Gary D. Monheit

Comparative Physical Properties of Hyaluronic Acid Dermal Fillers

BACKGROUND Hyaluronic acid (HA) fillers are becoming the material of choice for use in cosmetic soft tissue and dermal correction. HA fillers appear to be similar, but their physical characteristics can be quite different. These differences have the potential to affect the ability of the physician to provide the patient with a natural and enduring result. OBJECTIVE The objective of this article is to discuss the key physical properties and methods used in characterizing dermal fillers. These methods were then used to analyze several well‐known commercially available fillers. METHODS AND MATERIALS Analytical methods were employed to generate data on the properties of various fillers. The measured physical properties were concentration, gel‐to‐fluid ratio, HA gel concentration, degree of HA modification, percentage of cross‐linking, swelling, modulus, and particle size. RESULTS The results demonstrated that commercial fillers exhibit a wide variety of properties. CONCLUSION Combining the objective factors that influence filler performance with clinical experience will provide the patient with the optimal product for achieving the best cosmetic result. A careful review of these gel characteristics is essential in determining filler selection, performance, and patient expectations. Jeffrey Kablik, LiPing Yu, Grace Chang, and Julia Gershkovich are employees of Genzyme Corporation. The materials used in this study were provided by Genzyme.

Hyaluronic acid fillers

ABSTRACT:u2002 Although hyaluronic acids are a relatively new treatment for facial lines and wrinkles, they have provided numerous advances in the area of cosmetic surgery. This article discusses the inherent properties of hyaluronic acid fillers that make them ideal for treatment of facial lines. It encompasses a review of the current literature on U.S. Food and Drug Administration‐approved hyaluronic acid fillers and the role that each of these fillers currently has in facial cosmetics. This article also discusses the potential pitfalls and adverse effects that can be associated with using hyaluronic acids for filling facial lines. Finally, it serves as an overview of current techniques for clinical assessment of patients as well as administration and treatment of facial lines and wrinkles.

Evaluation of Variable-Dose Treatment with a New U.S. Botulinum Toxin Type A (Dysport) for Correction of Moderate to Severe Glabellar Lines: Results from a Phase III, Randomized, Double-Blind, Placebo-Controlled Study

Background: In April, the U.S. Food and Drug Administration approved a new U.S. formulation of botulinum neurotoxin type A (Dysport; Medicis Aesthetics, Inc., Scottsdale, Ariz.). This formulation has demonstrated inhibition of glabellar lines at a 50-unit dose. Standard clinical practice is to adjust the dose based on muscle mass. Methods: Patients stratified by race/ethnicity were randomized to receive a single treatment of Dysport administered in various doses or placebo. Dysport was administered in a total volume of 0.4 to 0.6 ml for women (50, 60, or 70 units) and 0.5 to 0.7 ml for men (60, 70, or 80 units), based on procerus/corrugator muscle mass. Efficacy was assessed by a blinded evaluator and patient self-evaluation on days 14, 30, 60, 90, 120, and 150 after treatment. Results: At day 30, 85 percent and 87 percent of Dysport-treated patients were responders as assessed by blinded evaluator and patient self-evaluation, respectively, compared with 3 percent and 5 percent of placebo-treated patients, respectively (p < 0.001). Median duration of effect was 109 days for Dysport versus 0 days for placebo (blinded evaluator) and 107 days for Dysport versus 0 days for placebo (patient self-evaluation). Response and duration of action were slightly higher in African American patients. The majority of treatment-emergent adverse events were mild or moderate in severity. Conclusion: A single treatment with Dysport, with the dose based on gender and muscle mass, is well tolerated and provides a greater and longer-lasting improvement in glabellar lines compared with placebo.

Twelve-month persistency of a novel ribose-cross-linked collagen dermal filler.

BACKGROUND The porcine collagen–derived dermal filler Dermicol-P35 (Evolence, Colbar LifeScience Ltd, Herzliya, Israel) has low immunogenicity and the potential to provide a long-lasting corrective response for soft-tissue contour deficiencies and deformities. OBJECTIVE The objective was to assess the persistence of the corrective response with Dermicol-P35 up to 12 months after obtaining an optimal cosmetic result (OCR) in a randomized, multicenter study comparing the efficacy and safety of Dermicol-P35 with the hyaluronic acid (HA) filler Restylane (Medicis Pharmaceutical Co.). METHODS & MATERIALS Subjects with moderate to deep nasolabial wrinkles (n=149) were randomized to injections of either Dermicol-P35 or HA on one side of the face and the alternative preparation on the contralateral side. If necessary, one touch-up injection could be given after 2 weeks to obtain an OCR. RESULTS Although the mean Modified Fitzpatrick Wrinkle Scale score increased gradually after achieving the OCR with Dermicol-P35, 95.3 and 76.5% of subjects, respectively, met the criteria for persistence of the corrective response after 9 and 12 months. Persistency rates were similar regardless of the requirement for a touch-up injection at Week 2. No unexpected, severe, or serious injection-related adverse events were experienced. CONCLUSION The effectiveness of Dermicol-P35 appears to be maintained for up to 1 year after achieving an OCR, both for touch-up and for non–touch-up subjects.

Multicenter, Randomized, Parallel-Group Study of the Safety and Effectiveness of OnabotulinumtoxinA and Hyaluronic Acid Dermal Fillers (24-mg/mL Smooth, Cohesive Gel) Alone and in Combination for Lower Facial Rejuvenation

BACKGROUND Combination treatment with toxins and fillers is the standard regimen in facial rejuvenation. Systematic studies of botulinum toxin alone and in combination with hyaluronic acid (HA) have not, however, been conducted in the lower face. OBJECTIVE To evaluate safety and effectiveness and compare combination treatment with onabotulinumtoxinA and a 24‐mg/mL smooth, cohesive HA gel filler with either treatment alone for rejuvenation of the perioral area and lower face in female subjects. METHODS Ninety female participants aged 35 to 55 were randomized to one of three groups: 24‐mg/mL cohesive gel alone (n=30), onabotulinumtoxinA alone (n=30), or the combination (n=30). Effectiveness outcomes included perioral, lip fullness, and oral commissure assessments and scores on the Cosmetic Improvement and Global Aesthetic Improvement Scales. Adverse events were monitored throughout. RESULTS For all end points and most time points, subjects treated with onabotulinumtoxinA plus the 24‐mg/mL cohesive gel had greater improvement from baseline than subjects treated with onabotulinumtoxinA or the 24‐mg/mL cohesive gel filler alone. CONCLUSION Based on a range of end points, onabotulinumtoxinA and 24‐mg/mL cohesive HA gel treatments are effective and safe when either alone or in combination to rejuvenate the lower face. Combination therapy is superior to either modality used alone. Drs. Alastair and Jean Carruthers are consultants and investigators and receive honoraria from Allergan, Inc. They are also consultants and investigators for Merz Pharmaceuticals and Solstice Neurosciences. Dr. Gary Monheit is a consultant and clinical investigator for Allergan, Galderma, Medicis, Merz Pharmaceuticals, and Revance Therapeutics.

ASDS guidelines of care: injectable fillers.

S 1 1 5 Injectable soft tissue augmentation materials available for use in the United States have proliferated during the past 5 years. In addition to bovine collagen and autologous fat, physicians can now choose between numerous other options, including hyaluronic acid derivatives, poly-L-lactic acid, injectable calcium hydroxylapatite, injectable liquid silicone, polymethylmethacrylate microspheres, and human collagen. While these materials are generally safe and versatile, each has specific features that inform its best use. The guidelines presented herein are not intended to delineate the standard of care but rather to present how most injectors commonly use these materials in patients. These guidelines are a consensus document produced by the ASDS Guidelines of Care Task Force in conjunction with recognized experts in the field who have volunteered their time. While efforts have been made to maintain accuracy and timeliness at the point of submission, these guidelines will no doubt evolve over time and should be considered in the context of the patients’ individual needs. In the 1970s, research into collagen production led to a bovine formulation that could be placed in a syringe and injected. Because of bovine collagen’s temporary persistence, and requirement for skin testing, other fillers were developed and tested in Europe, Asia, and North America in the 1990s. Today, there are a number of fillers to choose from, each with its own strengths and drawbacks.

Long-term Safety and Efficacy of a New Botulinum Toxin Type A in Treating Glabellar Lines

OBJECTIVEnTo evaluate the long-term safety of repeated administrations of a new botulinum toxin type A (Reloxin; Medicis Pharmaceutical Corp, Scottsdale, Arizona) in the treatment of moderate to severe glabellar lines.nnnMETHODSnOpen-label assessment of 1200 patients receiving as many as 5 treatments of Reloxin over a 13-month period. The product was diluted in 2.5-mL sterile physiologic saline solution, 0.9%, without preservative to a concentration of 50 U of Reloxin per 0.25 mL of solution. Investigators injected 0.05 mL of the solution (10 U each) into each of 5 injection sites in the glabellar area on day 0 of each treatment cycle. There was a minimum 85-day gap between treatments. Postinjection clinical evaluation was performed on days 14 and 30 and monthly thereafter until retreatment, study completion, or early termination. The patients were telephoned on day 7 to check for adverse events (AEs) and concomitant medications, and patient diaries were used to document the onset of treatment effect.nnnRESULTSnThe majority (72%) of treatment-emergent AEs were considered unlikely or not related to study treatment. Probably or possibly related treatment-emergent AEs occurred in 36% of patients. The most frequently occurring related AEs were injection site disorders (18%), nervous system disorders (14% and 12% headache), and eye disorders (9%). Related AEs around the injection site or eyes were usually reported by day 7 and then resolved. Reported ptosis does not differentiate between brow ptosis and eyelid ptosis. A total of 45 patients had a total of 55 instances of ptosis across all cycles, with most episodes lasting less than 3 weeks. The rates of ptosis decreased during successive cycles from 2.4% in cycle 1 to 0.6% in cycle 5. The proportion of patients reporting an onset of response by day 7 ranged from 93% to 95%. By investigator assessment, the response rate (patients reporting none or mild glabellar line severity scale scores on day 30) ranged from 80% to 91% during cycles 1 to 5.nnnCONCLUSIONSnThere was no evidence of cumulative AEs or tachyphylaxis with multiple Reloxin treatments over a period of 13 months. The treatments were well tolerated. The rates of ptosis decreased over successive cycles, and the proportion of responders by day 7 ranged from 93% to 95%.

A randomized study of the efficacy and safety of injectable poly-L-lactic acid versus human-based collagen implant in the treatment of nasolabial fold wrinkles

BACKGROUNDnInjectable poly-L-lactic acid (PLLA) is a synthetic, biodegradable, biocompatible polymer device.nnnOBJECTIVEnWe sought to compare the efficacy and safety of injectable PLLA with human-derived collagen in treating nasolabial fold wrinkles.nnnMETHODSnIn this randomized, evaluator-blinded, parallel-group, multicenter study, subjects received injectable PLLA (n = 116) or collagen (n = 117) injections (1-4 visits, 3-week intervals). Wrinkle Assessment Scale scores were calculated at screening; posttreatment week 3; months 3, 6, 9, and 13 (injectable PLLA or collagen groups); and months 19 and 25 (injectable PLLA group). Safety data were obtained from subject interviews and case report forms.nnnRESULTSnInjectable PLLA significantly improved mean Wrinkle Assessment Scale scores (all time points, P < .001). Improvements (up to 25 months after last treatment) were significantly greater (P < .001) than with collagen for posttreatment months 3 to 13.nnnLIMITATIONSnMostly white women and subjects with Fitzpatrick skin types II and III were included.nnnCONCLUSIONnInjectable PLLA provides well-tolerated, effective, and long-lasting (up to 25 months) nasolabial fold wrinkle correction.

Medium Depth Chemical Peels

The combination medium-depth chemical peel (Jessners solution +35% TCA) has been accepted as a safe, reliable, and effective method for the treatment of moderate photoaging skin. This article discusses the procedure in detail, including postoperative considerations.

The Nature of Long-Term Fillers and the Risk of Complications

&NA; Dr. Monheit is a consultant and/or clinical investigator for Allergan, Inc., Colbar Lifescience Ltd., Contura MLB, Dermik Laboratories, and Genzyme Corporation.