Validating the Reliability and Clinical Relevance of a Nasolabial Fold Photonumeric Scale.

BACKGROUND: The use of tissue fillers to treat age-related deepening of the nasolabial fold (NLF) has increased and become the standard clinical approach, creating a need for evidence-based, objective evaluation for pre- and post-procedure assessment of the NLF. METHODS: A 5-point rating scale was developed to assess the NLF, specifically the presence of depression and shadowing. Live validation of the scale was performed with a total of 73 participants representing the full range of NLF severities. Physicians board-certified in a core aesthetic specialty (3 trained raters) performed the scale validation over 2 rounds, 2 weeks apart. Training was carried out, and test-retest reliability was quantitated through the determination of intra- and inter-rater reliability by percentage of agreement, weighted kappa statistic with 95% confidence interval (CI), and intraclass correlation coefficient with 95% CI. To evaluate the clinical relevance of a 1-grade difference, rater assessments of 90 photo pairs were compared with previous designations of clinically different or not clinically different. RESULTS: The NLF scale achieved near-perfect intra- and inter-rater reliability when utilized by trained raters to assess a diverse group of live participants. Furthermore, clinically relevant differences between grades were established, and a 1-point difference was detectable by trained evaluators using the NLF scale. CONCLUSION: The clinically relevant and highly reliable validated NLF scale provides a standardized grading system with a user-friendly design for objectively assessing NLF in clinical practice and as a research tool for clinical approval studies of new aesthetic products and technologies. J Drugs Dermatol. 2024;23(1):1284-1291.   doi:10.36849/JDD.7316.

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.

The Role of Calcium Hydroxylapatite (Radiesse) as a Regenerative Aesthetic Treatment: A Narrative Review.

For decades, a wide variety of natural and synthetic materials have been used to augment human tissue to improve aesthetic outcomes. Dermal fillers are some of the most widely used aesthetic treatments throughout the body. Initially, the primary function of dermal fillers was to restore depleted volume. As biomaterial research has advanced, however, a variety of biostimulatory fillers have become staples in aesthetic medicine. Such fillers often contain a carrying vehicle and a biostimulatory material that induces de novo synthesis of major structural components of the extracellular matrix. One such filler, Radiesse (Merz Aesthetics, Raleigh, NC), is composed of calcium hydroxylapatite microspheres suspended in a carboxymethylcellulose gel. In addition to immediate volumization, Radiesse treatment results in increases of collagen, elastin, vasculature, proteoglycans, and fibroblast populations via a cell-biomaterial-mediated interaction. When injected, Radiesse acts as a cell scaffold and clinically manifests as immediate restoration of depleted volume, improvements in skin quality and appearance, and regeneration of endogenous extracellular matrices. This narrative review contextualizes Radiesse as a regenerative aesthetic treatment, summarizes its unique use cases, reviews its rheological, material, and regenerative properties, and hypothesizes future combination treatments in the age of regenerative aesthetics.

Novel, Validated 5-Point Photonumeric Scales for Assessment of the Neck and Décolleté.

BACKGROUND: There is a scarcity of scales that assess platysmal bands, wrinkles in the décolleté, and horizontal neck lines in the digital and live setting. OBJECTIVES: The objective of this investigation was to create and validate 5-point photonumeric scales that assess horizontal neck lines, platysmal bands, and wrinkles in the décolleté. METHODS: A medical team created 3 different novel 5-point photonumeric scales for the assessment of horizontal neck lines, platysmal bands, and décolleté wrinkling. Eleven international raters were involved in the digital validation, and 4 raters performed a live validation. RESULTS: The Croma (Leobendorf, Austria) Horizontal Neck Lines Assessment Scale showed substantial interrater agreement and almost perfect intrarater agreement in the digital and live validations, respectively. The Croma Platysmal Bands Assessment Scale showed substantial intrarater agreement in both digital and live validations. For the décolleté, a static scale and a dynamic scale were created and validated. The Croma Static Décolleté Wrinkles Assessment Scale showed substantial and almost perfect interrater agreement in the digital and live validations, respectively, and the intrarater agreement in both was almost perfect. The Croma Dynamic Décolleté Wrinkles Assessment Scale showed almost perfect agreement in both validation settings for both interrater and intrarater measures. CONCLUSIONS: The Croma Horizontal Neck Lines Assessment Scale and the Croma Static and Dynamic Décolleté Wrinkles Assessment Scales have sufficient interrater and intrarater agreement for justifiable use in clinical and research settings.

Skin Tightening With Hyperdilute CaHA: Dilution Practices and Practical Guidance for Clinical Practice.

BACKGROUND: Over the past several years, hyperdilute calcium hydroxylapatite (CaHA) has emerged as an effective modality for improving skin quality and managing laxity in the face, arms, hands, neck, décolletage, upper arms, abdomen, buttocks, and upper legs, as well as for treating cellulite and striae. Whereas undiluted CaHA is used to provide volume, hyperdilute CaHA is distributed across a much larger surface area in a more superficial plane to stimulate neocollagenesis and elastin formation over time. The absence of lymphocytic infiltrates and predominance of type 1 collagen in the tissue response to CaHA make hyperdilute CaHA a valuable tool for nonsurgical skin tightening. OBJECTIVES: The aim of this study was to provide practical step-by-step guidance on patient selection, dilution practices, and optimal injection technique to facilitate incorporation of the technique into clinical practice. METHODS: Over the course of 3 regional meetings in the United States, 12 expert physician injectors participated in live webinars as part of a continuing medical education program. RESULTS: The practical guidance in this manuscript is based upon the most frequently requested information by audience members and the information considered critical for success by the authors. CONCLUSIONS: The minimally invasive nature of filler injection results in little downtime, making this treatment particularly appealing. The recommendations presented are consistent with previously published consensus guidelines on hyperdilute CaHA but are intended to serve as "how-to" guidance based on the experience of expert injectors who have successfully treated the face and body.

AbobotulinumtoxinA for the Treatment of Moderate-to-Severe Glabellar Lines: A Randomized, Dose-Escalating, Double-Blind Study.

OBJECTIVE: To evaluate the efficacy and safety of AbobotulinumtoxinA (ABO) dose escalation in the correction of moderate-to-severe glabellar lines. DESIGN: Phase 2, 36-week, multicenter, randomized, dose-ranging, double-blind, placebo-controlled study. METHODS: Adults with moderate-to-severe glabellar lines received a single ABO treatment, dosed at 50, 75, 100, or 125 U, or placebo. Primary endpoint was week 4 composite ≥2-grade responder rate among those achieving a severity score of 0 (none) or 1 (mild) at maximum frown, evaluated using concurrent investigator and subject assessments. Secondary endpoints included ≥1-grade severity improvement, duration of effect, and reporting of treatment-emergent adverse events (TEAEs). RESULTS: Overall, 399 subjects were included (88.2% were female). Week 4 composite ≥2-grade ABO responder rate was 80.0% (50 U), 88.8% (75 U), 90.0% (100 U) and 95.1% (125 U), versus 2.6% with placebo (P<0.001). Responder rate (≥1-grade) ranged between 53% (50 U) and 69% (125 U) at week 24 and between 18% (50 U) and 31% (125 U) at week 36. Median time (weeks) to return to baseline severity/worse, among those scoring 0 (none) or 1 (mild), was 32.3 (50 U), 34.3 (75 U), 36.0 (100 U) and 36.6 (125 U), versus 23.7 (placebo). ABO-related TEAEs were reported in 4% of subjects (80% were mild). No seroconversion to ABO neutralizing antibodies was seen. CONCLUSION: A single ABO treatment provided rapid and effective improvements in glabellar line severity at all doses. Higher doses tended to demonstrate elevated response rates and longer duration of effect. All ABO doses were well-tolerated with low TEAE incidence. J Drugs Dermatol. 2021;20(9):980-987. doi:10.36849/JDD.6263.

Rheology of Polymethylmethacrylate-Collagen Gel Filler: Physiochemical Properties and Clinical Applications.

BACKGROUND: Soft tissue fillers are comprised of a range of materials with differing physiochemical and rheologic (ie, flow) properties. These properties can inform treatment selection for specific anatomic areas, planes of injection, and clinical applications. OBJECTIVES: The aim of this study was to characterize the rheologic properties of polymethylmethacrylate (PMMA)-collagen gel for comparison with other available fillers. METHODS: Commercially available PMMA-collagen gel, hyaluronic acid (HA), and calcium hydroxylapatite (CaHA) fillers were obtained from their respective manufacturers. Measures of complex viscosity (η*) and elastic modulus (G') for each filler were collected at 0.7 Hz in triplicate according to standard procedures on a rotational rheometer fitted with a 40-mm steel plate at 25°C on a Peltier plate (500-µm gap). RESULTS: The measured η* and G' values for HA and CaHA fillers were in agreement with previously published data. The difference in η* between CaHA (mean [standard deviation], 358.9 [21.56] Pa-s) and PMMA-collagen gel (656.41 [68.03] Pa-s) was statistically significant (P < 0.0001), as was the difference between the G' of CaHA (1424.8 [83.3] Pa) and the G' of PMMA-collagen gel (2815.27 [304.07] Pa; P < 0.0001). CONCLUSIONS: PMMA-collagen gel exhibited the highest η* and G' of all tested fillers. These properties likely underpin an increased capacity for lifting and support in areas where long-lasting revolumization is appropriate. In practice, PMMA-collagen gel is well suited for treatment of acne scars, as well as injection into the supraperiosteal plane in the temple, chin, mandible, and piriform by a retrograde linear threading technique. Additional clinical considerations are discussed.

Understanding Facial Muscle Aging: A Surface Electromyography Study.

BACKGROUND: Facial aging is a multifactorial process that involves all tissues of the face, including skin, muscles, fat, ligaments, and bone. Whereas robust evidence is available for age-related changes of bone and facial fat, the influence of age on facial muscle activity is poorly understood. OBJECTIVES: The objective of this study was to investigate the motor unit action potential of facial muscles by utilizing surface-derived, noninvasive electromyography in young and old healthy volunteers. METHODS: The study investigated a total of 32 healthy volunteers with a mean [standard deviation] age of 42.6 [19.6] years (range, 21-82 years) and a mean BMI of 23.9 [2.7] kg/m2 (range, 18.5-29.7 kg/m2) by performing surface-derived, noninvasive facial electromyography. Nine facial muscles were investigated bilaterally, resulting in a total of 1632 measurements of the signal, baseline noise, and signal-to-noise ratio of these muscles. RESULTS: The results of the study revealed that age does not significantly influence the signal (P = 0.234), the baseline noise (P = 0.225), or the signal-to-noise ratio (P = 0.432) of younger individuals (<30 years) vs older individuals (>50 years) in a gender- and BMI-matched statistical model. Exceptions were the zygomaticus major muscle (reduced activity), procerus muscle (increased activity), and corrugator supercilii muscle (increased activity). CONCLUSIONS: The results of this facial electromyography study may help to increase the understanding of facial aging. Future studies need to reproduce the results presented herein to further increase our understanding of facial aging.

The Second of Two One-Year, Multicenter, Open-Label, Repeat-Dose, Phase II Safety Studies of PrabotulinumtoxinA for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients.

BACKGROUND: PrabotulinumtoxinA is a 900-kDa botulinum toxin type A produced by Clostridium botulinum. OBJECTIVES: The authors sought to investigate the safety of prabotulinumtoxinA for treatment of glabellar lines. METHODS: This was a multicenter, open-label, repeat-dose, 1-year phase II safety study. Adults with moderate to severe glabellar lines at maximum frown, as independently assessed by both investigator and patient on the validated 4-point photonumeric Glabellar Line Scale (0 = no lines, 1 = mild, 2 = moderate, 3 = severe), were enrolled. On day 0, patients received an initial treatment (IT) of 20 U prabotulinumtoxinA (4 U/0.1 mL final vacuum-dried formulation injected into 5 glabellar sites). On and after day 90, patients received a repeat treatment (RT) if their Glabellar Line Scale score was ≥2 at maximum frown by investigator assessment. Safety outcomes were evaluated throughout the study. RESULTS: The 570 study patients received a median total dose of 60 U, that is, 3 treatments. Sixty-one patients (10.7%) experienced adverse events (AEs) assessed as possibly study drug related; 6.5% experienced study drug-related AEs after the IT. With each RT, progressively lower percentages of patients experienced study drug-related AEs. Eight patients (1.4%) experienced study drug-related AEs of special interest: 5 experienced eyelid ptosis (0.9%), 3 eyebrow ptosis (0.5%), 1 blepharospasm (0.2%), and 1 blurred vision (0.2%). Seven patients (1.2%) experienced serious AEs, but none were study drug related. A total of 4060 serum samples were tested for antibotulinum toxin antibodies; no seroconversion was observed. CONCLUSIONS: The safety of RTs of 20 U of prabotulinumtoxinA for moderate to severe glabellar lines was confirmed in this second phase II study based on a broad range of outcomes.

Multicenter Efficacy Trial of a Percutaneous Radiofrequency System for the Reduction of Glabellar Lines.

BACKGROUND: Bipolar percutaneous radiofrequency (RF) is an established method for ablation of distal peripheral branches of the facial nerve to produce weakness of the corrugator muscle. Recent developments to the Serene RF system (Serene Medical, Inc., Pleasanton, CA) allowing for safer and more predictable results highlighted a need for prospective clinical data. OBJECTIVES: The authors sought to assess the ability of percutaneous RF to safely improve the appearance of dynamic glabellar lines for a minimum of 3 months and up to 1 year. METHODS: This prospective study enrolled 78 patients across 5 centers in the United States. The most distal branches of the medial and lateral facial nerve innervation to the brow depressor/corrugator complex were treated. Follow-up was at 3 days by telephone and in-office at 7 days and 3, 6, 9, and 12 months posttreatment. Patients were evaluated employing the Merz scale for dynamic glabellar lines. RESULTS: At 3 months, 93.6% of patients had a ≥1-point Merz scale improvement in dynamic glabellar lines based on independent, blinded review. Sustained ≥2-point improvement was present in 60% and 20% of patients at 3 and 12 months, respectively. Overall satisfaction remained >60% through 6 months and >50% at 12 months. All device- or procedure-related adverse events were mild (90%) or moderate (10%) and resolved without medical intervention. CONCLUSIONS: Bipolar percutaneous RF may be adopted in conjunction with surgery or as an office-based procedure where it can serve as a minimally invasive alternative to, or in concert with, Botulinum Toxin A therapy.

Straight-Line Vector Planning for Optimal Results With Silhouette InstaLift in Minimally Invasive Tissue Repositioning for Facial Rejuvenation.

BACKGROUND: Absorbable suspension sutures for tissue repositioning represent a minimally invasive approach to facial rejuvenation. With 2015 FDA 510(k) approval of Silhouette InstaLift™ (Sinclair Pharma, Irvine, CA), a completely absorbable device comprised of 82% PLLA/18% PLGA sutures and bi-directional cones, came the challenge of developing optimal technique for achieving effective, precise, and durable tissue repositioning. Here, the authors discuss the importance of straight-line vector planning (SLVP) and positioning of the suture perpendicular to the plane to be elevated in obtaining optimal results for tissue repositioning. Both the scientific underpinnings of SLVP are presented, along with detailed discussion of technique for suture placement in the mid-face, jawline/jowls, and neck. METHODS: The authors are some of the earliest adopters of absorbable suspension sutures in the United States and have both used InstaLift™ sutures for tissue repositioning and facial recontouring in treatment of more than 500 patients and developed the principles of SLVP as a method to ensure optimal outcomes. RESULTS: Patient case studies illustrating the importance of SLVP are presented. In over 500 patients treated within the authors' practices since InstaLift approval there have been no serious adverse events and noticeable bruising has occurred in less than 5% of patients. Results of repositioning and recontouring are evident for up to 24 months. CONCLUSIONS: Absorbable suspension sutures are a highly adaptable, non-invasive device for lifting and repositioning of descended facial tissue. Outcomes are dependent upon proper technique, including SLVP. J Drugs Dermatol. 2018;17(7):786-793.

Expert Consensus on Achieving Optimal Outcomes With Absorbable Suspension Suture Technology for Tissue Repositioning and Facial Recontouring.

A complete approach to facial rejuvenation includes restoration of the skin's surface, relaxation of muscles that contribute to hyperkinetic movement, revolumization, and repositioning/recontouring of descended tissues and fat pads. After receiving 510(k) clearance from the US Food and Drug Administration (FDA) in 2015, the Silhouette InstaLift™ absorbable suspension suture became the only available non-surgical technique for repositioning of facial tissue. In January 2017, a consensus paper presented a review of the literature on the efficacy and safety of absorbable suspension sutures and provided information on treatment procedures. Since that time, the clinical experience of the authors has further shaped their treatment practices, highlighting the need for additional guidelines to support an optimal treatment approach. This update will expand upon the 2017 consensus paper on the safety and efficacy of absorbable suspension sutures and provide guidance for obtaining consistently high patient satisfaction with the procedure. Recommendations are based on the extensive clinical experience of expert physicians with absorbable suspension sutures over the past 2.5 years. Here, the authors provide guidance on full face assessment and treatment to support maximum benefit and provide patient selection and procedural recommendations. In addition, the authors stress the benefits of the dual mechanisms of action within the absorbable suspension suture: the immediate lift and volumizing over time that together lead to the outcome of recontouring. J Drugs Dermatol. 2018;17(6):647-655.

Physiochemical Characteristics of Calcium Hydroxylapatite (CaHA).

The clinical performance of fillers in soft tissue augmentation depends upon their physiochemical properties, anatomical areas injected, interaction with the recipient, and the skill and experience of the physician. Scientific measures of filler properties facilitate appropriate selection of treatments for optimal treatment outcomes, and inform adjustments to treatments that improve patient safety and aesthetic outcomes. The rheological properties of calcium hydroxylapatite (CaHA), elastic modulus (G') and viscosity, coupled with its capacity to offer both immediate results and continued stimulation of collagen type I deposition, support its distinction as an ideal treatment for the volume loss characteristic of aging. Furthermore, the comparatively higher G' of CaHA offers a physiochemical basis for the clinical performance observed by the authors, especially in regions such as the temple and chin, where the force exerted by CaHA against bone permits expansion of overlaying tissue, permitting it to behave as a liquid implant.

Physiochemical Characteristics of Poly-L-Lactic Acid (PLLA).

Poly-L-lactic acid (PLLA) is a synthetic, biocompatible, biodegradable polymer. For soft-tissue augmentation, the size and chemical attributes of the PLLA microparticles are central to this agent's ability to promote a subclinical inflammatory response that stimulates deposition of collagen in the extracellular matrix. The resultant restoration of facial volume occurs in a controlled, predictable manner and is long lasting. The unique physiochemical and biostimulatory properties of PLLA differentiate it from other available treatments and are the foundation of the unique treatment methodology required for optimal results.

Calcium Hydroxyapatite (CaHA) Indication for Hand Rejuvenation.

The recent approval in 2015 of Radiesse for injection into the hand by the FDA has spurred an increase in interest among patients and clinicians in nonsurgical hand rejuvenation using fillers. Application of the same techniques used to treat the face to the dorsum of the hands does not account for the unique nature of the skin and underlying anatomy, and can lead to suboptimal outcomes and an increased risk of adverse events such as the formation of nodules. Here, the authors discuss dilution strategies and injection techniques for hand rejuvenation using Radiesse for optimal patient safety and aesthetic outcomes.

Expanding Treatment Options for Injectable Agents.

Loss of facial volume and soft-tissue support are common to types of facial aging. Restoration of a youthful appearance relies upon correction of this loss, and can be achieved in various capacities through use of biostimulatory or hyaluronic acids (HA) injectable fillers. Here, the authors discuss the versatility of calcium hydroxylapatite (CaHA) in volume replacement and the applications and facial regions for which CaHA, poly-L-lactic acid (PLLA), and HA fillers are best suited.

Composite Facial Volumization With Calcium Hydroxylapatite (CaHA) for the Treatment of Aging.

Paradigms in the treatment of aging have evolved to address volume loss as a central and primary hallmark of the aging face. The concept of "composite volumization" was recently proposed by Dr. Z. Paul Lorenc to describe the effect of Radiesse (Merz Aesthetics, Inc., Raleigh, NC), when placed on bone in the supraperiosteal plane, on all overlying tissues (skin, superficial and deep fat compartments, and muscle). The physiochemical properties of Radiesse make it especially well suited for efficient and effective volumization of areas especially prone to volume loss; the temple, zygomatic arch, anterior cheek, pyriform aperture, and prejowl sulcus. Placement of Radiesse on bone in these areas creates a scaffold upon which additional restoration of fine lines and wrinkles may be accomplished, restoring a youthful appearance.

Differentiating Nonpermanent Injectable Fillers: Prevention and Treatment of Filler Complications.

Though the incidence of complications and adverse events with dermatological fillers is inherently low, practitioners should be well versed in both prevention of filler complications and the treatment algorithms for addressing "granulomas," nodules, infection, and vascular compromise. Appropriate preventative measures, coupled with timely and effective treatment, are critically important for patient safety and satisfaction. In addition to the preventive measures and treatment algorithms outlined here, the authors emphasize that the broad classification and treatment of nodules as "granulomas" is likely to lead to ineffective treatment, or worse, unnecessary exposure to incorrect treatment. In practice, nodules are classified and treated based on clinical manifestation (eg, late vs early or noninflammatory vs inflammatory) rather than on histology. Indeed, classification of a nodule as a granuloma requires a histological examination, rarely available (or necessary) in clinical practice to guide treatment. Thus, the apparent inflammatory nature of the nodule and the time of onset should drive treatment approach. The treatment algorithms presented here are based on these clinically meaningful parameters.

Factors Affecting the Rheological Measurement of Hyaluronic Acid Gel Fillers.

BACKGROUND: With the number of available dermal fillers increasing, so is the demand for scientifically based comparisons, often with rheological properties in focus. Since analytical results are always influenced by instrument settings, consensus on settings is essential to make comparison of results from different investigators more useful. OBJECTIVE: Preferred measurement settings for rheological analysis of hyaluronic acid (HA) fillers are suggested, and the reasoning behind the choices is presented by demonstrating the effect of different measurement settings on select commercial HA fillers. MATERIALS AND METHODS: Rheological properties of 8 HA fillers were measured in a frequency sweep from 10 to 0.01 Hz at 0.1% strain, using an Anton Paar MCR 301, a PP-25 measuring system with a gap of 1 mm at 25°C. A 30-min period was used for relaxation of the sample between loading and measuring. RESULTS: The data presented here, together with previously published data, demonstrate differences in G' from 1.6 to 7.4 times for the same product. CONCLUSION: A large part of the differences were concluded to be due to differences in rheometry measurement settings. The confusion from the many parameters involved in rheometry can be avoided by simply using the elastic modulus (G') to differentiate products.

J Drugs Dermatol. 2017;16(9):876-882.