Volume 28, Is
`
`Aesthetic Surger
`
`AESTHETIC SURSERY JOURNAL.
`
`~ ! o m mmnrn Im Hm~ !
`0730.384000
`Volume 28:Number 5(2008 )
`
`0
`
`A Peer-Reviewed International Journal
`
`www.aestheUcsurger~joumal. om
`
`lN 1 HIS ISSUE
`Effects of Common Laser lrearments on Hyaharonic Acad Fillers
`m a Porcine Model
`l..Jter.il Osleotomies I Rhinoplastv:
`.\ Safer and Less Traumc11ic Method
`Inverted T \.crsus Vertical Sl.'ar Breast Reduction; One Surgeon'!!
`Five-Year Experience \\ ith Conf-iecutl\e Pc1llents
`
`Quanh1c1tive Ehect of n1mesccn1 lnflltr.il.ion and Bupivacaine h jet 1io11
`in Oecreasit g Po5toperati e P,1m I Submuscular Breasl \u0 1 en dliua
`Photod} nam1c Therapv: Indications and Ir alm£>nt
`
`Companson of Filling ~gents for Lip \ugn entalion
`
`.\esthetic lrec1tment o( Leg Veins
`
`Office-Based Anes hesic1: Dispelling Commur M) ths
`
`•
`
`Ofdcial English-l.angu..1ge Journal of:
`
`OFFICIAL PUBUCAJION OF
`THE AMERlt:AN SOCll:."TY n>R
`- ---'ftoo-,- - AESTHETIC PLAS'nC SURcu,
`
`Exhibit 1016
`Prollenium v. Allergan
`
`

`

`Review Article
`
`Comparison of Filling Agents
`for Lip Augmentation
`
`Deborah S. Sarnoff, MD; RilU Saini, MD; and Robert H. Gocki11, MD
`
`The authors discuss vanous filling agents currently available that can be used to augment the lips, correct peri(cid:173)
`oral rhytJdes, and enhance overall hp appearance. Fillers are compared and information provided about choos(cid:173)
`ing the appropnate agent based on the needs of each patient to achieve the much coveted "pouty" look while
`avoiding hypercorrect1on. The authors posit that the goal for the upper lip is to create a form that harmonizes
`wrth the patient's unique features. taking into account age and ethmoty; the goal for the lower lip 1s to create
`bulk. greater prominence, and pro1ect1on of the vermilhon. (Aesthetic Surg J 2008,28"556-563 )
`
`In virtually all cultures since the beginning of record(cid:173)
`
`ed history, full lips have been .issociated with femal e
`youth , beauty, and voluptuousness. In youthful lips
`of white patients. for example, the ideal ratio of the
`upper to lower lip Is 1:1.6 (Figure t) .I However, the
`properties of the lips change with age, resulting in
`lengthening 01 the cutaneous portion of the upper lip
`and the upper lip vermillion gradually losing volume
`and becoming thinner (Figure 2). Genetics, intrinsic
`aging. sun exposure, smoking. and repetitive pursing of
`the orbicularis oris produce angular. radial. and vertical
`"lipstick bleed
`lines" (Figure 3). Gravit\', maxillo(cid:173)
`mandibular bony resorption and further soft tissue vol(cid:173)
`ume loss at the oral commissures cause the commissures
`to turn downward in a perpetual frown. creating venical
`gemomandibular lines which extend downward from the
`oral comm1ssures and are commonly called -marione11e
`lines" (Figure 4). In addition 10 this hard and soft tissue
`volume loss, the lip margin it$elf may become blunted
`with fla11ening of the philtrum columns and loss of pro(cid:173)
`jection of the cupid's bow (Figure 5) _2-1
`There are many products available to correct the signs
`of aging in the lips, including permanent and nonperma(cid:173)
`nent dermal fillers, implants, neurotoxins, lasers. and
`micropigmentation. The most popular and commonly
`used lip enh,rncers are the dermal fillers.
`/\ wide range 01 techmques are used bv physicians 10
`maximize results and minimize patient discomfort and
`potential adverse 0U1comes when injecting fillers. There
`is no single formula for successful lip augmemation; 10 a
`large degree. it is an an. Achieving a natural look
`
`Dr. Sarnoff is Asi,ociah! Clinic.ii Professor. Ron,1ld 0 . Perelm..111
`Dt>p,inmen1 oi OennJ1olog}", New York Universily School oi
`,\,l~dicinc, New York . NY. Dr. Saini is ,1 Fellow In Mohs Surgery.
`Dr. Golkin is Adjuncl Surgeon ,ll New York Eye & E.1r Infirmary,
`New York. Y.
`
`requires a 1horough untlers1anding of anatomy, available
`materials. and tech111que. "Sausage" or "duck " lips do
`not occur from mere overcorrecuon. but also from a poor
`understanding of the delicate contours of lip anatomy
`(Figure 6). In general. the objective in treating the upper
`lip is to create a form that aesthetically harmonizes with
`the patient's unique facial
`features and
`takes into
`account the age and ethnic background of the p,ltlent. In
`treating the lower lip. the goal is 10 create bulk, greater
`prominence and projection of rhe vermillion
`11 is the
`responsibility 01 the physician 10 educate the patie111
`regarding normal lip proportions 111 order to discourage
`the concept oi a bizarre, cartoon-like appearance.
`
`TECHNIQUE
`/\ variety of products mJy be used to augment the lips, a
`facial feature that easily conveys telltale signs 01 agmg.
`Regardless oi the modality chosen. the physici,111 must
`have nor only anatomic knowledge ,rnd technicJI skill
`but also the aesthetic sense 10 create natural-looking,
`youthful, and sensuous lips. Every lip is different, and
`there is no set iormula to ensure desired results. There
`are, however, some basic premises to follow gleaned
`irom the senior authors· (DSS and RHG) experience: ·
`( I l /\\'oid obli1era11on of the cupid's bow and cre(cid:173)
`ation of the "sausage" or "duck" lip (Figure 6).
`(2) Keep in mind the areas th.11 have a natural promi(cid:173)
`nence or protuberance: 2 tubercles iust later.ii to the
`midline on the lower lip, 2 tubercles laterallv in the
`upper hp, and I tubercle in the mitlhne on the upper lip
`(Figure 7). Mai111aining these landmarks will help 10
`achieve the frequently coveted "pouty'' look.
`(3) Massage after injecting to help ,lltain desired
`shape and structure.
`(4) Be aware of medicauons that may predispose
`patiems to ecchymosis (aspirin , wc1rfarin. nonsteroidal
`anti-inflammatorv drugs. and even V11amin E, herbal sup-
`
`556 • Volume 28 • Nu~ S • Sepl~r/October 2008
`
`At><thmr ~11,grry Journal
`
`

`

`Figure 1. In youthful lips of white patients, the ideal ratio of the upper to the lower lip is 1: 1.6.
`
`FILLER SELECTION
`Successful lip augmentation is highly dependent on
`choice of filler material. which is based on what the
`physician and pa1ienI are a11emp1ing 10 accomplish. There
`are 5 main elements of lip rejuvenation to consider:
`(I) Enhancement of the white roll, which is achieved
`by injecting along the vermillion-cu1aneous junction 10
`prevent "' lipstick bleeding" inlo the vertical rhy1ides of
`the lip.
`(2) Volume augmentation of the body of the lip,
`which is accomplished by injecting into the vermillion
`and mucosa with 1he intention of producing larger. more
`robust
`lips. Injection m,1y be in selected areas or
`throughout the lips.
`(3) Correction of the vertical rhytides, which Is
`achieved bv injecting perpendicular!\ IO the long axis of
`1he lip and parallel 10 the rhy1ides. These results can be
`further enhanced by Ihe iniecrion of a neuromodulator.
`such ,1s botu!inum toxin. to relax the dynamic action of
`1he orbicularis oris muscle.
`(4) Elevation of the oral commissures. which is
`achieved by placing filler in 1he most lateral aspect of
`the lower lip to provide support to the commissures.
`This effort can be supported by placement of a neurorox•
`in in the depressor anguli oris muscles.
`(SJ Enhancement of the ph1ltrum columns of the
`upper lip. which is accomplished by superficial vertical
`injection of filler into each philtrum column. It is impor•
`1an1 10 realize that the philtrum columns are 1101 parallel
`10 each other, bu1 rather form an inverted "V" shape that
`narrows as it approaches the nostril stlls and columella
`of the nose (Figure 8). 5
`Fillers may be segregated into several broad cate•
`gories. Among the temporary biodegradable fillers are
`those derived from bovine collagen (Zyderm and Zyplast;
`Allergan. Irvine. CA), those derived from human collagen
`(Cosmoderm and Cosmoplas1: Allergan). and one derived
`from porcine collagen (Evolence: Co!Bar LifeScience Ltd ..
`Herzliya, Israel). There are fillers derived from avian
`h}1aluronic acid (HA) (H}•laform and Hylaform Plus.
`Allergan) and many derived Crom bacterial or nonammal
`stabililed HAs (NASIIA) , such as Restylane (Medicis,
`Scottsdale, AZ); Perlane (Medicis); Prevelle (Mentor,
`
`Figure 1 . Thinning and loss of verm,llion volume and lengthening of
`the cutaneous portion of the upper lip with age.
`
`Figure l. Angular, radial, and vertical "lipstick bleed lines'" are often
`the result of genetics, intrinsic aging, sun exposure, smoking, and
`repetitive pursing of the orb,cularis oris muscle.
`
`plemcnrs and other preparations not approved by the US
`Food and Drug AdmmisIra1ion (FDA).
`(5) lniecl Lhe upper lip first so 1ba1 posunjection
`swelling will not prevent maintenance of the correct
`anatomic proportions between upper and lower lips.
`(6) Pay careful attention IC the patient·s request.
`making sure it is reasonable. Unrealisuc expec1aIions
`may be a sign ot body dysmorphic disorder. in which
`case 1rea1ment refusal may be appropriate.
`
`CompJrison o( Fllhng Agents tor Lip /\ugm('nt,111on
`
`Volume 28 • Number 5 • September/Gaober 2008 • 557
`
`

`

`Figure 4. Gravity, maxillomandibular bony resorption, and further soft
`tissue volume loss at the oral comm,ssures cause the commissures to
`turn downward in a perpetual frown.
`
`Figure 5. Vertical geniomandibular (•marionette") lines extend down(cid:173)
`ward from the oral commissures. Both hard and soft tissue volume
`loss cause the lip margin to become blunted with flattening of the
`phillrum columns and loss of projection of the cupid's bow.
`
`Santa Barbara, CA): and the Juvederm (Allergan) Iamily
`of products. Semipermanent fillers are stimulatory in
`nature and include calcium hydroxylapa1i1e (Radiesse:
`Biof:orm, San Mateo, CA) and poly-L-lactic acid
`(Sculptra; Sanofi Aventis, Bridgewater. NJ). Stimulatory
`fillers stimulate or induce new collagen
`formation.
`Rc1diesse is a biphasic bioactivator: the calcium hydroxy(cid:173)
`lapatite microspheres (the stimulatory component) are
`suspended in a carboxymethylcellulose gel. The la1ter
`gives immediate volume correction. bm is more rapidly
`metabolized. The calcium hydroxylapatite microspheres
`remain after the gel is metabolized and become sur(cid:173)
`rounded by new collagen bundles: these are the "stimula(cid:173)
`tory" component of
`the product. Sculptra
`is a
`monophasic stimulatory filler: it gives no immediate vol(cid:173)
`ume enhancement, but promotes neocollagenesis and
`dermal thickening over time. Sculptra requires several
`treatmems to obtain the desired clinical result. The stim(cid:173)
`ulatory fillers are more robust. generally require deeper
`placement. and seem 10 have ,1 higher mcidence of nod(cid:173)
`ules when placed m the lips. Therefore. they are not rec(cid:173)
`ommended for lip augmentation.
`Among
`the permanent
`fillers are polymethyl(cid:173)
`rne1hacryla1e (PMMA) beads suspended in a bovine col(cid:173)
`lagen gel (ArteFill. Artes Medical, San Diego. CA;
`
`another biphasic filler): silicone (Silikon 1000; Alcon
`Labs. Fort Worth. TX): and Adatosil 5000 (Bausch &
`Lomb. Rochester. NY) . These permanent fillers are also
`prone to nodule formation and should be used only by
`experienced
`injectors. Au tologous
`fat. surgical
`lip
`implants. botulinum toxin A. ablative and nonablative
`skin resurfacing, ablative and nonablative fractional skin
`resurfacing. and micropigmentation are all adjunctive
`therapies that may be used to .iugment or rejuvenate the
`lips. We will limit our discussion. however, to those der(cid:173)
`m.il .ind subdermal fillers that may be used in the lips
`(Table I).
`
`ColJagen
`The earliest fillers approved by the FDA were derived
`from bovine collagen. Zyderm and Zyplast were mlro(cid:173)
`duced to the cosmetic surgery market in the early I980s
`and became
`the standard against which all . other
`injectable fillers were measured.'' Because these products
`are derived from bovine collagen, they require a skin test
`10 determine allergic cross-reactivity: this necessitates a
`wait of at least 4 weeks before lip implantation. Human(cid:173)
`derived collagen, obtained
`from neonatal
`foreskin
`(Cosmoderm and Cosmoplast) was developed and
`approved by the FDA in 2003. The advantages of these
`
`Figure 6. A. •sausage• or ·duck• lips occur from overcorrect,on. but also from a poor understanding ol the delicate
`contours of lip anatomy. B. Avoid obliteration of the cupid's bow and creation ol the •sausage• or •duck" lip.
`
`558 • Volu!IM! 28 • Number S • September/October 2oo8
`
`AeSthetic Surge'} Joumnl
`
`

`

`Upper h1> tubercles
`
`L-ower hp tubercles
`
`Figure 7. Tubercles of the uppe·r and lower lips are interlaced and
`should be enhanced during lip augmentation.
`
`products are that they do noI require an <1llergy skin Ies1
`<1nd they were approved for res1ora1ion of the lip border.7
`The dis1inc1ion between boIh fillers in e,H.:h class is
`1haI Zyplast .ind Cosmoplast are cross-linked and there·
`fore useful for modera1e 10 deep lines. With respect to
`the lips, they <1re very useiul for placement into the ver(cid:173)
`million-cu1aneous iunc1ion of the upper and lower lips.
`In the senior authors· (D.S.S .. R.H.G.) experience,
`implantation just below the vermillion border will create
`a sharply defined margin generally requiring only l
`entry sues on either side of the lip. Accentuauon of the
`philtrum columns and cupid's bow is usually achieved
`in separate, precise injections. Zyderm and Cosmoderm
`are non-cross-linked and are ideal for upper lip rh} tides.
`They can be m1ec1ed superficially withoul the risk of
`forming nodules or creating Ihe bluish discoloraIion
`(Tyndall effect) frequently seen with the HA iillers. A
`distinct advantage of these 4 collagen fillers is their off
`the shelf admixture wiIh lidocame A limitauon with all
`of the collagen products, however, is Iha1 the .:iverage
`duration is only about 3 months. comp.ired to IIAs that
`generally last an average of 4 to I l months.~ Despite
`this. there is still a use for collagen in the lips. because 11
`appears 10 provide sIructure with mmimal swelling,
`bruising . .erythema. and downtime-characteristics more
`commonly seen with the HA products.9
`
`Hyaluronic Acid
`The next group of fillers is derived from HA. a natur,1lly
`occurring subsIance found in the connecIive tissues th,11
`cushions and lubric.1Ies. Because HAs are hvdrophilic.
`they amact water from surrounding tissues. further aug(cid:173)
`me11Iing sofl 1issue volume beyond what is expected
`from product implantation alone. For this reason. HA
`fi llers are often excellent choices for enhancing lip vol(cid:173)
`ume. Among lhese fillers is Restylane. a partially cross(cid:173)
`linked NASHA that is produced by formen1ation from
`cultured Streptococcus bacteria. Restylane was approved
`by the FDA in 2003 for the tre,11men t of moderaIe to
`severe fJcral wrinkles and folds. I0 Perl,rne is a more
`robus1. larger particle size form of HA compared with
`Restylane and is indicated for deeper implantation. It is
`
`also ,1pproved by the FDA for 1he correction of moderate
`10 severe f.1ci,1I wnnklL•s and folds and can thus provide
`good structure and long-lasIing correction when injected
`i11I0 the lips. lniecung a small amou111 11110 the oral com(cid:173)
`missures and 1he l,11eral asperI of lhe lower lip can help
`10 achieve ,1 more you1hiul appear,mce bv eleva1ing the
`corners oi till' mouth.
`1\~ previouslv me1111oned, limitJtions of the nonani(cid:173)
`mal derived HAs Jre s1gn1fica111 bruising. swelling. and
`eryIhema. Therefore. they would probably not be the
`filler of choice for someone with an important social
`event in Ihe days 1mmedia1ely following injection. 11
`These sequelae are even more evident m the lip, given a
`high degree of v.isculari1y and tendency for edema.
`Although skm tesung 1s not required for HAs, Ihere have
`been reports of granuloma1ous and hypersensitivity reac(cid:173)
`tions, including one associaIed with angioedema. 1z- 14
`Treatment of the nasolabial folds. albeit quiie common.
`has also been complicated by 2 reported cases of
`embolization of the dorsal nasal artery. 15· 16 A unique
`complication from too-superficial implantation of HA
`fillers is a bluish appe,1rance emana1ing from within the
`dermis as a result of the Tyndall effect. 17 The Tvndall
`effec1 and formation of nodules (especially with the larg(cid:173)
`er particle sized Perl.me) are largely a result of improper
`product placemen! and lack of adequate massage. which
`further highlights that skill and technique are of para(cid:173)
`mou111 importance. Fortunately. the temporJry nature of
`these materials and the accessibility of hyaluronidase to
`digest the product can .1llev1ate these problems.
`Another !IA-derived filler Is animal-based Hylaform
`(hvlan-B gel) . Approved by the FDA in April 2004 for
`injecIion into the mid to deep dermis for the correction
`of moder,11e 10 severe
`facial wrinkles and
`folds, 18
`Hylaform consists oi htgh molecular weight cross-linked
`hyaluronan polysaccharide chains obtained from rooster
`combs. Hyl,1form Plus is simply formed from a larger
`mean HA gel pamcle and used to correct deeper lines
`and folds. 19 Hylaform contrasts with Restylane and
`Perl,rne in !hill it is much "softer" and therefore an
`excellent filler for Ihe body of the lip. There seems to be
`much less bruising associated with it, making it an
`excellen1 choice if the patient has to allend a social
`event shortlv after treatment. The minimal bruising
`occurs beciluse Hylaform is already saturated with water
`and is in equilibrium hydration before injecIion as
`opposed 10 Restylane and Perlane, which are below
`hydration equilibrium Jnd thus absorb water after injec(cid:173)
`tion. PotenIi,1l pitfalls with Hylaform are that because it
`is avian-denved, it Is not a good choice in patients with
`an allergy 10 poultry and, just as with other HAs. there
`have been reports of granulomatous reactions. 20
`Among the newer HA-derived fillers are Juvederm Ultra
`and Juvederm Ultra-Plus. Both were approved by the FDA
`in 2006 for the correction of nasolabial folds.21 Whereas
`ResIylane contains 20 mg/ml of hyaluronan with a small
`uncross-linked proportion, Juvcderm Ultra is 24 mg/ml. of
`which 21 .6 mg/mL is cross-linked, and the Ultra Plus vJri-
`
`Comp.rn,on of Filhnit Agerm tor IJp AugmenlJtwn
`
`Volume 28 • Number 5 • Seplember/OClober 2008 • 559
`
`

`

`Table 1. Comparison of common filling agents available in the United States
`
`Description
`35 mwml
`65 mg/ml
`35 mg/ml, cross-linked with
`glutaraldehyde
`35 mg/ml
`35 mg/ml cross-linked with
`glutaraldehyde
`35 mg/ml, cross-linked with ribose
`(glycation); free of telopeptides
`
`Duration
`3 mos
`3 mos
`3+ mos
`
`3 mos
`3+ mos
`
`,s 12 mos
`
`20 mg/ml 100,000 particles/ml;
`BODE cross-linked
`500,000 particles/ml;
`BODE cross-linked
`
`6 mos
`
`6 mos
`
`Skin test
`Yes
`Yes
`Yes
`
`lidocaine
`Yes
`Yes
`Yes
`
`No
`No
`
`No
`
`No
`
`No
`
`Yes
`Yes
`
`No
`
`No
`
`No
`
`20 mg/ml 10,000 particles/ml;
`BODE cross-linked; particle
`size "' 1000 µm
`1000 particles/ml
`BODE cross.finked
`24 mg/ml; cross-linked
`24 mg/ml; cross-linked
`
`Medicis
`
`NASHA
`
`6 mos
`
`No
`
`No
`
`Product
`Zyderm I
`Zyderm 2
`Zyplas1
`
`Manufacturer
`Allergan
`Allergan
`Allergan
`
`Active ingredient
`Bovine collagen
`Bovine collagen
`Bovine collagen
`
`Cosmoderm
`Cosmoplas1
`
`Allergan
`Allergan
`
`ColBar
`LifeScience
`
`Medicis
`
`Medicis
`
`Evolence,•
`Evolence
`Breeze"
`Restylane
`
`Restylane
`Touch/Fine
`Line
`Perlane
`
`Human collagen
`Human collagen
`
`Porcine collagen
`
`NASHA
`
`NASHA
`
`Medicis
`
`NASHA
`
`NASHA
`NASHA
`
`Restylane
`Sub-Q"
`Juvederm Ultra Allergan
`Juvederm
`Allergan
`Ultra Plus
`Avian HA
`Allergan
`Hylafomi"
`Avian HA
`Hylaform Plusb Allergan
`Elevess
`Anika Therapeutics HA
`Puragen•
`Mentor
`NASHA
`
`Puragen Plus" Mentor
`
`Prevelle
`
`Mentor
`
`Prevelle Plus
`
`Mentor
`
`Radiesse
`
`Bioform
`
`Sculptra'
`
`Sanofi Aventis
`
`ArteFill
`
`Artes Medical
`
`Silikon IOOo<I
`
`Alcon
`
`Adatosil 5000" Bausch & Lomb
`
`Autologous fat
`
`NASHA
`
`NASHA
`
`NASHA
`
`Calcium
`hydroxylapatite
`PUA
`
`PMMA
`
`Autologous fat
`
`Cross-linked
`20 mg/ml; single cross-linked,
`additional ester bond
`20 mg/ml; single cross-linked,
`additional ester bond
`5.5 mg/ml; fully hydrated,
`not hydrophilic
`5.5 mg/ml; fully hydrated.
`not hydrophilic
`25-45 µm calcium HA microspheres Stimulatory:
`in aqueous polysaccharide gel
`semipermanent
`PLLA hydrogel synthesized from com Stimulatory:
`semipermanent
`Permanent
`
`6mos
`
`6-12 mos
`6-12 mos
`
`4-6 mos
`4-6 mos
`No data
`No data
`
`No data
`
`No data
`
`No data
`
`Permanent
`
`Permanent
`
`No
`
`No
`No
`
`No
`No
`No
`No
`
`No
`
`No
`
`No
`
`No
`
`Yes
`
`No
`
`No
`
`No
`No
`
`No
`No
`Yes
`Yes
`
`Yes
`
`Yes
`
`Yes
`
`No
`
`No
`
`Yes
`
`No
`
`No
`
`Months to years· No
`semipermanent
`
`If added
`by MD
`
`20% PMMA (32-40 µm),
`80% bovine collagen gel
`Polydimethylsilol@ne Highly purified medical grade
`silicone oil: 1000-CSt
`Polydimethylsilol@ne Highly purified medical grade
`silicone oil: 5000-C.St
`Transplantation by aspiration and
`· reinjection
`
`'lote: All prcxlucts dte dpprO\led b-, the FDA foe cosmet.c US<! as ,oh tJSSue fil!,ng agents unless othen\'!Se noted
`BODE, Butaned,okl,,ilyodyl ether, HA. hyaluromc a<:rd· NASHA nonammdl stabthred hyaluro111c dad. PUA, polv-L-lactc aod, P.',IMA. polymeth)1rrethdovlat.:
`·Pend,ng approval by the FDA
`Hylafom, and HylJform Plus have been phased out by Allergan and have been replaced rn the,r prcxluct hne by the Juvederm family of picxlucts
`Sculptra ,s approved by the HlA for the correcnon of HIV·dSSOOilted fdOdl hpoa11ophy; 111s pending dpprovdl for cosmetrc ~ ~ d soft ussue filler.
`'Sil, n 1000 and Ad.Jtosrl 5000 are both approved by rtie FDA fo, u-;e rr1 postoperanve wmponade followmg retrnal SUrget), their use as soft tJssue fille!s rs "olf-1.Jber
`
`560 • Volume 28 • Number 5 • September/October 2008
`
`A~srher,r Sur,;:ery Journal
`
`

`

`ety is 30 mg/mL. Consequently, the manufacturer claims
`thilt this higher degree of cross-linking confers longevity
`with a poiential to last up lO I year. With respect to the
`lips, Juvederm·s "Hylacross" gel technology gives it a soft(cid:173)
`er, smoother, more natural feel rather than the particulate
`or granular consistency that can be seen with other HA
`fillers. Thus. it is an ideal choice for the body of the lip as
`well as enhancing the vermillion border. Again, sequelae
`similar lO those seen with Restylane (nodule formation if
`injected too superficially and bluish hue) are possible.
`
`New fillers
`With the cosmetic market changing at lightning speed, it
`should be no surprise that there are several new nonper(cid:173)
`manent fillers on the horizon. While many are approved
`abroad, there are several that have received recent
`approval by the FDA or are on the verge of approval.
`Evolence is a porcine-derived, ribose-cross linked fibrillar
`type l collagen approved in Israel and Europe since 2004
`for the correction of contour deficiencies and deformities
`of soft tissue.22 It is produced by the in vitro polymeriza(cid:173)
`tion of highly purified monomeric porcine collagen, fol(cid:173)
`lowed by a cross-linking process using natural sugar
`(glycation). This process extends the life of the filler up
`lO 12 momhs. One early study showed that Evolence
`remained stable during 24 months in an animal model as
`compared with Zyplast and Zyderm, which lost their 3-
`dimensional shape aiter 6 momhs.n No pretesting is
`required because the collagen telopeptides present in the
`raw material are removed in order to minimize the anti(cid:173)
`genic potential of the product. 22 It has a concentration
`identical to that of Cosmoplast (35 mg/mL) but, unlike
`Cosmoplast, there is no lidocaine admixed with the filler.
`This product, along with its counterpart, Evolence
`Breeze, is pending approval by the FDA. Evolence Breeze.
`also 35 mg/mL, is being formulated to have excellem
`Ulility in lip augmentation and I year longevity.
`Elevess (Anika Therapeutics. Bedford. MA), a new
`filler, is the first commercially-available HA product lO
`incorporate lidocaine that has been approved by the
`FDA.24 This feature, along with the fact that it contains
`the highest concentration of cross-linked I-IA available in
`a dermal filler, will likely make it an amactive produm
`for lip enhancement when it becomes available later this
`year.25 The concept of having lidocaine already premixed
`into the syringe appears to be a common theme that is
`popular with other emerging fillers such as Prevelle
`(recenrly approved by the FDA) and Puragen (still pend(cid:173)
`ing approval by the FDA); both will be distributed by
`:vtentor in the United States.
`
`Semipermanent, Stimulatory fillers
`Semipermanent fillers are stimulatory and consist of
`Sculptra (poly-L-lactic acid) and Radiesse (calcium
`hydroxylapatite). Sculptra is a monophasic stimulatory
`"volumizmg" agent that is approved by the FDA for the
`treatment of HIV-associated facial lipoatrophy and is cur(cid:173)
`rently awaiting approval by the FDA for cosmetic use in
`
`the United Staces.26 It is comprised of tiny particles of
`poly-L-lactic acid that are diluted in sterile water and
`stimulate collagen formation once injected into the skin;
`therefore, dermal thickening and volume augmentation
`increase over time. The results are not immediate, and a
`series of 3 or more treatments, each 4 to 8 weeks apart,
`are usually necessary. When used in the lips. it is associ(cid:173)
`ated with nodules and granuloma formation and is thus
`1101 recommended for lip _augmentil!ion_H Radiesse. a
`biphasic stimulatory filler. utilizes calcium hydroxylap(cid:173)
`atite microspheres suspended
`in an aqueous car(cid:173)
`boxymethylcellulose gel carrier. Unlike Sculptra, the gel
`carrier gives immediate volume correction while the cal(cid:173)
`cium hydroxylapatite microspheres stimulate neocollage(cid:173)
`nesis for the long-term correction. Its use in the lip is
`also associated, however, with the potential for nodule
`formation and it should therefore not be used for aug(cid:173)
`mentation in this area. 28
`
`Permanent fillers
`An alternative to a temporary filler is, of course, one that
`is permanent. In this category, there are 2 main products:
`ArteFill and liquid silicone. ArteFill, the first permanent
`biphasic wrinkle filler approved for use in the United
`States market. is composed of 20% PMMA microspheres
`suspended in 80% bovine collagen gel admixed with
`lidocaine. After ArteFill is injected, the collagen degrades
`over the course of several weeks tO months ,rnd fibrob(cid:173)
`lasts are stimulated 10 lay down new collagen around the
`PMMA microspheres. Similar to the semipermanent
`fillers Radiesse and Sculptra, there have been reports of
`nodule and granuloma formation, especially in the set(cid:173)
`ting of immunostimulatory medications such ,1s interfer(cid:173)
`on (often prescribed for hepatitis CJ.l'>-32 A phenomenon
`unique to the microimplants is dislocation, a mechanical
`event. caused by the action of the orbicularis oris muscle,
`making the implant migrate from where it was originally
`placed.32 This is obviously more problematic in the set(cid:173)
`ting of permanent fillers, because they will require more
`invasive interventions for correction rather than just
`"tincture of time." Furthermore, with aging, there are
`changes in both hard and soft tissue as well as in self(cid:173)
`perception; this necessitates a "tweaking" of the antiag(cid:173)
`ing program, which becomes much more difficult if the
`previous intervention is permanent.
`Liquid silicone, purified polydimethylsiloxane (Silikon),
`is another popular permanent filler; it was developed for
`and approved by the FDA for use in the treatment of reti(cid:173)
`nal detachment and is used off-label as a pem1anem fill(cid:173)
`ing agent. It is important to be aware, however, that in
`some states, such as Nevada, it is illegal tO use silicone
`off-label for cosmetic purposes.
`Where it is legal, lip enhancement can be achieved
`by injecting very small amounts of silicone and strict(cid:173)
`ly adhering 10 the microdroplet technique.33- 34 This
`technique employs approximately 20 to 25 injections
`in the lower lip and 15 10 20 injections in the upper
`lip; the total volume injected in both lips during one
`
`CompJnson of Fllhng Agenis for Lip i\ugmen1a11on
`
`Volume 18 • Number 5 • Seplember/October 1008 • 561
`
`

`

`Figure 8. A. Pretreatment view of a 39-year-old woman. B, Posttreatment view 4 months following lip enhancement with hyaluronic gel.
`
`1rea1men1 session usually does not exceed 1.0 ml.~
`The m1crodrople1
`Iechnique effectively eliminates
`product migrdlion by the sIimula1ion of cl collagen
`capsule 1ha1 anchors the microdrople1 in place. The
`augmen1a1ion is not c,rnsed by the silicone i1self, but
`rather the body·s innammawry response that triggers
`neocollagenesis. 31- 15 The risk of inflammawry compli·
`cauons increases in pauents who have infectious
`processes. such as sinus or denial 111fec11ons, in close
`proximiIy 10 injection sites. 35 ·36 In addition 10 local
`erythemJ and edema and 11ie forma1ion of nodules
`and granulomas, more severe complica1ions, including
`cellulitis, ulcerations, and atypical mycobacterium
`iniections, have been reported. 36 Because 1h1s Is a per(cid:173)
`manen1 filler (like ArteFill). it is advisable for the
`patient to have had previous experience w11h tempo(cid:173)
`rary
`fillers before defini1ive treatment wi1h Silik
`on 1000.
`
`PERMANENT IMPLANTS AND AUTOLOGOUS FAT
`Aside from fillers and microimplants. it is important 10 be
`aware of other useful products m the cosmetic armamen(cid:173)
`tarium 10 trea1 signs of aging in the lips. Surgical impla111s
`made of expanded polytetranuoroethylene tePTFE). Gore(cid:173)
`Tex, W.L. Gore & Associates, Flagstaff. AZ; SoftForm,
`Tissue Technologies, San Francisco, CA, Ultra-Soft, Tissue
`Technologies. San Francisco, CA: and Advanta, Atrium
`Medical Corp .. Hudson, NY) and auwlogous fat can also
`be used. The benefit of the la1ter is that it is au!Ologous;
`1he disadvantage is tha1 ii is no! off-the-shelf and 1he
`results are often inconsisIen1 and unpredictable. The side
`effect prolile of the nonb1ologic ePTFE implants is similar
`to that of the permanent fillers; there have been cases of
`infection, foreign body granulomas, ulceration, and extru•
`sion of these impla111s from the lips.z9 Again, the concern
`with each of these products is that they are perrnane111
`and opera10r-dependenI-once implan1ed in 1he lip. Ihey
`
`cannot be removed unless some l}'pe of surgical interven(cid:173)
`Iion is employed.
`
`CONCLUSIONS
`Compared with jus1 a decade ago, there have been many
`additions 10 the cosme1ic armamcntarium of injectable
`products for lip enhancement With our current societal
`interest in maintainmg youth and beauty, i1 is fortunate
`Iha1 1here are many more products on the horizon that
`promise improved results with decreased pain
`for
`pa1ienIs and. in many cases, increased ease o f injection
`for the physician. Therefore. it behooves the physician 10
`gain experience with each produc1 and lO master the art
`of filling 1he lips. Both the science of the filler tproduc1)
`and the an of 1he filler (physician) are critical 10 ,m
`excellent cosmetic result (Figure 8). •
`
`DISCLOSURES
`
`Drs. Sanwff anti Co1ki11 arc consultants for Allergan and Biol-onn
`Medical. Dr. Saini has 110 disclosures u•ith regard 10 tht! co111e1t1.< of
`this article.
`
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`
`tlesrhetlc Surg~rv Journal
`
`

`

`Accep1ed for publlcanon June !O. 2008.
`
`Reprint requeslS: Deborah S. S.1m off. MD. 31 Nonhern Bll'd .. Cn.>emalc, NY
`11 548. E-nuil: ~1ndrew.s.1n10f1(,ico .. meriquemd.com.
`Cop) nght .. 200