Assessment of adverse events for a home-use intense pulsed light hair removal device using postmarketing surveillance.

BACKGROUND AND OBJECTIVES: Home-use intense pulsed light (IPL) hair removal devices are convenient for consumers. Consumer safety associated with home-use IPL devices, however, remains a subject of interest. In this descriptive analysis, we assessed the most commonly reported adverse events (AEs) for a home-use IPL device from postmarketing surveillance and qualitatively compared these with AEs from clinical studies and medical device reports of home-use IPL treatments. MATERIALS AND METHODS: For this analysis of voluntary reports, we queried a distributor's postmarketing database for IPL devices for the period beginning January 1, 2016, to December 31, 2021. All sources of comments, for example, phone, e-mail, company-sponsored web sites, were included in the analysis. AE data were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Also, we conducted a PubMed search to identify AE profiles from existing literature on home-use IPL devices and we searched the Manufacturer and User Facility Device Experience (MAUDE) database for reports on home-use IPL devices. These results were qualitatively compared to the data in the postmarketing surveillance database. RESULTS: A total of 1692 cases involving IPL were identified from voluntary reports of AEs between 2016 and 2021. The shipment-adjusted reporting rate for AE cases (number of AE cases/100,000 shipped IPL devices) was 67/100,000 during this 6-year period. The most commonly reported AEs were pain of skin 27.8% (470/1692), "thermal burn" 18.7% (316/1692), and erythema 16.0% (271/1692). Among the top 25 AEs reported, no unexpected health events were observed. The reported AEs were qualitatively similar to the pattern seen in clinical studies and the MAUDE database associated with such home-use IPL treatments. CONCLUSION: This is the first such report documenting AEs for home-use IPL hair removal from a postmarketing surveillance program. These data are supportive of the safety of such home-use low-fluence IPL technology.

Melanin-dependent tissue interactions induced by a 755-nm picosecond-domain laser: complementary visualization by optical imaging and histology.

Fractional picosecond-domain lasers (PSL) induce optical breakdown, which correlates histologically to vacuolization in the epidermis and dermis. In this ex vivo porcine study, we sought to establish a framework for the investigation of laser-tissue interactions and their dependence on melanin density. Light- (melanin index: 24.5 [0-100]), medium- (58.7), and dark-pigmented (> 98) porcine skin samples were exposed to a 755-nm fractional PSL and examined with dermoscopy, line-field confocal optical coherence tomography (LC-OCT), conventional OCT, and subsequently biopsied for digitally stained ex vivo confocal microscopy (EVCM) and histology, using hematoxylin and eosin (HE) and Warthin-Starry (WS) melanin staining. Dermoscopy showed focal whitening in medium- and dark-pigmented skin. Similarly, LC-OCT and OCT visualized melanin-dependent differences in PSL-induced tissue alterations. Vacuoles were located superficially in the epidermis in dark-pigmented skin but at or below the dermal-epidermal junction in medium-pigmented skin; in light-pigmented skin, no vacuoles were observed. Histology confirmed the presence of vacuoles surrounded by areas void of WS staining and disrupted stratum corneum in darker skin. The combined use of optical imaging for multiplanar visualization and histological techniques for examination of all skin layers may mitigate the effect of common artifacts and attain a nuanced understanding of melanin-dependent laser-tissue interactions.

Energy-based devices for the treatment of Acne Scars: 2022 International consensus recommendations.

BACKGROUND AND OBJECTIVES: Acne scars are one of the most distressing and long-term consequences of acne vulgaris, with damaging effect on a person's physical, mental, and social well-being. Numerous treatment options are available including surgical and nonsurgical techniques, depending on the clinical presentation. Although considerable advances in the development of new treatment technologies and applications have been made in the last decade, international treatment guidelines and reimbursement schemes have not yet caught up with current knowledge and practice in many centers. The authors intend to highlight the potential utility of energy-based devices (EBDs) for acne scarring, offer recommendations for safe and efficacious treatment, and provide consensus-based EBD treatment options based on varying presentations demonstrated in a series of real-life clinical photographs. STUDY DESIGN/MATERIALS AND METHODS: An international panel of 24 dermatologists and plastic surgeons from 12 different countries and a variety of practice backgrounds was self-assembled to develop updated consensus recommendations for the treatment of acne scars. A two-step modified Delphi method took place between March 2020 and February 2021 consisting of two rounds of emailed questionnaires. The panel members approved the final manuscript via email correspondence. RESULTS: The manuscript includes a comprehensive discussion and panel recommendations regarding the following topics: 1. the role of EBD in mitigating and treating acne scars in a patient with active acne, 2. the use of various EBDs for the treatment of different acne scar types with special focus on commonly used laser platform such as vascular lasers, ablative fractional lasers (AFLs) and non-AFLs (NAFLs), 3. treatment combinations, and 4. acne scar treatments in skin of color. The last part comprised of 10 photos of real-life clinical cases with the panel recommendation treatment plan to achieve best aesthetic outcome. CONCLUSION: Panel members were unanimous in their view that EBDs have a role in the management of acne scars, with AFLs, NAFLs, vascular lasers, and RF devices preferentially selected by most of the panel experts. EBDs are considered a first-line treatment for a variety of acne scar types and patients without access to these treatments may not be receiving the best available care for optimal cosmetic results. Future high-quality research and updated international treatment guidelines and reimbursement schemes should reflect this status.

Thermo-Mechanical Fractional Injury Enhances Skin Surface- and Epidermis- Protoporphyrin IX Fluorescence: Comparison of 5-Aminolevulinic Acid in Cream and Gel Vehicles.

BACKGROUND AND OBJECTIVES: Thermo-mechanical fractional injury (TMFI) impacts the skin barrier and may increase cutaneous drug uptake. This study investigated the potential of TMFI in combination with 5-aminolevulinic acid (ALA) cream and gel formulations to enhance Protoporphyrin IX (PpIX) fluorescence at the skin surface and in the skin. STUDY DESIGN/MATERIALS AND METHODS: In healthy volunteers (n = 12) a total of 144 test areas were demarcated on the upper back. Test areas were randomized to (i) TMFI (6 milliseconds, 400 µm at a single pass) or no pretreatment and (ii) 20% ALA in cream or gel formulations. Skin surface PpIX fluorescence was quantified by PpIX fluorescence photography and photometry in 30-minute intervals until 3 hours. PpIX fluorescence microscopy quantified separate PpIX fluorescence in the epidermis, and in superficial-, mid-, and deep- dermis from punch biopsies sampled after 3 hours of ALA incubation. Local skin reactions (LSR) and pain intensities (numerical rating scale 0-10) were evaluated immediately, at 3 hours and 14 days after the intervention. RESULTS: TMFI exposure before photosensitizer application significantly increased skin surface PpIX fluorescence, both for ALA cream (TMFI-ALA-cream 7848 arbitrary units [AU] vs. ALA-cream 5441 AU, 3 hours, P < 0.001) and ALA gel (TMFI + ALA-gel 4591 AU vs. ALA-gel 3723 AU, 3 hours, P < 0.001). The TMFI-mediated increase in PpIX fluorescence was similar for ALA-cream and -gel formulations (P = 0.470) at the skin surface. In the epidermis, PpIX fluorescence intensities increased from combination treatment with TMFI and ALA-cream (TMFI + ALA-cream 421 AU vs. ALA-cream 293 AU, P = 0.034) but not from combination with TMFI and ALA-gel (TMI + ALA-gel 264 AU vs. ALA-gel 261 AU, P = 0.791). Dermal fluorescence intensities (superficial-, mid-, or deep dermis) were unaffected by TMFI pretreatment in both ALA-cream and ALA-gel exposed skin (P = 0.339). ALA-cream generally induced higher PpIX fluorescence intensities than ALA-gel (skin surface P < 0.001 and epidermis P < 0.03). TMFI induced low pain intensities (median 3) and mild LSR that were resolved at 14 days follow-up. CONCLUSION: Given the present study design, TMFI, in combination with the standardized application of 20% ALA cream and gel formulations, significantly enhanced skin surface PpIX fluorescence compared to no pretreatment. Additionally, TMFI increased epidermal PpIX fluorescence combined with 20% ALA cream vehicle. Thus, TMFI pretreatment and formulation characteristics exert influence on PpIX fluorescence intensities in normal skin. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

A New Method for Percutaneous Drug Delivery by Thermo-Mechanical Fractional Injury.

BACKGROUND AND OBJECTIVES: Percutaneous drug delivery (PDD) is a means of increasing the uptake of topically applied agents into the skin. Successful delivery of a photosensitizer into the skin is an important factor for effective photodynamic therapy. To evaluate the efficacy of pretreatment by thermomechanical fractional injury (TMFI) (Tixel®, Novoxel®, Israel) at low-energy settings in increasing the permeability of the skin to a known hydrophilic-photosensitizer medication, 5-amino-levulinic-acid hydrochloride (ALA) in compounded 20% ALA gel. To compare the effect of TMFI on ALA permeation into the skin in compounded gel to three commercial photosensitizing medications in different vehicles: ALA microemulsion gel, methyl-amino-levulinic-acid hydrochloride (MAL) cream, and ALA hydroalcoholic solution. STUDY DESIGN/MATERIALS AND METHODS: Five healthy subjects were treated in two separate experiments and on a total of 136 test sites, with four topical photosensitizer preparations as follows: compounded 20% ALA gel prepared in a good manufacturing practice (GMP)-certified pharmacy (Super-Pharm Professional, Israel), 10% ALA microemulsion gel (Ameluz®, Biofrontera Bioscience GmbH, Leverkusen, Germany), 16.8% MAL cream (Metvix®, Galderma, Lausanne, Switzerland), and 20% ALA hydroalcoholic solution (Levulan Kerastick®, DUSA Pharmaceuticals, Inc., Wilmington, MA, USA). The dermal sites were pretreated by Tixel® (Novoxel® Ltd., Israel) prior to topical drug application. One site was untreated to serve as control. Protoporphyrin IX (PpIX) fluorescence intensity readouts were taken immediately and 1, 2, 3, 4, and 5 hours posttreatment. RESULTS: The highest average PpIX fluorescence intensity measurements were obtained for the compounded 20% ALA gel following pre-treatment by TMFI at 6 milliseconds pulse duration. After 2 and 3 hours, TMFI-treated sites exhibited an increased hourly rate in readouts of FluoDerm units, which were 156-176% higher than the control rates (P ≤ 0.004). TMFI pre-treatment did not enhance the percutaneous permeation of either ALA or MAL following the microemulsion gel, hydroalcoholic solution, and cream applications. CONCLUSIONS: Pretreatment with low-energy TMFI at a pulse duration of 6 milliseconds increased the percutaneous permeation of ALA linearly over the first 5 hours from application when the compounded 20% ALA gel was used. Formulation characteristics have substantial influence on the ability of TMFI pretreatment to significantly increase the percutaneous permeation of ALA and MAL. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Fractional 1,927 nm Thulium Laser Plus Photodynamic Therapy Compared and Combined for Photodamaged Décolleté Skin: A Side-by-Side Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Décolleté photodamage is a common condition typically treated with light and energy-based devices. This study investigated the efficacy and safety of a fractional 1,927 nm thulium laser (TL) alone and combined with photodynamic therapy (PDT). STUDY DESIGN/MATERIALS AND METHODS: In a 12-week follow-up study, participant décolletés were divided into four treatment areas and randomized to receive a single treatment with field-directed TL, PDT, combination TL-PDT, or lesion-directed curettage control. All actinic keratoses (AKs) underwent lesion-directed curettage before randomization. TL was delivered at 20 mJ/mb, 500 mJ/cm2 fluence, 5 W, and 8 (n = 6 pts.) or 16 (n = 6 pts.) passes. PDT was performed with 16% methyl aminolevulinate (MAL) creme incubated for 3 h, followed by red light-emitting diode light at 37 J/cm2 . Outcome measures included clinical assessment of overall photodamage and specific subcomponents, assisted by optical coherence tomography (OCT) imaging. RESULTS: Twelve women with moderate to severe photodamage on the décolleté and a cumulative total of 184 thin grade I AKs were included. Field-directed treatments TL and combination TL-PDT equally improved the overall photodamage, mottled pigmentation, and rhytides compared with lesion-directed control (P < 0.05). The skin texture improved by TL alone and was further improved by combining TL and PDT (P < 0.05). Median AK complete responses were similar for field-directed interventions TL-PDT (100%), TL (90%), PDT (82%), and lesion-directed curettage control (52%) (P = 0.464). Patients presented with mild local skin responses, slightly more pronounced when combining TL with PDT versus individual treatments (P < 0.05). No scarring or adverse events were observed. CONCLUSIONS: The 1,927 nm fractional thulium laser is an effective, tolerable, and safe field-directed treatment for décolleté photodamage. Provided alone, TL proved to be as effective as combined TL-PDT for overall photodamage, while a greater improvement in skin texture was achieved using TL and PDT in combination. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Laser Treatment of Traumatic Scars and Contractures: 2020 International Consensus Recommendations.

BACKGROUND AND OBJECTIVES: There is currently intense multidisciplinary interest and a maturing body of literature regarding laser treatments for traumatic scars, but international treatment guidelines and reimbursement schemes have not yet caught up with current knowledge and practice in many centers. The authors intend to highlight the tremendous potential of laser techniques, offer recommendations for safe and efficacious treatment, and promote wider patient access guided by future high-quality research. STUDY DESIGN/MATERIALS AND METHODS: An international panel of 26 dermatologists and plastic and reconstructive surgeons from 13 different countries and a variety of practice backgrounds was self-assembled to develop updated consensus recommendations for the laser treatment of traumatic scars. A three-step modified Delphi method took place between March 2018 and March 2019 consisting of two rounds of emailed questionnaires and supplementary face-to-face meetings. The panel members approved the final manuscript via email correspondence, and the threshold for consensus was at least 80% concurrence among the panel members. RESULTS: The manuscript includes extensive detailed discussion regarding a variety of laser platforms commonly used for traumatic scar management such as vascular lasers and ablative and non-ablative fractional lasers, special considerations such as coding and laser treatments in skin of color, and 25 summary consensus recommendations. CONCLUSIONS: Lasers are a first-line therapy in the management of traumatic scars and contractures, and patients without access to these treatments may not be receiving the best available care after injury. Updated international treatment guidelines and reimbursement schemes, additional high-quality research, and patient access should reflect this status. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Light-based home-use devices for hair removal: Why do they work and how effective they are?

OBJECTIVES: This review has the following objectives: Firstly, it provides an explanation of the evolution of laser/intense pulsed light (IPL) hair reduction modalities from high fluence professional devices to low fluence home-use appliances. Secondly, it summarises published literature reviews on home-use devices (HUDs) as evidence of their growing credibility. Thirdly, it proposes mechanistic differences in light delivery regimes and the resulting divergences in mode of action. MATERIALS AND METHODS: An extensive literature search was performed to review the progress of laser/IPL-induced hair reduction and determine what evidence is available to explain the mode of action of professional and HUDs for hair removal. Establishing the likely biological mode of action of professional high-fluence systems versus home-use low-fluence appliances was performed by combining data obtained using ex vivo hair follicle (HF) organ culture and the clinical results involving human participants. RESULTS: Significant basic science and clinical evidence has been published to confirm the clinical efficacy and technical safety of many laser and IPL home-use devices for hair removal. Clearly, HUDs are different compared to professional systems both in terms of fluence per pulse and in terms of biological mechanisms underlying hair removal. Here we presented data showing that a single low fluence pulse of both 810 nm laser (6.6 J/cm2 , 16 ms) and IPL (9 J/cm2 , 15 ms and 6.8 J/cm2 , 1.9 ms) leads to induction of catagen transition. Catagen transition was characterized by morphological changes similar to what occurs in vivo with occasional detection of apoptosis in the dermal papilla and outer root sheath cells. This suggests that high hair reduction can be expected in vivo and longer-term treatment might result in HF miniaturization due to a cumulative effect on the dermal papilla and outer root sheath cells. In line with this hypothesis, in this review we demonstrate that long-term application of a commercially-available home-use IPL appliance resulted in persistent hair reduction (80%) one year after last treatment. These data are in line with what was previously reported in the literature, where clinical studies with home-use IPL appliances demonstrated high efficacy of hair reduction on female legs, armpits and bikini zones, with full hair regrowth after four treatments following cessation of IPL administration. Limitations of HUDs include lack of hair clearance for very dark skin types and low speed of treatment compared with professional devices. Numerous uncontrolled and controlled clinical efficacy studies and technical safety investigations on consumer-use appliances support many of the leading manufacturers' claims. ANALYSIS & CONCLUSIONS: Manufacturers make consumer appliances safe and easy to use by considering "human factors," needs and capabilities of a variety of users. Safety is of primary concern to manufacturers, regulators and standards bodies as these appliances may be accessible to children or their use attempted on unsuitable skin types without full awareness of potential side effects. Consumer cosmetic appliances are provided with warnings and obvious safety notices describing the nature of any ocular or dermal hazard and precautions for reducing risk of accidental injury, infection, etc. HUDs employing optical energy are provided with design and engineering controls such as safety switches, alarms and sensors to prevent their incorrect operation or eye exposure. In-vivo studies demonstrated that low fluence home-use hair removal devices can result in high hair reduction efficacy after a short treatment regime, while prolonged and less frequent (once in six weeks) maintenance treatment over a year can lead to high and sustained hair reduction even one year after cessation of treatment. Home-use hair removal devices can be a useful adjunct to professional in-office treatments with high professional awareness. There are sufficient positive arguments for practitioners to make the case to patients for HUDs as "companion" products to professional treatments. In addition, devices for hair removal can be used effectively as stand-alone products by the consumer if they are willing to adopt a regime of regular or frequent use. Further clinical studies involving dynamic observation of HF cycle stage and type (terminal vs. vellus) over the total duration of treatment, for example, using biopsies or non-invasive imaging are necessary to confirm the proposed mode of action of low fluence pulses in a combination with treatment and maintenance regimes. Lasers Surg. Med. 51:481-490, 2019. © 2019 Wiley Periodicals, Inc.

Using normal and high pulse coverage with picosecond laser treatment of wrinkles and acne scarring: Long term clinical observations.

OBJECTIVE: The picosecond 755 nm alexandrite laser using a diffractive lens array has demonstrated consistent clinical efficacy for improving the appearance of acne scarring and wrinkles amongst other benefits. This small pilot study is to assess the difference, if any, in clinical benefit if a higher than the standard protocol for number of pulses delivered to a tissue area is used compared to the standard protocol guidelines. METHOD: Seven subjects received treatment to one side of the face with a standard protocol number of laser pulses with the other side of the face receiving higher than standard number of pulses from the same 755 nm picosecond laser using an additional diffractive lens array. Photographs at final follow up were compared to baseline by two blinded Board Certified Dermatologists and assessed for improvements to acne scarring using a 6-point grading score, for wrinkles using the Fitzpatrick Wrinkle & Elastosis 3-point grading scale and a Global Aesthetic Improvement Scale assessment. Subjects also completed a satisfaction questionnaire. RESULTS: For the acne scarring subjects, the average improvement from baseline to final follow up was 4.0 +/- 1.0 for the standard treated side and 4.5 +/- 0.5 for the high pulse side. There was no statistically significant difference between the two treated sides (P > 0.05, n = 3 paired t-test). For the wrinkle subjects, the average grading of the standard pulse side improved from 2.0 +/- 0.82 to 1.75 +/- 1.0 from baseline to final follow-up. The high pulse side improved from 1.5 +/- 1.0 to 1.125 +/- 0.25 from baseline to final follow-up. There was no statistically significant difference between the improvement of the standard and high pulse treatment sides (P > 0.05, n = 4 paired t-test). The comparison of baseline to final follow-up images of each subject found both sides to be Much or Very Much improved with no statistically significant difference between the standard and high pulse sides (P > 0.05, n = 7 paired t-test). Six of the seven subjects did not note any difference between the effect on different sides of the face and four of the seven rated their overall improvement after treatment as Good, three subjects as Reasonable and one subject with Slight Improvement. All subjects found the treatment comfortable and easy to tolerate and there was no increased incidence of side effects other than the mild occurrences typically observed for this type of treatment. CONCLUSION: This is a small pilot study with limited subject numbers and further data is needed to be able to make firm conclusions of observed trends, which suggest that the use of higher than standard suggested protocol number of pulses with the diffractive lens array and the 755 nm picosecond laser does not appear to offer any additional benefit over that that can already be achieved with the standard number of pulses, but also does not increase risk of detrimental post treatment effects either. Lasers Surg. Med. 50:51-55, 2018. © 2017 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Topical brimonidine reduces IPL-induced erythema without affecting efficacy: A randomized controlled trial in patients with facial telangiectasias.

BACKGROUND: Laser and intense pulsed light (IPL) are standard symptomatic treatments for superficial telangiectasias, but postoperative erythema, oedema, and pain may prolong downtime. OBJECTIVES: To investigate whether topical brimonidine reduces IPL-induced inflammation in patients with moderate to severe facial telangiectasias. METHODS: A randomized, two-centre, single-blinded, split-face trial on adjuvant brimonidine and air-cooling versus air-cooling alone (control) in 19 patients treated in Denmark (n = 10 patients) and Belgium (n = 9). Brimonidine was applied to the allocated side after each of three facial IPL-treatments, given at 3-week intervals. Patients were assessed up to 1 month after the final treatment. Outcome measures included blinded clinical on-site evaluation of erythema and oedema (5-point-scales), objective erythema-scores (red-filter analysis), patient-evaluated pain (Visual Analogue Scale), IPL-efficacy (blinded photo-evaluation of telangiectasia clearance), and patient preference. RESULTS: In total, 19 patients were enrolled and completed the study. IPL induced moderate to severe erythema after each treatment. Application of brimonidine, reduced erythema to baseline values compared to air-cooling alone and sustained efficacy 24 hours after treatment (median difference reduction: score 1 at each assessment, P ≤ 0.022). Objective erythema-scores supported clinical findings, demonstrating a median erythema reduction of 50-95% after application of brimonidine and air-cooling compared to 9-28% reduction after air-cooling alone (P ≥ 0.002). No difference in reduction of IPL-induced oedema was observed between facial sides (P ≥ 0.227). Brimonidine and air-cooling slightly and consistently reduced postoperative pain compared to air-cooling alone (VAS 1.0 after brimonidine versus VAS 1.5-2.0 after air-cooling alone at treatment 1-3, P ≤ 0.032). At 1-month follow-up, patients experienced excellent clearance of telangiectasias (75-100% clearance) on both facial sides (P = 1.000). Patient preference supported clinical data and 79% of patients preferred brimonidine to control (P = 0.019). CONCLUSION: Compared to air-cooling alone, adjuvant brimonidine reduces IPL-induced erythema and associated pain while maintaining a high IPL-efficacy. Lasers Surg. Med. 50:1002-1009, 2018. © 2018 Wiley Periodicals, Inc.

Effectiveness and Safety of Acne Scar Treatment With Nonanimal Stabilized Hyaluronic Acid Gel.

BACKGROUND: Acne scarring affects most patients with acne and have a negative impact on quality of life. New effective treatment options offering minimal downtime are therefore needed. OBJECTIVE: To evaluate improvement in overall facial appearance after hyaluronic acid (HA) treatment of atrophic acne scars. METHODS: Twelve subjects with moderate-to-severe acne scars were treated at 3 sessions 4 weeks apart. At each session, up to 2-mL HA gel was injected into each side of the face. Acne scar severity, global facial aesthetic improvement, and subject satisfaction were assessed up to 36 weeks after treatment. Safety assessments included subject diaries and adverse events. RESULTS: The overall facial appearance and the appearance of atrophic acne scars improved after treatment. Scar severity and subject satisfaction with the overall facial appearance and with the sensation and perception of the skin improved in most subjects. Subjects' self-esteem and self-confidence also improved. Adverse events were typically mild to moderate, expected, and procedure-related. CONCLUSION: Hyaluronic acid gel injections were effective and safe for treatment of moderate-to-severe atrophic acne scars. The treatment effect developed gradually over time with the highest improvement observed at the end of the study.

A randomized side-by-side study comparing alexandrite laser at different pulse durations for port wine stains.

BACKGROUND AND OBJECTIVES: Pulsed dye laser (PDL) represents the gold-standard treatment for port wine stains (PWS). However, approximately 20% of patients are poor responders and yield unsatisfactory end-results. The Alexandrite (Alex) laser may be a therapeutic alternative for selected PWS subgroups, but optimal laser parameters are not known. The aim of this study was to assess clinical PWS clearance and safety of Alex laser at a range of pulse durations. MATERIALS AND METHODS: Sixteen individuals (14 previously PDL-treated) with deep red (n = 4), purple macular (n = 5) and purple hypertrophic (n = 7) PWS were included. Four side-by-side test areas were marked within each lesion. Three test areas were randomized to Alex laser at pulse durations of 3, 5, or 10 ms (8 mm spot, DCD 60/40), while the fourth was untreated. The lowest effective fluence to create purpura within the entire test spot was titrated and applied to intervention areas. Standardized clinical photographs were taken prior to, immediately after laser exposure and at 6-8 weeks follow up. Clinical PWS clearance and laser-related side effects were assessed using clinical photos. RESULTS: Alex laser at 3, 5, and 10 ms pulse durations demonstrated significant clearance compared to untreated controls (P < 0.001). Three milli second pulse duration exhibited improved clearance versus 5 ms (P = 0.016) and 10 ms (P = 0.004), while no difference between five and 10 ms was shown (P = 0.063). Though not significant, good responders (>50% clearance) were more likely to have purple hypertrophic PWS (5/7) compared to purple macular (2/5) and deep red lesions (1/4). Eight laser-exposed test areas (17%) developed hypopigmented atrophic scarring. Side effects tended to be more frequently observed with 5 ms (n = 4) and 10 ms (n = 3) versus 3 ms pulse duration (n = 1). Correspondingly, 3 ms was associated with a superior (n = 6) or comparable (n = 10) overall cosmetic appearance for all individuals. CONCLUSION: Alex laser at 3 ms pulse duration offers superior clinical clearance and safety compared to 5 and 10 ms, and seems best suited for purple hypertrophic PWS. Treatment should be restricted to experienced personnel due to a particularly narrow therapeutic window. Lasers Surg. Med. 49:97-103, 2017. © 2016 Wiley Periodicals, Inc.

Non-ablative fractional laser provides long-term improvement of mature burn scars--a randomized controlled trial with histological assessment.

BACKGROUND AND OBJECTIVES: Non-ablative fractional laser-treatment is evolving for burn scars. The objective of this study was to evaluate clinical and histological long-term outcome of 1,540 nm fractional Erbium: Glass laser, targeting superficial, and deep components of mature burn scars. MATERIALS & METHODS: Side-by-side scar-areas were randomized to untreated control or three monthly non-ablative fractional laser-treatments using superficial and extra-deep handpieces. Patient follow-up were at 1, 3, and 6 months. Primary outcome was improvement in overall scar-appearance on a modified-Patient-and-Observer-Scar-Assessment-Scale (mPOSAS, 1 = "normal skin", 10 = "worst imaginable scar"). Secondary outcomes included histology, patient satisfaction (0-10), patient-assessed improvement, and safety. RESULTS: Study was completed by 17 of 20 randomized patients with normotrophic (n = 11), hypertrophic (n = 5) or atrophic (n = 1) scars. Scar-appearance improved from laser-treatments (P < 0.001 vs. untreated) and histology at 6 months supported collagen-remodeling. Improvement appeared continuously during the post-operative period (mPOSAS baseline: 7 [5-8], 6 months: 4 [3-5] P = < 0.001). At 6 months, patients were satisfied with treatment (6 [3-9]) and 82% reported improved scar-texture. Treatments caused mild to moderate pain (4 [2-7]). Adverse effects decreased during follow-up and at final assessment, discrete erythema, hyperpigmentation or imprints from laser-grid were present in 11 patients. No patients experienced worsening of scar-appearance. CONCLUSIONS: Combined superficial and deep non-ablative fractional laser-treatments induce long-term clinical and histological improvement of mature burn scars.

Transcutaneous laser treatment of leg veins.

Leg telangiectasias and reticular veins are a common complaint affecting more than 80% of the population to some extent. To date, the gold standard remains sclerotherapy for most patients. However, there may be some specific situations, where sclerotherapy is contraindicated such as needle phobia, allergy to certain sclerosing agents, and the presence of vessels smaller than the diameter of a 30-gauge needle (including telangiectatic matting). In these cases, transcutaneous laser therapy is a valuable alternative. Currently, different laser modalities have been proposed for the management of leg veins. The aim of this article is to present an overview of the basic principles of transcutaneous laser therapy of leg veins and to review the existing literature on this subject, including the most recent developments. The 532-nm potassium titanyl phosphate (KTP) laser, the 585-600-nm pulsed dye laser, the 755-nm alexandrite laser, various 800-983-nm diode lasers, and the 1,064-nm neodymium yttrium-aluminum-garnet (Nd:YAG) laser and various intense pulsed light sources have been investigated for this indication. The KTP and pulsed dye laser are an effective treatment option for small vessels (<1 mm). The side effect profile is usually favorable to that of longer wavelength modalities. For larger veins, the use of a longer wavelength is required. According to the scarce evidence available, the Nd:YAG laser produces better clinical results than the alexandrite and diode laser. Penetration depth is high, whereas absorption by melanin is low, making the Nd:YAG laser suitable for the treatment of larger and deeply located veins and for the treatment of patients with dark skin types. Clinical outcome of Nd:YAG laser therapy approximates that of sclerotherapy, although the latter is associated with less pain. New developments include (1) the use of a nonuniform pulse sequence or a dual-wavelength modality, inducing methemoglobin formation and enhancing the optical absorption properties of the target structure, (2) pulse stacking and multiple pass laser treatment, (3) combination of laser therapy with sclerotherapy or radiofrequency, and (4) indocyanin green enhanced laser therapy. Future studies will have to confirm the role of these developments in the treatment of leg veins. The literature still lacks double-blind controlled clinical trials comparing the different laser modalities with each other and with sclerotherapy. Such trials should be the focus of future research.

Safety, tolerance, and patient satisfaction with noninvasive cryolipolysis.

BACKGROUND: Comprehensive assessment of safety, tolerance, and patient satisfaction has not been established from noninvasive body contouring techniques, such as low-level laser therapy, ultrasound, radiofrequency, and infrared light, for reduction of subcutaneous fat. OBJECTIVE: This multicenter study investigated the clinical outcomes of noninvasive cryolipolysis in European subjects. METHODS: A retrospective study was performed at clinical sites in Belgium and France. Safety was assessed according to reports of side effects. Tolerance was evaluated according to pain scores and patient perception of treatment duration. Clinical outcomes were assessed according to patient surveys, caliper measurements, and assessment of photographs. RESULTS: The investigators treated 518 patients. No significant side effects or adverse events were reported. The procedure was well-tolerated, with 89% of respondents reporting a positive perception of treatment duration and 96% reporting minimal to tolerable discomfort. Survey results demonstrated 73% patient satisfaction and that 82% of patients would recommend the cryolipolysis procedure to a friend. Caliper measurements demonstrated 23% reduction in fat layer thickness at 3 months. Abdomen, back, and flank treatment sites were most effective, with 86% of subjects showing improvement per investigator assessment. CONCLUSIONS: With proper patient selection, cryolipolysis is a safe, well-tolerated, and effective treatment method for reduction of subcutaneous fat.

Highlighting nuances of blue light phototherapy: Mechanisms and safety considerations.

The efficacy of blue light therapy in dermatology relies on numerous clinical studies. The safety remains a topic of controversy, where potentially deleterious effects were derived from in vitro rather than in vivo experiments. The objectives of this work were (1) to highlight the nuances behind "colors" of blue light, light propagation in tissue and the plurality of modes of action; and (2) to rigorously analyze studies on humans reporting both clinical and histological data from skin biopsies with focus on DNA damage, proliferation, apoptosis, oxidative stress, impact on collagen, elastin, immune cells, and pigmentation. We conclude that blue light therapy is safe for human skin. It induces intriguing skin pigmentation, in part mediated by photoreceptor Opsin-3, which might have a photoprotective effect against ultraviolet irradiation. Future research needs to unravel photochemical reactions and the most effective and safe parameters of blue light in dermatology.

New and Advanced Picosecond Lasers for Tattoo Removal.

Early methods of tattoo removal ultimately resulted in unacceptable cosmetic outcomes. While the introduction of laser technology was an improvement over the existing chemical, mechanical, and surgical procedures, the use of nonselective tattoo removal with carbon dioxide and argon lasers led to scarring. Q-switched lasers with nanosecond (10-9) pulse domains were considered to have revolutionized tattoo treatment, by selectively heating the tattoo particles, while reducing the adverse sequelae to adjacent normal skin. Theoretical considerations of restricting pulse duration, to heat tattoo particles to higher temperatures, proposed the use of sub-nanosecond pulses to target particles with thermal relaxation times lower than the nanosecond pulses in Q-switched lasers. Initial studies demonstrated that picosecond (10-12) pulses were more effective than nanosecond pulses in clearing black tattoos. Advances in picosecond technology led to the development of commercially available lasers, incorporating several different wavelengths, to further refine pigment targeting.

Hair removal by lasers and intense pulsed light sources.

Laser and flash-lamp technology now offers the potential for rapid, safe, and effective treatment of unwanted hair. An ever-increasing number of published studies have confirmed the long-term efficacy of laser and flash-lamp treatment. The benefits of this technology have largely been limited to individuals with dark hair and relatively fair skin. The first studies using devices with a combination of longer wavelengths, longer pulse durations, and adequate epidermal cooling have shown that it is possible to safely and effectively treat individuals with darker skin types. The remaining challenge is to develop the means to eliminate light-colored hair as well. The increasing consumer demand for low-cost hair removal has driven the development of low-cost hair removal devices, such as small, pulsed flash lamps. The rapid pace of technologic advances and continued studies of hair follicle biology promise to improve this field over the years to come. In the future, small, low-cost laser-razors may replace all other means of hair removal.

Laser hair removal.

The presence of unwanted hair continues to plague many individuals for whom traditional methods of hair removal remain unsatisfactory. Laser and flashlamp technology now offers the potential for rapid, safe, and effective treatment of unwanted hair. An ever-increasing number of published studies have confirmed the long-term efficacy of laser and flashlamp treatment. For the most part, however, the benefits of this technology have been limited to individuals with dark hair and relatively fair skin. The remaining challenge is to develop the means to eliminate light-colored hair as well as the capability to safely treat individuals with darker skin. The rapid pace of technological advancement as well as continued studies of hair follicle biology promise to improve this field over the years to come.

Micro-fractional ablative skin resurfacing with two novel erbium laser systems.

BACKGROUND AND OBJECTIVES: Fractional ablation offers the potential benefits of full-surface ablative skin resurfacing while minimizing adverse effects. The purpose of this study was to evaluate the safety, damage profile, and efficacy of erbium fractional lasers. MATERIALS AND METHODS: Histology from animal and human skin as well as clinical evaluations were conducted with erbium YAG (2,940 nm) and erbium YSGG (2,790 nm) fractional lasers varying pulse width, microbeam (microb) energy, number of passes, and stacking of pulses. RESULTS: Single-pulse treatment parameters from 1 to 12 mJ per 50-70 microm diameter microbeam and 0.25-5 milliseconds pulse widths produced microcolumns of ablation with border coagulation of up to 100 microm width and 450 microm depth. Stacking of pulses generated deeper microcolumns. Clinical observations and in vivo histology demonstrate rapid re-epithelization and limited adverse side effects. Facial treatments were performed in the periorbital and perioral areas using 1-8 passes of single and stacked pulses. Treatments were well-tolerated and subjects could resume their normal routine in 4 days. A statistically significant reduction in wrinkle scores at 3 months was observed for both periorbital and perioral wrinkles using blinded grading. For periorbital treatments of four passes or more, over 90% had > or =1 score wrinkle reduction (0-9 scale) and 42% had > or =2. For perioral wrinkles, over 50% had substantial improvements (> or =2). CONCLUSION: The clinical observations and histology findings demonstrate that micro-fractional ablative treatment with 2,790 and 2,940 nm erbium lasers resulted in safe and effective wrinkle reduction with minimal patient downtime. The depth and width of the ablated microcolumns and varying extent of surrounding coagulation can be controlled and used to design new treatment procedures targeted for specific indications and areas such as moderate to severe rhytides and photodamaged skin.