Supplemental Digital Content is Available in the Text.
BACKGROUND
Skin quality may be assessed by degrees of skin smoothness, fine lines, and hydration. VYC-12L is a recently developed hyaluronic acid filler to improve skin quality.
OBJECTIVE
This was a randomized, evaluator-blind study assessing safety and effectiveness of intradermal VYC-12L treatment for improving cheek skin smoothness, fine lines, and hydration.
METHODS
Participants (≥22 years) with moderate-to-severe investigator-assessed Allergan Cheek Smoothness Scale (ACSS) scores were randomized in 2:1 ratio to receive VYC-12L or control (no treatment with optional treatment). Effectiveness was assessed 1 month after last injection (initial or touch-up) by a responder rate (≥1-grade improvement from baseline on both cheeks) using investigator-rated ACSS and Allergan Fine Lines Scale (AFLS), and tissue dielectric constant probe-measured skin hydration. Safety was evaluated throughout.
RESULTS
Participants (VYC-12L, n = 131; control, n = 71) were 86.1% female with a median age of 58.0 years. At month 1, ACSS and AFLS responder rates were statistically significantly higher in the VYC-12L group (57.9%, 58.3%, respectively) than in the untreated controls (4.5%, 5.4%, respectively; p < .001). VYC-12L ACSS and AFLS responder rates remained consistent throughout the 6-month follow-up. Six participants reported treatment-related adverse events; none led to study discontinuation.
CONCLUSION
VYC-12L is an effective, well-tolerated treatment for lasting improvement of cheek skin smoothness, fine lines, and hydration.
Skin quality is an important component of facial attractiveness.1,2 Smooth facial skin and good overall skin quality are indicative of overall health and well-being,3–5 whereas poor skin quality can negatively affect self-perception and quality of life.6,7 Intrinsic (e.g., aging) and extrinsic (e.g., pollution, UV light exposure) factors lead to visible signs of aging, including fine lines, wrinkles, and unevenness.1,8–10 Structural changes in the skin that produce these signs of aging can include disruptions to extracellular matrix dynamics and resulting reductions and dysfunction in collagen, elastin, and hyaluronic acid (HA).11–13 Reduction in skin hydration also affects skin quality by affecting skin biomechanical properties.14
Intradermal injections of HA fillers have been shown to improve multiple aspects of skin quality and produce high levels of patient satisfaction.15 VYC-12L (Allergan Aesthetics, an AbbVie company, Irvine, CA) is a recently developed investigational HA filler that contains 12-mg/mL HA with 0.3% w/w lidocaine. VYC-12L was designed to correct superficial cutaneous depressions, such as fine lines, and for additional improvements in skin quality. Recent European studies showed that VYC-12L improves facial skin quality, including fine lines and texture, and it is associated with high participant satisfaction that lasts 6 to 9 months after treatment.16–18 The aim of this study was to assess the safety and effectiveness of VYC-12L on skin quality using validated scales of skin smoothness and fine lines and by measuring skin hydration.
Materials and Methods
Scale Validation
The Allergan Cheek Skin Smoothness (ACSS19; Supplemental Digital Content, Figure S1, http://links.lww.com/DSS/B258) scale and Allergan Fine Lines Scale (AFLS20; Supplemental Digital Content, Figure S2, http://links.lww.com/DSS/B258) are 5-point photonumeric scales that were developed with 6 other photonumeric scales for assessing aesthetic indications. Detailed methods for these validation studies can be found in Supplemental Materials (http://links.lww.com/DSS/B259).
Study Design
This was a randomized, multicenter, evaluator-blind, delayed treatment control (DTC) study conducted at 14 US sites. Participants were randomized in 2:1 ratio to receive the investigational VYC-12L treatment or DTC. The VYC-12L group received initial treatment and optional touch-up at month 1 if needed to achieve optimal correction. DTC participants were followed for 1 month after randomization and then either completed the study or received optional treatment (initial and touch-up, if needed) in the delayed treatment period. For both groups, follow-up visits occurred 3 days after each treatment for safety assessments and at 1, 2, 4, and 6 months after last injection (initial or touch-up) for effectiveness assessments. The study schedule is summarized in Supplemental Digital Content, Figure S3 (http://links.lww.com/DSS/B258).
This study conformed to the ethical guidelines of the 1975 Declaration of Helsinki, was conducted in compliance with GCP, is registered at clinicaltrials.gov (NCT#03728309), and all participants provided informed consent before treatment. Institutional review board approval was obtained from Copernicus IRB (Cary, NC).
Participants
Eligible participants were healthy adults (≥22 years) with both cheeks rated as moderate (2) or severe (3) on the ACSS,19 assessed live by the blinded evaluating investigator (EI). Participants must have had a FACE-Q Satisfaction with Skin score of ≤69 and the treating investigator (TI) must have agreed that optimal correction for both cheeks combined could be achieved with ≤6 mL of filler.
Participants were excluded if they had received dermal fillers, mesotherapy, or other cosmetic procedures (e.g., laser) in the face within the 12 months of screening or were planning to undergo any such treatment during the study; had received any cross-linked HA filler in any anatomic area within 12 months of screening; had received botulinum toxin injections in the cheek area (including lateral canthal area) within 6 months of screening or were planning to undergo such a treatment during the study; had received semi-permanent or permanent facial implants; or had begun using any topical or oral (over-the-counter or prescription) antiwrinkle products on the face within 30 days of screening or were planning to during the study.
Treatment
Before treatment, the cheeks were thoroughly cleaned, prepped with alcohol/antiseptic, and topical anesthesia and/or ice were applied at the discretion of the TI. VYC-12L was administered through multiple intradermal microdepot injections to both cheeks. The allowable treatment area spanned from the zygomatic arch to the edge of the jaw, lateral from the nasolabial fold and oral commissures to the preauricular cheek (Supplemental Digital Content, Figure S4, http://links.lww.com/DSS/B258). VYC-12L was provided in sterile syringes prefilled to 1 mL. Needle length selection (32 G 1/2″ or 32 G 3/16″), total injection volume, and injection spacing (≤5 mm, >5 mm to 1 cm, or >1 cm) were determined by the TI in accordance with the maximum volume restrictions of 4 mL for initial and repeat treatments and 2 mL for touch-up treatment.
Effectiveness
Primary Endpoint
Skin Smoothness
A blinded EI live-assessed changes in cheek skin smoothness through responder rate on the ACSS (≥1-grade improvement from baseline on both cheeks) at months 1 (primary endpoint), 2, 4, and 6 after the final injection (initial or touch-up).
Secondary Endpoints Fine Lines
A blinded EI assessed changes in cheek fine lines through responder rate (≥1-grade improvement from baseline on both cheeks) on the AFLS20 at months 1 (secondary end point), 2, 4, and 6 after the final injection (initial or touch-up).
Skin Hydration
Skin hydration was measured using a MoistureMeterD instrument (Delfin Technologies Ltd., Kuopio, Finland). The MoistureMeter instrument probe measures the effective hydration of the stratum corneum,21 and different instrument probes can be used to assess water content of the epidermis or dermis. The XS 5 probe (0.5 mm depth of effective measurement) was used to measure treatment-related changes in hydration of the epidermis at baseline and months 1, 2, 4, and 6 after the final injection.
Participant-Reported Outcomes
Participant-reported outcome measures will be reported in a separate article.
Safety
Procedural pain was assessed at the initial treatment by the participant using an 11-point scale ranging from 0 (no pain) to 10 (worst pain imaginable). Participants recorded the incidence, severity, and duration of injection site reactions (ISRs) in an e-diary for each cheek for up to 1 month after any treatment, starting on the day of treatment. Participants' e-diaries were reviewed by the TI at the 3-day and 1-month follow-ups to determine whether the ISR qualified as an adverse event (AE). The TI could declare an ongoing ISR to be reported as an AE depending on the severity and complication of the ISR, and the type of intervention required to resolve the reaction. AEs were monitored throughout the study. Snellen visual acuity, confrontational visual field, and ocular motility tests were performed by the TI after the initial, touch-up, and repeat treatments and at 3-day and 1-month follow-up visits. The FACE-Q Recovery Early Life Impact questionnaire was completed by participants 3 days after the initial treatment to assess the degree of disruption VYC-12L treatment had on normal daily activities.
Statistical Analyses
The modified intent-to-treat (mITT) population includes all randomized participants minus a small cohort of participants (n = 7) enrolled for safety assessments only. The safety population includes all participants who were randomized and received at least 1 study treatment (VYC-12L treatment group) and participants who were randomized to DTC. Demographic and safety data are summarized descriptively. For the primary effectiveness end point, ACSS responder rate and corresponding 95% confidence interval (CI) are summarized; a 2-sided Fisher's exact test with α = 0.05 was used to test whether the ACSS responder rate at month 1 in the treatment group was significantly greater than that in the DTC group. AFLS responder rates and corresponding 95% CIs are summarized.
Results
ACSS and AFLS Validation
Ninety participants completed ACSS validation and 92 completed AFLS validation. Participants for both studies were majority female (ACSS: 52.2%; AFLS: 53.3%), White (ACSS: 81.1%; AFLS: 79.3%), not of Hispanic or Latino ethnicity (ACSS: 93.3%; AFLS; 89.1%), and had Fitzpatrick skin phototypes III (ACSS; 36.7%; AFLS: 37.0%) and IV (ACSS: 25.6%; AFLS: 26.1%). Median age was 54.0 and 52.5 years for ACSS and AFLS validation studies, respectively.
For ACSS validation, interrater agreement was almost perfect (ICC ≥ 0.80) and intrarater agreement was substantial (κ ≥ 0.71). For AFLS validation, interrater agreement was almost perfect (ICC ≥ 0.84) and intrarater agreement was substantial (κ ≥ 0.73) (Supplemental Digital Content, Table S1, http://links.lww.com/DSS/B260).
Participants
Of 255 screened participants, 209 were randomized in 2:1 ratio to the VYC-12L (n = 136) or DTC (n = 73) groups. A total of 195 participants (VYC-12L, n = 131; control, n = 74) completed the month 1 control period, and 171 participants (81.8%) completed the study. Reasons for study discontinuation included lost to follow-up (n = 16), participant withdrawal (n = 10), COVID-19 (n = 4), and non–treatment-related serious AE (n = 1).
Of the 202 participants in the mITT population, the majority of participants were female (86.1%), Caucasian (87.6%), not of Hispanic ethnicity (72.3%), and with a mean age of 57.1 years (range, 31–83 years) (Supplemental Digital Content, Table S2, http://links.lww.com/DSS/B261). The majority of participants had Fitzpatrick skin phototypes III/IV (58.8%), followed by I/II (32.0%), and V/VI (9.2%). Based on EI assessments, 61.9% of participants were moderate and 38.1% were severe on the ACSS. On the AFLS, 34.7% of participants were rated moderate and 34.7% were rated severe by the EI.
The VYC-12L treatment group comprised 135 participants who received initial treatment; 98 participants (72.6%) received touch-up treatment, and 79 (58.5%) received repeat treatment. The DTC group comprised 64 participants who received initial treatment; 44 (68.8%) received touch-up treatment.
Treatment Administration
Injection parameters are summarized in Supplemental Digital Content, Table S3 (http://links.lww.com/DSS/B262). Briefly, the median total volume injected for initial and touch-up treatments combined was 4.0 mL for both cheeks in the VYC-12L (range, 0.8–6.0 mL) and DTC (range, 1.0–6.0 mL) groups; injection volumes were similar for left and right cheeks. The target plane of injection was intradermal, and the most common injection technique was microdepot. For both groups, 32-G 1/2″ needles were used approximately twice as frequently as 32-G 3/16″ needles.
Effectiveness
At month 1, the ACSS responder rate (Figure 1A) was significantly greater for the VYC-12L group (57.9%; 95% CI, 49.3%-66.6%) than for the DTC group (4.5%; 95% CI, −0.5%-9.4%), with a difference of 53.5% (95% CI, 43.5%-63.5%; p < .001). At month 1, the median change from baseline in ACSS score was −1.0 (range, −2 to 1) in the VYC-12L group and 0 (range, −1 to 1) in the DTC group, with a decrease in score indicating improvement. Responder rates remained consistent for the VYC-12L group throughout the study, with a 55.6% responder rate at month 6 (Figure 1B).
Figure 1.
ACSS responder rate. (A) Proportion of participants in the mITT population meeting ACSS responder rate criteria, defined as a ≥ 1-grade improvement from baseline at month 1 post-treatment. (B) Proportion of ACSS responders at months 1, 2, 4, and 6 post-treatment for the VYC-12L group. Error bars indicate 95% CI. ACSS, Allergan Cheek Smoothness Scale.
The AFLS responder rate at month 1 (Figure 2A) was significantly greater for the VYC-12L group (58.3%; 95% CI, 47.8%-68.9%) than for the DTC group (5.4%; 95% CI, 0.0%-12.7%), with a difference of 52.9% (95% CI, 40.1%-65.7%; p < .001). AFLS responder rates remained consistent throughout the study, with a 63.2% responder rate at month 6 (Figure 2B).
Figure 2.
AFLS responder rate. (A) Proportion of participants in the mITT population meeting AFLS responder rate criteria, defined as a ≥ 1-grade improvement from baseline at month 1 post-treatment. (B) Proportion of AFLS responders at months 1, 2, 4, and 6 post-treatment for the VYC-12L group. Error bars indicate 95% CI. AFLS, Allergan Fine Lines Scale.
At month 1, MoistureMeterD measurements of skin hydration (Supplemental Digital Content, Figure S5A, http://links.lww.com/DSS/B258) showed mean increases from baseline of 2.353 and 0.113 for the VYC-12L and DTC groups, respectively. The increase in skin hydration following VYC-12L treatment remained consistent throughout the study, with a mean increase from baseline of 2.995 at month 6 (Supplemental Digital Content, Figure S5B, http://links.lww.com/DSS/B258).
Safety
Mean pain scores reported immediately after initial treatment were 3.0 for the VYC-12L treatment group and 2.4 for the DTC group. During the 1-month period after initial treatment, at least 1 ISR was reported by 81.5% (110 of 135) of the VYC-12L group and 75.0% (48 of 64) of the DTC group (Supplemental Digital Content, Figure S6, http://links.lww.com/DSS/B258). After initial treatment, the most frequently reported ISRs were redness, swelling, and lumps/bumps; after repeat treatment, they were redness, bruising, and swelling. The majority of ISRs were mild or moderate in severity and resolved within 7 days, ISRs were reported beyond 1 month in 15 participants (11.1%) in the VYC-12L group, after touch-up treatment in 3 participants (3.1%), and after repeat treatment in 4 participants (5.1%). Three VYC-12L participants reported lumps/bumps (2 mild, 1 moderate) that resolved without intervention approximately 12 to 15 months after initial treatment; these were not considered AEs by the TIs. Additionally, review of baseline photography of 1 of these participants showed that mild lumps/bumps were present prior to study treatment. The ISR most commonly reported more than 1-month pos-treatment was lumps/bumps (initial treatment: 8.9%; repeat: 5.1%)
Following initial and/or touch-up treatment, 36 participants (18.1%) had treatment-emergent AEs (TEAEs) that were mild to moderate in severity (Table 1). The most common TEAEs were headache (4.7%) and acne (3.1%), with all other TEAEs occurring in <2% of participants. Six participants (3.0%) had treatment-related TEAEs after initial and/or touch-up treatment, of which the majority were mild in severity and most commonly included pruritis (1.5%) and erythema (1.0%). One participant had severe injection site bruising that resolved without intervention. After repeat treatment, 5 participants (6.3%) had TEAEs; no treatment-related TEAEs were reported. One participant had an AE of special interest of blurred vision; however, it was determined by the TI to be unrelated to treatment. One participant had 2 mild injection site papules with onset 117 days after touch-up treatment; these were considered treatment-related TEAEs and resolved by study end. One participant with a TEAE unrelated to treatment discontinued the study after repeat treatment. There were no unanticipated adverse device effects, treatment-related serious AEs, or deaths.
TABLE 1.
Summary of AEs and TEAEs
| VYC-12L (n = 135) | Delayed Treatment Control (n = 64) | |
| All TEAEs, no. (%) | 22 (16.3) | 14 (21.9) |
| Treatment-related TEAEs | 3 (2.2) | 3 (4.7) |
| At injection site | 3 (2.2) | 3 (4.7) |
| Not at injection site | 0 (0.0) | 0 (0.0) |
| AESIs, no. (%)* | 0 (0.0) | 1 (1.6) |
| Treatment-related AESIs | 0 (0.0) | 0 (0.0) |
| All TESAEs, no. (%) | 6 (4.4) | 3 (4.7) |
| Treatment-related SAEs | 0 (0.0) | 0 (0.0) |
| Discontinued due to TEAE, no. (%) | 0 (0.0) | 0 (0.0) |
| Deaths, no. (%) | 0 (0.0) | 0 (0.0) |
Unrelated AESI was 1 blurred vision in left eye that was determined by an ophthalmologist to be related to aging and corrected by prescription glasses.
AE, adverse event; AESI, adverse event of special interest; SAE: serious adverse event; TEAE, treatment-emergent adverse event; TESAE, treatment-emergent serious adverse event.
Vision Assessments
Snellen visual acuity assessments showed that the majority (≥85%) of participants had the same or better visual acuity at all post-treatment assessments. A total of 6 eyes (5 participants) showed a ≥3-line worsening in visual acuity at any assessment; none of these changes were deemed clinically significant or related to intravascular injection or device. No changes were seen in confrontational visual field or ocular motility at any assessment or in either group.
FACE-Q Recovery Early Life Impact
Three days after treatment, the FACE-Q Recovery Early Life Impact questionnaire overall mean score was 90.5 for the VYC-12L group and 89.8 for the DTC group.
Discussion
This randomized, prospective, DTC study evaluated the safety and effectiveness of VYC-12L for improving skin quality. Findings from nearly 200 treated participants show that VYC-12L produces significant, lasting improvements in skin quality as assessed by facial skin smoothness, fine lines, and skin hydration in adults with moderate or severe cheek skin roughness (Figure 3).
Figure 3.
Images of a 49-year-old Caucasian woman at baseline (left), 1 month (middle), and 6 months (right) after VYC-12L treatment. At baseline, participant had ACSS scores of 3 on both cheeks and baseline AFLS scores of 2 and 3 on the right and left cheeks, respectively. Participant received 0.8 mL VYC-12L in the right cheek and 1.8 mL in the left cheek for initial treatment, and 0.4 mL and 0.6 mL in the right and left cheeks, respectively, for touch-up. At the 1-month post-treatment follow-up, participant had ACSS and AFLS scores of 1 on both cheeks. Six months post-treatment, participant had ACSS scores of 1 and 3 on the right and left cheeks, respectively, and AFLS scores of 1 and 3 on the right and left cheeks, respectively.
In preliminary studies to revalidate the ACSS and AFLS using balanced representation of each grade, there was almost perfect interrater agreement and substantial intrarater agreement on both scales, showing that the ACSS and AFLS are reliable for physician ratings of cheek smoothness and fine lines in the cheek area, respectively.
In the main VYC-12L study, the primary endpoint was met, with an ACSS responder rate (≥1-grade improvement) at month 1 of 57.9% in the VYC-12L group versus a 4.5% responder rate in the DTC group, indicating that VYC-12L improves cheek skin smoothness. The median change from baseline to month 1 was a 1-grade improvement in the VYC-12L group; the median change from baseline was 0 in the DTC group. The secondary endpoint (≥1-grade improvement on the AFLS at month 1) was also met. Furthermore, improvements in cheek smoothness and fine lines lasted through 6 months post-treatment and are comparable to results from prior nonrandomized studies of VYC-12L treatment.16,17 Responder rates on the ACSS and AFLS for the treatment group at month 1 appear lower than in prior studies that reported responder rates of ≥90% at 1-month posttreatment17; however, this may be due to methodological considerations, such as basing responder rates on both cheeks in this study versus 1 cheek, differing proportions of ACSS/AFLS severities at baseline, or different injection volumes. In addition, this study included a DTC group; at the month 1 effectiveness timepoint, the control group had not received treatment and the low responder rates (ACSS: 4.5%; AFLS: 5.4%) may represent natural fluctuations in skin quality due to various factors (e.g., diet, exercise, sleep), corresponding to large (∼53%), highly statistically significant (p < .001) treatment-related differences.
Skin hydration, as assessed by probe-measured dielectric constant, was also significantly improved by VYC-12L injection. Similar to what was reported in a recent prospective study,17 hydration was increased from baseline by a mean of approximately 1 to 2 points at all post-treatment time points. These improvements in skin hydration are also similar to those reported in studies of other HA fillers.22,23 Improved hydration may be due to properties of the HA gel that allow it to occupy space in the tissue and hold water15,24 and/or due to physical interactions of the HA gel with the surrounding tissue altering how skin regulates the transport of water.25
The total median injection volume (both cheeks added) for initial and touch-up treatments combined was 4.0 mL for the VYC-12L and DTC groups and was 4.7 mL for the repeat treatment group. Allowable injection volumes were based on a prior study of VYC-12L;17,18 however, in clinical practice injectors using VYC-12L may inject smaller volumes.26 Although VYC-12L is formulated with lidocaine, TIs could use additional pretreatment anesthesia at their discretion; topical anesthetics were used approximately twice as frequently as ice. Most injections were intradermal and done with microdepot technique. Injection spacing was predominately ≤5 mm or ≥5 mm to 1 cm, and 32-G 1/2” needles were used approximately twice as frequently as 32-G 3/16” needles.
The safety profile of VYC-12L injection in the cheeks is comparable with prior studies of VYC-12L and other HA fillers. Participant-rated pain scores after treatment were low (≤3), and high (∼90) mean FACE-Q Early Life Impact scores indicated that treatment was not disruptive to normal daily activities. Observed ISRs included redness, swelling, and lumps/bumps that were mild to moderate in severity, resolved within 1 week and occurred less frequently for touch-up and repeat treatments than for initial treatment. The majority of treatment-related TEAEs were mild in severity and resolved within 1 month. There were no treatment-related serious AEs, including no changes in vision related to treatment; unexpected adverse device effects; treatment-related TEAEs leading to study discontinuation; or deaths.
One potential limitation of this study is the small number of male participants because the 2:1 randomization design meant that only 8 male participants were allocated to the DTC group. However, the safety profile of VYC-12L treatment was similar between male and female participants. Future studies of male participants' outcomes following treatment with VYC-12L are warranted. Another limitation of the study is the small number of participants with Fitzpatrick skin phototypes V and VI, and future studies with increased diversity of participants are needed. Additionally, the full extent of treatment-related changes in skin smoothness and fine lines may be difficult to fully appreciate in 2D photographs. Of note, ACSS and AFLS ratings were assessed live during the participant's follow-up visit, allowing for a more thorough assessment of post-treatment improvements.
Conclusion
VYC-12L is a safe and effective injectable treatment for the improvement of skin quality as assessed by cheek skin smoothness and fine lines in participants with moderate or severe cheek roughness and by measured skin hydration. Improvements lasted through 6 months, and repeat treatment produced similar effects with lower injection volumes.
Data Sharing Statement
AbbVie is committed to responsible data sharing regarding the clinical trials they sponsor. This includes access to anonymized, individual, and trial-level data (analysis data sets), as well as other information (e.g., protocols, clinical study reports, or analysis plans), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent, scientific research and will be provided following review and approval of a research proposal, Statistical Analysis Plan (SAP), and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time after approval in the United States and Europe and after acceptance of this manuscript for publication. The data will be accessible for 12 months, with possible extensions considered. For more information on the process or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html.
Supplementary Material
Acknowledgments
The design, study conduct, and financial support for the study were provided by Allergan plc, Dublin, Ireland before its acquisition by AbbVie Inc. AbbVie participated in the interpretation of data, review, and approval of the publication. Medical writing and editorial assistance were provided by Sarah J. Cross, PhD, of AbbVie, and funded by AbbVie Inc.
Footnotes
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.dermatologicsurgery.org).
Medical writing and editorial support were provided by Sarah J. Cross, PhD, of AbbVie Inc, and funded by AbbVie Inc.
M. Alexiades is an investigator and consultant for AbbVie. M. Palm is a clinical investigator, consultant, and advisory board member for AbbVie, Galderma, and Merz. J. Kaufman-Janette is a principal investigator for AbbVie, Galderma, Revance, Croma, and Evolus; an advisory board member for AbbVie and Revance; and a patent holder for AbbVie. I. Papel is a consultant and investigator for AbbVie. S.J. Cross, S. Chawla, and S. Abrams are employees of AbbVie Inc and may own stock/stock options in the company.
Contributor Information
Melanie D. Palm, Email: melanie.palm@gmail.com.
Joely Kaufman-Janette, Email: drjkaufman@gmail.com.
Ira Papel, Email: ira.papel.md@gmail.com.
Sarah J. Cross, Email: sarahjoy.cross@abbvie.com.
Steve Abrams, Email: steve.abrams@abbvie.com.
Smita Chawla, Email: smita.chawla@abbvie.com.
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