COSMETIC
`
`The Role of Hyaluronic Acid Fillers (Restylane)
`in Facial Cosmetic Surgery: Review and
`Technical Considerations
`
`Rod J. Rohrich, M.D.
`Ashkan Ghavami, M.D.
`Melissa A. Crosby, M.D.
`Dallas and Houston, Texas; and Los
`Angeles, Calif.
`
`Background: Bioengineered hyaluronic acid derivatives are currently available
`that provide for safe and effective soft-tissue augmentation in the comprehensive
`approach to nonsurgical facial rejuvenation. Current hyaluronic acid fillers do
`not require preinjection skin testing and produce reproducible, longer-lasting,
`nonpermanent results compared with other fillers, such as collagen.
`Methods: A review of the authors’ extensive experience at the University of
`Texas Southwestern Medical Center was conducted to formulate the salient
`requirements for successful utilization of hyaluronic acid fillers. Indications,
`technical refinements, and key components for optimized product administra-
`tion categorized by anatomical location are described. The efficacy and longevity
`of results are also discussed.
`Results: Bioengineered hyaluronic acid fillers allow for safe and effective aug-
`mentation of selected anatomical regions of the face, when properly adminis-
`tered. Combined treatment with botulinum toxin type A can enhance the effects
`and longevity by as much as 50 percent. Key components to optimal filler
`administration include proper anatomical evaluation, changing or combining
`various fillers based on particle size, altering the depth of injection, using
`different injection techniques, and coadministration of botulinum toxin type A
`when indicated. Concomitant administration of hyaluronic acid fillers along
`with surgical methods of facial rejuvenation can serve as a powerful tool in
`maximizing a comprehensive treatment plan.
`Conclusions: Current techniques in nonsurgical facial rejuvenation and shap-
`ing with hyaluronic acid fillers are safe, effective, and long-lasting. Combination
`regimens that include surgical facial rejuvenation techniques and/or coadmin-
`istration of botulinum toxin type A further optimize results, leading to greater
`(Plast. Reconstr. Surg. 120 (Suppl.): 41S, 2007.)
`patient satisfaction.
`
`Soft-tissue augmentation with the various
`
`soft-tissue filler materials has become one
`of the most popular aesthetic procedures
`available to patients who desire nonsurgical fa-
`cial rejuvenation. The plethora of soft-tissue fill-
`ers currently available in the United States today
`also serves as a powerful adjunct to surgical tech-
`niques in facial rejuvenation and facial shaping.
`The 2003 data from the American Society of
`
`From the Department of Plastic Surgery, University of Texas
`Southwestern Medical Center; Department of Plastic and
`Reconstructive Surgery, University of Texas Southwestern
`Medical School; and Division of Plastic and Reconstructive
`Surgery, M. D. Anderson Medical Center.
`Received for publication January 30, 2006; accepted Sep-
`tember 6, 2006.
`Copyright ©2007 by the American Society of Plastic Surgeons
`DOI: 10.1097/01.prs.0000248794.63898.0f
`
`Plastic Surgeons demonstrated a 150 percent
`increase from 2002 in the use of soft-tissue fillers,
`with 744,283 procedures performed in this non-
`surgical category.1,2 Soft-tissue fillers are particu-
`larly attractive to younger, middle-aged patients
`who display minimal to moderate signs of facial
`aging and who want minimal downtime.
`
`FDA Status and Approved Uses: Restylane is
`FDA approved as an injectable gel to treat
`facial wrinkles. Juve´derm is FDA approved.
`The three product formulations include Juve´-
`derm 24 HV, a highly cross-linked formulation
`for more versatility in contouring and volumi-
`zing of facial wrinkles and folds; Juve´derm 30
`HV dermal filler, a more highly cross-linked
`Continued
`
`www.PRSJournal.com
`
`41S
`
`Exhibit 1010
`Prollenium v. Allergan
`
`

`

`Plastic and Reconstructive Surgery • November Supplement 2007
`
`As the search for an ideal filler material con-
`tinues, hyaluronic acid derivatives have gained
`popularity among aesthetic surgeons because of
`their numerous advantages. An ideal filler mate-
`rial is one that is biocompatible, nonantigenic,
`nontoxic, easy to use, long-lasting (yet nonper-
`manent), inexpensive, and reversible. It should
`demonstrate a high safety profile and produce a
`predictable result with minimal downtime.
`Many of the new fillers available for use in the
`United States are longer-lasting and have shifted
`the paradigm between permanent and nonper-
`manent fillers. Use of permanent or “more per-
`manent” fillers allows less room for error and
`can produce irreversible changes in facial shape
`that may not retain the aesthetic changes as the
`patient ages. With the introduction of hyal-
`uronic acid derivatives for use in soft-tissue aug-
`mentation, a safer, longer-lasting, and yet tem-
`porary alternative has been made available.
`
`WHAT IS HYALURONIC ACID?
`Hyaluronic acid is common among many or-
`ganisms and is present in connective tissues of
`skin, cartilage, bone, and synovial fluid. Hyal-
`uronic acid is unique in that it is natively present
`in the intracellular matrix of the dermis and iden-
`tical in form in all mammalian species.3,4 In human
`skin, it aids in bulk, lubrication, and shock ab-
`sorption. Its viscoelastic properties and role in cell
`membrane protection and stabilization make it a
`natural choice for dermal soft-tissue augmenta-
`tion. The amount of hyaluronic acid residing in
`native tissue decreases with age, leading to re-
`duced dermal hydration and increased folding.5,6
`Hyaluronic acid is a glycosaminoglycan biopoly-
`mer of alternating D-glucuronic acid and N-acetyl-
`D-glucosamine monosaccharide residues cross-
`linked into long, repeated, unbranched polyanionic
`chains. The repeating chains are hydrated and coil
`
`robust formulation for volumizing and correc-
`tion of deeper folds and wrinkles; and Juve´d-
`erm 30, a highly cross-linked formulation for
`subtle correction of facial wrinkles and folds.
`Captique is approved for injection into the
`mid- to deep dermis for correction of moder-
`ate to severe facial wrinkles. Hylaform is ap-
`proved for injection into the mid- to deep
`dermis for correction of moderate to severe
`facial wrinkles and folds (such as nasolabial
`folds).
`
`42S
`
`upon themselves, providing the substance with
`elasticity and viscosity. Hyaluronic acid acts by
`binding water molecules, which leads to increased
`skin hydration and turgor. Its hydrophilic prop-
`erties help the product maintain its volume and
`viscoelasticity when it is injected.
`Exogenous hyaluronic acid is rapidly elimi-
`nated by lymphatics and degraded in the liver to
`carbon dioxide and water.5 Without cross-linking,
`the tissue half-life is only 1 to 2 days. Manufactur-
`ers, therefore, have had to modify the physical and
`chemical properties to allow long-lasting results.
`The goal of bioengineered hyaluronic acid is
`to improve its stabilization via increased tissue res-
`idency, viscosity, and elasticity while preserving its
`innate biocompatibility. The bioengineered hyal-
`uronic acid derivative is chemically cross-linked,
`which alters its solubility and rheological profile so
`that it becomes a more viscous, water-insoluble
`gel. This process has dramatically improved its
`stability when it is injected into tissue. The hyal-
`uronic acid gel properties are, therefore, con-
`trolled by varying the molecular weight, concen-
`tration, and degree of cross-linking. This process
`helps retain the biological compatibility of the
`native polymer, slow its dissolution rate, and in-
`crease its residence time when it is injected into
`dermis.7–12
`Hyaluronic acid derivatives first received Food
`and Drug Administration approval in the United
`States for soft-tissue augmentation in December of
`2003 with the introduction of Restylane (Medicis
`Aesthetics, Inc., Scottsdale, Ariz.) followed by Hy-
`laform (Inamed, Santa Barbara, Calif.) in April of
`2004, Hylaform Plus in October of 2004, and Cap-
`tique (Allergan, Santa Barbara, Calif.) in Decem-
`ber of 2004.13–15 The majority of the long-term
`experience with these filler products can be found
`in both the European and Canadian literature,
`with up to 9 years of experience in more than one
`million patients. The hyaluronic acid derivatives
`available in these countries include Hylaform Gel,
`Hylan Rofilan Gel, Achyal, Restylane, Restylane
`Fine Lines, and Perlane.16 These various hyal-
`uronic acid derivatives differ in particle size, mo-
`lecular weight, and degree of cross-linking, mak-
`ing each optimal for injection into specific dermal
`layers and facial regions (Table 1).
`For example, Restylane Fine Lines is a lower-
`density, less viscous filler that is indicated for the
`more superficial dermis (dermoepidermal junc-
`tion), whereas Restylane is composed of medium-
`density particles, more viscous, and better suited
`for augmentation of the mid-dermis. Perlane is a
`high-density, longer-lasting hyaluronic acid filler
`
`

`

`Volume 120, Number 6S • Hyaluronic Acid Fillers
`
`Table 1. Characteristics of Various Hyaluronic Acid Fillers
`
`Hylaform
`Restylane
`DVS
`BDDE
`Cross-linking agent
`5.5 mg/ml
`20 mg/ml
`HA concentration
`500 ␮m
`250 ␮m
`Particle size
`BDDE, 1,4-butandiol diglycidylether; DVS, divinyl sulfone; HA, hyaluronic acid.
`
`Hylaform Plus
`DVS
`5.5 mg/ml
`750 ␮m
`
`Captique
`DVS
`5.5 mg/ml
`500 ␮m
`
`that is very useful for deep dermal injection. Per-
`lane is currently the largest hyaluronic acid com-
`pound available. Perlane is an effective, long-last-
`ing filler indicated for augmentation of the deeper
`dermal level. However, thicker hyaluronic acid
`fillers (i.e., larger particle size) can be less forgiv-
`ing in more superficial dermal layers and can pro-
`duce lumpiness and more erythema if caution is
`not used.
`
`COMMERCIALLY AVAILABLE
`HYALURONIC ACID PRODUCTS
`(UNITED STATES)
`
`Restylane
`Restylane is a partially cross-linked hyaluronic
`acid derivative obtained from a bacterial (Strepto-
`coccus) fermentation process that forms a viscoelas-
`tic, transparent gel. Because it is a non–animal-
`derived compound, there is no risk of transmitting
`diseases and minimal risk of allergic reactions, so
`the need for preinjection skin testing is elimi-
`nated. As with other bioengineered hyaluronic
`acid derivatives, Restylane binds water with great
`affinity and can maintain its bulk as it undergoes
`“isovolemic degradation.” This stability is pro-
`vided by the high degree of cross-linking, which
`allows for its long-lasting effect (up to 4 to 6
`months, depending on the location and injection
`technique).17 Restylane is indicated for mid- to
`deep dermal implantation for moderate to severe
`facial wrinkles and folds/nasolabial folds.14,17 Re-
`stylane is provided in 0.4-ml and 1.0-ml preloaded,
`30-gauge, 1.5-inch-long needle syringes contain-
`ing 20 mg/ml of stabilized hyaluronic acid.18,19
`The product syringes have a shelf life of 1.5 years.
`
`Hylaform/Hylaform Plus
`Hylaform and Hylaform Plus, both hyaluronic
`acids derived from avian proteins, were approved
`by the Food and Drug Administration in April and
`October of 2004, respectively.15 These products
`are indicated for injection into the mid- to deep
`dermis for correction of moderate to severe facial
`wrinkles and folds. Both products are supplied in
`individual treatment syringes, with 30-gauge nee-
`dles packaged for single-patient use and ready for
`injection. Each syringe contains a solution of hy-
`
`lan B gel (5.5 mg/ml), sodium chloride (8.5 mg/
`ml), and water. Hylaform Plus has a larger particle
`size compared with Hylaform.15,20 –22 As with other
`hyaluronic acid derivatives, no skin testing is re-
`quired.
`
`Juve´derm
`Juve´derm (Allergan, Inc., Irvine, Calif.) was
`approved by the Food and Drug Administration in
`June of 2006 for use as a dermal filler. The makers
`of Juve´derm consider it to be “next generation”
`hyaluronic acid– based dermal filler.22 It possesses
`all the benefits of a hyaluronic acid– based filler
`and reportedly comes in a smooth gel form that is
`different from other hyaluronic acid fillers that
`use particle suspension technology.22 In addition,
`the manufacturer states that it contains the high-
`est concentration of nonanimal and cross-linked
`hyaluronic acid currently available.22 There are
`three formulations available: Juve´derm 24 HV, a
`highly cross-linked formulation; Juve´derm 30 HV
`dermal filler, a more highly cross-linked robust
`formulation intended for deeper filling; and Juve´-
`derm 30, for more shallow and superficial dermal
`augmentation.
`
`Captique
`Captique is a newer hyaluronic acid derivative,
`manufactured and packaged in the same manner
`as Hylaform. It was approved by the Food and
`Drug Administration in December of 2004 based
`largely on the approval of Hylaform. Captique
`differs from Hylaform in that it is derived from a
`bacterial source rather than an avian source. Cap-
`tique is indicated for injection into the mid- to
`deep dermis for correction of moderate to severe
`facial wrinkles.13,22
`
`EFFICACY
`The efficacy of hyaluronic acid fillers has been
`demonstrated in numerous clinical trials. Olenius16
`found in his series of 100 patients treated with Re-
`stylane that 60 percent of the effect was present at the
`12-month follow-up. In a prospective, randomized,
`controlled study using a non–animal-sourced hyal-
`uronic acid [or NASHA (Restylane)] in combina-
`tion with botulinum toxin type A (Botox; Allergan,
`
`43S
`
`

`

`Plastic and Reconstructive Surgery • November Supplement 2007
`
`purported longevity of 6 months has not been
`seen in all areas of injection. In the tear trough,
`malar, and glabellar regions, the longest longevity
`we have seen has been approximately 6 months.
`This has been enhanced to as long as 9 months
`with concomitant Botox treatment in the glabellar
`and forehead regions. In the nasolabial fold, ad-
`junctive injections are usually necessary within 4 to
`6 months and are required less often as injection
`sessions proceed. A layering technique in this area
`can also prolong injection intervals. The shortest
`duration, of approximately 3 to 4 months, has
`been seen in the lip region in our patients, chiefly
`in long-lip patients with minimal initial bulk. Be-
`fore injection, all patients are informed of the
`inherent variability in duration of effect; this is a
`critical part of the informed consent process. Re-
`injections (not including touch-ups) of specific
`areas are usually performed 4 to 6 months after the
`initial injection. In our experience, an additive
`effect is evident as the number of injections in-
`creases. Often, progressively less product volume
`is required with each subsequent injection.
`
`INDICATIONS
`With aging, the skin loses its viscoelasticity,
`which is maintained in part through the innate
`properties of hyaluronic acid. Volume loss, espe-
`cially in the lips, nasolabial, and malar regions, is
`seen with advanced age. Useful, more objective
`methods of rating the severity of facial rhytides
`and the corrective results have been described by
`Fitzpatrick et al.,24 Glogau,25 and Lemperle et al.26
`Lemperle et al.26 developed a 0- to 5-point rating
`scale to assess results after soft-tissue augmenta-
`tion with fillers (Table 3).
`
`Table 3. Classification of Facial Wrinkles*
`
`Irvine, Calif.), Carruthers and Carruthers23 dem-
`onstrated an improved and longer-lasting aes-
`thetic response for glabellar rhytides when Resty-
`lane was used in combination with Botox. At a
`follow-up of 16 weeks, 83 percent of the Restylane
`group, compared with 95 percent of the Botox/
`Restylane group, had aesthetic improvement.23
`This finding may be explained by the reduction in
`dynamic muscle action that could reduce filler
`deformation within the dermis. In addition, the
`subjects in the study commented on more “instan-
`taneous” results when Restylane was added to Bo-
`tox treatment for severe glabellar folds.23
`In a pivotal one-to-one randomized, double-
`blind, multicenter trial, Narins et al.17 compared
`the efficacy of Zyplast [bovine collagen (Allergan,
`Santa Barbara, Calif.)] to that of Restylane in the
`treatment of nasolabial folds. Using a Wrinkle Se-
`verity Rating Scale and a Global Aesthetic Im-
`provement Scale, the authors found that Restylane
`required less volume and fewer treatments to
`achieve an “optimal cosmetic result,” as evaluated
`by blinded investigators.16 In addition, both Re-
`stylane and Zyplast demonstrated a similar safety
`profile.16
`The pivotal trial for Hylaform compared the
`safety and efficacy of Hylaform viscoelastic gel with
`those of Zyplast for the correction of nasolabial
`folds in a prospective, multicenter, randomized,
`double-blind, parallel-group study conducted dur-
`ing an initial 12-week treatment phase.15,20 Hy-
`laform gel was found by an independent review of
`photographs to be equivalent to Zyplast (control
`filler) in the correction of nasolabial folds.20 As of
`this writing, there have been no clinical trials in-
`volving the use of Captique; Food and Drug Ad-
`ministration approval of this product was based on
`trials involving other hyaluronic acid fillers.13
`
`LONGEVITY
`One significant advantage of hyaluronic fillers
`over more traditional nonpermanent fillers, such
`as fat and collagen, is their increased tissue lon-
`gevity (Table 2). In our clinical experience, the
`
`Table 2. Longevity of Hyaluronic Acid
`
`Treatment Area
`Lips
`Nasolabial fold
`Tear trough
`Glabellar and forehead region
`
`Longevity
`3–4 months
`4–6 months
`⬎6 months
`6 months (up to 9
`months with Botox*)
`3–4 months
`Oral commissures
`*Efficacy is enhanced by up to 50 percent in the lip, glabellar, fore-
`head, and oral commissure areas with coadministration of Botox.
`
`44S
`
`Description
`No wrinkles
`Just perceptible
`wrinkle
`Shallow wrinkles
`Moderately deep
`wrinkle
`Deep wrinkle,
`well-defined
`edges
`Very deep
`wrinkle,
`redundant
`fold
`
`Grade
`0
`1
`
`2
`3
`
`4
`
`Areas Assessed
`Horizontal forehead lines
`Glabellar frown lines
`
`Periorbital lines
`Preauricular lines
`
`Cheek lines
`
`5
`
`Nasolabial folds
`Radial upper lip lines
`Radial lower lip lines
`Marionette lines
`Labiomental crease
`*Adapted from Lemperle, G., Holmes, R. E., Cohen, S. R., and
`Lemperle, S. M. A classification of facial wrinkles. Plast. Reconstr. Surg.
`108: 1735, 2001.
`
`

`

`Volume 120, Number 6S • Hyaluronic Acid Fillers
`
`Fig. 1. Aesthetic upper-to-lower lip height balance. The upper
`lip is approximately one-third of the height and the lower lip is
`two-thirds of the total lip height. This corresponds to the relative
`volume differences between the upper and lower lips.
`
`The lips and perioral region are the central
`aesthetic component of the lower third of the face.
`Lips express emotion, sensuality, and vitality. In
`evaluating the aesthetic lip, it is critical to assess
`the surrounding soft tissues as well as the maxil-
`lofacial harmony (Fig. 1). Some of the character-
`istics of an aesthetic and youthful lip are listed in
`Table 4 and shown in Figures 1 through 5. With
`aging, the lips undergo changes in vermilion bulk
`(pout) and exposure (thin lips) that can be ex-
`aggerated by bony retrusion and changes in den-
`tition (Fig. 4). Patients who require subtle refine-
`ments in lip fullness, projection, and degree of
`eversion are ideal candidates for augmentation
`with hyaluronic acid fillers (Fig. 5). In addition,
`
`Table 4. Comparative Features of the
`Youthful/Aesthetic Lip and the Aging Lip
`
`Aesthetic Lip
`One-third upper to two-
`thirds lower lip height
`ratio
`Distinct Cupid’s bow
`Central fullness of the
`upper lip
`Concave sloping of the
`upper and lower lips
`
`Upper lip 1–2 mm anterior
`to the lower lip
`Vermilio-cutaneous borders
`thickened with a pout
`Philtral columns prominent
`and full
`Commissures slightly
`upturned
`
`Aging Lip
`Upper and lower lips equal
`out, thin, and stretch out
`
`Loss of Cupid’s bow
`Thin, uniform, contoured
`upper lip
`Convex, ill-defined sloping
`projection from the nasal
`base and labiomental
`groove
`Equalized projection of the
`lips
`Loss of vermilio-cutaneous
`pout
`Philtral columns flattened
`
`Commissures downturned
`
`Fig. 2. The Cupid’s bow is sharp and well defined in youthful lips.
`
`marionette lines, the deep mental groove, and the
`anterior jowl line must also be evaluated and aug-
`mented when indicated, to optimize overall lip
`and perioral aesthetics.
`With increasing nasolabial fold depths, the
`face appears older and lacking in midface support.
`Hyaluronic acid fillers are ideal for blunting prom-
`inent nasolabial folds. Malar atrophy, resulting
`from fat, muscle, and skeletal atrophy, and soft-
`tissue descent contribute to the aging appearance
`of the middle third of the face (Fig. 6). Combining
`both surgical and nonsurgical options to provide
`support and fullness to the midface can result in
`marked rejuvenation in this facial region. It is not
`uncommon to perform a face lift and inject hyal-
`uronic acid filler into the lips, nasolabial folds, and
`malar or nasojugal areas. Hyaluronic acid aug-
`
`Fig. 3. Youthful lips have full philtral columns that add upper
`lip–to–nasal base fullness.
`
`45S
`
`

`

`Plastic and Reconstructive Surgery • November Supplement 2007
`
`Fig. 4. (Left) Aged lips with ill-defined and convex upper and lower lip sloping. (Right) Youthful lips demonstrate gentle concave
`sloping from the nasal base and labiomental groove. This provides the lips with a pleasing “pouty” appearance.
`
`mentation can be beneficial for rejuvenation of
`numerous regions of the face (Table 5).
`Combining fillers with Botox adds to the har-
`monious facial aesthetic balance. The amplified
`aesthetic result was shown by Carruthers and
`Carruthers,23 as discussed above. In our opinion,
`optimum efficacy is achieved by coinjection of
`Botox in numerous facial regions when indicated,
`including the brow/lateral canthal area, depres-
`sor angular oris, and glabella (Fig. 7). Hyaluronic
`acid can then be used to fill the nasolabial and
`deep glabellar folds, augment the lips, and blunt
`the tear trough (Fig. 1). In our experience, using
`Botox to relax the upper face and hyaluronic acid
`fillers to fill the lower face has provided our pa-
`
`Fig. 5. The upper lip should project 1 to 2 mm anterior to the
`lower lip.
`
`46S
`
`tients with an excellent aesthetic result that is fur-
`ther enhanced by up to 50 percent (Table 2).
`
`TECHNIQUE
`Annually, the senior author (R.J.R.) injects
`more than 350 patients with hyaluronic acid fillers
`at University of Texas Southwestern Medical Cen-
`ter. The majority of experience has been with
`Restylane alone or in combination with Botox.
`Satisfactory injections require a thorough under-
`standing of the product’s potential and the pa-
`tient’s expectations. Product knowledge includes
`proper technique, preparation, and training for
`the physician and office staff, as well as an under-
`standing of
`the product’s characteristics and
`guidelines. Patient knowledge includes expecta-
`tions, prior experience with injected filler mate-
`rial(s), and perceived downtime. Close patient fol-
`low-up is paramount to successful incorporation
`of fillers into one’s practice. In the senior author’s
`practice, all patients are seen at 2 weeks after in-
`jection to ensure treatment success. Touch-up in-
`jections at this time are needed in less than 5
`percent of patients, and the next visit is scheduled
`at 3 to 4 months. Regular follow-up allows for
`lower filler volume requirements with subsequent
`visits, especially in the perioral and nasolabial fold
`regions.
`The depth of hyaluronic acid injection is a
`critical consideration in optimizing the aesthetic
`result. Hyaluronic acid fillers with smaller gel par-
`ticles are best suited for injection into the super-
`ficial or upper part of the dermis. These fillers are
`
`

`

`Volume 120, Number 6S • Hyaluronic Acid Fillers
`
`Fig. 6. (Left) Descent of the oral commissures is seen with aging. (Right) Commissure downturning is also seen on the lateral view,
`along with flattened upper lip sloping.
`
`used to correct superficial lines, such as forehead
`(“worry” lines), periorbital, and perioral (vertical)
`rhytides. More moderate facial areas, such as gla-
`bellar and forehead lines, nasolabial folds, and
`atrophic scars, are best augmented in the mid-
`dermis level with hyaluronic acid fillers with me-
`dium-sized gel particles. Layering the filler(s) at
`different depths can further improve the final con-
`tour and efficacy.
`is ob-
`informed consent
`Before injection,
`tained from the patient. The majority of patients
`receive a combination of topical, local, and re-
`gional anesthesia. Topical anesthetic creams in-
`clude benzocaine, lidocaine, and tetracaine (New
`England Compound, Farmingham, Mass.) and
`are applied 20 minutes before injection of local
`anesthesia. Regional anesthesia includes infraor-
`bital and mental nerve blocks with 1% lidocaine
`and 1:200,000 epinephrine, or septocaine, which
`we have found to produce less discomfort and
`stinging. Supplemental, low-volume local anes-
`
`Table 5. Potential Treatment Areas for Hyaluronic
`Acid Filler Injection
`
`Injection Site
`Mental groove
`Infraorbital and supraorbital hollows
`Soft acne or other scars
`Temporal hollow
`Malar region
`
`Primary
`Treatment Area
`Lips*
`Nasolabial folds
`Glabellar lines
`Marionette lines
`Nasojugal fold
`(“tear trough”)
`Philtral columns
`Forehead lines
`*“Lips” includes the vermilio-cutaneous border, volume enhance-
`ment, and vertical rhytides.
`
`thetic is given in the perioral area, with an average
`requirement of 1.5 cc of 0.5% lidocaine per side
`with 1:200,000 epinephrine, buffered with 0.5 cc
`of bicarbonate, and injected via a 30-gauge needle.
`In our experience, this does not distort the treat-
`ment area.
`The following are guidelines for injection into
`specific facial regions based on our institutional
`experience. As mentioned earlier, injection around
`the nose and mouth is approved by the Food and
`Drug Administration. All other areas of injection
`are considered off-label use.
`
`INJECTION TECHNIQUES
`Various injection techniques have been de-
`scribed. Familiarity with all of these techniques is
`
`Fig. 7. Botox injected into the upper lip orbicularis oris and de-
`pressor anguli oris (DAO) muscles is combined with Restylane
`soft-tissue augmentation to enhance efficacy.
`
`47S
`
`

`

`Plastic and Reconstructive Surgery • November Supplement 2007
`
`Fig. 8. (Above, left) Serial puncture. (Above, right) Linear threading. (Below, left) Fanning. (Below, right) Cross-radial (cross-hatching).
`
`vital to improving efficacy and aesthetic results
`(Fig. 8).
`
`Serial Puncture
`Serial puncture is optimal for the glabella, for
`philtral column enhancement, and for fine rhyt-
`ides. It can also be used for the nasolabial folds.
`Multiple injections are made serially along the fine
`wrinkle or fold. The injection sites should be close
`together, so that the injected material merges into
`a smooth, continuous line that ultimately lifts the
`wrinkle or fold. It is helpful to pull the skin slightly
`away and out from the injection area while inject-
`ing. No spaces should remain between the serially
`injected material. If some minimal gaps are present,
`postinjection molding and massage can be used to
`blend the material into a smooth layer.
`
`Linear Threading
`The vermilio-cutaneous border and nasolabial
`folds are best treated using linear threading. The
`full length of the needle is inserted into the mid-
`
`dle of the wrinkle or fold to create a channel. The
`product is usually injected while the needle is
`slowly pushed forward, so that “threads” are de-
`posited along the length of the wrinkle or fold.
`One can inject while advancing the needle, which
`may push blood vessels out of the way, or one can
`utilize a retrograde injection technique, inserting
`product while withdrawing the needle from the
`tissue. Which approach to use is largely the pref-
`erence of the surgeon.
`
`Fanning
`We have not found fanning to be particularly
`useful. The needle is inserted in a fashion similar
`to that used in the linear threading technique, but
`immediately before the needle is withdrawn, its
`direction is changed and a new line is injected
`(without withdrawing the needle tip from the
`skin). The fanning pattern of lines should be
`evenly spaced in a progressive clockwise or coun-
`terclockwise direction, so that the contour is
`evenly filled and shaped. This technique is best
`suited for deep malar injection.
`
`48S
`
`

`

`Volume 120, Number 6S • Hyaluronic Acid Fillers
`
`Cross-Hatching (Cross-Radial)
`Cross-hatching is especially effective for filling
`the oral commissures. The needle is inserted in a
`fashion similar to that used in the linear threading
`technique, but before beginning the procedure,
`the cross-hatching lines should be carefully de-
`marcated. A series of linear threading injections is
`made in the treatment region. The pattern of lines
`should be evenly spaced in a progressive grid so
`that the contour is evenly filled and shaped. This
`technique is used when a relatively large area re-
`quires correction (i.e., facial contours) to maxi-
`mize filler coverage of the treatment area. This
`technique is particularly useful for the perioral
`area.
`
`TECHNIQUE REFINEMENTS
`
`Lips
`As with all aesthetic procedures, accurate and
`comprehensive aesthetic analysis is the first step
`(see above). Any asymmetries, previous injection
`sites, irregularities, and scars should be noted and
`pointed out to the patient and improved upon if
`feasible. Hyaluronic acid fillers are more viscous
`than collagen material, and injection may be more
`difficult until familiarity with the product is at-
`tained. While materials with smaller particle sizes,
`such as Restylane Fine Lines, flow more easily from
`the syringe and demonstrate less tissue resistance
`when injected in the proper plane, it is still im-
`perative to release the material from the syringe in
`a smooth and even fashion to avoid lumping and
`surface irregularities.
`Optimal lip rejuvenation involves two main
`components: volume enhancement and vermilio-
`cutaneous border enhancement. Volume filling is
`often required in older patients and those who
`have thin lips. Vermilio-cutaneous enhancement
`is usually required in younger individuals who
`have enough volume, but it is also indicated in
`older patients, along with volume augmentation.
`Linear threading and/or serial puncture tech-
`niques are implemented starting at the oral com-
`missures and proceeding in a lateral to medial
`direction. Marionette lines are a key element in
`overall lip enhancement; otherwise, results are
`destined to be disappointing to both the patient
`and the physician. A cross-radial technique is used
`around the oral commissure and marionette line
`to enhance and “lift,” or fill in, the corners of the
`mouth. Botox injection into the depressor anguli
`oris can further enhances this lifting effect. The
`dermal level is, once again, the mid-dermis. A
`range of 0.5 to 1.5 cc is often needed for each lip.
`
`Care should be taken to avoid superficial injection
`in this region, as a light blue hue may become
`visible. Intrainjection and postinjection palpation
`for surface irregularities is important. If material
`tracks away from the intended injection plane and
`created tunnel, then immediate massage is nec-
`essary to recontour the area. Massaging should be
`instituted immediately by the physician, as this is
`the best time to achieve molding and shaping.
`This avoids later discomfort that can be present if
`the patient is given that task.
`Injection of the lip itself can be accomplished
`at the submucosal level, within the superficial or-
`bicularis oris muscle mass. Placing the hyaluronic
`acid in this deeper level decreases its visibility and
`augments lip volume. Minimal augmentation of
`the philtral columns can further enrich the peri-
`orbital and lip augmentation. Restylane can also
`be used to refine the white rolls, which will en-
`hance the overall aesthetic result. More superfi-
`cial, finer vertical rhytides are augmented with
`smaller-particle hyaluronic acid (Restylane Fine
`Line) or collagen. Concomitant injection of 2 to
`4 U of Botox will further improve the longevity of
`lip rejuvenation by as much as 50 percent.
`The final result of overall lip rejuvenation
`should be evident immediately after the injec-
`tions, unless excess bruising and edema are
`present (Fig. 9). Immediate swelling is uncommon
`and may be a result of histamine release or im-
`mediate particle expansion by water absorption.
`Bruising, if present, should be controlled with
`compression during the injection so that there is
`no compromise of the final result from blood
`staining or volume due to extravasated blood.
`
`Nasolabial Fold
`An assessment of the depth and character of
`the nasolabial fold is critical to a successful out-
`come. Lemperle et al.26 provide a useful classifi-
`cation system for grading nasolabial fold depth. A
`concomitant face lift will also affect the degree to
`which the fold will require soft-tissue filler aug-
`mentation (blunting). The fold will never fully
`correct, and this would be unnatural even if it were
`possible. Nevertheless, a 50 percent or