Efficacy and Safety of PrabotulinumtoxinA in Subjects With Benign Masseteric Hypertrophy: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Phase 3 Trial and Open-Label Extension Study.

BACKGROUND: Despite the widespread use of botulinum toxin (BTX) injection for the treatment of masseter muscle hypertrophy (MMH), there is no standard treatment option. OBJECTIVE: We report the efficacy and safety for BTX in MMH over a period of 48 weeks. METHODS: In double-blinded, placebo-controlled phase 3 trials, 180 patients (randomized 1:1) received treatment with placebo (normal saline) or prabotulinumtoxinA (48 units). Masseter muscle thickness (at maximal clenching and resting positions), 3D imaging analysis, and masseter muscle hypertrophy scale grades were analyzed at each time point. After the 24-week CORE study, all patients who met the same criteria of the CORE study at week 24 ( n = 114) received only prabotulinumtoxinA, regardless of previous treatment, for an additional 24 weeks (48 weeks in total) for the open-label extension study. RESULTS: The largest differences in mean and percent changes from baseline in masseter muscle thickness were observed at 12 weeks, and there were significant differences between the 2 groups at all time points (all p < .001). The effect was independent of the number of injections. No serious adverse event was observed. CONCLUSION: PrabotulinumtoxinA could effectively ameliorate MMH without major complications.

Subcutaneous infection caused by Mycobacterium abscessus following botulinum toxin injections: A case report and literature review.

BACKGROUND: The rapid development of cosmetic injections has led to an increased incidence of nontuberculous mycobacterial (NTM) infection. PATIENTS AND METHODS: Here, we presented a case of cutaneous Mycobacterium abscessus infection subsequent to botulinum toxin injection for treating masseter hypertrophy, and reviewed the literature on skin and soft tissue infections caused by NTM after cosmetic injections. RESULTS AND CONCLUSIONS: The patient underwent surgical excision and regular antibiotic therapy and has had nearly 2 months of follow-up without any signs of infection. The diagnosis and treatment of NTM infection have always been challenging, and further research is needed to standardize and guide the treatment.

Neuromodulator Finesse for Masseter Hypertrophy and Bruxism.

SUMMARY: A particularly prominent mandibular angle or a hypertrophied masseter muscle can result in an excessively wide facial appearance, which some individuals may find less aesthetically pleasing. Although normally a benign condition and strictly an aesthetic concern, a hypertrophied masseter can also cause pain, bruxism, and headaches. Neuromodulator for masseter reduction and treatment of bruxism has become first-line treatment. In this article, the authors present the senior author's (R.J.R.) anatomic approach to neuromodulator injection of the masseter, with a corresponding video of the injection technique.

Assessment of Electromyographic Changes in a Patient with Masseter Hypertrophy and Muscle Pain after Botulinum Injections: A Case Report and 5 Months Follow-up.

AIM: To determine if botulinum injections in masseters could be an option to avoid surgery and prolonged treatment with occlusal splints and/or drugs to care for both painful bruxism and cosmetic improvement in a patient with a square jaw, bruxism, and orofacial pain. BACKGROUND: Masseter muscle hypertrophy (MMH) is a benign, unilateral, or bilateral, painless enlargement in the lower face. It presents as a symmetrical or asymmetrical increase in the masseter muscle. Masseter muscle hypertrophy (MMH) sometimes can be related to bruxism symptoms like muscle and/or temporomandibular joint (TMJ) pain. CASE DESCRIPTION: A 38-year-old woman complained of bilateral pain at palpation in the masseter body. She also complained about esthetics because of the prominent masseter muscle in the face and square face shape. A diagnosis of bruxism-related myalgia was performed, and treatment with botulinum injections into the masseter muscles was opted for. An oral electromyography was performed to detect the electrical muscular activity of masseter muscles over time. CONCLUSION: After a drastic reduction in the mean electrical activity immediately after the botulinum injections, a progressive increase in strength over time was noted, testifying about the decrease in the effect of botulinum over time. The pain disappeared for 5 months after the injections of botulinum. The reduction of the masseter muscle mass led to a softening of the face shape. CLINICAL SIGNIFICANCE: This case report shows that treatment with botulinum can lead, in the short term, to a reduction in orofacial pain due to a decrease in muscle electrical activity.

Efficacy of botulinum toxin in masseter muscle hypertrophy for lower face contouring.

BACKGROUND: Masseter muscle hypertrophy (MMH) usually presents with cosmetic concerns as it may lead to widening of the lower face. Apart from the traditional surgical approaches, botulinum toxin type A (BTA) injection is a non-invasive treatment option available. There are no standard guidelines for this procedure. OBJECTIVES: To study the efficacy of botulinumtoxin A in MMH for lower face contouring. METHODOLOGY: The Cochrane Library, PubMed/MEDLINE, Google-scholar, Science-Direct database, and ResearchGate from inception until September 2021 were searched using the keywords "botulinumtoxin type A," "masseter muscle hypertrophy," "lower face contouring," and "masseter botox." All available retrospective and prospective studies, case-series, case-reports, and expert reviews were included with an emphasis on efficacy of BTA in MMH and units injected into the muscle, points of placement, adverse events, and the duration of its effect. Reference lists of the resultant articles, as well as relevant reviews, were also searched. RESULT: 40 articles were shortlisted for the review, of which 14 studies with sample-size ≥10 in accordance with the study requirements were summarized in a tabular form for analysis and easy comparison and reference. CONCLUSION: BTA injection is a non-invasive, safe, and effective treatment for MMH. The optimum number of BTA units could not be ascertained due to wide variability in the studies as well as ethnicity of patients and extent or some measurement of MMH. The points of placement of injection should be well within the boundaries of the masseter muscle. The maximum effect of BTA after a single injection session is usually seen in ~3 months, and the duration may last for 6-12 months. Multiple injection sessions may be required to maintain a long-term effect. Injection technique and total number of injection units of neuromodulator must be individualized for each patient.

A Cadaveric Study of Dye Spreading: Determining the Ideal Injection Pattern for Masseter Hypertrophy.

BACKGROUND: Masseter hypertrophy is the main cause of an asymmetrical and squared lower facial contour in the Asian community. Botulinum toxin injection technique is crucial to treat this condition. OBJECTIVE: To improve injection techniques for masseter hypertrophy by elucidating the distribution of the injections within the masseter. METHODS: Thirty masseter muscles were divided into 6 groups of 5 muscles each. Each group received one 0.2- or 0.3-mL injection at Point A, B, or C according to a three-point technique. Muscle dimensions and dye of the primary and secondary dye spreading were measured. RESULTS: The average muscle length, width, and thickness were 69.87, 33.50, and 11.23 mm, respectively. The average primary longitudinal and horizontal spreading was 36.56 and 15.60 mm, respectively. No statistically significant difference was found between 0.2- and 0.3-mL injections at each point. CONCLUSION: The three-point technique best fits in the safe zone and should be the standard injection technique for masseter hypertrophy. Injection at Points B and C may create secondary spreading that affect the risorius muscle and the parotid gland which are the cause of asymmetrical smiling and xerostomia, respectively. The dosage should be adjusted according to the muscle volume and not only the thickness.

Ultrasonographic Considerations for Safe and Efficient Botulinum Neurotoxin Injection in Masseteric Hypertrophy.

There are still concerns about masseteric bulging due to a lack of knowledge about the internal architecture of the masseter muscle. Further investigations are therefore required of the most-effective botulinum neurotoxin (BoNT) injection points and strategies for managing masseteric bulging. The purpose of this study was to identify safer and more effective botulinum neurotoxin injection points and strategies by using ultrasonography to determine the structural patterns of the deep inferior tendon. We also measured the precise depths and locations of the deep inferior tendon of the masseter muscle. Thirty-two healthy volunteers participated in this study, and ultrasonography was used to scan the masseter muscle both longitudinally and transversely. Three structural patterns of the deep inferior tendon were identified: in type A, the deep inferior tendon covered the anterior two-thirds of the masseter muscle (21.8%); in type B, the deep inferior tendon covered the posterior two-thirds of the masseter muscle (9.4%); and in type C, the deep inferior tendon covered most of the inferior part of the masseter muscle (68.8%). Depending on the ultrasonography scanning site, the depth from the skin surface to the mandible in the masseteric region ranged from 15 to 25 mm. The deep inferior tendon was typically located 2 to 5 mm deep from the mandible. Ultrasonography can be used to observe the internal structure of the masseter muscle including the deep inferior tendon in individual patients. This will help to reduce the side effects of masseteric bulging when applying retrograde or dual-plane injection methods depending on the structural pattern of the deep inferior tendon.

Management of unilateral idiopathic masseter muscle hypertrophy with botulinum toxin type A.

Masseter hypertrophy (MH) is an uncommon disorder which can cause both aesthetic and functional problems. The most common aetiological factors associated with MH are habit of chewing gum, clenching and/or bruxism. The treatment of MH includes conservative management as well as surgical resection of the enlarged muscle and/or bone. Injection of botulinum toxin type A is a relatively new and minimally invasive method for management of masseter muscle hypertrophy, which offers many advantages over conventional surgical management. This paper reports a case of unilateral MH of unknown origin which was treated with injection of botulinum toxin type A, resulting in satisfactory reduction in the volume of muscle and improvement of facial aesthetics.

Efficacy and Safety of a Novel Botulinum Toxin A for Masseter Reduction: A Randomized, Double-Blind, Placebo-Controlled, Optimal Dose-Finding Study.

BACKGROUND: A wide lower face and a square jaw are considered esthetic problems, particularly in Asia. OBJECTIVE: To investigate the optimal dose of a novel botulinum toxin (prabotulinum toxin A) for treating masseteric hypertrophy. METHODS: Ninety subjects with masseteric hypertrophy were randomly divided into 5 groups and treated with placebo (A, normal saline) or prabotulinum toxin A (B: 24, C: 48, D: 72, and E: 96 units). Photography, ultrasonography, and 3-dimensional imaging were performed before and after injection at baseline and at 4, 8, 12, and 16 weeks after treatment. The participants also rated their satisfaction. RESULTS: Masseter thickness significantly reduced in all groups at 12 weeks, compared with that in the placebo group. A dose-dependent reduction in masseter thickness was observed at the resting and maximal clenching positions. Sonography and 3-dimensional imaging revealed a gradual reduction in masseter thickness and volume, respectively, during the first 12 weeks. Despite being slightly effective, a dose of 24 units might be insufficient for resolving square face problems. Patients in Group E reported discomfort during jaw movement. CONCLUSION: Prabotulinum toxin A could effectively improve lower face contour without major complications, with an optimal dose of 48 to 72 units, followed by reinjection after 12 weeks.

Alternative Clinical Indications of Botulinum Toxin.

Botulinum toxin type A (BoNTA) is a powerful neurotoxin that inhibits acetylcholine release from presynaptic vesicles. The potency and safety profile of BoNTA grant the toxin vast therapeutic potential. It has been used off-label for a variety of dermatologic conditions. This review aims to analyze published literature regarding the benefits and risks of the off-label use of BoNTA beyond facial lines, including eccrine hidrocystomas, enlarged pores, keloids and hypertrophic scars, hidradenitis suppurativa, hyperhidrosis, masseter muscle hypertrophy, and salivary gland hypertrophy, among others. A MEDLINE search from January 2000 to December 2019 was conducted on the off-label uses of botulinum toxin in dermatology.

Efficacy of Incobotulinum toxin-A for the treatment of masseter muscle hypertrophy in Asian Indian patients: A 2-year follow-up study.

BACKGROUND: With the changing trends, more and more patients are opting for nonsurgical or minimally invasive options for reshaping the face. Noninvasive treatments such as incobotulinumtoxinA (Xeomin Cosmetic® ; Merz Pharma Canada Ltd., Burlington, ON, Canada) are a preferred modality for reducing the volume of the muscle and therefore reducing the width of masseter. AIMS: To evaluate the efficacy of Xeomin treatment in long-term management of bilateral masseter hypertrophy in Asian Indian patients. PATIENTS/METHODS: A total of 30 patients were enrolled in the study and were injected with 30 U Xeomin on each side of face, at baseline. Fifteen patients received a second session of Xeomin injection at 12th week, and remaining 15 patients received an additional third session, at 12th and 24th weeks post the first injection, respectively. Follow-up was done at 4th-, 12th-, 24th-, and 36th-week and at first- and second-year follow-ups. RESULTS: For the patients who received two injections, the maximum reduction of 26.85% was observed at 24th week, which was maintained as 20.04% reduction until second follow-up year. The patients who received three injections exhibited very high reduction of 43.12% of masseter volume at 36th week, which was maintained at 38.72 % until the second follow-up year. Three sessions of Xeomin injections were proved to be more effective in long-term maintenance of reduced masseter volume than 2 sessions of injections. CONCLUSIONS: Xeomin injections were found to be effective in long-term management of bilateral masseter hypertrophy. This is the first of its kind paper, which evaluates the long-term effects of Xeomin injections for the treatment of masseter hypertrophy.

Temporal volume increase after reduction of masseteric hypertrophy utilizing incobotulinumtoxin type A.

BACKGROUND: Treating the lower face with neuromodulators and targeting the masseter muscle can reduce masseteric hypertrophy but can also change the facial shape. A novel observation after the treatment of the masseter muscle with incobotulinumtoxin Type A was the increase in temporal volume. AIM: Objectively assess temporal volume increase following treatment of masseteric hypertrophy using incobotulinumtoxin Type A. METHODS: Nine female patients with a mean age of 35.11 years ± 9.1 [Asian (11.1%) and Caucasian (88.9%)] were treated with incobotulinumtoxin Type A for masseteric hypertrophy. Masseteric prominence and temporal volume were assessed by two independent raters, and temporal fossa volume was measured via 3-dimensional volumetric imaging. RESULTS: Independent of the neuromodulator injection technique (ie, single-injection versus multi-injection), a reduction in masseteric hypertrophy occurred represented by a decrease in the masseter prominence scale. In addition, the treatment resulted in a significant improvement of the temporal volume scale and an increase in the measured volume of the temporal fossa. None of the presented measurements were statistically significantly different between the two utilized injection techniques. CONCLUSIONS: This study supports using a full-face approach when performing aesthetic treatments. Anatomical concepts can help to guide treatments: the compensatory increase in temporalis function after masseter muscle treatment resulted in an increased in temporal fossa volume. The findings presented herein should not be considered as a new concept for treating the temporal fossa but rather as an additional possibility for increasing the temporal volume.

Efficacy of Botulinum Toxin in Treating Asian Indian Patients with Masseter Hypertrophy: A 4-Year Follow-Up Study.

BACKGROUND: Asian Indians usually have wide lower faces because of masseter hypertrophy. The authors evaluated the efficacy of botulinum toxin type A in long-term management of bilateral masseter hypertrophy in Asian Indian patients. METHODS: Fifty patients were enrolled in the study and injected with 30 U of botulinum toxin type A to each side of the face, at baseline. Based on masseter muscle thickness and response to the injections, 25 patients underwent a second injection session at week 12, and the other 25 patients underwent additional third sessions, at week 24 after the first injection, respectively. Standardized photography and ultrasonography were performed to assess facial contour and masseter muscle thickness at baseline and at 1-, 2-, 3-, and 4-year follow-ups. A p value < 0.05 was considered statistically significant. RESULTS: The authors observed 12 percent (p < 0.0001) average masseter muscle size reduction at week 12. The maximum reduction (26.6 percent; p < 0.0001) was observed at week 24 for the patients who received two injections and maintained an average 24.43 percent (p < 0.0001) reduction until follow-up at year 4. Patients who received three injections exhibited very high reduction (42.52 percent; p < 0.0001) of masseter volume at week 36 and maintained an average 40.64 percent (p < 0.0001) reduced volume until year 4. CONCLUSIONS: Botulinum toxin type A treatment is effective for long-term management of bilateral masseter hypertrophy. Doses repeated at 12-week intervals accentuate masseter volume reduction and also help maintain reduced masseter volume for 4-year follow-up, with satisfactory facial contour.

Ultrasonographic Evaluation of The Effects of Orthodontic or Functional Orthopaedic Treatment on Masseter Muscles: A Systematic Review and Meta-Analysis.

Objectives: This review investigated the effects of orthodontic or functional orthopedic therapy on masseter muscle thickness through the use of ultrasonography (US) in growing subjects when compared with untreated subjects. Materials and Methods: This review systematically assessed studies that investigated growing subjects undergoing orthopedic therapy for the correction of malocclusion of vertical, sagittal and transversal plane. Electronic databases (CENTRAL, MEDLINE-PubMed, Scopus and Web of Science) were searched up to February 2019, including available RCTs and CCTs, without language restrictions. The primary outcome was the effect of orthopedic or functional treatment on masseter muscle thickness. The risk of bias of included studies was assessed through the Newcastle-Ottawa quality assessment scale with the aim of defining their methodological quality. A random-effects meta-analysis analyzing mean differences with 95% confidence intervals was used for quantitative analysis. Results: The search retrieved 749 titles, but the studies selection resulted in a final sample of 5 CCTs. The studies retrieved data from 233 children (age range: 5-22 years) and were conducted at university dental clinics. Children were treated for Class II malocclusion, increased vertical dimension or lateral cross-bite variably with rapid or slow maxillary expansion, twin block, bite block, mandibular activators, quad helix, alone or in combination. Risk of bias was assessed as medium for three studies, low for one and high for another. The meta-analysis determined that at the end of orthopedic or functional treatment masseter muscle thickness, measured through the use of US, is significantly reduced (MD -0.79 mm; 95% CI -1.28 to -0.31). The reduction in muscle thickness, therefore, could be considered an indicator for the evaluation of the success of therapy with orthodontic appliances. Conclusions: Although the meta-analysis revealed that US could be considered a less invasive and effective method to evaluate the masseter muscle thickness, single-blinded RCTs, are required to confirm US reliability in this field of application. This review was registered on PROSPERO with the following registration number: CRD42018068402.

Botulinum Toxin Injections for Masseter Reduction in East Asians.

BACKGROUND: Cultural ideals for a slimmer face have led to an upsurge in interest in facial contouring among East Asians. Although surgical resection has traditionally been the main treatment option, botulinum toxin injection is becoming a popular, noninvasive alternative. OBJECTIVE: To describe the use of botulinum toxin injection for masseter reduction in East Asians. METHODS: An electronic search of the PubMed database was performed for studies published from 2000 to 2017 that meet the word combination of botulinum toxin, masseter, hypertrophy, and/or lower face contouring. Only the studies conducted in East Asian countries were analyzed in this review, exception of one study from Thailand. RESULTS: A total of 12 publications were identified. Each study was reviewed to extract relevant information on patient selection, injection techniques, efficacy, dosage, frequency, and main side effects of treating masseters with botulinum toxin. CONCLUSION: Botulinum toxin injection for masseter reduction in East Asians is efficacious and generally considered safe with no significant side effects. Future areas for investigation include defining the criteria for benign masseteric hypertrophy, minimum effective dosage of botulinum toxin, and the potential long-term effects of the injection.

Assessment of changes in masseter muscle by three-dimensional close-range photogrammetry after Botulinum toxin type-A injection: A case report with review of literature.

Masseter muscle hypertrophy (MMH) is a benign, unilateral or bilateral, painless enlargement. Treatment protocols include surgical excision or a non-invasive option, using botulinum toxin type A (BTX-A). There is no study in the literature that measures this dimensional change in the masseter muscle (MM). The aim of this case report is to present changes in volume and surface area in MM with three-dimensional closer an gestereophotogrammetry (3DCS). For treatment 30 units of BTX-A was injected into the three points hypertrophic muscle and patient records were taken to compare with 3DCS with a non-metric Canon EOS 550 D camera before and after injection. The changes in the surface area and volume of this muscle were mapped and the objective data were obtained. This technique is useful for predicting the results of BTX-A application, and can be a useful tool for better physicianpatient communication.

Masseter Muscle Volume Changes Evaluated by 3-Dimensional Computed Tomography After Repeated Botulinum Toxin A Injections in Patients With Square Facial Morphology.

INTRODUCTION: Botulinum neurotoxin A (BoNT-A) is a minimally invasive and technically straightforward treatment of masseter muscle (MM) volume reduction and facial contouring, but the literature on its long-term effect on MM volume remains unclear. OBJECTIVE: This study aimed to assess quantitatively for progressive volume changes of lower facial contour after 3 BoNT-A injections in patients with bilateral MM hypertrophy causing square facial morphology using 3-dimensional computed tomographic scans. MATERIALS AND METHODS: Ten female patients with square facial morphology due to bilateral MM hypertrophy were recruited to, and 6 completed, this clinical study. Each received 24 U of BoNT-A into the inferior portion of each MM on both sides, repeated 6 monthly to complete 3 treatments. Masseter muscle volume changes were assessed using 3-dimensional computed tomography at pretreatment (before injections) and posttreatment (1 year after the third injection). RESULTS: Mean MM volume significantly reduced from 26.39 ± 4.18 cm before treatment to 23.26 ± 4.31 cm 1 year after treatment (P = 0.002). CONCLUSION: Three consecutive 6-monthly BoNT-A injections into the MMs reduced their volume by 12% when assessed 1 year after completion of treatment.