Dermal fillers: an update.

Injection of dermal fillers is the second most frequent nonsurgical cosmetic procedure performed in the USA. Dermal fillers are an option in the treatment of volume deficiency, scars, and rhytides; facial sculpting; facial contouring; and augmentation of specific anatomical sites such as the lips. The number of injectable dermal fillers available on the market increases yearly. Dermatologists and cosmetic surgeons should regularly review treatment options to provide patients with safe and effective filler options. This paper extensively reviews the properties of the available fillers, such as their rheology, longevity, and adverse effects, and how these properties affect the choice of filler agent for a particular patient or a particular site. Also, trends in dermal filler injections are discussed.

Efficacy of incobotulinumtoxinA for treatment of glabellar frown lines: a post hoc pooled analysis of 2 randomized, placebo-controlled, phase 3 trials.

BACKGROUND: Botulinum neurotoxin type A trials in aesthetic indications have used differing efficacy parameters and responder definitions. OBJECTIVE: To analyze the treatment efficacy and duration of incobotulinumtoxinA for glabellar frown lines using pooled data from 2 large, Phase 3, placebo-controlled trials, and end points similar to those used in previous botulinum neurotoxin type A studies. MATERIALS AND METHODS: IncobotulinumtoxinA and placebo groups comprised 366 and 181 subjects, respectively. The efficacy of a single 20-U treatment of incobotulinumtoxinA or placebo was evaluated by investigator-assessed and subject-assessed responder rates (≥ 1-point improvement from baseline), mean score, and mean change from the baseline glabellar frown line severity score. RESULTS: At all follow-up visits, responder rates and mean change from the baseline score (investigator-assessed and subject-assessed) were significantly greater for incobotulinumtoxinA versus placebo (p < .0001). The maximum investigator-assessed responder rate (93.1%) was achieved at Day 30 after treatment, when the mean improvement on the 4-point facial wrinkle scale peaked at 1.88. Treatment effect declined over time but the investigator-assessed responder rate was 45.7% at the end of the study. CONCLUSION: Superiority of incobotulinumtoxinA over placebo for treating glabellar frown lines was confirmed. IncobotulinumtoxinA achieved a maximum responder rate of 93.1% and a long duration of treatment effect: 45.7% of subjects showed efficacy at 120 days.

Long-term efficacy, safety and durability of Juvéderm® XC.

Over the last decade, there has been increasing interest in minimally invasive cosmetic treatments, especially for facial rejuvenation. Next to botulinum toxin injection, the injection of soft tissue fillers is the second most frequent minimally invasive procedure performed in the USA. Hyaluronic acid (HA) is the most commonly used dermal filler. One of patients' main concerns about filler injections pertains to pain and discomfort. Topical anesthetics, nerve blocks, and/or the incorporation of lidocaine to the filler have been applied in order to reduce distress and pain. Despite nerve blocks being an effective form of anesthesia, they may distort the area to be treated, as well as lengthen and complicate the procedure. Studies have shown that the incorporation of lidocaine to HA fillers significantly reduces pain and discomfort. Yet, one of the dilemmas about the addition of lidocaine solution to HA fillers is the possible alteration of the physical characteristics of the product by negatively impacting the efficacy and/or duration of the filler. The concern is that the addition of lidocaine could dilute the product, creating less correction per mL, changing the product's viscosity and consequently the "lifting" ability. Also, this dilution could reduce the product's duration. There may be a difference between a physician adding an aqueous solution into a lidocaine-free version of HA and the pre-incorporated lidocaine version of HA. An aqueous solution might dilute the product, while the pre-incorporated powder lidocaine appears to avoid this problem. Juvéderm® XC is manufactured with powder lidocaine 0.3%; it is associated with significantly less injection pain than Juvéderm® and other lidocaine-free versions of HA. Studies have shown that lidocaine enhances treatment comfort and optimizes the injection experience while maintaining a similar safety and effectiveness profile. Regarding the longevity, further study is necessary to determine if there is any difference in durability.

Systematic review of clinical trials of small- and large-gel-particle hyaluronic acid injectable fillers for aesthetic soft tissue augmentation.

BACKGROUND: Hyaluronic acid (HA) is the most frequently injected filler for soft tissue augmentation in the United States. OBJECTIVE: To systematically review published evidence for aesthetic use of small- and large-gel-particle HA. METHODS AND MATERIALS: Clinical data on anatomic area, level of evidence, patient population, trial design, endpoints, efficacy, and safety were extracted from PubMed. RESULTS: Fifty-three primary clinical reports were analyzed. The highest-quality efficacy evidence was for the nasolabial folds (NLFs), with 10 randomized, blind, split-face, comparative trials. Several randomized, blind trials supported treatment of the glabella, lips, and hands. Lower-level evidence (from studies with nonrandomized, open-label, or retrospective designs) was recorded for the nasojugal folds (tear troughs), upper eyelids, nose, infraorbital hollows, oral commissures, marionette lines, perioral rhytides, temples, and cheeks. Common adverse events (AEs) across anatomic areas were pain, bruising, swelling, and redness. Serious AEs were uncommon (8 events in 8 patients of 4,605 total patients) and were considered to be unrelated (7 events) or probably unrelated (1 event) to treatment. CONCLUSION: The efficacy and safety of small- and large-gel-particle HA are well established for NLFs; evidence for the glabella, lips, and hands is more limited. Preliminary reports in other anatomic regions suggest efficacy without major complications.

Development and validation of a new clinically-meaningful rating scale for measuring lateral canthal line severity.

BACKGROUND: Several scales have been employed for evaluating the effects of cosmetic treatments in the periorbital area. The Food and Drug Administration (FDA) has recently issued new recommendations specifying a rigorous process to validate new aesthetic scales. OBJECTIVES: The authors describe and validate a new clinical rating scale: the Investigator's Global Assessment of Lateral Canthal Line (IGA-LCL) severity scale. METHODS: The new FDA recommendations were utilized to validate the new scale. The first step was concept elicitation (based on direct input from clinicians, patients, and literature) and evaluation of content validity (appropriateness of concepts). The resulting five-point scale provided detailed descriptions of the lateral canthal lines (LCL), including quantitative assessment of LCL length and depth. Performance parameters, including intra- and interrater reproducibility and construct validity, were then evaluated in clinical studies. Finally, the scale's threshold for clinically-meaningful benefit and the ability of the scale to detect change were confirmed in two Phase 2b clinical studies involving a total of 270 subjects. RESULTS: Content validity was established and the IGA-LCL scale showed excellent interrater reliability (weighted Kappa = 0.89) and interrater reliability (weighted Kappa = 0.77; Kendall's coefficient of concordance = 0.89). In clinical trials, the scale was sensitive enough to detect clinically-meaningful one- and two-point changes in LCL severity following treatment with topical botulinum toxin type A (BoNT-A). The authors observed statistically-significant correlations between the physician-rated IGA-LCL results and patient-reported outcomes. CONCLUSIONS: The IGA-LCL scale was shown to be reliable, appropriate, and clinically meaningful for measuring LCL severity.

Long-term effectiveness and safety of small gel particle hyaluronic acid for hand rejuvenation.

BACKGROUND: Fillers to reverse the effects of fat atrophy can help restore the hands' youthful appearance. OBJECTIVE: To evaluate the effectiveness and safety of small gel particle hyaluronic acid (SGP-HA) for hand rejuvenation through 1 year. MATERIALS AND METHODS: A prospective open-label study recruited adults with moderate to severe vascular, bony, and tendon prominence. After a topical anesthetic was applied, SGP-HA (maximum dose of 4.0 mL) was injected into the dorsum using a threading technique and distributed by massage. RESULTS: There were 16 patients with a mean ± SD age of 60.1 ± 5.3. Two weeks after treatment, vascular, tendon, and bony prominence and skin turgor were improved by 60.9%, 65.2%, 73.7%, and 26.3%, respectively. Substantial or complete global aesthetic improvement was rated in 75% of patients by investigators and in 56% by self-report; 81% of patients were satisfied or very satisfied. Five needed a touch-up (maximum 1.0 mL/hand). Improvements were largely maintained at 6 months, with 85% patient satisfaction, and assessments approached pretreatment levels at 1 year, with 50% patient satisfaction. One patient reported itching on one hand, which was judged to be unrelated to treatment. CONCLUSION: SGP-HA produced lasting improvements in aging hands and was safe and well tolerated.

Cosmeceuticals: current trends and market analysis.

The desire to maintain a youthful image combined with an emerging global market with disposable income has driven the development of many new industries. The cosmeceutical industry is based on the development and marketing of products that lie between cosmetics and pharmaceuticals. Today, there are over 400 suppliers and manufacturers of cosmeceutical products, and the industry is estimated to grow by 7.4% by 2012. Although a number of products advertise predictable outcomes, the industry is largely unregulated and any consumers of cosmeceutical products should consult a dermatologist prior to use. This review will provide a snapshot of the current trends of this industry and provide an analysis of this multi-billion dollar market.

Investigator global evaluations of efficacy of injectable poly-L-lactic acid versus human collagen in the correction of nasolabial fold wrinkles.

BACKGROUND: Injectable poly-L-lactic acid (PLLA) is indicated in the United States for use in immune-competent patients for correction of shallow-to-deep nasolabial fold contour deficiencies and other facial wrinkles in which a deep dermal grid pattern injection technique is appropriate. It is also indicated for restoration and/or correction of signs of lipoatrophy in patients with human immunodeficiency virus. OBJECTIVE: The authors examine the efficacy of injectable PLLA for correction of nasolabial fold wrinkles, based on Investigator Global Evaluations (IGE). METHODS: A randomized, multicenter, subject-blinded, parallel-group study compared injectable PLLA versus human collagen for correction of nasolabial fold wrinkles for 13 months after up to four treatments (intent-to-treat population, 233). Injectable PLLA-treated subjects were followed up for an additional 12 months (total, 25 months) after the final treatment session. Efficacy was also assessed through secondary IGE for improvement, which is the subject of this report. RESULTS: IGE reports of improvement were significantly greater in subjects who received injectable PLLA versus those who received human collagen (p < .001). Overall improvement with injectable PLLA was 100% three weeks after the final treatment, remaining above 85% through month 25. Overall IGE of improvement with human collagen declined from 94.0% at week three to 6.0% at month 13. Both treatment groups had similar safety profiles. CONCLUSIONS: IGE of improvement were significantly greater with injectable PLLA treatment than with human collagen treatment at all time points following the last treatment. Injectable PLLA treatment continued to show a beneficial effect for up to 25 months.

Subject global evaluation and subject satisfaction using injectable poly-L-lactic acid versus human collagen for the correction of nasolabial fold wrinkles.

BACKGROUND: This is a report of the secondary endpoints, Subject Global Evaluation (overall improvement) and Subject Satisfaction scores, from a study designed to examine the efficacy of injectable poly-L-lactic acid for the correction of nasolabial fold wrinkles over 25 months. METHODS: A randomized, subject-blinded, parallel-group, multicenter clinical study was conducted to compare the effects of injectable poly-L-lactic acid with those of human collagen for the treatment of nasolabial fold wrinkles at 13 months following the last treatment. Injectable poly-L-lactic acid-treated subjects were followed for 25 months. RESULTS: From month 3 through month 13 following the last treatment, injectable poly-L-lactic acid-treated subjects (n = 116) reported significantly higher Subject Global Evaluation scores compared with human collagen-treated subjects (n = 117; p < 0.001). Overall Subject Global Evaluation scores for injectable poly-L-lactic acid-treated subjects were 99 percent at week 3, 91 percent at month 13, and 81 percent at month 25 (all times following the last treatment). In contrast, for human collagen-treated subjects, overall Subject Global Evaluation scores declined by 84 percent, from 96 percent at week 3 to 15 percent at month 13. Subject Satisfaction scores were significantly different (p < 0.01) between treatment groups beginning week 3 and continuing through month 13. Overall Subject Satisfaction scores were maintained for over 80 percent of injectable poly-l-lactic acid-treated subjects (n = 106) at month 25 after the last treatment. CONCLUSIONS: Treatment of nasolabial fold wrinkles with injectable poly-l-lactic acid resulted in statistically significantly higher Subject Global Evaluation and Subject Satisfaction scores compared with human collagen at 13 months. Injectable poly-l-lactic acid-treated subjects maintained improvements for up to 25 months after treatment.

Persistence of nasolabial fold correction with a hyaluronic acid dermal filler with retreatment: results of an 18-month extension study.

BACKGROUND: An 18-month persistence study reported nasolabial fold (NLF) improvements using a small gel-particle hyaluronic acid (SGP-HA) dermal filler lasted up to 18 months after one retreatment. OBJECTIVE: [corrected] To evaluate the efficacy and persistence of SGP-HA for the correction of NLFs for up to 36 months. METHODS & MATERIALS: Subjects completing the 18-month persistence study were permitted to enroll in an 18-month extension trial. Most required second retreatments to achieve optimal correction of their NLFs. Subjects were followed for up to 36 months after their initial treatment. The primary efficacy measure was a 1-point improvement from baseline Wrinkle Severity Rating Scale (WSRS) score as determined by a blinded evaluator at different time points. RESULTS: The study enrolled 52 subjects. Forty subjects required a second retreatment for optimum NLF correction. Mean retreatment volume was less than 50% of the initial treatment volume. Twenty-six subjects completed the study. Blinded assessments revealed that 94% to 100% of subjects maintained WSRS scores of 1 point or more higher than baseline throughout the study. CONCLUSIONS: Participants in the 18-month extension of an 18-month SGP-HA persistence study continued to demonstrate improvement of NLFs up to 36 months after a second retreatment. The mean volume of SGP-HA required for optimum NLF correction decreased substantially with each retreatment. Subjects reported no treatment-related adverse events after the second retreatment.

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.

BACKGROUND: Injectable poly-L-lactic acid (PLLA) is a synthetic, biodegradable, biocompatible polymer device. OBJECTIVE: We sought to compare the efficacy and safety of injectable PLLA with human-derived collagen in treating nasolabial fold wrinkles. METHODS: In 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. RESULTS: Injectable 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. LIMITATIONS: Mostly white women and subjects with Fitzpatrick skin types II and III were included. CONCLUSION: Injectable PLLA provides well-tolerated, effective, and long-lasting (up to 25 months) nasolabial fold wrinkle correction.

An analysis of efficacy data from four phase III studies 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) has recently been approved in the United States for the treatment of moderate to severe glabellar lines. OBJECTIVE: We describe the results of four phase III studies of BoNTA-ABO for the treatment of glabellar lines. METHODS: Of the four studies reported here, three were double-blind, multicenter, randomized, placebo-controlled studies and one was an open-label extension study. A second phase III, open-label extension study is ongoing. Studies enrolled ethnically diverse, healthy adults with glabellar lines of at least moderate severity at maximum frown. Patients were followed for up to 180 days after treatment. The fixed-dose, single treatment study randomized 158 patients to receive placebo or a single 50-unit BoNTA-ABO dose. The fixed-dose, repeat treatment study enrolled 311 patients to assess treatment following repeat BoNTA-ABO treatment of 50 units. A variable-dose study randomized 816 patients to receive placebo or a single variable dose (50 to 80 units, based on gender and muscle mass assessment). The fourth phase III study was open-label to evaluate repeat dosing (50 units). Clinical evaluations were performed on days 14 and 30, and monthly thereafter. Primary efficacy endpoints were based on the investigators' and patients' assessment of glabellar line severity at day 30 using wrinkle severity rating scales. Responders were defined as patients who had a composite 2+ grade improvement in wrinkle severity, meaning that a patient had a baseline Glabellar Line Severity Scale (GLSS) score of 2 (moderate glabellar lines) and a day 30 GLSS score of 0 (no glabellar lines/none), or a baseline GLSS score of 3 (severe glabellar lines) and a day 30 GLSS score of 0 (no glabellar lines/none) or 1 (mild glabellar lines), for both the blinded investigator's and patient's assessments. RESULTS: Patients (1116 total; 720 BoNTA-ABO, 396 placebo) treated with BoNTA-ABO received 50 to 80 units. The median duration of response was 85 days for fixed dosing and 109 days for variable dosing. Similar efficacy occurred at doses adjusted for gender and muscle mass, although male patients required higher doses than female patients in the variable-dose study. Responses appeared as early as 24 hours, with a median time to onset of three days. The open-label extension study evaluated 1200 patients for 13 months. Maintenance of efficacy was seen after multiple treatment cycles, indicating that patients did not develop a tolerance. A second open-label study is ongoing and is not included in this report. CONCLUSIONS: BoNTA-ABO significantly improved moderate to severe glabellar lines compared with placebo, with onset of effect seen as soon as 24 hours after treatment and a median duration of effect of 85 and 109 days for fixed and variable dosing, respectively.

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.

Hyaluronic acid gel fillers in the management of facial aging.

Time affects facial aging by producing cellular and anatomical changes resulting in the consequential loss of soft tissue volume. With the advent of new technologies, the physician has the opportunity of addressing these changes with the utilization of dermal fillers. Hyaluronic acid (HA) dermal fillers are the most popular, non-permanent injectable materials available to physicians today for the correction of soft tissue defects of the face. This material provides an effective, non invasive, non surgical alternative for correction of the contour defects of the face due to its enormous ability to bind water and easiness of implantation. HA dermal fillers are safe and effective. The baby-boomer generation, and their desire of turning back the clock while enjoying an active lifestyle, has expanded the popularity of these fillers. In the US, there are currently eight HA dermal fillers approved for commercialization by the Food and Drug Administration (FDA). This article reviews the innate properties of FDA-approved HA fillers and provides an insight on future HA products and their utilization for the management of the aging face.

A randomized, multicenter study of the safety and efficacy of Dermicol-P35 and non-animal-stabilized hyaluronic acid gel for the correction of nasolabial folds.

BACKGROUND: Non-animal-stabilized hyaluronic acid (NASHA) offers longer-lasting cosmetic improvement and reduced risk of hypersensitivity and requires less injection volume than bovine collagen-derived dermal fillers. Porcine collagen-derived Dermicol-P35 has low immunogenicity and has the potential to provide durability at least equivalent to that of NASHA. OBJECTIVE: The objective was to evaluate the efficacy and safety of Dermicol-P35 and NASHA for correction of nasolabial folds (NLFs). METHODS AND MATERIALS: A total of 149 subjects with moderate NLFs were randomized to receive Dermicol-P35 and NASHA on contralateral sides of the face. If needed, subjects could receive a repeat injection 2 weeks later to obtain an optimal cosmetic result (OCR). RESULTS: Significant (p<.001) improvement in the Modified Fitzpatrick Wrinkle Scale scores relative to screening was observed after treatment with Dermicol-P35 and NASHA. Relative to the OCR visit, mean scores increased (p<.001) over time, but there were no significant differences between treatments (+0.39 and +0.37 at 6 months; p=.626). Greater proportions of subjects experienced swelling, bruising, and pain at the NASHA site. Several subjects had more induration at the Dermicol-P35 site. There was no evidence of any adverse immunologic effect. CONCLUSION: The effectiveness of Dermicol-P35 is maintained for at least 6 months and is equivalent to NASHA for the correction of NLFs.

Hyaluronic acid fillers: Restylane and Perlane.

The list of injectable skin fillers available for soft-tissue augmentation is constantly growing, giving aesthetic surgeons more options in the treatment of scars, lines, and wrinkles. Various products for soft-tissue augmentation are currently available in the United States based on hyaluronic acid. One should keep in mind that for these hyaluronic acid gel to have the desired longevity they must have repeating chemical bridges to withstand the constant mechanical and chemical enzymatic degradation to which they are subjected once implanted. Restylane and Perlane have proved to be safe, effective, and liked by patients. The Restylane family of products is currently expanding and soon practitioners will be able to have a diversified arsenal of cross-linked hyaluronic acid products to rejuvenate the aging face.

Botulinum toxin for the treatment of neck lines and neck bands.

Rejuvenation of the aging neck with botulinum toxin injections is a minimally invasive, safe, and effective treatment modality with a very high patient satisfaction rate. Treatments are usually started early in the aging process of the neck to prevent further degenerative changes and are performed thereafter at 4- to 6-month intervals. It is the ideal alternative to rhytidectomy when the patient is too young for face-lift surgery or for patients unwilling to take recuperation time. Furthermore, botulinum toxin therapy can be used to correct jowl and platysmal band asymmetry occurring after suboptimal rhytidectomy. Botulinum exotoxin should not be used in pregnant or lactating women or in patients with a known sensitivity to human albumin or with a history of neuromuscular disorders.

Botulinum toxin for rejuvenation of the neck.

The use of botulinum toxin for cosmetically restoring an aging neck is a simple procedure that has great patient satisfaction. It is also a safe and effective therapeutic modality for any patient desiring rejuvenation of his or her neck, but who at the same time does not desire any recuperation time or is unwilling to undertake the potential risks associated with plastic surgery. Currently, both botulinum toxin type A (BTX-A) and B are being used to treat the aging neck with great success. However, our clinical experience has been more vast with BTX-A, and the accomplishment of several clinical trials with it has yielded more precise results. BTX-A can be used to correct early signs of aging as well as more advanced forms. It helps correct jowl formation and platysmal banding as well as horizontal rhytides in the neck.