"Filler-Associated Acute Stroke Syndrome": Classification, Predictive Modelling of Hyaluronidase Efficacy, and Updated Case Review on Neurological and Visual Complications.

INTRODUCTION: The rising use of soft tissue fillers for aesthetic procedures has seen an increase in complications, including vascular occlusions and neurological symptoms that resemble stroke. This study synthesizes information on central nervous system (CNS) complications post-filler injections and evaluates the effectiveness of hyaluronidase (HYAL) treatment. METHODS: A thorough search of multiple databases, including PubMed, EMBASE, Scopus, Web of Science, Google Scholar, and Cochrane, focused on publications from January 2014 to January 2024. Criteria for inclusion covered reviews and case reports that documented CNS complications related to soft tissue fillers. Advanced statistical and computational techniques, including logistic regression, machine learning, and Bayesian analysis, were utilized to dissect the factors influencing therapeutic outcomes. RESULTS: The analysis integrated findings from 20 reviews and systematic analyses, with 379 cases reported since 2018. Hyaluronic acid (HA) was the most commonly used filler, particularly in nasal region injections. The average age of patients was 38, with a notable increase in case reports in 2020. Initial presentation data revealed that 60.9% of patients experienced no light perception, while ptosis and ophthalmoplegia were present in 54.3 and 42.7% of cases, respectively. The statistical and machine learning analyses did not establish a significant linkage between the HYAL dosage and patient recovery; however, the injection site emerged as a critical determinant. CONCLUSION: The study concludes that HYAL treatment, while vital for managing complications, varies in effectiveness based on the injection site and the timing of administration. The non-Newtonian characteristics of HA fillers may also affect the incidence of complications. The findings advocate for tailored treatment strategies incorporating individual patient variables, emphasizing prompt and precise intervention to mitigate the adverse effects of soft tissue fillers. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Photoaging and cosmeceutical solutions in sun-overexposed countries: The experience of Australia and Brazil.

Skin aging is the result of physiological changes determined by genetically driven processes and intrinsic factors, and exacerbated by a combination of multiple environmental factors, the main one being sun exposure. The effects of photoaging are particularly apparent on the face, where the appearance of aging signs can have a significant impact on the emotions conveyed and well-being. Photoprotection and facial skin care for managing photoaging signs are thus of particular importance for both physical and mental health. Countries, like Australia and Brazil, where the level of sun exposure is high and the populations have predominantly outdoor lifestyles, are particularly aware of the harms of photoaging and have implemented several measures to help reduce the risk of skin cancer in their populations. However, sun-seeking behaviours are difficult to change, and it takes time before interventions provide perceptible results. Australia still has some of the highest skin cancer incidence and mortality rates in the world. Solutions that target individuals can also be used for minimizing the clinical signs of facial aging and for improving skin quality, with the ultimate aim being not only to improve the appearance of the skin but also to mitigate the occurrence of pre-malignant and malignant lesions. This review summarizes the features of facial skin photoaging in photo-exposed populations, based on evidence gained from studies of Australian individuals, and discusses the various available solutions for skin photoaging, in particular those that are most popular in Brazil, which is a country with many years of experience in managing photoaged skin.

A review of the topical management of acne and its associated sequelae in the Asia-Pacific region with a spotlight on trifarotene.

Acne, a highly prevalent skin disease, can be particularly bothersome for patients of Asian background because of its impact on self-confidence and social interactions. In addition to active acne lesions, some patients may develop sequelae such as scarring, macular/postinflammatory hyperpigmentation, or erythema. The tendency of Asian skin to develop sequelae because of its increased susceptibility to irritation, cultural preferences for lighter skin phototypes, and differences in skincare regimens may all contribute to the increased burden of acne. Moreover, many Asia-Pacific countries do not have their own guidelines for acne management, and those that do often have no schedule in place for regular updates. In this article, we provide a critical review of the published guidance for the management of acne and its sequelae in the Asia-Pacific region, identifying gaps in current recommendations that could be addressed to enhance standards of acne care in Asia-Pacific countries. Along with highlighting the importance of a comprehensive skincare regimen to increase treatment efficacy and adherence, we discuss topical retinoids and retinoid combination options in the acne armamentarium that may be beneficial for sequelae prevention and management, such as adapalene 0.3% ± benzoyl peroxide 2.5%, tretinoin 0.05%, tazarotene 0.1%, and trifarotene 0.005%. In particular, trifarotene 0.005% has been observed to significantly reduce acne scar counts in a Phase 4 study. The recent data highlight the need to establish up-to-date guidance for acne and acne sequelae management in Asia-Pacific countries to provide optimal care to Asian patients.

Quantifiable Changes in the Submental Area and Mandible Border After Dual-Modality Treatment With ATX-101 and VYC-20L for Overall Improvement in Jawline Contour.

BACKGROUND: A phase 4, prospective, open-label, multicenter study showed that treatment with deoxycholic acid injections (ATX-10) followed by a hyaluronic acid filler (VYC-20L) is safe and effective for reducing submental fullness and improving jawline definition. OBJECTIVE: To quantify changes in the jawline and submental area using 3-dimensional (3D) photogrammetry and conduct an immunohistochemical analysis of submental tissue.  Methods: Participants received 1 to 6 ATX-101 treatments (8 weeks apart) followed by VYC-20L (optional touch-up after 14 days). Changes from baseline in jawline and submental volumes, submental major and minor strain events, submental skin displacement, and submental angles were quantified using photogrammetry. Submental skin biopsies (N=13) were excised for histologic analysis. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: Fifty-three participants were treated. From baseline to the final study visit, the mean volume increased for the jawline and decreased for the submental area. There was a larger percentage change from baseline in the minor versus major strain event, indicating greater skin surface compression than expansion within the submental area. Mean change from baseline in submental skin position indicated superior and posterior movement from a lateral perspective, while the mean submental angle decreased between baseline and exit. Collagen I and III expression significantly increased from baseline (P<0.05). All participants reported at least 1 TEAE; the majority were mild or moderate in severity. CONCLUSIONS: Dual-modality treatment with ATX-101 and VYC-20L reduces submental fat and improves jawline definition with quantifiable changes in jawline volume, submental volume, strain, skin displacement, and angle, as well as collagen expression. J Drugs Dermatol. 2024;23(1):1325-1331.        doi:10.36849/JDD.7458.

An absence of imperfections: A proposed framework for defining, assessing, and achieving skin glow.

BACKGROUND: Skin glow is a subcomponent of skin quality. It has become entrenched in the cosmeceuticals and aesthetics lexicons as a synonym for health and youth, but is not well-defined as a scientific metric. AIMS: To examine the concept of skin glow and determine if it is an objective concept that can be defined and quantified. METHODS: Literature review was used to develop a survey on current concepts relating to skin quality. The survey results were analyzed descriptively and presented to a focus group comprising five dermatologists and four aesthetic physicians. This group then discussed the concept of skin glow, how to define it and what metrics could be used to assess it. RESULTS: Surveyed practitioners (n = 38) ranked skin quality as the fourth most important factor related to a person's overall aesthetic first impression. Almost all (95%) respondents reported routinely assessing skin quality, citing serial photography (83%), and visual inspection (67%) as the main means of achieving this. The focus group defined skin glow as even reflectance from an unaffected papillary and reticular dermal collagen layer, which is created only when skin does not exhibit any characteristics that detract from this even reflectance. Due to its complexity, the focus group proposed a hierarchal framework for assessment, encompassing patient self-rating, practitioner severity rating, and supplemental use of validated measurement devices. CONCLUSIONS: Skin glow can be defined and quantified. More work is warranted to develop a practical skin glow assessment tool suitable for use in the clinic setting.

Decades of beauty: Achieving aesthetic goals throughout the lifespan.

BACKGROUND: Several elements, including age, influence judgments of beauty and attractiveness. Aging is affected by intrinsic factors (e.g., genetics, race/ethnicity, anatomical variations) and extrinsic factors (e.g., lifestyle, environment). AIMS: To provide a general overview of minimally invasive injectable procedures for facial beautification and rejuvenation to meet the aesthetic goals of patients across their lifespan, organized by decade. METHODS: This case study review describes aesthetic considerations of females in their third to sixth decade of life (i.e., 20-60 years of age or beyond). Each case study reports the treatments, specifically botulinum toxin type A and soft tissue fillers, used to address aesthetic concerns. RESULTS: Signs of aging, as well as aesthetic goals and motivations, vary by age groups, cultures, and races/ethnicities. However, there are overarching themes that are associated with each decade of life, such as changes in overall facial shape and specific facial regions, which can be used as a starting point for aesthetic treatment planning. Appropriate patient selection, thorough aesthetic evaluation, product knowledge, and injection technique, as well as good physician-patient communication, are essential for optimal treatment outcomes. CONCLUSIONS: Nonsurgical facial injectable treatments can successfully enhance and rejuvenate facial features across different age ranges. A comprehensive understanding of facial aging and the aesthetic considerations of patients by the decade contributes to optimal treatment planning and maintenance.

Making Sense of Late Tissue Nodules Associated With Hyaluronic Acid Injections.

BACKGROUND: The pathogenesis of delayed-onset tissue nodules (DTNs) due to hyaluronic acid (HA) injections is uncertain. OBJECTIVES: To formulate a rational theory for DTN development and their avoidance and treatment. METHODS: A multidisciplinary and multicountry DTN consensus panel was established, with 20 questions posed and consensus sought. Consensus was set at 75% agreement. RESULTS: Consensus was reached in 16 of 20 questions regarding the pathogenesis of DTNs, forming the basis for a classification and treatment guide. CONCLUSIONS: The group believes that filler, pathogens, and inflammation are all involved in DTNs and that DTNs most likely are infection initiated with a variable immune response. Injected filler may incorporate surface bacteria, either a commensal or a true pathogen, if the skin barrier is altered. The initially high molecular weight HA filler is degraded to low molecular weight HA (LMWHA) at the edge of the filler. Commensals positioned within the filler bolus may be well tolerated until the filler is degraded and the commensal becomes visible to the immune system. LMWHA is particularly inflammatory in the presence of any local bacteria. Commensals may still be tolerated unless the immune system is generally heightened by viremia or vaccination. Systemic pathogenic bacteremia may also interact with the filler peripheral LMWHA, activating Toll-like receptors that induce DTN formation. Given this scenario, attention to practitioner and patient hygiene and early systemic infection treatment deserve attention. Classification and treatment systems were devised by considering each of the 3 factors-filler, inflammation, and infection-separately.

Efficacy of a Novel Injection Lipolysis to Induce Targeted Adipocyte Apoptosis: A Randomized, Phase IIa Study of CBL-514 Injection on Abdominal Subcutaneous Fat Reduction.

BACKGROUND: CBL-514 is a novel injectable drug that may be safe and efficacious for localized abdominal subcutaneous fat reduction. OBJECTIVES: The aim of this study was to assess the safety and efficacy of CBL-514 in reducing abdominal subcutaneous fat volume and thickness. METHODS: This Phase IIa, open-label, random allocation study consisted of a 6-week treatment period and follow-up at 4 and 8 weeks following the last treatment. Participants were randomly allocated to receive 1.2 mg/cm2 (180 mg), 1.6 mg/cm2 (240 mg), or 2.0 mg/cm2 (300 mg) of CBL-514 with up to 4 treatments, each comprising 60 injections into the abdominal adipose layer. Changes in abdominal subcutaneous fat were assessed by ultrasound at follow-up visits. Treatment-emergent adverse events were recorded. RESULTS: Higher doses of CBL-514 (unit dose, 2.0 and 1.6 mg/cm2) significantly improved the absolute and percentage reduction in abdominal fat volume (P < 0.00001) and thickness (P < 0.0001) compared with baseline. Although the COVID-19 pandemic halted some participant recruitment and follow-ups, analysis was unaffected, even after sample size limitations. CONCLUSIONS: CBL-514 injection at multiple doses up to 300 mg with a unit dose of 2.0 mg/cm2 is safe, well-tolerated, and reduced abdominal fat volume and thickness by inducing adipocyte apoptosis. Although other procedures exist to treat abdominal fat, they have limitations and may cause complications. At a dose of 2.0 mg/cm2, CBL-514 safely and significantly reduced abdominal fat volume by 24.96%, making it a promising new treatment for routine, nonsurgical abdominal fat reduction in dermatologic clinics.

Movement of the Syringe During Filler Aspiration: An Ultrasound Study.

BACKGROUND: Aspiration prior to hyaluronic acid filler injection is often taught as a safety maneuver to minimize the risk of intravascular injection; however, the validity of this technique in aesthetic practice is being increasingly challenged. One key assumption underpinning the validity of the aspiration test is that the needle tip does not move during the aspiration and subsequent injection of filler. OBJECTIVES: The aim of this study was to visualize and measure needle tip movement in real time during aspiration and injection of filler. Secondary objectives were to assess the impact of injector experience and double-handed versus single-handed aspiration technique in maintaining stability of the syringe. METHODS: Under real-time ultrasound visualization, 3 injectors with different levels of experience injected hyaluronic acid filler into pork belly tissue utilizing both double-handed and single-handed aspiration techniques. Needle tip movements were recorded and measured by means of ultrasound and video. RESULTS: The aspiration maneuver is in all cases associated with retrograde movement of the needle tip, ranging from 1.1 to 5.3 mm (mean, 2.9 mm), whereas injection leads to anterograde movement ranging from 0.6 to 4.1 mm (mean, 1.9 mm). Double-handed aspiration is associated with less needle tip movement than single-handed aspiration (P = 0.037). Greater experience is also associated less movement of the needle tip (P < 0.0001). CONCLUSIONS: In all cases, the aspiration and injecting maneuver is associated with micromovements of the needle tip, of a magnitude consistently significant relative to the typical size of facial vessels. Although needle tip movement is only a single factor limiting the usefulness of the aspiration test, the results of this study suggest that it is not advisable to rely only on aspiration as a method to prevent intravascular injection.

Aspiration Before Tissue Filler-An Exercise in Futility and Unsafe Practice.

BACKGROUND: Aesthetic physicians rely on certain anecdotal beliefs regarding the safe practice of filler injections. These include a presumed safety advantage of bolus injection after a negative aspiration. OBJECTIVES: The authors sought to review and summarize the published literature on inadvertent intravascular injection of hyaluronic acid and to investigate whether the technique of aspiration confers any safety to the practitioner and the patient. METHODS: Pertinent literature was analyzed and the current understanding of the safety of negative and positive aspiration outlined. RESULTS: The available studies demonstrate that aspiration cannot be relied on and should not be employed as a safety measure. It is safer to adopt injection techniques that avoid injecting an intravascular volume with embolic potential than utilize an unreliable test to permit a risky injection. CONCLUSIONS: To prevent intravascular injection, understanding "injection anatomy" and injection plane and techniques such as slow, low-pressure injection are important safety measures. Assurance of safety when delivering a bolus after negative aspiration does not appear to be borne out by the available literature. If there is any doubt about the sensitivity or reliability of a negative aspiration, there is no role for its utilization. Achieving a positive aspiration would just defer the risk to the next injection location where a negative aspiration would then be relied on.

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.

Randomized, Placebo-Controlled Phase 1/2 Study to Determine the Appropriate ATX-101 Concentration for Reduction of Submental Fat.

BACKGROUND: ATX-101 is indicated for submental fat treatment. OBJECTIVE: Evaluate ATX-101 versus placebo for reducing submental fat. MATERIALS AND METHODS: Adults with unwanted submental fat across 6 global sites were randomized to ATX-101 (0.5%, 1.0%, or 2.0%) or placebo for ≤4 treatments every 28 days. Outcomes included safety (adverse events and pain visual analog scale) throughout the study and efficacy (submental fat rating, patient satisfaction, and submental fat improvements) at Week 16. RESULTS: Eighty-four of 85 enrolled patients received ≥1 ATX-101 treatment (0.5% [n = 20], 1.0% [n = 20], 2.0% [n = 22] or placebo [n = 22]). Most patients (n = 82) experienced adverse events, which were mostly mild/moderate, seemed to be dose-related, and led to no study discontinuations. The mean pain scores were highest in the ATX-101 1.0% and 2.0% groups. Week-16 change from baseline in the submental fat rating scale was significantly greater for ATX-101 0.5% and 1.0% versus placebo (p ≤ .05). At Week 16, 71%, 74%, 53%, and 40% of patients in the ATX-101 0.5%, 1.0%, 2.0%, and placebo groups, respectively, achieved a ≥1-grade reduction in submental fat from baseline. Satisfaction with appearance and patient-assessed global improvement ratings increased in all ATX-101 treatment groups versus placebo. CONCLUSION: All ATX-101 concentrations were safe and efficacious for moderate/severe submental fat reduction.

Consensus on Changing Trends, Attitudes, and Concepts of Asian Beauty.

BACKGROUND: Asians increasingly seek non-surgical facial esthetic treatments, especially at younger ages. Published recommendations and clinical evidence mostly reference Western populations, but Asians differ from them in terms of attitudes to beauty, structural facial anatomy, and signs and rates of aging. A thorough knowledge of the key esthetic concerns and requirements for the Asian face is required to strategize appropriate facial esthetic treatments with botulinum toxin and hyaluronic acid (HA) fillers. METHODS: The Asian Facial Aesthetics Expert Consensus Group met to develop consensus statements on concepts of facial beauty, key esthetic concerns, facial anatomy, and aging in Southeastern and Eastern Asians, as a prelude to developing consensus opinions on the cosmetic facial use of botulinum toxin and HA fillers in these populations. RESULTS: Beautiful and esthetically attractive people of all races share similarities in appearance while retaining distinct ethnic features. Asians between the third and sixth decades age well compared with age-matched Caucasians. Younger Asians' increasing requests for injectable treatments to improve facial shape and three-dimensionality often reflect a desire to correct underlying facial structural deficiencies or weaknesses that detract from ideals of facial beauty. CONCLUSIONS: Facial esthetic treatments in Asians are not aimed at Westernization, but rather the optimization of intrinsic Asian ethnic features, or correction of specific underlying structural features that are perceived as deficiencies. Thus, overall facial attractiveness is enhanced while retaining esthetic characteristics of Asian ethnicity. Because Asian patients age differently than Western patients, different management and treatment planning strategies are utilized. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Re Facial aesthetic injections in clinical practice: Pretreatment and post-treatment consensus recommendations to minimise adverse outcome Region-specific changes in line with the Covid-19 pandemic.

Despite the recent publication in March 2020 of guidelines for facial injectable treatments, the speed of the COVID-19 pandemic and its safety implications necessitate changes to these guidelines The authors described what would constitute safest practice in the provision of facial injectable treatments and summarised these in table form. Adherence to a high standard of asepsis and infectious disease precautions remain a key patient safety requirement when performing facial aesthetic injections. A revision and update of these guideline summary tables follows. Changes made should enhance both patient and staff safety regarding COVID-19/SARS-CoV-2, a highly infective respiratory pathogen transmitted by respiratory droplets, respiratory/mucosal secretions and contaminated fomites. Some of the additions are COVID-19 specific and are likely to evolve and change, particularly should serological tests determining acquired immunity become available. Other additions represent further tightening of our infection control precautions.

Delayed Inflammatory Reactions to Hyaluronic Acid Fillers: A Literature Review and Proposed Treatment Algorithm.

BACKGROUND AND OBJECTIVES: There is a wide diversity of opinions regarding the management of delayed inflammatory reactions (DIRs) secondary to hyaluronic acid (HA)-based fillers. The plethora of approaches has led the authors to conduct a review regarding management and treatment of DIRs as well as establish therapeutic guidelines for this purpose. MATERIALS AND METHODS: A review of the literature was performed through databases such as PubMed using keywords including HA-fillers and complications, delayed HA filler sequelae and therapy, soft tissue and dermal filler reactions and management. Additionally, a survey comprised of questions regarding the management and treatment of DIRs was sent to 18 physicians highly experienced with soft-tissue filler injections in 10 countries. Their answers and recommendations were analyzed and debated amongst these panelists. RESULTS: Sixteen panelists favored antibiotic therapy as first-line treatment for DIRs, specifically dual antibiotic therapy consisting of a fluoroquinolone along with a tetracycline or macrolide for a period of 3-6 weeks. The majority refrained from the use of intralesional (IL) or systemic steroids except in the case of disfiguring or recalcitrant reactions. IL hyaluronidase was recommended by 13 panelists; however, some preferred a watchful waiting approach for a period of 48 hours to 2 weeks prior to IL hyaluronidase, and in cases where antibiotics did not lead to improvement. CONCLUSION: A consensus was reached and summarized to propose a clear, easy-to-follow, stepwise algorithm for the treatment of DIRs.