[ORIGINAL
RESEARCH]
Treatment of Age-related Mid-face Atrophy by Injection of Cohesive Polydensified Matrix Hyaluronic Acid Volumizer PATRICK MICHEELS, MD; bJOAN VANDEPUTTE, MD; aMARIA KRAVTSOV, MSc
a
a
Geneva, Switzerland; bOudenaarde, Belgium
ABSTRACT Objective: Cohesive Polydensified Matrix® Hyaluronic Acid Volumizer is designed to be injected subcutaneously or in deeper soft tissue layers to restore facial volumes. This post-marketing clinical follow-up was performed to confirm the safety and effectiveness of the product up to 18 months. Design: Injections were performed according to standard clinical practice and patients were followed-up at Months 1, 3, 6, 9, 12, and optionally at Month 18. Effectiveness measures included facial volume loss scale, global aesthetic improvement scale and patients’ satisfaction. Injection site reactions were recorded to evaluate safety. Results: Twenty patients with intermediate-to-severe volume loss in the lateral cheek hollows and/or cheekbone area were treated. Facial volume loss scale scores dropped significantly from a mean value of 3.1 at baseline to 1.3 at Day 1. Significant volume enhancement was maintained at each follow-up visit with mean scores ranging from 1.3 at Month 1 to 1.8 at Month 12. Investigators’ global aesthetic improvement scale assessment showed that up to Month 6 at least 94 percent of patients were rated as “very much improved” or “much improved.” At Month 9, all patients still showed a benefit of treatment with 81 percent rated as “very much” or “much improved” and 19 percent as “improved.” Patients’ evaluation was consistent with investigators’ results. A few expected transient injection site reactions of mild-to-moderate intensity were reported immediately after treatment. These reactions were considered related to the injection procedure, rather than the product. Conclusion: Cohesive Polydensified Matrix Hyaluronic Acid Volumizer is safe and effective for mid-face volume augmentation lasting up to Month 12 and most probably up to Month 18. The aesthetic effect was demonstrated by the effectiveness evaluations and high patient satisfaction. (J Clin Aesthet Dermatol. 2015;8(3):28–34.)
ith an increase in average life expectancy and a historical strive for beauty, a growing interest in methods to achieve a natural, rejuvenated, and youthful appearance is expressed by many individuals worldwide. Minimally invasive non-permanent rejuvenation methods, such as injectable dermal fillers based on cross-linked sodium hyaluronate have become one of the most frequently performed aesthetic procedures.1 They represent a versatile and elegant tool for facial sculpting, contouring, and treatment of facial wrinkles. Currently available fillers differ in composition, duration of action, palpability, administration techniques, complications, and other factors.2 Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan with a strong hydrophilic capacity. In the dermal extracellular matrix it provides structural
W
support and plays a role in nutrient exchange as well as adding volume and fullness to the skin.3,4 Natural HA in the skin has an extremely rapid rate of turn-over, mostly due to catabolism by endogeneous hyaluronidases.5 Therefore, commercially available HAs are stabilized by different manufacturing technologies. As a result, the products vary in formulation, concentration, and degree of crosslinking. These properties affect the duration of action as well as post-procedural risks of swelling.2 Cohesive Polydensified Matrix® (CPM®) Hyaluronic Acid (HA) Volumizer (Modélis® SHAPE, Anteis S.A, Geneva, Switzerland; also commercialized as Belotero® Volume, Merz Pharmaceuticals GmbH, Frankfurt, Germany) is a CE-marked dermal filler manufactured with the patented CPM technology. It is composed of 26mg/mL HA from biofermentation origin cross-linked with 1,4-butanediol
DISCLOSURE: Drs. Micheels and Vandeputte are consultants for Anteis S.A. Dr. Kravtsov is an emploee of Anteis S.A. The evaluation was sponsored by Anteis S.A. The post-marketing clinical follow-up was sponsored by Anteis S.A. Analysis of the results as well as scientific writing was supported by Anteis S.A and Merz Pharmaceuticals GmbH. Statistical support was offered by Moritz Heinz from Merz Pharmaceuticals GmbH. ADDRESS CORRESPONDENCE TO: Joan Vandeputte, MD; E-mail: [email protected]
28
[March 2015 • Volume 8 • Number 3]
28
diglycidyl ether (BDDE). CPM HA volumizer is designed to be injected subcutaneously or in deeper soft tissue layers to restore facial volumes. The CPM technology creates a product with variable cross-linking densities within the gel, where denser areas ensure volumizing effect and less dense areas ensure cohesivity of the matrix. These properties allow the gel to be easily extruded through the needle during the injection and prevent it from migrating once implanted. CPM HA volumizer is also characterized by the plasticity of the gel, which allows the practitioner to mold and sculpt the product easily into the desired shape once injected in order to achieve optimal aesthetic results. Facial volume loss is one of the major signs of aging, but it can also be inherited or acquired through disease or trauma.6 During facial aging, the atrophy of the underlying skeleton becomes prominent and subcutaneous cell components (fat, muscle, and fascia) progressively break down resulting in an altered shape and relative position of the fat pads.7–9 Volumetric changes in the mid-face area are associated with a sad and tired look. Enhancement of the lateral cheek hollows and cheekbone area recreates midface volume, smoothens nasolabial folds, and gives a more harmonious appearance associated with a younger age.10,11 The objective of this post-marketing clinical follow-up was to confirm the safety and effectiveness of CPM HA volumizer for enhancement of the lateral cheek hollows and cheekbone area. The durability of the aesthetic effect was evaluated up to 18 months.
The effectiveness and safety of the CPM HA volumizer were evaluated per side by both patients and investigators immediately after injection and at all follow-up visits performed at Months 1, 3, 6, 9, 12, and optionally at Month 18. Investigators took photographs and evaluated device effectiveness based on FVLS at each visit. Investigators and patients evaluated device effectiveness based on global aesthetic improvement scale (GAIS) with scores ranging from “1=very much improved” to “5=worse.”6 Additionally, patients reported their satisfaction with the treatment in a questionnaire. Safety was evaluated based on reporting of injection site reactions (ISR), including redness, pain, edema, bruising, itching, firmness/induration, coloration/discoloration, necrosis, and infection. The intensity of each ISR was rated from “0” to “+++” depending on the severity of the observed reactions. The attendance at the follow-up visits by patients was as follows: Month 1=20 patients, Month 3 and Month 6=18 patients, Month 9=16 patients, Month 12=20 patients, optional Month 18=11 patients. The statistical analysis was performed in an explorative manner using observed cases. Patients’ individual values were calculated using the mean between left and right side scores. For effectiveness assessments, summaries in the form of mean (+/- standard deviation [SD]) are presented. In addition, explorative pvalues for a two-sided t-test for paired samples have been taken to compare the values from baseline and follow-up visits.
MATERIALS AND METHODS
RESULTS
The evaluation was conducted in two private practices located in Belgium and Switzerland according to the standard clinical practice procedures and with respect to the product’s instructions for use. Patients were recruited at the discretion of the investigators who obtained their written informed consent prior to the treatment. Baseline and injection visits were performed on the same day. Patients received injections of CPM HA volumizer for treatment of age-related facial volume loss in the lateral cheek hollows, cheekbone area, or both up to an optimal correction. Investigators determined the appropriate volume to inject based on clinical experience and severity of facial depressions, as well as the area of injection. An optional touch-up injection could be performed if deemed necessary. No anaesthetics were used during the procedures. At the baseline and the injection visit, investigators recorded patient’s age, treated area, and volume of the injected product per side. At baseline, patients were rated on the facial volume loss scale (FVLS).6 The grades were attributed as follows: 1=mild flattening/no visibility of underlying tissue; 2=intermediate between mild and moderate; 3=moderate concavity of one or more facial regions/prominence of bony landmarks/may have visibility of underlying musculature; 4=intermediate between moderate and severe; 5=severe indentation of one or more facial regions/clear visibility of underlying tissue.
Twenty patients (n=20) of both genders with a mean age of 57 years (range from 28 to 73 years) were treated with CPM HA volumizer for facial volume enhancement. A total of eight patients received injections only in their lateral cheek hollows with a mean product volume of 2.1mL for both sides of the face. A total of six patients received injections only in their cheekbone area with a mean product volume of 2.1mL for both sides of the face. A total of six patients received injections in their lateral cheek hollows and cheekbone area with a mean product volume of 3.37mL for both sides of the face. Two patients received a touch-up in the lateral cheek hollows, one in the cheekbone area, and one at both sites. Investigators used both needles and cannulae at their discretion. One of the investigators started injecting with the deposition of an anterior bolus no larger than 0.3mL per side in the levator anguli oris muscle origin with a sharp 22g needle. Most of the product was injected on the periosteum by introducing a 22g cannula medially in the deep medial cheek fat pad, then crossing the zygomatic muscles origin and moving deep in the middle and lateral superficial cheek fat pad overlying the zygomatic arch. The product was released while retracing the cannula. Finally, a retrograde injection of no more than 0.2mL per side was performed over the anterior maxilla in the linear anterior cheek depression. The rigidity and length of a 22g cannula allowed easy penetration into all injected
[March 2015 • Volume 8 • Number 3]
29
Figure 1. Mean FVLS results as evaluated by the investigators. Mean FVLS score per patient was used to calculate an overall mean score for all patients per visit; * p
RESEARCH]
Treatment of Age-related Mid-face Atrophy by Injection of Cohesive Polydensified Matrix Hyaluronic Acid Volumizer PATRICK MICHEELS, MD; bJOAN VANDEPUTTE, MD; aMARIA KRAVTSOV, MSc
a
a
Geneva, Switzerland; bOudenaarde, Belgium
ABSTRACT Objective: Cohesive Polydensified Matrix® Hyaluronic Acid Volumizer is designed to be injected subcutaneously or in deeper soft tissue layers to restore facial volumes. This post-marketing clinical follow-up was performed to confirm the safety and effectiveness of the product up to 18 months. Design: Injections were performed according to standard clinical practice and patients were followed-up at Months 1, 3, 6, 9, 12, and optionally at Month 18. Effectiveness measures included facial volume loss scale, global aesthetic improvement scale and patients’ satisfaction. Injection site reactions were recorded to evaluate safety. Results: Twenty patients with intermediate-to-severe volume loss in the lateral cheek hollows and/or cheekbone area were treated. Facial volume loss scale scores dropped significantly from a mean value of 3.1 at baseline to 1.3 at Day 1. Significant volume enhancement was maintained at each follow-up visit with mean scores ranging from 1.3 at Month 1 to 1.8 at Month 12. Investigators’ global aesthetic improvement scale assessment showed that up to Month 6 at least 94 percent of patients were rated as “very much improved” or “much improved.” At Month 9, all patients still showed a benefit of treatment with 81 percent rated as “very much” or “much improved” and 19 percent as “improved.” Patients’ evaluation was consistent with investigators’ results. A few expected transient injection site reactions of mild-to-moderate intensity were reported immediately after treatment. These reactions were considered related to the injection procedure, rather than the product. Conclusion: Cohesive Polydensified Matrix Hyaluronic Acid Volumizer is safe and effective for mid-face volume augmentation lasting up to Month 12 and most probably up to Month 18. The aesthetic effect was demonstrated by the effectiveness evaluations and high patient satisfaction. (J Clin Aesthet Dermatol. 2015;8(3):28–34.)
ith an increase in average life expectancy and a historical strive for beauty, a growing interest in methods to achieve a natural, rejuvenated, and youthful appearance is expressed by many individuals worldwide. Minimally invasive non-permanent rejuvenation methods, such as injectable dermal fillers based on cross-linked sodium hyaluronate have become one of the most frequently performed aesthetic procedures.1 They represent a versatile and elegant tool for facial sculpting, contouring, and treatment of facial wrinkles. Currently available fillers differ in composition, duration of action, palpability, administration techniques, complications, and other factors.2 Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan with a strong hydrophilic capacity. In the dermal extracellular matrix it provides structural
W
support and plays a role in nutrient exchange as well as adding volume and fullness to the skin.3,4 Natural HA in the skin has an extremely rapid rate of turn-over, mostly due to catabolism by endogeneous hyaluronidases.5 Therefore, commercially available HAs are stabilized by different manufacturing technologies. As a result, the products vary in formulation, concentration, and degree of crosslinking. These properties affect the duration of action as well as post-procedural risks of swelling.2 Cohesive Polydensified Matrix® (CPM®) Hyaluronic Acid (HA) Volumizer (Modélis® SHAPE, Anteis S.A, Geneva, Switzerland; also commercialized as Belotero® Volume, Merz Pharmaceuticals GmbH, Frankfurt, Germany) is a CE-marked dermal filler manufactured with the patented CPM technology. It is composed of 26mg/mL HA from biofermentation origin cross-linked with 1,4-butanediol
DISCLOSURE: Drs. Micheels and Vandeputte are consultants for Anteis S.A. Dr. Kravtsov is an emploee of Anteis S.A. The evaluation was sponsored by Anteis S.A. The post-marketing clinical follow-up was sponsored by Anteis S.A. Analysis of the results as well as scientific writing was supported by Anteis S.A and Merz Pharmaceuticals GmbH. Statistical support was offered by Moritz Heinz from Merz Pharmaceuticals GmbH. ADDRESS CORRESPONDENCE TO: Joan Vandeputte, MD; E-mail: [email protected]
28
[March 2015 • Volume 8 • Number 3]
28
diglycidyl ether (BDDE). CPM HA volumizer is designed to be injected subcutaneously or in deeper soft tissue layers to restore facial volumes. The CPM technology creates a product with variable cross-linking densities within the gel, where denser areas ensure volumizing effect and less dense areas ensure cohesivity of the matrix. These properties allow the gel to be easily extruded through the needle during the injection and prevent it from migrating once implanted. CPM HA volumizer is also characterized by the plasticity of the gel, which allows the practitioner to mold and sculpt the product easily into the desired shape once injected in order to achieve optimal aesthetic results. Facial volume loss is one of the major signs of aging, but it can also be inherited or acquired through disease or trauma.6 During facial aging, the atrophy of the underlying skeleton becomes prominent and subcutaneous cell components (fat, muscle, and fascia) progressively break down resulting in an altered shape and relative position of the fat pads.7–9 Volumetric changes in the mid-face area are associated with a sad and tired look. Enhancement of the lateral cheek hollows and cheekbone area recreates midface volume, smoothens nasolabial folds, and gives a more harmonious appearance associated with a younger age.10,11 The objective of this post-marketing clinical follow-up was to confirm the safety and effectiveness of CPM HA volumizer for enhancement of the lateral cheek hollows and cheekbone area. The durability of the aesthetic effect was evaluated up to 18 months.
The effectiveness and safety of the CPM HA volumizer were evaluated per side by both patients and investigators immediately after injection and at all follow-up visits performed at Months 1, 3, 6, 9, 12, and optionally at Month 18. Investigators took photographs and evaluated device effectiveness based on FVLS at each visit. Investigators and patients evaluated device effectiveness based on global aesthetic improvement scale (GAIS) with scores ranging from “1=very much improved” to “5=worse.”6 Additionally, patients reported their satisfaction with the treatment in a questionnaire. Safety was evaluated based on reporting of injection site reactions (ISR), including redness, pain, edema, bruising, itching, firmness/induration, coloration/discoloration, necrosis, and infection. The intensity of each ISR was rated from “0” to “+++” depending on the severity of the observed reactions. The attendance at the follow-up visits by patients was as follows: Month 1=20 patients, Month 3 and Month 6=18 patients, Month 9=16 patients, Month 12=20 patients, optional Month 18=11 patients. The statistical analysis was performed in an explorative manner using observed cases. Patients’ individual values were calculated using the mean between left and right side scores. For effectiveness assessments, summaries in the form of mean (+/- standard deviation [SD]) are presented. In addition, explorative pvalues for a two-sided t-test for paired samples have been taken to compare the values from baseline and follow-up visits.
MATERIALS AND METHODS
RESULTS
The evaluation was conducted in two private practices located in Belgium and Switzerland according to the standard clinical practice procedures and with respect to the product’s instructions for use. Patients were recruited at the discretion of the investigators who obtained their written informed consent prior to the treatment. Baseline and injection visits were performed on the same day. Patients received injections of CPM HA volumizer for treatment of age-related facial volume loss in the lateral cheek hollows, cheekbone area, or both up to an optimal correction. Investigators determined the appropriate volume to inject based on clinical experience and severity of facial depressions, as well as the area of injection. An optional touch-up injection could be performed if deemed necessary. No anaesthetics were used during the procedures. At the baseline and the injection visit, investigators recorded patient’s age, treated area, and volume of the injected product per side. At baseline, patients were rated on the facial volume loss scale (FVLS).6 The grades were attributed as follows: 1=mild flattening/no visibility of underlying tissue; 2=intermediate between mild and moderate; 3=moderate concavity of one or more facial regions/prominence of bony landmarks/may have visibility of underlying musculature; 4=intermediate between moderate and severe; 5=severe indentation of one or more facial regions/clear visibility of underlying tissue.
Twenty patients (n=20) of both genders with a mean age of 57 years (range from 28 to 73 years) were treated with CPM HA volumizer for facial volume enhancement. A total of eight patients received injections only in their lateral cheek hollows with a mean product volume of 2.1mL for both sides of the face. A total of six patients received injections only in their cheekbone area with a mean product volume of 2.1mL for both sides of the face. A total of six patients received injections in their lateral cheek hollows and cheekbone area with a mean product volume of 3.37mL for both sides of the face. Two patients received a touch-up in the lateral cheek hollows, one in the cheekbone area, and one at both sites. Investigators used both needles and cannulae at their discretion. One of the investigators started injecting with the deposition of an anterior bolus no larger than 0.3mL per side in the levator anguli oris muscle origin with a sharp 22g needle. Most of the product was injected on the periosteum by introducing a 22g cannula medially in the deep medial cheek fat pad, then crossing the zygomatic muscles origin and moving deep in the middle and lateral superficial cheek fat pad overlying the zygomatic arch. The product was released while retracing the cannula. Finally, a retrograde injection of no more than 0.2mL per side was performed over the anterior maxilla in the linear anterior cheek depression. The rigidity and length of a 22g cannula allowed easy penetration into all injected
[March 2015 • Volume 8 • Number 3]
29
Figure 1. Mean FVLS results as evaluated by the investigators. Mean FVLS score per patient was used to calculate an overall mean score for all patients per visit; * p
