Ophthalmic Plastic and Reconstructive Surgery
`Vol. 22, No. 3, pp 188-191
`©2006 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.
`
`Hyaluronic Acid Gel (Restylane) Filler for Facial Rhytids:
`Lessons Learned From American Society of Ophthalmic Plastic
`and Reconstructive Surgery Member Treatment of 286 Patients
`
`Michael S. McCracken, M.D.*, Jemshed A. Khan, M.D.t, Allan E. Wulc, M.D.:j:, John B. Holds, M.D.§,
`Robert G. Fante, M.D.11, Michael E. Migliori, M.D.<J[, Daniel A. Ebroon, M.D.#,
`Malena M. Amato, M.D.**, Rona Z. Silkiss, M.D.tt, and Bhupendra C. K. Patel, M.D.:j::j:
`
`*Department of Ophthalmology, University of Colorado Health Sciences Center, Denver, Colorado, U.S.A.; fOverland Park, Kansas,
`U.S.A.; :/:Department of Ophthalmology, University of Pennsylvania and Drexel Hahnemann Hospital; §Departments of Ophthalmology
`and Otolaryngology-Head and Neck Surgery, Saint wuis University, St. wuis, Missouri, U.S.A. ; IIDepartments of Ophthalmology and
`Otolaryngology, University of Colorado Health Sciences Center, Denver, Colorado, U.S.A.; '!Department of Ophthalmology, Brown
`University School of Medicine, Providence, Rhode Island, U.S.A.; #Jules Stein Eye Institute, David Geffen School of Medicine, UCLA,
`ws Angeles, California, U.S.A.; **Department of Ophthalmology, University of Maryland, and Georgetown University; ft Division of
`Ophthalmic Plastic, Reconstructive, and Orbital Surgery, California Pacific Medical Center, San Francisco, California, U.S.A.; and
`# Department of Ophthalmology, University of Utah, Salt Lake City, Utah, U.S.A.
`
`Purpose: To review injection techniques and patient satisfaction with injection of Restylane in various facial
`areas by American Society of Ophthalmic Plastic and Reconstructive Surgery members.
`Methods: Data from 286 patients treated with Restylane in nine American Society of Ophthalmic Plastic and
`Reconstructive Surgery practices were abstracted to a spreadsheet for analysis.
`Results: Nine practices performed Restylane injections for 8.8 months on average (range, 2 to 28 months).
`Average practice volume per patient was 1.2 ml (range, 0.7 to 2.1 ml). Nine of nine practices injected the
`nasolabial and melolabial folds, 9 of 9 practices injected the lips, and 6 of 9 injected the glabella. Only 2 of 9
`practices injected other fillers concurrently. Botox was injected concurrently by 8 of 9 practices. On a scale of
`I to 10, physicians rated average patient discomfort during Restylane injection 4.6 with topical anesthesia and 2.1
`with injectable lidocaine, with or without topical anesthesia. The end point for injection was determined by visual
`cues, volume of injection, extrusion of the product, and palpation. "Problematic" complications, including
`bruising, swelling, bumpiness, and redness each had an incidence of 5% or less. Patient satisfaction on a scale
`of 1 to 10 had an average rating of 8.1, compared with that of Botox injection (8.9), upper blepharoplasty (8.9),
`and collagen injection (6.6). The source of Restylane patients was estimated to be existing Botox patients ( 45% );
`existing non-Botox patients (18%); word of mouth (14%); and new patients for other services (13%).
`Conclusions: Injection techniques, volume, end points, and anesthesia vary for different facial areas and
`between practices. Patients experience mild to moderate injection discomfort that is lessened with injectable
`lidocaine. Self-limited problems occur in about 5% of patients. Physician-determined patient satisfaction is
`perceived to be higher than that of collagen injection but slightly lower than that of botulinum toxin injection. The
`major source of Restylane patients was from existing practice patients, especially botulinum toxin patients.
`
`R estylane (Medicis Aesthetics Inc., Scottsdale, AZ,
`
`U.S.A.) is a nonanimal, stabilized hyaluronic acid
`that is FDA approved for dermal implantation to correct
`facial wrinkles and folds. It is produced by bacterial
`fermentation and undergoes cross-linking to increase its
`tissue half-life. In contrast, Hylaform (!named Aesthet-
`
`Accepted for publication October 24, 2005.
`Presented in part at the American Society of Ophthalmic Plastic and
`Reconstructive Surgeons Annual Fall Scientific Symposium in New
`Orleans, Louisiana, U.S.A., November 9-10, 2001.
`Address correspondence and reprint requests to Dr. Michael S.
`McCracken, Colorado Laser Surgeons, 55 Madison Street, Suite 300,
`Denver, CO 80206, U.S.A. E-mail: mrnccracken@hotrnail.com
`DOI: 10.1097/01.iop.0000217562.64529.ff
`
`ics, Irvine, CA, U.S.A.) is injectable hyaluronic acid
`derived from rooster combs. Because hyaluronic acid,
`unlike collagen, does not differ cheinically from species
`to species, 1 it has a low risk of allergic reaction. Resty(cid:173)
`lane is a viscous, transparent gel, composed of stabilized
`hyaluronic acid (20 mg/ml). The particle size is 250
`Inilliinicrons. Medicis Aesthetics Inc. also produces sim(cid:173)
`ilar compounds with different particle sizes (Perlane,
`1,000 Inilliinicrons, and Restylane Fine Lines, 250 Inil(cid:173)
`liinicrons), but Restylane is currently its only FDA(cid:173)
`approved dermal filler.
`Unlike injectable collagen fillers, Restylane does not
`contain a local anesthetic. Although it was initially sup-
`
`188
`
`y
`
`rl
`
`Exhibit 1017
`Prollenium v. Allergan
`
`

`

`ASOPRS MEMBER TREATMENT OF 286 PATIENTS WITH RESTYLANE
`
`189
`
`plied in 0.7-ml glass syringes, it is currently supplied in
`syringes containing approximately 1.0 ml or 0.4 ml of
`material. Restylane does not require refrigeration before
`injection, but each syringe is manufactured for single
`use, and the product does not have a preservative.
`Restylane binds water and undergoes isovolernic deg(cid:173)
`radation. As it is resorbed, the remaining Restylane
`molecules bind more water,2 resulting in a longer-lasting
`fill than collagen injections. In fact, Restylane has been
`shown clinically to provide a more durable improvement
`in wrinkles than bovine collagen. 3 Furthermore, concur(cid:173)
`rent botulinum toxin injection has been demonstrated to
`improve and prolong the results of Restylane injection in
`the glabella.4
`
`METHODS
`The study was a multicenter retrospective review. Data from
`286 Restylane patients treated in 9 American Society of Oph(cid:173)
`thalmic Plastic and Reconstructive Surgery (ASOPRS) prac(cid:173)
`tices were abstracted to a spreadsheet for analysis.
`
`RESULTS
`Respondents were ASOPRS members who had been in
`practice for an average of 13.1 years (range, 2 to 20 years).
`These practices were early adopters of Restylane and had
`performed Restylane injections for an average of 8.8 months
`(range, 2 to 30 months). One of the practices was not injecting
`any other dermal fillers. The other 8 all used collagen in some
`patients. Two of the 9 practices injected collagen in the same
`area concurrently with Restylane in some patients. The average
`volume injected per application was 0.8 ml or less. Other fillers
`in use in these 9 practices included collagen (7 practices),
`autologous fat and Radiance (2 practices each), and micronized
`Alloderm (one practice). Of note, none of the practices was
`injecting Hylaform at the time of the survey. Eight of 9
`practices injected botulinum toxin concurrently. The average
`volume injected per patient was 1.2 ml (range, 0.7 to 2.1 ml).
`The average number of patients treated per practice and aver(cid:173)
`age volume injected for the most common applications are
`summarized in the Table. Typical results of treatment are
`demonstrated for the nasolabial folds (Fig. 1) and nasolabial
`folds and lips (Fig. 2). Other sites less frequently injected
`included depressed scar augmentation (3 practices) and sub(cid:173)
`mental furrow, cheeks, and alar retraction (one practice each).
`When respondents were asked about the maximum volume that
`could be safely injected in one setting, the average response
`was 2.9 ml (range, 1.4 to 5.0 ml).
`When used, topical anesthetics were applied for an average
`of 36 minutes (range, 15 to 100 minutes). These included
`various formulations (e.g., topical lidocaine gel, benzocaine/
`lidocaine/tetracaine gel, and tetracaine gel). In all patients, the
`glabella was exclusively treated with topical anesthesia.
`The nasolabial folds were pretreated exclusively with topical
`agents in all patients of four of the nine practices, and one
`practice used both injectable and topical anesthesia in all
`patients. Two practices used injectable anesthesia for all naso(cid:173)
`labial folds and also used topical for 30%. Of the remaining two
`
`FIG. 1. Typical patient before (A) and after (B) Restylane injec(cid:173)
`tion to the nasolabial folds.
`
`practices, one used supplemental local anesthesia and the other
`used half topical anesthesia and half local anesthesia.
`For lip injection, 5 of the 9 practices used topical anesthesia
`
`Ophthal Plast Reconstr Surg, Vol. 22, No. 3, 2006
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`190
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`M. S. MCCRACKEN ET AL.
`
`Average volume per patient for most common sites
`Practices
`Volume
`(ml)
`injecting
`
`Patients/practice
`
`Application
`
`Nasolabial folds
`Melolabial folds
`Vermillion border
`Lip volume enhancement
`Glabellar furrows
`
`9
`9
`9
`8
`6
`
`26
`6
`22
`18
`3
`
`0.8
`0.5
`0.5
`0.6
`0.3
`
`used both topical and injectable anesthesia, and the remaining
`practices used topical anesthesia exclusively.
`Protective wincing movements were reported in 20% of
`patients treated with topical anesthetic. The estimated patient
`discomfort scale averaged 4.6 of 10 for topical anesthesia and
`2.1 of 10 for injectable lidocaine with or without topical
`anesthesia.
`Commonly used injection techniques included serial puncture,
`linear threading, fanning, and cross-hatching. Most respondents (7
`of 9) estimated the injection end point by visual cues. Other end
`points included volume of injection, extrusion of the product, and
`palpation.
`Of the nine practices, one routinely administered prophylactic
`oral antiviral medication and six used antivirals for patients with a
`history of HSY. Two practices do not prescribe antivirals.
`All complications occurred locally. "Problematic" compli(cid:173)
`cations included bruising (5%), swelling (4%), bumpiness
`(3% ), asymmetry (3% ), and redness (1 % ).
`Physician respondents rated their perception of patient sat(cid:173)
`isfaction after Restylane injection to be 8.1 on a 1 (low) to 10
`(high) scale. The physician's perception of patient satisfaction
`after Restylane injection compared well with that of botulinum
`toxin injection (8.9), upper blepharoplasty (8.9), and collagen
`injection (6.6). Analysis of the source of Restylane patients
`revealed existing botulinum toxin patients to be the largest
`source. Other sources included existing non-botulinum toxin
`patients (18%), word of mouth (14%), and new patients for
`other services (13%).
`
`DISCUSSION
`An early analysis of 9 ASOPRS practices reveals that
`injection techniques, volume, end points, and anesthesia
`vary for different facial areas and between practices.
`However, patient satisfaction with Restylane injection is
`higher than that of collagen injection and comparable to
`that of botulinum toxin injection and upper blepharo(cid:173)
`plasty. Patients experience mild to moderate discomfort,
`which is lessened by injectable lidocaine.
`At the time of the survey, the product was only
`available in 0.7-ml syringes, but it is now distributed in
`both 1.0-ml and 0.4-ml syringes. This change may affect
`the volumes that the participants now use for the various
`applications. As the number of applications for the prod(cid:173)
`uct continues to grow, we find ourselves injecting higher
`total volumes as patients receive correction in multiple
`areas. Restylane may be injected at the same time
`as botulinum toxin, and concurrent injection of both
`products has been shown to increase the longevity of
`
`B
`
`FIG. 2. Typical patient before (A) and after (B) Restylane injec(cid:173)
`tion to the nasolabial folds and lips.
`
`in more than 75% of patients, and 5 of the 9 practices used
`injectable lidocaine in more than 75% of patients. Two prac(cid:173)
`tices used both topical and injectable anesthesia in all patients.
`For melolabial fold (marionette lines) injection, one practice
`
`Ophthal Plast Reconstr Surg, Vol. 22, No. 3, 2006
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`ASOPRS MEMBER TREATMENT OF 286 PATIENTS WITH RESTYLANE
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`191
`
`Restylane.4 During injection, patients may experience mild
`to moderate discomfort, which is lessened with injectable
`lidocaine for most sites. When injections are used for the
`lips or nasolabial folds, we recommend injecting lidocaine
`to balloon the mucosa of the gingival sulcus in the plane of
`the third tooth from the midline. This plane corresponds to
`the infraorbital nerve superiorly and the mental nerve infe(cid:173)
`riorly. Our preferred injectable anesthetic is lidocaine 2%
`with epinephrine 1:200,000 injected as 0.5 to 1.0 ml at each
`site. Self-limited complications occur in approximately 5%
`of patients.
`In summary, we found Restylane to be a safe, predict(cid:173)
`able, and effective treatment for static wrinkles. We
`await the results of long-term experience with the inclu(cid:173)
`sion of additional areas such as the eyebrows and tear
`trough.
`
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`4. Carruthers J, Carruthers A. A prospective, randomized, parallel
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