Volumizing Hyaluronic Acid Filler for Midface Volume

Volumizing Hyaluronic Acid Filler for Midface Volume Deficit: Results After Repeat Treatment Leslie Baumann, MD,* Rhoda S. Narins, MD, FAAD,† Kenneth Beer, MD, FAAD,‡ Arthur Swift, MD,x Kimberly J. Butterwick, MD,k Julius Few, MD,¶ Adrienne Drinkwater, PhD,# and Diane K. Murphy, MBA**

´ BACKGROUND Juvederm 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 SelfPerception 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. L. Baumann serves as a consultant for, has received a research grant from, and is a stockholder of Allergan plc. R. S. Narins, K. Beer, A. Swift, and K. J. Butterwick have received a research grant from Allergan plc. J. Few serves on an advisory board for Allergan, Inc.; as a remunerated consultant and speaker for Allergan plc and has received research grants as an investigator for Allergan plc. A. Drinkwater provided medical writing assistance at the request of the authors, funded by Allergan plc. D. K. Murphy is an employee and stockholder of Allergan, Inc. The opinions expressed in this article are those of the authors. The authors received no honorarium or other form of financial support related to the development of this article. Supported by Allergan plc, Dublin, Ireland. Editorial assistance was provided by Peloton Advantage, Parsippany, NJ and was funded by Allergan plc, Dublin, Ireland.

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ver the past decade, there has been a trend away from surgery and toward the use of injectable fillers to reduce the appearance of sagging skin and skin folds seen with midface volume deficit (MVD).1–3 The hyaluronic acid (HA) dermal filler Juvéderm Voluma XC (VYC-20L; Allergan plc, Dublin, Ireland), a 20 mg/mL HA gel containing 0.3%

lidocaine, was the first injectable filler approved by the US Food and Drug Administration (October 2013) to correct age-related MVD.4 In the pivotal study,5 85.6% of subjects treated with VYC-20L improved by $1 point on the validated 6-point Allergan Mid-Face Volume Deficit Scale (MFVDS) at Month 6 (primary endpoint), and correction of MVD was maintained for

*Baumann Cosmetic and Research Institute, Miami, Florida; †Dermatology Surgery and Laser Center, New York, New York; ‡Beer Cosmetic, Surgical and General Dermatology, West Palm Beach and Jupiter, Florida; xThe Westmount Institute of Plastic Surgery, Montreal, QC, Canada; kCosmetic Laser Dermatology, San Diego, California; ¶Clinical Professor of Surgery, Division of Plastic Surgery, University of Chicago Pritzker School of Medicine, The Few Institute for Aesthetic Plastic Surgery, Chicago, Illinois; #Suffield, Connecticut; **Allergan plc, Irvine, California © 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 1076-0512 Dermatol Surg 2015;41:S284–S292 DOI: 10.1097/DSS.0000000000000541

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up to 2 years. Additionally, 89.8% and 75.8% of VYC-20 L–treated subjects reported improvement in satisfaction with their facial appearance at 6 months and 2 years, respectively.6 On completion of the extended follow-up period in the pivotal study, subjects treated with VYC-20L were offered an optional repeat treatment. The current report describes the effectiveness and safety of VYC20L after repeat treatment in subjects with moderate to severe MVD.

Methods Study Design A multicenter, single-blind, randomized, controlled study was conducted from August 2009 to April 2014 at 15 investigational sites in the United States and Canada. The study was registered at www. clinicaltrials.gov (NCT00978042) and was approved by applicable institutional review boards. All subjects signed informed consent before any study-related procedures. The study design and subject selection criteria were previously reported.5 Briefly, the study enrolled subjects 35 to 65 years of age who desired cheek augmentation to correct moderate, significant, or severe age-related MVD. Each study site had a treating investigator and 2 blinded evaluating investigators (EIs). Subjects were randomized to treatment with VYC-20L or to a no-treatment control group. Control subjects were permitted to receive VYC-20L after Month 6. VYC-20L was injected into the zygomaticomalar region, the anteromedial cheek, and/or the submalar region, with optional touchup treatment performed after 30 days. The treating investigator determined the appropriate volume of VYC-20L (#12 mL) for initial and touch-up treatments combined and for the optional repeat treatment. Subjects who lost their correction between 12 and 24 months after initial treatment were eligible for repeat treatment at that time, and all subjects who completed the extended follow-up period were offered repeat treatment at 24 months, regardless of the correction maintained at that visit. Loss of correction was

defined as overall MFVDS score and MFVDS score in all subregions that returned to the baseline value (or below the baseline value). After repeat treatment, follow-up visits were scheduled at Months 1, 3, 6, 9, and 12. Safety could be assessed by telephone at 3, 6, and 9 months after repeat treatment. Office visits for evaluation of effectiveness were required at Months 1 and 12 after repeat treatment. Response Measures and Statistics Effectiveness Evaluating investigators assessed MVD overall and for each facial subregion based on the MFVDS, with severity graded as none (0), minimal (1), mild (2), moderate (3), significant (4), or severe (5).5,7 Response was defined as a $1 point reduction in MFVDS score derived from the average of the 2 EIs’ scores relative to baseline. Evaluating investigators and subjects rated overall aesthetic improvement on the Global Aesthetic Improvement Scale (GAIS) by comparing the subject’s appearance at follow-up visits with baseline photographs on a 5-point scale ranging from “much improved” to “much worse.”7 Investigator scores were based on the average of the EIs’ assessments. Subjects assessed their satisfaction with facial appearance with an 11-item Facial Appearance Evaluation, with each item rated on a 5-point scale from 0 (“not at all”; “never”; or “no,” depending on the question) to 4 (“completely”; “always”; “definitely”). The overall score of satisfaction with facial appearance, calculated from responses to individual questions, is reported on a scale from 0 (least satisfaction) to 100 (greatest satisfaction). Increases from baseline in overall satisfaction with facial appearance were considered statistically significant if the lower limit of the confidence interval was greater than 0. At each follow-up visit, subjects assessed whether their baseline treatment goals had been met. In addition, the Self-Perception of Age, a single-item validated questionnaire, was used to ascertain whether subjects felt that they looked younger, their age, or older and, if applicable, how many years younger or older they felt they looked.8–10

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For subjects who completed the extended follow-up period after Month 12 and before Month 24 due to loss of correction per the MFVDS, missing data up to Month 24 were imputed using the MFVDS scores from the study completion visits. A subgroup analysis of key effectiveness measures, beginning with initial treatment, was also performed for the subgroup that had repeat treatment assessments.

Safety Safety was assessed in all subjects who received repeat treatment. Subjects completed diaries for 30 days after each treatment to record the incidence, severity, and duration of any common treatment site responses (TSRs). Those that were ongoing at the end of the 30-day diary were classified as adverse events (AEs). Treating investigators could additionally report other AEs throughout the study. Results Subjects Subject disposition for the initial treatment period (Figure 1) has been described in detail previously.5 Briefly, 282 subjects were randomized to the treatment group (n = 235) or the control group (n = 47). Of the 270 subjects who received treatment with VYC-20L, 167 subjects underwent repeat treatment, including 141 subjects in the treatment group and 26 subjects in the control group. Effectiveness results for the extended 24-month follow-up phase, before repeat treatment, were based on results from subjects in the

treatment group. Results for the repeat treatment phase were based on results from subjects in the treatment group who received repeat treatment. Safety results for the repeat treatment phase were based on results from the subjects in the treatment and control groups who selected repeat treatment. Subject characteristics were previously reported.5 In brief, subjects were primarily female (80.1%) and white (58.5%); median age at study entry was 55 years. All Fitzpatrick skin types were represented, and most subjects had moderate or significant MVD. The treatment and control groups shared similar characteristics. Treatment Treatment characteristics for initial and touch-up treatment have previously been reported.5 Of those who underwent optional repeat treatment, fewer subjects had repeat treatment in the submalar region than the zygomaticomalar region or anteromedial cheek (Table 1). Various types of anesthesia were administered in preparation for repeat treatment (Table 1). For initial treatment, most subjects received injections in both the subcutaneous and the supraperiosteal planes; small proportions received only subcutaneous or supraperiosteal injections. Similarly, during repeat treatment, most received injections in both planes and fewer received only subcutaneous or supraperiosteal injections. Tunneling, serial puncture, and fanning were each used in more than half of subjects, and cross-hatching was used in one-quarter of subjects (Table 1). Similar proportions of subjects

Figure 1. Subject disposition. mITT, modified intent to treat.

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TABLE 1. Treatment Characteristics for Repeat Treatment Characteristic Anesthetic administered, n (%)

N = 167 113 (67.7)

Type of anesthesia, n/N (%) Topical

95/113 (84.1)

Ice Nerve block

48/113 (42.5) 13/113 (11.5)

Local

23/113 (20.4)

for initial and touch-up treatment combined of 6.6 mL. For repeat treatment of midface regions, a median (range) bilateral injection volume of 1.0 mL (0.1–4.0 mL) was injected into the zygomaticomalar region, 0.9 mL (0.1–5.0 mL) was injected into the anteromedial cheek, and 1.0 mL (0.1–7.0 mL) was injected into the submalar region. After repeat treatment, subjects rated pain as an average of 2.1 on a standard pain scale (0 = no pain, 10 = worst pain imaginable).

Treatment site, n (%) Zygomaticomalar region

150 (89.8)

Anteromedial cheek

145 (86.8)

Submalar region

116 (69.5)

Injection plane, n (%) Subcutaneous and supraperiosteal Only subcutaneous Only supraperiosteal

115 (68.9) 25 (15.0) 27 (16.2)

Injection technique, n (%) Tunneling

99 (59.3)

Serial puncture

108 (64.7)

Fanning

100 (59.9)

Cross-hatching Ferning Injection volume Mean (SD) Median (range)

42 (25.1) 4 (2.4) 3.13 (2.75) 2.0 (0.4–12.0)

were treated using 25-gauge 1-inch or 27-gauge 0.5inch ultra-thin, wall needles. The median bilateral injection volume for repeat treatment was 2.0 mL compared with the median injection volume for initial treatment of 4.8 mL, and

Effectiveness Mean overall MFVDS scores improved from baseline through 24 months (Figure 2). Similarly, after optional repeat treatment, the mean overall MFVDS score was improved compared with baseline through Month 12 after treatment. Changes from baseline were statistically significant at all time points (p = 0.0002 at Month 2 after initial treatment and p < 0.0001 at all other time points). Most subjects improved by $1 point on the MFVDS at Months 6, 12, and 24 (Figure 3). After repeat treatment, high percentages of subjects improved by $1 point on the MFVDS at Months 6 and 12. Midfacial regions demonstrated similar results as seen on the overall MFVDS. Overall, most EIs and subjects rated midface volume as improved or much improved on the GAIS at 6 months after initial treatment; similar or higher percentages were seen at 6 and 12 months after repeat treatment (Figure 4).

Figure 2. Mean overall Mid-Face Volume Deficit Scale (MFVDS) score as assessed by evaluating investigators.


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Figure 3. Percentage of subjects with $1 point improvement from baseline in Mid-Face Volume Deficit Scale score.

A high proportion of subjects demonstrated an improvement in the overall satisfaction with facial appearance score since baseline at each time point after initial and repeat treatment (Figure 5). Increases from baseline in mean scores were statistically significant at all time points. The percentage of subjects who agreed that their treatment goals had been achieved after initial treatment was 67.8% at Month 6, 58.2% at Month 12, and 49.0% at Month 24 after treatment. After optional repeat treatment, 82.8% and 80.7% of subjects agreed that their treatment goals had been met at Month 6 and Month 12, respectively. Representative examples of aesthetic outcomes after treatment with VYC-20L are shown in Figures 6 and 7.

At each time point after initial and repeat treatment, most subjects perceived themselves as appearing younger versus baseline (Figure 8). The mean decrease in perceived age after initial treatment ranged from 4.9 years at Month 6 to 3.3 years at Month 24 (Figure 9). After repeat treatment, the mean decrease in perceived age was 5.0 years at 6 months and 6.2 years at 12 months. When analysis was limited to subjects in the treatment subgroup who had $1 effectiveness assessment after repeat treatment (n = 100), the percentage of subjects who improved by $1 point on the MFVDS was 90.1% at Month 6, 91.8% at Month 12, and 72.6% at Month 24 after initial treatment and 82.8% and 91.1% at

Figure 4. Global Aesthetic Improvement Scale responder rates by month.

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bruising (1.2%), pain (0.6%), papule (0.6%), and swelling (0.6%). There were no unanticipated adverse device effects. Two subjects each reported 1 serious AE (hip fracture and cerebrovascular accident) after repeat treatment; both were considered unrelated to treatment.

Figure 5. Subjects’ overall satisfaction with facial appearance since baseline. *Overall score of satisfaction with facial appearance was calculated as the average score from the responses to the 6 questions of the facial appearance evaluation multiplied by 25, resulting in a scale from 0 (least satisfaction) to 100 (greatest satisfaction).

Months 6 and 12 after repeat treatment, respectively. Overall, 97.8%, 93.1%, and 93.0% of subjects rated midface volume as improved or much improved on the GAIS at Month 6 after initial treatment and Months 6 and 12 after repeat treatment, respectively. Safety The TSRs most frequently reported after repeat treatment were tenderness (76.5% of subjects), swelling (67.9%), firmness (66.0%), and bruising (62.3%). Most TSRs were mild or moderate in severity (85.6%). For 72.6% of subjects, TSR duration was #2 weeks after repeat treatment. Adverse events considered related to treatment were reported in 14/167 subjects (8.4%) after repeat treatment and included injection site induration (4.2% of subjects), mass (diary term: lumps/bumps) (4.2%),

When analysis was limited to the subgroup who received repeat treatment (n = 167), the incidences of treatment-related AEs were 33.5% after initial and 8.4% after repeat treatment. Compared with initial treatment, fewer subjects experienced severe TSRs; TSR duration was also decreased after repeat treatment compared with initial treatment.

Discussion There is a trend in facial surgery toward less invasive surgical techniques to lift the midface for correction of age-related changes.11 Correcting MVDs with injectable HA fillers has become a preferred option for treatment of central facial aging because it offers a versatile, safe, and effective means of restoring a youthful appearance while being less invasive and disruptive than surgery.1,3 While the correction achieved with VYC-20L can last for up to 2 years,5 many patients will eventually desire repeat treatment to maintain their appearance. This analysis in subjects with moderate to severe MVD demonstrated that subjects experienced high rates of improvement in MVD and high levels of satisfaction with their overall facial appearance after repeat treatment with VYC20L. Repeat treatment was well tolerated, with low rates of TSRs and treatment-related AEs.

Figure 6. Aesthetic treatment outcomes in a female subject (A) at baseline, (B) Month 6, and (C) Month 24 after initial treatment. Injection volume of VYC-20L at initial and touch-up treatment combined was 3.2 mL and at repeat treatment was 3.4 mL. Mid-Face Volume Deficit Scale scores at baseline, Month 6, and Month 24 after initial treatment were 4, 1.5, and 1, respectively. Mid-Face Volume Deficit Scale score after repeat treatment (Month 12+) was 1.


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Figure 7. Aesthetic treatment outcomes in a female subject at (A) baseline, (B) Month 6, and (C) Month 24 after initial treatment. Injection volume of VYC-20L at initial and touch-up treatment combined was 6.9 mL and at repeat treatment was 1.0 mL. Mid-Face Volume Deficit Scale scores at baseline, Month 6, and Month 24 after initial treatment were 3.5, 1.5, and 2, respectively. Mid-Face Volume Deficit Scale score after repeat treatment (Month 12) was 1.

Despite requiring approximately half the injection volume as initial treatment, repeat treatment was effective and produced results that were consistent with those observed after initial treatment. The median injection volume was 4.8 mL for initial treatment and 6.6 mL for initial plus touch-up treatment combined, but only 2.0 mL for repeat treatment. The use of lower injection volumes of VYC-20L for repeat compared with initial treatment is consistent with the trend reported in a 24-month open-label study in 103 Australian subjects with mild to severe MVD who had the option of re-treatment.7 Mean injection volumes in that study were also lower for repeat treatments (2.6 mL at Week 78, 1.8 mL at Week 104) than initial treatment (3.4 mL). The reasons underlying the use of smaller injection volumes on repeat treatment have not been studied but may include that some subjects electing repeat treatment at Month 24 had not returned to their original baseline volume deficit, injectors may become more adept at maximizing placement to achieve optimal results with less volume with increasing experience, and/or an overall trend to

Figure 8. Percentage of subjects reporting that their perceived age was younger than their chronologic age after repeat treatment compared with baseline.

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a more conservative approach to injection volumes of HA filler that has arisen over time based on injectors’ accumulated treatment experience. Over the course of the study, subjects demonstrated strong initial positive results that began to diminish after 12 to 15 months and returned to high levels with repeat treatment. The percentage of subjects who improved by $1 point on the MFVDS after 6 months was similar after initial and repeat treatment. Furthermore, the percentage of subjects rated by the EI as “improved” or “much improved” on the GAIS was higher 6 months after repeat treatment versus 6 months after initial treatment, although GAIS responder rates based on subject ratings were similar at the corresponding time points. It is notable that the proportion of subjects who perceived themselves as appearing younger versus baseline was similar at 6 months after initial and repeat treatment, considering that subjects were 1 to 2 years older at the time of repeat treatment than at the time of initial treatment. This observation suggests that repeat treatment with

Figure 9. Subject’s self-perception of age: summary of perceived age.



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VYC-20L was able to maintain a youthful appearance from the subject’s perspective despite the passage of time. Because repeat treatment was optional, and subjects who elected to undergo repeat treatment may have been more pleased with their aesthetic outcomes, this self-selection could influence results after repeat treatment. In this analysis, the incidence, severity, and duration of common TSRs was lower with repeat treatment versus initial/touch-up treatment. In addition, there was a decreased incidence of treatment-related AEs after repeat treatment (8.4% of subjects) versus initial/ touch-up treatment (34.1% of subjects). The 24month open-label study of VYC-20L described above also observed a lower incidence of TSRs after repeat versus initial treatment.7 As those authors noted, improved injection techniques (due to greater experience at later dates) and lower injection volumes associated with repeat treatment may have contributed to this finding. In this analysis, subjects who underwent repeat treatment may have differed in important ways (e.g., age, initial treatment response, sensitivity to TSRs and AEs) from subjects who did not opt for repeat treatment. Thus, it is difficult to draw conclusions based on comparisons of effectiveness and AEs after initial versus repeat treatment. For example, factors other than a desire to restore initial treatment results, such as bothersome TSRs or AEs after initial treatment, may have influenced the decision to opt for repeat treatment. Such a self-selection may confound interpretation of comparisons between initial and repeat treatment. However, similar safety and effectiveness results in the overall group and in the subgroup of those who received repeat treatment provide evidence that this subgroup may be representative of the overall sample. Although needle choice was similar for both initial and repeat treatment,5 there were some potentially important differences in treatment characteristics between the initial treatment phase, reported in the pivotal study5 and the current analysis. Choice of injection plane more strongly favored subcutaneous plus supraperiosteal for initial versus repeat treatment.

In addition, tunneling, serial puncture, fanning, and cross-hatching were used more frequently during initial treatment versus repeat treatment. An analysis of data from a study in which 283 patients received treatment with a nonanimal-stabilized HA filler for midface volume correction of the nasolabial folds and oral commissures found that injection techniques that increased the dissection of the subepidermal plane (e.g., fanning, higher volumes) were associated with an increased incidence of local AEs, whereas injection plane and depth of injection were unrelated to the incidence of local AEs.12 Thus, differences in both injection technique and injection volume may have contributed to observed differences in incidence and duration of TSRs after initial and repeat treatment in this study. In conclusion, VYC-20L was safe and effective for agerelated MVD, with correction lasting up to 2 years. Repeat treatment was safe and well tolerated and achieved high levels of effectiveness, as was seen after initial treatment. Acknowledgments Deepali Paradkar, PhD (an employee of Allergan plc at the time of this study) performed statistical analysis of the data. The Voluma US Study Group included Derek Jones, MD, Gregory Mueller, MD, and Naissan Wesley, MD (Los Angeles, CA); Kimberly Butterwick, MD, Mitchel Goldman, MD, and Douglas Keel, DO (San Diego, CA); Vic Narurkar, MD, Kathleen Welsh, MD, and Usha Rajagopal, MD (San Francisco, CA); Rhoda Narins, MD, David Narins, MD, and Robert Bernard, MD (White Plains, NY); Victor Lacombe, MD, Charles Perry, MD, and Keith Denkler, MD (Santa Rosa, CA); Cheryl Burgess, MD, Beverly Johnson, MD, and Valerie Callender, MD (Washington, DC); Julius Few, MD, Michael Lee, MD, and James Platis, MD (Chicago, IL); Sue Ellen Cox, MD, John Soderberg, MD, and J. Charles Finn, MD (Chapel Hill, NC); David Goldberg, MD, Mussarat Hussain, MD, Zeena Al-Dujaili, MD, Susan Bard, MD, David Ciocon, MD, and Jennifer Chwalek, MD (Hillsborough, NJ); Leslie Baumann, MD, Heather Woolery-Lloyd, MD, and Brandon Kallman, MD (Miami Beach, FL); Dee Anna Glaser, MD, Natalie Semchyshyn, MD, Quenby Erickson,


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DO, and Jordan Slutsky, MD (Des Peres, MO); Jeffrey Kenkel, MD, Andrew Trussler, MD, Tae Woon Chong, MD, and Ron Hoxworth, MD (Dallas, TX); Jean Carruthers, MD, Alastair Carruthers, MD, and Andrew Denton, MD (Vancouver, BC); Arthur Swift, MD, William Papanastasiou, MD, and Andreas Nikolis, MD (Westmount, Quebec); and Kenneth Beer, MD, Daniel Kapp, MD, and Richard Schwartz, MD (West Palm Beach, FL). References 1. Pontius AT, Chaiet SR, Williams EF III. Midface injectable fillers: have they replaced midface surgery? Facial Plast Surg Clin North Am 2013; 21:229–39. 2. Bernardin A, Pierre S, Pather S, et al. Vycross: an innovative dermal filler technology. Presented as a poster at: Anti-Aging Medicine European Congress; October 11–12, 2013; Paris, France. 3. Jones D. Volumizing the face with soft tissue fillers. Clin Plast Surg 2011;38:379–90. 4. Juvéderm Voluma XC—P110033. U.S. Food and Drug Administration. Available from: http://www.fda.gov/MedicalDevices/ ProductsandMedicalProcedures/DeviceApprovalsandClearances/ Recently-ApprovedDevices/ucm374231.htm. Accessed July 29, 2015. 5. Jones D, Murphy DK. Volumizing hyaluronic acid filler for midface volume deficit: 2-year results from a pivotal single-blind randomized controlled study. Dermatol Surg 2013;39:1602–11.

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6. Few J, Cox SE, Paradkar-Mitragotri D, Murphy DK. A multicenter, single-blind randomized, controlled study of a volumizing hyaluronic acid filler for midface volume deficit: patient-reported outcomes at 2 years. Aesthet Surg J 2015;35:589–99. 7. Callan P, Goodman GJ, Carlisle I, Liew S, et al. Efficacy and safety of a hyaluronic acid filler in subjects treated for correction of midface volume deficiency: a 24 month study. Clin Cosmet Investig Dermatol 2013;6:81–9. 8. Carruthers J, Carruthers A. Botulinum toxin type A treatment of multiple upper facial sites: patient-reported outcomes. Dermatol Surg 2007;33:S10–7. 9. Fagien S, Cox SE, Finn JC, Werschler WP, et al. Patient-reported outcomes with botulinum toxin type A treatment of glabellar rhytids: a double-blind, randomized, placebo-controlled study. Dermatol Surg 2007;33:S2–9. 10. Carruthers A, Carruthers J. A single-center dose-comparison study of botulinum neurotoxin type A in females with upper facial rhytids: assessing patients’ perception of treatment outcomes. J Drugs Dermatol 2009;8:924–9. 11. Seitz IA, Llorente O, Few JW. The transconjunctival deep-plane midface lift: a 9-year experience working under the muscle. Aesthet Surg J 2012;32:692–9. 12. Glogau RG, Kane MA. Effect of injection techniques on the rate of local adverse events in patients implanted with nonanimal hyaluronic acid gel dermal fillers. Dermatol Surg 2008;34(Suppl 1): S105–9.

Address correspondence and reprint requests to: Leslie Baumann, MD, Baumann Cosmetic and Research Institute, 4500 Biscayne Boulevard, Miami, FL, or e-mail: [email protected]

