Clinical Procedures in Laser Skin Rejuvenation - part 9 pps

Autologous fat was first reported as a soft tissue filler by Neuber in 1893.13Paraffin was later used, but with significant drawbacks.13,14The ensuing years brought the use of vegetable

the need for a fundamental understanding of this muscular

anatomy.7 It is clear, however, that, due to diffusion

effects and the relative safety of Botox, the variability in

points of injection and dosages has not significantly

reduced the product’s overall satisfactory clinical results

In our opinion, required dosages for a given anatomical

area can be reduced by precise localization and direct

injection into the targeted muscle or muscle groups

It is imperative that one keep in mind not only the

specific muscle locations when providing

neuromodula-tor treatment, but also the functional interrelationships

of the muscle action Many of these act as antagonist–

protagonists in the position of the brow The use of

Botox in general has evolved with experienced and

thoughtful injectors from a simple wrinkle treatment to

a means of reshaping, contouring, and softening the

facial features associated with aging and the stigmata of

the frowning, angry or worried facial form

Botox is frequently used to specifically target

differ-ent muscular units In the glabellar region, targeting of

the procerus and corrugator muscles is used to

elimi-nate furrowing along the radix and medial eyebrow

region The lateral orbital region, which is commonly

referred to as the ‘crow’s feet’, is also a region in which

Botox may be of use to target the orbicularis oculi

mus-cle and reshape the upper face.The use of Botox in the

forehead must be conservative in order to balance the

risk of brow ptosis by targeting the only brow elevator,

the frontalis muscle Perioral lip lines have also been

treated with sparing amounts of Botox to suppress the

pursing effect of the orbicularis oris muscle One must

be careful not to compromise oral competence as aresult of this treatment Botox injection into thedepressor anguli oris muscle can target marionettelines, and its use for contraction of the mentalis musclecan alleviate complaints of a dimpled chin appearance,but one must be careful to avoid the lower lip depres-sors Platysmal banding in the neck due to overactiveplatysmal muscle action can be treated using Botox.However, this works best for younger patients withgood skin elasticity or postoperative residual bands.8

This facial characteristic may ultimately only be treatedoptimally with surgical intervention

The use of botulinum toxin type A and laser facing has been studied recently due to the prolifera-tion of nonsurgical treatments for the aging face andthe desire to perform more than one treatment in onevisit It has been demonstrated that the use of Botox inconjunction with laser resurfacing results in improvedoutcomes in the periorbital region.9Other areas of theface have also been studied and have been shown tohave less rhytids after Botox and laser than those areastreated with laser alone, and these results were clini-cally most significant in the crow’s feet region.10It hasalso been shown that the use of Botox as an adjunctivetreatment will prolong the beneficial results of laserresurfacing and should therefore be offered as anoption to patients wishing to have longer-lastingelimination of rhytids.11It is safe to use laser resurfac-ing after treatment with Botox, as this will have noeffect on the efficacy of the Botox injection or otherapparent untoward effects.12

resur-182 Clinical procedures in laser skin rejuvenation

Fig 16.1 The glabellar complex as demonstrated before and after injection of botulinum toxin

HISTORICAL PERSPECTIVE

The search for an ideal product to be used for soft

tissue augmentation has been ongoing with varying

degrees of success since the end of the 19th century

Autologous fat was first reported as a soft tissue filler

by Neuber in 1893.13Paraffin was later used, but with

significant drawbacks.13,14The ensuing years brought

the use of vegetable oils, mineral oil, lanolin, and

beeswax; all demonstrating the problems that continue

to be associated with fillers in use today, namely

chronic inflammation and migration.15–18 Purified

bovine dermal collagen was first developed in an

injectable form in 1977 by Knapp et al.19 In early

trials, the most common complications seen were

cellulitis, urticaria, and hyperpigmentation of the

skin making it superior to its predecessors.19

Teflon, polytetrafluoroethylene paste, was initially

thought to be a useful soft tissue filler However, its

consistency and injectability limit its main commercial

use today to vocal cord augmentation procedures.20

It is reasonable to divide soft tissue fillers into the

biologicals and the nonbiologicals.We will first discuss

the biologicals, both tissue-derived and synthetic

Finally, we will discuss the nonbiologicals, i.e., fillers

not based on animal tissue Table 16.1 is offered as a

reference to help guide clinicians in the selection of a

soft tissue filler

BIOLOGICAL MATERIALS USED AS

INJECTABLE IMPLANTS

The use of biological materials for injection is thought

to be advantageous in that the inflammatory response

should be less for a substance that is of

nonimmuno-genic biological origin However, cross-reactivity has

not been eliminated altogether, and although

biologi-cal fillers do result in less fibrosis and contraction

around the injection site, problems still exist The

most common side-effect seen with the use of soft

tis-sue fillers is the localized reaction to the injection or

implantation Swelling, redness, and pain can all be

treated with conservative measures Allergies and

delayed hypersensitivity responses are more serious

complications, and indeed preclude the further use of

the material

CollagenCollagen was the first material to be approved by theFDA for used as an injectable soft tissue filler, in 1981.15

Many derivatives are available today, including Zyderm I(35 mg/dl), Zyderm II (65 mg/dl), and Zyplast(Collagen Corp., Palo Alto, CA) Cosmoderm andCosmoplast (Inamed Corp., Santa Barbara, CA) differfrom Zyderm and Zyplast only in that they areinjectable human collagen products derived from a sin-gle cell line source Zyderm I was the first nonautolo-gous agent to be approved for use as a soft tissue filler inthe USA, in 1981.21Zyderm II was soon developed as amore concentrated form.These substances work on thebasis of low-grade focal inflammation and are of a for-giving nature.They are easy to inject, and precise injec-tion technique is not very important Zyderm is derivedfrom bovine dermal collagen, with 95% type I and 5%type III collagen The processing of Zyderm removesthe telopeptide regions of the molecule without dis-rupting the natural helical structure However, 3–3.5%

of the population still demonstrate a hypersensitivity tothe substance, and after one negative skin test, 1–5 % ofpatients will still show an allergic reaction when thematerial is placed in the face.22

Zyplast is crosslinked by the addition of hyde, which lessens the immune response to it and alsoserves to increase resistance to bacterial collagenase.Zyderm injections will provide cosmetic results for2–3 months, at which time repeat injections areneeded Zyplast provides longer results (on average2–4 months) due to its crosslinking, but eventually

glutaralde-The bioscience of the use of botulinum toxins and fillers for non-surgical facial rejuvenation 183

Table 16.1 Soft tissue fillers

Synthesized Synthetic Biological filler bioactive non-resorbable materials fillers polymers Bovine collagen Sculptra Artecoll Recombinant Reviderm intra Silicone human collagen

Juvederm Radiesse Ultrasoft Hyaluronic acid Softform Dermal matrices Advanta,

Dermalive, Dermadeep

repeat injections are also necessary Zyderm and

Zyplast have to be injected intradermally Zyderm is

infiltrated into the papillary dermis, whereas Zyplast is

preferably placed into the midreticular or deep

reticu-lar dermis at the dermal–subcutaneous interface

Zyplast should not be injected into the superficial

pap-illary dermis or in areas of thin skin, because it forms

beads on placement.23

Hyaluronic acid

Hyaluronic acid is a biopolymer of glycosaminoglycan

chains, which coil on themselves resulting in an elastic

and viscous matrix It is found naturally in the dermis

and has a high affinity for water, thereby serving to

hydrate and plump the skin.24The loss of hyaluronic acid

with age leads to dermal dehydration and the formation

of rhytids.25Crosslinking can lengthen the half-life of

hyaluronic acid, but cannot eliminate its degradation

Products clinically available include Hyalform, Hyalform

Plus and Hyalform Fine Line (Biomatrix, Inc.,

Ridgefield, NJ), Restylane (Q-Med, Uppsala, Sweden),

and Captique (Genzyme, Ridgefield, NJ), and other

forms, such as Juvederm (Allergan, Irvine, CA), are

under clinical trail in the USA Q-Med is also

responsi-ble for Restylane Fine Line and Perlane Perlane is

designed for subcutaneous injection and is primarily

used for volume replacement It is a larger particle than

that found in Restylane, and therefore has a longer

duration

While Juvederm is a pure hyaluronic acid form that is

rapidly absorbed, Hyalform is a crosslinked xenogenic

variety derived from rooster combs, which was

submit-ted for FDA approval as an equivalent product to

Restylane.The latter is only partially crosslinked and is

processed from a streptococcal fermentation.24Neither

material requires skin testing Restylane, not being

derived from an animal source, has a lower risk of

immune reaction Both forms are reabsorbed, albeit at a

slower rated than the collagen products It has been

reported that effects last up to 6 months.26Hylaform is

less viscous, and this may decrease the duration of its

effect to 2–4 months, although no side-by-side trials

have been published

Hylaform is a modified form of hyaluronan, a

natu-rally occurring substance found in human skin and

throughout the body Since Hylaform is based on

natural hyaluronan, the human body accepts it as itsown Hylaform also mimics the hydrating and liftingeffect of hyaluronan, which keeps the skin hydrated andelastic In side-by-side comparison with Restylane,Hyalform showed a higher incidence of skin reaction.26

Hyalform also behaves as a stronger hydrogel thanRestylane and contains a lower amount of crosslinkedhyaluronic acid Restylane can contain up to four times

as much protein, from bacterial fermentation, asHyalform for the same volume Finally, hyaluronanderived from rooster combs has been in use longer thanthat derived from streptococci, and has demonstratedits reliability and safety

A randomized study of 138 patients comparingRestylane and Zyplast for the correction of nasolabialfolds demonstrated that a more durable aestheticimprovement was found with Restylane.27Less injectionvolume was required with Restylane, which was alsosuperior to Zyplast in retaining its shape A comparison

of Restylane with and without the addition of Botoxdemonstrated that glabellar rhytides responded better tothe combination of Restylane and Botox.28 Thosepatients who present with deep vertical glabellar lines atrest may not be able to eliminate those lines with the use

of Botox alone Restylane can serve to fill the restinglines, and the addition of Botox prevents the deforma-tion of the filler residing in the dermis, thereby perform-ing a protective function Restylane is also useful as a softtissue filler for microchelia (Fig 16.2)

Captique is a filler that utilizes a recombinant form

of hyaluronic acid that lowers the probability ofimmunological reactions The profiles of this filler aremuch the same as those of Hyalform, with a duration

of 2–4 months and a similar injection and viscosityprofile

Materials that are resorbable by the body areless likely to provoke a longstanding immunologicalresponse, because of their transient nature However,substances that are derived from nonautologoussources have the potential to evoke cross-reactivity.Restylane and Hylaform are newer materials that arebeginning to undergo long-term studies, which arebeginning to show side-effects A study of 709 patientsover 4 years showed positive skin tests in those whodeveloped delayed skin reactions to these materials.The manufacturer does not recommend skin testingfor these materials – but these reports may suggest

184 Clinical procedures in laser skin rejuvenation

otherwise.29Case reports have also shown the potential

for granuloma formation with the use of hyaluronic

acid derivatives.30 Positive skin tests have

demon-strated chronic inflammatory reactions at up to 11

months and serum immunoglobulin G (IgG) and IgE

antibodies to hyaluronic acid.32 Of course, these

aesthetic complications must be fully addressed with

the patient before any procedure is performed

Dermal matrices

The search for soft tissue fillers free of antigenicity

has led to the development of Alloderm and Cymetra

(LifeCell Corp., Branchburg, NJ).Alloderm is processed

from cadaveric skin, preserving the basement

mem-brane and dermal collagen matrix After the fibroblasts

have been extracted, the material is cryoprotected,

which enables it to be freeze-dried in a two-step

proce-dure Alloderm is screened and monitored for bacterial

contamination before it is shipped to the physician It is

supplied in sheets of differing sizes and thicknesses,

which must be rehydrated by the physician before use

The sizing of this material makes it ideal for repairing

large tissue defects Skin testing is not necessary,

because it is an acellular graft It is also less likely to

develop secondary infection However, if infection doesoccur, it is not necessary to remove the implant, only totreat the infection.22Alloderm does not appear to last aslong or be as consistent as originally described, which,along with its high cost, has decreased its use and popu-larity.The requirement for a surgical procedure has alsolimited its use Zyplast was studied in direct comparisonwith Alloderm with follow-up at 1 year, by Sclafani

et al.32Superior results were seen with Alloderm whichstabilized in resorption at 6 months, while Zyplast wasprogressively absorbed

Cymetra is a micronized injection of Alloderm tissue

It is created by homogenizing an Alloderm sheet cut intostrips In a study of 44 patients involving the use ofCymetra and Zyplast to fill upper lip lines, there was astatistically significant improvement at 1 year in lipappearance among those randomized to receiveCymetra Some reports suggest that Cymetra does notreabsorb as Zyplast is observed to do, and thereforerepeated treatments provide an additive effect and aremore effective.33Cymetra carries an increased incidence

of inflammatory reactions and has not been shown to lastlonger than Zyplast It also requires mixing into a thickpaste, usually with 1% or 2% lidocaine This thickmixture can be difficult to inject Due to the lack ofThe bioscience of the use of botulinum toxins and fillers for non-surgical facial rejuvenation 185

Fig 16.2 Restylane used as a soft tissue filler for lip augmentation

long-term results and the increased cost, Cymetra is not

used as frequently as other soft tissue fillers

Small-intestinal submucosa, marketed as Oasis,

Surgisis, or Stratasis, is a sterile acellular graft material

extracted from the small intestine of pigs Its main uses

continue to be for nasal reconstructive surgery, but

increasing experience may broaden its applications

Isolagen (Isolagen Tech., Metuchen, NJ) is currently

under FDA investigation It consists of injectable

fibroblasts derived from an autologous source and

cultured for 4–6 weeks Skin is harvested from the

preauricular region in a 3 mm punch biopsy.34Repeat

injections, most commonly three, are required, spaced

2 weeks apart A 6-month study by Watson et al35

showed increased thickness and density of the

postau-ricular dermal collagen and no inflammatory reaction

Due to the viability of the fibroblasts, Isolagen must be

shipped, processed, and injected within 24 hours

However, it theoretically has the advantage of low

immunoreactivity, as with the other human

deriva-tives A significant drawback is that patients must also

be willing to wait up to 18 months to see results, as the

fibroblasts must first produce new collagen

SYNTHESIZED BIOACTIVE FILLERS

The search for the ideal soft tissue fillers has led to the

development of materials that do not mimic collagen

but rather serve to increase volume for a longer period

of time due to their preformed microsphere shapes

Sculptra (Biotech Industry, SA, Luxembourg) is a

powder of poly-L-lactic acid microspheres ranging

from 2 to 50 µm Studies comparing the various soft

tissue fillers have shown the microspheres of Sculptra

to be histologically degraded at 9 months Sculptra has

only been FDA-approved for the treatment of HIV

lipodystrophy, and provokes an intense inflammatory

reaction leading to a fibroblastic response resulting in

increased appearance of the tissue The complications

reported include draining granulomas, and (like other

fillers) it must be injected subcutaneously

Reviderm intra (Medical International, Netherlands),

available in Europe, is a suspension of 2.5% dextran

microspheres of 40 µm in 2.0% hyaluronic acid

Radiesse (formerly Radiance FN) (Bioform Inc.,

Franksville, WI) is a suspension of 30% calcium

hydroxyapatite (similar to the composition of bone)microspheres ranging in size from 25 to 40 µm in acarboxymethylcellulose gel The microspheres ofReviderm produced the greatest amount of granula-tion tissue, but were also disintegrated at 9 months.Radiesse microspheres were gone at 9 months, butthey stimulated almost no foreign body reaction.36

Few macrophages were visualized surrounding themicrospheres of Radiesse, suggesting that they aredegraded by enzymatic processes rather than cellularone Radiesse is not recommended for use in lip aug-mentation, as the microspheres will be compressedinto strands during the act of mastication Radiesse is athick paste, which can be difficult to inject and must beinjected only in deep dermis It is used in thenasolabial folds, but we caution use in the lips, which isalso the policy of the manufacturer It has an increasedincidence of nodule formation, which can only bedealt with by surgical excision

SYNTHETIC NONRESORBABLE POLYMERS

Materials that are foreign to the human body have alsobeen used in the development of soft tissue fillers inboth injectable and implantable forms

Injectable

Artecoll (Artes Medical Inc., San Diego, CA) is asuspension of 20% microspheres 40 µm in diametermade of polymethylmethacrylate (PMMA) in 3.5%bovine collagen solution.Artecoll works by microgranu-loma formation, which may not be controllable Thisproduct produces immediate correction with collagenand also permanent replacement with new collagen pro-duced as part of the inflammatory response.22Artecoll,unlike the other microspheres, does not become reab-sorbed, and histologically new collagen deposits arevisible at 1 month.36A minimal immunogenic responsehas been observed due to the fact that the telopeptidesare removed from the collagen.As with other xenogenicinjectables, skin testing is required before use

The smooth surface of the microsphere prevents aforeign body reaction, and the size prevents migration

186 Clinical procedures in laser skin rejuvenation

and phagocytosis.37 It should not be used in areas of

fine skin, as the implants may be more visible, and

should be avoided in those patients prone to keloids, as

any foreign material may serve to increase the incidence

of keloids However, Artecoll demonstrates a much

lower incidence of immunological response, 0.06%, as

compared with Zyderm, which has an incidence of

3%.36 Migration has only been observed when the

material is injected into the dermis in trials with guinea

pigs, and has not been observed with correct placement

of the material.38Artes Medical may reformulate the

product in a US version with hyaluronic acid to meet

FDA requirements All injectable filler materials may

lead to overexpression of the host’s foreign body-type

immunological reaction.This may, in rare cases, lead to

the formation of a granuloma

The combination of materials is foreshadowed

in the development of Dermalive and Dermadeep

(Dermatech, Paris, France) In Europe, 30 or more

synthetic polymers are available for use in general,

although this may vary somewhat by country Examples

of such polymers include Dermalive, and Dermadeep,

which are combinations of pure hyaluronic acid (40%

and 60%, respectively) and an acrylic hydrogel The

hyaluronic acid is used as a carrier for the acrylic

poly-mer.They have been developed in response to the need

for repeat injections when using such materials as

pure hyaluronic acid and collagen The tolerance of

Dermalive is excellent and it has been supplemented

with injections of Juvederm or Restylane for fine line

and superficial defects.39A 3-year study of this

combi-nation therapy in 455 patients demonstrates an 88%

patient satisfaction rate with minimal side effects.39

Silicone, much maligned due to its history in breast

augmentation, is another synthetic injectable Its

use has been associated with the development of

connective tissue ingrowth and granulomas from

macrophages and foreign body cells (Fig 16.3).40This

is more commonly seen in patients with very lax

skin, which facilitates the migration of the silicone,

and with the substitution of cheaper,

non-medical-grade silicone fluids used by nonprofessionals.36

When used as silicone fluid, the material is injected

via the microdroplet technique In the rare case of

siliconoma development, the use of corticosteroids

has proven helpful, but this is rarely a completely

sat-isfactory treatment.41Late-term granulomas are not

uncommon As a result, we do not recommend thismaterial

ImplantableImplantable expanded polytetrafluoroethylene (e-PTFE) (WL Gore and Assoc., Flagstaff, AZ) has beenused in the field of vascular surgery for over 30 years,demonstrating its safety and reliability.42 Tissueingrowth is marginal into the material, but when it isshaped into a tube, longitudinal growth occurs Thisserves to strengthen the filler and secure it to the site

of implantation.43Ultrasoft is a thinner, softer form ofthe tubular form of implantable expanded polytetra-fluoroethylene (Fig 16.4)

The tubular form was originally marketed under thename SoftForm (Collagen Corp., Palo Alto, CA), andwas used as soft tissue filler for lip augmentation.There still exists a risk of extrusion or exposure of theends of the material at the entrance wound where theimplant is delivered Softform showed wall stiffeningdue to the abundance of ePTFE creating an accordioneffect The risk of extrusion at the insertion sites cre-ates a potential source of infection If complications doarise, the implant is always removable Due to thehigher content of ePTFE, Softform shortens and hard-ens with time This can create an ‘accordion effect’.Ultrasoft, with its thinner walls, has addressed thisissue, with early success being reported

The bioscience of the use of botulinum toxins and fillers for non-surgical facial rejuvenation 187

Fig 16.3 Granuloma and foreign body reaction afterinjection of silicone

Advanta (Atrium Medical Corp., Hudson, NH) is

a dual-porosity implant developed to provide softer

palpability, less migration, and reduced shrinkage.The

outer core measures 40 µm and the inner 100 µm,

with the inner core being exposed to the surrounding

tissue A study comparing Softform with Advanta

demonstrated neovascularization and cellular

integra-tion into the interstices of the Advanta implant, while

the Softform implant demonstrated a cellular capsule,

more inflammatory cells, and fewer vascular elements

within the devices.44Advanta is designed for use in the

nasolabial folds and for lip augmentation

TECHNIQUES

When considering injectables, there are basically three

techniques used to deliver material to the deep dermis

or subcutaneous level: linear threading, serial puncture,

and droplet Linear threading is a technique by which an

agent is delivered in a uniform fashion while the needle

is slowly withdrawn from the tissue It is particularly

effective when performing lip augmentation along the

mucocutaneous border.The serial puncture technique is

used to deliver small aliquots of filler at multiple spots

to achieve even distribution over a two-dimensional

area Finally, the droplet technique is used in a mannersimilar to that in linear threading However, instead of

an even distribution of filler as the needle is withdrawn,microdroplets of filler are delivered into the tissue bygentle pumping on the syringe as the needle is with-drawn The droplet technique has been advocated foruse when injecting silicone The depth of injection,however, is dependent on the injectable material beingused Most clinicians prefer the serial injection tech-nique for use in fine lines and the lips.The other optionsinclude the microdroplet technique or surgical implan-tation in the subcutaneous plane

CONCLUSIONS

Many patients who present to their physicians withcomplaints of an aging face or cosmetic deformities areeager to avoid surgical intervention As such, they arewilling to use newly introduced minimally invasiveoptions for their desired corrections Today, there is amyriad of injectable and implantable soft tissue augmen-tation options at the experienced clinician’s disposal Aconcern with the use of permanent filler is the potentialfor migration to other areas outside of the injection site,which can lead to potential deformities The choice of

188 Clinical procedures in laser skin rejuvenation

Fig 16.4 Ultrasoft used for lip augmentation

which product to use can be based on a number of

factors, including the desires of the patient, the cost to

the patient, and the experience of the clinician Caution

must be exercised, however, when considering the use

of soft tissue fillers that have been newly introduced to

the market and have not yet undergone long-term

observation and study.With more knowledge and

expe-rience, one will be better able to tailor the use of specific

materials to the particular desires of each patient

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augmentation Part II: Clinical investigations Plast Reconstr Surg 1995;96:627–34.

38 McClelland M, Egbert B, Hanko V, Berg RA, DeLustro F Evaluation of artecoll polymethylmethacrylate implant for soft-tissue augmentation: biocompatibility and chemical characterization Plast Reconstr Surg 1997;100:1466–1474.

39 Bergeret-Galley C, Latouche X, Illouz YG The value of a new filler material in corrective and cosmetic surgery: DermaLive and DermaDeep Aesthetic Plast Surg 2001; 25:249–55.

40 Rapaport MJ, Vinnik C, Zarem H Injectable silicone: cause of facial nodules, cellulitis, ulceration, and migration Aesthetic Plast Surg 1996;20:267–76.

41 Bigata X, Ribera M, Bielsa I, Ferrandiz C Adverse granulomatous reaction after cosmetic dermal silicone injection Dermatol Surg 2001;27:198–200.

42 Costantino PD Synthetic biomaterials for soft-tissue augmentation and replacement in the head and neck Otolaryngol Clin North Am 1994;27:223–62.

43 Ahn MS MN, Maas CS Soft tissue augmentation Facial Plast Surg Clin North Am 1999;7:35–41.

44 Truswell WH Dual-porosity expanded fluoroethylene soft tissue implant: a new implant for facial soft tissue augmentation Arch Facial Plast Surg 2002;4:92–7.

polytetra-190 Clinical procedures in laser skin rejuvenation

Constantly evolving technology has given cosmetic

physicians and surgeons an ever-increasing

armamen-tarium with which to deliver more effective

treat-ments with minimal or no downtime Combining a

variety of therapeutic options can yield an enhanced

effect that is more than the sum of its individual

parts Understanding the balance of facial

muscula-ture is essential for facial rejuvenation and facial

reshaping utilizing botulinum toxin The concept of

facial muscle relaxation and balance is the foundation

on which further rejuvenation with fillers can

be built The expanding menu of fillers gives us an

enlarging palate of materials for facial filling,

volumizing, and rhytid ablation (Fig 17.1)

BOTULINUM TOXIN TYPE A

DILUTION AND INJECTION

TECHNIQUE

Botulinum toxin type A (Botox and Botox Cosmetic)

binds to the nerve endplate and blocks the release of

acetylcholine, decreasing the strength of muscle

con-traction and reducing dynamic rhytidosis.1,2This bond is

permanent, and acetylcholine release begins again when

the nerve sprouts a new endplate One hundred units of

Botox is packaged as a powder.This purified protein is

reconstituted in sterile saline, typically in 1, 2, or 4 ml

to give the desired dose in 0.1ml aliquots.3Differentvials can be mixed for different strengths for differentmuscles (Figure 17.1) During the actual mixing ofBotox, the vacuum seal must be broken with two needlepunctures before instilling the saline to avoid an overex-uberant mixing and frothing of the Botox, which canaffect potency.The saline should be added slowly, angledagainst the side of the vial, avoiding frothing of the mix-ture Although it is claimed that the use of preservedsaline diminishes discomfort during injection (there isless of a burning sensation) and that it lengthens thetime that reconstituted refrigerated Botox can last, wecontinue to use non-preserved saline for reconstitutingBotox.We feel that it may retain its potency for a longerperiod of time.4When storing reconstituted Botox, itshould be refrigerated and not frozen Adequate dosagefor each muscle group is key.While an insufficient dosewill yield an insufficient result, overtreating is also not adesired cosmetic result Because the patient may notbegin to notice the clinical effect for at least 3–5 days,and the full effect may not be evident for 7–10 days, werequest a revisit for a dose adjustment in 1–2 weeks fol-lowing the initial treatment session

After cleansing the injection sites with alcohol (there

is some discussion about alcohol reducing the effect

of botulinum toxin), we prefer to apply a topicallidocaine/tetracaine anesthetic cream, Photocaine(Universal Pharmacy, Salt Lake City, Utah), for 15–20minutes Further vasoconstriction is encouraged by

17 Adjunctive techniques II: clinical aspects

of the combined use of botulinum toxins and fillers for non-surgical facial rejuvenation Stephen Bosniak, Marian Cantisano-Zilkha, Baljeet K Purewal,

and Ioannis P Glavas

application of iced compresses; we have not noted any

rebound effect after using this technique In addition, to

avoid bruising, patients are given Arnica Montana C5

pellets (Boison, Newton Square, PA) sublingually

immediately preceding their injections and asked to

continue taking them four times a day for 2–3 days

Injections are given subcutaneously and tangentially

when possible Because of the diffusion characteristics

of botulinum toxin, it is not necessary to inject into the

muscle plane Avoiding deep injections will avoid

hematoma formation with accompanying bruising (and

patient perception that this is an invasive procedure)

Following the injections, direct pressure is applied

until there is no sign of oozing from the injection sites

We follow a general guideline of doses that we have

found to work safely and effectively for the different

anatomical areas of the face (Table 17.1).While dosing

may vary slightly on an individual basis, this may be

adjusted on subsequent follow-up visits

Dysport is also a type A botulinum toxin, but has amore marked spreading effect; these diffusion charac-teristics may affect the clinical outcome and the dura-tion of the effect, but the exact differences betweenBotox™ and Dysport has yet to be determined It iscurrently being used in Europe and South America,and will be available in the USA probably in 2007 or

2008, under the name Reloxan Approximately 3–5units of Dysport (Reloxan) are equivalent to one unit

of Botox Like Botox, Dysport (Reloxan) has to bereconstituted with sterile saline

OVERVIEW OF FILLERS AND INJECTION TECHNIQUE

Due to the wide variety of injectable fillers availabletoday, when choosing the appropriate product, it isimportant to match the product with the tissue

192 Clinical procedures in laser skin rejuvenation

Fig 17.1 Facial asymmetries can be corrected with an intimate knowledge of the balance of facial musculature Botulinumtoxin can be used to weaken the overactive muscles, allowing opposing musculature to function normally, thereby creating abalance (a) This patient had a hemifacial spasm following Bell’s palsy (b) Facial symmetry was achieved by understanding thebalance of the facial musculature and injecting the appropriate muscles with botulinum toxin

b a

The evolution of safer, longer-lasting and more

conve-nient, readily available materials for adding volume to

facial structures and filling in static facial lines and

furrows has added a new dimension to noninvasive

facial rejuvenation

An ideal filler should meet a number of

require-ments It has to be long-lasting, nontoxic, fully

bio-compatible, nonimmunogenic, nonmigratory, and

inexpensive, with the ability to be stored, shaped,

removed, and sterilized easily.5While we have not yet

achieved filler nirvana, the non-animal-derived

stabi-lized hyaluronic acid products are the current state of

the art, fulfilling many of our criteria.6

Fillers can be classified as nonpermanent or

perma-nent; biodegradable versus nonbiodegradable;

animal-based versus non-animal-animal-based; and autologous versus

nonautologous

While autologous fat is historically the oldest

avail-able filler, bovine collagen in the form of Zyderm I,

Zyderm II, and Zyplast was the most frequently used

substance until hyaluronic acid products were

approved by the US Food and Drug Administration

(FDA) in 2003.7The hyaluronic acids can be derived

from avian or bacterial sources; each product has its

own specific characteristics8 (Table 17.2) Hyaluronic

acid must be crosslinked through chemical alteration

to stabilize the molecule

While more crosslinking may increase the longevity

of the clinical effect, it is difficult to compare the

clin-ical efficacy of different products based on the amount

of crosslinking alone Excessive crosslinking may

impair the ability of the hyaluronic acid molecules to

retain and attract water molecules and secondarily

limit the ultimate clinical effect So it remains to be

seen which product will yield the best possible clinicaloutcome More than likely, the multitude of availableproducts will eventually have their own specific goalsfor indication of use

Gel particle size is, however, relevant for son of Q-Med Sweden hyaluronic acid products (Table17.3) The more viscous products have a larger parti-cle size This is important in considering the area anddepth of implantation of the product Juvederm iscomposed of blended random-sized particles, whichmay conceivably affect its flow characteristics

compari-INJECTION TECHNIQUES

There are four different implantation techniques thatare generally utilized: linear threading, serial punc-ture, fanning, and cross-hatching It is important toremember that for each technique, the more slowlythe infection is performed, the less discomfort iscaused to the patient and bruising is reduced

Serial puncture is technically the easiest method,since the needle tip does not move during injection.The needle enters the skin to the desired depth, asmall aliquot of filler is deposited, and the needle iswithdrawn.9

The linear threading technique consists of holdingthe needle parallel to the length of the wrinkle or fold

to be treated, piercing the skin, and advancing theneedle and injecting in either a retrograde or antero-grade fashion, making sure to stop injecting prior toneedle withdrawal.9

The fanning and cross-hatching techniques are tions of the linear threading technique These tech-niques can be implemented in areas where a largervolume of filler is needed or a multicontoured area isbeing filled Even though theoretically the fanningtechnique should yield less bruising, we have foundthat this is not necessarily true In our experience,applying the fanning technique via multiple puncturesites has produced less bruising

varia-Regardless of the product to be used, each patient isprepped with alcohol and treated while sitting in theupright position The patient is given three sublingualArnica C5 pellets and asked to continue taking themfour times daily for 3 days We use topical anesthetic(Photocaine) on every patient and rarely use regionalblocks

Clinical aspects of the combined use of botulinum toxins and fillers 193

Table 17.1 Botox dosages

Anatomical region Dose (units)

Crow’s feet and lateral brow depressors 15–20

Lower eyelids (pretarsal) 2

Depressor angulii oris 2–5

Platysmal bands 20–50