Hyaluronic acid gel ( Juvéderm™) preparations
`in the treatment of facial wrinkles and folds
`
`R E V I E W
`
`Inja 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, 4701 N.
`Meridian Avenue, Nichol Bldg., Suite 7450,
`Miami Beach, Florida 33140, USA
`Tel +1 305 532 5552
`Fax +1 305 534 5224
`Email lbmd@derm.net
`
`Abstract: Soft tissue augmentation with temporary dermal fi llers is a continuously growing fi eld,
`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) fi llers are encompassing by far the biggest share of the temporary dermal fi ller market.
`Since the approval of the fi rst HA fi ller, Restylane®, there are at least 10 HA fi llers that have
`been approved by the FDA. Not all of the approved HA fi llers are available on the market,
`and many more are coming. The Juvéderm™ product line (Allergan, Irvine, CA), consisting
`of Juvéderm™ Plus and Juvéderm™ Ultra Plus, was approved by the FDA in 2006. Juvéderm™
`is a bacterium-derived nonanimal stabilized HA. Juvéderm™ 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. Juvéderm™ Ultra Plus is used for volumizing and correcting deeper folds, whereas
`Juvéderm™ Ultra is best for contouring and volumizing medium depth facial wrinkles and lip
`augmentation. Various studies have shown the superiority of the HA fi ller products compared
`with collagen fi llers for duration, volume needed, and patient satisfaction. Restylane®, Perlane®,
`and Juvéderm™ are currently the most popular dermal fi llers used in the United States.
`Keywords: hyaluronic acid gel, Juvéderm™, facial wrinkles, facial folds
`
`Dermal fi llers have become an integral part of any aesthetic physician’s intervention. The
`growing importance of the temporary dermal fi ller industry is refl ected 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, refl ect all the procedures performed, as it does not
`include the procedures performed by dermatologists or other physicians.
`The fi rst dermal fi llers used in the 1980s were animal-derived collagen fi llers
`(Zyplast® and Zyderm®; Allergan, formerly Inamed). However, the need for products
`with longer clinical duration and no requirements for prior skin allergy testing lead to
`the development of the HA fi llers. Of the two biologic fi llers currently used – collagen
`and HAs – HAs have become the new gold standard, and have almost replaced col-
`lagen fi llers (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 fi llers currently used are synthetic fi llers, such as Sculptra®
`(Dermik Laboratories, Sanofi -Aventis, Bridgewater, NJ), Radiesse® (BioForm Medical,
`San Mateo, CA), and Artefi ll® (Artes Medical, Inc., San Diego, CA).
`
`Clinical Interventions in Aging 2008:3(4) 629–634
`© 2008 Dove Medical Press Limited. All rights reserved
`
`629
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`Page 1
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`

`

`Bogdan Allemann and Baumann
`
`HA or hyaluronan is a naturally occurring linear
`polysaccharide (Figure 1). It can be found in skin, connec-
`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. Unmodifi ed, natural HA has a half-life of approxi-
`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 fi llers, but this has not been proven. The naturally occur-
`ring break down of HA by hyaluronidase depicts an important
`feature of the HA fi llers as well as a major advantage over
`the collagen fi llers, namely, rarely occurring areas of excess
`fullness, too superfi cial placement of the fi ller, or overcor-
`rection can easily be dissolved or improved by intralesional
`injection of hylauronidase.
`Features that differentiate the various HA fi llers are par-
`ticle size, the type of crosslinking agent used, the degree of
`crosslinking, the percentage of cross-linked HA, the amount
`of free (unmodifi ed) HA present, and G´ (elastic modulus).
`All these physical and chemical attributes will infl uence the
`clinical characteristics of each fi ller, such as clinical indica-
`tion, ease of injection, degree of tissue fi lling, longevity,
`clinical appearance, and side effects.
`Currently 6 temporary HA fi llers 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
`
`−
`COO Na+
`
`4
`
`HO
`
`O
`O
`
`HO
`
`O
`
`OH
`
`1
`1
`
`Na glucuronate
`
`Figure 1 Structure of hyaluronic acid.
`
`CH2OH
`
`O
`
`O
`
`1
`
`3
`
`NH
`C=O
`CH3
`N-acetylGlucosamine
`
`Juvéderm™ (Allergan, Inc., Irvine, CA) (Table 1). Hylaform®
`and Captique® are no longer on the market in the US.
`Juvéderm™ (Allergan, Inc., Irvine, CA), which is also
`known as Hydrafi ll, was approved by the FDA in June 2006
`for the correction of moderate to severe facial wrinkles and
`folds. Juvéderm™ fi ller agents have been on the market in
`European countries and Canada since 2003 (marketed as
`Juvéderm™ by the Corneal Group and by Allergan, formerly
`Inamed, and in some countries as Hydra Fill® by Allergan,
`formerly Inamed). The Juvéderm™ line comprises various
`products, such as Juvéderm™ 18, Juvéderm™ 24, Juvéderm™
`24 HV, Juvéderm™ 30, and Juvéderm™ 30 HV, of which only
`Juvéderm™ 24 HV (also known as Juvéderm™ Ultra) and
`Juvéderm™ 30 HV (also known as Juvéderm™ 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
`Juvéderm™ is derived from Streptococcus equi and manu-
`factured by a bacterial fermentation process. Juvéderm™ is
`produced by a proprietary manufacturing process referred
`to as “Hylacross technology”, which refers to the fact that
`Juvéderm is not “sized” in contrast to the other HA fi llers
`(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 fi ller’s performance, or if they offer
`any benefi t in the effi cacy of the product. Many claims
`about the benefi ts of Hylacross technology have been made
`without scientifi c substantiation. For example, Smith (2007)
`noted a difference of the homologous Juvéderm™ gel fi llers
`compared to fi llers with gel particle suspensions, mentioned
`in his publication on the practical use of Juvéderm™. He
`claimed that after injection, the Juvéderm™ fi ller remained in
`the area where it was injected because of its cohesive nature
`and high viscosity, and did not fl ow away from the injection
`point. Also, in his opinion, Juvéderm fi lls more precisely and
`more effi ciently. He stated that gel-particle fi llers in contrast
`seem to fl ow away from the injection point, causing fi lling
`of unintended areas and waste of product. It is important to
`realize that this is one person’s opinion and has not been sub-
`stantiated by scientifi c research. To the authors’ knowledge,
`no studies have scientifi cally characterized the diffusion and
`spread of the various HA fi llers.
`
`630
`
`Clinical Interventions in Aging 2008:3(4)
`
`
`Page 2
`
`

`

`Table 1 Hyaluronic acid (HA) fi llers: crosslinking agents and concentration of HA
`Product
`Captique
`Hylaform
`Juvéderm Ultra
`and Ultra Plus
`BDDE
`
`Crosslinking agent
`
`DVS
`
`HA gel for facial wrinkles and folds
`
`Puragen
`
`Prevelle
`
`DEO
`
`DVS
`
`Restylane
`and Perlane
`BDDE
`
`DVS
`
`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; DVS, 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-
`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 fi ller
`product to increase its ease of injection as it functions as a
`lubricant. Both Juvéderm™ Ultra and Ultra Plus consist of
`24 mg/mL of HA. Juvéderm™ Ultra is 9% crosslinked while
`Juvéderm™ Ultra Plus is 11% crosslinked (Table 2).
`
`Type of crosslinking agent used
`The crosslinking agent used in Juvéderm™ is 1,4-butanediol
`diglycidyl ether (BDDE). Other fi llers 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 fi ller. Each crosslinking agent
`has characteristics that affect the performance of the fi ller.
`
`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-
`mine the appropriate placement of an HA dermal fi ller. For
`
`example more robust products (higher G´ values and higher
`cohesivities) such as Juvéderm™ 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 fl uid products
`such as Juvéderm™ 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 fi llers
`with indications.
`
`Recommended injection sites
`In contrast to Juvéderm™ Ultra, Juvéderm™ 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 Juvéderm™ Ultra is best suited
`for contouring and volumizing facial wrinkles and folds
`(Figures 2 and 3) (FDA 2006). Juvéderm™ Ultra and Ultra
`Plus can be grouped in the medium range of product stiff-
`ness, which makes them suitable for the use in any wrinkles,
`moderate or deep, as well as scar correction. Both Juvéderm™
`products contain unmodifi ed or uncross-linked, free HA.
`Unmodifi ed HA is included as a lubricant to help decrease
`extrusion force and make injection easier. Juvéderm™ Ultra
`is injected into the mid-dermis via 30-gauge needle while
`Juvéderm™ 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 Juvéderm™,
`including serial puncture and tunneling. As Juvéderm™ is not
`
`Table 2 Percentage crosslinking in Juvéderm™ products
`Juvéderm 30
`
`Juvéderm 24 HV (Ultra)
`
`Juvéderm 30 HV (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 Juvedérm™ 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,
`Juvéderm™ 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 Juvéderm™ 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
`Juvéderm™ 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 Juvedérm™ Ultra to right Marionette line.
`
`of 24 months. The adverse-event profi le of Juvéderm™ is
`mild and transient. As with all HA products, Juvéderm™ can
`cause erythema, swelling, and bruising after implantation. As
`Juvéderm™ 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 Juvéderm™ 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-
`tion, for the correction of marionette folds, prejugal sulci, and
`as volume fi llers for atrophy and acne scars. Furthermore,
`Juvéderm™ 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 superfi cial injections of Juvéderm™ can
`result in a bluish hue. Juvéderm™ 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 vermillion border
`due to postponed expansion of the product.
`As Juvéderm™ has been on the US marked only since
`late 2006, only a few publications have assessed the vari-
`ous characteristics of the Juvéderm™ products. These are
`reviewed below.
`
`Review of publications
`In the pivotal trial that led to FDA approval of Juvéderm™,
`Baumann et al (2007) compared the safety and effective-
`ness of 3 types of smooth-gel HA dermal fi llers vs cross-
`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 fi ller in one NLF and cross-linked
`bovine collagen in the other. The three different smooth-gel
`HAs used were J30 (Juvéderm™ 30), 24 HV (Juvéderm™
`Ultra), or 30 HV (Juvéderm™ Ultra Plus), of which only the
`latter two are currently marketed in the US. The cross-linked
`bovine collagen fi ller used was Zyplast® (Allergan, formerly
`Inamed). The NLFs were to be fi lled to full correction (100%
`of the defect), and not overcorrected, and a maximum of
`3 treatments – fi rst 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)
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`

`(moderately deep wrinkle); 3 = severe (deep wrinkle, well-
`defi ned edges but not overlapping); 4 = extreme (very deep
`wrinkle, redundant fold with overlapping skin). The results
`showed that all three dermal fi llers proved longer-lasting
`clinical corrections than bovine collagen. Twenty-four weeks
`after the last treatment, 90% of subjects treated with 30 HV
`(Juvéderm™ Ultra Plus) dermal fi ller retained a clinically
`signifi cant improvement, 88% treated with 24 HV (Juvé-
`derm™ Ultra) and 81% with J30 dermal fi ller. 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 fi llers 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 fi ller 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 fi ller
`by the patients used was 24 HV (Juvéderm™ Ultra) with 88%,
`followed by 84% for 30 HV (Juvéderm™ Ultra Plus) and 78%
`for J30; the majority of subjects preferred HA fi llers to the
`collagen fi llers.
`In an almost identical study design (Pinsky et al 2007),
`the safety and effectiveness of Juvéderm™ dermal fi llers
`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 Juvéderm™ Ultra
`or Juvéderm™ Ultra Plus in one NLF and Zyplast® bovine
`collagen in the other NLF. The treating investigators were
`instructed to fi ll each NLF to full correction (100% of the
`defect), but not to overcorrect. A maximum of 3 treatments
`– fi rst 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
`Juvéderm™ dermal fi ller 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 signifi cant mean level of improvement
`for the NLFs treated with Juvéderm™ Ultra or Juvéderm™
`Ultra Plus, but not for NLFs treated with Zyplast®, supporting
`the above stated fi ndings by showing a longer longevity for
`Juvéderm™ Ultra and Ultra Plus than for Zyplast®. The mean
`
`HA gel for facial wrinkles and folds
`
`level of improvement was still clinically signifi cant for
`subjects who returned for a follow-up treatment beyond
`9 months, with the proportion of NLFs still showing clinically
`signifi cant improvement in 75% with Juvéderm™ Ultra and
`81% with Juvéderm™ Ultra Plus. Juvéderm™ Ultra Plus was
`shown to last even 12 months or longer. Again, the frequency
`and severity of treatment site reactions (eg, erythema, indura-
`tion, pain, edema, nodule formation, bruising, pruritus, and
`discoloration) were mild or moderate and were similar for all
`fi llers. The authors concluded, that due to its superior longev-
`ity, individuals treated with these Juvéderm™ dermal fi llers
`may require to repeat treatments less frequently than those
`treated with bovine collagen fi llers, 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 Juvéderm™
`Ultra Plus HA fi ller with Zyplast® bovine collagen in a mul-
`ticenter, double-blind, randomized, within-subject, controlled
`study (Lupo et al 2008). In a split face mode, severe NLFs
`of 87 subjects were treated, one side with Juvéderm™ Ultra
`Plus and the other side with Zyplast®. In the study popula-
`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 Juvéderm™ Ultra Plus fi ller showed signifi cantly better
`NLF severity scores compared to Zyplast® at each follow-up
`time point from 4 to 24 weeks. At 24-week follow-up clini-
`cally signifi cant correction of NLF treated with Juvéderm™
`were shown in 96% compared with 41% Zyderm®. The
`clinical correction with Juvéderm™ 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-
`ment was still 1.7 with the Juvéderm™ 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% of NLFs treated with Juvéderm™. The median volume of
`Juvéderm™ required was 0.7 mL (one syringe), signifi cantly
`less than for Zyplast® (1.6 mL). For the initial treatment,
`the median volume of Juvéderm™ 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 Juvéderm™ Ultra
`Plus and Zyplast® and were similar to those in the above-
`mentioned trials. As for patient satisfaction, most subjects
`preferred Juvéderm™ Ultra Plus (85%) versus collagen
`(10%); 5% showed no preference.
`
`Clinical Interventions in Aging 2008:3(4)
`
`633
`
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`Page 5
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`

`

`Bogdan Allemann and Baumann
`
`Table 3 Factors to consider when choosing an hyaluronic acid
`(HA) fi ller
`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
`
`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 Juvéderm™
`scored lowest, even lower than Perlane®.
`There are many factors to be understood, in order to know
`which HA fi ller to use (Table 3). Because no peer-reviewed
`scientifi c publications have reviewed the above-mentioned
`properties, it is impossible at this point to know how
`important these various characteristics are in choosing a
`fi ller. 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 fi llers
`reach the market and more data are collected.
`
`In summary, all three studies above show superior longevity
`of the HA Juvéderm™ fi llers compared to bovine collagen
`fi llers. Juvéderm™ Ultra Plus was shown to exert longer lasting
`clinical results than Juvéderm™ Ultra. Initial treatments required
`roughly two syringes of Juvéderm™, 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 fi llers, HA and collagen, and were always
`short in duration (less than 7 days) and mild in severity. Most
`patients seem to prefer Juvéderm™ fi llers to bovine collagen.
`Juvéderm™ Ultra Plus was compared with Radiesse® in an
`European study by Moers-Capri et al (2007) that compared the
`hydroxylapatite fi ller with two HA fi llers for the treatment of
`the nasolabial folds. The objective of this multicenter, blinded,
`randomized trial was to compare patient satisfaction, effi cacy
`and durability of the various fi llers. A total of 205 patients
`were randomized into 3 arms, receiving Radiesse® (CaHA
`gel), Juvéderm™ Ultra, or Perlane®. After the fi rst treatment
`a touch-up was performed 4 months later and patients were
`followed up at 8, and 12 months, without any additional touch-
`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 signifi cantly more improved, than
`with any HA, as assessed by Global Aesthetic Improvement
`
`Disclosures
`None of the authors has any confl icts to disclose.
`
`References
`
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