Evaluation of a New, Advanced Antioxidant Containing Topical Allyl Pyrroloquinoline Quinone: Analysis of Antioxidant Properties and Visible Effects in Subjects with Facial Photodamage.

Objectives: Evaluate the effects of a new antioxidant containing topical allyl pyrroloquinoline quinone (TAP) on expression of key markers and assess the efficacy and tolerability in subjects with photodamaged skin. Methods: Donor skin tissue was irradiated prior to and following application of study products (TAP; a leading antioxidant cream [L-VC]). Expression of markers related to epidermal homeostasis and oxidative stress were assessed at 48 hours and compared to untreated, irradiated control (n=3 each). Evaluation of lines/wrinkles, skin texture, skin tone, dullness, and erythema from baseline occurred over 12 weeks in subjects with mild-to-moderate photodamaged skin. Histological evaluation occurred at Weeks 6 and 12 (n=4). Results: Following application of TAP, significant expression of markers related to epidermal homeostasis and repair, recycling and removal, and oxidative stress were demonstrated, compared to control (p<0.05). Reduced expression of collagen degrading enzymes, compared to control, were observed (p<0.05). Application of L-VC demonstrated nonsignificant expression of markers versus control. In 40 subjects evaluated over 12 weeks, significant mean improvements from baseline were observed at Week 4 in skin texture and dullness (both p<0.0001) and skin tone and lines/wrinkles (both p=0.01). The study product was highly tolerable. Histologic evaluation demonstrated reductions in solar elastosis from baseline at Weeks 6 (33%, p=0.01) and 12 (60%, p=0.002). Conclusion: An antioxidant containing TAP addresses internal and external manifestations of photoaging. TAP demonstrated significant expression of key markers associated with epidermal homeostasis and counteracting oxidative stress. Significant, early improvements in the appearance of photodamaged skin and histological improvements in solar elastosis were observed.

Protective effects of a comprehensive topical antioxidant against ozone-induced damage in a reconstructed human skin model.

Tropospheric ozone (O3) is a source of oxidative stress. This study examined the ability of a topical antioxidant (WEL-DS) to inhibit O3-mediated damage in a human epidermal skin model. Four groups of tissues (N = 24) were compared: Group 1 (control) were untreated and unexposed; Group 2 were untreated and exposed to O3 (0.4 ppm, 4 h); Group 3 were pretreated with WEL-DS and unexposed; Group 4 were pretreated with WEL-DS and exposed to O3 (0.4 ppm, 4 h). Pretreated tissues were topically treated with 20 uL of WEL-DS and incubated for up to 20 h at 37 °C [humidified, 5% carbon dioxide (CO2)]. After 24 h, tissues were re-treated with WEL-DS and exposed to O3. Tissues were evaluated for Reactive Oxygen Species (ROS), hydrogen peroxide (H2O2), 4-hydroxynonenal (4-HNE) protein adducts, NF-κB p65 response and histology. In O3-exposed groups, WEL-DS significantly inhibited ROS formation vs. untreated tissues (p < 0.05). Pretreatment with WEL-DS inhibited H2O2 production vs. untreated tissues (p < 0.05), and decreased NF-κB p65 transcription factor signal. Oxidative stress induction in O3-exposed tissues was confirmed by increased levels of 4-HNE protein adducts (marker of lipid peroxidation); WEL-DS application reduced this effect. WEL-DS inhibited damage in tissues exposed to O3 with no significant changes in epidermal structure. A comprehensive topical antioxidant significantly diminished O3-induced oxidative damage in a human epidermal skin model.

In vitro and in vivo evaluation of a moisture treatment cream containing three critical elements of natural skin moisturization.

OBJECTIVES: To evaluate skin barrier and hydration effects of a new rebalancing moisture treatment (TRMT) and to assess efficacy and tolerability in subjects with photodamaged skin. METHODS: In an epidermal skin model, tissues (n = 5/group) were topically treated with 25 µL of TRMT, 25 µL of a market-leading moisturizer (MLM), or untreated for 60 minutes. Hydration was measured at 0, 15, and 30 minutes. Tissues were harvested for gene expression analysis of markers associated with skin barrier and hydration: Claudin (CLD), Aquaporin (AQP), Hyaluronic Acid Syntheses (HAS), and Hyaluronidase (HYAL). A clinical study evaluated twice-daily application of TRMT, assessing changes in fine lines/wrinkles, brightness, texture, erythema, and tolerability from baseline through week 8. Hydration was measured using electrical impedance. RESULTS: TRMT and MLM demonstrated significant increases in hydration vs untreated tissue at each timepoint (P < .005), with greater hydration effects observed for TRMT vs MLM. TRMT-treated tissues demonstrated greater expression of CLD, AQP, and HA, and reduced expression of HYAL vs untreated and MLM-treated tissues. Twice-daily application of TRMT demonstrated significant improvements at 2 weeks in fine lines/wrinkles (P < .001), brightness (P < .0001), texture (P < .0004), and hydration (P < .004). At 8 weeks, statistically significant improvements were achieved in all categories. CONCLUSION: In an epidermal skin model, TRMT demonstrated significant increases in hydration, greater hydration effects, and expression of key markers associated with skin barrier and hydration vs a MLM. Twice-daily application of TRMT was well tolerated and resulted in early, significant improvements in hydration and visible improvements in skin brightness, texture, fine lines/wrinkles, and erythema at 8 weeks.

In Vitro and In Vivo Efficacy and Tolerability of a Non-Hydroquinone, Multi-Action Skin Tone Correcting Cream

Background: Pigmentation disorders are therapeutically challenging to treat, requiring complicated regimens. Objectives: Alternatives to hydroquinone (HQ) are desired. We evaluated the efficacy and tolerability of a non-HQ multi-action skin tone corrector (ETCS) developed to inhibit melanin production and improve skin quality. Design and Methods: Twice-daily use of ETCS and ETCS + AHA-Ret, a retinoid-based alpha hydroxy acid cream, was evaluated in subjects with mild to severe dyschromia. Digital images were obtained at baseline, 4, 8, and 12 weeks and included assessment of dyschromia, erythema, fine lines/wrinkles, pores, texture, and global improvement. Melanin Index (MI) measurements were obtained at baseline, 4, 8, and 12 weeks. Subject self-assessments were obtained over the course of the study. Adverse Events (AEs) were collected throughout the study. An extension study evaluated use over 16-weeks. Results: Significant mean reductions from baseline occurred in dyschromia for ETCS (n=42) and ETCS + AHA-Ret (n=10) over 12 weeks (P<0.0001, each). Significant mean reductions from baseline in MI were achieved in both groups at every timepoint (ETCS: P<0.0001; ETCS + AHA-Ret: P<0.02, 4 weeks; P<0.0001, 8 and 12 weeks). Substantial improvements were demonstrated in global improvement, fine lines/wrinkles, erythema, pores, and texture at 12 weeks. Reductions from baseline occurred in dyschromia and MI (P<0.0001, each) at 16 weeks. High levels of subject satisfaction were reported with nearly all subjects reporting reduced appearance of uneven skin tone/discoloration and lightened darker patches, and improvement in overall skin tone. Mild, transient AEs were reported with no discontinuations due to an AE. Conclusions: Twice daily use of ETCS led to early, significant reductions in dyschromia and melanin index. Combination use with a retinoid-based, AHA cream in the evening demonstrated enhanced reductions. ETCS effectively reduced hyperpigmentation, improved overall skin appearance, and was highly tolerable. J Drugs Dermatol. 2019;18(7):642-648.

Evaluation of the Antioxidant Capacity and Protective Effects of a Comprehensive Topical Antioxidant Containing Water-soluble, Enzymatic, and Lipid-soluble Antioxidants.

Objectives: Investigators sought to evaluate the antioxidant capacity of a comprehensive topical antioxidant (WEL-DS), its ability to protect skin against the oxidizing effects of UVA/UVB radiation, and to assess the effectiveness and tolerability of WEL-DS for visible improvements in facial photodamage. Study Designs: In-vitro testing utilized a hydrogen peroxide assay to detect activity in human skin explants following application with WEL-DS, a leading antioxidant serum (L-AOX), and a saline control. Clinical studies included a minimal erythema dose (MED) trial in female subjects, aged 35 to 60 years. Skin was initially irradiated to determine each subject's MED. WEL-DS was applied for four days to one site on the lower back of subjects; the other site remained untreated. Both sites were irradiated with 1X, 2X and 3X each subject's MED, digital images were obtained, and punch biopsies were collected from the 3X MED irradiated areas for histological analysis. A second clinical study evaluated efficacy and tolerability of twice daily application of WEL-DS in female subjects, aged 25 to 65 years with mild-to-moderate photodamage. Changes in fine lines/ wrinkles, dyschromia, erythema, skin tone, pores, and tolerability were assessed at baseline and Weeks 4, 8, and 12. A subset of subjects were evaluated through Week 16. Results: Skin treated with WEL-DS neutralized up to 53 percent more oxidative stress relative to L-AOX. WEL-DS-treated skin demonstrated significantly less UV-induced erythema at 1X, 2X, and 3X MED and demonstrated cellular protective effects versus untreated irradiated skin (N=5). WEL-DS demonstrated average improvements from baseline of 37 percent, fine lines/ wrinkles; 17 percent, skin tone; 13 percent, dyschromia; 18 percent, erythema; and four percent, pores (N=21; Week 12). Continued improvements were demonstrated in all parameters in an extension study (n=14; week 16). WEL-DS was well-tolerated. Conclusion: These studies demonstrate WEL-DS's innate ability to quench free radicals, protect skin from the oxidizing effects of UV radiation, and reduce the visible effects of facial photodamage.

Self-reported Patient Motivations for Seeking Cosmetic Procedures.

Importance: Despite the growing popularity of cosmetic procedures, the sociocultural and quality-of-life factors that motivate patients to undergo such procedures are not well understood. Objective: To estimate the relative importance of factors that motivate patients to seek minimally invasive cosmetic procedures. Design, Setting, and Participants: This prospective, multicenter observational study was performed at 2 academic and 11 private dermatology practice sites that represented all US geographic regions. Adult patients presenting for cosmetic consultation or treatment from December 4, 2016, through August 9, 2017, were eligible for participation. Exposures: Participants completed a survey instrument based on a recently developed subjective framework of motivations and a demographic questionnaire. Main Outcomes and Measures: Primary outcomes were the self-reported most common motivations in each quality-of-life category. Secondary outcomes were other frequently reported motivations and those associated with specific procedures. Results: Of 529 eligible patients, 511 agreed to participate, were enrolled, and completed the survey. Typical respondents were female (440 [86.1%]), 45 years or older (286 [56.0%]), white (386 [75.5%]), and college educated (469 [91.8%]) and had previously received at least 2 cosmetic procedures (270 [52.8%]). Apart from motivations pertaining to aesthetic appearance, including the desire for beautiful skin and a youthful, attractive appearance, motives related to physical health, such as preventing worsening of condition or symptoms (253 of 475 [53.3%]), and psychosocial well-being, such as the desire to feel happier and more confident or improve total quality of life (314 of 467 [67.2%]), treat oneself or celebrate (284 of 463 [61.3%]), and look good professionally (261 of 476 [54.8%]) were commonly reported. Motivations related to cost and convenience were rated as less important (68 of 483 [14.1%]). Most motivations were internally generated, designed to please the patients and not others, with patients making the decision to undergo cosmetic procedures themselves and spouses seldom being influential. Patients younger than 45 years were more likely to undertake procedures to prevent aging (54 of 212 [25.5%] vs 42 of 286 [14.7%] among patients ≥45 years; P < .001). Patients seeking certain procedures, such as body contouring (19 of 22 [86.4%]), acne scar treatment (36 of 42 [85.7%]), and tattoo removal (8 of 11 [72.7%]), were more likely to report psychological and emotional motivations. Conclusions and Relevance: This initial prospective, multicenter study comprehensively assessed why patients seek minimally invasive cosmetic procedures. Common reasons included emotional, psychological, and practical motivations in addition to the desire to enhance physical appearance. Differences relative to patient age and procedures sought may need further exploration.

Efficacy and tolerability of a double-conjugated retinoid cream vs 1.0% retinol cream or 0.025% tretinoin cream in subjects with mild to severe photoaging.

BACKGROUND: Topical retinoids are used to treat the visible signs of photoaging. While efficacious, they are irritating. OBJECTIVE: Evaluate the effectiveness and tolerability of a double-conjugate retinoid cream (AlphaRet Overnight Cream; AHA-Ret) in improving visible signs of photoaging vs 1.0% retinol or 0.025% tretinoin. METHODS: A 12-week, split-face, randomized trial was conducted in 48 female subjects, aged 30-65 years with mild to severe photodamage. AHA-Ret was applied to one side of the face and either retinol (n=24) or tretinoin (n=24) to the other side (PM). Expert blinded evaluation of images and Nova measurements occurred at 4, 8, and 12 weeks. Tolerability was assessed throughout the study. RESULTS: Forty-seven subjects completed the study. AHA-Ret demonstrated significant reductions in average severity from baseline: Fine Lines/Wrinkles (P<.001; all time points); Erythema (P=.004, P<.0001; 8 and 12 weeks, respectively); Dyschromia (P<.0001; all time points); Skin Tone (P<.0001; all time points), and Pore Size (P=.035, P<.0001; 8 and 12 weeks, respectively). AHA-Ret induced less Erythema vs retinol at 8 (P=.008) and 12 (P<.02) weeks. AHA-Ret was noninferior to prescription tretinoin in all categories at 4 and 8 weeks, and for Fine Lines/Wrinkles, Erythema, Dyschromia, and Skin Tone at 12 weeks. Improvements in Hydration occurred at every time point with AHA-Ret only (P<.04, P<.03, P<.01). Less irritation was reported with AHA-Ret vs retinol or tretinoin. CONCLUSIONS: Treatment with a double-conjugate retinoid cream demonstrated early reductions in photodamage and improvements in Hydration. AHA-Ret induced less Erythema vs retinol and was more tolerable vs retinol and tretinoin.

The Role of Elastic Fibers in Scar Formation and Treatment.

BACKGROUND: Laser therapy is a continuously evolving treatment option for scars, and the underlying therapeutic mechanisms continue to be elucidated. OBJECTIVE: To comprehensively review the literature to summarize the role of elastin in the formation scars, as well as treatment via therapeutic lasers. METHODS: Review of the PubMED/MEDLINE database for available studies pertaining to the role of elastic fibers in scar formation and after laser-based therapy. RESULTS: The loss and disorganization of elastic fiber components plays a role in the development of atrophic, hypertrophic, and keloid scars. While the majority of histologic studies focus on the underlying changes in collagen, neoelastogenesis and reorganization of elastic fibers have also been demonstrated in studies using ablative, nonablative, and fractional laser devices for the treatment of scars. CONCLUSION: Production of novel elastin and normalization of elastic fiber organization occur after a variety of resurfacing procedures to treat scarring. As the treatment modalities to manage scars continue to evolve, further characterization of the role of elastin in the skin and in scar formation is merited.

A multicenter, placebo-controlled, double-blind clinical trial assessing the effects of a multicomponent nutritional supplement for treating photoaged skin in healthy women.

BACKGROUND: Dietary or supplementary intake of nutrients and other ingredients positively affects skin appearance. AIMS: Evaluate a multicomponent nutritional supplement on photoaged skin. PATIENTS/METHODS: This multicenter, double-blind, placebo-controlled trial randomized healthy 35- to 65-year-old women with Fitzpatrick skin types I-IV and Glogau classification types II-III to a multicomponent nutritional supplement or placebo for 24 weeks. The primary endpoint was Investigator Global Assessment of overall facial appearance at week 24. Secondary endpoints included investigator- and subject-rated assessments of the face, décolletage, and hands; facial photography assessments (conducted by an independent panel of dermatologists); and instrumental measures. Analysis of variance was used to assess between-group differences (P ≤ 0.05). RESULTS: Of 194 randomized subjects, 171 completed the study. Subjects had a mean age of 53 years and were primarily white (81%), had Glogau II (58%) and Fitzpatrick III (45%; significantly more supplement subjects had Fitzpatrick III [54%] vs. placebo [35%]; P = 0.039). At week 24, Investigator Global Assessment of overall facial appearance was numerically but not statistically better for supplement over placebo (mean difference: 0.14 [95% confidence interval: -0.16-0.44]; P = 0.358). A significant treatment-by-site interaction (P = 0.073) was observed; by-site analyses revealed a significant difference at one of three geographical sites for supplement vs. placebo (P = 0.001). Differences on secondary endpoints were generally not significant. CONCLUSIONS: In the first multicenter study conducted with this multicomponent nutritional supplement, no significantly greater effects vs. placebo were observed on the primary endpoint, perhaps because of significant between-site variability.

Safety and efficacy of a novel diffractive lens array using a picosecond 755 nm alexandrite laser for treatment of wrinkles.

INTRODUCTION: Picosecond lasers have been reported to be effective for removal of tattoo pigment. This prospective study evaluated the efficacy and safety of the treatment of peri-oral and -ocular wrinkles using a novel diffractive lens array coupled with a picosecond 755 nm alexandrite laser. METHODS: Forty female subjects presenting with wrinkles from photodamage were enrolled in an IRB approved study. Subjects received four picosecond diffractive lens array treatments to the full face at 1 month intervals. Six subjects were biopsied (two subjects at 1 month, two subjects at 3 months, and two subjects at 6 months). Digital photographic images were taken at 1, 3, and 6 months post-final treatment visits. Images were graded by blinded physicians for fine lines/wrinkles, erythema, dyschromia, and global improvement. Data on discomfort level, satisfaction, and side effects were recorded. RESULTS: Overall blinded physician rated global improvement ranged from improved to much improved at 1-, 3-, and 6-month time points. At baseline the average Fitzpatrick wrinkle score was 5.48. At the 6-month follow-up the average score was 3.47. The overall average change in score from pre-treatment to post-treatment was 1.97. Subject self-assessment at 6 months indicated that 90% of subjects were extremely or satisfied with their results. Unanticipated adverse events were absent with anticipated post-treatment erythema lasting for just several hours. CONCLUSIONS: A novel diffractive lens array used with a picosecond 755 nm alexandrite laser for treatment of wrinkles is highly effective and safe for wrinkles and other signs of photoaging. Lasers Surg. Med. 49:40-44, 2017. © 2016 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

ASDS Cosmetic Dermatologic Surgery Fellowship Milestones.

BACKGROUND: The American Council of Graduate Medical Education, which oversees much of postgraduate medical education in the United States, has championed the concept of "milestones," standard levels of achievement keyed to particular time points, to assess trainee performance during residency. OBJECTIVE: To develop a milestones document for the American Society for Dermatologic Surgery (ASDS) Cosmetic Dermatologic Surgery (CDS) fellowship program. METHODS: An ad hoc milestone drafting committee was convened that included members of the ASDS Accreditation Work Group and program directors of ASDS-approved Cosmetic Dermatologic Surgery (CDC) fellowship training programs. Draft milestones were circulated through email in multiple rounds until consensus was achieved. RESULTS: Thirteen milestones were developed in the 6 Accreditation Council for Graduate Medical Education (ACGME) competency areas, with 8 of these being patient-care milestones. Additional instructions for milestone administration more specific to the CDS fellowship than general ACGME instructions were also approved. Implementation of semiannual milestones was scheduled for the fellowship class entering in July 2018. CONCLUSION: Milestones are now available for CDS fellowship directors to implement in combination with other tools for fellow evaluation.

Total Defense + Repair: A Novel Concept in Solar Protection and Skin Rejuvenation.

For more than a century, solar radiation has been known to contribute significantly to the extrinsic aging of skin. Until recently, this was almost exclusively attributed to the photodamage caused by ultraviolet (UV) light. However, a growing body of evidence now indicates that both infrared (IR) and visible light may also contribute to extrinsic skin aging. Infrared radiation, comprised of IR-A, IR-B, and IR-C, accounts for 54.3% of the total solar radiation reaching the skin. Studies have shown that IR radiation is also responsible for skin aging. Thus, IR-A radiation regulates hundreds of genes in skin, with roles in extracellular matrix (ECM) homeostasis regulation, apoptosis, cell growth, and stress responses. IR-B and IR-C radiation are primarily responsible for the increase in skin temperature associated with solar exposure, and are implicated in heat-related skin destruction of collagen and elastin, which is characterized by an increase in the expression of matrix metalloproteinases (MMPs). The contribution of visible light to photoaging is less well understood; however, some preliminary indication associates visible light with the upregulation of MMPs' expression, DNA damage, and keratinocyte proliferation. Interestingly, the common denominator that links skin damage to the different solar wavelengths is the enhanced production of reactive molecule species (RMS) and therewith increased oxidative stress. SkinMedica® Total Defense + Repair (TD+R; SkinMedica Inc., an Allergan company, Irvine, CA) is a "superscreen," which combines broad spectrum UV protection with a unique blend of antioxidants (SOL-IR Advanced Antioxidant Complex™) that provide protection from IR radiation while promoting skin repair. Preclinical studies have indicated that TD+R SPF34 prevents the formation of UV-induced sunburn cells and cyclobutane pyrimidine dimers while preserving or improving the expression of ECM genes. In addition, it prevents IR-A-triggered fragmentation of elastin fibers and expression of MMP-1. Initial clinical studies indicate that TDR+R SPF34 reduces the increase in surface temperature seen with IR radiation. A significant improvement in the appearance of lines and wrinkles was reported as early as week 2 in patients using TDR+R SPF34. In summary, we observed that the unique blend of antioxidants present in TD+R acts in harmony with SPF active ingredients, expanding solar protection beyond UV radiation and counterbalancing the deleterious effects of free radicals on skin cells by promoting endogenous repair.

Nonablative 1927 nm fractional resurfacing for the treatment of facial photopigmentation.

BACKGROUND: Long-term exposure to sunlight, including ultraviolet A and B, produces signs associated with photoaging and photodamage, including laxity and discoloration of the skin. Initial laser treatment for dyspigmentation included the use of ablative lasers, followed by Q-switched lasers and more recently fractional lasers. OBJECTIVE: We investigated the safety and efficacy of a fractionated 1927nm non-ablative thulium laser for the treatment of photo-induced pigmentation. METHODS: Prospective multi-center study of subjects with clinically identifiable photopigmentation. The study protocol was approved by BioMed Institutional Review Board (San Diego, CA). Subjects received two treatments with a non-ablative 1927nm fractionated thulium laser (Fraxel Dual 1550/1927 Laser System, Solta, Hayward CA), energy level of 10mJ, coverage of 40% and 4-6 passes. Subject pain, erythema and edema were recorded immediately after treatment. Two dimensional photography was obtained before each treatment and at one and three month follow up visits. Independent blinded physician assessment was performed evaluating overall improvement in appearance as well as pigment specific improvement. RESULTS: Forty men and women, ages 30 to 80 years, Fitzpatrick skin types I-IV, with photo-induced facial pigmentation were enrolled and treated, and 39 completed the three month follow up visit. Mean pain sensation for subjects during laser treatments was reported to be 4.3 on a 10-point scale. Mean scores for erythema, edema, and skin roughness throughout all treatments indicated moderate erythema, mild edema and mild skin roughness. Assessment of overall improvement was graded as moderate to very significant in 82% of subjects at one month and in 69% of subjects at three months after the second treatment. Assessment of lentigines and ephelides demonstrated moderate to very significant improvement in approximately 68% of subjects at the one month and in 51% of subjects at three months after the second treatment. Independent blinded physician assessment of randomized photography also demonstrated a durable response at three month follow up visit. Treatment was well tolerated and no serious adverse events related to treatment were observed or reported. Study limitations included a limited number of male subjects, lack of Fitzpatrick skin types V and VI, and decrease in improvement at 3 months post-treatment. CONCLUSIONS: Two treatments with a 1927nm non-ablative fractionated thulium laser produced moderate to marked improvement in overall appearance and pigmentation with high patient satisfaction. The response to treatment was maintained at one and three months follow up.