Ov e rview of Bot ulin u m

Tox i n s f o r A e s t h e t i c U s e s
Michael S. Gart, MDa, Karol A. Gutowski, MDb,*

KEYWORDS
 Botox  Xeomin  Dysport  Myobloc  Botulinum toxin  Neurotoxins  Neuromodulators

KEY POINTS
 Botulinum type A injections are an integral part of facial aesthetics.
 OnabotulinumtoxinA (Botox Cosmetic), abobotulinumtoxinA (Dysport), and incobotulinumtoxinA
(Xeomin) can all be used with similar results and effectiveness.
 Individual patient assessment, injection site selection, dosing, and follow-up is critical for optimal
results.

INTRODUCTION muscle activity led to similar applications in treat-

The clinical use of botulinum toxin to selectively
depress skeletal muscle activity in treating facial
spasmodic disorders began in the 1970s. Its
aesthetic uses were discovered incidentally but
have dramatically changed the landscape of facial
rejuvenation. Since US Food and Drug Administra-
tion (FDA) approval in 1992, injection of botulinum
toxin has become the most popular cosmetic
procedure in the United States, with more than
6.6 million injections of botulinum toxin type A
(BTA) in 2014 alone.1 Furthermore, there are
increasing off-label uses to treat a variety of
ophthalmologic, urologic, gastrointestinal, hyper-
secretory, and pain disorders because of its versa-
tility and favorable safety profile.2 Here, the current
uses of BTA for aesthetic rejuvenation of the face
are reviewed.
HISTORY
The first clinical uses of BTA were reported in the
early 1970s to selectively weaken the extraocular
muscles as a treatment for strabismus.3 The suc-
ing blepharospasm and hemifacial spasm. In
1989, the FDA approved the use of onabotulinum
toxin A (Botox) for the treatment of facial spas-
modic disorders. In that same year, Clark and
Berris4 reported the use of Botox as a treatment
for facial asymmetry resulting from iatrogenic
facial nerve damage during rhytidectomy. This
use is widely considered the first aesthetic use of
botulinum neurotoxin.
In 1987, ophthalmologist Jean Carruthers,
discovered the effect of botulinum toxin on facial
rhytides when a patient she treated for blepharo-
spasm requested to have her forehead injected
because of the improvement she observed in her
periorbital region.5 Fortuitously, her husband,
dermatologist Alastair Carruthers, had several pa-
tients asking him for ways to improve facial rhyti-
des. The following day, Jean injected the
glabellar frown lines of her receptionist—a willing
participant—and the aesthetic use of BTA was
born. These preliminary successes led to further
experimentation culminating in a report6 that set
the stage for the development of Botox Cosmetic
and several other products marketed specifically
plasticsurgery.theclinics.com

cess of BTA as a selective depressor of skeletal for aesthetic indications.1

Conflicts of Interest: None.

Disclosures: Neither author has any financial interests or relationships with the product manufacturers.
a
Division of Plastic and Reconstructive Surgery, Department of Surgery, Northwestern Memorial Hospital,
Chicago, IL 60611, USA; b Division of Plastic Surgery, University of Illinois, Chicago, IL 60611, USA
* Corresponding author. 820 South Wood Street, Suite 515 CSN, Chicago, IL 60612-7316.
E-mail address: Karol@DrGutowski.com

Clin Plastic Surg 43 (2016) 459–471

http://dx.doi.org/10.1016/j.cps.2016.03.003
0094-1298/16/$ – see front matter Ó 2016 Elsevier Inc. All rights reserved.
460 Gart & Gutowski
Over the last 42 years, the clinical indications for
BTA have increased, with various FDA-approved
and off-label uses in urology, gastroenterology,
ophthalmology, neurology, and several other
fields.7 This article focuses on the aesthetic uses
of injectable BTA and reviews the most common
treatment sites for improvement of facial rhytides.
Currently, BTA is approved for the treatment of
glabellar frown lines and crow’s feet; all other facial
aesthetic uses remain off-label.
PHARMACOLOGY
Botulinum neurotoxins are produced by several
strains of bacteria from the Clostridium genus,
principally Clostridium botulinum. There are 7
known serotypes of botulinum neurotoxin (A–G),
of which, types A (BTA) and B (BTB) are commer-
cially produced for clinical use. Botulinum toxin is
synthesized as a 150-kDa protein that undergoes
posttranslational modification into a 100-kDa
heavy chain and a 50-kDa light chain, linked by a
disulfide bridge.8 The heavy chain binds to the pre-
synaptic neurons at the neuromuscular junction
and facilitates entry of the light chain into the cell
cytoplasm. There, each serotype’s light chain
targets a component of the soluble N-ethylmalei-
mide-sensitive factor attachment protein receptor
(SNARE) complex, which it cleaves to and thereby
inactivates. The components of the SNARE com-
plex are all essential for microvesicle fusion and
release of stored neurotransmitter. BTA targets
synaptosomal-associated protein, 25 kDa BTB
target synaptobrevin, also known as vesicle-asso-
ciated membrane protein.9
By inhibiting the release of stored neurotrans-
mitter at the neuromuscular junction, botulinum
neurotoxins cause a flaccid paralysis of target
muscles. Paralysis and a near-complete loss of
motor end plate potentials occur within a few
hours of botulinum neurotoxin injection7; however,
the clinical effect may not become evident for up
to 1 week after administration.10 The latency to
clinical effect may be caused by spontaneous,
non–vesicle-associated release of acetylcholine
at the neuromuscular junction.11 The neuromus-
cular blockade from botulinum toxin administra-
tion is irreversible. Axonal sprouting and the
formation of new neuromuscular junctions are
responsible for the dissipation of clinical effects
over time.12
PRODUCT COMPOSITION/AVAILABLE
PRODUCTS
Pure botulinum toxin is synthesized as a 150-kDa
protein that complexes with varying amounts of
nontoxic proteins and hemagglutinin.13 Each
commercially available product has its toxin com-
plexed with a varied quantity of unique proteins.
Doses of each product are measured in units,
with one unit corresponding to the median lethal
intraperitoneal dose (LD50) in mice. However, the
method for performing this assay is specific to
each manufacturer, which precludes comparison
among similar products.10,14–16 Approximate,
commonly accepted dosing equivalencies have
been determined clinically and are discussed
below.
Currently, there are 4 commonly used prepara-
tions of botulinum toxin: onabotulinumtoxinA
(Botox; Botox Cosmetic, Allergan, Irvine, CA), abo-
botulinumtoxinA (Dysport; Ipsen, Ltd, Berkshire,
UK), incobotulinumtoxinA (Xeomin; Merz Pharma-
ceuticals, Frankfurt, Germany), and rimabotuli-
numtoxinB (Myobloc; Solstice Neurosciences,
San Francisco, CA).10,14–16 Although the clinical
effect of each is similar, they differ in their chemical
structure, associated proteins, manufacturing and
purification processes, mechanism of action, and
clinical efficacy.17,18 Because of these differences,
there are no established dosing equivalencies be-
tween products, although some general clinical
guidelines have emerged.19 Most experienced
BTA injectors use the following BTA dose conver-
sions for aesthetic facial uses: 1 unit of onabotuli-
numtoxinA 5 1 unit of incobotulinumtoxinA 5 3
units of abobotulinumtoxinA. There is not enough
experience to convert BTA doses to rimabotuli-
numtoxinB doses.
This article provides treatment guidelines using
onabotulinumtoxinA as the reference standard,
as most of the available literature focuses on clin-
ical recommendations with this product.
STORAGE AND RECONSTITUTION
Myobloc (rimabotulinumtoxinB) is available in
reconstituted form, and does not require addi-
tional diluent before use. BTA is supplied in pow-
der form and must be reconstituted before use.
The manufacturer of each BTA preparation
recommends reconstitution exclusively with
preservative-free 0.9% sodium chloride solu-
tion10,14,16; however, many clinicians have
switched to sodium chloride solution preserved
with benzalkonium alcohol to reduce patient
discomfort. Several clinical trials have found
equivalent success and reduced patient discom-
fort, attributed to the more favorable pH balance
of the preserved saline.20,21
Once reconstituted, BTA is commonly consid-
ered fragile, despite evidence to the contrary.
Several studies found that vigorous agitation and

storage for up to 6 weeks has no effect on the
clinical outcomes of reconstituted BTA.22–26
One study even found no change in potency of
onabotulinumtoxinA after 6 weeks of continuous
agitation.27
DURATION OF EFFECT
The typical duration of botulinum toxin effect is 3
to 4 months, depending on several factors,
including dose, concentration, injection tech-
nique, patient immune response, and others. In
the preapproval studies for each of the commer-
cially available products, the glabellar region
was treated and the number of patients maintain-
ing a response was recorded monthly.
Three months after treatment, the percentages
of patients maintaining a clinical response were
approximately 50% for Botox,28 40% to 50% for
Dysport,29 and 15% to 25% for Xeomin.16 The
ranges presented for Dysport and Xeomin were
owing to differences in clinician versus patient
assessment of response. Importantly, the Xeomin
study defined a response as at least a 2-point
clinical improvement, whereas the Dysport study
defined a response as at least a 1-point clinical
improvement. Taking this into consideration, Xeo-
min may not be inferior to Botox or Dysport.
Regardless of the product used, fewer than
20% of patients maintained a response beyond
4 months.
It is possible that increased doses at each injec-
tion site may prolong the clinical duration and
numbers of responders,30 but maximum doses,
after which no clinical benefit is achieved, have
not yet been established.
BOTULINUM TOXIN INJECTION IN THE FACE
The aesthetic uses of injectable botulinum toxins
in the face are extensive, and patient satisfaction
with treatment has been very high, with signifi-
cant improvement in patient-reported out-
comes.31 Selective weakening of the muscles
of facial expression is found to improve the
appearance of the overlying dynamic rhytides
caused by muscle activity. Over time, the goals
of treatment have shifted from a completely
paralyzed, “frozen” look to a softer, more
expressive dampening of muscular activity.
Weakening the underlying facial musculature
can significantly improve dynamic facial rhytides
but cannot ameliorate static rhytides and cannot
substitute for other skin resurfacing procedures.
All patients should be counseled regarding the
anticipated effects and the limitations of botuli-
num toxin injection.
Botulinum Toxins for Aesthetic Uses 461
General Injection Guidelines
Patients should discontinue any medications or
supplements that interfere with hemostasis 10 to
14 days before the procedure to minimize bruising.
Before injecting, ice packs or topical anesthetic
can be used to minimize patient discomfort. The
smallest gauge needle available should be used
for injection, as smaller needles significantly
reduce pain and limit bruising.32
The concentration of BTA can be varied to limit
or increase the diffusion when treating localized
or broad areas, respectively. Electromyogram
studies have found that injected BTA can spread
up to 3 cm from the site of injection.21,33 Therefore,
care must be taken and concentration considered
when attempting highly selective facial muscle
weakening.
With regard to dose administration, clinical
practice varies widely, and we can only provide
a framework from which to approach the patient
presenting for botulinum toxin treatment. Clinical
consensus recommendations for the use of
Botox Cosmetic34 and Dysport35 have been pub-
lished. Owing to its relatively recent market
approval, Xeomin does not currently have pub-
lished recommendations, but dose administra-
tion is found to be interchangeable with Botox
Cosmetic.36
TREATMENT OF THE UPPER FACE
Compared with the middle and lower thirds, the
upper face experiences less volume loss over
time, and many of the telltale signs of aging are
related to the development of rhytides. As a result,
treatment with botulinum toxins in this area gener-
ally yields good results.
Transverse Forehead Rhytides
Although considered an off-label use of BTA,
treatment of transverse forehead rhytides can
provide excellent results and high levels of satis-
faction in properly selected patients. Each individ-
ual must be assessed to determine the relative
degree of static versus dynamic forehead rhyti-
des. Although treatment with botulinum neuro-
toxin can produce significant smoothing of
dynamic transverse rhytides, static rhytides may
require dermal fillers or a skin resurfacing
procedure for marked improvement. Furthermore,
the anatomy of each patient’s forehead region,
with particular attention to the relative muscle
strength, muscle orientation, brow height, and
overall forehead anatomy should be carefully
considered in the treatment plan to maximize out-
comes and patient satisfaction.
462 Gart & Gutowski
Anatomy
Contraction of the frontalis muscle elevates the
brown and results in dynamic transverse forehead
rhytides. The frontalis is the principal elevator of
the brow, originating in the galea aponeurotica
and inserting into the subcutaneous tissues and
deep dermis of the skin overlying the superciliary
arch. Although commonly depicted as 2 distinct
muscle bellies, anatomic variation is common,
with many showing significant medial overlapping
and structural difference between the medial and
lateral aspects.37
Treatment recommendations
The goals of treating the forehead are to soften the
appearance of dynamic rhytides without giving an
unnatural, unexpressive appearance and avoiding
iatrogenic brow ptosis. The efficacy and safety of
BTA in treating this area of the face have been
well documented in the literature.37–42
Treatment of the forehead is highly variable
because of the anatomic variability of the frontalis
muscle and characteristics of each patient’s ani-
mation patterns. Moreover, some patients exhibit
several fine transverse rhytides, where others
have only 1 or 2 deep transverse creases. Before
injection, any brow asymmetry is noted and dis-
cussed with the patient, as this may only come
to their attention after treatment. Patients are
asked to forcefully elevate their brow to assess
the strength of frontalis contraction and the loca-
tion of dynamic rhytides. The frontalis is typically
injected in 4 to 6 sites, with care taken to stay at
least 1 to 2 cm above the supraorbital rim to avoid
brow or eyelid ptosis.34 The authors prefer to inject
each belly of the frontalis in a V-shaped pattern
(Fig. 1); however, this varies based on each
Fig. 1. Typical injection sites in frontalis muscle for
forehead lines. May range from 4 to 10 injections
points (2 U of Botox or Xeomin or 6 U of Dysport
per injection point).
patient’s muscular anatomy. In women, 10 to 20
units are spread among the predetermined num-
ber of injection sites, with lower doses used in
toxin-naive patients. As with most treatment
areas, men typically require a higher dose (16–24
units) to achieve the same effect because of larger,
stronger muscles.
Glabellar Region
Treatment of vertical glabellar rhytides was the
first FDA-approved aesthetic use of BTA in 2002
and remains the most frequent indication for its
use. BTA has become widely used in this region
with many published experiences.6,43–49 Several
randomized, placebo-controlled trials showed effi-
cacy of BTA in treating this area. Moreover, treat-
ment of glabellar rhytides with botulinum toxin
type A can improve quality of life and may reduce
negative moods.50,51 A recent multicenter study in
Europe found high levels of patient satisfaction
and improved perception of self up to 4 months af-
ter injection of the glabellar complex with botuli-
num neurotoxin type A.52
Anatomy
The glabellar complex depresses the medial brow
and consists of the paired corrugator supercilii
muscles and the central procerus muscle. The ac-
tion of the medial orbicularis is also to depress the
brow, but its contribution is weak by comparison.
The corrugators originate on the frontal bone
medially, where their fibers can interdigitate with
those of the medial preorbital orbicularis oculi,
and insert into the dermis of the forehead, just
above the eyebrow at the midpupillary line. Their
primary action is to medialize and depress the
medial brow. Hyperactivity contributes to vertical
glabellar rhytides.
The procerus muscle is a vertically oriented,
midline structure, originating from the soft tissues
overlying the nasal bones and inserting into the
skin of the lower central forehead, superior to the
nasal root. Contraction of this muscle produces
transverse horizontal rhytides at the nasal root.
Treatment recommendations
Muscle size, strength, and location can be esti-
mated by asking the patient to frown maximally.
Any asymmetry in muscle strength or contraction
should be carefully evaluated before injection.
The authors typically inject in a 5-point V pattern,
with 2 injection sites in each corrugator and 1 in
the central procerus (Fig. 2). Injections should be
kept a minimum of 1 cm above the orbital rim to
avoid diffusion into the levator palpebrae superio-
ris muscle, causing iatrogenic ptosis. The patient
is asked to frown to confirm the location of each

Fig. 2. Typical injection sites in corrugator muscle for
glabellar lines. May range from 3 to 5 injection points
(2–5 U of Botox or Xeomin or 6–15 U of Dysport per
point).
muscle belly just before injection. In patients with
mild muscle activity, 3 injection points may be
used instead.
The deeper location of the brow depressors
relative to the brow elevators has led to the belief
that deep injection of botulinum toxins can selec-
tively target brow depressors and, thus, result in
brow elevation. This technique has been recom-
mended for chemical brow lifting and correction
of brow asymmetries but has not been found to
be effective because of diffusion of the toxin be-
tween muscle layers.53
The recommended total treatment dose of
Botox Cosmetic in this region is 20 U divided
among 5 injection sites; however, clinical practice
varies widely in terms of total dose and number of
injection sites.11,36 As with other areas, male pa-
tients have been found to require higher doses of
botulinum toxin to effectively treat the glabellar re-
gion, presumably because of relative increase in
muscle mass.2,44,54 One study found a dose-
dependent improvement in results when men
were treated with higher doses (20 vs 40 units) of
botulinum toxin for treatment of the glabellar
region.55
Brow Lift
The lateral brow lift is most often performed as a
component of treating the rest of the face. When
combined with treatment of the glabellar complex
and frontalis, an aesthetically pleasing contour of
the brow can be achieved. The lateral brow lift
can also be used to camouflage an overelevated
medial brow, which can occur after chemically
weakening the glabellar complex.
Botulinum Toxins for Aesthetic Uses 463
Injection in the medial brow depressors can
modestly elevate the medial and central brow,
but also has an elevating effect on the lateral
brow. In fact, glabellar complex treatment alone
has also been found to lift the lateral brow by as
much or more than the medial brow.56 It is theo-
rized that diffusion of toxin from the glabellar com-
plex injections weakens the inferomedial frontalis
fibers, resulting in increased tone in the lateral
frontalis fibers.
Anatomy
As described above, the brow is a complex struc-
ture, and its position is determined by the relative
balance between the forces of brow elevation
and depression. Using BTA to selectively weaken
the depressors of the brow is the foundation for
the so-called chemical brow lift.57–61 At the lateral
orbital rim, the vertical fibers of the lateral compo-
nent of the orbicularis oculi muscle act as depres-
sors of the lateral brow.
Treatment recommendations
Chemically weakening the lateral fibers of the pre-
orbital orbicularis oculi can result in lateral brow
elevation by 2 to 4 mm.61 Typical starting doses
are from 2 to 5 U of Botox Cosmetic injected intra-
dermally, just beneath the tail of the lateral brow
(Fig. 3). If the lateral brow is inadvertently overele-
vated, the upward pull of the lateral frontalis can
later be weakened with additional botulinum toxin
to balance brow elevation and depression forces.
Lateral Orbital Region (Crow’s Feet)
Among the earliest signs of aging, lateral canthal
lines, commonly referred to as crow’s feet, are
the result of hyperkinetic orbicularis oculi muscles.
BTA to soften the appearance of these rhytides
(crow’s feet), has been well documented.39,62
Anatomy
The orbicularis oculi muscle is a sphincter muscle
that encircles the orbit and allows forceful closure
Fig. 3. Typical injection sites in the superior portion of
orbicularis oculi muscle for lateral brow elevation (2–4
U of Botox or Xeomin or 6–12 U of Dysport per point).
464 Gart & Gutowski
of the eye. It also contributes minimally to medial
and lateral brow depression. Traditionally, this
muscle is considered in 3 parts: pretarsal, presep-
tal, and preorbital. The preorbital division is the
most peripherally located and is the target of bot-
ulinum toxin treatment. Because of the important
function of the orbicularis oculi, it is important to
avoid such a profound paresis that eye closure is
impaired.
Treatment recommendations
It is important to discuss expectations with pa-
tients, as dynamic rhytides are just one element
of a multifactorial periorbital aging process and
cannot single handedly restore a youthful appear-
ance; however, in properly selected patients,
treatment of the lateral canthal region can be
very satisfying. Patients with excessive skin dam-
age and static rhytides should be counseled
regarding resurfacing procedures in conjunction
with neurotoxin treatment.
Crow’s feet are typically treated with 3 equal
injections of 2 to 4 U of Botox Cosmetic at each
site (Fig. 4). These injections should be placed
superficially (intradermal), producing a visible
bleb beneath the skin. The middle injection is
placed in line with the lateral canthus, and the
remaining 2 injections are placed 8 to 10 mm
above and below this point. Total starting doses
should range between 8 to 16 U and 12 to 16 U
of Botox Cosmetic per side in women and men,
respectively.34
As with other periorbital treatments, injection
points should be kept at least 1 cm away from
the orbital rim to target the orbital subdivision of
the orbicularis oculi muscle and prevent inadver-
tent diffusion to the lid retractors or extraocular
muscles. In patients with lax lower eyelids, caution
should be used when injecting medially to avoid
disrupting proper lid function.
Fig. 4. Typical injection sites for lateral portion of or-
bicularis oculi muscle canthal lines (crow’s feet). May
range from 2 to 4 injections points (2–4 U of Botox
or Xeomin or 6–12 U of Dysport per point).
Although lateral canthal lines can extend well
beyond the orbital rim, because of the size of the
individual’s orbicularis muscle, they should not
be injected with botulinum toxin below the
zygoma, as this may result in paresis of the zygo-
maticus muscle, affecting perioral movement and
smile. Lines extending well beyond the periorbita
should be evaluated for treatment with dermal
fillers.
TREATMENT OF THE MIDFACE
As with the lower face, many of the changes asso-
ciated with aging in the midface are the result of
relative volume loss and descent. Therefore, treat-
ment with botulinum toxin has a more limited role
than dermal fillers or surgical resuspension of
tissues.
Bunny Lines
Some patients will present with complaints of obli-
que nasal sidewall rhytides, caused by hyperactiv-
ity of the transverse portion of the nasalis muscle.
These rhytides are commonly referred to as bunny
lines, owing to the patient appearance with
maximal contraction of the nasalis muscle.
Anatomy
The nasalis muscle is a paired structure, each con-
sisting of an alar and transverse portion. The trans-
verse nasalis muscle originates on the maxilla near
the medial canthus and converging in a medial
aponeurosis that overlies the nasal dorsum.
Contraction results in superomedial elevation of
the nasal sidewall skin and production of oblique
skin rhytides.
Treatment recommendations
The nasalis muscles can effectively be treated by
injection in each muscle belly or a single, central
injection. We prefer the 2-injection technique to
soften the appearance of bunny lines (Fig. 5).
Fig. 5. Typical injection sites in nasalis muscle (lateral)
and procerus muscle (midline) for nasal lines (bunny
lines). May range from 1 to 3 injections points (2–4
U of Botox or Xeomin or 6–15 U of Dysport per point).

Common doses are between 2 and 5 U of Botox
Cosmetic per side.34 Injection sites should be
kept high on the nose and superficial to avoid
excessive paralysis of the deeper and more inferior
levator labii superioris and levator labii alaeque
nasi, important elevators of the upper lip. Exces-
sive chemodenervation of these muscles may
lead to upper lip ptosis.
Upper Lip
The sphincter action of the orbicularis oris muscle
is responsible for dynamic vertical rhytides of the
upper lip. Vertical perioral rhytides are a common
complaint among patients seeking facial rejuvena-
tion. Although some activities, including excessive
sun exposure or smoking, can accentuate or has-
ten the appearance of these lines, they are almost
universally found with increasing age. As with
other areas of the face, aging in the perioral region
is multifactorial; although BTA can improve
dynamic—and to some extent, static—rhytides,
they are rarely, if ever, used in isolation to treat
this area of the face. Dermal fillers are most often
used to improve the contour of static rhytides
and address volume loss in the upper lip. Howev-
er, judicious use of BTA in the upper lip has been
found to improve lip contour, eversion, and
fullness.63–65
Anatomy
The orbicularis oris muscle encircles the upper and
lower lips, originating from the modiolus complex
and inserting into the skin and subcutaneous tis-
sues of the upper lip. Its primary function is as a
sphincter to aid in oral competence and speech.
It also functions to protrude the upper and lower
lips. Because of its disruption in congenital clefts
of the upper lip, the anatomic and functional study
of this muscle is vast, and a complete discussion is
beyond the scope of this article.
Treatment recommendations
Before treatment, patients should be advised that
they may have difficulty with activities that require
pursed lips, including pronunciation of certain plo-
sives and drinking through a straw. Moreover, in
this area, we prefer to err on the side of possible
undercorrection with subsequent touch-ups rather
than overtreat and risk excessive paresis of the
perioral musculature.
To avoid iatrogenic paralysis of the upper lip el-
evators, injections should be kept medial to a ver-
tical line dropped from the lateral nasal ala to the
upper lip vermillion (Fig. 6). Small aliquots (1–2 U
of Botox Cosmetic each, total dose 4–6 U) are
injected between 2 to 4 symmetric sites along
the superior vermillion border. The lower lip
Botulinum Toxins for Aesthetic Uses 465
Fig. 6. Typical injection sites in orbicularis oris muscle
for upper lip lines (smoker’s lines). May range from 2
to 4 injections points (2–3 U of Botox or Xeomin or
6–9 U of Dysport per point).
injections should similarly stay at least 1 cm medial
to the oral commissures and should mirror or
bisect the upper lip injections.
TREATMENT OF THE LOWER FACE AND NECK
As with the midface, the mainstays of treating
aging-related changes in the lower face and neck
are restoration of volume and resuspension of
descended tissues; however, there are several
aesthetic indications for treatment with BTA.
Depressor Anguli Oris
Contraction of the depressor anguli oris (DAO)
muscle produces a downturn to the corners of
the mouth. Hyperactivity of the DAO contributes
to accentuation of the melomental fold, also
known as the marionette line and can give the
impression of sadness or anger by inverting the
corners of the mouth. Patients often present with
complaints of an angry look to their face, which
they attribute in part to a down-turned mouth at
rest. Chemodenervation of these muscles can
reduce the downward pull and provide a subtle
lift to the oral commissures, correcting an inverted
smile.
Anatomy
The DAOs are fan-shaped muscles originating with
a broad base along the mandibular body, anterior
to the masseter, and inserting into the oral com-
missures at the modiolus complex. At each oral
commissure, the fibers of the DAO interdigitate
with other muscles of the modiolus complex, the
orbicularis oris, and risorius muscles. The DAO
functions primarily as a depressor of the modiolus
complex.
Treatment recommendations
As mentioned above, the modiolus complex is an
anatomically complex structure, with interdigitation
466 Gart & Gutowski
of depressors, elevators, and sphincters of the lips.
As a result, accurate placement of BTA is essential
to avoid complications of asymmetry, phonation,
or impaired oral competence.
The location of the DAO is most readily identi-
fied indirectly, by palpating the anterior border of
the masseter muscle. The patient is asked to
clench their jaw, which facilitates palpation of
the anterior border of the masseter. The DAO
muscle belly can be safely injected 1 cm medial
from this point, 2 to 3 mm above the inferior
border of the mandible (Fig. 7). Although the
muscle belly is centered medial to this, injection
at this point will target the lateral fibers respon-
sible for pulling the modiolus downward while
minimizing the risk of diffusion to surrounding
musculature. As an additional reference point, in-
jections should be kept at least 1 cm lateral to
the lateral oral commissure.65
Typical starting doses are low, with 2 to 5 units
of Botox Cosmetic recommended.66,67
Mentalis
Hyperdynamic activity of the mentalis muscle can
create the undesirable appearance of wrinkling or
dimpling of the skin overlying the chin, often
referred to as a peau d’orange appearance. This
is most evident during periods of facial expression.
Although a less commonly used indication, these
patients can also be treated with botulinum toxin
to relax the underlying mentalis muscle.
Anatomy
The mentalis is a paired muscle that serves as the
primary evertor of the lower lip and also serves to
elevate the skin of the chin. It arises from the inci-
sive fossa on the anterior mandible and inserts into
the subcutis of the chin on either side of the lower
lip frenulum. The mentalis lies deep to, but inter-
digitates with, the fibers of the orbicularis oris
and the depressor labii inferioris.68
Fig. 7. Typical injection sites in DAO muscle for down-
turned smile with 2 injection points (4–6 U of Botox or
Xeomin or 12–18 U of Dysport per point).
Treatment recommendations
Injection of the mentalis can be either be accom-
plished with a single injection in the midline at
the origin of both bellies of the mentalis or, more
commonly, with an injection into each muscle
belly. For the 2-injection method, treatment points
are located 2 mm above the inferior border of the
mandible and approximately 5 mm to the left or
right of midline. In either pattern, injections should
be kept deep to avoid inadvertent spread to the
overlying orbicularis oris and depressor labii infe-
rioris muscles. Typical starting doses are between
5 and 10 U total of Botox Cosmetic.34
Masseteric Hypertrophy
Hypertrophy of the masseter can create a square
appearance to the lower third of the face and convey
an impression of heaviness to the face. Moreover, a
hypertrophic masseter can impart a masculine
appearance to a female face. Although genetic
and habitual components are involved in the patho-
genesis, the underlying treatment is similar, regard-
less of cause. Several reports describe treatment of
masseteric hypertrophy with BTA, predominantly in
Asian populations.69–73 Moreover, each of the
commercially available forms of injectable botuli-
num toxin has been independently shown to reduce
undesirable hypertrophy.74–76
Anatomy
The masseter is a primary muscle of mastication,
with origins on the zygoma and zygomatic process
of the maxilla and insertion along the ramus and
angle of the mandible. The muscle consists of a
superficial and smaller deep head and functions
synergistically with—but much stronger than—
the medial pterygoid muscles to elevate the
mandible. The mandible is overlapped by the risor-
ius muscle, which arises on the parotid fascia and
inserts near the angle of the mouth to retract the
commissure laterally, as in a false smile or smirk.
Superiorly, the masseter is overlapped by the
zygomaticus muscle, which functions to elevate
the angle of the mouth in true smile.
Treatment recommendations
Treatment of the masseter with BTA differs from
other areas in that the primary indication for treat-
ment is to induce muscle atrophy rather than limit
muscle contractions to alleviate skin wrinkling.
Care must be taken to avoid excessive paralysis
that would weaken mastication.70,71,73 Other com-
plications include asymmetry, changes in facial
expression,70,71 speech disturbances,72 dysgeu-
sia,70 and transient muscle bulging.71
When injecting in the mandible, it is important to
keep in mind the location of the surrounding

musculature, most notably the risorius muscle, but
also the zygomaticus muscle (Fig. 8). Inadvertent
injection to either of these would alter the kinetics
of the angle of the mouth, causing facial asymme-
try. Further, injecting deep into the substance of
the muscle bellies will reduce the incidence of un-
wanted medication diffusion.
The point of maximal muscle hypertrophy is
identified and marked as the starting point. Two
additional injection points are marked above this,
one medial and one lateral to the first. Attention
is paid to keep the injections inferior and lateral
to limit diffusion to the surrounding risorius and
zygomaticus muscles that run medial and supe-
rior, respectively. Average starting doses are
among the highest of any area in the face, approx-
imately 30 to 35 U of Botox Cosmetic.35
Platysmal Banding
Despite advances in nonsurgical rejuvenation of
the face, the aging neck remains a challenge to
the aesthetic surgeon. Lipodystrophy, horizontal
rhytides, thinning of the skin and subcutaneous
tissues, underlying skeletal changes, blunting of
the cervicomental angle, and tissue laxity are
just a few of the components of the aging neck.
Although many of these components require sur-
gical techniques to address, there remains a role
for nonsurgical rejuvenation of the aging neck
with botulinum toxins. Static rhytides and lipodys-
trophy are not amenable to treatment with BTA,
but vertical platysmal banding and horizontal rhy-
tides can be improved with chemodenerva-
tion.77,78 Furthermore, patients seeking improved
contour and definition of the jawline have been
Fig. 8. Typical injection sites in masseter muscle for
masseter hypertrophy. May range from 1 to 3 injec-
tion points (10–15 U of Botox or Xeomin or 30–45 U
of Dysport per point).
Botulinum Toxins for Aesthetic Uses 467
successfully treated with chemodenervation of
the lower face and neck.
Anatomy
The platysma is a broad, thin muscle that origi-
nates in the deltopectoral fascia and extends
cephalad to insert along the inferior border of
the mandible and the superficial musculoapo-
neurotic system of the lower face. These inser-
tions make the platysma a powerful depressor
of the lower face and mandible. Although classi-
cally depicted as a distinct muscle on either
side of the anterior neck, fibers often decussate
across the midline.
Treatment recommendations
In patients looking to soften the appearance of
their platysmal bands, but are not candidates
for—or do not desire—a platysmaplasty, BTA in-
jection to the platysmal bands is a safe and effec-
tive procedure. Furthermore, techniques are
available for those seeking improved contour of
the mandibular border. Matarasso and Mata-
rasso79 developed a system for staging the aging
neck that guides treatment doses and predicts
which patients will respond most favorably to
treatment.
The patient is asked to contract the platysma
muscle, which can often be elicited by asking
them to show the examiner their bottom teeth.
This contraction allows the examiner to grasp
each band between the thumb and index finger
of the nondominant hand. Direct injections into
the bands in 3 to 5 sites, at 1-cm intervals along
the muscle are suggested. A significant variability
in dosing has been reported in the literature, with
consensus recommendations averaging 30 to
40 U of Botox Cosmetic and varying based on
number of bands and muscle mass.43,78–83 In gen-
eral, 4 to 5 U per injection site should provide
adequate correction of banding.
Care must be taken to inject specifically into
the bands, in the deep dermal layer, as diffusion
of BTA to the strap muscles or deeper muscles of
the neck can cause dysphagia, dysphonia,
dysarthria, or life-threatening breathing diffi-
culties.10,14,16 The complications, although rare,
can be minimized or eliminated by keeping injec-
tion doses to less than 50 U per session.80
BTA can also be used to sharpen the mandib-
ular contour to elongate the appearance of the
neck. This technique, the Nefertiti lift, is named
for an Egyptian queen with a jawline considered
to be ideal. Injections are directed into the pla-
tysma along the mandible and posterior platysmal
bands to better define the mandible-neck
junction.84
468 Gart & Gutowski
PATIENT FOLLOW-UP AND BOTULINUM
TOXIN TYPE A ADJUSTMENTS
As with any other procedure, injection records
should be kept to allow reproducible future treat-
ments. Especially after an anatomic areas is treated
the first time, patients should be seen 2 weeks after
BTA injections to assess the outcome, consider
additional injections, and make adjustments for
future treatments.
IMMUNOGENICITY
As with any foreign substance, BTA is recognized
by the body’s immune system and trigger a hu-
moral response. Antibody formation can block
the therapeutic action of BTA, resulting in partial
secondary therapy failure or complete secondary
therapy failure.85 Most cases of therapy failure
have been documented in patients receiving large
doses of BTA for treatment of spasticity and dys-
tonia; however, several reports of therapy failure
in patients receiving aesthetic treatments have
been published.86–88 Various factors have been
implicated in promoting the formation of anti-
bodies against BTA, including large single doses,
short injection intervals, and booster treatments
closely following initial treatment89; the prepara-
tion used for injection90; and the individual charac-
teristics of a patient’s immune system.89 An
accurate determination of the incidence of therapy
failure is difficult, as patient behaviors (receiving
treatment from more than 1 practitioner, irregular
follow-up), and physician practices (injection tech-
nique, dosing, frequency of administration) are
nonstandardized. Similarly, we do not currently
understand which patients may progress to sec-
ondary therapy failure.87 The available data sug-
gest that the frequency of antibody conversion
after onabotulinumtoxinA treatment is low and
infrequently leads to loss of clinical efficacy.91
The complexing proteins that accompany inject-
able botulinum toxin have been implicated as ad-
juvants in stimulating the immune response.
Commercial preparations devoid of any complex-
ing proteins (Xeomin) are available and may
reduce antibody formation.92 In nonaesthetic indi-
cations, there is evidence that switching from
complexed toxin preparations (Botox, Dysport) to
purified neurotoxin (Xeomin) may be efficacious
in secondary nonresponders.93
Furthermore, although botulinum toxin types A
and B are found to be equally effective in treatment
of cervical dystonia, botulinum toxin type B shows
higher levels of immunogenicity than type A. The
primary indication for type B botulinum toxins
may, therefore, be in treating patients who have
shown immunologic resistance to botulinum toxin
type A preparations.94
SUMMARY/DISCUSSION
Although there is extensive clinical experience with
all of the commercially available types of injectable
BTA, dose equivalencies have not been estab-
lished; variations in patient anatomy, behaviors,
and injection patterns can have an impact on
dosing. Therefore, although clinical guidelines are
presented here, each patient should be considered
individually when selecting a product, the treatment
areas, and the appropriate dosing.
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