Retrospective Evaluation of Micro-focused Ultrasound for Lifting and Tightening the Face and Neck SABRINA G. FABI, MD,
BACKGROUND neck skin.
AND
MITCHEL P. GOLDMAN, MD
Microfocused ultrasound (MFU) is an effective means for tightening and lifting lax facial and
OBJECTIVE To evaluate the safety and efficacy of MFU with visualization (MFU-V) for noninvasive treatment of facial and neck skin laxity 180 days after treatment and determine what lifestyle factors affect treatment outcomes. MATERIALS AND METHODS Healthy women (N = 48) previously treated with MFU-V on the face and upper neck were enrolled. Depending on when MFU-V treatment occurred, subjects completed 90- or 180-day followup visits or both. Digital images of each subject were obtained before treatment and at follow-up visits. RESULTS Data were obtained at 90 (N = 16) and 180 days (N = 45), and physician Global Aesthetic Improvement Scale (GAIS) scores demonstrated that 81.3% and 77.7% patients achieved improvement, respectively. At 90 and 180 days, subject GAIS scores showed 75% and 77.8% of subjects perceived improvement, respectively. At 180 days, blinded reviewer assessments indicated that 67% of subjects showed improvement in appearance. There was no association between improvement and age, Fitzpatrick skin type, alcohol intake, or major illness. One minor adverse event was reported. DISCUSSION Although the data obtained at 90 days must be interpreted cautiously because of the smaller number of patients, subjects achieved significant lifting and tightening of facial and neck skin up to 180 days after one MFU treatment. The authors have indicated no significant interest with commercial supporters.
T
he superficial musculoaponeurotic system (SMAS) is a viscous, extracellular matrix consisting of collagen and elastic fibers with viscoelastic properties.1,2 Like tempoparietal fascia or fascia elsewhere on the body, the SMAS is intimately associated with specific facial muscles, including the platysma, orbicularis oculi, occipitofrontalis, zygomatici, and levator labii superioris.3 Collagen turnover decreases 6% with each decade, with its content in the dermis falling, and SMAS. This decrease in collagen contributes to hooding of the brow, prominent nasolabial folds, and jowls.4,5 Numerous technologies have been used in an effort to tighten sagging facial skin and improve the
appearance of rhytides. The earliest of these were radiofrequency6–8 and laser devices.9–12 More recently, microfocused ultrasound (MFU) has emerged as an effective means for not only tightening, but also lifting lax skin of the face and neck. MFU is capable of heating tissue to >60°C, producing small (~1 mm3) zones of thermal damage to a depth of up to 5 mm within the mid- to deep reticular layer of the dermis and subdermis while sparing overlying papillary dermal and epidermal layers of skin.13 The delivery of MFU to targeted areas in the SMAS and platysma results in immediate contraction of denatured collagen and the initiation of neocollagenesis and collagen remodeling.14 The result is noninvasive tightening and lifting
*All the authors are affiliated with the Goldman, Butterwick, Fitzpatrick, Groff and Fabi Dermatology Cosmetic Laser, San Diego, California © 2014 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2014;40:569–575 DOI: 10.1111/dsu.12471 569
MFU-V RETROSPECTIVE ANALYSIS
of sagging facial and neck skin associated with improvement in wrinkle appearance. By manipulating ultrasound energy and focal depth, MFU with visualization (MFU-V) can be customized to meet the unique physical characteristics of each patient. Several clinical studies have demonstrated that MFU is a safe and effective means for tightening and improving the appearance of aging facial and neck skin.15–18 The Food and Drug Administration has cleared a MFU device to noninvasively lift tissues of the eyebrow, neck and submentum.19 This device also integrates MFU with high-resolution ultrasound imaging (MFU-V) to visualize the treated tissue, ensuring proper acoustic coupling before treatment. Previous studies have evaluated the efficacy of MFU-V for treating facial areas after 60 days17 and the face and neck after 90 days.15,18 The primary objective of this retrospective study was to evaluate the efficacy and safety of MFU-V for noninvasive treatment of skin laxity 180 days after treatment using the manufacturer’s 2011 treatment protocol20 and to determine what factors, if any, affect improvement after treatment, such as smoking, alcohol use, self-reported stress level, Fitzpatrick skin type, and age.
Methods Subjects The study retrospectively enrolled healthy men and women aged 25–85 who paid for and received a full MFU-V treatment of the face and upper neck treatment using the 4-MHz, 4.5-mm and 7-MHz, 3.0-mm depth transducers (Ulthera System, Ulthera, Inc., Mesa, AZ). Depending on how long it had been since a subject’s treatment when they were enrolled, data were collected 90 and 180 days or 180 days after treatment. Subjects expressed their willingness to adhere to all requirements of the study. Procedures Standardized photographs of each subject were obtained using fixed camera and lighting conditions
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before the MFU-V procedure and at each follow-up visit using a two-dimensional digital imaging system. Analgesia was administered at the discretion of the physician and subject. Approximately 10% of subjects received topical application of 23% lidocaine/ 7% tetracaine alone applied 60 min before the procedure, and 15% received it in combination with oral diazepam (5–10 mg) 30 min before treatment was given, but the majority of subjects received a combination of topical anesthesia, oral diazepam (5–10 mg), and an intramuscular injection of 50 to 100 mg of meperidine and 50 mg of hydroxyzine 30 min before treatment. Treatment was performed in our clinic between May 2011 and October 2011 following the manufacturer’s recommended protocol that called for 370–420 treatment lines at the highest energy settings.20 Depending on when MFU-V treatment occurred, each enrolled subject completed 90 or 180-day posttreatment follow-up visits or both. Efficacy Measures The primary measure of efficacy was overall improvement in skin laxity (skin lifting, tightening, and texture improvement) in the areas treated with MFU-V. Three blinded reviewers performed a qualitative assessment of digital images obtained before and 180 days after treatment. The images were examined randomly so that the reviewers did not know which images were before and after treatment. Each reviewer first determined whether there was any improvement or no change. If there was improvement, the reviewer was asked to choose the correct post-treatment image and assess degree of improvement using the following scale:
(1) (2) (3) (4)
Slight, 1–25% improvement Fair, 26–50% improvement Good, 51–75% improvement Excellent, 76–100% improvement.
Secondary efficacy measures included the physician Global Aesthetic Improvement Scale (PGAIS), derived by comparing a live assessment of the subject with pretreatment digital images
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and scoring them as 1 (very much improved), 2 (marked improvement), 3 (improved) 4 (no change), or 5 (worse). Other secondary efficacy measures included self-reported subject Global Aesthetic Improvement Scale (SGAIS) scores and measuring subject lifestyle satisfaction using subject lifestyle and patient satisfaction questionnaires (PSQ). Safety At the time of enrollment, the medical history and concomitant medications of each subject were reviewed. The treatment site was visually examined, and the subject was queried about treatment-related adverse events. At each subsequent visit, the treatment site was re-examined, and each subject was queried again about adverse events and changes in medication use. Statistical Analysis Associations between demographic and lifestyle covariates were tested using the Student t-test or Wilcoxon rank sum test for continuous variables, Fisher exact test for categorical variables, and logistic regression for ordinal variables. Tests were two-sided, with .05 significance levels. Analyses were performed using SAS version 9.2 (SAS Institute, Inc., Cary, NC). Ethics An independent institutional review board (Asentral, Inc. IRB, Newburyport, MA) approved the protocol and informed consent forms used in this study. Each subject provided written informed consent and Health Insurance Portability and Accountability Act authorization before undergoing any study-related procedures and provided written release for the use of study-related digital images. ClinicalTrials.gov Identifier: NCT01519934.
Results Demographic Characteristics The study enrolled 48 women with a median age of 58.5 (range 31–85). Three were lost to follow-up for
non-study-related reasons such as moving out of San Diego. Of the remaining 45 subjects, 16 completed the 90-day follow-up visit, and 45 completed the 180-day visit. The demographic characteristics of the enrolled subjects are provided in Table 1. Primary Endpoint Of subjects in the blinded assessment (N = 45), 66.7% were assessed as improved, and a correct post-treatment image was selected, 17.8% of subjects were assessed as having no change, and 15.5% of subjects were assessed as improved, although an incorrect pretreatment versus post-treatment image selection was made. Secondary Endpoints Global Assessment of Improvement The proportions of subjects showing any level of improvement based on investigator assessment at 90 and 180 days were 81.3% and 77.7%, respectively (Figures 1–3). The proportion of subjects who believed that they demonstrated improvement in appearance was 75% at 90 days and 77.8% at 180 days. The GAIS results are summarized in Table 2.
TABLE 1. Patient Characteristics Characteristic
Value
Female, n (%) Age, mean (range) Baseline body mass index, mean (range) Race or ethnicity, n (%) Caucasian Hispanic Native Hawaiian or Pacific Islander Asian Mixed race Fitzpatrick skin type, n (%) I II III IV
48 (100) 58 (39, 85) 22.1 (17.9, 30.8)
42 (87.5) 3 (6.3) 1 (2.1) 1 (2.1) 1 (2.1)
1 24 17 6
(2.1) (50) (35.4) (12.5)
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TABLE 2. Global Aesthetic Improvement Scale Scale
Figure 1. Sixty-seven-year old woman status-post one MFU-V treatment, 6 months later.
Physician* Very much improved Much improved Improved No change Worse Any improvement Subject† Very much improved Much improved Improved No changed Worse Any improvement
Day 90, N = 16 n (%) –
Day 180, N = 45
6 (13.3) 7 (43.8)
8 (17.7)
6 (37.5) 3 (18.8)
21 (46.7) 10 (22.2) – 35 (77.7)
– 13 (81.3)
–
6 (13.3) 3 (18.8)
4 (8.9)
9 (56.3) 4 (25)
25 (55.6) 10 (22.2) – 35 (77.8)
– 12 (75)
*p = .005 for Day 90 and p < .001 for Day 180. † p = .001 for Day 90 and p < .001 for Day 180 (chi-square goodness-of-fit).
Figure 2. Fifty-five-year-old woman status-post one MFU-V treatment to the face and upper neck, 6 months later.
Figure 3. Sixty-nine-year-old woman status-post one MFUV treatment, 6 months later.
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Subject Lifestyle Questionnaire The Subject Lifestyle Questionnaire revealed that most subjects were nonsmokers, consumed alcohol in moderation, and had average to high levels of stress in their life. Approximately 90% of subjects reported no major surgeries or prolonged illnesses at either follow-up time points since their MFU-V treatment. On average, subjects reported 6–7 h of sleep per night, with most feeling that this was an almost ideal amount of sleep. At both post-treatment visits, most subjects reported that they followed a skin care routine, with the vast majority routinely using facial cleansers, moisturizers, and sunscreens (Table 3). Similarly, most subjects reported following a sun protection routine including avoidance of excessive sun exposure, daily use of sunscreen, and wearing protective garments. Patient Satisfaction Questionnaire At 90 days after treatment, 62.5% of subjects who had completed the PSQ indicated that they were very satisfied (25%) or satisfied (37.5%) with the
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TABLE 3. Demographic and Lifestyle Questionnaire Day 90, N = 16
TABLE 4. Patient Satisfaction
Day 180, N = 45
Smoker, n (%) Never 13 (81.3) 30 (66.7) Former or current 3 (18.8) 15 (33.3) Alcohol use, n (%) Never 4 (25) 9 (20) Former or current 12 (75) 36 (80) Stress level, n (%) Very low – 1 (2.2) Low 3 (18.8) 6 (13.3) Average 5 (31.3) 19 (42.2) High 5 (31.3) 13 (28.9) Very high 3 (18.8) 6 (13.3) Major surgery or prolonged illness since MFU-V Yes 2 (12.5) 3 (6.7) No 14 (87.5) 42 (93.3) Sleep duration, 6 (4–8) 7 (5–9) hours, mean (range) Quality of sleep, n (%) Extremely – 1 (2.2) insufficient Insufficient 6 (37.5) 9 (20.0) Sufficient – – Almost ideal 8 (50) 31 (68.9) Ideal 2 (12.5) 4 (8.9) Skin care routine, n (%) Facial cleanser 15 (93.8) 42 (93.3) Toner 9 (56.3) 22 (48.9) Serum 9 (56.3) 24 (53.3) Retinoid product 8 (50.0) 23 (51.1) Moisturizer 14 (87.5) 43 (95.6) Sunscreen 15 (93.8) 40 (88.9) Sun protection routine, n (%) Daily sunscreen use 12 (75) 23 (51.1) Reapply sunscreen 3 (18.8) 8 (17.8) frequently Avoid excessive sun 14 (87.5) 31 (68.9) exposure Protective garments 8 (50.0) 23 (51.1)
treatment results (Table 4). At 180 days after treatment, 60% of subjects continued to be very satisfied (11.1%) or satisfied (48.9%) with their treatment. More than 80% of subjects indicated that they noticed improvement in face and neck characteristics at both time points. Ninety and 180 days after treatment, 43.8% and 48.9% of subjects reported improvement in skin laxity, and 62.5% and 60.0% reported tighter or lifted skin, respectively.
90 days, N = 16 n (%)
180 days, N = 45
Overall rating Very satisfied 4 (25) 5 (11.1) Satisfied 6 (37.5) 22 (48.9) Dissatisfied 5 (31.3) 13 (28.9) Very dissatisfied 1 (6.3) 5 (11.1) Very satisfied + 10 (62.5) 27 (60.0) satisfied Subject noticed improvement Yes 13 (81.3) 38 (84.4) No 3 (18.8) 7 (15.6) Specific areas of improvement subject noticed Improvement in 5 (31.5) 14 (31.1) lines and wrinkles Less skin laxity 7 (43.8) 22 (48.9) (sagging) Tighter, lifted skin 10 (62.5) 27 (60.0) More even skin 6 (37.5) 10 (22.2) tone (color) Smoother skin 6 (37.5) 18 (40.0) texture Overall skin health 6 (37.5) 12 (26.7)
Covariate Analysis A covariate analysis of patient demographic and lifestyle characteristics according to patient satisfaction, PGAIS and SGAIS scores at day 180 revealed that higher levels of self-reported stress were correlated with higher PGAIS scores (p = .03) and that patients with lower BMI reported higher SGAIS scores (p = .04). Patients who reported having less than a sufficient amount of sleep showed a trend toward significantly better SGAIS scores (p = .09). No correlation was seen between different age groups (≤60 vs >60), Fitzpatrick skin type, alcohol intake, major illness, and sun avoidance and PGAIS or SGAIS score at Day 180. There was also no correlation between any baseline patient characteristics and level of patient satisfaction. Safety Endpoints There were no reports of serious or permanent adverse events. One patient showed evidence of a 2-mm white dermal papule on the upper neck after
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treatment that resolved after being injected with 0.1 mL of 10 mg/mL triamcinolone acetonide. This was most likely a result of pulse stacking in that area. At both time points, there was no evidence of acute skin damage or long-term sequelae such as scars, burns, or hypo- or hyperpigmentation.
Discussion The goal of this retrospective study was to evaluate the efficacy of MFU-V for noninvasive treatment of skin texture and laxity 180 months after treatment in paying patients. Although one published study demonstrated improvement of the infraorbital area 180 days after treatment with MFU-V,21 other studies reported the efficacy of MFU-V for treating facial areas after only 60 days17 and the face and neck after 90 days.15,18 Based on the blinded reviewer assessments, the majority of subjects (67%) demonstrated an improvement in appearance 180 days after treatment with MFU-V. More than 80% of subjects indicated that they noticed improvement in face and neck characteristics 90 and 180 days after treatment. There was no evidence of an association between improvement and age, Fitzpatrick skin type, alcohol intake, or major illness. For unknown reasons, subjects self-reporting high levels of stress were found to have significantly higher PGAIS scores, coinciding with the trend seen that subjects reporting having less than sufficient sleep had higher SGAIS scores. Those with lower BMI (≤25 kg/m2) also were found to have significantly higher SGAIS scores. Although the smaller number of patients at the 90day time point limited the effect of the demographic characteristics of the enrolled patients such as stress, sleep quality, and smoking, we believe that these are important considerations for future studies. Significant improvement in skin laxity and appearance were achieved after a single MFU-V treatment session with a treatment protocol that called for half
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the density that is now recommended to achieve even greater and more consistent results. Furthermore, the older protocol used to treat these patients defaulted to the highest energy settings, requiring a greater degree of analgesia than is now necessary with the newer protocol that defaults to two lowerenergy settings. These results are superior to those of radiofrequency devices that require multiple treatment sessions over several weeks or months22,23 and have not shown SGAIS and patient satisfaction rates as high as those demonstrated in actual paying patients.24
Conclusion This study demonstrated significant lifting and tightening of facial and neck skin, resulting in improved skin texture up to 180 days after a single MFU-V treatment. A study limitation was its retrospective nature and that data at 90 days were limited because of timing of enrollment. These results need to be confirmed in a larger, prospective, controlled study. Similar to previous studies, there were no significant or long-term adverse events.
Acknowledgment This study was sponsored by Ulthera, Inc, Mesa, Arizona. The authors acknowledge the editorial assistance of Dr. Carl Hornfeldt during the preparation of this manuscript.
References 1. Har-Shai Y, Bodner SR, Egozy-Golan D, Lindenbaum ES, et al. Mechanical properties and microstructure of the superficial musculoaponeurotic system. Plast Reconstr Surg 1996;98:59–70. 2. Ghassemi A, Prescher A, Riediger D, Axer H. Anatomy of the SMAS revisited. Aesthetic Plast Surg 2003;27:258–64. 3. Cilento BW. Superficial musculoaponeurotic system (SMAS). In: Kountakis SE, editor. Encyclopedia of otolaryngology, head and neck surgery. Philadelphia: Springer; 2013. 4. Psillakis JM, Rumley TO, Camargos A. Subperiosteal approach as an improved concept for correction of the aging face. Plast Reconstr Surg 1988;82:383–94. 5. Kikkawa DO, Lemke BN, Dortzbach RK. Relations of the superficial musculoaponeurotic system to the orbit and characterization of the orbitomalar ligament. Ophthal Plast Reconstr Surg 1996;12:77–88.
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6. Alster TS, Tanzi EL. Noninvasive lifting of arm, thigh, and knee skin with transcutaneous intense focused ultrasound. Dermatol Surg 2012;38:754–9.
17. Suh DH, Shin MK, Lee SJ, Rho JH, et al. Intense focused ultrasound tightening in Asian skin: clinical and pathologic results. Dermatol Surg 2011;37:1595–602.
7. Fitzpatrick R, Geronemus R, Goldberg D, Kaminer M, et al. Multicenter study of noninvasive radiofrequency for periorbital tissue tightening. Lasers Surg Med 2003;33:232–42.
18. Lee HS, Jang WS, Cha YJ, Choi YH, et al. Multiple pass ultrasound tightening of skin laxity of the lower face and neck. Dermatol Surg 2012;38:20–7.
8. Zelickson BD, Kist D, Bernstein E, Brown DB, et al. Histology and ultrastructural evaluation of the effects of a radiofrequencybased nonablative dermal remodeling device. Arch Dermatol 2004;140:204–9.
19. ULTHERAâOperation & Maintenance Manual. Ulthera, Inc., Mesa, AZ.
9. Fitzpatrick RE, Goldman MP, Satur NM, Tope WD. Pulsed carbon dioxide laser skin resurfacing of photoaged facial skin. Arch Dermatol 1996;132:393–402. 10. Goco PE, Stucker FJ. Subdermal carbon dioxide laser cutaneous contraction. Arch Facial Plast Surg 2002;6:37–40. 11. Kim KH, Geronemus RG. Nonablative laser and light therapies for skin rejuvenation. Arch Facial Plast Surg 2004;6:398–409. 12. Kirsh KM, Zelickson BD, Zachary CB, Tope WD. Ultrastructure of collagen thermally denatured by microsecond domain pulsed carbon dioxide laser. Arch Dermatol 1998;134:1255–9. 13. Laubach HJ, Makin IR, Barthe PG, Slayton MH, et al. Intense focused ultrasound: evaluation of a new treatment modality for precise microcoagulation within the skin. Dermatol Surg 2008;34:727–34. 14. White WM, Makin IR, Barthe PG, Slayton MH, et al. Selective creation of thermal injury zones in the superficial musculoaponeurotic system using intense ultrasound therapy: a new target for noninvasive facial rejuvenation. Arch Facial Plast Surg 2007;9:22–9. 15. Alam M, White LE, Martin N, Witherspoon J, et al. Ultrasound tightening of facial and neck skin: a rater-blinded prospective cohort study. J Am Acad Dermatol 2010;62:262–9.
20. UltherapyâTreatment Guideline (5.0 PLUS). Ulthera, Inc., Mesa, AZ. 21. Suh DH, Oh YJ, Lee SJ, Rho JH, et al. A intense-focused ultrasound tightening for the treatment of infraorbital laxity. J Cosmet Laser Ther 2012;14:290–5. 22. Taub AF, Tucker RD, Palange A. Facial tightening with an advanced 4-MHz monopolar radiofrequency device. J Drugs Dermatol 2012;11:1288–94. 23. Elman M, Vider I, Harth Y, Gottfried V, et al. Non-invasive therapy of wrinkles and lax skin using a novel multisource phasecontrolled radio frequency system. J Cosmet Laser Ther 2010;12:81–6. 24. Edwards AF, Massaki A, Fabi SG, Goldman MP. Clinical efficacy and safety evaluation of a new monopolar radiofrequency (mRF) device with comfort pulsed technology for the treatment of facial skin laxity: 10 month experience with 64 patients. Derm Surg 2013;39:104–10.
Address correspondence and reprint requests to: Sabrina Fabi, MD, Goldman, Butterwick, Fitzpatrick, Groff and Fabi Dermatology Cosmetic Laser, 9339 Genesee Avenue, Suite 300, San Diego, California 92121, or e-mail: [email protected]
16. Chan NP, Shek SY, Yu CS, Ho SG, et al. Safety study of transcutaneous focused ultrasound for non-invasive skin tightening in Asians. Lasers Surg Med 2011;43:366–75.
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BACKGROUND neck skin.
AND
MITCHEL P. GOLDMAN, MD
Microfocused ultrasound (MFU) is an effective means for tightening and lifting lax facial and
OBJECTIVE To evaluate the safety and efficacy of MFU with visualization (MFU-V) for noninvasive treatment of facial and neck skin laxity 180 days after treatment and determine what lifestyle factors affect treatment outcomes. MATERIALS AND METHODS Healthy women (N = 48) previously treated with MFU-V on the face and upper neck were enrolled. Depending on when MFU-V treatment occurred, subjects completed 90- or 180-day followup visits or both. Digital images of each subject were obtained before treatment and at follow-up visits. RESULTS Data were obtained at 90 (N = 16) and 180 days (N = 45), and physician Global Aesthetic Improvement Scale (GAIS) scores demonstrated that 81.3% and 77.7% patients achieved improvement, respectively. At 90 and 180 days, subject GAIS scores showed 75% and 77.8% of subjects perceived improvement, respectively. At 180 days, blinded reviewer assessments indicated that 67% of subjects showed improvement in appearance. There was no association between improvement and age, Fitzpatrick skin type, alcohol intake, or major illness. One minor adverse event was reported. DISCUSSION Although the data obtained at 90 days must be interpreted cautiously because of the smaller number of patients, subjects achieved significant lifting and tightening of facial and neck skin up to 180 days after one MFU treatment. The authors have indicated no significant interest with commercial supporters.
T
he superficial musculoaponeurotic system (SMAS) is a viscous, extracellular matrix consisting of collagen and elastic fibers with viscoelastic properties.1,2 Like tempoparietal fascia or fascia elsewhere on the body, the SMAS is intimately associated with specific facial muscles, including the platysma, orbicularis oculi, occipitofrontalis, zygomatici, and levator labii superioris.3 Collagen turnover decreases 6% with each decade, with its content in the dermis falling, and SMAS. This decrease in collagen contributes to hooding of the brow, prominent nasolabial folds, and jowls.4,5 Numerous technologies have been used in an effort to tighten sagging facial skin and improve the
appearance of rhytides. The earliest of these were radiofrequency6–8 and laser devices.9–12 More recently, microfocused ultrasound (MFU) has emerged as an effective means for not only tightening, but also lifting lax skin of the face and neck. MFU is capable of heating tissue to >60°C, producing small (~1 mm3) zones of thermal damage to a depth of up to 5 mm within the mid- to deep reticular layer of the dermis and subdermis while sparing overlying papillary dermal and epidermal layers of skin.13 The delivery of MFU to targeted areas in the SMAS and platysma results in immediate contraction of denatured collagen and the initiation of neocollagenesis and collagen remodeling.14 The result is noninvasive tightening and lifting
*All the authors are affiliated with the Goldman, Butterwick, Fitzpatrick, Groff and Fabi Dermatology Cosmetic Laser, San Diego, California © 2014 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2014;40:569–575 DOI: 10.1111/dsu.12471 569
MFU-V RETROSPECTIVE ANALYSIS
of sagging facial and neck skin associated with improvement in wrinkle appearance. By manipulating ultrasound energy and focal depth, MFU with visualization (MFU-V) can be customized to meet the unique physical characteristics of each patient. Several clinical studies have demonstrated that MFU is a safe and effective means for tightening and improving the appearance of aging facial and neck skin.15–18 The Food and Drug Administration has cleared a MFU device to noninvasively lift tissues of the eyebrow, neck and submentum.19 This device also integrates MFU with high-resolution ultrasound imaging (MFU-V) to visualize the treated tissue, ensuring proper acoustic coupling before treatment. Previous studies have evaluated the efficacy of MFU-V for treating facial areas after 60 days17 and the face and neck after 90 days.15,18 The primary objective of this retrospective study was to evaluate the efficacy and safety of MFU-V for noninvasive treatment of skin laxity 180 days after treatment using the manufacturer’s 2011 treatment protocol20 and to determine what factors, if any, affect improvement after treatment, such as smoking, alcohol use, self-reported stress level, Fitzpatrick skin type, and age.
Methods Subjects The study retrospectively enrolled healthy men and women aged 25–85 who paid for and received a full MFU-V treatment of the face and upper neck treatment using the 4-MHz, 4.5-mm and 7-MHz, 3.0-mm depth transducers (Ulthera System, Ulthera, Inc., Mesa, AZ). Depending on how long it had been since a subject’s treatment when they were enrolled, data were collected 90 and 180 days or 180 days after treatment. Subjects expressed their willingness to adhere to all requirements of the study. Procedures Standardized photographs of each subject were obtained using fixed camera and lighting conditions
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before the MFU-V procedure and at each follow-up visit using a two-dimensional digital imaging system. Analgesia was administered at the discretion of the physician and subject. Approximately 10% of subjects received topical application of 23% lidocaine/ 7% tetracaine alone applied 60 min before the procedure, and 15% received it in combination with oral diazepam (5–10 mg) 30 min before treatment was given, but the majority of subjects received a combination of topical anesthesia, oral diazepam (5–10 mg), and an intramuscular injection of 50 to 100 mg of meperidine and 50 mg of hydroxyzine 30 min before treatment. Treatment was performed in our clinic between May 2011 and October 2011 following the manufacturer’s recommended protocol that called for 370–420 treatment lines at the highest energy settings.20 Depending on when MFU-V treatment occurred, each enrolled subject completed 90 or 180-day posttreatment follow-up visits or both. Efficacy Measures The primary measure of efficacy was overall improvement in skin laxity (skin lifting, tightening, and texture improvement) in the areas treated with MFU-V. Three blinded reviewers performed a qualitative assessment of digital images obtained before and 180 days after treatment. The images were examined randomly so that the reviewers did not know which images were before and after treatment. Each reviewer first determined whether there was any improvement or no change. If there was improvement, the reviewer was asked to choose the correct post-treatment image and assess degree of improvement using the following scale:
(1) (2) (3) (4)
Slight, 1–25% improvement Fair, 26–50% improvement Good, 51–75% improvement Excellent, 76–100% improvement.
Secondary efficacy measures included the physician Global Aesthetic Improvement Scale (PGAIS), derived by comparing a live assessment of the subject with pretreatment digital images
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and scoring them as 1 (very much improved), 2 (marked improvement), 3 (improved) 4 (no change), or 5 (worse). Other secondary efficacy measures included self-reported subject Global Aesthetic Improvement Scale (SGAIS) scores and measuring subject lifestyle satisfaction using subject lifestyle and patient satisfaction questionnaires (PSQ). Safety At the time of enrollment, the medical history and concomitant medications of each subject were reviewed. The treatment site was visually examined, and the subject was queried about treatment-related adverse events. At each subsequent visit, the treatment site was re-examined, and each subject was queried again about adverse events and changes in medication use. Statistical Analysis Associations between demographic and lifestyle covariates were tested using the Student t-test or Wilcoxon rank sum test for continuous variables, Fisher exact test for categorical variables, and logistic regression for ordinal variables. Tests were two-sided, with .05 significance levels. Analyses were performed using SAS version 9.2 (SAS Institute, Inc., Cary, NC). Ethics An independent institutional review board (Asentral, Inc. IRB, Newburyport, MA) approved the protocol and informed consent forms used in this study. Each subject provided written informed consent and Health Insurance Portability and Accountability Act authorization before undergoing any study-related procedures and provided written release for the use of study-related digital images. ClinicalTrials.gov Identifier: NCT01519934.
Results Demographic Characteristics The study enrolled 48 women with a median age of 58.5 (range 31–85). Three were lost to follow-up for
non-study-related reasons such as moving out of San Diego. Of the remaining 45 subjects, 16 completed the 90-day follow-up visit, and 45 completed the 180-day visit. The demographic characteristics of the enrolled subjects are provided in Table 1. Primary Endpoint Of subjects in the blinded assessment (N = 45), 66.7% were assessed as improved, and a correct post-treatment image was selected, 17.8% of subjects were assessed as having no change, and 15.5% of subjects were assessed as improved, although an incorrect pretreatment versus post-treatment image selection was made. Secondary Endpoints Global Assessment of Improvement The proportions of subjects showing any level of improvement based on investigator assessment at 90 and 180 days were 81.3% and 77.7%, respectively (Figures 1–3). The proportion of subjects who believed that they demonstrated improvement in appearance was 75% at 90 days and 77.8% at 180 days. The GAIS results are summarized in Table 2.
TABLE 1. Patient Characteristics Characteristic
Value
Female, n (%) Age, mean (range) Baseline body mass index, mean (range) Race or ethnicity, n (%) Caucasian Hispanic Native Hawaiian or Pacific Islander Asian Mixed race Fitzpatrick skin type, n (%) I II III IV
48 (100) 58 (39, 85) 22.1 (17.9, 30.8)
42 (87.5) 3 (6.3) 1 (2.1) 1 (2.1) 1 (2.1)
1 24 17 6
(2.1) (50) (35.4) (12.5)
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TABLE 2. Global Aesthetic Improvement Scale Scale
Figure 1. Sixty-seven-year old woman status-post one MFU-V treatment, 6 months later.
Physician* Very much improved Much improved Improved No change Worse Any improvement Subject† Very much improved Much improved Improved No changed Worse Any improvement
Day 90, N = 16 n (%) –
Day 180, N = 45
6 (13.3) 7 (43.8)
8 (17.7)
6 (37.5) 3 (18.8)
21 (46.7) 10 (22.2) – 35 (77.7)
– 13 (81.3)
–
6 (13.3) 3 (18.8)
4 (8.9)
9 (56.3) 4 (25)
25 (55.6) 10 (22.2) – 35 (77.8)
– 12 (75)
*p = .005 for Day 90 and p < .001 for Day 180. † p = .001 for Day 90 and p < .001 for Day 180 (chi-square goodness-of-fit).
Figure 2. Fifty-five-year-old woman status-post one MFU-V treatment to the face and upper neck, 6 months later.
Figure 3. Sixty-nine-year-old woman status-post one MFUV treatment, 6 months later.
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Subject Lifestyle Questionnaire The Subject Lifestyle Questionnaire revealed that most subjects were nonsmokers, consumed alcohol in moderation, and had average to high levels of stress in their life. Approximately 90% of subjects reported no major surgeries or prolonged illnesses at either follow-up time points since their MFU-V treatment. On average, subjects reported 6–7 h of sleep per night, with most feeling that this was an almost ideal amount of sleep. At both post-treatment visits, most subjects reported that they followed a skin care routine, with the vast majority routinely using facial cleansers, moisturizers, and sunscreens (Table 3). Similarly, most subjects reported following a sun protection routine including avoidance of excessive sun exposure, daily use of sunscreen, and wearing protective garments. Patient Satisfaction Questionnaire At 90 days after treatment, 62.5% of subjects who had completed the PSQ indicated that they were very satisfied (25%) or satisfied (37.5%) with the
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TABLE 3. Demographic and Lifestyle Questionnaire Day 90, N = 16
TABLE 4. Patient Satisfaction
Day 180, N = 45
Smoker, n (%) Never 13 (81.3) 30 (66.7) Former or current 3 (18.8) 15 (33.3) Alcohol use, n (%) Never 4 (25) 9 (20) Former or current 12 (75) 36 (80) Stress level, n (%) Very low – 1 (2.2) Low 3 (18.8) 6 (13.3) Average 5 (31.3) 19 (42.2) High 5 (31.3) 13 (28.9) Very high 3 (18.8) 6 (13.3) Major surgery or prolonged illness since MFU-V Yes 2 (12.5) 3 (6.7) No 14 (87.5) 42 (93.3) Sleep duration, 6 (4–8) 7 (5–9) hours, mean (range) Quality of sleep, n (%) Extremely – 1 (2.2) insufficient Insufficient 6 (37.5) 9 (20.0) Sufficient – – Almost ideal 8 (50) 31 (68.9) Ideal 2 (12.5) 4 (8.9) Skin care routine, n (%) Facial cleanser 15 (93.8) 42 (93.3) Toner 9 (56.3) 22 (48.9) Serum 9 (56.3) 24 (53.3) Retinoid product 8 (50.0) 23 (51.1) Moisturizer 14 (87.5) 43 (95.6) Sunscreen 15 (93.8) 40 (88.9) Sun protection routine, n (%) Daily sunscreen use 12 (75) 23 (51.1) Reapply sunscreen 3 (18.8) 8 (17.8) frequently Avoid excessive sun 14 (87.5) 31 (68.9) exposure Protective garments 8 (50.0) 23 (51.1)
treatment results (Table 4). At 180 days after treatment, 60% of subjects continued to be very satisfied (11.1%) or satisfied (48.9%) with their treatment. More than 80% of subjects indicated that they noticed improvement in face and neck characteristics at both time points. Ninety and 180 days after treatment, 43.8% and 48.9% of subjects reported improvement in skin laxity, and 62.5% and 60.0% reported tighter or lifted skin, respectively.
90 days, N = 16 n (%)
180 days, N = 45
Overall rating Very satisfied 4 (25) 5 (11.1) Satisfied 6 (37.5) 22 (48.9) Dissatisfied 5 (31.3) 13 (28.9) Very dissatisfied 1 (6.3) 5 (11.1) Very satisfied + 10 (62.5) 27 (60.0) satisfied Subject noticed improvement Yes 13 (81.3) 38 (84.4) No 3 (18.8) 7 (15.6) Specific areas of improvement subject noticed Improvement in 5 (31.5) 14 (31.1) lines and wrinkles Less skin laxity 7 (43.8) 22 (48.9) (sagging) Tighter, lifted skin 10 (62.5) 27 (60.0) More even skin 6 (37.5) 10 (22.2) tone (color) Smoother skin 6 (37.5) 18 (40.0) texture Overall skin health 6 (37.5) 12 (26.7)
Covariate Analysis A covariate analysis of patient demographic and lifestyle characteristics according to patient satisfaction, PGAIS and SGAIS scores at day 180 revealed that higher levels of self-reported stress were correlated with higher PGAIS scores (p = .03) and that patients with lower BMI reported higher SGAIS scores (p = .04). Patients who reported having less than a sufficient amount of sleep showed a trend toward significantly better SGAIS scores (p = .09). No correlation was seen between different age groups (≤60 vs >60), Fitzpatrick skin type, alcohol intake, major illness, and sun avoidance and PGAIS or SGAIS score at Day 180. There was also no correlation between any baseline patient characteristics and level of patient satisfaction. Safety Endpoints There were no reports of serious or permanent adverse events. One patient showed evidence of a 2-mm white dermal papule on the upper neck after
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treatment that resolved after being injected with 0.1 mL of 10 mg/mL triamcinolone acetonide. This was most likely a result of pulse stacking in that area. At both time points, there was no evidence of acute skin damage or long-term sequelae such as scars, burns, or hypo- or hyperpigmentation.
Discussion The goal of this retrospective study was to evaluate the efficacy of MFU-V for noninvasive treatment of skin texture and laxity 180 months after treatment in paying patients. Although one published study demonstrated improvement of the infraorbital area 180 days after treatment with MFU-V,21 other studies reported the efficacy of MFU-V for treating facial areas after only 60 days17 and the face and neck after 90 days.15,18 Based on the blinded reviewer assessments, the majority of subjects (67%) demonstrated an improvement in appearance 180 days after treatment with MFU-V. More than 80% of subjects indicated that they noticed improvement in face and neck characteristics 90 and 180 days after treatment. There was no evidence of an association between improvement and age, Fitzpatrick skin type, alcohol intake, or major illness. For unknown reasons, subjects self-reporting high levels of stress were found to have significantly higher PGAIS scores, coinciding with the trend seen that subjects reporting having less than sufficient sleep had higher SGAIS scores. Those with lower BMI (≤25 kg/m2) also were found to have significantly higher SGAIS scores. Although the smaller number of patients at the 90day time point limited the effect of the demographic characteristics of the enrolled patients such as stress, sleep quality, and smoking, we believe that these are important considerations for future studies. Significant improvement in skin laxity and appearance were achieved after a single MFU-V treatment session with a treatment protocol that called for half
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the density that is now recommended to achieve even greater and more consistent results. Furthermore, the older protocol used to treat these patients defaulted to the highest energy settings, requiring a greater degree of analgesia than is now necessary with the newer protocol that defaults to two lowerenergy settings. These results are superior to those of radiofrequency devices that require multiple treatment sessions over several weeks or months22,23 and have not shown SGAIS and patient satisfaction rates as high as those demonstrated in actual paying patients.24
Conclusion This study demonstrated significant lifting and tightening of facial and neck skin, resulting in improved skin texture up to 180 days after a single MFU-V treatment. A study limitation was its retrospective nature and that data at 90 days were limited because of timing of enrollment. These results need to be confirmed in a larger, prospective, controlled study. Similar to previous studies, there were no significant or long-term adverse events.
Acknowledgment This study was sponsored by Ulthera, Inc, Mesa, Arizona. The authors acknowledge the editorial assistance of Dr. Carl Hornfeldt during the preparation of this manuscript.
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6. Alster TS, Tanzi EL. Noninvasive lifting of arm, thigh, and knee skin with transcutaneous intense focused ultrasound. Dermatol Surg 2012;38:754–9.
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9. Fitzpatrick RE, Goldman MP, Satur NM, Tope WD. Pulsed carbon dioxide laser skin resurfacing of photoaged facial skin. Arch Dermatol 1996;132:393–402. 10. Goco PE, Stucker FJ. Subdermal carbon dioxide laser cutaneous contraction. Arch Facial Plast Surg 2002;6:37–40. 11. Kim KH, Geronemus RG. Nonablative laser and light therapies for skin rejuvenation. Arch Facial Plast Surg 2004;6:398–409. 12. Kirsh KM, Zelickson BD, Zachary CB, Tope WD. Ultrastructure of collagen thermally denatured by microsecond domain pulsed carbon dioxide laser. Arch Dermatol 1998;134:1255–9. 13. Laubach HJ, Makin IR, Barthe PG, Slayton MH, et al. Intense focused ultrasound: evaluation of a new treatment modality for precise microcoagulation within the skin. Dermatol Surg 2008;34:727–34. 14. White WM, Makin IR, Barthe PG, Slayton MH, et al. Selective creation of thermal injury zones in the superficial musculoaponeurotic system using intense ultrasound therapy: a new target for noninvasive facial rejuvenation. Arch Facial Plast Surg 2007;9:22–9. 15. Alam M, White LE, Martin N, Witherspoon J, et al. Ultrasound tightening of facial and neck skin: a rater-blinded prospective cohort study. J Am Acad Dermatol 2010;62:262–9.
20. UltherapyâTreatment Guideline (5.0 PLUS). Ulthera, Inc., Mesa, AZ. 21. Suh DH, Oh YJ, Lee SJ, Rho JH, et al. A intense-focused ultrasound tightening for the treatment of infraorbital laxity. J Cosmet Laser Ther 2012;14:290–5. 22. Taub AF, Tucker RD, Palange A. Facial tightening with an advanced 4-MHz monopolar radiofrequency device. J Drugs Dermatol 2012;11:1288–94. 23. Elman M, Vider I, Harth Y, Gottfried V, et al. Non-invasive therapy of wrinkles and lax skin using a novel multisource phasecontrolled radio frequency system. J Cosmet Laser Ther 2010;12:81–6. 24. Edwards AF, Massaki A, Fabi SG, Goldman MP. Clinical efficacy and safety evaluation of a new monopolar radiofrequency (mRF) device with comfort pulsed technology for the treatment of facial skin laxity: 10 month experience with 64 patients. Derm Surg 2013;39:104–10.
Address correspondence and reprint requests to: Sabrina Fabi, MD, Goldman, Butterwick, Fitzpatrick, Groff and Fabi Dermatology Cosmetic Laser, 9339 Genesee Avenue, Suite 300, San Diego, California 92121, or e-mail: [email protected]
16. Chan NP, Shek SY, Yu CS, Ho SG, et al. Safety study of transcutaneous focused ultrasound for non-invasive skin tightening in Asians. Lasers Surg Med 2011;43:366–75.
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