Oral intake of bucillamine, carvedilol, metformin, or phenformin does not protect against UVR-induced squamous cell carcinomas in hairless mice.

Squamous cell carcinoma represents the second most common type of keratinocyte carcinoma with ultraviolet radiation (UVR) making up the primary risk factor. Oral photoprotection aims to reduce incidence rates through oral intake of photoprotective compounds. Recently, drug repurposing has gained traction as an interesting source of chemoprevention. Because of their reported photoprotective properties, we investigated the potential of bucillamine, carvedilol, metformin, and phenformin as photoprotective compounds following oral intake in UVR-exposed hairless mice. Tumour development was observed in all groups in response to UVR, with only the positive control (Nicotinamide) demonstrating a reduction in tumour incidence (23.8%). No change in tumour development was observed in the four repurposed drug groups compared to the UV control group, whereas nicotinamide significantly reduced carcinogenesis (P = 0.00012). Metformin treatment significantly reduced UVR-induced erythema (P = 0.012), bucillamine and phenformin increased dorsal pigmentation (P = 0.0013, and P = 0.0005), but no other photoprotective effect was observed across the repurposed groups. This study demonstrates that oral supplementation with bucillamine, carvedilol, metformin, or phenformin does not affect UVR-induced carcinogenesis in hairless mice.

Impact of skin hydration on patterns of microthermal injury produced by fractional CO2 laser.

OBJECTIVES: The impact of skin hydration on patterns of thermal injury produced by ablative fractional lasers (AFLs) is insufficiently examined under standardized conditions. Using skin with three different hydration levels, this study assessed the effect of hydration status on microchannel dimensions generated by a fractional CO2 laser. METHODS: A hydration model (hyperhydrated-, dehydrated- and control) was established in ex vivo porcine skin, validated by changes in surface conductance and sample mass. After, samples underwent AFL exposure using a CO2 laser (10,600 nm) at two examined pulse energies (10 and 30 mJ/mb, fixed 10% density, six repetitions per group). Histological assessment of distinct microchannels (n = 60) determined three standardized endpoints in H&E sections: (1) depth of microthermal treatment zones (MTZs), (2) depth of microscopic ablation zones (MAZs), and (3) coagulation zone (CZ) thickness. As a supplemental in vivo assessment, the same laser settings were applied to hyperhydrated- (7-h occlusion) and normohydrated forearm skin (no pretreatment) of a human volunteer. Blinded measurement of MAZ depth (n = 30) was performed using noninvasive optical coherence tomography (OCT). RESULTS: Modest differences in microchannel dimensions were shown between hyperhydrated, dehydrated and control skin at both high and low pulse energy. Compared to controls, hyperhydration led to median reductions in MTZ and MAZ depth ranging from 5% to 8% (control vs. hyperhydrated at 30 mJ/mb; 848 vs. 797 µm (p < 0.003) (MAZ); 928 vs. 856 µm (p < 0.003) (MTZ)), while 14%-16% reductions were shown in dehydrated skin (control vs. dehydrated at 30 mJ/mb; MAZ: 848 vs. 727 µm (p < 0.003); MTZ: 928 vs. 782 µm (p < 0.003)). The impact of skin hydration on CZ thickness was in contrast limited. Corresponding with ex vivo findings, hyperhydration was similarly associated with lower ablative depth in vivo skin. Thus, median MAZ depth in hydrated skin was 10% and 14% lower than in control areas at 10 and 30 mJ/mb pulse energy, respectively (10 mJ: 210 vs. 180 µm (p < 0.001); 30 mJ: 335 vs. 300 µm (p < 0.001)). CONCLUSION: Skin hydration status can exert a minimal impact on patterns of microthermal injury produced by fractional CO2 lasers, although the clinical implication in the context of laser therapy requires further study.

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.

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.

High Oral Vitamin D3 Intake Does Not Protect Against UVR-induced Squamous Cell Carcinoma in Mice.

BACKGROUND/AIM: The effect of vitamin D on skin carcinogenesis is unclear. Vitamin D derivatives may protect against ultraviolet radiation (UVR)-induced DNA damage, immune suppression, and skin carcinogenesis. However, some epidemiological studies have reported an increased incidence of skin cancer associated with high serum vitamin D levels. We investigated the effect of vitamin D supplementation on serum, skin, and tumor vitamin D levels and on skin cancer development in hairless immunocompetent mice. MATERIALS AND METHODS: Female C3.Cg-Hrhr/TifBomTac immunocompetent mice (n=125) were randomly separated into five groups. Two groups received a high vitamin D3 diet (4.5 µg/day/mouse). One group received a medium vitamin D3 diet (2.3 µg/day/mouse). Two groups received a standard diet (0.045 µg/day/mouse). Three standard erythema doses of UVR were given three times per week to three groups. RESULTS: Animals on a high vitamin D3 diet had ~150-fold higher serum vitamin D3 levels (p=0.00016) and 3-fold higher serum 25-hydroxyvitamin D3 [25(OH)D3] levels (p=0.00016) than those on a standard diet. For mice on the medium vitamin D3 diet, serum vitamin D3 and 25(OH)D3 levels were 18-fold and 2.3-fold higher than for the standard diet, respectively (p=0.00016). All UVR-exposed mice developed tumors. Vitamin D3 levels were lower in the tumor than the skin (p<0.0001). High and medium supplementation with vitamin D3 did not affect tumor development (p>0.05). CONCLUSION: In mice, vitamin D levels in the serum, skin, and tumors were augmented by supplementation, but this did not affect the development of UVR-induced skin tumors.

The Copenhagen Actinic Keratosis Study (COAKS). A decentralised clinical trial to evaluate tolerability, safety and efficacy of daily field-directed topical treatment with cytosolic phospholipase A2 inhibitor, AVX001, in participants with actinic keratosis: protocol for a randomised controlled phase I/IIa trial.

INTRODUCTION: Actinic keratosis (AK) is the most common precancerous skin condition caused by long-term UV exposure. Given the high recurrence rate of 15%-53%, identifying safe and effective treatment options is warranted. AVX001, a cytosolic phospholipase A2α (cPLA2α) enzyme inhibitor, is a novel anti-inflammatory drug for field-directed, self-administered, topical therapy of AK. METHODS AND ANALYSIS: This study is a single-centre, randomised, vehicle-controlled, double-blind, parallel-group hybrid clinical trial in adults with multiple AK lesions Olsen grade 1 or 2. The hybrid design combines decentralised participant tasks and assessments with conventional in-clinic visits. Recruitment using targeted advertising on social media and eligibility prescreening are conducted via the Studies&Me online recruitment platform. Participants (n=60) are randomly assigned to 1 of 3 treatment arms: AVX001 gel 1%, AVX001 gel 3% or vehicle gel. The trial consists of a 4-week treatment period with daily field-directed topical application of the gel and an 8-week follow-up period. Participants attend in-clinic visits at baseline, week 4 and week 12. The remote participant trial tasks include questionnaires and upload of smartphone-obtained photos of the treated skin area using a study-specific web-based app. Both remote and in-clinic assessments of safety and efficacy will be performed. The primary objective is to evaluate the local tolerability of daily application of AVX001 gel (1% or 3%) compared with vehicle gel. Secondary objectives include safety, efficacy, dose-response efficacy relationship, treatment satisfaction and cosmetic outcome. Exploratory objectives include evaluations of tolerability and efficacy assessed by dermatologists using smartphone photos uploaded by participants, comparisons of in-clinic and remote assessments and assessment of AK-related skin changes by non-invasive optical imaging. ETHICS AND DISSEMINATION: Approved by the Ethics Committee of the Capital Region of Denmark (H-21018064) and the Danish Medicines Agency (2021032485). Results will be submitted for publication in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBERS: 2021-000934-32; NCT05164393.

Local vasoregulative interventions impact drug concentrations in the skin after topical laser-assisted delivery.

INTRODUCTION: The ability of ablative fractional lasers (AFL) to enhance topical drug uptake is well established. After AFL delivery, however, drug clearance by local vasculature is poorly understood. Modifications in vascular clearance may enhance AFL-assisted drug concentrations and prolong drug dwell time in the skin. Aiming to assess the role and modifiability of vascular clearance after AFL-assisted delivery, this study examined the impact of vasoregulative interventions on AFL-assisted 5-fluorouracil (5-FU) concentrations in in vivo skin. METHODS: 5-FU uptake was assessed in intact and AFL-exposed skin in a live pig model. After fractional CO2 laser exposure (15 mJ/microbeam, 5% density), vasoregulative intervention using topical brimonidine cream, epinephrine solution, or pulsed dye laser (PDL) was performed in designated treatment areas, followed by a single 5% 5-FU cream application. At 0, 1, 4, 48, and 72 h, 5-FU concentrations were measured in 500 and 1500 µm skin layers by mass spectrometry (n = 6). A supplemental assessment of blood flow following AFL ± vasoregulation was performed using optical coherence tomography (OCT) in a human volunteer. RESULTS: Compared to intact skin, AFL facilitated a prompt peak in 5-FU delivery that remained elevated up to 4 hours (1500 µm: 1.5 vs. 31.8 ng/ml [1 hour, p = 0.002]; 5.3 vs. 14.5 ng/ml [4 hours, p = 0.039]). However, AFL's impact was transient, with 5-FU concentrations comparable to intact skin at later time points. Overall, vasoregulative intervention with brimonidine or PDL led to significantly higher peak 5-FU concentrations, prolonging the drug's dwell time in the skin versus AFL delivery alone. As such, brimonidine and PDL led to twofold higher 5-FU concentrations than AFL alone in both skin layers by 1 hour (e.g., 500 µm: 107 ng/ml [brimonidine]; 96.9 ng/ml [PDL], 46.6 ng/ml [AFL alone], p ≤ 0.024), and remained significantly elevated at 4 hours (p ≤ 0.024). A similar pattern was observed for epinephrine, although trends remained nonsignificant (p ≥ 0.09). Prolonged 5-FU delivery was provided by PDL, resulting in sustained drug deposition compared to AFL alone at both 48 and 72 hours in the superficial skin layer (p ≤ 0.024). Supporting drug delivery findings, OCT revealed that increases in local blood flow after AFL were mitigated in test areas also exposed to PDL, brimonidine, or epinephrine, with PDL providing the greatest, sustained reduction in flow over 48 hours. CONCLUSION: Vasoregulative intervention in conjunction with AFL-assisted delivery enhances and prolongs 5-FU deposition in in vivo skin.

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.

Efficacy and Safety of Laser-Assisted Combination Chemotherapy: An Explorative Imaging-Guided Treatment With 5-Fluorouracil and Cisplatin for Basal Cell Carcinoma.

BACKGROUND AND OBJECTIVES: Rising incidences of basal cell carcinoma (BCC) have increased the need for effective topical therapies. By enhancing cutaneous uptake of the chemotherapeutic agents, cisplatin and 5-fluorouracil (5-FU), laser-assisted delivery may provide a new combination treatment for BCC. Accordingly, this study aimed to evaluate tumor response, safety, and drug biodistribution in tumors and blood after topical laser-assisted 5-FU + CIS treatment in BCC patients. STUDY DESIGN/MATERIALS AND METHODS: This open-label, proof-of-concept trial investigated laser-assisted combination cisplatin + 5-FU treatment in 20 patients with histologically verified, low-risk superficial or nodular BCCs on the face (<20 mm) or trunk/extremities (<50 mm). After tumor demarcation guided by optical coherence tomography (OCT), BCCs were exposed to ablative fractional CO2 laser followed by 60 minutes topical cisplatin solution and 7-day exposure to 5% 5-FU cream under occlusion. After 30 days, treatment was repeated if any tumor residual was identified. Tumor response at day 30 and month 3 was assessed clinically as well as by OCT, reflectance confocal microscopy, and ultrasound, supplemented by histological verification at 3 months. Local skin reactions (LSRs) and side effects were evaluated on days 1, 3-5, 14, 30, and month 3. Drug detection in tumors and blood was performed in a subset of patients 1- and 24 hours after treatment. RESULTS: Nineteen patients completed the trial, with 32% (6/19) receiving a single treatment and 68% (13/19) treated twice. At 3 months, clinical clearance was seen in 18/19 patients with a corresponding 94% (17/18) achieving histological clearance. Baseline tumor thickness and subtype did not influence treatment number or clearance rate (P ≥ 0.61). LSRs were well-tolerated and consisted of erythema, edema, and erosion, followed by crusting by day 14. Erythema declined gradually by month 3, with 94% of patients and 79% of physicians rating cosmesis as "good" or "excellent." Scarring or hyperpigmentation was noted in 50% and 56%, respectively, while pain and infection were not observed during the follow-up period. Although chemotherapy uptake was visualized extending to deep skin layers, no systemic exposure to cisplatin or 5-FU was detected in patient blood. CONCLUSION: Laser-assisted cisplatin + 5-FU shows potential as an effective and tolerable treatment option for low-risk BCC, particularly in instances where self-application is not possible or where in-office, non-surgical therapy is preferred. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Acne Treatment With Light Absorbing Gold Microparticles and Optical Pulses: An Open-Label European Multi-Centered Study in Moderate to Moderately Severe Acne Vulgaris Patients.

BACKGROUND AND OBJECTIVE: Recently, a novel acne treatment based on selective photothermolysis of pilosebaceous units with follicular delivery of inert gold microparticles as an exogenous chromophore and diode laser pulses has been developed. To evaluate the efficacy and safety of a single monotherapy treatment regimen with gold microparticles and diode laser exposure in patients with moderate and moderately severe acne. Further, to evaluate the added benefit of a second treatment regimen combined with pharmaceutical acne treatment in patients with inadequate initial response. MATERIALS AND METHODS: Patients with moderate and moderately severe facial acne were recruited in this open-label, pilot study. A single treatment regimen consisted of three weekly facial treatments with topically applied gold microparticles and diode laser pulses. Outcome measures were the proportion of patients with ≥40% improvement in number of acne lesions (weighted lesion count [WLC]) at 12 weeks (single treatment regimen, primary outcome measure), 24, and 36 weeks from baseline (two treatment regimens), safety, and patient satisfaction. RESULTS: A total of 28 patients were enrolled in the study (18 males, 10 females, 19 patients with moderate acne severity, 9 with moderately severe, mean age: 19.8 years). Twenty-five patients underwent analysis for outcome measures. After a single monotherapy treatment regimen, 76% patients (19/25) achieved ≥40% reduction in WLC (mean WLC reduction: 63%; SD: 13%). Of the patients undergoing two treatment regimens (n = 9 patients), 56% experienced a reduction in acne lesion burden (WLC) ≥40% at 24 weeks and 89% 36 weeks post-baseline. Mean pain score was 4.0 (SD: 1.3), and transient erythema and perifollicular edema were commonly noted after treatment. Most patients (81%) were either "satisfied" or "very satisfied" with the treatment. CONCLUSION: Acne therapy based on selective photothermolysis with gold microparticles shows promise and may be used in treatment of moderate to moderately severe acne. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

New lasers and light sources - old and new risks?

Recent developments (new wavelengths, treatment concepts, and combinations) in the field of lasers, intense pulsed light (IPL), LED, as well as new energy and light sources have opened up new therapeutic options that extend beyond mere aesthetic indications. Thus, while fractional lasers used to be employed to merely treat wrinkles, the same devices - in the context of laser-assisted drug delivery - have now become important tools in the treatment of scars, field cancerization, and epithelial tumors. The requirements posed to physicians, both with respect to establishing the indication and conducting treatment, have been growing along with the increase in technological complexity as well as the rising number of comorbidities and comedications in a patient population that continues to age. At the same time, home-use devices have been introduced for a variety of indications. These devices are characterized by low power and special safety features aimed at preventing accidents, risks, and side effects. Despite the reduced efficacy of such self-treatment devices, there is an increased risk of misuse, given that the basic prerequisite for adequate treatment cannot be ensured, to wit, the exact diagnosis and therapeutic indication. Consequently, during hair removal or anti-wrinkle treatment, pigmented lesions and cutaneous neoplasms may be altered, thus giving rise to expected, unexpected and new side effects and complications. In the aforementioned setting, it is important that all potential users of these new technologies be properly trained in a manner that ensures those treated a maximum of safety and efficacy in accordance with the guiding principle "diagnosis certa - ullae therapiae fundamentum".

Skin reactions after photodynamic therapy are unaffected by 839 nm photobiomodulation therapy: A randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is associated with erythema and edema. Photobiomodulation (PBM) therapy may stimulate the skin recovery process. We investigated the potential of PBM to reduce PDT-induced skin reactions. STUDY DESIGN AND METHODS: Healthy volunteers (n = 20) were randomized to receive left- or right side PBM (near-infrared 839/595 nm) or placebo-PBM (595 nm) on their buttocks. Corresponding test areas were exposed to standardized PDT reactions, using ablative fractional laser-assisted PDT (AFXL-PDT) with methyl-aminolevulinate (MAL) incubated for 30, 90, and 180 minutes before red-light illumination. Each buttock received PBM and placebo-PBM for five consecutive days, starting one day before PDT interventions. Follow-up visits were performed 4 and 11 days after PDT. Outcome measure included blinded, observer-assessed skin reactions, substantiated by objectively measured erythema and pigment percentages and skin temperatures. RESULTS: PDT interventions induced a standardized range of erythema and edema in all subjects. Skin reactions were clinically unaffected by PBM throughout the active treatment period and at all subsequent follow-up visits (PBM vs. placebo-PBM, P = 1.000). Clinical results were supported by similar erythema intensities and skin temperatures in PBM and placebo-PBM treated skin: median erythema 28.1% versus 30.3% (AFXL-PDT with 30 minutes MAL-incubation), 36.1% versus 35.2% (90 minutes MAL-incubation) and 39.4% versus 40.9% (180 minutes MAL-incubation) (Day 4, P > 0.05). No differences in clinical hyperpigmentation or pigment percentages were observed between corresponding test areas in any subject on the final 11-day follow-up. CONCLUSION: Under the current study conditions, PDT-induced skin reactions were unaffected by PBM. Lasers Surg. Med. 49:810-818, 2017. © 2017 Wiley Periodicals, Inc.

Side effects from intense pulsed light: Importance of skin pigmentation, fluence level and ultraviolet radiation-A randomized controlled trial.

BACKGROUND AND OBJECTIVE: Intense pulsed light (IPL) is a mainstream treatment for hair removal. Side effects after IPL are known, but risk factors remain to be investigated. The objective of this study was to assess the contribution of skin pigmentation, fluence level, and ultraviolet radiation (UVR) on IPL-induced side effects. METHODS: The study was a blinded, randomized intra-individual controlled trial including 16 healthy subjects with Fitzpatrick Skin Types (FST) II-V. Three test areas were each divided into four sites, randomized to a single IPL exposure of 22, 34, 46 J/cm2 or triple stacking of 46 J/cm2 . Areas were subsequently randomized to no UVR or single solar-simulated UVR exposure of 3 Standard Erythema Dose at 30 minutes or 24 hours after IPL. Each area had a corresponding control, resulting in 15 treatment sites. Follow-up visits were scheduled up to 4 weeks after IPL. Outcome measures were: (i) blinded clinical skin reactions; (ii) objectively measured erythema and pigmentation; (iii) pain measured by visual analog scale (VAS); (iv) histology (H&E, Fontana-Masson); and (v) mRNA-expression of p53. RESULTS: Fifteen subjects with FST II-IV completed the protocol. IPL induced a wide range of skin reactions, including erythema (87% of subjects), purpura (27%), blisters (20%), edema (13%), crusting (13%), hyper- (60%), and hypopigmentation (20%). Darker skin pigmentation and increasing IPL fluence were determinants for IPL-induced side effects (P ≤ 0.002), while a single exposure of UVR did not exacerbate side effects (P ≥ 0.180). Clinical findings were confirmed objectively by reflectance spectrometry and qualitatively by histological changes in skin architecture, inflammatory infiltration, and pigmentation. Marker of cellular DNA damage, that is, p53, did not increase after IPL (P ≥ 0.24). CONCLUSIONS: Skin pigmentation and IPL fluence are major determinants of side effects after IPL exposure, while a single exposure to three SED of UVR at 30 minutes or 24 hours after IPL, does not amplify such side effects. Lasers Surg. Med. 49:88-96, 2017. © 2016 Wiley Periodicals, Inc.

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.

[Dermatological laser- and light treatments of scars].

Many patients struggle with tender, rigid and erythematous scars. Various modalities are used to treat cutaneous scars and in recent years, laser treatments are emerging as promising procedures. This article describes laser systems used for scar treatment according to scar type, evaluates the highest available level of evidence from randomized controlled trials (RCTs) and introduces a guideline for laser treatment of scars. Twelve RCTs documented effect on acne, burn and surgical scars. It is recommended that laser- and light-based treatments are considered according to the scar type.

Translational medicine in the field of ablative fractional laser (AFXL)-assisted drug delivery: A critical review from basics to current clinical status.

BACKGROUND: Ablative fractional lasers enhance uptake of topical therapeutics and the concept of fractional laser-assisted drug delivery has now been taken into clinical practice. OBJECTIVES: We systematically reviewed preclinical data and clinical evidence for fractional lasers to enhance drug uptake and improve clinical efficacy. METHODS: We searched PubMed and Embase databases; 34 articles met the inclusion criteria. Studies were categorized into experimental preclinical studies and clinical trials, the latter graded according to level of evidence. RESULTS: All preclinical trials (n = 16) documented enhanced topical drug uptake into skin after ablative fractional laser treatment. Clinical evidence encompassed 18 studies, of which 9 were randomized controlled trials and 2 were controlled trials, examining neoplastic lesions, photodamaged skin, scars, onychomycosis, and topical anesthetics. The highest level of evidence was reached for actinic keratoses treated with methylaminolevulinate for photodynamic therapy (level IB, 5 randomized controlled trials), substantiating superior and long-lasting efficacy versus conventional photodynamic therapy. No adverse events were reported, but ablative fractional laser-assisted drug delivery implies risks of systemic drug absorption, especially when performed over large skin areas. CONCLUSIONS: Fractional laser-assisted drug delivery is beneficial in enhancing preclinical and clinical outcomes for certain skin conditions.

Ultraviolet radiation after exposure to a low-fluence IPL home-use device: a randomized clinical trial.

The prevailing advice is to avoid sun exposure after intense pulsed light (IPL) hair removal. However, no systematic evaluation of ultraviolet radiation (UVR) after IPL hair removal exits. Therefore, we investigated the occurrence of side effects in subjects receiving solar-simulated UVR after a low-fluence IPL treatment with a home-use device. Sixteen subjects with Fitzpatrick skin types (FST) II-V were enrolled. Three constitutive buttock blocks (4.4 × 6.4 cm) were each subdivided into four sites, randomized to one IPL exposure of 0, 7, 8, or 10 J/cm2 (spectral output 530-1100 nm). Blocks were randomized to no UVR or three standard erythema doses (SEDs) UVR either 30 min or 24 h after IPL. Follow-up visits were 48 h, 1 week, and 4 weeks after IPL. Outcome measures were (i) clinical skin reactions, (ii) reflectance measurements of erythema and pigmentation, and (iii) pain. Subjects with FST II-IV experienced no skin reactions up to 4 weeks after IPL, neither erythema, edema, blisters, crusting, textual, nor pigment changes. Reflectance confirmed no change in erythema and pigmentation (p ≥ 0.090). UVR exposure induced erythema and increased pigmentation. The combination of IPL and UVR induced skin reactions not different to responses from UVR (IPL-UVR vs. UVR, p ≥ 0.164). Pain was generally low (median 1, range 0-4) and correlated positively with fluence and pigmentation (Spearman's rho ≥ 0.394, p < 0.001). One subject with FST V experienced perifollicular hyperpigmentation after IPL and slightly more intense when exposed to UVR. A single UVR exposure of three SEDs either shortly or 1 day after low-fluence IPL causes no amplification of skin responses in constitutive skin of individuals with FST II-IV.

Fractional CO2 laser resurfacing for atrophic acne scars: a randomized controlled trial with blinded response evaluation.

BACKGROUND: The treatment of acne scars with fractional CO(2) lasers is gaining increasing impact, but has so far not been compared side-by-side to untreated control skin. OBJECTIVE: In a randomized controlled study to examine efficacy and adverse effects of fractional CO(2) laser resurfacing for atrophic acne scars compared to no treatment. METHODS: Patients (n = 13) with atrophic acne scars in two intra-individual areas of similar sizes and appearances were randomized to (i) three monthly fractional CO(2) laser treatments (MedArt 610; 12-14 W, 48-56 mJ/pulse, 13% density) and (ii) no treatment. Blinded on-site evaluations were performed by three physicians on 10-point scales. Endpoints were change in scar texture and atrophy, adverse effects, and patient satisfaction. RESULTS: Preoperatively, acne scars appeared with moderate to severe uneven texture (6.15 ± 1.23) and atrophy (5.72 ± 1.45) in both interventional and non-interventional control sites, P = 1. Postoperatively, lower scores of scar texture and atrophy were obtained at 1 month (scar texture 4.31 ± 1.33, P < 0.0001; atrophy 4.08 ± 1.38, P < 0.0001), at 3 months (scar texture 4.26 ± 1.97, P < 0.0001; atrophy 3.97 ± 2.08, P < 0.0001), and at 6 months (scar texture 3.89 ± 1.7, P < 0.0001; atrophy 3.56 ± 1.76, P < 0.0001). Patients were satisfied with treatments and evaluated scar texture to be mild or moderately improved. Adverse effects were minor. CONCLUSIONS: In this single-blinded randomized controlled trial we demonstrated that moderate to severe atrophic acne scars can be safely improved by ablative fractional CO(2) laser resurfacing. The use of higher energy levels might have improved the results and possibly also induced significant adverse effects.

Lasers or light sources for treating port-wine stains.

BACKGROUND: Port-wine stains are birthmarks caused by malformations of blood vessels in the skin. Port-wine stains manifest themselves in infancy as a flat, red mark and do not regress spontaneously but may, if untreated, become darker and thicker in adult life. The profusion of various lasers and light sources makes it difficult to decide which equipment is the best for treating port-wine stains. OBJECTIVES: To study participant satisfaction, clinical efficacy, and adverse effects of the treatment of port-wine stains by lasers and light sources. SEARCH METHODS: We searched the following databases up to April 2010: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), LILACS (Latin American and Caribbean Health Science Information database, from 1982), and reference lists of articles. We also searched online trials registries for ongoing trials and contacted trial authors where appropriate. SELECTION CRITERIA: Randomised clinical trials (RCTs) of lasers or light sources for the treatment of port-wine stains. DATA COLLECTION AND ANALYSIS: Our outcomes of interest were participant satisfaction, reduction in redness of the port-wine stain as determined by clinical evaluation, and short- and long-term adverse effects of the treatments. Three authors independently extracted data and assessed trial quality. MAIN RESULTS: We included 5 RCTs involving a total of 103 participants; all of the trials used a within-participant design. The interventions and outcomes were too varied to be combined statistically. All trials used the pulsed dye laser for comparisons.None of the studies focused on participant satisfaction, which was one of our primary outcomes, but participant preference was evaluated in three of five studies. Participants preferred the pulsed dye laser to intense pulsed light based on the clinical effect. They marginally preferred the Neodymium:YAG (yttrium-aluminium-garnet) (Nd:YAG) laser to the pulsed dye laser due to shorter lasting purpura, and pulsed dye laser in conjunction with cooling was preferred to treatment with pulsed dye laser alone.All trials examined short-term efficacy of less than six months after treatments with the pulsed dye laser, intense pulsed light, and Nd:YAG laser. The pulsed dye laser was evaluated in all five trials. Depending upon the setting of the pulsed dye laser, this resulted in more than 25% reduction in redness. This was after 1 to 3 treatments for up to 4 to 6 months postoperatively in 50% to 100% of the participants. There was only one study each of intense pulsed light and Nd:YAG laser.Two trials had no occurrence of long-term adverse effects, i.e. six months after treatment. Three trials reported pigmentary alterations in 3% to 24% of the participants, with the highest percentage occurring in Chinese participants with darker skin types. In one study one participant experienced scarring of the skin caused by a too-high dose of the laser used. Short-term side-effects included pain, crusting, and blistering in the first two weeks after treatment. AUTHORS' CONCLUSIONS: The pulsed dye laser leads to clinically relevant clearance of port-wine stains. A limited number of RCTs evaluated the efficacy from intense pulsed light and other laser types. High-quality RCTs are needed to assess individual efficacy from different lasers and light sources, as well as participant satisfaction.

Hair removal.

Hair removal with optical devices has become a popular mainstream treatment that today is considered the most efficient method for the reduction of unwanted hair. Photothermal destruction of hair follicles constitutes the fundamental concept of hair removal with red and near-infrared wavelengths suitable for targeting follicular and hair shaft melanin: normal mode ruby laser (694 nm), normal mode alexandrite laser (755 nm), pulsed diode lasers (800, 810 nm), long-pulse Nd:YAG laser (1,064 nm), and intense pulsed light (IPL) sources (590-1,200 nm). The ideal patient has thick dark terminal hair, white skin, and a normal hormonal status. Currently, no method of lifelong permanent hair eradication is available, and it is important that patients have realistic expectations. Substantial evidence has been found for short-term hair removal efficacy of up to 6 months after treatment with the available systems. Evidence has been found for long-term hair removal efficacy beyond 6 months after repetitive treatments with alexandrite, diode, and long-pulse Nd:YAG lasers, whereas the current long-term evidence is sparse for IPL devices. Treatment parameters must be adjusted to patient skin type and chromophore. Longer wavelengths and cooling are safer for patients with darker skin types. Hair removal with lasers and IPL sources are generally safe treatment procedures when performed by properly educated operators. However, safety issues must be addressed since burns and adverse events do occur. New treatment procedures are evolving. Consumer-based treatments with portable home devices are rapidly evolving, and presently include low-level diode lasers and IPL devices.