Effectiveness and Safety of a New Hyaluronic Acid Injectable for Augmentation and Correction of Chin Retrusion.

BACKGROUND: A hyaluronic acid (HA) filler intended for non-surgical improvement of chin appearance should ideally be of high strength/firmness (high G') to allow for deep injections on the bone. HASHA (Restylane Shaype) is a new hyaluronic acid (HA) injectable with high G' and high HA concentration (25 mg/mL), engineered by the new NASHA-HD (High Definition) technology. HASHA is suitable to be placed periosteally, aiming to mimic the natural shape of the bony chin. This pivotal clinical investigation evaluated effectiveness and safety of HASHA for augmentation and correction of chin retrusion.  Methods: Subjects 18 years or older with mild or moderate chin retrusion by the Galderma Chin Retrusion Scale (GCRS), were randomized 3:1 to HASHA (n=103) or no treatment (n=37). Assessments included GCRS (blinded evaluator), aesthetic improvement (Global Aesthetic Improvement Scale [GAIS]), subject satisfaction, and safety.  Results: GCRS responder rate (1-grade or greater improvement from baseline) was significantly higher for HASHA (83.3%) versus controls (10.8%) at month 3 (P<0.001) and maintained through month 12 (P<0.001). Aesthetic improvement was high throughout the study in the HASHA group, according to investigators (97% or greater) and subjects (89% or greater). Overall, subject satisfaction was high at month 3 and maintained at month 12. Product- or injection-related adverse events were mostly mild or moderate and transient. No product- or injection-related serious adverse events were reported. CONCLUSIONS: HASHA, a new NASHA-HD injectable with extra strength/firmness, was safe and effective for chin augmentation and correction of chin retrusion, with high aesthetic improvement and subject satisfaction throughout 12 months. J Drugs Dermatol. 2024;23(4):255-261.     doi:10.36849/JDD.8145.

Update on Blindness From Filler: Review of Prognostic Factors, Management Approaches, and a Century of Published Cases.

BACKGROUND: Vision loss secondary to aesthetic filler treatment is a rare but disastrous complication. OBJECTIVES: The aim was to update the published cases of blindness after filler injection that have occurred since our group published reviews of 98 cases in 2015 and an additional 48 cases in 2019. METHODS: A literature review was performed to identify all cases of visual complications caused by filler injection published between September 2018 and March 2023. The cases were analyzed independently and in combination with previously reviewed cases. Analyses are based on the number of cases with data available. RESULTS: 365 new cases of partial or complete vision loss after filler injection were identified. The sites that were highest risk were the nose (40.6%), forehead (27.7%), and glabella (19.0%). The filler injected was hyaluronic acid in 79.6% of cases. The most common associated signs were ptosis (56.2%), ophthalmoplegia (44.1%), pain (31.2%), and skin changes (73.2%). Stroke-like features were seen in 19.2% of cases. Of the cases reporting visual outcomes (318), 6.0% experienced complete vision recovery, 25.8% had partial improvement in visual acuity, and 68.2% had no vision recovery. Partially preserved visual acuity at onset was a significant predictor of visual improvement (p < .001). The three most common treatments were subcutaneous hyaluronidase at or near the filler site (70.1%), systemic steroids (57.3%), and intra-arterial thrombolytic therapy (56.0%). No treatments were significantly associated with visual improvement (p > .05). CONCLUSIONS: Although blindness and stroke from fillers is a rare complication, practitioners who inject filler should have a thorough knowledge of prevention and management strategies.

Immunogenicity of DaxibotulinumtoxinA for Injection in Glabellar Lines.

DaxibotulinumtoxinA-lanm for injection (DAXI), a novel botulinum toxin type A formulation, contains a purified 150-kD core neurotoxin (daxibotulinumtoxinA) and proprietary stabilizing peptide (RTP004), and is approved for glabellar line treatment. As with any biologic product, DAXI may potentially be immunogenic and elicit unwanted antibody formation, possibly resulting in partial or complete treatment failure. The immunogenicity of DAXI was assessed in 2 double-blind, placebo-controlled, single-dose studies and an open-label safety study of up to 3 repeat treatments. Of the 2737 evaluable patients, none developed neutralizing antibodies to daxibotulinumtoxinA and 0.8% developed treatment-related nonneutralizing anti-daxibotulinumtoxinA-binding antibodies. Of evaluable patients exposed to RTP004 with either DAXI or placebo, 1.3% developed treatment-related anti-RTP004-binding antibodies, which were mostly transient. No patient developed binding antibodies to both daxibotulinumtoxinA and RTP004. All patients with treatment-related binding antibodies to daxibotulinumtoxinA or RTP004 achieved a clinical response (none or mild glabellar line severity) at Week 4 following each DAXI treatment cycle. The duration of clinical response was not different between treatment cycles when antibodies were detected vs when they were absent. Although the analysis population was small compared to the number of patients likely to receive repeated treatment in clinical practice, these results suggest that DAXI administration at the approved glabellar lines dose has low immunogenic potential and that nonneutralizing antibodies to daxibotulinumtoxinA or RTP004 occur infrequently and often transiently, and have no impact on clinical efficacy, safety, or duration of action. Real-world data encompassing larger numbers of patients is needed to substantiate these results.

Clinical Immunogenicity of DaxibotulinumtoxinA for Injection in Glabellar Lines: Pooled Data from the SAKURA Phase 3 Trials.

DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin type A product containing daxibotulinumtoxinA with a stabilizing excipient peptide (RTP004). DAXI immunogenicity was assessed in three phase 3 glabellar line studies (two placebo-controlled, single-dose studies and an open-label repeat-dose safety study). Binding antibodies to daxibotulinumtoxinA and RTP004 were detected by validated ELISAs. Samples positive for daxibotulinumtoxinA-binding antibodies were evaluated further for titer and neutralizing antibodies by mouse protection assay. Overall, 2786 subjects received DAXI and 2823 subjects were exposed to RTP004 as DAXI (n = 2786) or placebo (n = 37). Treatment-related anti-daxibotulinumtoxinA binding antibodies were detected in 21 of 2737 evaluable subjects (0.8%). No subject developed neutralizing antibodies. Treatment-related anti-RTP004 binding antibodies were detected in 35 (1.3%) of 2772 evaluable subjects. Binding antibodies were generally transient, of low titer (<1:200), and no subject had binding antibodies to both daxibotulinumtoxinA and RTP004. All subjects with treatment-induced binding antibodies to daxibotulinumtoxinA or RTP004 achieved none or mild glabellar line severity at Week 4 following each DAXI cycle, indicating no impact on DAXI efficacy. No subjects with binding antibodies to daxibotulinumtoxinA or RTP004 reported immune-related adverse events. This evaluation of anti-drug antibody formation with DAXI shows low rates of antibody formation to both daxibotulinumtoxinA and RTP004.

Treatment of Upper Facial Lines With DaxibotulinumtoxinA for Injection: Results From an Open-Label Phase 2 Study.

BACKGROUND: Simultaneous treatment of moderate-to-severe upper facial lines is reflective of real-world clinical practice. OBJECTIVE: To evaluate the efficacy and safety of daxibotulinumtoxinA-lanm for injection (DAXI) for simultaneous treatment of glabellar, forehead, and lateral canthal (LC) lines. METHODS: In this open-label, single-arm Phase 2 study, patients (48 enrolled, 94% completed, follow-up 24-36 weeks) received DAXI 40U (glabellar), 32U (forehead), and 48U (LC) lines. Key efficacy endpoints: percentages of patients achieving none/mild wrinkle severity (investigator-rated) for each upper facial line scale at Week 4. RESULTS: At Week 4, most patients achieved none/mild wrinkle severity (investigator-rated): glabellar (96%), forehead (96%), and LC (92%). Median times to loss of none/mild response (investigator- and patient-rated) among all patients were: 24.6 (glabellar), 20.9 (forehead), and 24.9 (LC) weeks; and 25.0, 24.0, and 28.1 weeks, respectively, among Week-4 responders. At Week 4, most patients reported improvements (Global Aesthetic Improvement Scale: 96%-98%) and high satisfaction rates (85%-98%). Five patients experienced treatment-related adverse events: injection-site erythema (3 patients/7 events), facial discomfort (2 patients/2 events), and headache (1 patient/1 event). No patients experienced eyebrow or eyelid ptosis. CONCLUSION: Simultaneous treatment of upper facial lines with DAXI was well tolerated and demonstrated high response rates, extended duration, and high patient satisfaction. CLINICAL TRIAL REGISTRY: https://clinicaltrials.gov/ct2/show/NCT04259086.

Hyaluronidase for Treating Complications Related to HA Fillers: A National Plastic Surgeon Survey.

Background: Hyaluronic acid (HA) fillers have become a popular modality to address changes in the ageing face. There are many described indications of hyaluronidases in aesthetic medicine which include their use in the management of HA-associated complications. To better understand the current practice patterns, we surveyed Canadian plastic surgeons on their use of hyaluronidases. Methods: With the approval of the Canadian Society of Plastic Surgeons, an electronic survey was emailed to members. A total of 350 surveys were distributed and 98 surveys were completed for a response rate of 28%. Results: Approximately half (48%) of the survey respondents used HA fillers in their practice. Skin testing for hypersensitivity reactions was performed by less than 10% of hyaluronidase users. Nearly all respondents used hyaluronidase for filler over-correction (95.5%) and asymmetry (86.4%). Over half of the respondents have used hyaluronidase for inflammatory or infectious nodules and the Tyndall effect. Other reported applications included restoration of vascular compromise, and one respondent reported using hyaluronidase for assisting with haematoma resolution. When compared with the most recent guidelines, there was a wide range of doses used for common side effects and complications. Twenty-four percent of the respondents reported that their hyaluronidase formulation was prepared by a compounding pharmacy, and 20% of respondents who inject HA fillers did not stock hyaluronidase. Conclusion: There are many indications for hyaluronidase in aesthetic plastic surgery. Plastic surgeons should stock hyaluronidase and develop a specific plan in anticipation of adverse events. Although hyaluronidase is commonly used by plastic surgeons for over-correction and asymmetry, the dosages used in aesthetic practice is rather diverse and heterogeneous. When possible, plastic surgeons should perform allergy testing before hyaluronidase use.

Historique: Les agents de comblement à base d'acide hyaluronique (AH) sont devenus populaires pour modifier la face vieillissante. De nombreuses indications sont décrites pour utiliser les hyaluronidases en médecine esthétique, y compris pour la prise en charge des complications liées à l'AH. Pour mieux comprendre les modes de pratique actuels, les chercheurs ont sondé les plasticiens canadiens pour connaître leur utilisation d'hyaluronidases. Méthodologie: Avec l'approbation de la Société canadienne des chirurgiens plasticiens, les membres ont reçu un sondage électronique par courriel. Au total, 350 sondages ont été distribués, et 98 ont été remplis, pour un taux de réponse de 28 %. Résultats: Environ la moitié des répondants au sondage (48 %) utilisent les agents de comblement à base d'AH dans leur pratique. Moins de 10 % d'entre eux effectuaient des tests d'hypersensibilité cutanée. Presque tous les répondants se servaient de l'hyaluronidase pour corriger les surcorrections (95,5 %) et l'asymétrie (86,4 %). Plus de la moitié utilisent l'hyaluronidase pour les nodules inflammatoires ou infectieux et l'effet Tyndall. La restauration d'une atteinte vasculaire était une autre application, et un répondant a déclaré y recourir pour contribuer à la résolution des hématomes. Par rapport aux directives les plus récentes, les doses utilisées étaient très variables pour les effets secondaires et les complications. Ainsi, 24 % des répondants ont déclaré qu'ils obtenaient leur formulation d'hyaluronidase par des préparations magistrales, et 20 % des répondants qui injectent les agents de comblement à base d'AH n'en conservaient pas en stock. Conclusion: Il y a de nombreuses indications pour utiliser l'hyaluronidase en chirurgie plastique. Les plasticiens devraient conserver des provisions d'hyaluronidase et se doter d'un plan détaillé en cas d'événements indésirables. L'hyaluronidase est souvent utilisée par les plasticiens pour corriger les surcorrections et l'asymétrie, mais les dosages utilisés en esthétique sont plutôt diversifiés et hétérogènes. Dans la mesure du possible, les plasticiens devraient effectuer des tests d'allergie avant d'utiliser l'hyaluronidase.

Submental Area Treatment with ATX-101: Relationship of Mechanism of Action, Tissue Response, and Efficacy.

ATX-101 is an injectable, synthetically derived formulation of deoxycholic acid used for submental fat reduction. Methods: A narrative review of references relevant to the mechanism of action of ATX-101 and its relationship to efficacy and inflammatory adverse events was conducted. Results: When injected into subcutaneous fat, deoxycholic acid physically disrupts adipocyte cell membranes, leading to local adipocytolysis, cell death, and a mild, local inflammatory reaction consisting of macrophage infiltration and fibroblast recruitment. At Day 28 postinjection, inflammation largely resolves, and key histologic features include fibrotic septal thickening, neovascularization, and atrophy of fat lobules. Based on the mechanism of action of ATX-101 and the demonstrated inflammatory response, localized inflammation and swelling are expected following treatment. Indeed, postinjection swelling and other local injection-site events, including pain, erythema, and bruising, are common during and after treatment. Because of inflammatory sequelae following injection, reduction in submental fat is gradual and may require months before the full response is apparent. Patients may also require multiple treatment sessions to achieve their treatment goals. Repeated treatments may result in less pain and swelling over time owing to a combination of factors, including less target tissue allowing for lower doses/injection volumes, persistent numbness, and greater tissue integrity from thickened fibrous septa. Conclusions: Physicians can manage expectations by counseling patients that, based on the mechanism of action of ATX-101 and data from pivotal clinical trials, ATX-101 treatment results in localized inflammation/swelling and gradual submental fat reduction. Patient education about common local adverse events is critical.

The impact of COVD-19 on North American dermatology practices.

COVID-19 continues to affect the delivery of healthcare services, as practices across North America gradually re-open with new safety measures and practice guidelines. Specifically in dermatology, clinical care is delivered in close physician-patient proximity through physical examination and the use of additional diagnostic and therapeutic procedures. We designed a 10-question survey to better understand how COVID-19 has impacted the delivery of care in North American dermatology practices. Survey questions explored themes including changes in patient volumes, the use of virtual visits/teledermatology, the frequency of aesthetic and surgical procedures, and other related topics. We invited 102 board-certified dermatologists working in a variety of medical, aesthetic, surgical, and mixed practices, to participate in our survey hosted through Qualtrics XM. These dermatologists were selected based on their geographic location and our ability to access their contact information. Each dermatologist received an individualized e-mail and survey link; however, all survey responses were anonymized. In 2.5 weeks after survey invitations were sent, the survey was viewed and completed by 71 and 54 dermatologists, respectively. The second wave of e-mails was sent to the remaining 48 dermatologists who had not yet completed the survey, after which 15 participants both viewed and completed the survey. In total, 69 responses were recorded with an overall response rate of 67.6%. We report decreased patient volume capacity, fewer aesthetic and surgical procedures, and an increase in the use of virtual medicine among board-certified North American dermatologists. However, this represents a reflection on perspectives at a single time point in a rapidly evolving situation. Understanding the full scope of the impact that COVID-19 continues to have on dermatologic care is paramount to effectively serve our patients.

Clinical Relevance of Elastin in the Structure and Function of Skin.

Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors. With advancing age and exposure to environmental insults, elastic fibers degrade. This degradation contributes to the loss of the skin's structural integrity; combined with subcutaneous fat loss, this results in looser, sagging skin, causing undesirable changes in appearance. The most dramatic changes occur in chronically sun-exposed skin, which displays sharply altered amounts and arrangements of cutaneous elastic fibers, decreased fine elastic fibers in the superficial dermis connecting to the epidermis, and replacement of the normal collagen-rich superficial dermis with abnormal clumps of solar elastosis material. Disruption of elastic fiber networks also leads to undesirable characteristics in wound healing, and the worsening structure and appearance of scars and stretch marks. Identifying ways to replenish elastin and elastic fibers should improve the skin's appearance, texture, resiliency, and wound-healing capabilities. However, few therapies are capable of repairing elastic fibers or substantially reorganizing the elastin/microfibril network. This review describes the clinical relevance of elastin in the context of the structure and function of healthy and aging skin, wound healing, and scars and introduces new approaches being developed to target elastin production and elastic fiber formation.

Defining Skin Quality: Clinical Relevance, Terminology, and Assessment.

BACKGROUND: Flawless skin is one of the most universally desired features, and demand for improvements in skin quality is growing rapidly. Skin quality has been shown to substantially impact emotional health, quality of life, self-perception, and interactions with others. Although skin quality improvements are a common end point in studies of cosmeceuticals, they are rarely assessed in clinical studies of other aesthetic treatments and products. Descriptive terminology for skin quality parameters also varies considerably within the aesthetic field, relying on a range of redundant and occasionally contradictory descriptors. In short, skin quality has not been clearly defined. OBJECTIVE: The goal of this review is to highlight the importance of skin quality to patients and physicians, explore known and unknown factors comprising skin quality, and provide clarity regarding terminology, descriptors, and evaluation tools for assessing skin quality. MATERIALS AND METHODS: A review of the literature on skin quality was performed without limitation on publication date. Relevant articles are presented. RESULTS AND CONCLUSION: We propose a framework of attributes contributing to skin quality rooted in 3 fundamental categories-visible, mechanical, and topographical-with the aim to provide information to help guide clinicians and inform future clinical studies.

89% Vichy mineralizing water with hyaluronic acid is a well-tolerated adjunct treatment that helps restore skin barrier function in dry skin-related inflammatory dermatoses and post-procedure skin care: A Canadian study.

INTRODUCTION: Minéral 89 (M89), comprised of 89% Vichy mineralizing water and hyaluronic acid, has been formulated to help strengthen and restore skin barrier. AIM: Assess tolerance and efficacy of M89 in post-esthetic procedures and dry skin-related facial dermatoses. METHOD: Adults post-esthetic procedure or presenting with inflammatory dermatoses (47 subjects; mean age 40.9 ± 13.2 years; any Fitzpatrick or skin phototype), applied M89 for 4 weeks, once or twice daily, as an adjuvant treatment. Information on clinical signs and subject-reported symptoms, skin characteristics, tolerance, and subject and investigator satisfaction were collected. RESULTS: Following 4 weeks of M89 use, significant decreases with complete resolution of erythema (27.6%), desquamation (29.8%), irritation (32%), and skin dehydration (35.8%), as compared to baseline signs and symptoms, were observed. Overall grading improvements for erythema (84.8%; p < 0.001), desquamation (91.7%; %; p < 0.003), irritation (91.7%; %; p < 0.015), and skin hydration (46.2%; p < 0.015) were noted. There was no significant improvement in papules and pustules. Evaluation of subjective signs demonstrated significant decreases in skin sensations such as burning (-73%; p < 0.0001), itching (-71%; p < 0.0001), stinging-tingling (-66.7%; p < 0.0001), as well as in skin dryness (-60%; p < 0.0001). M89 texture was rated very pleasant by 90% of patients. Investigators assessed M89 tolerance to be either good or very good (93%), and satisfactory or highly satisfactory impact on patient's skin (91.5%). CONCLUSION: M89 is a highly tolerable adjuvant treatment that significantly improved clinical signs and symptoms related to a compromised skin barrier in various facial dermatoses and post-aesthetic procedures.

Improvements in Submental Contour up to 3 Years After ATX-101: Efficacy and Safety Follow-Up of the Phase 3 REFINE Trials.

BACKGROUND: ATX-101 (deoxycholic acid) significantly reduced submental fat (SMF) severity in two 24-week Phase 3 studies (REFINE-1 and REFINE-2). OBJECTIVES: The aim of this study was to evaluate the durability of effect and long-term safety of ATX-101. METHODS: REFINE study patients who maintained ≥1-grade improvement on the Clinician-Reported SMF Rating Scale (CR-1 responders) 12 weeks after their last REFINE treatment were eligible for enrollment in this multicenter, double-blind, nontreatment, long-term, follow-up study (NCT02163902). The primary endpoint was CR-1 response at Years 1, 2, and 3. Patient-reported satisfaction, psychological impact, and adverse events were monitored. RESULTS: In total, 224 patients (ATX-101, n = 113; placebo, n = 111) were enrolled. Maintenance of CR-1 response was significantly better in the ATX-101 group than in the placebo group at Year 1 (86.4% vs 56.8%; P < 0.001), Year 2 (90.6% vs 73.8%; P = 0.014), and Year 3 (82.4% vs 65.0%; P = 0.03). Most (74%) ATX-101‒treated patients satisfied at 12 weeks remained satisfied at Year 3. Significant reductions from baseline in psychological impact scores were sustained through Year 3 (P < 0.001). No new treatment-related adverse events were reported. CONCLUSIONS: Improvements in submental contour achieved with ATX-101 are maintained for 3 years in most patients. No new safety signals emerged.