Comparison of Hyaluronic Acid Gel With (HARDL) and Without Lidocaine (HAJUP) in the Treatment of Moderate-To-Severe Nasolabial Folds: A Randomized, Evaluator-Blinded Study.

BACKGROUND: Injectable fillers, such as those containing hyaluronic acid (HA), are increasingly used to smooth age-related facial creases and wrinkles. OBJECTIVE: To compare efficacy and safety of a HA gel with lidocaine formulated by XpresHAn Technology (HARDL) with a HA gel without lidocaine produced by Hylacross technology (HAJUP) in the treatment of moderate-to-severe nasolabial folds. MATERIALS AND METHODS: Subjects (n = 162) received initial and touch-up injections with HARDL and HAJUP on either side of the face. Investigator- and subject-assessed wrinkle severity was measured up to 48 weeks after final injection. RESULTS: Mean (SD) Wrinkle Severity Rating Scale was improved by 1.1 (0.75) and 1.1 (0.68) with HARDL and HAJUP, respectively, at 24 weeks; improvements were sustained up to Week 48 with both treatments. Noninferiority of HARDL was demonstrated (mean difference -0.09 [95% confidence interval: -0.18 to -0.01], p = .032) at 24 weeks. Adverse events were reported in 43% subjects, 12% were treatment related, with a similar distribution for both treatments. CONCLUSION: Effectiveness and safety profiles of HARDL and HAJUP were comparable.

Anatomical Basis for Safe and Effective Volumization of the Temple.

BACKGROUND: One of the earliest but often unaddressed signs of facial aging is volume loss in the temple. Treatment of the area can produce satisfying results for both patient and practitioner. OBJECTIVE: Safe injection requires explicit knowledge of the anatomy to avoid complications related to the multitude of vessels that course throughout the region at various depths. The authors aim to detail the anatomy of the area and provide a safe and easy-to-follow method for injection. MATERIALS AND METHODS: The authors review the relevant anatomy of the temporal region and its application to cosmetic filler injections. RESULTS: The authors describe an easy-to-follow approach for a safe and effective injection window based on numerous anatomical studies. Injection in this area is not without risk, including potential blindness. The authors review the potential complications and their treatments. CONCLUSION: Hollowing of the temple is an early sign of aging that, when corrected, can lead to significant patient and practitioner satisfaction. Proper anatomically knowledge is required to avoid potentially severe complications. In this study, the authors present a reliable technique to safely and effectively augment this often undertreated area of the aging face.

Volumizing Hyaluronic Acid Filler for Midface Volume Deficit: Results After Repeat Treatment.

BACKGROUND: Juvéderm Voluma XC (VYC-20L; hyaluronic acid gel) is approved in the United States for correction of age-related midface volume deficit (MVD). OBJECTIVE: Assess safety and effectiveness of VYC-20L after repeat treatment. METHODS: Subjects with MVD underwent optional repeat treatment 12 to 24 months after initial treatment if correction was lost or at 24 months regardless of loss of correction (n = 167). Investigators rated outcomes on the Mid-Face Volume Deficit Scale (MFVDS) and the Global Aesthetic Improvement Scale (GAIS). Subject-rated outcomes were the GAIS, overall satisfaction with facial appearance, achievement of treatment goal, and Self-Perception of Age questionnaire. Subjects recorded treatment-site responses in 30-day diaries. RESULTS: Mean injection volume for repeat treatment (3.13 mL) was approximately half the mean total injection volume for initial/touch-up treatment (6.8 mL). After repeat treatment, effectiveness was demonstrated on all investigator-rated and subject-rated measures, consistent with results observed after initial treatment. The percentage of subjects improving by ≥1 point on the MFVDS was 82.8% and 91.1% at 6 and 12 months after repeat treatment, respectively. The incidence, severity, and duration of common treatment-site responses were lower after repeat versus initial treatment. CONCLUSION: Repeat treatment with VYC-20L was well tolerated and resulted in high levels of effectiveness and subject satisfaction.

Five-Year Safety and Satisfaction Study of PMMA-Collagen in the Correction of Nasolabial Folds.

BACKGROUND: A polymethylmethacrylate-collagen filler is generally believed to give long-term benefits, but the risk of granuloma formation over time remains unclear. OBJECTIVE: To determine the incidence of granuloma formation and response to treatment and assess the degree of patient satisfaction over 5 years. MATERIALS AND METHODS: Adults seeking correction of nasolabial folds underwent up to 3 injection sessions over 2 months. Subjects were then queried regularly for the development of signs and symptoms of a granuloma. Any positive responses were evaluated, and lesions suspicious for granulomas were confirmed by biopsy. Granulomas were treated at the discretion of the investigator. Subjects also completed regular satisfaction questionnaires. RESULTS: A total of 1,008 subjects were enrolled and 871 completed the full 5 years of the study. A biopsy-confirmed granuloma developed in 1.7% of subjects. Almost all granulomas responded to treatment. At study exit, 0.9% of subjects had an unresolved granuloma. Patient satisfaction remained high throughout the duration of the study. CONCLUSION: The incidence of granuloma formation with a polymethylmethacrylate-collagen dermal filler is low, and almost all lesions are manageable with simple therapeutic measures. Patient satisfaction remains durable over 5 years. Polymethylmethacrylate-collagen offers a well-characterized and very favorable risk/benefit profile.

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.

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 investigator's rating on the FWS, and 2-point or more responders at maximum frown on Day 30 according to the patient's 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.

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.

Validated composite assessment scales for the global face.

BACKGROUND: Twenty grading scales have been developed to assess age-related facial changes. Until now, the validity with regard to the patient's actual age and the clinical importance of combined measurement tools to describe facial aging was unclear. OBJECTIVE: To investigate the reliability and validity of a total face score and three global face assessment scales for estimated age, estimated aesthetic treatment effort, and signs of aging in the facial units. MATERIALS AND METHODS: Descriptive, reliability, correlation, and principal component analyses based on the assessment of 50 subjects by 12 raters using the 20 grading scales and the global face assessment scales. RESULTS: Inter- and intrarater reliability was high for the total face score and for the scales on estimated age and aesthetic treatment effort. Actual age was highly correlated with these three measures. Facial aging was indicated particularly by scales of the lower face. CONCLUSION: The aesthetic grading scales and global scales on estimated age and aesthetic treatment effort are reliable and valid instruments. The results suggest that a more-comprehensive evaluation of the human face and its age-related changes can help to identify important areas of facial aging and to define optimal aesthetic treatment strategies.

Validated assessment scales for the upper face.

BACKGROUND: Age-related upper face changes such as wrinkles, lines, volume loss, and anatomic alterations may affect quality of life and psychological well-being. The development of globally accepted tools to assess these changes objectively is an essential contribution to aesthetic research and routine clinical medicine. OBJECTIVE: To establish the reliability of several upper face scales for clinical research and practice: forehead lines, glabellar lines, crow's feet (at rest and dynamic expression), sex-specific brow positioning, and summary scores of forehead and crow's feet areas and of the entire upper face unit. METHODS AND MATERIALS: Four 5-point photonumerical rating scales were developed to assess glabellar lines and sex-specific brow positioning. Twelve experts rated identical upper face photographs of 50 subjects in two separate rating cycles using all eight scales. Responses of raters were analyzed to assess intra- and interrater reliability. RESULTS: Interrater reliability was substantial for all upper face scales, aesthetic areas, and the upper face score except for the brow positioning scales. Intrarater reliability was high for all scales and resulting scores. CONCLUSION: Except for brow positioning, the upper face rating scales are reliable tools for valid and reproducible assessment of the aging process.

Validated assessment scales for the mid face.

BACKGROUND: The improvement of aesthetic treatment options for age-related mid face changes, such as volume loss, and the increase in patient expectations necessitates the development of more-complex and globally accepted assessment tools. OBJECTIVE: To develop three grading scales for objective assessment of the infraorbital hollow and upper and lower cheek fullness and to establish the reliability of these scales for clinical research and practice. METHODS AND MATERIALS: Three 5-point rating scales were developed to assess infraorbital hollow and upper and lower cheek fullness objectively. Twelve experts rated identical mid face photographs of 50 subjects in two separate rating cycles using the mid face scales. Test responses of raters were analyzed to assess intra- and interrater reliability. RESULTS: Interrater reliability was substantial for the infraorbital hollow, upper cheek fullness, and lower cheek fullness scales. Intrarater reliability was high for all three scales. Both of the cheek fullness scales yielded higher reliabilities when three rather than two views were used to assess the volume changes of the cheek. CONCLUSION: The mid face scales are reliable tools for valid and reproducible assessment of age-related mid face changes.

Validated assessment scales for the lower face.

BACKGROUND: Aging in the lower face leads to lines, wrinkles, depression of the corners of the mouth, and changes in lip volume and lip shape, with increased sagging of the skin of the jawline. Refined, easy-to-use, validated, objective standards assessing the severity of these changes are required in clinical research and practice. OBJECTIVE: To establish the reliability of eight lower face scales assessing nasolabial folds, marionette lines, upper and lower lip fullness, lip wrinkles (at rest and dynamic), the oral commissure and jawline, aesthetic areas, and the lower face unit. METHODS AND MATERIALS: Four 5-point rating scales were developed to objectively assess upper and lower lip wrinkles, oral commissures, and the jawline. Twelve experts rated identical lower face photographs of 50 subjects in two separate rating cycles using eight 5-point scales. Inter- and intrarater reliability of responses was assessed. RESULTS: Interrater reliability was substantial or almost perfect for all lower face scales, aesthetic areas, and the lower face unit. Intrarater reliability was high for all scales, areas and the lower face unit. CONCLUSION: Our rating scales are reliable tools for valid and reproducible assessment of the aging process in lower face areas.

Validated assessment scale for neck volume.

BACKGROUND: Sagging of the neck aesthetic area is an important indicator of age. The development of complex and globally accepted tools for proper assessment of the change in neck volume is an essential contribution to aesthetic research and the routine clinical setting. OBJECTIVE: To develop a grading scale for the objective assessment of the neck volume and to establish the reliability of this scale for clinical research and practice. MATERIALS AND METHODS: A 5-point rating scale was developed to assess neck volume objectively. Twelve experts rated frontal and lateral neck photographs of 50 subjects in two separate rating cycles using the neck volume scale. Responses of raters were analyzed to assess inter- and intrarater reliability. RESULTS: Interrater reliability for the neck volume scale was almost perfect, with intraclass correlation coefficients for the first and second rating cycles of 0.85 and 0.84, respectively. Intrarater reliability for the neck volume scale was high (0.90) and Pearson correlation coefficients ranged between 0.88 and 0.95 and were statistically significant. CONCLUSION: The neck volume scale demonstrates optimal reliability for clinical research and practice.

Polyacrylamide hydrogel differences: getting rid of the confusion.

Polymer hydrogels have been used for many years in European and Asian countries, and these products are often considered to be the same material in different packaging. This, however, is not the case. Performance and safety profiles depend on many factors including chemical and physical characteristics (including rheological properties), manufacturing process and control (cross linking, impurities, stability, etc.), injection technique, and interaction with surrounding tissues. Polyacrylamide hydrogel (PAAH) products, although often considered equal, have clear differences in composition, manufacturing, and injection technique as well as ability to interact with surrounding tissues, characteristics that determine the safety and effectiveness profiles of each of these gels.

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.