Mark S. Nestor

Treatment of Hyaluronic Acid Filler–Induced Impending Necrosis With Hyaluronidase: Consensus Recommendations

Injection-induced necrosis is a rare but dreaded consequence of soft tissue augmentation with filler agents. It usually occurs as a result of injection of filler directly into an artery, but can also result from compression or injury. We provide recommendations on the use of hyaluronidase when vascular compromise is suspected. Consensus recommendations were developed by thorough discussion and debate amongst the authors at a roundtable meeting on Wednesday June 18, 2014 in Las Vegas, NV as well as significant ongoing written and verbal communications amongst the authors in the months prior to journal submission. All authors are experienced tertiary care providers. A prompt diagnosis and immediate treatment with high doses of hyaluronidase (at least 200 U) are critically important. It is not felt necessary to do a skin test in cases of impending necrosis. Some experts recommend dilution with saline to increase dispersion or lidocaine to aid vasodilation. Additional hyaluronidase should be injected if improvement is not seen within 60 minutes. A warm compress also aids vasodilation, and massage has been shown to help. Some experts advocate the use of nitroglycerin paste, although this area is controversial. Introducing an oral aspirin regimen should help prevent further clot formation due to vascular compromise. In our experience, patients who are diagnosed promptly and treated within 24 hours will usually have the best outcomes.

A randomized, placebo-controlled, double-blind phase III trial investigating the efficacy and safety of incobotulinumtoxinA in the treatment of glabellar frown lines using a stringent composite endpoint.

BACKGROUND A prospective, randomized, double‐blind, multicenter, Phase III trial of incobotulinumtoxinA using new Food and Drug Administration endpoints. OBJECTIVE To investigate the efficacy and safety of a single dose of incobotulinumtoxinA for the treatment of glabellar frown lines. MATERIALS AND METHODS Two hundred seventy‐one subjects with moderate to severe glabellar frown lines at maximum frown—as assessed by an investigator according to the facial wrinkle scale (FWS)—were randomized 2:1 to receive one treatment of 20 U of incobotulinumtoxinA or placebo, respectively, and assessed over 120 days. The primary efficacy variable was a composite endpoint consisting of patients who were 2‐point or more responders at maximum frown on Day 30 according to the investigators rating on the FWS, and 2‐point or more responders at maximum frown on Day 30 according to the patients assessment on a 4‐point scale. Safety analyses were performed throughout the study. RESULTS IncobotulinumtoxinA was statistically significantly more efficacious than placebo using a new rigorous composite endpoint (p < .0001). CONCLUSION A single dose of 20 U of incobotulinumtoxinA is superior to placebo in the treatment of glabellar frown lines at Day 30 and is well‐tolerated.

Understanding the Functional Anatomy of the Frontalis and Glabellar Complex for Optimal Aesthetic Botulinum Toxin Type A Therapy

BackgroundBotulinum neurotoxin type A (BoNTA) is approved for the treatment of glabellar lines and also is commonly injected in an off-label fashion in the frontalis (i.e., frontalis epicranius) muscle to improve the appearance of horizontal forehead lines. This study aimed to review and discuss both the anatomy and physiology of the frontalis muscle and its relationship with antagonist muscles in the upper face and to provide a guide for the use of BoNTA to treat forehead rhytides while minimizing the occurrence of complications such as brow ptosis.MethodsA PubMed search was conducted to identify practitioner opinion and clinical publications on the efficacy and safety of BoNTA for aesthetic treatment of the upper face.ResultsThe use of BoNTA produces durable improvement in the appearance of moderate to severe horizontal forehead lines. Dose and injection technique must be adjusted and individualized based on the variable anatomy and function/mass of muscles in the forehead and upper face as well as on patient goals. Optimal aesthetic outcomes can be achieved by skillfully balancing the opposing effects of the frontalis muscle and its intricate interactions with the procerus, corrugator supercilii, depressor supercilii, and orbicularis oculi muscles.ConclusionsThe use of BoNTA to improve the aesthetic appearance of horizontal forehead lines is optimized when clinicians take into account variations in frontalis muscle function and position, anatomy of the brow, and proper injection technique when they devise individualized treatment regimens.Level of Evidence VThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

A randomized, evaluator-blinded, controlled study of the effectiveness and safety of small gel particle hyaluronic acid for lip augmentation.

OBJECTIVES To assess the effectiveness and safety of small gel particle hyaluronic acid (SGP‐HA) for lip augmentation. METHODS Adults (n = 180; aged 18–65) scoring 1 (very thin) to 2 (thin) on the 5‐point validated Medicis Lip Fullness Scale (MLFS) for the upper or lower lip were randomized (3:1) to SGP‐HA (≤1.5 mL/lip) or no treatment. Co‐primary effectiveness end points were blinded‐evaluator MLFS score for upper or lower lip at week 8. Secondary end points (MLFS score, independent photographic review, Global Aesthetic Improvement Scale [GAIS], safety assessments) were measured throughout the study. RESULTS Statistically significantly more MLFS responders (≥1 grades of MLFS improvement at week 8) received SGP‐HA (93% combined upper and lower lip responders [95% upper lip; 94% lower lip]) than no treatment (29% combined; p < .001). SGP‐HA improved self‐assessed combined lip GAIS (97% week 8; 74% week 24) significantly more than no treatment (0% throughout; p < .001). The SGP‐HA group reported anticipated swelling (58%) and bruising (44%), 88% mild or 11% moderate severity, without unanticipated device adverse events. CONCLUSIONS SGP‐HA is highly effective and well tolerated for lip augmentation. Statistically significant improvement was evident based on the MLFS at 8 weeks, with visible results reported in the majority of participants 6 months after treatment.

Consensus panel's assessment and recommendations on the use of 3 botulinum toxin type A products in facial aesthetics.

In this summary article, the authors discuss the characteristics of abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA. With 3 neuromodulators available in the US market, comparisons between and among products will invariably be made, so arguments for the most effective facial aesthetic uses of each neuromodulator are presented. Topics addressed in this article include patient expectations, toxin reconstitution and preparation, patient positioning, differences among products, the role of complexing proteins, and dosing and injection strategies. Recommendations are also provided by treatment area.

An Analysis of Safety Data from Five Phase III Clinical Trials on the Use of Botulinum Neurotoxin Type A-ABO for the Treatment of Glabellar Lines

BACKGROUND A new formulation of a botulinum neurotoxin type A (BoNTA-ABO; Dysport [abobotulinumtoxinA]; Medicis Aesthetics, Scottsdale, AZ) was recently approved by the US Food and Drug Administration for the treatment of moderate to severe glabellar lines. OBJECTIVE This article summarizes the safety data from five phase III clinical trials investigating the use of BoNTA-ABO in the treatment of glabellar lines. METHODS Of the five phase III studies conducted, three were multicenter, randomized, placebo-controlled, double-blind studies and two were multicenter, open-label, repeat-dose studies (one of which was an extension trial). Two fixed-dose, placebo-controlled studies randomized a total of 416 patients to receive one 50-unit dose of BoNTA-ABO. The single variable-dose study randomized 544 patients to receive 50 to 80 units of BoNTA-ABO, as determined by gender and patient muscle mass. A substudy of this variable-dose study on QT/QTc prolongation included 50 patients randomized to BoNTA-ABO. One open-label repeat-dose study administered 50 units of BoNTA-ABO to 1200 patients. The single extension study (N = 1415) included both fixed (5423 treatments) and variable dosing (1337 treatments) following a protocol amendment. The extension study included patients from the four previously mentioned studies. Safety endpoints were adverse events (AE), laboratory data, and changes in vital signs. Of 2485 healthy adult patients with moderate to severe glabellar lines enrolled in the trials, 2160 received at least one cycle of BoNTA-ABO. RESULTS Treatment of glabellar lines with 50 units of BoNTA-ABO was well tolerated, with similar rates of treatment-emergent adverse events (TEAE) observed in the active treatment and placebo groups in terms of type, frequency, severity, and relatedness-with the exception of injection site reactions and ptosis. In the variable-dose, single-treatment study, BoNTA-ABO was well tolerated, with an incidence of active TEAE (31%) only slightly greater than that observed for placebo (28%). In the repeat-dose studies, there was no evidence of cumulative safety issues, the incidence of TEAE decreased over time, and patients did not drop out because of TEAE. The most frequently reported AE were nasopharyngitis, sinusitis, upper respiratory tract infection, headache, and injection site reactions. The majority of TEAE were considered unlikely to be related or were not related to BoNTA-ABO treatment. In all studies, the TEAE that were considered possibly related to treatment were primarily headaches (with rates comparable to those observed for placebo), injection site reactions, and eye disorders (such as blepharospasm and eyelid ptosis). There were no clinically significant changes in hematologic or biochemical parameters or in vital signs. The cardiovascular substudy revealed that BoNTA-ABO had no effect on QT/QTc prolongation. CONCLUSIONS Treatment of glabellar lines with BoNTA-ABO is well tolerated. Overall, the safety profile of BoNTA-ABO is comparable to that of placebo in terms of type, frequency, severity, and relatedness of AE.

A review of onabotulinumtoxinA (Botox).

OnabotulinumtoxinA was introduced to the US market in 2002 as the first botulinum toxin type A (BoNTA) approved for facial aesthetics. This article provides an overview of onabotulinumtoxinAs uses and indications as well as safety and efficacy data. As with other BoNTA products, onabotulinumtoxinA is generally well tolerated. Consideration is also given to clinical applications of the product. Information on handling, storage, and dosing is provided.

IncobotulinumtoxinA (Xeomin): background, mechanism of action, and manufacturing.

IncobotulinumtoxinA is the third botulinum neurotoxin type A (BoNTA) to be approved for aesthetic use in the United States. This article introduces the new product with an overview of clinical applications and a discussion of the neurotoxins molecular structure. The role and clinical relevance of complexing proteins in BoNTA products are discussed. Finally, incobotulinumtoxinAs mechanism of action is described.

A review of AbobotulinumtoxinA (Dysport).

AbobotulinumtoxinA was approved by the US Food and Drug Administration in 2009 as the second botulinum neurotoxin type A (BoNTA) for use in facial aesthetics. This article provides an overview of abobotulinumtoxinAs applications and indications as well as safety and efficacy data. AbobotulinumtoxinA is generally well tolerated. Adverse events from abobotulinumtoxinA are similar to those reported with other BoNTA products. Clinical applications of the product are also discussed in this article. Information on handling, storage, and dosing is provided.

Physical Modalities (Devices) in the Management of Acne

Treatment options for acne vulgaris are enhanced by laser and light therapy. Both visible and laser light are effective treatments for acne. Visible light and many lasers target Propionibacterium acnes porphyrins while others act as anti-inflammatory mediators or reduce sebaceous gland activity. Compared with topical and systemic therapies, laser and light therapies have few if any side effects and appear to be safe during pregnancy. If patients prefer at home light treatments, several devices are currently available and have been shown to have efficacy. Ultimately, combining laser and light with topical therapy may well become the mainstay of acne treatment.