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Figure 1.
Percentage of 61 Patients Reporting Very Much or Moderate Improvement
Percentage of 61 Patients Reporting Very Much or Moderate Improvement

Data are stratified by total injection volume (initial volume plus touch-up volume of hyaluronic acid filler).

Figure 2.
Physician-Graded Rating of 61 Patients Using the Global Aesthetic Improvement Scale (GAIS) at 12 Months
Physician-Graded Rating of 61 Patients Using the Global Aesthetic Improvement Scale (GAIS) at 12 Months

Data are stratified by initial injection volume.

Figure 3.
Percentage of 61 Patients Reporting That They Were Somewhat or Very Satisfied With Their Aesthetic Outcome
Percentage of 61 Patients Reporting That They Were Somewhat or Very Satisfied With Their Aesthetic Outcome

Data are stratified by initial injection volume. GAIS indicates Global Aesthetic Improvement Scale.

1.
Rohrich  RJ, Pessa  JE.  The fat compartments of the face: anatomy and clinical implications for cosmetic surgery. Plast Reconstr Surg. 2007;119(7):2219-2227.
PubMedArticle
2.
Shaw  RB  Jr, Kahn  DM.  Aging of the midface bony elements: a three-dimensional computed tomographic study. Plast Reconstr Surg. 2007;119(2):675-681.
PubMedArticle
3.
Humphrey  S, Carruthers  J, Carruthers  A.  Clinical experience with 11,460 mL of a 20-mg/mL, smooth, highly cohesive, viscous hyaluronic acid filler. Dermatol Surg. 2015;41(9):1060-1067.
PubMed
4.
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(11):1602-1612.
PubMedArticle
5.
Callan  P, Goodman  GJ, Carlisle  I,  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;6:81-89.
PubMedArticle
6.
Hoffmann  K; Juvéderm Voluma Study Investigators Group.  Volumizing effects of a smooth, highly cohesive, viscous 20-mg/mL hyaluronic acid volumizing filler: prospective European study. BMC Dermatol. 2009;9:9.
PubMedArticle
7.
Few  J, Cox  SE, Paradkar-Mitragotri  D, Murphy  DKA.  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(5):589-599.
PubMedArticle
8.
Raspaldo  H.  Volumizing effect of a new hyaluronic acid sub-dermal facial filler: a retrospective analysis based on 102 cases. J Cosmet Laser Ther. 2008;10(3):134-142.
PubMedArticle
9.
World Medical Association.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053
PubMedArticle
10.
Glaser  DA, Kenkel  JM, Paradkar-Mitragotri  D, Murphy  DK, Romagnano  L, Drinkwater  A.  Duration of effect by injection volume and facial subregion for a volumizing hyaluronic acid filler in treating midface volume deficit. Dermatol Surg. 2015;41(8):942-949.
PubMedArticle
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Original Investigation
October 20, 2016

Correction of Age-Related Midface Volume Loss With Low-Volume Hyaluronic Acid Filler

Author Affiliations
  • 1Cosmetic Laser Dermatology, San Diego, California
  • 2Greene.MD Plastic Surgery & Laser Center, Weston, Florida
JAMA Facial Plast Surg. Published online October 20, 2016. doi:10.1001/jamafacial.2016.1274
Key Points

Question  What is the efficacy, longevity, and patient satisfaction associated with correction of age-related midface volume loss using the low volumes of hyaluronic acid filler commonly used in day-to-day practice?

Findings  In this 2-center, retrospective cohort study of 61 adults, the mean initial treatment volume was 1.6 mL. At 12 months, 42 of 51 patients (82%) reported looking very much or moderately improved, and 43 (84%) were satisfied with their results.

Meaning  Patients can achieve sustained, satisfactory aesthetic correction 12 months after injection with low volumes of hyaluronic acid filler.

Abstract

Importance  The pivotal approval trial for a smooth, highly cohesive, viscous, 20-mg/mL hyaluronic acid filler demonstrated sustained aesthetic improvement, with a mean injection volume of 6.65 mL. In daily practice, however, it is not often practical or necessary to use large injection volumes to achieve the desired cosmetic outcome.

Objective  To assess the efficacy, longevity, and patient satisfaction associated with correction of age-related midface volume loss using the low volumes of hyaluronic acid filler more commonly used in day-to-day practice.

Design, Setting, and Participants  A 2-center, retrospective cohort study examined medical records of 61 healthy patients who underwent treatment for facial volume loss with hyaluronic acid filler from November 1, 2013, through April 31, 2014. Follow-up visits were conducted at 1, 3, 6, and 12 months after the procedure. Data were pooled from a private facial plastic surgery practice in Weston, Florida, and a private cosmetic dermatology practice in San Diego, California.

Interventions  Patients were treated with hyaluronic acid filler according to the investigator’s usual practices.

Main Outcomes and Measures  The main outcome measure was patient-graded Global Aesthetic Improvement Scale scores at 1, 3, 6, and 12 months after treatment. Scores range from 1 to 5; 1 indicates very much improved and 5, worse.

Results  A total of 61 consecutive, healthy adult patients (mean [SD] age, 57.4 [12.8] years) with mild to severe facial volume loss were enrolled in the study. A total of 46 patients (75%) were white, 3 (5%) were black/African American, 9 (15%) were Hispanic/Latino, 1 (2%) was Asian/Pacific Islander, and 2 (3%) were other. Three patients (5%) were male, and 58 (95%) were female. Mean initial treatment volume was 1.6 mL. At follow-up, 29 patients (48%) elected to have a touch-up treatment; mean total touch-up volume was 1.4 mL. The patient-graded Global Aesthetic Improvement Scale scores at 1, 3, 6, and 12 months after treatment demonstrated that 73% (41 of 56) to 89% (24 of 27) of the study patients reported being very much or moderately improved. Most patients were rated by investigators on the Global Aesthetic Improvement Scale as very much or moderately improved at the 12-month follow-up. At 12 months after the procedure, 43 of 51 patients (84%) reported satisfaction with their outcome. At all time points, most patients would elect to undergo the procedure again (range, 17 [68%] to 61 [100%]). Adverse events were mild, and all resolved spontaneously within 14 days. At the 2-year follow-up, there were no reports of delayed adverse events.

Conclusions and Relevance  Midface volumization using the low volumes of hyaluronic acid filler more commonly used in daily clinical practice is effective and well tolerated.

Level of Evidence  3.

Introduction

Facial aging is understood to be a multifactorial process that includes thinning of the skin, decreased skin elasticity, collagen degradation, bone resorption, and fat pad atrophy.1,2 The philosophy of aesthetic rejuvenation has evolved to target each of these anatomical processes to achieve optimal, natural-looking results.

Restoring the lost volume of the deep facial fat pads, especially that of the deep medial cheek, is critical to achieving an aesthetically appealing appearance. Although calcium hydroxylapatite and poly-l-lactic acid can both be used to replace lost facial volume, there are now several injectable hyaluronic acid (HA) fillers with high cohesivity that are specifically designed to provide the lift needed to restore midface volume.

The HA filler used in this study is a 20-mg/mL, smooth, highly cohesive, viscous HA filler (Juvéderm Voluma; Allergan Inc) composed of a proprietary mixture of low- and high-molecular-weight HA with low hydrophilicity.3 Since its initial approval by the US Food and Drug Administration, studies performed all over the world have found this filler to be a safe and effective means of restoring midface volume loss, with results lasting up to 24 months.

The pivotal US trial was a multicenter randomized clinical study in which 235 individuals were injected with a total mean of 6.65 mL of product between the initial session and touch-up treatments, with a mean of 5.07 mL at the initial treatment and 1.93 mL for touch-up. With these volumes, 44.6% of patients continued to see clinical benefit at 2 years after the procedure.4

Another study5 of 103 individuals found high posttreatment satisfaction, with 91.6% of patients satisfied or very satisfied with their treatment. The mean volume injected at the initial treatment visit in this study was 5.1 mL, whereas the mean touch-up was 2.6 mL. A pan-European study6 of 70 patients who underwent treatment with an HA filler similarly found that 88% of physicians and 76% of patients rated the outcomes as much improved or very much improved 14 days after injection of a mean of 4.6 mL of HA filler (3.8 mL of which was injected into the midface). Of these patients, 13% received a mean 1.5-mL touch-up at 14 days. The correction attained with the HA filler is not only significant but also long-lasting. Few et al7 reported clinical improvement and patient satisfaction at the 2-year follow-up after injection of a mean total volume of 6.68 mL of HA filler (range, 1.2-13.9 mL), with a mean initial treatment volume of 5.09 mL and a touch-up volume of 1.93 mL.

A retrospective analysis8 of 102 patients used smaller volumes of HA filler than those in most other studies (mean, 2.8 mL), but the product was injected using a subcutaneous fanning technique rather than a vertical, supraperiosteal technique. Investigators graded 64% of patients as very much improved at 6 to 18 months of follow-up.

The literature has clearly demonstrated that injection of large volumes of HA filler is a safe, efficacious method of addressing age-related volume loss. However, many, if not most, patients do not require such large volumes to achieve the desired correction. In addition, most patients cannot afford several syringes of a temporary filler, especially if they will require additional treatment several months later. It is also unclear whether the long duration of HA filler is related to these large treatment volumes or whether high patient satisfaction and clinical results can still be seen when small injection volumes are used. This study sought to assess the efficacy, longevity, and patient satisfaction associated with correction of age-related midface volume loss using the low volumes of HA filler more commonly used in day-to-day practice.

Methods
Study Design

This retrospective, observational, open-label, nonrandomized study was conducted in accordance with the principles outlined in the Declaration of Helsinki9 that evaluated the use of HA filler at 2 sites (Cosmetic Laser Dermatology, San Diego, California, and Greene.MD Plastic Surgery & Laser Center, Weston, Florida) with 1 injector per site (S.G.F. and R.G.). The location of injections, technique, and volumes used were at the discretion of the injectors. The institutional review boards at the study sites do not require that retrospective studies be submitted for approval.

Patients

The study population was composed of the first 100 healthy adults with mild to severe facial volume loss who requested rejuvenation of the midface area from November 1, 2013, through April 31, 2014. Written informed consent was obtained from every patient, and all data were deidentified. Patients were excluded from the study if they had a history of midface implants, evidence of infection at the time of treatment, or a known history of sensitivity to HA; were pregnant or lactating; or had received midface fillers within the previous 12 months. Patients did not receive a stipend for their participation in the study.

Study Procedures

Medical record information gathered included sex, age, and race. Locations injected, volume of product used, and amount paid per syringe were also captured. Standardized pretreatment and posttreatment digital photography, including frontal, lateral, and oblique views of the face, was performed at the initial treatment visit and at each follow-up visit. Patients were treated with HA filler in the midface, temples, chin, and/or nasolabial folds. The technique and location of injection were decided after consultation with the patient and according to the investigator’s usual practices.

Outcome Measures

At 1, 3, 6, and 12 months after treatment, patients were administered questionnaires to assess aesthetic correction, satisfaction, and adverse events. Aesthetic correction was scored using the patient-graded Global Aesthetic Improvement Scale (GAIS), which uses the following scale: 1, very much improved; 2, moderately improved; 3, somewhat improved; 4, no change; and 5, worse. Investigators, masked to the patient questionnaire responses, also completed a physician-graded GAIS for each patient using the same scale to grade midface correction.

Overall patient satisfaction was evaluated on a 5-point scale from very satisfied (score of 1) to very dissatisfied (score of 5). Patients were asked if they would have the procedure again, with response options of yes, no, and undecided.

Adverse events, including pain, edema, bruising, erythema, infection, and nodule formation, were noted. If the patient reported an adverse event, he or she was asked to rate its severity on a scale of 1 (least) to 10 (most) and to detail how many days it lasted.

Patients were stratified into groups according to the volume of HA filler they received at their initial treatment (1, 2, and >2 mL). The patient- and physician-grade GAIS scores, satisfaction, and willingness to undergo the procedure again at all follow-up time points were stratified by these injection volume groups. The data were summarized with descriptive statistics, such as percentages, means, ranges, and SDs.

Statistical Analysis

Statistical tests, when applicable, were performed using 2-tailed t tests and by calculating the Spearman correlation coefficient. P < .05 was considered statistically significant.

Results
Patients

Of the 100 patients treated during the study period, 61 (61%) were successfully contacted and asked a series of questions from a standardized questionnaire. The mean (SD) age of the 61 patients was 57.4 (12.8) years (range, 33-76 years). Three patients (5%) were male, and 58 (95%) were female. A total of 46 patients (75%) were white, 3 (5%) were black/African American, 9 (15%) were Hispanic/Latino, 1 (2%) was Asian/Pacific Islander, and 2 (3%) were other. Patients represented a variety of ethnic groups and skin types.

Treatment Characteristics

The mean total volume injected at the first treatment session was 1.6 mL (range, 1-4 mL). A total of 30, 27, 2, and 2 patients received 1, 2, 3, and 4 mL, respectively. The most commonly treated site was the malar cheek, comprising 60 of 70 treatments (86%) performed. The next most common treatment sites were the temples (5 [7%]), followed by the chin or nasolabial folds (5 [7%]). The mean price paid by the patients per syringe of HA filler was $749 (range, $0-$1000).

At follow-up, 29 of 61 patients (48%) received a touch-up treatment. The mean total touch-up volume injected was 1.4 mL (range, 1-4 mL). Six patients (10%) opted to undergo a second touch-up injection. These treatments averaged 2.67 mL (range, 1-7 mL). Thus, the total mean product injected for volumization, including all touch-ups at all time points, was 2.43 mL (range, 1-10 mL).

Because this study was meant to examine the real-world use of a 20-mg/mL smooth, highly cohesive HA filler, patients were allowed to receive touch-ups with alternative products if desired and deemed appropriate by the treating physician. Of the 29 patients who had touch-ups, 2 had touch-ups with non-HA products; one was treated with calcium hydroxylapatite and the other with poly-l-lactic acid.

Efficacy

Overall patient-graded midface aesthetic improvement at 1, 3, 6, and 12 months was very high. The patient-graded GAIS at 1 month after treatment demonstrated that 24 of 27 patients (8%) reported being very much or moderately improved. At 3 months, 39 of 46 (85%) reported that they were very much or moderately improved. At 6 months, 41 of 56 (73%) reported that they were very much or moderately improved, and at the 12-month follow-up, 42 of 51 (82%) reported the same. No patient reported looking worse than at baseline at any time point.

At each follow-up, patients who received 1 mL or more than 2 mL of filler at the initial treatment visit rated themselves as having a greater improvement than those who received exactly 2 mL, although this difference did not reach statistical significance (P = .52). At 1 month, 13 of 15 patients (87%) in the 2-mL group rated themselves as very much or moderately improved, whereas 12 (100%) of the 1-mL and greater than 2-mL groups rated themselves as such. At 12 months, 19 of 25 patients (76%) in the 2-mL group considered themselves to be very much or moderately improved compared with 20 of 23 (87%) and 2 of 2 (100%) in the 1-mL and greater than 2-mL groups, respectively.

When the patient-graded GAIS data are stratified by total injection volume (initial treatment plus any touch-ups with HA filler), more patients who received 1 and 2 mL reported significant improvement at the 1-, 3-, and 6-month follow-up than those who received higher volumes (Figure 1). Patients who received more than 3 mL reported the greatest improvement at the 12-month follow-up.

Most patients in all volume groups were rated by investigators as very much or moderately improved at the 12-month follow-up (Figure 2). However, although 8 patients (32%) who received 1 mL of filler at the initial visit were rated as very much improved at 12 months, 9 (43%) and 3 (75%) of the 2-mL and greater than 2-mL groups were rated as very much improved, respectively. This finding suggests that notable improvement, as judged by physicians, may be more likely to be achieved with larger volumes, but the small sample sizes prevented this difference from reaching statistical significance (P = .42).

Investigators rated the outcomes of patients who received initial treatment only and those who opted for touch-ups similarly, with 18 patients (72%) in the single-injection group being graded as very much or moderately improved at 12 months and 21 patients (84%) in the touch-up group being rated as such.

Satisfaction

Overall, patients reported high satisfaction with low-volume correction, even at 12 months after the procedure. At 1 month, 25 patients (93%) indicated that they were very or somewhat satisfied with their aesthetic outcome. At 3 months, 40 patients (87%) reported satisfaction. At 6 months, 48 patients (86%) were satisfied, and at 12 months, 43 (84%) were satisfied.

Patient satisfaction was higher at all time points for patients who received 1 mL and greater than 2 mL of filler at the initial treatment when compared with those who received 2 mL (Figure 3). This trend, although not statistically significant, reflects that of the patient-graded GAIS.

Satisfaction rates between those who did and did not undergo touch-up treatment were similar at the 1-, 3-, and 6-month follow-up. However, at 12 months, 19 patients (73%) who only received an initial injection reported feeling very or somewhat satisfied, whereas 23 (96%) of those who received at least 1 touch-up reported satisfaction with their outcome.

The high overall patient satisfaction is evident in patient willingness to undergo the procedure again. At all time points and for all initial treatment volumes, most patients would elect to undergo the procedure again (range, 17 [68%] to 61 [100%]); again, the patients most likely to report a willingness to repeat the injections were those in the 1-mL and greater than 2-mL groups. At 12 months, 28 patients (87%) in the 1-mL group, 20 (77%) in the 2-mL group, and 4 (100%) in the greater than 2-mL group indicated they would undergo the procedure again.

Safety

Overall, the 20-mg/mL smooth, highly cohesive HA filler was well tolerated. Adverse events, such as edema, erythema, and bruising, were mild, and all resolved spontaneously within 14 days. Pain associated with the procedure was rated on a scale of 0 (no pain) to 10 (extreme pain). The mean (SD) pain level reported by patients was 1.9 (1.8), with no significant difference among treatment volume groups. Four patients reported nodules, but these resolved spontaneously within 7 days. There were no reports of infection. Of note, there were no adverse events among the 10 patients who underwent off-label injection of HA filler into the temples and chin or nasolabial folds. At the 2-year follow-up, there have been no reports of delayed adverse events at either study site.

Discussion

Ultimately, the key to successful rejuvenation with low volumes of HA filler is to not only accurately assess who can anatomically benefit from the procedure but also predict who will be satisfied with the outcome. This study offers some interesting initial insights into satisfaction, correction, and the need for touch-ups in this population.

We attempted to characterize patients who pursued touch-up treatment because it might provide practical guidance for physicians seeking to identify patients who will likely need or want a touch-up after the first visit. Contrary to expectations, the initial injection volume was not different among these groups. Patients who did not undergo a touch-up were slightly younger (mean age, 51.2 years) than those who did (mean age, 56.9 years), but this difference did not reach statistical significance (P = .28).

In this study, dissatisfied patients at 12 months were few (8 patients [16%]) and not differentiated from satisfied patients by initial injection volume or likelihood to undergo touch-up treatment. The mean initial injection volume of patients who reported feeling neutral or dissatisfied with their results at the 12-month follow-up was 1.88 mL, whereas the mean volume of those who reported satisfaction was 1.56 mL; this difference was not statistically significant (P = .08). Of the 8 patients who were neutral or dissatisfied at 12 months, only 1 had a touch-up treatment (with poly-l-lactic acid). These data suggest that the treating physician cannot predict that a patient is less likely to be satisfied with his or her outcome based on initial treatment volume or touch-up status.

At all follow-up time points, patients who received 2 mL at the initial treatment reported less improvement than those who received 1 mL. Perhaps patients who opt for injection of only 1 mL have more conservative or natural-looking aesthetic goals or, conversely, those who receive 2 mL are paying twice as much for treatment and thus expect a more significant correction.

At the 3- and 6-month follow-up, patient satisfaction was correlated with patient-graded GAIS (P = .005). This finding is not surprising because one would expect patients who perceive a more significant improvement to be more satisfied with their treatment. Interestingly, patients who paid more per syringe were somewhat more likely to report satisfaction with their results. Satisfaction was not correlated with other parameters, such as practice site, volume injected, or patient age.

Patient satisfaction also did not correlate with physician-guided GAIS score (P = .34). Furthermore, patient-guided and physician-guided GAIS scores were inversely correlated (r = −0.436, P = .008), with high physician-guided GAIS scores correlating with low patient-guided GAIS scores. This strange association is likely attributable to the small sample size and overwhelmingly positive results, which make small deviations in the data significant. Taken together, this association suggests that the perception of improvement by the treating physician may not be an accurate predictor of a patient’s perception.

In their analysis of the pivotal US trial data, Glaser et al10 found that overall MidFace Volume Deficit Scale improvement at 6 months was similar between patients who received initial treatment only and patients who received initial and touch-up treatment. Similarly, our study found that patient-guided GAIS scores and patient satisfaction were not necessarily higher at the 12-month follow-up for patients who received higher-volume rejuvenation. These findings support the idea that low-volume rejuvenation can provide long-lasting aesthetic improvement in the appropriate patients.

Previously described techniques for filler placement in the cheek, such as placing the product in the submalar region last, can help minimize the amount of HA filler needed to achieve the desired correction. Careful patient selection is also critical; those with adequate skin elasticity and more soft-tissue than bony deficit typically require less volume for clinical improvement. Nonetheless, patients should be counseled about the temporary nature of filler treatments and the possibility of touch-up treatments to achieve their desired outcome.

The findings of this study are limited by the relatively small sample size and the overwhelmingly female sample population. These limitations make the results of this study hard to generalize to men. Because the purpose of this study was to capture the real-world use of HA filler in clinical practice, the injection technique, anatomical locations of injections, and order of injections were left to the discretion of the treating physician rather than being standardized. This information was not captured by this study.

Conclusions

The published literature reveals the safety and efficacy of correction with large volumes of HA filler. This study characterizes the efficacy and patient satisfaction associated with the use of HA filler at the much lower volumes commonly used in daily clinical practice. Correction and patient satisfaction remain high at 12 months even with the use of low-volume HA filler. Proper patient selection and injection technique are important in using low volumes of HA filler successfully.

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Article Information

Corresponding Author: Monique Vanaman Wilson, MD, Cosmetic Laser Dermatology, 9339 Genesee Ave, Ste 300, San Diego, CA 92122 (mwilson@clderm.com).

Accepted for Publication: July 29, 2016.

Published Online: October 20, 2016. doi:10.1001/jamafacial.2016.1274

Author Contributions: Drs Wilson and Fabi had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Wilson, Fabi.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Wilson.

Study supervision: Fabi.

Conflict of Interest Disclosures: Dr Greene reported serving on the speakers bureau and as a consultant for Allergan and Galderma. Dr Fabi reported serving on the speakers bureau and advisory board and serving as a consultant for Allergan, Galderma, and Merz. No other disclosures were reported.

References
1.
Rohrich  RJ, Pessa  JE.  The fat compartments of the face: anatomy and clinical implications for cosmetic surgery. Plast Reconstr Surg. 2007;119(7):2219-2227.
PubMedArticle
2.
Shaw  RB  Jr, Kahn  DM.  Aging of the midface bony elements: a three-dimensional computed tomographic study. Plast Reconstr Surg. 2007;119(2):675-681.
PubMedArticle
3.
Humphrey  S, Carruthers  J, Carruthers  A.  Clinical experience with 11,460 mL of a 20-mg/mL, smooth, highly cohesive, viscous hyaluronic acid filler. Dermatol Surg. 2015;41(9):1060-1067.
PubMed
4.
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(11):1602-1612.
PubMedArticle
5.
Callan  P, Goodman  GJ, Carlisle  I,  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;6:81-89.
PubMedArticle
6.
Hoffmann  K; Juvéderm Voluma Study Investigators Group.  Volumizing effects of a smooth, highly cohesive, viscous 20-mg/mL hyaluronic acid volumizing filler: prospective European study. BMC Dermatol. 2009;9:9.
PubMedArticle
7.
Few  J, Cox  SE, Paradkar-Mitragotri  D, Murphy  DKA.  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(5):589-599.
PubMedArticle
8.
Raspaldo  H.  Volumizing effect of a new hyaluronic acid sub-dermal facial filler: a retrospective analysis based on 102 cases. J Cosmet Laser Ther. 2008;10(3):134-142.
PubMedArticle
9.
World Medical Association.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053
PubMedArticle
10.
Glaser  DA, Kenkel  JM, Paradkar-Mitragotri  D, Murphy  DK, Romagnano  L, Drinkwater  A.  Duration of effect by injection volume and facial subregion for a volumizing hyaluronic acid filler in treating midface volume deficit. Dermatol Surg. 2015;41(8):942-949.
PubMedArticle
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