Hyaluronic acid gel (Juvederm ™) preparations
`in the treatment of facial wrinkles and folds
`
`REVIEW
`
`lnja Bogdan Allemann
`Leslie Baumann
`
`University of Miami Cosmetic Group,
`Leonard M. Miller School of Medicine,
`Miami Heart Institute, Miami Beach,
`Florida, USA
`
`Correspondence: Leslie Baumann
`Director, University of Miami Cosmetic
`Group, Leonard M. Miller School of
`Medicine, Miami Heart Institute, 470 I N.
`Meridian Avenue, Nichol Bldg., Suite 7450,
`Miami Beach, Florida 33140, USA
`Tel +I 305 532 5552
`Fax+ I 305 534 5224
`Email lbmd@derm.net
`
`Abstract: Soft tissue augmentation with temporary dermal fillers is a continuously growing field,
`supported by the ongoing development and advances in technology and biocompatibility of the
`products marketed. The longer lasting, less immunogenic and thus more convenient hyaluronic
`acid (HA) fillers are encompassing by far the biggest share of the temporary dermal filler market.
`Since the approval of the first HA filler, Restylane®, there are at least 10 HA fillers that have
`been approved by the FDA. Not all of the approved HA fillers are available on the market,
`and many more are corning. The Juvederm™ product line (Allergan, Irvine, CA), consisting
`of Juvederm™ Plus and Juvederm™ Ultra Plus, was approved by the FDA in 2006. Juvederm™
`is a bacterium-derived nonanimal stabilized HA. Juvederm™ Ultra and Ultra Plus are smooth,
`malleable gels with a homologous consistency that use a new technology called "Hylacross™
`technology". They have a high concentration of cross-linked HAs, which accounts for its
`longevity. Juvederm™ Ultra Plus is used for volumizing and correcting deeper folds, whereas
`Juvederm™ Ultra is best for contouring and volurnizing medium depth facial wrinkles and lip
`augmentation. Various studies have shown the superiority of the HA filler products compared
`with collagen fillers for duration, volume needed, and patient satisfaction. Restylane®, Perlane®,
`and Juvederm™ are currently the most popular dermal fillers used in the United States.
`Keywords: hyaluronic acid gel, Juvederm™, facial wrinkles, facial folds
`
`Dermal fillers have become an integral part of any aesthetic physician's intervention. The
`growing importance of the temporary dermal filler industry is reflected by the increasing
`growth in demand during the past years and a multitude of new products, which have
`come to market. According to the American Academy of Aesthetic Plastic Surgeons,
`1,448,716 people received hyaluronic acid (HA) injections by plastic surgeons in 2007.
`This number does not, however, reflect all the procedures performed, as it does not
`include the procedures performed by dermatologists or other physicians.
`The first dermal fillers used in the 1980s were animal-derived collagen fillers
`(Zyplast® and Zyderm®; Allergan, formerly lnamed). However, the need for products
`with longer clinical duration and no requirements for prior skin allergy testing lead to
`the development of the HA fillers. Of the two biologic fillers currently used- collagen
`and HAs - HAs have become the new gold standard, and have almost replaced col(cid:173)
`lagen fillers (Cosmetic Surgery National Data Bank Statistics 2005). This is explained
`by the advantages of HAs over collagen, such as its longer duration ( 6-12 months
`compared with 2-4 months), no request for skin testing, fewer allergic side effects,
`and better pliability.
`A third group of dermal fillers currently used are synthetic fillers, such as Sculptra®
`(Derrnik Laboratories, Sanofi-Aventis, Bridgewater, NJ), Radiesse® (BioForm Medical,
`San Mateo, CA), and Artefill® (Artes Medical, Inc., San Diego, CA).
`
`Clinical Interventions in Aging 2008:3(4) 629-634
`© 2008 Dove Medical Press Limited. All rights reserved
`
`629
`
`Exhibit 1035
`Prollenium v. Allergan
`
`

`

`Bogdan Allemann and Baumann
`
`HA or hyaluronan is a naturally occurring linear
`polysaccharide (Figure 1). It can be found in skin, connec(cid:173)
`tive, epithelial, and neural tissues. It is ubiquitous across
`all species and does not require skin allergy testing prior
`to injection, which makes it very convenient for daily use.
`This glycosaminoglycan has the ability to bind 1,000 times
`its volume in water, which makes it the perfect substance for
`adding volume to the skin. In humans, the amount of naturally
`occurring HA in the skin decreases with age, which plays an
`important role in the development of the aging features and
`wrinkle formation, resulting in decreased tissue elasticity and
`hydration. Unmodified, natural HA has a half-life of approxi(cid:173)
`mately 24 hours before it is enzymatically broken down and
`metabolized in the liver into byproducts, water and carbon
`dioxide (Duranti et al 1998). In the skin, HA is broken down
`by hyaluronidase and by free radicals. Supplementation with
`oral antioxidants theoretically will increase the duration of
`HA fillers, but this has not been proven. The naturally occur(cid:173)
`ring break down of HA by hyaluronidase depicts an important
`feature of the HA fillers as well as a major advantage over
`the collagen fillers, namely, rarely occurring areas of excess
`fullness, too superficial placement of the filler, or overcor(cid:173)
`rection can easily be dissolved or improved by intralesional
`injection of hylauronidase.
`Features that differentiate the various HA fillers are par(cid:173)
`ticle size, the type of crosslinking agent used, the degree of
`crosslinking, the percentage of cross-linked HA, the amount
`of free ( unmodified) HA present, and G' ( elastic modulus).
`All these physical and chemical attributes will influence the
`clinical characteristics of each filler, such as clinical indica(cid:173)
`tion, ease of injection, degree of tissue filling, longevity,
`clinical appearance, and side effects.
`Currently 6 temporary HA fillers are FDA approved and
`on the market in the US: Restylane® (Medicis, Scottsdale, AZ),
`Perlane® (Medicis, Scottsdale, AZ), Prevelle Silk® (Mentor
`Corp., Santa Barbara, CA), Hylaform Plus® (Allergan,
`Irvine, CA), Anika® (Anika Therapeutics, Inc., MA), and
`
`Figure I Structure of hyaluronic acid.
`
`630
`
`Juvederm™ (Allergan, Inc., Irvine, CA) (Table 1 ). Hylaform®
`and Captique® are no longer on the market in the US.
`Juvederm™ (Allergan, Inc., Irvine, CA), which is also
`known as Hydrafill, was approved by the FDA in June 2006
`for the correction of moderate to severe facial wrinkles and
`folds. Juvederm™ filler agents have been on the market in
`European countries and Canada since 2003 (marketed as
`Juvederm™ by the Corneal Group and by Allergan, formerly
`!named, and in some countries as Hydra Fill® by Allergan,
`formerly !named). The Juvederm™ line comprises various
`products, such as Juvederm™ 18, Juvederm™ 24, Juvederm™
`24 HV, Juvederm™ 30, and Juvederm™ 30 HV, of which only
`Juvederm™ 24 HV (also known as Juvederm™ Ultra) and
`Juvederm™ 30 HV (also known as Juvederm™ Ultra Plus)
`are available on the US market. The various products in the
`line differ in the concentration of HA as well as the amount
`and regularity of crosslinking.
`
`Particle size and sizing technology
`Juvederm™ is derived from Streptococcus equi and manu(cid:173)
`factured by a bacterial fermentation process. Juvederm™ is
`produced by a proprietary manufacturing process referred
`to as "Hylacross technology", which refers to the fact that
`Juvederm is not "sized" in contrast to the other HA fillers
`(Prevelle Silk®, Restylane®, Perlane®) which use sizing
`technology. "Sizing" is the process by which crosslinked
`HA is pushed through a specially sized screen and broken
`into pieces. The medium size pieces of HA are made into
`Restylane® while the larger ones are made into Perlane®. It is
`unknown what effect the sizing technology or the Hylacross
`technology have on a filler's performance, or if they offer
`any benefit in the efficacy of the product. Many claims
`about the benefits ofHylacross technology have been made
`without scientific substantiation. For example, Smith (2007)
`noted a difference of the homologous Juvederm™ gel fillers
`compared to fillers with gel particle suspensions, mentioned
`in his publication on the practical use of Juvederm™. He
`claimed that after injection, the Juvederm™ filler remained in
`the area where it was injected because of its cohesive nature
`and high viscosity, and did not flow away from the injection
`point. Also, in his opinion, Juvederm fills more precisely and
`more efficiently. He stated that gel-particle fillers in contrast
`seem to flow away from the injection point, causing filling
`of unintended areas and waste of product. It is important to
`realize that this is one person's opinion and has not been sub(cid:173)
`stantiated by scientific research. To the authors' knowledge,
`no studies have scientifically characterized the diffusion and
`spread of the various HA fillers.
`
`Clinical Interventions in Aging 2008:3(4)
`
`

`

`Table I Hyaluronic acid (HA) fillers: crosslinking agents and concentration of HA
`Product
`Captique
`Hylaform
`Juvederm Ultra
`and Ultra Plus
`BDDE
`
`Crosslinking agent
`
`DYS
`
`HA gel for facial wrinkles and folds
`
`Puragen
`
`Prevelle
`
`DEO
`
`DYS
`
`Restylane
`and Perlane
`BDDE
`
`DYS
`
`Concentration
`
`4.5-6.5 mg/ml
`
`4.5-6.5 mg/ml
`
`24 mg/ml
`
`20 mg/ml
`
`4.5-6.5 mg/ml
`
`20 mg/ml
`
`Abbreviations: BDDE , 1,4-butanediol diglycidyl ether; DYS, divinyl sulphone; DEO, 2, 7, 8-diepoxyoctane.
`
`HA concentration
`The amount of HA in a product may contribute to its stiffness
`and longevity. Theoretically, the higher the amount of HA
`in the product, the stiffer it is and the longer it will last.
`However, not all of the HA in the product is crosslinked so
`one must take into account the overall percentage of cross(cid:173)
`linking (how much of the HA is crosslinked) and the degree
`of crosslinking (is the HA molecule completely or partially
`crosslinked). Often, uncrosslinked HA is added to a filler
`product to increase its ease of injection as it functions as a
`lubricant. Both Juvederm™ Ultra and Ultra Plus consist of
`24 mg/mL of HA. Juvederm™ Ultra is 9% crosslinked while
`Juvederm™ Ultra Plus is 11 % crosslinked (Table 2).
`
`example more robust products (higher G ' values and higher
`cohesivities) such as Juvederm™ Ultra Plus and Perlane®,
`should be used in deeper lines, such as nasolabial folds and
`marionette lines, as well as to lift the lateral brow, to correct
`the nasal bridge, to give the ear lobe youthful volume, to evert
`the nipples, and to raise the nasal tip. More fluid products
`such as Juvederm™ Ultra and Restylane® are more suited to
`be used over large areas such as the cheekbones and cheeks.
`Low G' products such as Hylaform® and Prevelle Silk® are
`necessary in areas that require a softer agent, such as the
`body of the lip or the tear trough. As new products reach the
`market, knowing the G' will help practitioners match fillers
`with indications.
`
`Type of crosslinking agent used
`The crosslinking agent used in Juvederm™ is 1,4-butanediol
`diglycidyl ether (BDDE). Other fillers are cross-linked
`with different crosslinking agents, such as divinyl sulphone
`(DVS) for Prevelle®, Captique®, and Hylaform®. Puragen®
`is cross-linked with 2, 7, 8-diepoxyoctane (DEO), which
`forms both ether and ester crosslinks. Crosslinking quality
`has to be in the right balance to maintain both duration and
`the biocompatibility of the HA filler. Each crosslinking agent
`has characteristics that affect the performance of the filler.
`
`Elastic modules
`The stiffness or G' (pronounced G prime) of a product is one
`of the most important considerations. G' is a measurement of
`gel hardness. It is obtained when a gel is placed on a plate.
`A second plate is placed over the gel and a lateral force is
`applied. The measurement of resistance to deformation is
`known as the elastic modulus or the G'. Together with the
`cohesivity of the product, G' values could be used to deter(cid:173)
`mine the appropriate placement of an HA dermal filler. For
`
`Recommended injection sites
`In contrast to Juvederm™ Ultra, Juvederm™ Ultra Plus has
`a higher proportion ( 11 % ) of crosslinked HA, which makes
`Ultra Plus more viscous. Consequently, Ultra Plus is more
`suitable for adding volume and correcting the deeper facial
`grooves and furrows, whereas JuvedermT"' Ultra is best suited
`for contouring and volumizing facial wrinkles and folds
`(Figures 2 and 3) (FDA 2006). Juvederm™ Ultra and Ultra
`Plus can be grouped in the medium range of product stiff(cid:173)
`ness, which makes them suitable for the use in any wrinkles,
`moderate or deep, as well as scar correction. Both Juvederm™
`products contain unmodified or uncross-linked, free HA.
`Unmodified HA is included as a lubricant to help decrease
`extrusion force and make injection easier. Juvederm™ Ultra
`is injected into the mid-dermis via 30-gauge needle while
`Juvederm™ Ultra Plus is implanted deeper via a 27-gauge
`needle. It is important to tightly attach the needles to the
`Luer-lock syringe to prevent detachment during injections.
`Various techniques of injection can be used with Juvederm™·
`including serial puncture and tunneling. As Juvederm™ is not
`
`Table 2 Percentage crosslinking in Juvederm ™ products
`Juvederm 30
`
`Juvederm 24 HY (Ultra)
`
`Juvederm 30 HY (Ultra Plus)
`
`Concentration
`
`Crosslinking rate
`
`24 mg/g
`
`9%
`
`24 mg/g
`
`9%
`
`24 mg/g
`11%
`
`Clinical Interventions in Aging 2008:3(4)
`
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`

`

`Bogdan Allemann and Baumann
`
`Figure 2 Before Juvederm ™ to the Marionette lines.
`
`completely hydrated with water in the syringe, and HA is
`well known to be able to bind 1,000 times its weight in water,
`Juvederm ™ will absorb water after injections and thus slightly
`expand within 24 hours after correction. The patients can thus
`be informed, that the effect will be "even better" 24 hours
`after the injection. However, it is important to consider this
`feature in clinical practice, especially when injecting the
`body of the lips, therefore one should always undercorrect
`to allow for expansion. Restylane® and Puragen® are also
`not completely hydrated in the syringe, whereas Captique®,
`Hylaform®, and Prevelle® are completely hydrated and will
`not expand after injection.
`The longevity of Juvederm™ Ultra is about 6-9 months
`and Ultra Plus may last up to 12 months, which is similar
`to Restylane® and Perlane®. Captique® and Prevelle Silk®
`are thought to last 4--6 months and the duration of Puragen®
`is unknown at the time of publication of this article. Both
`Juvederm™ products are packaged in 0.8-mL syringes as a
`clear gel and are stored at room temperature with a shelf-life
`
`Figure 3 24 hours after Juvederm ™ Ultra to right Marionette line.
`
`of 24 months. The adverse-event profile of Juvederm™ is
`mild and transient. As with all HA products, Juvederm™ can
`cause erythema, swelling, and bruising after implantation. As
`Juvederm™ Ultra and Ultra Plus lack an anesthetic, patients do
`feel pain during injection. Therefore, a topical anesthetic or a
`nerve block can be used to minimize discomfort.
`Both Juvederm™ Ultra and Ultra Plus have been approved
`for use in the nasolabial folds. In the authors' experience,
`both products may also be used off-label for lip augmenta(cid:173)
`tion, for the correction of marionette folds, prejugal sulci, and
`as volume fillers for atrophy and acne scars. Furthermore,
`Juvederm™ can be placed in the tear trough area, but extra
`care is necessary, due to the proximity to the eye with the
`risk of the needle popping off, thus one should inject very
`slowly with only moderate extrusion force. The needle is
`more likely to pop off when the syringe is almost empty so
`inject the tear trough area with a new syringe and save the
`last part of the syringe for less dangerous areas such as the
`nasolabial folds. Too superficial injections of Juvederm™ can
`result in a bluish hue. Juvederm™ Ultra can easily be placed
`in the vermillion border or the body of the lip. Again, one
`should be cautious as not to over-inject the verrnillion border
`due to postponed expansion of the product.
`As Juvederm™ has been on the US marked only since
`late 2006, only a few publications have assessed the vari(cid:173)
`ous characteristics of the Juvederm™ products. These are
`reviewed below.
`
`Review of publications
`In the pivotal trial that led to FDA approval of Juvederm™,
`Baumann et al (2007) compared the safety and effective(cid:173)
`ness of 3 types of smooth-gel HA dermal fillers vs cross(cid:173)
`linked collagen in the treatment of NLF in 439 subjects in
`a multicenter, double-masked, randomized, within-subject
`study. The subjects randomly received one of three types of
`smooth-gel HA dermal filler in one NLF and cross-linked
`bovine collagen in the other. The three different smooth-gel
`HAs used were J30 (Juvederm™ 30), 24 HV (Juvederm™
`Ultra), or 30 HV (Juvederm™ Ultra Plus), of which only the
`latter two are currently marketed in the US. The cross-linked
`bovine collagen filler used was Zyplast® (Allergan, formerly
`!named). The NLFs were to be filled to full correction (100%
`of the defect), and not overcorrected, and a maximum of
`3 treatments - first treatment and up to 2 touch-ups at
`roughly 2-week intervals - were allowed to achieve optimal
`correction. NLF severity was assessed using the 5-point Wrinkle
`Assessment Scale (WAS), with 0 = none (no wrinkle);
`1 = mild (shallow, just perceptible wrinkle); 2 = moderate
`
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`Clinical Interventions in Aging 2008:3(4)
`
`

`

`(moderately deep wrinkle); 3 = severe (deep wrinkle, well(cid:173)
`defined edges but not overlapping); 4 = extreme (very deep
`wrinkle, redundant fold with overlapping skin). The results
`showed that all three dermal fillers proved longer-lasting
`clinical corrections than bovine collagen. Twenty-four weeks
`after the last treatment, 90% of subjects treated with 30 HV
`(Juvederm™ Ultra Plus) dermal filler retained a clinically
`significant improvement, 88% treated with 24 HV (Juve(cid:173)
`derm™ Ultra) and 81 % with BO dermal filler. The bovine
`collagen-treated NLFs showed clearly shorter longevity
`with lasting improvement after 24 weeks ranging from 36%
`to 45%. In addition to its superior longevity, the injection
`volume for HA dermal fillers proved to be lower (median,
`1.6 mL) compared with bovine collagen (median, 2.0 mL),
`representing an additional important advantage for the patient
`in treatment costs and comfort. The only treatment-related
`adverse events observed were localized site reactions in the
`area of injection, which were mild to moderate in severity
`and did not differ between any filler type. In decreasing
`percentage those were injection site induration, erythema,
`edema, pain, nodule formation, bruising, discoloration, and
`pruritus; they lasted no more than 7 days. The preferred filler
`by the patients used was 24 HV (Juvederm™ Ultra) with 88%,
`followed by 84% for 30 HV (Juvederm TM Ultra Plus) and 78%
`for BO; the majority of subjects preferred HA fillers to the
`collagen fillers.
`In an almost identical study design (Pinsky et al 2007),
`the safety and effectiveness of JuvedermTM dermal fillers
`compared to Zyplast® bovine collagen for the correction
`of nasolabial folds (NLFs) was assessed in a multicenter,
`double-blind, randomized, within-subject controlled trial.
`292 subjects were randomly treated with Juvederm™ Ultra
`or JuvedermTM Ultra Plus in one NLF and Zyplast® bovine
`collagen in the other NLF. The treating investigators were
`instructed to fill each NLF to full correction (100% of the
`defect), but not to overcorrect. A maximum of 3 treatments
`- first treatment and up to 2 touch-ups at roughly 2-week
`intervals - were allowed to achieve optimal correction.
`An average injection volume of 1.5 mL (2 syringes) of
`Juvederm™ dermal filler was used for initial treatment and
`0.7 mL (1 syringe) for repeat treatment. NLF severity was
`assessed using the 5-point Wrinkle Assessment Scale (WAS),
`and a validated photographic guide. After 6 month subjects
`showed a clinically significant mean level of improvement
`for the NLFs treated with Juvederm™ Ultra or Juvederm™
`Ultra Plus, but not for NLF s treated with Z yplast®, supporting
`the above stated findings by showing a longer longevity for
`JuvedermTM Ultra and Ultra Plus than for Zyplast®. The mean
`
`HA gel for facial wrinkles and folds
`
`level of improvement was still clinically significant for
`subjects who returned for a follow-up treatment beyond
`9 months, with the proportion ofNLFs still showing clinically
`significant improvement in 75% with Juvederm™ Ultra and
`81 % with Juvederm™ Ultra Plus. Juvederm™ Ultra Plus was
`shown to last even 12 months or longer. Again, the frequency
`and severity of treatment site reactions ( eg, erythema, indura(cid:173)
`tion, pain, edema, nodule formation, bruising, pruritus, and
`discoloration) were mild or moderate and were similar for all
`fillers. The authors concluded, that due to its superior longev(cid:173)
`ity, individuals treated with these Juvederm™ dermal fillers
`may require to repeat treatments less frequently than those
`treated with bovine collagen fillers, and that less product will
`be needed at repeat treatments.
`The results of the above mentioned studies are supported
`by a recent study by Lupo et al which compared Juvederm ™
`Ultra Plus HA filler with Zyplast® bovine collagen in a mul(cid:173)
`ticenter, double-blind, randomized, within-subject, controlled
`study (Lupo et al 2008). In a split face mode, severe NLFs
`of87 subjects were treated, one side with Juvederm™ Ultra
`Plus and the other side with Zyplast®. In the study popula(cid:173)
`tion all Fitzpatrick skin types were represented, 36% having
`darker skin types (Fitzpatrick types IV through VI). Up to
`two touch-up treatments were allowed at 2-week intervals.
`Effectiveness was assessed using the validated, static, 5-point
`Wrinkle Assessment Scale (WAS) with a photographic guide.
`The Juvederm™ Ultra Plus filler showed significantly better
`NLF severity scores compared to Zyplast® at each follow-up
`time point from 4 to 24 weeks. At 24-week follow-up clini(cid:173)
`cally significant correction ofNLF treated with JuvedermTM
`were shown in 96% compared with 41% Zyderm®. The
`clinical correction with Juvederm TM Ultra Plus remained high,
`whereas the scores for Zyplast® nearly returned to baseline
`over the period of 24 weeks. At 24 weeks, the mean improve(cid:173)
`ment was still 1.7 with the Juvederm™ Ultra Plus product
`but only 0.5 with bovine collagen. Longevity was shown by
`maintenance of the clinical correction for 1 year or more in
`81 % ofNLFs treated with Juvederm™. The median volume of
`Juvederm TM required was 0. 7 mL ( one syringe), significantly
`less than for Zyplast® (1.6 mL). For the initial treatment,
`the median volume of Juvederm™ Ultra Plus injected was
`2 syringes (1.6 mL), and less than 1 syringe (0.7 mL) for the
`retreatment at after 6-9 months.
`Treatment site reactions were similar for Juvederm TM Ultra
`Plus and Zyplast® and were similar to those in the above(cid:173)
`mentioned trials. As for patient satisfaction, most subjects
`preferred Juvederm™ Ultra Plus (85%) versus collagen
`(10%); 5% showed no preference.
`
`Clinical Interventions in Aging 2008:3(4)
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`

`Bogdan Allemann and Baumann
`
`Table 3 Factors to consider when choosing an hyaluronic acid
`(HA) filler
`
`Concentration of HA
`
`Cost
`
`Choices of syringe size
`
`Degree of crosslinking
`
`Design of the syringe
`
`Duration of correction
`
`G prime (stiffness)
`
`How much of the HA is crosslinked vs uncrosslinked
`
`Hydration level of product in the syringe
`
`Presence of lidocaine
`
`Required needle size for injection
`
`Sizing technology
`
`Type of crosslinking technology used
`
`In summary, all three studies above show superior longevity
`of the HA Juvederm™ fillers compared to bovine collagen
`fillers. Juvederm ™ Ultra Plus was shown to exert longer lasting
`clinical results than Juvederm™ Ultra. Initial treatments required
`roughly two syringes of Juvederm ™, and retreatments required
`only one syringe. Volumes required for collagen were higher
`throughout the studies. Treatment site reactions and side effects
`were similar for all fillers, HA and collagen, and were always
`short in duration (less than 7 days) and mild in severity. Most
`patients seem to prefer Juvederm™ fillers to bovine collagen.
`Juvederm™ Ultra Plus was compared with Radiesse® in an
`European study by Moers-Capri et al (2007) that compared the
`hydroxylapatite filler with two HA fillers for the treatment of
`the nasolabial folds. The objective of this multicenter, blinded,
`randomized trial was to compare patient satisfaction, efficacy
`and durability of the various fillers. A total of 205 patients
`were randomized into 3 arms, receiving Radiesse® (CaHA
`gel), Juvederm™ Ultra, or Perlane®. After the first treatment
`a touch-up was performed 4 months later and patients were
`followed up at 8, and 12 months, without any additional touch(cid:173)
`ups. The injections were performed with a 27-gauge needle
`into the mid to deep dermis. At 8 months follow-up, NLFs
`treated with CaHA gel were significantly more improved, than
`with any HA, as assessed by Global Aesthetic Improvement
`
`Scale (GAIS) (Narins et al 2003). Moreover, the volumes
`used for CaHA gel were lower than for the HAs. In the patient
`satisfaction CaHA consistently scored highest, and Juvederm™
`scored lowest, even lower than Perlane®.
`There are many factors to be understood, in order to know
`which HA filler to use (Table 3). Because no peer-reviewed
`scientific publications have reviewed the above-mentioned
`properties, it is impossible at this point to know how
`important these various characteristics are in choosing a
`filler. More data need to be collected to properly understand
`if, for example, sizing technology makes a difference or if
`ester bonds last longer than ether bonds. These distinctions
`will become clearer and more important as more HA fillers
`reach the market and more data are collected.
`
`Disclosures
`None of the authors has any conflicts to disclose.
`
`References
`Cosmetic Surgery National Data Bank Statistics. 2005. Los Alamitos (CA):
`American Society of Aesthetic Plastic Surgery [ online]. Accessed 2006
`Jun 7. URL: http://www.surgery.org/download/2005stats.pdf
`Duranti F, Salti G, Bovani B, et al. 1998. Injectable hyaluronic acid gel for
`soft-tissue augmentation: A clinical and histological study. Dermatol
`Surg,24:1317.
`Smith KC. 2007. Practical use of Juvederm: early experience. Plast Reconstr
`Surg, 120(Suppl):67S-73S.
`[FDA] Food and Drug Administration. 2006. Summary of safety and
`effectiveness data. Rockville (MD) [online]. Accessed 2006 Aug 23.
`URL: http://www.fda.gov/cdrh/ pdf5/p050047b.pdf
`Baumann LS, Shamban AT, Lupo MP, et al. 2007. Juvederm vs Zyplast,
`Nasolabial Fold Study Group. Comparison of smooth-gel hyaluronic
`acid dermal fillers with cross-linked bovine collagen: a multicenter,
`double-masked, randomized, within-subject study. Dermatol Surg,
`33(Suppl 2):Sl28- 35.
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