Search

Summary: Aging of the face is the result of the interrelation of three-dimensional changes occurring over time among the 5 different layers of the face and its associated structures. Knowledge regarding the causes of these changes and identification of new key anatomic structures have helped elucidate one of the most complex areas of the human body. This has resulted in the introduction of pharmacologic agents to help stop, mitigate, or counteract signs of aging and restore the youthful appearance of the face. The authors performed a systematic search of the literature to review the current highest-level evidence of facial antiaging pharmacologic agents. Pharmacologic and minimally invasive antiaging treatments can target different components of facial aging and continue to evolve. With continuous research efforts, traditional treatments, such as botulinum toxin type A, injectable fillers, and chemical peels, are emerging in newer, more effective formulations, with longer lasting clinical results. However, for soft-tissue descent and facial volume loss, surgery remains the standard treatment. An adequate understanding of the three-dimensional process of facial aging over time (the fourth dimension), facial anatomy, and the pharmacologic properties of antiaging/rejuvenation agents are the sine qua non of facial antiaging treatment. The specific modality should be tailored to patient characteristics, preferences, and goals., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Although the efficacy of botulinum toxin type A (BoNTA) has been shown to vary depending on injection layer, reconstitution volume, and BoNTA formulation, the effect of injection pattern has rarely been mentioned. The authors compared the therapeutic effects in patients treated with BoNTA with retrograde linear and traditional spot injection techniques., Methods: Twenty-eight participants were enrolled in a split-face, patient-blinded randomized clinical trial. Each patient received BoNTA injected with linear injection technique on one side and with spot injection technique on the other side. Outcomes included wrinkle improvement rates (WIRs) of the 2 injection techniques determined by wrinkle scores derived from an Antera 3-dimensional camera, muscle activity assessed by ultrasound, and patient-reported pain rating on a numeric rating scale., Results: All participants completed the study. For forehead wrinkles, WIR on the linear side was significantly larger than that on the spot side at 1 week and 1 month ( P < 0.02). For glabellar wrinkles, WIR on the linear injection side was significantly larger than that on the spot side at 1 week ( P = 0.04). However, for periorbital wrinkles, WIR on the spot side was significantly larger than that on the linear side at 1 week ( P < 0.03). No significant difference was observed between the injection patterns in terms of muscle contraction and numeric rating scale pain scores., Conclusions: Compared with the traditional spot injection, retrograde linear injection was superior in reducing forehead lines and glabellar lines, but less effective in reducing periorbital lines when identical dosages were injected., Clinical Question/level of Evidence: Therapeutic, II., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Carbon-assisted, Q-switched, neodymium-doped yttrium-aluminum-garnet laser treatment consists of applying a topical carbon suspension all over the face, followed by irradiation with a Q-switched 1064-nm neodymium-doped yttrium-aluminum-garnet laser. The delivery of multiple microdroplets of dilute onabotulinum toxin type A into the dermis has been investigated as a tool for facial rejuvenation. The aim of this study was to assess the effectiveness of the combined treatment with botulinum toxin and carbon peel laser (performed with a standardized technique) in patients with seborrhea, dilated pores, and wrinkles, and to demonstrate its benefits in improving the overall skin aspect., Methods: Patients enrolled in this prospective pilot study underwent 3 sessions of the combined treatment carried out 3 months apart. To evaluate the improvement of skin texture, wrinkles, dilated pores, and acne lesions, the Fitzpatrick Wrinkle Assessment Scale, the Physician Global Aesthetic Improvement Scale, a photographic scale for the pore assessment, and the Investigator Global Assessment of Acne scale were used. The FACE-Q was also administered to assess patient satisfaction. The scores obtained were compared using a paired t test., Results: Twenty patients were recruited. The differences between pretreatment and posttreatment scores were statistically significant ( P < 0.05) on the Fitzpatrick Wrinkle Assessment Scale, Physician Global Aesthetic Improvement Scale, Investigator Global Assessment of Acne scale, FACE-Q, and photographic scale for the pore assessment., Conclusions: This combined protocol could be considered as a useful tool to treat skin flaws that affect texture, microroughness, and seborrhea and to reduce the size of enlarged pores. Its versatility allows for customized treatment with minimal discomfort to patients., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)

Background: Despite the increasing popularity of various materials for ischemia-reperfusion (I/R) injury mitigation, research on botulinum toxin type A (BoNTA) remains limited. This study assesses BoNTA's efficacy in protecting flaps from I/R injury by inhibiting the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system and reducing reactive oxygen species (ROS) production., Methods: Seventy-six Sprague-Dawley rats were studied. We examined the effects of BoNTA on superoxide production in four rats using a lucigenin-enhanced chemiluminescence assay (LECL). Another group of 60 rats had their superficial inferior epigastric artery (SIEA) flaps treated with either BoNTA or saline and clamped for 0, 1, and 4 hours before reperfusion. Flap survival and histological outcomes were assessed five days post-operation. ROS production in SIEA flaps and femoral vessels was analyzed in 12 additional rats, post-I/R injury., Results: The LECL results showed that the BoNTA group had significantly lower superoxide production compared to controls, with notable reductions at 4 hours. While no significant differences were noted at the 0 and 1-hour marks, the 4-hour mark showed significant protective effects in BoNTA-treated groups. The survival rate was 90% for BoNTA-treated rats versus 60% for controls ( P = 0.028). Significant reductions in ROS were also observed in the 4-hour I/R group., Conclusions: BoNTA effectively protects against I/R injury by inhibiting the NADPH oxidase system and reducing ROS levels. These results support further investigation into the specific mechanisms of NADPH oxidase inhibition by BoNTA and its potential clinical applications, given its safety profile., Clinical Relevance Statement: The findings from the present study are expected to provide a basis for clinical studies regarding this use of BoNTA., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)

Background: As a minimally invasive therapy, botulinum toxin A (BTXA) treatment effectively reduces the hypertrophy of the gastrocnemius muscle (GM). Patient satisfaction is, however, reported to be low after treatment, with a possible correlation between high satisfaction and thinner subcutaneous fat. The goal of this study was to classify the subcutaneous fat of calves to understand the relation between fat thickness and patient satisfaction after BTXA treatment., Methods: The maximal leg circumference was measured, and B-mode ultrasound was used to measure the thickness of the medial head of the GM and of the subcutaneous fat. Patients were followed up at 1 and 6 months after BTXA treatment., Results: A total of 50 cases were classified into the following levels of fat thickness: slim (<0.55 cm), moderate (0.55 to 0.85 cm), and bulge (>0.85 cm). All patients were treated with 300 units of BTXA. Patients in the slim and bulge groups reported higher satisfaction rate than patients in the moderate group, with patients in the slim and bulge groups reporting complete satisfaction (100%) with calf contour at the 6-month follow-up. The satisfaction rate with the improvement in total leg circumference was low in all 3 groups. No severe complications were encountered in this study., Conclusions: This study identified a U-shaped correlation between calf subcutaneous fat thickness and patient satisfaction rate after treatment. The authors' results provide a theoretical basis for BTXA treatment and suggest the importance of preprocedure conversations in GM hypertrophy treatment., Clinical Question/level of Evidence: Risk, II., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Botulinum toxin A to the glabella is a popular cosmetic intervention. Functional musculature differences may arise from chronic behavioral adjustment to high sun exposure levels, requiring greater doses. This could affect clinical practice globally. This study investigated the effect of climate on real-world doses., Methods: The authors conducted a comparative cohort study using data from a registry from a single provider practicing across two centers: the United Kingdom and Malta. They classified one center as low sun exposure (United Kingdom winter month treatment) and the other as high sun exposure (Malta summer months). Patients were followed up once every 3 weeks and received top-up doses until full clinical paralysis was achieved. To standardize the comparison, the study included only women aged 35 to 60 years undergoing glabellar botulinum toxin treatment by experienced clinicians following standard procedures from 2012 to 2019. Smokers, those not seeking maximal paralysis, those documented as not compliant with posttreatment advice, those with colds or fevers, and those with broken cold supply chains were excluded. Univariable and multivariable analyses were undertaken., Results: A total of 523 patients were included: 292 "high-sun" patients and 231 "low-sun" patients. Mean total doses were significantly higher in the high-sun group (29.2 units versus 27.3 units; P = 0.0031). When correcting for age in multivariable analysis, the low-sun group still had lower total dose requirements ( P = 0.00574)., Conclusion: Patients injected with glabellar botulinum toxin in high-sun climates may have significantly increased dose requirements to achieve maximal paralysis., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Benign masseteric hypertrophy (BMH) is a condition in which the thickness of the masseter muscle is increased, resulting in jawline prominence with an undesirable cosmetic appearance. Botulinum toxin type A (BTA) injection is a promising treatment option, but its effective dose remains debated., Methods: Adults older than 19 diagnosed with BMH through visual examination and palpation related to a masseter muscle prominence were selected, and 80 patients were randomly assigned into five groups (placebo group and four groups with different doses of BTA: 24 U, 48 U, 72 U, or 96 U, on both sides of the jaw) and treated with placebo or BTA once at their baseline visit. During each follow-up, the treatment efficacy was evaluated with ultrasound examination of the masseter muscle, three-dimensional facial contour analysis, visual evaluation by the investigator, and patient satisfaction evaluation., Results: The mean age of the 80 patients was 42.7 ± 9.98 years; 68.75% were women. The mean change in masseter muscle thickness during the maximum clenching state after 12 weeks of drug administration compared with baseline in the 24-U, 48-U, 72-U, and 96-U groups were -2.33 ± 0.41 mm, -3.35 ± 0.42 mm, -2.86 ± 0.42 mm, and -3.79 ± 0.42 mm, respectively. All treatment groups showed a statistically significant decrease compared with placebo. Regarding subjective satisfaction, all treatment groups, except the 24-U group at 4 weeks, showed higher satisfaction than the placebo group during all visits. No significant adverse events were noted., Conclusion: BTA administration of at least 48 U for BMH is more cost-effective than high-dose units and has a low risk of side effects., Clinical Question/level of Evidence: Therapeutic, II., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Nerve decompression surgery is an effective treatment modality for patients who experience migraines. Botulinum toxin type A (Botox) injections have been traditionally used as a method to identify trigger sites; however, there is a paucity in data regarding its diagnostic efficacy. The goal of this study was to assess the diagnostic capacity of Botox in successfully identifying migraine trigger sites and predicting surgical success., Methods: A sensitivity analysis was performed on all patients receiving Botox for migraine trigger site localization followed by a surgical decompression of affected peripheral nerves. Positive and negative predictive values were calculated., Results: A total of 40 patients met our inclusion criteria and underwent targeted diagnostic Botox injection followed by a peripheral nerve deactivation surgery with at least 3 months' follow-up. Patients with successful Botox injections (defined as at least 50% improvement in Migraine Headache Index scores after injection) had significantly higher average reduction in migraine intensity (56.7% versus 25.8%; P = 0.020), frequency (78.1% versus 46.8%; P = 0.018), and Migraine Headache Index (89.7% versus 49.2%; P = 0.016) postsurgical deactivation. Sensitivity analysis shows that the use of Botox injection as a diagnostic modality for migraine headaches has a sensitivity of 56.7% and a specificity of 80.0%. The positive predictive value is 89.5% and the negative predictive value is 38.1%., Conclusions: Diagnostic targeted Botox injections have a very high positive predictive value. It is therefore a useful diagnostic modality that can help identify migraine trigger sites and improve preoperative patient selection., Clinical Question/level of Evidence: Diagnostic, II., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Demand for less-invasive procedures for treating gummy smile, such as botulinum toxin A injections, has increased substantially over the years. Meanwhile, the optimal injection site for botulinum toxin A injection is debated. The authors aimed to investigate the efficacy of botulinum toxin A injection at the Yonsei point for treating gummy smile., Methods: In this double-blind, single-site, randomized clinical trial, healthy participants with a gummy smile (anterior gingival exposure of ≥3.0 mm) were enrolled and randomized (1:1 ratio) into two groups. The experimental group was administered 6 U of botulinum toxin A at the Yonsei point (a single-site injection of 3 U to the right Yonsei point and 3 U to the left Yonsei point), and the control group received the same dose in the bilateral levator labii superioris alaeque nasi muscle sites. The patients were assessed at baseline and 4, 12, 24, and 48 weeks after the first injection using a digital vernier caliper., Results: A total of 49 participants were enrolled. Anterior and bilateral posterior gingival exposure were reduced at 4, 12, and 24 weeks ( P ≤ 0.05) and returned to baseline at 48 weeks in both groups; there was no difference between the groups at these time points. The increase in satisfaction among patients was significant, and few adverse events were observed., Conclusion: Both the Yonsei point and the levator labii superioris alaeque nasi muscle site can be used as botulinum toxin A injection sites for treating gummy smile., Clinical Question/level of Evidence: Therapeutic, I., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Botulinum toxin injection is the accepted standard treatment for synkinesis and gustatory hyperlacrimation in patients with facial paralysis. However, poor injection accuracy can result in inconsistent treatment outcomes, variable treatment durations, and complications. Ultrasound guidance should increase injection accuracy in the facial region; however, this has not been proven., Methods: Twenty-six hemifaces of nonembalmed cadavers were studied in a randomized split-face manner. Ink was injected with ultrasound or landmark guidance into the lacrimal gland and three common synkinetic muscles: the orbicularis oculi, depressor anguli oris, and mentalis. Injection accuracy was evaluated using several measures., Results: Using ultrasound guidance, most ink (>50%) was found inside the correct target in 88% of cases, compared with 50% using landmark guidance ( P < 0.001). This was most pronounced in the lacrimal gland (62% versus 8%), depressor anguli oris (100% versus 46%), and mentalis (100% versus 54%) ( P < 0.05). All ink was found inside the correct target (no ink outside) in 65% using ultrasound guidance versus 29% without ( P < 0.001). Injection accuracy (any ink in target) was 100% when using ultrasound guidance versus 83% without ( P < 0.01). Twenty-three percent of the landmark-guided depressor anguli oris injections stained the facial artery ( P = 0.22)., Conclusions: Ultrasound guidance significantly increased injection accuracy and reduced the amount of ink lost in the surrounding tissue compared with landmark guidance. Clinical trials are needed to explore the effects of ultrasound guidance on treatment outcome, duration, and complications in patients with facial paralysis., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Botulinum neurotoxin type A (BTX-A) to the masseter muscle is a useful tool for the aesthetic narrowing of the width of the lower face. The administration of BTX-A to visible parotid glands is also effective to reduce lower facial width. However, no studies have quantitatively analyzed the effect of BTX-A on the parotid glands., Methods: The purpose of this study was to confirm the impact of BTX-A injection on the parotid gland and to suggest the effective dosage of BTX-A in facial slimming. This study was conducted by selecting patients who desired facial slimming from among patients who required surgery for a facial bone fracture. Patients undergoing BTX-A injection were randomized to high-dose, low-dose, and placebo groups, and different doses of BTX-A for each group were injected into both parotid glands during facial bone surgery., Results: A total of 30 patients were enrolled in this study. Ten patients in the high-dose group, eight in the low-dose group, and nine in the control group completed the clinical trial. There were significant changes in both the high- and low-dose groups compared with the control group ( P < 0.001, P < 0.001), and in interaction of time and group ( P < 0.001). Volume recovery after 3 months was found in 7.6% in the high-dose group and in 4.8% in the low-dose group., Conclusion: BTX-A injection into parotid glands can be an effective treatment option in managing salivary gland enlargement for lower face contouring., Clinical Question/level of Evidence: Therapeutic, II., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Summary: The frontalis muscle is situated across the forehead and is a representative target muscle for botulinum neurotoxin (BoNT) injections aimed at treating horizontal wrinkles in this region. However, a lack of anatomical information regarding the shape and thickness of the frontalis may lead to unexpected adverse effects, such as ptosis and samurai eyebrows, caused by the lack of detail on anatomical variation. Achieving the maximum effect using the minimal amount of BoNT requires a precise injection into the frontalis muscle. The anatomical factors associated with BoNT injection into the frontalis muscle have been reviewed in the current study. Up-to-date understanding of the localization of the BoNT injection point according to an updated understanding of the anatomy leads to more accurate localization of the injection point into the frontalis muscle. Optimal injection sites have been provided for the frontalis muscle, and the injection method has been recommended. The authors suggest optimal injection sites according to the external anatomical landmarks of the forehead. Furthermore, these proposals could aid in a more precise procedure that avoids the deleterious effects of BoNT., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Minimally invasive techniques for treatment-resistant migraine have been developed on recent insights into the peripheral pathogenesis of migraines. Although there is a growing body of evidence supporting these techniques, no study has yet compared the effects of these treatments on headache frequency, severity, duration, and cost., Methods: PubMed, Embase, and Cochrane Library databases were searched to identify randomized placebo-controlled trials that compared radiofrequency ablation, botulinum toxin type A (BT-A), nerve block, neurostimulation, or migraine surgery to placebo for preventive treatment. Data on changes from baseline to follow-up in headache frequency, severity, duration, and quality of life were analyzed., Results: A total of 30 randomized controlled trials and 2680 patients were included. Compared with placebo, there was a significant decrease in headache frequency in patients with nerve block ( P = 0.04) and surgery ( P < 0.001). Headache severity decreased in all treatments. Duration of headaches was significantly reduced in the BT-A ( P < 0.001) and surgery cohorts ( P = 0.01). Quality of life improved significantly in patients with BT-A, nerve stimulator, and migraine surgery. Migraine surgery had the longest lasting effects (11.5 months) compared with nerve ablation (6 months), BT-A (3.2 months), and nerve block (11.9 days)., Conclusions: Migraine surgery is a cost-effective, long-term treatment to reduce headache frequency, severity, and duration without significant risk of complication. BT-A reduces headache severity and duration, but it is short-lasting and associated with greater adverse events and lifetime cost. Although efficacious, radiofrequency ablation and implanted nerve stimulators have high risks of adverse events and explantation, whereas benefits of nerve blocks are short in duration., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Botulinum toxin A injection for masseter reduction is generally considered minimally invasive, safe, and effective. However, this approach may lead to facial flaccidity and sagging, especially in older patients with reduced elasticity of the skin and the soft tissue., Methods: The authors analyzed 27 cases of patients who presented with the above complications and treated them with botulinum toxin A injections into the platysma and the depressor anguli oris muscle. The efficacy of treatment was evaluated by both patients and physicians., Results: Ninety-six percent of patients were satisfied with the treatment outcome. One patient considered the treatment outcome unsatisfactory because of the lack of significant improvement in nasolabial folds. Physician evaluation suggests significant improvement in all patients, including the one who considered the treatment outcome unsatisfactory., Conclusion: Botulinum toxin A injection into the platysma and the depressor anguli oris muscles is a safe, convenient, and effect treatment to correct the complication of facial flaccidity and sagging after masseter reduction., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: In postparetic synkinesis, muscle tone imbalance between upper and lower lip depressors and elevators results in the inability to produce an effective smile. Surgical treatments to improve smile focus on restoring tonicity balance between perioral muscles by weakening hypertoned muscles through selective myectomies or selective neurectomies. The goal of this study was to compare objective outcomes between selective myectomies alone with those of selective myectomies combined with selective neurectomies., Methods: A retrospective cohort study was performed on postparetic synkinesis patients who underwent depressor anguli oris (DAO) myectomies or DAO and platysma myectomies with selective neurectomies. Objective outcomes included preoperative and postoperative analyses of smile measures (excursion, angle, and dental show) and botulinum toxin type A administration (periorbital and platysmal)., Results: Thirty-seven patients underwent DAO myectomies only (myectomy group), and 18 patients underwent DAO and platysma myectomies with selective neurectomies (myectomy-neurectomy group). Within-group analyses showed significant angle improvement in both groups ( P < 0.05) and improved smile excursion in the myectomy-neurectomy group ( P < 0.05). Between-group comparisons showed significant closed mouth smile excursion improvement (difference in means, -1.14 mm; 95% CI, -2.19 to -0.09 mm; P = 0.034) and a significant decrease in platysmal botulinum toxin type A administration (difference in means, 27.36 units; 95% CI, 18.72 to 36.00 units; P < 0.001) in the myectomy-neurectomy group compared with the myectomy group., Conclusions: This study suggests that selective myectomies and selective myectomies with selective neurectomies provide overlapping and differing benefits to perioral synkinesis. Selective neurectomies and platysma myectomy provided slightly improved excursion and significantly decreased botulinum injections to the platysma., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Botulinum toxin type A is an easy and efficacious treatment for gingival smile. However, the optimal dose and injection site are controversial. The authors compared the reduction in gingival exposure using two methods with different doses and injection sites., Methods: In this prospective self-controlled study, healthy participants with gingival smile (anterior gingival exposure of >3 mm) underwent two treatment methods. First, participants received a single-point injection of 2 U of botulinum toxin type A per side (simplified method). After 8 months, the individualized method was performed with 2 to 5 U of botulinum toxin type A (total, 4 to 10 U), which was injected at one or two sites according to pretreatment severity. Data were collected at baseline and at 4, 12, and 32 weeks of follow-up., Results: Fifty-five participants were enrolled. Anterior gingival exposure and bilateral posterior gingival exposure were significantly reduced 4 and 12 weeks after botulinum toxin type A injection ( P ≤ 0.05) with both methods. These parameters returned to baseline by 32 weeks ( P > 0.05). Posttreatment anterior gingival exposure at 4 weeks and 12 weeks with the individualized method was significantly lower compared with the simplified method (both P ≤ 0.05). Patient satisfaction with the individualized method was preferred compared with the simplified method ( P ≤ 0.05). Few adverse events were observed with both methods without statistical significance., Conclusion: It is necessary to increase the injection dose and tailor the injection site according to the pretreatment severity of anterior gingival smile., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Scars can cause pain, long-term physical dysfunction, and psychological harm. Botulinum toxin type A (BoNT-A) is one treatment choice for scars, but further evidence is needed to confirm its efficacy., Methods: This systematic review included randomized controlled trials that investigated the effectiveness of BoNT-A on scars. The mean and standard deviation for the Vancouver Scar Scale, Stony Brook Scar Evaluation Scale, visual analog scale for appearance evaluation, visual analog scale for scar pain evaluation, and scar width were extracted for subgroup analysis., Results: Twenty-one randomized controlled trials were included. The BoNT-A group had a lower Vancouver Scar Scale score than the saline group (standardized mean difference, -0.73; 95 percent CI, -1.12 to -0.35; p = 0.0002) but a higher score than the steroid group (standardized mean difference, 0.85; 95 percent CI, 0.27 to 1.43; p = 0.004). The BoNT-A group exhibited a higher Stony Brook Scar Evaluation Scale grade than the saline group (standardized mean difference, 1.42; 95 percent CI, 0.83 to 2.00; p < 0.00001). The visual analog scale for appearance evaluation revealed higher scores in the BoNT-A group than in the saline group (standardized mean difference, 1.14; 95 percent CI, 0.69 to 1.60; p < 0.00001). As for pain evaluation, the BoNT-A group had a lower visual analog scale score than the steroid group (standardized mean difference, -2.57; 95 percent CI, -4.40 to -0.74; p = 0.006). Furthermore, scar width was significantly shorter in the BoNT-A group than in the control group (standardized mean difference, -1.11; 95 percent CI, -1.38 to -0.83; p < 0.00001)., Conclusions: BoNT-A is more effective in treating scars than saline, although steroids may exhibit higher potency. Therefore, it can be considered an alternative in patients not amenable to steroid treatment., Clinical Question/level of Evidence: Therapeutic, II., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Botulinum toxin type A has been used to treat a wide array of neurologic, medical, and aesthetic indications. Several factors contribute to the formation of neutralizing antibodies, such as shorter intervals of treatment, higher dosage, amounts of antigenic proteins, serotypes, and storage of formulations., Method: This overview followed the Cochrane guideline for overview reviews. The AMSTAR-2 (revised version of A Measurement Tool to Assess Systematic Reviews) tool was used for the critical appraisal of the selected systematic reviews., Results: Five systematic reviews consisting of 203 studies (17,815 patients) were included, and their AMSTAR-2 scores were low to critically poor. There was high heterogeneity between the studies. Across the clinical indications, neutralizing antibody prevalence was significantly higher in dystonia, spasticity, and urologic conditions, and nil to insignificant in hyperhidrosis and aesthetic indications. The overall rate for the neutralizing antibody formation across three different formulations, abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA, was 1 to 2.1 percent, with no significant difference between them., Results: Although there is debate on the prevalence rate across the different botulinum toxin type A formulations in individual systematic reviews, the overall frequency of the development of neutralizing antibodies and the immunogenicity of abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA remain low to insignificant., Conclusions: Properly designed comparative trials are required to explore the difference in the prevalence of neutralizing antibodies across the commercially available botulinum toxin type A products. Such studies should also examine the relevance of neutralizing antibody titer to clinical responsiveness and nonresponse., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Benign parotid hypertrophy makes the earlobe area appear swollen and weakens the lateral facial contour and aesthetics. Efficacious treatment for benign parotid hypertrophy is not available. The authors evaluated the efficacy and safety of botulinum toxin type A for benign parotid hypertrophy treatment., Methods: Thirty-six participants with benign parotid hypertrophy were enrolled and treated with botulinum toxin type A injection. After 6 months of follow-up, changes in the thickness and length of the superficial lobe of the parotid gland were assessed. Analyses of patient subgroups and image analyses were also undertaken to assess improvement., Results: Thirty-three participants completed this study. Superficial lobe of the parotid gland thickness was reduced significantly after botulinum toxin type A injection, but the longitudinal diameter of the parotid gland was not changed significantly ( p < 0.001 and p = 0.146, respectively). Subgroup analyses showed that the degree of parotid gland hypertrophy affected treatment efficacy and degree of improvement, but age and sex did not ( p < 0.001, p = 0.137, and p = 0.138, respectively). Image analyses showed improvement in the facial contour ( p < 0.05). Serious adverse reactions or complications were not observed., Conclusion: Botulinum toxin type A can be used to treat benign parotid hypertrophy, reduce parotid gland volume, and improve the facial contour., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Summary: We are living in an aging society. In 2019, 1 billion individuals were already aged over 60. The number of people in this demographic is predicted to reach 1.4 billion by 2030 and 2.1 billion by 2050 (WHO). In the USA, individuals over 65 represent the fastest growing segment of the population (US census bureau). Similar trends are seen in the UK, with 16.2 million people already aged over 60, equivalent to 24% of the total population (Age UK; https://www.ageuk.org.uk/globalassets/age-uk/documents/reports-and-publications/later&#95;life&#95;uk&#95;factsheet.pdf). Indeed, in the UK, people over the age of 60 outnumbered those under the age of 18, for the first time in 2008. This statistic still prevails today. Because of medical and biopharmaceutical progress, lifespan is increasing rapidly, but healthspan is failing to keep up. If we are to increase healthy living, then we need to begin to understand the mechanisms of how we age across the life course, so that relevant interventions may be developed to facilitate "life in our years," not simply "years in our life." It is reported that only 25% of aging is genetically predetermined. This fits with observations of some families aging very quickly and poorly and others aging slowly and well. If this is indeed the case and the rate of aging is not fixed, then this knowledge provides a significant opportunity to manipulate the impact of environmental influencers of age. With that in mind, it begs the question of what are the mechanisms of aging and is there potential to manipulate this process on an individual-by-individual basis? The focus of this article will be on the process of muscle wasting with aging (sarcopenia) and the potential of exercise and its underlying mechanisms to reverse or delay sarcopenia. There will be a focus on epigenetics in muscle wasting and the capability of exercise to change our skeletal muscle epigenetic profile for the good. The article ends with considerations relating to facial aging, Botox treatment, and gene editing as a tool for plastic surgeons in the future., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Summary: The hypertrophied temporalis and masseter muscles give a muscular shaped and bulky contour to the face. Botulinum neurotoxin injection methods are commonly used for facial contouring; however, adverse effects have been reported owing to a lack of delicate anatomical information. The anatomical considerations when injecting botulinum neurotoxin into the temporalis and masseter muscles were reviewed in the present study. Current knowledge on the localization of the botulinum neurotoxin injection point with more recent anatomical dissection and modified Sihler staining procedures was assessed. The authors found that, for the muscles, the injection point can be more precisely demarcated. Optimal injection sites are presented for the temporalis and masseter muscles, and the injection technique is suggested. The authors propose the optimal injection sites in relation to external anatomical landmarks for the frequently injected muscles of the face to facilitate the efficiency of botulinum neurotoxin injections. In addition, these guidelines would aid in more precise practice without the adverse effects of botulinum neurotoxin., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Surgical intervention with combined myectomy and neurectomy followed by functioning free muscle transplantation has been proposed to effectively resolve the problem of postparalytic facial synkinesis since 1985, and it continues to be the authors' standard of care. The authors aim to provide evidence that this surgical strategy is effective for treatment of synkinesis and smile quality., Methods: One hundred three patients with postparalytic facial synkinesis were investigated (1985 to 2020). They all underwent extensive removal of the synkinetic muscles and triggered facial nerve branches in the cheek, nose, and neck regions, followed by gracilis functioning free muscle transplantation for facial reanimation. Ninety-four patients (50 with type II and 44 with type III postparalytic facial synkinesis), all of whom had at least 1 year of postoperative follow-up, were included in the study. Patient demographics and functional and aesthetic evaluations before and after surgery were collected., Results: In the yearly distribution of the facial paralysis reconstruction, the incidence of surgical intervention increased from 15 percent before 2012 up to 24 percent in the years after. Young adults (79 percent) and female patients (63 percent) were the dominant population. Results showed a significant improvement of the facial smile quality, with more teeth visible while smiling, and a long-lasting decrease of facial synkinesis. Ninety-six percent of patients did not require botulinum toxin type A injection after surgery. Revision surgery for secondary deformity was 53 percent., Conclusions: Combined myectomy and neurectomy followed by functioning free muscle transplantation for type II and III synkinetic patients leads to promising and long-lasting results despite high revision rates. Refined techniques to decrease the revision rates are needed in the future., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Botulinum neurotoxin treatment is the most common aesthetic procedure in the United States. A number of serotypes and formulations are available worldwide. Similarities and differences among these toxins were evaluated by reviewing the existing literature., Methods: Reports of botulinum neurotoxin for aesthetic use, published in peer-reviewed literature or presented at recent professional congresses, were reviewed to summarize key features of different toxins. Data from therapeutic uses in comparable anatomical areas were included in the review when aesthetic literature was limited., Results: Serotypes of neurotoxins share molecular structures and mechanisms of action but exhibit important differences between serotypes and between different formulations within the same serotype, including differences in distribution/diffusion patterns and risk/benefit profiles. The differences attributable to dissimilarities in bacterial strains, manufacturing techniques, and assays are likely to influence clinical performance., Conclusions: Injection patterns, techniques, dilutions diffusion, and injection volumes established for a specific formulation of botulinum neurotoxin are not likely to be applicable to other formulations, and formulations are not interchangeable by any single conversion ratio. A large proportion of the clinical literature documents the aesthetic uses of the Allergan formulation of botulinum toxin type A. Additional studies are needed to establish optimal procedures for the Ipsen formulation and botulinum neurotoxin, and for diverse aesthetic uses.

Background: Depression is a leading cause of disability worldwide. Preliminary evidence suggests that glabellar onabotulinumtoxinA injections improve depression scores with few side effects compared to current first-line antidepressant medications. The authors' review reports on these studies, hypothesizing that glabellar onabotulinumtoxinA injections can be an alternative safe and effective treatment for depression., Methods: A systematic review and meta-analysis of the relevant literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Cochrane Library, Embase, and Scopus databases were searched in August of 2020 using the keywords ["botox" OR "botulinum"] AND ["mood" OR "depression"] for articles published between 1980 and 2020. Prospective studies and randomized controlled trials on the use of glabellar onabotulinumtoxinA injections for the primary purpose of treating depression were considered. The primary endpoint for the meta-analysis was the mean difference in primary depression scores after treatment, along with a second endpoint of the standardized mean difference in depression scores among treated patients including all nine studies., Results: Of the 499 reviewed articles, nine studies were included that reported improvement in mean depression scores from baseline. All five randomized controlled trials reported an improvement in mean depression scores at 6 weeks after treatment, with a weighted average change of -8.39 points ( p < 0.0001). The aggregate standardized mean difference from baseline to the primary endpoint across all nine prospective studies was -1.61 SD ( p < 0.0001)., Conclusion: Meta-analysis and systematic review of the included studies provide support for an antidepressant effect of glabellar onabotulinumtoxinA injections., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Patients access online cosmetic health information to help with decision making. This information is unregulated, variable in quality, and may be biased. This study compared the most popular cosmetic injectables websites to assess their readability, quality, and technical performance., Methods: A Google search for "Botox" (botulinum toxin type A) and "fillers" was performed in July of 2020, identifying the most popular health information websites. Sites were analyzed for their readability and quality of health information using the validated DISCERN criteria and the Health on the Net Foundation Code of Conduct principles. Technical qualities were evaluated using two website performance algorithms, WooRank and WebsiteGrader., Results: Eighty-five websites were analyzed (13 academic/hospital websites, seven commercial websites, 25 private practice board-certified websites, seven private practice not-board-certified websites, 16 online health reference websites, and 17 other websites). The mean readability consensus score was 11 (eleventh grade reading level). The mean DISCERN quality scores were higher for online health reference websites compared to academic/hospital websites (p = 0.045), commercial websites (p = 0.045), private practice board-certified websites (p < 0.001), and private practice not-board-certified websites (p = .002). No correlation between a website's rank and its DISCERN score was found (ρ = -0.07; p = 0.49)., Conclusions: Cosmetic injectable websites are too difficult to read by the sixth grade standard recommended by the National Institutes of Health and the American Medical Association. Online health reference sites are higher in quality than physician sites. This has implications for the ability of many patients to be fully informed consumers. The readability, quality, and technical aspects of websites may affect the overall accessibility of patient health information., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Summary: The depressor anguli oris acts to lower the lateral corners of the mouth and can cause an individual to appear sad or angry and contribute to the development of the labiomental folds. Many patients can benefit from the injection of small amounts of botulinum neurotoxin into the depressor anguli oris to enable the lip elevators to reposition the corners of the mouth. Although effective, the procedure is off-label, and the proximity of the depressor anguli oris to the depressor labii inferioris, particularly inferiorly, can lead to inadvertent treatment of the latter, resulting in lip asymmetry. The authors have taken a threefold approach to establish a depressor anguli oris injection technique that provides optimal aesthetic outcomes with a low incidence of adverse events. This involved, first, reviewing the limited existing literature for studies discussing depressor anguli oris anatomy and botulinum neurotoxin treatment technique; second, supplementing information from the published literature with information from cadaver dissections to demonstrate the relationship between the depressor anguli oris and surrounding anatomical structures; and third, performing a retrospective chart review of 275 patients treated with the authors' three-point injection technique. Combining data from published studies, cadaver dissections, and clinical experience, the authors demonstrate that a three-point technique performed in the upper half of the depressor anguli oris is associated with good clinical outcome and avoids common side effects related to injection or spread of neurotoxin to adjacent muscles., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Pain is an unpleasant experience resulting from either tissue damage or insults to the somatosensory system. Approaches to pain management evolve as we better understand both pain pathways and the tools available to interrupt these. The interest surrounding botulinum neurotoxin as a chemodenervating agent has expanded to include its potential applications in painful pathologies, both within and beyond the confines of plastic surgery. In this article, the authors discuss botulinum neurotoxin's mechanism of action as it pertains to both muscular paralysis and its interplay in the modulation of proinflammatory pain mediators. In addition, the authors review evidence supporting the use of botulinum neurotoxin in common painful conditions, in order to prepare the readership to aptly provide their patients with evidence-based recommendations. After reading this article, the participant should be able to discuss both mechanism of action and common applications of botulinum neurotoxin in painful conditions.

Background: Chronic migraines affect approximately 2 percent of the U.S. population and cost an estimated $17 billion per year. OnabotulinumtoxinA (botulinum toxin type A) is a U.S. Food and Drug Administration-approved prophylactic medication for chronic migraine headaches and is best injected in a targeted fashion into specific trigger sites. The purpose of this study was to determine the cost-effectiveness of long-term, targeted botulinum toxin type A versus peripheral trigger site deactivation surgery for the treatment of migraine headaches., Methods: A Markov model was constructed to examine long-term, targeted botulinum toxin type A versus peripheral trigger site deactivation surgery. Costs, utilities, and other model inputs were identified from the literature. One-way and probabilistic sensitivity analyses were performed. An incremental cost-effectiveness ratio under $50,000 per quality-adjusted life-year was considered cost-effective., Results: The mean cost of peripheral trigger site deactivation surgery was $10,303, with an effectiveness of 7.06; whereas the mean cost of long-term, targeted botulinum toxin type A was $36,071, with an effectiveness of 6.34. Trigger-site deactivation surgery is more effective and less costly over the time horizon of the model. One-way sensitivity analysis revealed that surgery is the most cost-effective treatment in patients requiring treatment for greater than 6.75 years., Conclusions: Based on this model, peripheral trigger site deactivation surgery is the more cost-effective option for treating refractory migraine headaches requiring treatment beyond 6.75 years. The model reveals that peripheral trigger-site deactivation surgery is more effective and less costly than long-term, targeted botulinum toxin type A over the course of a patient's lifetime.

Background: Microbotulinum refers to the systematic injection of tiny blebs of diluted botulinum toxin at repeated intervals into the skin. This targets the superficial fibers of the facial muscles, and weakens their insertion into the undersurface of the skin, which is responsible for the fine lines and wrinkles on the face. The authors present a pilot study based on quantitative evaluation, by means of a skin-scanning technology, of the aesthetic improvement of skin texture, microroughness, and enlarged pore size in a patient group treated with microbotulinum injections for cosmetic purposes., Methods: The treatment was performed using a 32-gauge needle to deliver injections on a regular 1-cm grid from the forehead to the cheek and down to the jawline., Results: Sixty of the 62 patients completed the study. All analyzed parameters improved significantly (p < 0.0001) at 90 days with respect to the pretreatment time point (skin texture, -1.93 ± 0.51; microroughness, -2.48 ± 0.79; and pore diameter, 2.1 ± 0.43). Best results have been obtained in patients aged between 42.7 and 46.8 years, and standard deviation calculation allows us to recommend it in patients aged between 36.5 and 53 years., Conclusions: The results of this pilot study suggest that intradermal botulinum toxin injection, or so-called microbotulinum, is a safe and effective method to treat skin flaws. Because of the high satisfaction rate among both physicians and patients, further studies are indeed mandatory to determine the optimal number of units needed for a longer and lasting effect with this particular novel dilution., Clinical Question/level of Evidence: Therapeutic, IV.

Background: DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin type A formulation in clinical development. A phase 2 dose-ranging study identified an optimal dose and demonstrated efficacy with a median duration of 24 weeks., Methods: In two phase 3, multicenter, randomized, double-blind, placebo-controlled studies (SAKURA 1 and SAKURA 2), subjects with moderate or severe glabellar lines at maximum frown were assigned randomly to receive placebo or 40 U of DAXI. Glabellar lines were evaluated at least every 4 weeks for at least 24 weeks until severity returned to baseline (≤36 weeks)., Results: Overall, 609 subjects were enrolled (DAXI, n = 405; placebo, n = 204). DAXI was significantly more effective than placebo in achieving the primary efficacy outcome (≥2-point improvement in glabellar line severity at maximum frown at week 4 according to both investigator and subject ratings): 73.6 percent versus 0.0 percent (SAKURA 1), and 74.0 percent versus 1.0 percent (SAKURA 2) (both p < 0.0001). Composite investigator and subject ratings of maximum frown after DAXI treatment showed that glabellar line severity of none or mild was maintained for a median of 24.0 weeks (SAKURA 1) and 23.9 weeks (SAKURA 2), and glabellar line severity did not return to baseline levels for a median of 27.7 and 26.0 weeks, respectively. DAXI was generally well tolerated, with the most common adverse events related to DAXI treatment being headache (SAKURA 1, 7.0 percent; SAKURA 2, 5.9 percent) and injection-site pain (5.0 percent and 2.4 percent, respectively)., Conclusions: Results from both studies were highly consistent. DAXI may offer a prolonged duration of response (median, ≥24 weeks) and is generally well tolerated., Clinical Question/level of Evidence: Therapeutic, I.