New and Future Developments in Neurotoxins.

BACKGROUND: There are 7 known serotypes of botulinum neurotoxins (A through G). Currently, commercially available toxins are those in serotypes A and B. This paper will discuss new toxins on the horizon, developments in prolonging and shortening the duration of outcomes, and novel therapeutic indications on the horizon. OBJECTIVE: To provide insight into new toxins and new therapeutic modalities surrounding toxins on the horizon. METHODS: The authors have reviewed the relevant literature and shared their insights and opinions as to future developments in toxin research and potential clinical applications. CONCLUSION: Botulinum neurotoxin type E's faster onset and shorter duration of effect represent true clinical differentiators. Future development of botulinum neurotoxin type E for aesthetic and therapeutic uses will be in areas where fast onset and short duration of effect are desirable. Current challenges with neuromodulators include the need for frequent treatments and lack of reversal agents. Agents to address both challenges and novel indications, including inhibition of melanogenesis, are being developed.

Efficacy and Safety of Tapencarium (RZL-012) in Submental Fat Reduction.

BACKGROUND: Tapencarium (RZL-012) (5-(3.6-dibromo-9H-carbazol-9-yl)-N, N, N-trimethylpentan-1-aminium chloride) is a novel injectable synthetic molecule with cytolytic properties, capable of reducing subcutaneous fat volume. OBJECTIVES: The goal of this 3-armed, randomized, double-blind, placebo-controlled phase 2b study was to determine the safety and efficacy of low- and high-dose RZL-012 vs placebo on submental fat (SMF) reduction. METHODS: Patients (n = 151, age 18-65 years) with excess SMF received a single treatment session of RZL-012 or placebo in the submental area, after which they were monitored for 84 days. SMF was assessed at baseline and after dosing with newly developed scales, namely the Clinician Chin Assessment Tool (C-CAT) and Subject Chin Assessment Tool (S-CAT). SMF was also assessed by magnetic resonance imaging (MRI) at screening and on Day 84 after treatment. RESULTS: The proportion of patients who had a 1-grade or 2-grade improvement in C-CAT and/or S-CAT on Day 84 vs baseline was significantly higher in the high-dose RZL-012 group vs the placebo group (P < .002). The relative percentage reduction in MRI-measured SMF volume (Day 84 vs screening) was significantly greater in the high-dose RZL-012 group vs the low-dose RZL-012 or the placebo group (P < .0001). Local injection site reactions were the most common adverse events (AEs). CONCLUSIONS: A single administration of RZL-012 into SMF resulted in significant improvement in submental appearance as assessed by clinicians, patients, and MRI. From a safety perspective, there were no serious AEs and no clinically significant changes in vital signs or laboratory tests over the course of the study.

The Use of a Novel Artificial Intelligence Platform for the Evaluation of Rhytids.

BACKGROUND: Artificial intelligence (AI) platforms are increasingly being utilized in various healthcare applications. There are few platforms that provide quantifiable assessments of dermatologic or aesthetic conditions by employing industry established scales. OBJECTIVES: The authors sought to report the results of a pilot study that evaluated the utilization and functionality of an AI engine to measure and monitor rhytids (fine lines). For this study, glabellar frown lines were employed as the clinical model. METHODS: Seventy-one patients were enrolled and monitored remotely employing current high-quality mobile phone cameras over a 14-day period. The patients were prompted to take photographs employing this platform at preset intervals, and these photographs were then rated by the AI platform and qualified raters experienced in the field of facial aesthetics. RESULTS: The AI platform had concordance with 2 qualified raters of 46% to 68%, and the inter-rater concordance between 2 rates ranged from 44% to 66%. The intra-rater concordance for the raters was between 57% and 84%, whereas the AI platform had a 100% concordance with itself. The participant and investigator satisfaction ratings of the platform were high on multiple dimensions of the platform. CONCLUSIONS: This AI platform evaluated photos on a comparable level of accuracy as the qualified raters, and it evaluated more consistently than the qualified raters. This platform may have high utility in clinical research and development, including the management of clinical trials, and efficient management of patient care at the clinical practices.

IncobotulinumtoxinA Demonstrates Safety and Prolonged Duration of Effect in a Dose-Ranging Study for Glabellar Lines.

BACKGROUND: To further explore clinical trial results indicating increasing doses of botulinum toxin A prolong duration of effect, a 2-stage, phase 2, randomized, double-blind study investigated the duration of effect and safety of incobotulinumtoxinA (INCO; Xeomin®, Bocouture®) doses higher than the US Food and Drug Administration-approved 20 units (U) for glabellar frown lines (GFL). The stage 1 primary efficacy and safety results were reported previously. Here, we report the results of the final analysis (stage 1 and 2), including primary and secondary efficacy and safety endpoints. METHODS: A total of 241 subjects with moderate-to-severe GFL were randomized to receive a single treatment with 20 (N=61), 50 (N=60), 75 (N=61), or 100U (N=59) INCO. The primary efficacy endpoint was duration of ≥ 1-point improvement from baseline assessed by investigator at maximum frown on the Facial Wrinkle Scale. RESULTS: The median duration of effect was 175 days for the 20U group (95% CI 142, 185), 185 days for the 50U group (95% CI 182, 205), 210 days for the 75U group (95% CI 182, 217), and 215 days for the 100U group (95% CI 183, 237). The incidence of treatment-related adverse events was low across all doses and there were no treatment-related serious adverse events. CONCLUSIONS: These results demonstrate that all INCO doses were well tolerated, consistent with the known safety profile of 20U, and increasing dose prolongs the duration of effect for GFL. J Drugs Dermatol. 2021;20(10):1052-1060. doi:10.36849/JDD.6377THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

A Prospective, Multicenter, Single-Blind, Randomized, Controlled Study of VYC-15L, a Hyaluronic Acid Filler, in Adults for Correction of Infraorbital Hollowing.

BACKGROUND: Rejuvenation of the under-eye area is a popular facial aesthetic treatment option. OBJECTIVES: This study evaluated the safety and effectiveness of VYC-15L for the correction of moderate or severe infraorbital hollowing. METHODS: This was a randomized, controlled, single-blind study with a primary endpoint defined as the proportion of participants with ≥1-grade improvement at Month 3 assessed by an evaluating investigator employing the Allergan Infraorbital Hollow Scale. Three-dimensional imaging was conducted to assess infraorbital volume up to Month 12. Procedure pain and injection-site responses (ISRs) were documented, and safety was monitored throughout the study. RESULTS: At Month 3, the difference between treatment (83.1%) and control (15.6%) was 67.5% (95% CI = 52.9 to 82.0, P < 0.0001). 3D imaging showed a mean volume increase from baseline of 0.733 mL (left) and 0.777 mL (right) at Month 12. Mean pain scores were ≤1.7 (scale of 0 to 10). Most ISRs with initial treatment were mild/moderate and resolved in ≤1 week, including tenderness (49.5%), bruising (42.7%), and swelling (41.7%). Thirty-four participants had treatment-emergent adverse events (TEAEs), of which 14 (10.3%) had treatment-related TEAEs, including bruising (3.8%) and swelling/edema (2.9%), which resolved in ≤2 weeks. Three participants had swelling/edema starting >30 days posttreatment; 2 resolved in ≤4 days, 1 by 45 days. No treatment-related serious AEs were reported. CONCLUSIONS: VYC-15L was safe and effective for the correction of moderate or severe infraorbital hollowing and lasted through 1 year.

DaxibotulinumtoxinA for Injection has a prolonged duration of response in the treatment of glabellar lines: Pooled data from two multicenter, randomized, double-blind, placebo-controlled, phase 3 studies (SAKURA 1 and SAKURA 2).

BACKGROUND: DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin type A in clinical development. Phase 2 data have shown it offers a more prolonged duration of response than onabotulinumtoxinA. OBJECTIVE: To further evaluate the efficacy, duration of response, and safety of 40 U DAXI compared with placebo in the treatment of glabellar lines. METHODS: Two identical, multicenter, randomized, double-blind, placebo-controlled, phase 3 studies were performed (NCT03014622 and NCT03014635 on www.clinicaltrials.gov). Participants with moderate or severe glabellar lines were randomly assigned (2:1) to receive 40 U DAXI or placebo into the corrugator/procerus muscles. Glabellar line severity was assessed by investigators and participants for up to 36 weeks (≥24 weeks). RESULTS: Among 609 participants enrolled (405 DAXI, 204 placebo), 92% completed. DAXI was significantly more effective than placebo in reducing glabellar line severity and maintained none or mild glabellar line severity for a median of 24.0 weeks. It was also generally well tolerated-treatment-related adverse effects were most commonly headache (6.4% vs 2.0%) and injection site pain (3.7% vs 3.9%). LIMITATIONS: The study population was predominantly female and white and received only a single treatment. CONCLUSIONS: DAXI offers a prolonged duration of response for glabellar line reduction and is well tolerated.

ATX-101 (Deoxycholic Acid Injection) Leads to Clinically Meaningful Improvement in Submental Fat: Final Data From CONTOUR.

BACKGROUND: Submental fat (SMF) can negatively affect perceptions of health and attractiveness. The Condition of Submental Fullness and Treatment Outcomes Registry (CONTOUR) was designed to understand SMF treatment in clinical practice. OBJECTIVE: To report efficacy, treatment characteristics, and safety associated with real-world use of ATX-101 (deoxycholic acid injection). METHODS: CONTOUR enrolled adults considering treatment for SMF reduction. ATX-101-treated patients who completed the end-of-treatment questionnaire were divided into those who ended treatment because they met their treatment goals (n = 197) and those who did not (n = 196). RESULTS: Patients who met their goals (a more defined jawline, looking younger, and looking thinner) were more likely to have less SMF at baseline and to receive ≥2 ATX-101 treatments. More patients who met their goals achieved clinically meaningful reduction in SMF and reported increased satisfaction with their appearance (90% vs 57%). Moderate and severe patients' ATX-101 volume was similar for both those who met goals and those who did not, but extreme patients who met their goals required 10 mL more than those patients who did not. CONCLUSION: Careful patient selection, adequate volume administration, and an appropriate number of treatments (dependent on baseline SMF severity) contribute to successful outcomes with ATX-101.

ABOUT FACE: Navigating Neuromodulators and Injection Techniques for Optimal Results

Interest in the cosmetic use of neuromodulators for facial rejuvenation is increasing among physicians, other practitioners, and patients alike, and an expanding array of formulations and reported applications might be helping to drive this trend. Safety, efficacy, and a high level of patient satisfaction can be achieved with all the available botulinum neurotoxin type A (BTXA) products. With any of the formulations, optimal results require knowledge of the individual product's unique properties and dosing, along with an understanding of the patient's goals, relevant anatomy, and proper injection technique. This educational activity reviews these topics on the basis of the published literature and expert opinion. A series of case narratives is also included that provides readers with information and insights for achieving success in clinical practice. J Drugs Dermatol. 2020;19(4 Suppl 2):s5-15.

CME/CE: ABOUT FACE: Navigating Neuromodulators and Injection Techniques for Optimal Results.

Interest in the cosmetic use of neuromodulators for facial rejuvenation is increasing among physicians, other practitioners, and patients alike, and an expanding array of formulations and reported applications might be helping to drive this trend. Safety, efficacy, and a high level of patient satisfaction can be achieved with all the available botulinum neurotoxin type A (BTXA) products. With any of the formulations, optimal results require knowledge of the individual product’s unique properties and dosing, along with an understanding of the patient’s goals, relevant anatomy, and proper injection technique. This educational activity reviews these topics on the basis of the published literature and expert opinion. A series of case narratives is also included that provides readers with information and insights for achieving success in clinical practice.J Drugs Dermatol. 2020;19(4 Suppl 2):s5-15.

IncobotulinumtoxinA Demonstrates Safety and Prolonged Duration of Effect in a Dose-Ranging Study for Glabellar Lines.

BACKGROUND: Recently reported clinical data provides evidence that increasing the dose of botulinum toxin A increases the duration of efficacy. A 2-stage Phase 2, randomized, double-blind study investigated the duration of effect and safety of IncobotulinumtoxinA (INCO; Xeomin®, Bocouture®; Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany) at doses higher than the approved 20 units (U) for glabellar frown lines (GFL). Primary safety and efficacy endpoints of Stage 1 are reported here. METHODS: 151 subjects with moderate-to-severe GFL were randomized 1:2:2 to receive a single treatment with 20U, 50U, or 75U INCO. The primary efficacy endpoint was median duration of at least 1-point improvement from baseline as assessed by investigator at maximum frown on the Facial Wrinkle Scale. RESULTS: The median duration of effect was 185 days for the 50U dose group (95% CI:[182, 205]) and 210 days for the 75U dose group (95% CI:[182, 217]). Duration of effect was significantly longer for 75U vs 50U (P=0.0400) and 20U (P=0.0166) despite the study not being powered for confirmatory statistical significance testing between the dose groups. Duration of effect was also longer for 50U vs 20U, however; statistical significance was not reached (P=0.4349). The incidence of treatment-related adverse events was low across all doses (20U:2[6.7%], 50U:6[10.0%] and 75U:8[13.1%]). CONCLUSIONS: These results demonstrate a dose effect of at least 6 months duration with higher doses in the majority of GFL subjects. All doses were well tolerated and safety was consistent with the known safety profile of 20U INCO for GFL. J Drugs Dermatol. 2020;19(10):985-991. doi:10.36849/JDD.2020.5454.

A Double-Blind, Placebo-Controlled, Phase 3b Study of ATX-101 for Reduction of Mild or Extreme Submental Fat.

BACKGROUND: ATX-101 (deoxycholic acid injection) is approved for reduction of moderate or severe submental fat (SMF). OBJECTIVE: To evaluate the efficacy and safety of ATX-101 in subjects with mild or extreme SMF. PATIENTS AND METHODS: Adults with mild or extreme SMF (based on clinician assessment) were randomized to receive ≤6 treatments with ATX-101 or placebo. Efficacy end points, evaluated at 12 weeks after last treatment, included percentage of subjects who achieved ≥1-grade improvement in SMF from baseline based on both clinician and patient assessment (composite CR-1/PR-1 response) as well as multiple subject-reported outcomes. Safety end points included change in skin laxity and incidence of adverse events. RESULTS: Overall, 61.3% of ATX-101-treated subjects versus 6.7% of placebo-treated subjects with mild SMF and 89.3% versus 13.3% of subjects, respectively, with extreme SMF achieved a composite CR-1/PR-1 response (p < .001 for both). ATX-101-treated subjects also reported higher levels of satisfaction and greater reductions in the psychological impact of SMF versus placebo-treated subjects regardless of baseline SMF severity. Skin laxity was unchanged or improved in most of the subjects. Adverse events were mainly mild/moderate, transient, and associated with the injection site. CONCLUSION: ATX-101 was efficacious and well tolerated for reduction of mild or extreme SMF.

The Platysma Contraction Pattern in Healthy Adults: A Vector Analysis Study.

BACKGROUND: The platysma muscle's role in lower face dynamics is complex. Multiple insertion points to soft-tissue structures at various levels in the lower face create a multifaceted contraction pattern. To avoid adverse effects in cosmetic procedures when targeting the platysma, its anatomy and physiology must be understood. Clinical observations hint at a bidirectional contraction pattern. METHODS: Eighteen healthy volunteers (13 women and five men) with a mean age of 44.2 ± 10.1 years were enrolled. Skin displacement vector analysis was used on maximal platysma contraction to characterize and calculate the movement of the neck and lower face skin. RESULTS: In all of the participants, a bidirectional movement of the skin was observed: the skin of the lower face and inferior to the jawline moved caudally, whereas the skin of the lower neck moved cephalad. Both movements converged at a line situated at 54% ± 10% and 55% ± 8% of the length between the clavicle and the inferior base of the ear lobe in men and women, respectively ( P = 0.70). CONCLUSIONS: The platysma is a bidirectional muscle with a line of convergence. Whereas the superior portion acts as lip depressor, the lower portion elevates the skin of the upper chest and lower neck. This transition can explain some of the clinically observed adverse effects of neuromodulation of the neck area. It can potentially direct neuromodulation injections to focus above the convergence line to better address lower face descent.

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

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

Creating Lift in the Lower Face With Botulinum Toxin A Treatment: An Anatomical Overview With Videos and Case Studies Illustrating Patient Evaluation and Treatment.

Background: Relaxation of depressor muscles in the lower face with botulinum toxin A (BoNT-A) can create a lifting effect and dramatically improve jawline contour and resting facial expression. Even with the recent increase in interest in lower face rejuvenation, BoNT-A is a relatively under-recognized tool for treatment of this area. When treating the lower face, an understanding of anatomy and the relationship between the facial muscles is especially important, as injection patterns must be customized for consistently positive outcomes. Objectives: This study was aimed to provide basic knowledge of the activities of the muscles in the lower face and neck and to describe the basis for injecting BoNT-A to create lift in this area. Expert guidance for injection is also provided. Methods: As part of a continuing medical education course on differentiating botulinum toxin products, a panel of 4 expert physician injectors participated in a live webinar to discuss the implications of increasing toxin use. Results: The practical guidance in this manuscript is based on the most frequently requested information by audience members and the information considered critical for success by the authors. The authors outline the functional anatomy of the lower face most relevant for BoNT-A treatment and case studies as well as methods for patient evaluation and injection technique are also provided. Videos showing treatment planning and injection technique for the lower face and neck are included. Conclusions: BoNT-A is an important nonsurgical tool for creating lift in the lower face.

High-Dose Neuromodulators: A Roundtable on Making Sense of the Data in Real-World Clinical Practice.

BACKGROUND: For aesthetic treatment with botulinum neurotoxin type A (BoNTA), interest in maximizing treatment duration and efficacy has prompted study of doses higher than those used in registration studies. As data emerge, it is important that physicians understand how to apply study findings to their own practice so that patient demand is satisfied. OBJECTIVES: To bring together leading experts in neuromodulators for a roundtable discussion on the implications of high-dose BoNTA studies for patient care. METHODS: The authors reviewed and discussed recent data from high-dose BoNTA studies for abobotulinum toxin A, incobotulinum toxin A, and Oonobotulinumtoxin A. RESULTS: Discussion focused on the challenges of data interpretation and extrapolation of study findings for real-world patient care. The authors participated in a candid discussion of whether the observed improvements in treatment duration and patient satisfaction warrant treatment with high-dose regimens delivered as high-concentration injections. Safety was also discussed, as well as economic considerations for both practices and patients. Of note, for BoNTA products, the registration dose, when administered in a smaller total volume, appears to give rise to more durable results than those observed in pivotal trials, implicating product concentration as an important consideration. Importantly, at higher doses, extended duration of effect does not appear to be at the expense of natural-looking results. CONCLUSIONS: While the authors provide considerations for the development of individual clinical practice, there is no one-size-fits-all recommendation. It may be that "high-dose" BoNTA is in reality the optimal dose; however, important economic considerations may prevent rapid uptake for all patients.

Best Clinical Practices with ATX-101 for Submental Fat Reduction: Patient-related Factors and Physician Considerations.

BACKGROUND: Submental fat can be reduced with ATX-101 (deoxycholic acid injection), a customizable and minimally invasive alternative to liposuction. In the years since its approval, the treatment patterns of ATX-101 have evolved. METHODS: A panel of experienced physicians from the United States gathered to generate best practices for the use of ATX-101 in submental contouring. RESULTS: The expert panel provided their insights on appropriate patient selection, managing patient expectations of ATX-101 treatment outcomes, and adverse events, and guidance on ATX-101 administration for optimal outcomes are presented here. CONCLUSION: These best clinical practices on the use of ATX-101 for the reduction of submental fat should enable physicians to enhance the patient treatment experience and outcomes.

Safety, effectiveness, and subjective experience with topical bimatoprost 0.03% for eyelash growth.

BACKGROUND: Ocularly applied bimatoprost 0.03% is associated with increased eyelash growth. OBJECTIVE: To assess the safety, efficacy, and subjective experience of using dermal application of bimatoprost 0.03% for the growth of natural eyelashes. METHODS: Prospective, open-label study of subjects who desired longer, thicker (fuller), and darker natural eyelashes. Bimatoprost was applied to the upper lid margin once daily for 12 weeks. Adverse events and intraocular pressure were assessed, and subjects completed health outcomes questionnaires. Eyelash growth and darkening were scored using photographs taken at weeks 1 and 12. RESULTS: All subjects were female (N=28). No serious or unexpected adverse events were reported. The mean change from baseline intraocular pressure was less than 1 mmHg at each time point, but was statistically significant at weeks 1 and 4 (p< or =.047). At week 12, all subjects had noticed significant growth or darkening. Post hoc analysis of photographs corroborated these reports (p<.001). CONCLUSION: Bimatoprost was found safe for eyelid application and was associated with enhanced eyelash growth. All subjects noticed favorable changes in the appearance of their eyelashes.

Safety and Efficacy of EB-001, a Novel Type E Botulinum Toxin, in Subjects with Glabellar Frown Lines: Results of a Phase 2, Randomized, Placebo-Controlled, Ascending-Dose Study.

BACKGROUND: Botulinum neurotoxins, which are widely used commercially for therapeutic and cosmetic applications, have historically belonged to serotypes A and B. Serotype E has a distinct profile with a faster onset and shorter duration of effect. EB-001 is a proprietary formulation of serotype E in development for aesthetic (cosmetic) and therapeutic uses. METHODS: This first-in-human, randomized, double-blinded, placebo-controlled, ascending-dose cohort study enrolled 42 subjects who received EB-001 (n = 35) or placebo (n = 7). The efficacy primary outcome was the proportion of subjects with a two-grade investigator-rated improvement in glabellar frown line severity at maximum frown. Safety evaluations included adverse events, laboratory tests, and physical examinations. RESULTS: A two-grade investigator-rated response was observed starting in the third cohort (EB-001), with increased rates observed at higher doses. Onset of clinical effect was within 24 hours, with a duration ranging between 14 and 30 days for the highest doses. Adverse event incidence was low, with the most common being mild to moderate headache. There were no serious adverse events or ptosis, and there were no clinically significant changes in other safety assessments. CONCLUSIONS: In this clinical study in glabellar frown lines, EB-001 showed favorable safety, tolerability, and dose-dependent efficacy, with an 80 percent response rate at the highest dose. The maximum clinical effect of EB-001 was seen within 24 hours and lasted between 14 and 30 days. This differentiated EB-001 profile supports its development for aesthetic and therapeutic applications where fast onset and short duration of effect are desirable. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Lower Face: Clinical Anatomy and Regional Approaches with Injectable Fillers.

The use of injectable fillers enables facial sculpting through treatment of volume depletion and modeling of facial contours. Injectable fillers are among the most frequently performed minimally invasive cosmetic procedures.However, treatment of the lower third of the face can be challenging and requires expertise in facial anatomy. In this article, the authors provide a comprehensive review of the anatomy of the lower third of the face, highlighting danger zones. In addition, the authors describe their preferred approach and detailed technique used in the treatment of each specific area, namely the jawline, prejowl sulcus, melomental folds, and lips.