]. Ablative fractional laser (AFXL) resurfacing has over the past 5 years gained increasing popularity due to its clinical efficacy and short healing times compared to conventional ablative laser treatment [6]. AFXL creates microscopic vertical channels in the skin, surrounded by undamaged viable tissue. These vertical laser channels, socalled microscopic ablation zones (MAZ), are surrounded by a microscopic treatment zone, which consists of a thin necrotic layer and a coagulated tissue zone [7]. Fractional ablative lasers are available as CO2 lasers (10,600 nm), erbium yttrium aluminium garnet lasers (Er:YAG, 2,940 nm) and yttrium scandium gallium garnet lasers (YSGG, 2,790 nm), all of which have a high absorption in the target chromophore, water, and thus target intraand extracellular water-rich components such as keratinocytes and vessels [6]. AFXL resurfacing is currently used in the treatment of photodamaged skin, wrinkles, and acne and burn scars, but so far not for malignant or premalignant lesions, which is the case for conventional ablative lasers [9–13]. The immediate tissue damage after AFXL and the dimensions of the laser-ablated channels can be characterized histologically [9, 15]. MAZ dimensions have previously been investigated in animal models [14] and normal skin [15–17], whereas no data to our knowledge are available on MAZ dimensions from NMSC and dysplastic lesions. As premalignant and malignant lesions differ histologically from normal skin in several aspects including content of cell types, tumour load, vascularization, and collagen and water content, AFXL may induce different ablation patterns in dysplastic skin and normal skin. Recently, AFXL-assisted drug delivery has been introduced as a novel treatment concept to intensify the biodistribution of topical pharmaceuticals [18]. In vivo studies in pigs have shown that AFXL enhances deep tissue penetration and photoactivation of topically applied methyl aminolevulinate, which is a photosensitizer used for photodynamic therapy (PDT) [18, 19]. PDT is based on photosensitizer uptake by tumour tissue followed by illumination with visible light, which in the presence of oxygen forms cytotoxic oxygen species, causing apoptosis and necrosis of tumour tissue. PDT is approved for the treatment of BCC and premalignant lesions with high cure rates of 90% being reported for superficial malignant lesions, but less effective cure rates of 70–80% for thicker lesions [20]. The inferior treatment outcome in thick lesions K. Togsverd-Bo (*) : C. S. Haak :M. Haedersdal Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, 2400 Copenhagen, NV, Denmark e-mail: ktogsverdbo@dadlnet.dk

A study of fractional CO2 laser resurfacing: the best fluences through a clinical, histological, and ultrastructural evaluation

Fractional resurfacing is a laser treatment modality to create numerous microscopic thermal injury zones of controlled width, depth, and density that are surrounded by a reservoir of spared epidermal and dermal tissue, allowing rapid repair of laser-induced thermal injury. To evaluate the safety and efficacy of a fractional CO(2) laser system in the treatment of photo-damaged skin with clinical, histological, and ultrastructural evaluation, with special attention to one of the parameters of this laser system: the fluences. Twelve patients with Fitzpatrick skin types II to III with photo-damage skin underwent fractional laser treatment with one single-pass superficial on the face and forearm. Clinical outcome and histological and ultrastructural changes were assessed. Light microscopy of biopsies gave important information about skin changes at three different times after fractional treatment, especially revealing some differences between the fluences used in the three groups of patients. Fractional resurfacing offers significant surgical advantages allowing to achieve excellent esthetic results in balance with the biological structure. Besides, our study shows already that with 2.07 and 2.77 J/cm(2) , instead of 4.15 J/cm(2) , it is possible to reach a biological response without scar formation.

A study of multiple full-face treatments with low-energy settings of a 2940-nm Er:YAG fractionated laser

Background and objective: Fractional Er:YAG 2940-nm laser resurfacing is a relatively new approach to the treatment of photodamaged skin. Typically, this approach uses fairly high delivered energies in order to create ‘microscopic wounds’ of tissue coagulation at various dermal depths. The purpose of this study was to evaluate the efficacy, safety and tolerability of low-energy, multiple-treatment, fractional Er:YAG laser resurfacing for the treatment of photoaged skin. Methods: Sixteen subjects with photoaged skin received six, lower-fluence laser treatments with a 2940-nm wavelength Er:YAG laser, using a fractionated handpiece and a maximum energy of 30 mJ per micro-spot. Subject satisfaction, treatment tolerability, and subject outcome assessment were performed. Results: Of the 12 subjects who completed the trial, all recorded improvement in their treated skin; half reported over 50% improvement. Most patients reported none or only mild stinging and burning during and after treatment. There was no downtime associated with the procedure. No adverse events were reported. Patient satisfaction rates were high. Conclusion: Low-energy, multiple treatment, 2940-nm Er:YAG laser resurfacing with this novel device is a safe and well-tolerated method for the treatment of superficial to moderate photoaged skin.

Influence of trichloroacetic acid peeling on the skin stress response system

Although trichloroacetic acid (TCA) peeling is widely applied for cosmetic treatment of photodamaged skin, the entire biological mechanisms have yet to be determined. The skin stress response system (SSRS) involves corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) products that are locally-generated in response to locally-provided stressors or pro-inflammatory cytokines. This system would restrict tissue damage and restore local homeostasis. To determine the influence of TCA peeling on the SSRS in vitro and in vivo, expressions of POMC, melanocortin receptor 1 (MC1R), CRH and CRH receptor 1 (CRHR1) mRNA were examined by reverse transcription polymerase chain reaction in Pam212 murine keratinocytes, murine plantar and healthy human abdominal skin specimens after TCA treatment. In addition, their protein expressions as well as those of POMC-derived peptides were examined immunohistochemically. After TCA treatment, transient upregulation of POMC and MC1R mRNA expressions was observed in both murine and human skin, as well as in Pam212. Enhanced POMC protein, recovery of once-impaired MC1R protein, and no enhancement of POMC-derived peptide productions were revealed immunohistochemically in both murine and human epidermis. In contrast, neither expression levels of CRH and CRHR1 mRNA nor epidermal protein were enhanced after TCA application in murine and human skin, except for induction of human CRH mRNA expression. These results suggest that TCA activates the SSRS by inducing POMC and MC1R productions of keratinocytes in the CRH-independent manner, and that the biological effects of POMC itself are responsible for the TCA-induced epidermal SSRS activation.

Photodamage therapy using an electro‐optic q‐switched Nd:YAG laser

Q-Switched Nd:YAG lasers produce photoacoustic effects in addition to photothermal effects which may allow for greater tissue collagen production. The objective of the study is to determine the effectiveness and tolerability of an Electro-Optic (EO) Q-switched Nd:YAG laser with Single Pulse and novel Double Pulse (DP) options in the treatment of photodamaged skin. Sixteen subjects with photoaging were enrolled in this prospective, randomized, split-faced study. Subjects received 6 bi-weekly laser treatments. One half of the face was treated with a Single Pulse while the other half was treated with energies divided into a DP. Blinded investigators and subjects assessed improvement after the sixth treatment for wrinkles, coarseness, pigmentation, redness, laxity, comedones, pore size, and overall skin condition. Subjects also rated the tolerability of the treatments. For the Single Pulse side of the face, the investigators rated 33% of the patients as having a good to excellent (51% or greater) improvement in the overall condition of the skin while 47% of the subjects reported these levels. On the DP side, the overall improvement was good to excellent at a 27% rate by the investigators and 54% by the subjects. Distributions of improved ratings among investigators and subjects were similar for both sides of the treatment area. The majority of stinging/burning sensations during treatment were reported as mild on the DP side (62.8%) and moderate (63.8%) on the Single Pulse side. The chance of reporting none or only mild stinging/burning sensation during treatment was four times greater on the side of the face treated with the DP (P < 0.0001). Results have shown that treatment with the EO QS Nd:YAG laser provides a safe and effective method of skin rejuvenation with the additional benefit of significantly lower patient discomfort during use of the DP mode.

Clinical evaluation of a single‐wavelength fractional laser and a novel multi‐wavelength fractional laser in the treatment of photodamaged skin

Nonablative fractional lasers are well recognized for rejuvenating photoaged skin. We previously reported favorable outcomes with short follow-up after the use of 1,440-nm Nd:YAG laser energy used alone or in combination with a 1,320-nm laser to effect rejuvenation and wrinkle reduction. We now report longer follow-up data. Nineteen Caucasian subjects (average age 47+/-8.4; range 33-62) exhibiting mild-to-moderate photoaging of the face and neck were treated four times (average interval 18.1+/- 4.1 days; range 11-37 days) with the 1,440-nm Nd:YAG fractional laser (average fluence 3.7+/-0.3 J/cm(2)) or the 1,320/1,440-nm multiplex Nd:YAG fractional laser (1,320-nm average fluence 8.4+/-0.4 J/cm(2); 1,440-nm average fluence 2.3+/-0.2 J/cm(2)). Outcomes were assessed by subjects and the treating physician using a quartile scale to evaluate skin tightening, surface texture, rhytids, dyschromia, erythema, and global appearance after 1, 3, and 6 months. Retroauricular punch biopsies from three patients were used to evaluate wound healing. Three patients withdrew from the study prior to evaluation, one missed the 1-month evaluation, and one missed the 6-month evaluation. Assessment by subjects and the treating physician revealed clinical improvement for all outcomes after 1, 3, and 6 months. The differences between the treatment groups were not statistically significant. Subjects demonstrated the greatest average 6-month improvements in surface texture and global skin appearance. Subjects treated with the multiplex laser reported more skin tightening than the group treated only with the 1,440-nm laser. Histological evaluation revealed wound healing within 10 days and significant neocollagenesis at 3 months. No adverse events were reported in any subject. The 1,440-nm Nd:YAG and 1,320/1,440-nm multiplex Nd:YAG lasers safely and effectively produced improved surface texture, rhytids, dyschromia, erythema, global skin appearance, and skin tightening. Histopathologic findings correlated with clinical observations.