Whitney P. Bowe MDa and Silvina Pugliese MDb
Photoaging is a leading concern for patients and many of these patients will express a desire to utilize natural ingredients as treatment.
Mushrooms, feverfew, green tea, licorice, olive oil, soy, and coffee berry have been shown to have antioxidant properties and may
play a role in the treatment and prevention of photoaging. In this manuscript, the most recent select basic science and clinical studies
examining the mechanisms and efficacy of these ingredients will be discussed.
J Drugs Dermatol. 2014;13(9):1021-1025.
Oscar Hevia MD,a,b Bernard H. Cohen MD,b,c and David J. Howell PhDd
BACKGROUND: Utilizing a soft-tissue filler that is more fluid and less resistant to deformation may be advantageous for correction of
OBJECTIVE: The objective of this study was to determine the safety and efficacy of the latest hyaluronic acid filler, created with a cohesive
polydensified matrix, with a low elasticity and viscosity, for infraorbital hollows correction.
METHODS AND MATERIALS: Subjects (49) with at least a grade 2 Merz infraorbital hollow scale in the Validated Assessment Scales for the
mid face (0-4) of the right and/or left side were photographed and treated at baseline, and with a touch up treatment after 2 weeks if
necessary. Subjects were also photographed at 2, 6, and 10 months after baseline, with optional retreatment at 6 months. The photographs
were graded by a blinded sub-investigator.
RESULTS: Mean hollowness scores for both eyes, either individually or combined, at 2, 6, and 10 months were considerably improved
compared to baseline (P <.001). No serious adverse events were reported. Of the 46 subjects completing the study, 31 (66%) did not
request retreatment after 6 months. At 10 months, 27/31 (87%) still exhibited a hollowness improvement of at least 1-point from baseline.
CONCLUSION: Belotero Balance was safe and effective for the correction of infraorbital hollows.
J Drugs Dermatol. 2014;13(9):1030-1036.
Deborah S. Sarnoff MD FAAD FACPa,b and Robert H. Gotkin MD FACSb,c
BACKGROUND: Cervicofacial aging is often characterized by a combination of skin and subcutaneous tissue laxity, midfacial deflation, an accumulation of excess submental fat, an obtuse cervicomental angle, jowls, and rhytides of the face and neck. Traditional treatment, and the “gold standard” against which other treatments are compared, is a facelift.
OBJECTIVE: To demonstrate that a combination technique called ACELIFT – an acronym for the Augmentation of Collagen and Elastin using Lasers, Injectable neurotoxins, Fillers, and Topicals – in selected patients, is a viable, safe, and effective alternative to a facelift.
METHODS: Ten healthy women, ages 50 to 62 (mean age = 58), with cervical and facial stigmata of aging were enrolled in a prospective study conducted in the authors’ private practice. Patients underwent a two-step procedure; the first step was laser lipolysis of the submental and anterior cervical areas with a pulsed 1440nm Nd:YAG laser with a side-firing fiber (PrecisionTx, Cynosure, Westford, MA). Three months later, the patients were treated in a single session that combined injectable neurotoxin, fillers, and fractional (Fx) CO2
laser resurfacing delivered in a novel “hammock” distribution. After two weeks, following complete re-epithelialization, the patients were started on a topical regimen that included daily use of sunscreen and antioxidants and nightly use of retinoids and peptides. This regimen was continued for a period of six months when all patients returned for final evaluation.
RESULTS: Nine months following the initiation of treatment, all patients were evaluated by the following: Global Aesthetic Improvement Scale, cervicomental angle scale, physician, and subject evaluation. Clinical improvement was evident, and often marked, for all subjects. Both physician and subject satisfaction scores were high, indicating overall satisfaction with the procedure and the outcomes. Side-effects were mild and transient; there were no incidents of adverse scarring, thermal injuries, permanent nerve injury, or dyschromia, hematomas, seromas, or infection. Subjects were likely to recommend the procedure to a friend.
CONCLUSIONS: In properly selected patients, the ACELIFT proved to be a safe and effective, minimally invasive alternative to a facelift. There was little downtime and high patient satisfaction.
J Drugs Dermatol. 2014;13(9):1038-1046.
Yana Yutskovskaya MD,a Evgenjia Kogan MD,b and Eugene Leshunov MDa
BACKGROUND: Soft-tissue augmentation with fillers is an aesthetic procedure for restoring age-related volume loss.
OBJECTIVE: To compare neocollagenesis and elastin production stimulated by Radiesse® (calcium hydroxylapatite; CaHA, Merz Pharmaceuticals
GmbH) and a hyaluronic acid-based filler (HA; Juvéderm® VOLUMA®).
METHODS: Twenty-four women, aged 35–45, participated in this split-face, comparative study. Punch biopsies were taken 4 and 9
months after supraperiostal injection of each filler into the ipsilateral or contralateral postauricular area. Samples were analyzed for
collagens type I and III, elastin, Ki-67, and inflammatory and angiogenic markers.
RESULTS: At month 4, collagen type III was greater with CaHA vs HA (P=0.0052). By month 9, type I staining was higher with CaHA vs
HA (P=0.0135), whereas type III was lower with CaHA than HA (P=0.0019). Staining for elastin, Ki-67 and angiogenesis was greatest
with CaHA at both timepoints. Inflammatory markers increased most with HA treatment.
CONCLUSIONS: CaHA resulted in more active, physiologic remodeling of the extracellular matrix than HA by stimulating a two-step
process whereby collagen type I gradually replaced type III. Increased elastin stimulated by CaHA also indicates active remodeling.
The results of this study suggest that, in the first 9 months after treatment, by reconstituting tissue homeostasis without inducing
inflammation suggests CaHA has more desirable characteristics for a dermal filler than HA.
J Drugs Dermatol. 2014;13(9):1047-1052.
Veena Rao MD,a Sulene Chi MD PhD,a and Julie Woodward MDa,b
INTRODUCTION: Hyaluronidase (HA) degrades hyaluronic acid, allowing flexibility in the use of hyaluronic acid-based fillers commonly used in facial correction. Potentially differing properties of available hyaluronidases and fillers may influence their interaction, leading to important differences in ultimate cosmetic results. This study examines the physical properties of various fillers after exposure to commonly available hyaluronidases in vitro to better inform their in vivo clinical use.
METHODS: Four commonly used HA fillers were exposed to varying concentrations of Vitrase (ovine testicular hyaluronidase) and Hylenex (human recombinant hyaluronidase) in vitro. The gross properties of these fillers were then observed to evaluate time- and dose-response; photographs were obtained to allow visual comparison at 1 minute and 5 minutes post-exposure.
RESULTS: At a concentration of 0.1 mL Vitrase to 0.2 mL filler, Restylane dissipated most followed by Juvéderm; Belotero most retained its form. Hylenex at the same concentration showed similar results, again affecting Restylane most and Belotero least. Response to treatment with both hyaluronidases increased substantially over time, increasing progressively from exposure to 5 minutes post-exposure. When exposed to Hylenex at 15 U and 30 U to 0.2 mL filler, Belotero retained its form most, followed by Juvéderm, Juvéderm Voluma, and then Restylane. The effects on filler structure increased with 30 U concentration vs 15 U concentration of Hylenex.
DISCUSSION: Available hyaluronidases and HA fillers appear to have differing physical properties that influence their interaction in a time and dose-dependent manner. Knowledge of the ways in which specific fillers interact with different hyaluronidases may help achieve desired cosmesis when aiming to adjust delicate facial fillers.
J Drugs Dermatol. 2014;13(9):1053-1056.
Redaelli Alessio MD,a Berthold Rzany MD ScM,b Linda Eve MD,c Yann Grangier MD,d
Pedro Herranz MD,e Frédérique Olivier-Masveyraud MD,f and Danny Vleggaar MDg
Over the last few years, there have been a number of important changes in how we appreciate and understand the aging face. Volume
loss is now recognized as a major component of facial aging. Treatment options that replace lost volume are increasingly used for
recontouring and rejuvenation of the aging face. In this review we present and discuss the European Expert Group recommendations
on the ideal use of the unique collagen stimulator, poly-L-lactic acid (PLLA, Sculptra®, Sinclair Pharmaceuticals) for facial rejuvenation
lasting up to 25 months. Optimal results are achieved based on a detailed knowledge of facial anatomy, correct treatment procedure,
specifically the right dilution, the correct injection technique, as well as appropriate patient aftercare. PLLA is an effective and safe collagen
stimulator that treats the whole face. PLLA is simple to use, provides the foundation for facial rejuvenation, is easy to combine
with other treatments, and gives long-lasting effects with a high level of patient satisfaction.
J Drugs Dermatol. 2014;13(9):1057-1066.
Thomas M. Proebstle MD PhD,a Gary Chung MS,b Ruth Weissberg MD,c and Tatjana Pavicic MDd
BACKGROUND: A quantitative numerical method for assessing the extent and duration of the inhibitory action of botulinum neurotoxin type A on mimetic muscles would potentially enable more detailed evaluation of the overall efficacy of this aesthetic treatment.
AIM: To evaluate skin displacement analysis (SDA) as a tool for assessment of the extent and duration of effect of incobotulinumtoxinA on mimetic muscles in the glabellar region in routine daily practice.
METHODS: A total dose of 30 U incobotulinumtoxinA was injected into the fronto-glabellar region of 16 subjects. SDA was performed at baseline and during onset and recovery from incobotulinumtoxinA treatment at various timepoints up to 24 weeks after treatment. The reference point for SDA was located at the upper margin of the eyebrow, 30 mm lateral to the median line. To correlate and validate SDA results, semi-quantitative wrinkle score assessments were performed in parallel.
RESULTS: At baseline, the mean horizontal skin displacement was 5.4 mm (standard deviation: ±1.4 mm). During onset of action after treatment, skin displacement values decreased from baseline (100%) by 46%, 85%, and 90% at day 2, week 1, and week 2, respectively. During recovery from incobotulinumtoxinA action, skin displacement values increased to 33%, 50%, and 93% of the baseline value at 6, 12, and 24 weeks after treatment, respectively. The inhibitory effect of incobotulinumtoxinA was highly variable among subjects, ranging from 25% to 68% of the baseline value 12 weeks after treatment. Overall agreement between SDA values and wrinkle scores was good.
CONCLUSION: SDA represents a novel, objective method for the quantitative evaluation of the effect of incobotulinumtoxinA on mimetic muscles underlying the fronto-glabellar region, and showed good correlation with wrinkle score assessments. Both SDA and wrinkle score indicated the persistence of treatment effects 24 weeks after injection.
J Drugs Dermatol. 2014;13(9):1067-1072.
Suzanne Bruce MD,a Jwala Karnik MD,b Laurence Dryer PhD,c and David Burkholder PhDd
BACKGROUND AND OBJECTIVES: The etiology of aging human skin includes intrinsic physiologic changes greatly accelerated by photoaging,
predominantly through exposure to UV light. Consumer interest and demand for anti-aging skin care products is extremely high especially
in light of aging populations. Prenatal (fetal) tissue has been shown to possess healing characteristics and regenerative effects.
A proprietary tissue engineering technology has been developed to produce a soluble human extracellular matrix material with growth
factors and proteins. Neonatal cells are cultured on microbeads under conditions of low oxygen tension. This human cell-conditioned
media (hCCM) contains a variety of growth factors and cytokines similar to those found in fetal cells and has been incorporated into a
topical preparation for use in facial wound healing (after laser resurfacing procedures) and improving the appearance of aging skin. The
objective of this study was to observe the effects of an MRCxTM-containing topical skincare regimen on subjects with demonstrated
aging skin damage (photodamage) when used consistently over a 3 month time period.
METHODS: Female subjects age 35-65 with Fitzpatrick Skin Type I-IV and mild to moderate amounts of photodamage, fine lines, and
wrinkles used Regenica® Replenishing Crème and Regenica® Renew SPF 15 for 3 months. At each visit, photos were taken of subjects
while investigators completed skin grading assessments and subjects completed self-assessments. Investigator assessments
included evaluation of tactile roughness, visual texture, wrinkles, blotchiness, skin tone evenness, radiance, and translucence on a
5-point scale. Subjects’ self-assessments included assessment of fine lines and wrinkles, firmness, evenness of skin tone, brightness,
resilience, clarity, and radiance. Changes from baseline were evaluated for each parameter and P values for changes from baseline to
each study visit for investigator’s assessments and to end-of-study for self-assessments were calculated.
RESULTS: Eighteen of 21 enrolled female subjects completed the study. Three subjects chose to drop from the study. Statistically significant
improvements in investigator assessments of tactile roughness, visual texture, wrinkles, blotchiness, skin tone evenness, radiance
and translucency compared to baseline were observed at weeks 4, 8, and 12 after initiating treatments. Progressive improvement
was seen through the last study visit (visit 5, week 12). Similar statistically significant improvements in subjects’ self-assessments
were seen comparing the first post-baseline visit (visit 2, week 2) to subsequent visits. 93.5 % subjects agreed (somewhat or strongly)
with all of the positive subject assessment statements at week 12. Importantly, 100 % of subjects indicated at the end of the study
that they would recommend the product to a friend and would want to purchase the product. No treatment-related adverse events
were recorded during the study.
CONCLUSIONS: Regenica was safe and clinically effective in reducing anti-aging effects in this group of female subjects aged 35-65 years
as measured by both investigator assessments and subjects’ self-assessments.
J Drugs Dermatol. 2014;13(9):1074-1081.
David M. Pariser MD,a Phoebe Rich MD,b Fran E. Cook-Bolden MD,c and Andrew Korotzer PhDd
OBJECTIVE: To evaluate efficacy, safety, and tolerability of a fixed combination clindamycin phosphate 1.2% and benzoyl peroxide 3.75% (clindamycin-BP 3.75%) aqueous gel in moderate to severe acne vulgaris.
METHODS: A total of 498 patients, 12-40 years of age, were randomized to receive clindamycin-BP 3.75% or vehicle in a double-blind, controlled 12-week, 2-arm study evaluating safety and efficacy using inflammatory and noninflammatory lesion counts, Evaluator Global Severity Scores (EGSS) and subject self-assessment (SSA). In addition, patients completed a patient satisfaction survey (PSS), acne-specific QoL questionnaire, and assessed their facial skin for shininess/oiliness.
RESULTS: Clindamycin-BP 3.75% demonstrated statistical superiority to vehicle in reducing both inflammatory and noninflammatory lesions and acne severity. Clindamycin-BP 3.75% showed greater efficacy relative to vehicle in assessments of skin oiliness, SSA and PSS. No substantive differences were seen in cutaneous tolerability among treatment groups and no patients discontinued treatment with Clindamycin-BP 3.75% because of adverse events.
LIMITATIONS: Data from controlled studies may differ from clinical practice. It is not possible to determine the contributions from the individual active ingredients.
CONCLUSIONS: Clindamycin-BP 3.75% provides statistically significant greater efficacy than vehicle with a favorable safety and tolerability profile.
J Drugs Dermatol. 2014;13(9):1083-1089.
Patrícia M.B.G. Maia Campos PhD, Mirela D.Gianeti PhD, Daiane G. Mercurio ScM, and Lorena R. Gaspar PhD
This study aimed to evaluate the effects of cosmetic formulations containing green tea (GT) and/or Ginkgo biloba (GB) extracts by preclinical
and clinical studies. For the preclinical study, histological analysis was performed after 5 day-period of formulations application on the
dorsum of hairless mice. For the clinical study, the formulations were applied on the forearm skin of 48 volunteers, and assessed before
and after 3 hours and after a 15 and 30 day-period of application. Histological analysis showed that the formulation with GT (FGT) and the
association of GT and GB (FBlend) significantly enhanced viable epidermis thickness and the number of cell layers, suggesting a moisturizing
effect in skin deeper layers and increased cell renewal. The clinical efficacy studies showed that the extracts had a moisturizing
effect and improved skin microrelief. In addition they synergistically acted on the skin elasticity and skin barrier function. In conclusion,
the formulation containing a combination of green tea and Ginkgo biloba extracts effectively improved skin conditions and the effect
of formulation FBlend on the improvement of skin elasticity was more pronounced. Finally, the results of the present study revealed
other important clinical benefits of Ginkgo biloba and green tea extracts on the skin besides their already known antioxidant action.
J Drugs Dermatol. 2014;13(9):1092-1097.
Laura Jordan OMS4 MS MA MLS,a Sarah Malerich DO,b Summer Moon DO,c James Spencer MDd
Skin cancer is the most commonly diagnosed cancer in the United States. A number of UV protection programs have been developed and initiated both globally and domestically, and this article will review and assess the effectiveness of each of these programs. The programs reviewed in this article target grade school aged children, as this is a time when adult health behaviors are being formed. Among these programs, multiunit programs were more effective at changing behavior as they were given over a longer period of time with more frequent interventions and included various learning techniques.
J Drugs Dermatol. 2014;13(9):1099-1103.
Staci Brandt PA-C MBA MS,a Matthew H. Meckfessel PhD,a and Peter A. Lio MDb
Atopic dermatitis is a common skin disease characterized by eczematous eruptions and impaired skin barrier function. Patients,
as well as their families, frequently report reductions in quality of life. Pruritus, lack of sleep, and impaired social functioning
all contribute to this reduction. A skincare regimen of gentle cleansing and daily moisturization is integral to managing atopic
dermatitis. While there are a multitude of reports supporting the use of moisturizers, there is a paucity regarding the use of
cleansers, especially cleansers formulated with ingredients known to improve skin hydration. A clinical study was conducted to
assess the tolerability and cosmetic acceptability of a body wash formulated with the filaggrin break-down products arginine and
pyrrolidone carboxylic acid in subjects with atopic dermatitis-prone skin (Cetaphil® RestoraDerm® Body Wash). The results of this
study indicate that Cetaphil RestoraDerm Body Wash was well tolerated, reduced itch, improved quality of life, and was well-liked
by subjects with atopic dermatitis-prone skin.
J Drugs Dermatol. 2014;13(9):1108-1111.
David McDaniel MD,a Robert Weiss MD,b Margaret Weiss MD,b Chris Mazur BS,a and Charmaine Griffin CCRPa
Multiple devices are currently on the market that employ radiofrequency to non-invasively treat skin laxity and wrinkle reduction. The study device was a unique monopolar radiofrequency device FDA cleared for the treatment of wrinkles and rhytids. The delivery system allows constant monitoring of the real-time local skin impedance changes, which allows radiofrequency energy to be more uniformly dosed over an entire treatment area.
OBJECTIVE: The objective was to validate effectiveness of a modified treatment protocol for a unique monopolar radiofrequency device, which has been engineered with greater power and self-monitoring circuitry.
METHODS: Twenty-four female subjects received bilateral monopolar radiofrequency treatments to the mid and lower face from the sub malar region to the submentum. Subjects completed 1 and 3 month follow ups with digital imaging. Skin biopsies (on 4 subjects) and ultrasound measurements (on 12 subjects) were completed.
RESULTS: Assessments demonstrated a reduction in skin laxity of 35%, a reduction in fine lines/wrinkles of 42%, and a reduction in the appearance of global photodamage of 33%. Expert photograding demonstrated 92% of subjects showing at least a mild improvement in skin laxity at three months post treatment. 50MHz ultrasound measurements in 12 subjects showed an increase of 19% in skin density. Histology showed a marked increase in dermal collagen and elastin fibers in two subjects who demonstrated a clinically noticeable reduction in skin laxity and minimal changes in two subjects who demonstrated minimal clinical improvements. There were no significant adverse events reported.
CONCLUSION: This modified radiofrequency device and treatment protocol was well tolerated and produced improvements in the appearance of skin laxity and overall anti-aging effects in the majority of subjects. Objective measurements including ultrasound and histology help explain the clinical outcome.
J Drugs Dermatol. 2014;13(9):1112-1117.
Anh N. Tran MSa,b and John Y. Koo MDa
The eutectic mixture of lidocaine and prilocaine (EMLA, APP Pharmaceuticals, LLC.) is an anesthetic cream frequently used by dermatologists.
Although side effects of EMLA are usually mild local skin reactions (ie, edema, pallor, erythema), more severe complications
can be encountered including methemoglobinemia, central nervous system toxicity, and cardiotoxicity. This article reviewed
the literature regarding risk of systemic toxicity associated with use of EMLA in the pediatric and adult population. All 12 clinical trials
evaluating the safety of EMLA in either the pediatric or adult population generally followed dosing and administration guidelines set
by the manufacturer and reported clinically insignificant plasma levels of methemoglobin, lidocaine, prilocaine, and their respective
metabolites. To date, nine pediatric cases and three adult cases of systemic toxicity associated with EMLA have been published.
Possible factors that contributed to the development of systemic toxicity include excessive amount of EMLA, large application area,
prolonged application time, diseased and/or inflamed skin (eg, vascular malformations, molluscum contagiosum, eczema, previously
abraded skin), age less than 3 months, prematurity, and concomitant use of a methemoglobin-inducing agent. Recommendations
are provided on how to safely use EMLA to minimize the risk of systemic toxicity.
J Drugs Dermatol. 2014;13(9):1118-1122.
Mirna E. Toledo-Bahena MD,a Alicia Bucko DO JD,b Jorge Ocampo-Candiani MD,c Maira E. Herz-Ruelas MD,c
Terry M. Jones MD,d Michael T. Jarratt MD,e Richard A. Pollak DPM MS,f Lee T. Zane MDg
OBJECTIVE: To assess the potential efficacy, safety, and optimal dosing concentration of tavaborole, a novel, boron-based pharmaceutical agent with broad-spectrum antifungal activity, for the treatment of onychomycosis of the toenail due to dermatophytes.
METHODS: One double-blind, randomized, vehicle-controlled study (study 1) and two open-label studies (studies 2 and 3) examined the efficacy, safety, and optimal dosing concentration of tavaborole topical solution applied once daily or three times weekly for 180 days at concentrations of 1.0%, 2.5%, 5.0%, or 7.5%. Patient cohort 3 of study 2 received open-label tavaborole 5.0% once daily for 360 days. All three studies assessed day 180 treatment success, defined as complete or partial clinical evidence of clear nail growth plus negative fungal culture.
RESULTS: A total of 336 patients were included in the intent-to-treat (ITT) or modified ITT populations and efficacy analyses across the 3 studies. In study 1, treatment success rates at day 180 were higher with tavaborole 2.5%, 5.0%, and 7.5% vs vehicle (27%, 26%, and 32% vs 14%, respectively; slope P=0.030). In cohort 3 of study 2, 7% of patients achieved treatment success with tavaborole 5.0% at day 360. Negative culture rates at day 180 in study 1 were numerically higher for tavaborole 2.5%, 5.0%, and 7.5% vs vehicle (slope P=0.046). Application-site reactions of general irritation, erythema, scaling, and stinging/burning were most common with tavaborole 7.5%, were generally mild to moderate, and resolved with treatment discontinuation and/or a reduction in dosing frequency. No systemic safety concerns were observed.
CONCLUSION: Tavaborole solution demonstrated favorable efficacy and safety in phase 2 clinical studies. Based on these findings, tavaborole
topical solution, 5% was further investigated in larger, more definitive phase 3 studies. Results from these completed phase
3 studies will provide additional evidence regarding the safety and efficacy of tavaborole in the treatment of toenail onychomycosis.
J Drugs Dermatol. 2014;13(9):1124-1132.
Robert A. Weiss MD FAAD FACPh and Margaret A. Weiss MD
BACKGROUND / OBJECTIVE: This study investigates the efficacy, tolerance, and usability of a single product containing cycloastragenol,
growth factors, peptides, and antioxidants to decrease the visible signs of aging, including fine lines, and wrinkles, texture, pore size,
elasticity, skin color/clarity, redness, hydration, and overall skin quality.
METHODS: Twenty subjects were enrolled in a 12-week, open-label, patient-assessment study. Subjects used a gentle cleanser,
cycloastragenol, growth factors, peptides, and antioxidants (Regeneration Booster™, Jan Marini Skin Research (San Jose, CA) and
a broad spectrum SPF for the duration of the 12-week study. Assessments were taken at baseline, 2, 4, 8, and 12 weeks. All assessments
were compared against baseline for statistical significance.
RESULTS: Eighteen of the twenty subjects completed the 12-week study. Improvement was significant after just 2 weeks of use for
all measured categories except erythema and significant for all categories at 12 weeks. One hundred percent of study subjects noted
improvement in at least 3 or more of the 8 assessed categories with an average improvement in 6.7 categories. Improvement response
rate for individual categories ranged from 67% to 100% of study subjects. There were zero cases of sensitivity or irritation and product
smell, feel and ease of application were rated “positive” by 100% of study subjects. Photographic improvement was most notable in
texture and lines on the cheeks and eye area.
CONCLUSION: Regeneration Booster, when used as a stand–alone anti-aging solution, delivers rapid and significant reduction in the
visible signs of aging. Subject satisfaction was extremely high and there were zero reported cases of sensitivity or irritation. Based
on these observations, Regeneration Booster is a safe and effective topical product for individuals seeking significant improvement
in the appearance of aging skin.
J Drugs Dermatol. 2014;13(9):1135-1139.