Treatment of the Forehead
Joel L. Cohen, MD (FAAD, FACMS)1,2,3 and Ramin Fathi, MD4
1Director, AboutSkin Dermatology and DermSurgery, Greenwood Village and Lone Tree, Colorado, USA
2Associate Clinical Professor, University of Colorado Department of Dermatology, Denver, USA
3Assistant Clinical Professor, University of California Irvine Department of Dermatology, Irvine, USA
4Resident Physician, Department of Dermatology, University of Colorado, Aurora, USA
Introduction
The forehead, comprising over a third of
the face, is a prominent and very expres-
sive region of our emotional lexicon. Con-
sidering that forehead wrinkling is also one
of the earliest indicators of aging, it is not
surprising that transverse forehead rhytides
or “worry lines” are a presenting concern
of many patients seeking facial rejuvena-
tion with botulinum toxin. The highly active
musculature of the forehead contributes to
repeated wrinkling of the overlying skin
from a very young age, making this region
extremely prone to the formation of trans-
verse horizontal rhytides long before the
cumulative effects of aging set in. Even in rel-
atively young populations of patients, when
the rest of the face still retains its youthful
contour and skin texture, deep dynamic wrin-
kles can be easily observed on elevation of the
brow (Figure 11.1).
The
use
of
botulinum
toxin
type
A
(BoNTA) for the treatment of hyperfunc-
tional facial rhytides has been successfully
documented since the early 1990s [1]. It
has become the most popular cosmetic
procedure, primarily due to its temporary
and minimally invasive nature, and because it
avoids surgery-related risks [2]. Upper facial
lines, including glabellar frown lines, lateral
canthal lines and horizontal forehead lines
were the first documented areas for aesthetic
application of BoNTA and have the longest
safety and efficacy record for aesthetic usage.
When injected into muscles, BoNTA blocks
the release of acetylcholine from the motor
nerve end plate, thereby reducing muscle
activity, which leads to smoother skin and
improved patient quality of life measures
[3]. There are three BoNTA formulations
available in the United States at present, but
several more in the FDA process of clinical
trials. OnabotulinumtoxinA (Botox®, Aller-
gan, Irvine, CA) was approved in April 2002,
AbobotulinumtoxinA (Dysport®, Galderma,
Switzerland) was approved in April 2009,
and IncobotulinumtoxinA (Xeomin®, Merz,
Germany) was approved in September 2011.
Treatment of the glabellar muscle com-
plex
(Onabotulinum,
Abobotulinum,
Incobotulinum) and lateral canthal rhytids
(Onabotulinum) are the only FDA-labeled
aesthetic indications of BoNTA. Neverthe-
less, physicians routinely inject BoNTA into
the forehead region to soften horizontal fore-
head lines, and many clinical studies along
with expert consensus recommendations
are available to guide the approach to this
region [4].
This chapter will serve to familiarize the
injector with a thoughtful approach to the
Botulinum Toxins: Cosmetic and Clinical Applications, First Edition. Edited by Joel L. Cohen and David M. Ozog.
© 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.
Companion Website:
Botulinum Toxins
(a)
(b)
Figure .A 46-year-old woman (a) at rest showing some imprinting of forehead lines, (b) at animation lifting
her eyebrows and contracting her frontalis muscle, demonstrating how lines at rest form over time.
aesthetic treatment of horizontal forehead
rhytides
using
BoNTA.
This
approach
requires careful consideration of eyebrow
positioning to the extent that it is affected
by musculature in the forehead area. This
chapter will focus on the functional anatomy
of the forehead and anatomic basis for
various aesthetic changes that occur in this
region that are amenable to rejuvenation
with BoNTA. When injections with BoNTA
are
appropriately
performed,
desirable
and reproducible results with high patient
satisfaction can be achieved.
Anatomy
The anatomic boundaries of the forehead
region are the supraorbital ridge and the root
Figure .A 47-year-old at rest, showing imprinted
lines in the forehead that demonstrate the anatomic
boundaries of the forehead region.
of the nose (inferiorly), the zygomatic arch
(inferolaterally) and the hairline (superiorly)
(Figure 11.2) [5]. The eyebrows are located
at the inferior boundary of the forehead and
their positioning is strongly influenced by
muscle groups in this area. In cases with a
receding hairline, the superior border of the
forehead is determined by the superior extent
of the frontalis muscle (Figure 11.3). The fore-
head may be further subdivided into a single
central region that overlies the frontalis mus-
cle and two lateral portions that extend into
the temporal zones.
The skin of the forehead is the thickest
skin of the face and is involved in many
facial expressions. The skin is densely adher-
ent to the underlying connective tissue layer
and muscle layer via numerous transverse
fibrous septa that are partially responsible for
Figure .A 54-year-old man with a receding
hairline.
11 Treatment of the Forehead
the deep transverse forehead rhytides that
develop over time [6].
The muscular layer of the forehead is
below the subcutaneous tissue. This layer is
composed of the elevator muscle (frontalis)
at the superior aspect of the forehead and
the depressor muscles (procerus, corruga-
tor supercilii, and orbital portion of the
orbicularis oculi) inferiorly (Figure 11.4). The
frontalis is enclosed by a layer of fascia known
as the galea aponeurosis, a thin sheet of con-
nective tissue that encircles the entire skull
[5, 7]. The galea is a fibromuscular extension
of the superficial musculoaponeurotic sys-
tem (SMAS) of the lower face, which invests
and connects the muscles of facial expres-
sion. Contraction of the occipitofrontalis
muscle-group tightens the scalp and allows
for movement of the galea aponeurosis over
underlying loose areolar tissue and perios-
teum.
The frontalis is comprised of two mus-
cle bellies that originate superiorly from
the galea with vertically oriented muscle
fibers beginning approximately at the coro-
nal suture. The frontalis bellies are sometimes
discontinuous across the forehead, which cre-
ates a midline dehiscence or split. Cadaveric
studies established average midline dehis-
cence locations at 3.5 cm in men and 3.7 cm
in women above the superior orbital rim
[7, 8]. Interestingly, a smaller interpupillary
distance is predictive of a continuous or
more midline frontalis muscles, indicating
that those with a smaller head circumference
are more likely to have active frontalis fibers
across the entire forehead [8]. Clinically this
means that women may have muscle fibers
Frontalis
Corrugator supercilli
Procerus
Orbicularis oculi
Depressor labii inferioris
Depressor anguli oris
Mentalis
Platysma
Levator labii superioris
alaeque nasi
Levator labii
superioris
Zygomaticus minor
Zygomaticus major
Levator anguli oris
Brow Depressors
Lip Depressors
Brow Elevator
Lip Elevators
Figure .Protagonist/antagonist muscles of facial expression. Redrawn based on an original drawing by
Margaret Ditr´e.
Botulinum Toxins
in the midline higher up on their forehead
than men. In planning BoNTA intervention
for transverse forehead rhytides, it is impor-
tant to approximate the location of the dehis-
cence point, as injections above this area will
not be focused at significantly active muscle
fibers. From a practical clinical standpoint,
however, many injectors simply examine the
wrinkle pattern with animation, and inject in
specific areas of movement.
The inferior insertion of the frontalis is
at the level of the brow where it interdig-
itates with the three depressor muscles –
the lateral fibers are blended with the pars
orbitalis of the orbicularis oculi muscle, the
medial fibers are continuous with the pro-
cerus and the intermediate fibers mixed with
those of the corrugator supercilii. Contrac-
tion of the frontalis raises the eyebrows and
creases the forehead skin transversely, antag-
onistic to the depressor actions of the orbicu-
laris oculi, procerus, and corrugator supercilii
muscles [9].
Sensory innervation of the forehead is
via branches of the ophthalmic division of
the trigeminal nerve (first branch of cranial
nerve V). The ophthalmic nerve divides into
the supraorbital and supratrochlear branches
near the orbital rim. The nerves are part of
neurovascular bundles with a correspond-
ing artery and vein that supply the same
region as the nerve. The facial nerve (cra-
nial nerve VII) provides motor innervation to
all the facial muscles. It innervates the mus-
cles in the forehead region via its temporal
branch [9].
It is important to keep in mind that
the frontalis is the only elevator muscle
of the forehead, thus any treatment of the
frontalis may result in the unopposed action
of the depressor muscles and vice versa. This
becomes especially important when consid-
ering the effect of forehead BoNTA injec-
tions on the position and shape of the eye-
brows, which is determined by the combined
activity of the elevator and depressor mus-
cles. Therefore, optimal outcomes are some-
times accomplished only through a calcu-
lated compromise of elevator and depressor
activity with well-planned BoNTA injection
patterns.
Aging and the Forehead
Facial
characteristics
undergo
several
changes
as
a
result
of
the
cumulative
effects of aging. Sebaceous activity declines,
skin loses elasticity, subcutaneous tissue
bulk decreases, attachments to underlying
structures weaken allowing sagging due to
gravitational forces, and bone resorption
occurs [10, 11]. The combined effect of
these factors is the formation of sagging
redundancies in tissues evident as folds and
wrinkles.
In the forehead, the effects of aging are
compounded by repeated contraction of
frontalis muscle that causes development of
dynamic horizontal wrinkling during a vari-
ety of facial expressions as young as the 20s.
Repetitive facial expression over many years
eventually leads to the formation of static,
etched-in lines present at rest – also, associ-
ated with and exacerbated by the decreased
collagen content of the dermis and connec-
tive tissue with increasing age. For individu-
als with predominantly static wrinkles, inac-
tivation of the frontalis with BoNTA will not
yield as dramatic of an effect since BoNTA
primarily addresses dynamic lines [12]. For
this reason, we feel that BoNTA injections in
the forehead are best suited for the younger to
early mid-age patient who has not yet devel-
oped significant static wrinkles but would like
to prevent them (Figure 11.5). The typical age
range for this subset of patients is between
20 and 50 years depending on their intrinsic
frontalis use for facial expression. With aging,
the brow loses soft tissue support, which can
result in a descent or loss of projection of
the eyebrow causing brow-ptosis that tends
to be more prominent laterally. The descent
of the eyebrows below the supraorbital rim
results in dermatochalasis or “hooding” of the
upper lid with excess skin, which can often
be exacerbated from significant sun-exposure
and smoking.
11 Treatment of the Forehead
(b)
(a)
Figure .Forehead animation pretreatment (a) in a 29-year-old woman treated with 6 U Botox Cosmetic
reconstituted 1 U/0.1 cm3 (b) and posttreatment.
The notion of aging prophylaxis with
BoNTA is a concept that is being explored
[13–15]. Many experts advocate initiating
regular treatment with a neuromodulator in
an individual’s 20s or 30s with the argument
that this will have a dramatic effect on the
appearance of the face as seen in the person’s
40s or 50s. There will be few, if any, lines of
facial expression present [16]. Although no
prospective, controlled clinical study has yet
to examine aging prophylaxis with BoNTA,
several case reports have suggested the
potential of BoNTA for this purpose [13,14].
A case-report examined prophylactic efficacy
of BoNTA in identical 38-year-old twin sis-
ters. One twin was regularly treated with
BoNTA in the forehead and the glabella
regions two to three times per year for 13
years. The second twin received only two
total treatments with BoNTA in the forehead
and the glabella within the previous 3 years
[13]. In the twin undergoing regular treat-
ment, photographic documentation showed
no transverse forehead lines at rest, while the
minimally treated twin demonstrated static
transverse rhytides in the forehead [13]. At
6-year follow-up (age 44), the treated twin
continued to show diminished signs of facial
aging and delayed appearance of hyperfunc-
tional facial lines when compared to the
sporadically treated twin [17]. Another case
report examined two unrelated subjects in
their 50s who were treated by the same clini-
cian for over 7 years for non-reducible, hyper-
functional forehead lines [14]. Photographic
documentation demonstrated effacement of
static transverse lines at rest in both sub-
jects, no evidence of the development of
new wrinkles, and subjective improvement in
skin quality over the 7-year treatment period
[14]. Improvement in resting lines over repeat
BoNTA injection has also been described by
Carruthers through the reanalysis of previous
clinical trial data [18].
While anecdotal and clinical data reveal
the positive effect of BoNTA on resting
lines, there are limited studies examining
the biomechanical and anatomical factors
Botulinum Toxins
involved. Current histological models of skin
aging suggest that the development of static
or nonreducible wrinkles could be secondary
to actinic elastosis and the disappearance
of microfibrils and collagen fibers from the
dermal–epidermal junction [19]. It may be
possible that BoNTA injections, by reducing
the mechanical stress on the skin, enable the
skin repair systems to work more efficiently,
laying down connective tissue and improving
skin quality. Of note, BoNTA has been shown
to function in this capacity when used at the
time of surgical repair of skin cancer defects
and lacerations [20,21]. More studies are nec-
essary to evaluate the cellular response sec-
ondary to muscle relaxation and the mech-
anisms behind long-term and prophylactic
reduction of forehead lines.
Approaching the Patient
(Evaluation and Selection)
When approaching a cosmetic patient, the
physician should be aware that a “good result”
always depends on the physician meeting
the patient’s expectations and pleasing the
patient. A Treat-to-Goal (TTG) approach
was recently described to objectively define
start points and treatment goals for BoNTA
treatment, utilizing the Merz Aesthetics Scale
[22]. The Merz Aesthetics Scale is a visual
tool that facilitates assessment of wrinkle
severity via a dynamic 5-point photonumeric
scale. This was developed as an effort to stan-
dardize means of establishing patient expec-
tations and measuring treatment success as
an integral part of the consent process. The
rationale of the TTG approach is that with a
standard consent, patients are not provided
with an objective assessment of the likely cos-
metic effect of their treatment. The study
by Jandyhala demonstrated that the TTG
approach represented a significant improve-
ment over the standard consent approach
because it enabled patients to gain a fuller
understanding of what they should expect
from their treatment [22].
The evaluation should begin with a dis-
cussion of what the patient perceives as
undesirable in their appearance and the spe-
cific goals that the patient has for the treat-
ment. The notion that BoNTA produces an
unnatural “frozen” look is a common mis-
conception and is an adverse outcome that
has been frequently depicted in the media
as overzealous cosmetic intervention. From
surveys that examined parameters of patient
satisfaction, it is clear that the trend in
BoNTA rejuvenation is towards a “natural
and relaxed look” [15]. Subjective patient sat-
isfaction with BoNTA treatment is achieved
when patients feel they look as good as possi-
ble for their age, look rested and relaxed with-
out looking like they had any treatments per-
formed, and convey less negative emotions
while maintaining some degree of expres-
sion [15]. It is important the patient and
physician discuss the degree of muscle soft-
ening versus overall paralysis they want to
achieve – which will then determine the opti-
mal treatment dosage. Although patients may
welcome more extensive paralysis in the
glabellar area (which is associated with con-
veying mostly negative emotions), highly
expressive patients may desire only partial
effect in the forehead to retain some ani-
mation activity (Figure 11.6). Two important
consensus papers only 4 years apart docu-
ment the trend of patients and physicians
toward more forehead movement and less
overall dosing of BoNTA in the frontalis
(Table 11.1) [4, 23]. Recommended forehead
dosages were reduced by about 50% in the
subsequent paper in favor of less muscle
immobilization and an overall more “natural”
appearance.
Active and resting tranverse forehead
rhytides will be assessed at the initial con-
sultation. The patient should be asked to
elevate the brows to determine the strength
of the frontalis muscle as well as the location
of the lines that are generated by forceful
contraction. As described earlier, dynamic
wrinkles generated by muscle contraction
will benefit the most from treatment with
BoNTA. If static wrinkles are the primary
11 Treatment of the Forehead
(a)
(b)
Figure .Forehead animation pretreatment (a) and posttreatment (b) in a 42-year-old woman treated with
3 U Botox Cosmetic.
concern of the patient, the treatment plan
should
encompass
skin-resurfacing
and
sometimes volume replacement strategies in
combination with BoNTA [24–28]. During
forceful contraction, the clinician should
evaluate the degree of muscle contraction in
the midline to assess the level of dehiscence
or continuity of the frontalis. Muscles should
be palpated at rest and with contraction
to assess muscle mass, tonicity, and the
contribution of underlying subcutaneous
tissue and facial skeleton to overall contour.
Resting transverse forehead lines are often
most prominent if the frontalis is used as a
compensatory mechanism to clear the supe-
rior visual field when it is compromised by
brow ptosis, dermatochalasis, upper lid pto-
sis alone or in combination. In contrast to
treating other areas of the upper face with
BoNTA where there may be few functional
consequences to relaxing the musculature,
treatment of the frontalis requires careful
additional consideration. Any current brow
ptosis, extra eyelid hooding or reduction
Table .Treatment guidelines for horizontal forehead lines.
Recommended No.
Total starting dose
Target indication
Muscles involved
injection points
Botox/Xeomin
Dysport
Horizontal
forehead lines
Frontalis, possible
interactions with
procerus, corrugators,
and orbicularis oculi
4–9, spaced at least
1 cm apart and dictated
by overall forehead
shape
Women: 6–15 U;
Men: 6–15 U
20–60 U
Adapted and updated from Carruthers 2008 [23] and Ascher 2010 [51].
Botulinum Toxins
Figure .A 78-year old woman demonstrating
profound dermatochalasis. Her eyelids are literally
hanging over her eyelashes, and she is using her
frontalis muscle even at rest to try to hoist up her
eyebrows.
of the visual field must be noted because
BoNTA in these patients may exacerbate
the descent of the brow resulting in a tired
look or compromised visual field. Patients
that rely on the frontalis to constantly ele-
vate the brow can be identified by multi-
ple fine low-lying wrinkles immediately above
the eyebrow (Figure 11.7). These patients
should be made aware of these low-lying
lines and advised on other options rather
than botulinum toxin – such as ablative laser
resurfacing, deeper chemical peel or even
dermal fillers [29].
Any clinical assessment of the forehead
requires close attention to brow position,
which is of primary importance in convey-
ing a range of emotions and moods. The
physician should note the brow’s shape and
position, and also the relationship to the
superior orbital rim as well as any potential
redundancies of the eyelid itself. The eyebrow
usually extends in a smooth arch laterally but
often shows variation between ethnic groups
and genders. In men, the eyebrows are gener-
ally straighter with less lateral arching than in
women, and they are located more inferiorly,
level with the superior orbital rim. In women,
the eyebrows are usually located above the
orbital rim and have a natural lateral arch that
peaks superior to the lateral limbus at the lat-
eral third of the brow [30,31].
All
patients
should
be
evaluated
for
pre-existing asymmetry. Almost all faces
will have a natural degree of asymmetry
that is often overlooked by the patient.
Pre-treatment asymmetry and scars should
always be pointed out to the patient and
documented in the patient’s chart. Pre- and
post-procedure photographs are of critical
importance in managing patient expectations
and assessing outcomes. Patients who do not
consent to having their pictures taken should
be approached with extra caution. The
physician should explain the mode of action
of BoNTA, the estimated onset and duration
of effect (shorter durations are expected with
lower dosing used for “more natural look”),
the potential for adverse events, and the
treatment options for undesired outcomes
should they occur. Patients should be clearly
informed that they are about to receive injec-
tions at an off-label site. Consent is typically
in the form of an oral discussion as well as
the standard signed written document that is
completed before treatment is performed.
To assess treatment outcome, especially for
new patients or more challenging patients,
a follow-up appointment is often recom-
mended 2 to 3 weeks after initial injection –
when there is expected to be more maximal
BoNTA effect. This will provide an oppor-
tunity to compare before and after treat-
ment photographs, and assess the patient’s
level of satisfaction. At this optional follow-
up appointment, patients can receive any
necessary touch-up treatment with small
doses to correct residual frontalis activity or
asymmetry if present. Accurate documenta-
tion is key to successful utilization of BoNTA.
In addition to taking photographs, record-
ing the specific sites of injection and the
total units injected during each procedure
will allow the clinician to duplicate successful
treatment in the future or modify treatment
where outcomes could be improved.
Toxin and Dosage Selection
Several commercial preparations of BoNTA
products are available for clinical usage.
Though these are covered comprehensively
in individual chapters, it is helpful to review
here as a preface to some of the important
11 Treatment of the Forehead
toxin comparison studies that are relevant to
the forehead region. Among these botulinum
toxin agents, Botox (onabotulinumtoxinA)
(Allergan Inc., Irvine, CA, USA) and Dysport
(abobotulinumtoxinA) (Galderma, Switzer-
land) are the two most widely used from
an aesthetic standpoint. They are produced
from different strains of bacteria, purified and
stabilized via different methods and there-
fore have distinct biological properties. As
such, the units of these BoNTA preparations
are not interchangeable. Bioassays that deter-
mine the potency of a neurotoxin quantify
1 unit (U) of purified BoNTA-Botox as the
amount that is lethal to 50% of female Swiss
Webster mice, known as the mean lethal
dose (LD50). To distinguish between the dif-
ferent preparations and potencies, BoNTA-
Dysport is quantified in Speywood Units
(s.U.). Both preparations contain the 150 kDa
neurotoxin, but they differ in the size of
their complexing proteins. The Botox prod-
uct consists of uniformly sized complexes
of 900 kDa, while Dysport is composed of a
heterogeneous mixture of 500–900 kDa com-
plexes [32, 33]. Additionally, in the United
States a third preparation of BoNTA, Xeomin
(incobotulinumtoxinA) (Merz Pharmaceuti-
cals, Frankfurt, Germany) has been FDA
approved for the treatment of cervical dys-
tonia and blepharospasm, and obtained FDA
approval for aesthetic use in the glabella
in 2011. Xeomin is free from complex-
ing proteins and contains only the 150 kDa
neurotoxin component, which the manufac-
turer claims may result in a lower immune
response, but this has not yet been validated
clinically [34, 35]. The current clinical con-
version rate of Botox to Xeomin is reported
as 1:1 in the treatment of focal dystonias,
with Xeomin demonstrating comparable effi-
cacy, duration of effect, and tolerability as
compared to Botox [36–38]. A recent ran-
domized, double-blinded trial of 250 females
aged 18–50 years old investigated the dose
equivalence of Xeomin and Botox for glabel-
lar frown lines. The investigators found 20 U
of both products had equivalent primary effi-
cacy at 1 month and 4 months after treatment
with similar tolerability by the patient [39].
Several studies have looked at compara-
tive dosages of Botox and Dysport prepa-
rations, with a wide range of 2–4 s.U. of
Dysport required to achieve the same ther-
apeutic effect as 1 U Botox [40–44]. How-
ever, many experienced physicians seem to
agree that the most suitable dose equivalence
is between 2.5 s.U. of Dysport and 1 U of
Botox based on several studies. Additionally,
the FDA approved dosages in the glabella are
20 U Botox and 50 s.U. Dysport. One double-
blind, randomized study that examined the
conversion ratio of 1 : 2.5 (Botox : Dysport)
for the treatment of mild-to-moderate mod-
erate facial lines found that both products
produced similar improvements from base-
line at 8 and 12 weeks. However, differences
emerged at the 16-week follow-up – showing
a greater duration of effect for Botox, indi-
cating that a larger dose of Dysport may be
necessary to achieve duration equality [42].
A dosing study evaluating the Botox : Dysport
conversion ratio of 1 : 4 for the cosmetic treat-
ment of hyperfunctional facial lines, includ-
ing transverse forehead rhytides, investigator
assessment found Dysport statistically supe-
rior in reducing horizontal forehead lines
at maximum contraction [45]. The adverse
event profile showed no differences between
the different formulations, leading the inves-
tigators to conclude that a larger dose ratio
of Botox : Dysport can be safely utilized in the
upper face.
Various lines of research suggest that the
two commonly employed formulations of
BoNTA (Botox and Dysport) exhibit differ-
ent diffusion tendencies from the site of injec-
tion. Diffusion rates, or the “spread” of the
toxin from the site of injection, result in dif-
ferent “fields of effect” or surface area that
is affected by the toxin. The diffusion poten-
tial of BoNTA is dependent on various factors
including most importantly the dose injected
as well as likely the volume of injection, but
potentially also the molecular size, structure,
and subtype of the toxin, and site of injection.
The possibility of diffusion is of great clini-
cal relevance in certain areas with small, thin,
and closely positioned muscles of the upper
face (but also the lower face as well). When
Botulinum Toxins
planning the choice of BoNTA (including
dilution ratios and injection sites), it is imper-
ative to understand the anticipated migra-
tion of the toxin in the thin frontalis muscle
and the effect this will have on the treatment
outcome. The impact of neurotoxin complex
size on diffusion potential is, at least theoret-
ically, based on the principle that larger pro-
teins diffuse more slowly through an identical
aqueous medium compared with smaller pro-
teins, predicting that BoNTA formulations of
greater molecular weight will have lower dif-
fusion potential [46]. However, it has been
shown that the complexing proteins imme-
diately disassociate from the naked neuro-
toxin literally right after dilution of each of
the BoNTA formulations. Therefore, other
factors may play a greater role in the diffusion
properties – such as the total injection vol-
ume. When diffusion was evaluated in rela-
tion to the injected volume and BoNTA con-
centration, Hsu et al. [47] found that higher
dilutions (lower concentration in a higher
volume) were associated with a wider area
of effect in the forehead. They saw a 50%
increase in the treatment zone by diluting
the same concentration of BoNTA in a five-
fold larger volume leading to the conclu-
sion that a higher dilution and a larger vol-
ume can be utilized for broad, flat muscles
with fewer injection points [47]. However,
this was a small study involving 10 patients
that investigated only the Botox prepara-
tion and did not correlate higher injected
volume to any indication of duration of
toxin action.
Building on these findings, several groups
attempted to contrast the diffusion poten-
tial between Botox and Dysport. In a double-
blinded study of 20 patients, diffusion of
Botox and Dysport were compared by assess-
ing forehead hyperhidrosis [44]. Patients
were randomly injected with 3 U of Botox
or Dysport at a conversion ratio of 1 : 2.5,
1 : 3, and 1 : 4 in four areas of the forehead.
Identical volumes (0.06 ml) were used for all
injections. Patients were assessed by using
the starch–iodine test after 24 hours, 1 week,
2 weeks, and monthly up to 6 months to eval-
uate anhidrotic halos. Dysport produced a
larger area of anhidrosis in 93% of compar-
isons at all dose ratios [44]. Another study
compared 12 healthy volunteers who were
randomly assigned to receive three 0.1 ml
intradermal injections in their forehead: 4 U
Botox on one side, 12 s.U. Dysport (con-
version ratio of 1 : 3) on the contralateral
side, and saline in the center [48]. Anhidro-
sis was assessed by the starch-iodine test at
the 14-day follow-up visit. A higher mean
area of anhidrosis was observed on the Dys-
port side in 11 of the 12 subjects. The
authors concluded that Dysport has a higher
migration potential than Botox [48]. How-
ever, another study failed to duplicate these
diffusion results when a lower volume of
injection was used [49]. This latter smaller
volume study was an open-label, random-
ized study treating 18 subjects for dynamic
rhytides in the frontal region. Investigators
examined the diffusion potential of Dysport
and Botox by assessing the action halo, or
degree of muscle paralysis, and the zone
of anhidrosis. Only one conversion ratio of
1 : 2.5 (Botox : Dysport) was utilized in an
equal volume of 0.02 ml, delivering 2 U and
5 s.U. respectively on opposite sides of the
frontalis at the midpupillary line. Evaluations
were performed at 28-day follow-up. Results
showed no statistical difference between the
average area of action halos for muscular
weakness or anhidrosis between Botox and
Dysport. However, the action halo for muscu-
lar relaxation was bigger than the anhidrotic
halo for both preparations, albeit this was not
statistically validated [49]. A higher diffusion
potential will likely result in fewer required
injections in the treated area. This can be
beneficial in patients who bruise easily or are
very injection-phobic, but it could be detri-
mental in patients with a redundant brow-
lid complex where tight control of diffusion is
necessary to prevent brow ptosis. More stud-
ies are needed to determine if an increased
field of effect provides an advantage in clinical
outcomes and patient satisfaction, and how to
best utilize the migration potential of BoNTA
when planning patient care.
While it may not be ideal to compare dilu-
tion ratios, it is important to know the relative
11 Treatment of the Forehead
dosages of the different toxins, since patients
sometimes switch to a different preparation
of BoNTA for various reasons including per-
sonal preference or even recommendation
from someone for aesthetic or even logisti-
cal reasons. For most forehead patients, it
is recommended to start with a small initial
dose to avoid the “frozen” look. The dosage
recommendations from the 2008 Facial Aes-
thetics Consensus group reflect the Botox
experience of a multidisciplinary group of
aesthetic experts [23]. The current set of
guidelines updates the previous Botox spe-
cific recommendations, decreasing the initial
starting dose by about 50% in the forehead [4,
23]. The current recommended total starting
dose for injecting the forehead in women is
approximately 6–15 5 BoNTA for the Botox
formulation with 3–5 t per injection point.
The consensus recommendation in men is
to also start with 6–15 5; however, greater
dosages are frequently employed due to the
greater muscle mass in men (Figure 11.8). On
average, treatment of the forehead in men
will require an additional 25–50% of toxin
(especially for those who want the muscle
pretty much immobile) when compared to
women with a similar degree of wrinkling.
The only BoNTA study that was specifically
undertaken to examine BoNTA dosing in
men examined the dose-response relation-
ship in the glabella [50]. In this glabellar study,
the authors’ conclusions supported starting
men at a dose approximately twice the stan-
dard dose used in women – but again, this
was a glabella specific study where the mus-
cles are typically fully-treated, rather than
“minimized” as is more “natural” of a look
in the forehead. In current clinical practice
when treating the forehead, the authors com-
monly use 4–6 Botox/Xeomin in women
(10–15 5 Dysport) and 8–12 2 Botox/Xeomin
in men (20–30 0 Dysport).
There is currently no dose-optimization
study with Dysport performed for transverse
forehead rhytides. The 2010 international
consensus recommendation for this prepara-
tion is a total dose of 20–60 s.U. with 5–10
s.U. per injection point (Ascher 2010). The
consensus recommendation for the Dysport
formulation did not include specific recom-
mendations based on gender [51]. Previous
guidelines on Dysport for different aesthetic
regions, published by Matarasso and Shafer
in 2009, also recommended 30–60 over three
to six injection sites into the frontalis, but also
did not make specific gender-based dosing
recommendations [52].
One of the authors of this chapter (JLC)
uses Botox in the forehead with a 4 ne3 dilu-
tion and in the glabella and crow’s feet with
1 it3 dilution. For Dysport, JLC uses a 3 di3
dilution in forehead and 1 di3 in glabella.
Tighter control of dilution in the glabella is
usually much more important, whereas facili-
tating some spread in the forehead helps limit
injection sites but also may help to achieve a
more natural overall smoothness to the fore-
head as more areas of the large frontalis may
be softened.
(a)
(b)
Figure .A 40-year-old male patient demonstrating significant muscle mass of the frontalis from eyebrow all
the way up into the hairline.
Botulinum Toxins
Toxin Administration
Given the natural individual variation of the
frontalis muscle, there is no single tech-
nique or landmark that is followed when
choosing injection points. Each patient’s dis-
tinctive musculature, wrinkle pattern, and
eyebrow position must be considered. Indi-
vidualization of the treatment is key to a suc-
cessful outcome and patient satisfaction.
The dimensions of the forehead, and thus
the frontalis muscle, differ from one patient
to another [8, 53, 54]. Forehead injections
of BoNTA are generally placed over four
to nine injection sites. A vertical length of
over 70 mm between the glabella and the
frontal midline hairline characterizes a wide
forehead, which may benefit from two rows
of injection sites. A vertical length of less
than 60 mm characterizes a narrow forehead
which can often be treated with a single
row of injection sites [53]. As illustrated by
the anhidrosis diffusion studies, the effect of
BoNTA is not confined to the area where it
is injected. Diffusion of the toxin into sur-
rounding tissue leads to spread of the effect in
an area roughly 3 cm in diameter. In patients
with particularly narrow foreheads, there is
a larger potential for brow asymmetry and
brow ptosis due to diffusion of toxin. To min-
imize diffusion-related complications, injec-
tions should generally not be placed any
closer than 1.5 cm above the bony orbital rim
with Botox and about 1.5–2 cm above the
bony orbital rim for Dysport. Another poten-
tially useful guideline is to avoid treatment
of the first row of horizontal rhytides above
the brow, or consider just a very low-dose
in this area to simply “soften” the muscula-
ture slightly without fully knocking it out to
avoid significant repositioning of the brow
downward.
In female patients, injection sites should
often follow the curve of the brow to pre-
serve the natural arch (Figure 11.9). In
men, it is more common for rhytides to
extend up to the superior portion of the
frontalis near the hairline. Failure to treat
these superior rhytides can result in patient
Figure .Animating forehead demonstrating the
relationship of the frontalis musculature on shape
and positioning of the eyebrows.
dissatisfaction and an unnatural appearance.
In men with a receding hairline, recruitment
of more superior frontalis fibers can occur
after mid-forehead injection – leading to the
appearance of new rhytides superiorly at the
attachments of the frontalis to the galea. It
is important to identify the potential for this
compensatory mechanism and treat balding
patients with at least two rows of injections
(Figure 11.10).
The authors most commonly use the BD
0.3 ml or 0.5 ml insulin syringes with a
31 gauge, short incorporated needle (BD.
Franklin Lakes, NJ, USA). This syringe type
allows for precise treatment and accurate
dosing due to the small volume of solution
Figure .Receding hairline with high recruitment
of muscle fibers, particularly laterally.
11 Treatment of the Forehead
that is loaded. Multiple syringes are often
used for a single treatment providing a sharp,
less painful needle that is discarded after a
few injections. The patient is treated in a
seated or semireclined position to allow for
better visualization of the anatomy of the
muscles. It is important, especially for newer
injectors, to mark the planned injection
points (we use a dry-erase marker that wipes
off easily with water) to ensure accurate injec-
tion. Injections are placed adjacent to but not
through the marker ink to avoid a potential
ink tattoo. With the patient’s forehead at rest,
botulinum toxin injections are injected intra-
muscularly or often superficially raising blebs
on the skin surface. Care should be taken to
avoid injecting below the muscular layer of
the frontalis or into the periosteum, where
injections are more painful for the patient
and can potentially have a reduced clinical
effect. If the bony skull is felt while injecting,
withdraw the needle about 3–4 mm before
infiltrating BoNTA. Postinjection, the area is
often iced to try to prevent possible signifi-
cant swelling or ecchymosis, and the patient
is advised not to manipulate the treated area
for a couple of hours after the injection
[55,56].
BoNTA
rejuvenation
is
very
often
requested in more than one facial area.
A placebo-controlled, double blind study
examined the efficacy and safety of treating
the forehead, glabellar area, and crow’s feet in
a single session with the Botox formulation.
No significant adverse events were reported,
and the study validated the common clinical
experience that Botox can be used safely and
effectively to treat multiple areas of the upper
face [57]. However, for novice injectors, it
is recommended to split up the treatment
areas – treating the glabella before the fore-
head. Otherwise, if the forehead is treated
first, the depressor function of the glabellar
muscles may predispose to brow ptosis.
When BoNTA rejuvenation is planned in
combination with fillers, it is recommended
to stage the treatments – treating first
with BoNTA and then with filler [25]. This
allows for the assessment of residual static
lines after the onset of BoNTA action, and
has been shown to increase the durability
of the filler correction as well [25]. In all
combination treatments, the most important
consideration is careful documentation of
the injection sites and units placed.
Key Points of Technique
Avoid treating the most inferiorly positioned
horizontal forehead line in patients who
demonstrate excessive eyelid skin, or derma-
tochalasis [58]. While sagging eyelids are usu-
ally a cosmetic concern, they can lead to
visual field loss, ocular or eyelid irritation,
and headaches due to forced brow elevations
to increase the visual field. Significant and
independent risk factors for sagging eyelids
included age, male sex, lighter skin color, and
higher body mass index according to a large
study of 5578 patients with sagging eyelids
[58]. Prior to injection, evaluation of the eye-
lids should occur, especially in higher risk
patient populations to ensure dermatochala-
sis is not induced or worsened.
Contraindications and
Complications
BoNTA is contraindicated in the presence
of infection at the proposed injection site
and in patients with a known hypersensitiv-
ity to any ingredient in the formulation. Cau-
tion should be exercised in treating patients
with peripheral neuropathic disease or neu-
romuscular junction disorders such as myas-
thenia gravis, Lambert–Eaton syndrome, or
amyotrophic lateral sclerosis. Concomitant
aminoglycoside antibiotics may interfere with
neuromuscular transmission and potentiate
the effects of BoNTA [56]. Use in preg-
nant and breastfeeding women has not been
clinically evaluated and there is no reliable
human data available to define the degree of
risk in these situations. Therefore, treatment
of pregnant or breastfeeding women is not
Botulinum Toxins
recommended. In cases where there is a pre-
vious history of surgery to the area, cau-
tion should be exercised as the underly-
ing anatomy may be altered. For example,
one study of patients with cervical dystonia
treated with BoNTA found an odds ratio of
9.8 (p = 0.013) for secondary nonresponse if
they had a prior surgical treatment for cervi-
cal dystonia [59].
As with other regions of BoNTA treat-
ment, injection-site reactions such as ery-
thema, edema, and ecchymosis are the most
common adverse events of treatment in the
forehead. Patients are cautioned to consider
avoiding any agents that may inhibit clotting
such as nontherapeutic aspirin (as long as
patients are not on aspirin for a specific medi-
cal purpose such as a history of a heart attack,
stroke, blood clot or atrial fibrillation) as
well as nonsteroidal anti-inflammatory drugs
and alcohol for at least several days prior to
treatment, but this is certainly not manda-
tory. Focal firm pressure and ice are always
recommended postinjection if an injection
site displays immediate bleeding or signifi-
cant swelling. Removal of makeup and gentle
cleansing of the treatment area with alcohol
are recommended prior to all BoNTA treat-
ments in our office.
The primary complication of concern with
forehead BoNTA injections is brow pto-
sis, which is cosmetically unacceptable and
sometimes visually significant. If encoun-
tered, this complication is not completely
treatable, but the patient can be reassured
that it is temporary and will fully reverse in
3–4 months, although clinically significant
improvement is often noted as soon as 4–
6 weeks. Some patients with a lateral brow
ptosis, however, may benefit from injection
of the superior aspect of the lateral orbicu-
laris oculi area to lead to a functional brow
lift by decreasing the baseline downward pull
of this portion of the orbicularis oculi. Simi-
larly, some patients with a medial brow ptosis
may benefit from injecting the brow depres-
sors of the glabella to try to lift this area of
the brow. Due to the lack of complete treat-
ment of this complication, the best strategy
is a judicious and fastidious technique in the
first place. For these reasons performing infe-
rior injections at least 1.5 cm above the eye-
brows, or at least significantly lower doses in
this area, for the entire width of the frontalis
muscle is recommended as well as avoidance
of treating patients with significant frontalis
compensation at baseline for brow ptosis –
as is common in older patients. As with most
cosmetic procedures, it is always possible to
add more product to touch-up some resid-
ual activity rather than overdo it in the first
place. It is suggested that the initial starting
dose of any preparation of BoNTA be reduced
in older patients who are more reliant on the
frontalis to elevate the brow. This subset of
patients should be carefully counseled about
the risks of brow ptosis and the possibility
that the aesthetic result they seek will be more
amenable to surgery.
One of the most common forehead compli-
cations from BoNTA is caused from glabella
injections either treated too broadly or too
high, resulting in a partially treated forehead
and an unnatural appearance (Figure 11.11).
This usually happens with novice injectors
Figure .Arc of BTX effect when glabella treated
too broadly, and adjacent spread makes the cut-off
of treated versus untreated forehead too distinct.
Source: Courtesy of David M. Ozog.
11 Treatment of the Forehead
Figure .Missed area on right forehead after
forehead BTX treatment by a novice injector. Source:
Courtesy of David M. Ozog.
and inappropriately high dosing and is best
resolved by treating the remainder of the fore-
head with neuromodulator. Novice injectors
are also more likely to miss areas as they get
accustomed to injecting small aliquots in the
forehead (Figure 11.12).
A quizzical or cock-eyed appearance of the
eyebrow (Mephisto or “Mr. Spock” brow) can
be seen when the medial forehead is para-
lyzed and the lateral frontalis fibers remain
functional. Injecting 1–3 t BoNTA Botox for-
mulation into untreated lateral fibers that are
causing the upward pull can correct this.
Some asymmetry may result despite con-
sistent technique due to intrinsic patient
variability. It is best to evaluate any reports
of asymmetry at least 10 days posttreatment
to allow the full onset of effect of the BoNTA
in case one side responds quicker than the
other side.
Utilization of greater doses than those rec-
ommended for the forehead may lead to the
suboptimal outcome of the “frozen” look or
a state of inexpressivity [15]. Although some
patients may express the desire for a high
degree of immobility, it is up to the prac-
titioner to adjust the patient’s expectations
to a more realistic and aesthetically pleas-
ing outcome. Patient education during every
visit and by all members of the treatment
team is the best approach for correcting mis-
information regarding BoNTA practice and
to foster a long-term and trusting relation-
ship with the patient. We generally coun-
sel patients that ideal outcomes in forehead
treatment often require relatively low dosing
that may necessitate more frequent injections
every 2–3 months for maintenance (versus
other areas that typically receive higher doses
and are usually treated every 3–4 months or
even longer).
Although there is more than one prepa-
ration of BoNTA available, caution must
be utilized in using different varieties of
BoNTA concurrently in the same patient –
particularly if they are new to botulinum
toxin treatment in your office. It is advised
by some experts to start treating the patient
with a single type of toxin. Otherwise, should
an adverse event occur, or should a patient
have an extremely rare reaction precipitated
by treatment, it will be difficult to tell which
toxin is causing it. This can result in the
patient discontinuing all further interven-
tions with BoNTA and abandoning the treat-
ment plan.
Conclusions
r Patient education and counseling are inte-
gral parts of BoNTA treatment. It is essen-
tial for patients to have a realistic expecta-
tion of the treatment outcome to achieve
satisfaction with the treatment and the
provider.
r In general, beginning practitioners need to
understand precise regional anatomy and
the muscle vectors that contribute to the
aesthetic concern.
r Common
considerations
include
toxin
agent, dose, dilution, and patient selection.
r Keep in mind the greater muscle mass
in men when planning total forehead
dose. But overall, the forehead musculature
is commonly “softened” or “minimized”
Botulinum Toxins
rather than fully knocked-out like in other
areas of treatment.
r BoNTA use for cosmetic applications
in the forehead rarely produces serious
adverse events; however, caution should be
utilized when treating low-lying rhytides
that may cause toxin diffusion below the
orbital rim.
References
Carruthers JD, Carruthers JA. Treatment of
glabellar frown lines with C. botulinum-A
exotoxin. The Journal of dermatologic
surgery and oncology. 1992;18(1):17–21.
The American Society for Aesthetic Plastic
Surgery (2016) Top 5 surgical and
non-surgical cosmetic procedures.
Highlights of the ASAPS 2016 statistics on
cosmetic surgery. 2016 10 April 2016.
Available from:
sites/default/files/ASAPS-Stats2016.pdf
Cox SE, Finn JC. Social implications of
hyperdynamic facial lines and patient
satisfaction outcomes. International
ophthalmology clinics. 2005; 45(3):13–24.
Carruthers J, Fagien S, Matarasso SL.
Consensus recommendations on the use of
botulinum toxin type a in facial aesthetics.
Plast Reconstr Surg 2004; 114(6 Suppl):
1s–22s.
Sherris DA, Larrabee WF, editors.
Principles of Facial Reconstruction. New
York: Raven Press; 1995.
Tarbet KJ, Lemke BN. Clinical anatomy of
the upper face. Int Ophthalmol Clinic 1997;
37(3):11–28.
Abramo AC. Anatomy of the forehead
muscles: the basis for the videoendoscopic
approach in forehead rhytidoplasty. Plast
Reconstr Surg 1995; 95(7):1170–1177.
Spiegel JH, Goerig RC, Lufler RS, Hoagland
TM. Frontalis midline dehiscence: an
anatomical study and discussion of clinical
relevance. J Plast Reconstr Aesthet Surg
2009; 62(7):950–954.
Zimbler MS, Kokoska MS, Thomas JR.
Anatomy and pathophysiology of facial
aging. Facial Plast Surg Clinics North Am
2001; 9(2):179–187, vii.
Coleman SR, Grover R. The anatomy of the
aging face: volume loss and changes in
3-dimensional topography. Aesthet Surg
J/Am Soc Aesthet Plast Surg 2006; 26(1s):
S4–S9.
Imayama S, Braverman IM. A hypothetical
explanation for the aging of skin.
Chronologic alteration of the
three-dimensional arrangement of collagen
and elastic fibers in connective tissue. Am J
Pathol 1989; 134(5):1019–1025.
Branford OA, Dann SC, Grobbelaar AO.
The quantitative assessment of wrinkle
depth: turning the microscope on
botulinum toxin type A. Ann Plast Surg
2010; 65(3):285–293.
Binder WJ. Long-term effects of botulinum
toxin type A (Botox) on facial lines: a
comparison in identical twins. Arch Facial
Plast Surg 2006; 8(6):426–431.
Bowler PJ. Dermal and epidermal
remodeling using botulinum toxin type A
for facial, non reducible, hyperkinetic lines:
two case studies. J Cosmet Dermatol 2008;
7(3):241–244.
Carruthers A, Cohen JL, Cox SE, et al.
Facial aesthetics: achieving the natural,
relaxed look. Journal of cosmetic and laser
therapy : official publication of the Eur Soc
Laser Dermatol 2007; 9(Suppl 1):6–10.
Hamilton HK, Arndt KA. When is “too
early” too early to start cosmetic
procedures? JAMA Dermatol 2013;
149(11):1271.
Rivkin A, Binder WJ. Long-term effects of
onabotulinumtoxinA on facial lines: a
19-year experience of identical twins.
Dermatol Surg 2015; 41(Suppl 1):
S64–S66.
Carruthers A, Carruthers J, Lei X, et al.
OnabotulinumtoxinA treatment of mild
glabellar lines in repose. Dermatol Surg
2010; 36(Suppl 4):2168–2171.
11 Treatment of the Forehead
Bosset S, Barre P, Chalon A, et al. Skin
ageing: clinical and histopathologic study of
permanent and reducible wrinkles. Eur J
Dermatol 2002; 12(3):247–252.
Flynn TC. Use of intraoperative botulinum
toxin in facial reconstruction. Dermatol
Surg 2009; 35(2):182–188.
Gassner HG, Brissett AE, Otley CC, et al.
Botulinum toxin to improve facial wound
healing: A prospective, blinded,
placebo-controlled study. Mayo Clinic Proc
2006; 81(8):1023–1028.
Jandhyala R. Improving consent procedures
and evaluation of treatment success in
cosmetic use of incobotulinumtoxinA: an
assessment of the treat-to-goal approach.
J Drugs Dermatol 2013; 12(1):72–78.
Carruthers JD, Glogau RG, Blitzer A.
Advances in facial rejuvenation: botulinum
toxin type a, hyaluronic acid dermal fillers,
and combination therapies – consensus
recommendations. Plast Reconstr Surg
2008; 121(5 Suppl):5S–30S; quiz 1S–6S.
Carruthers J, Carruthers A, Zelichowska A.
The Power of Combined Therapies:
BOTOX and Ablative Facial Laser
Resurfacing. Am J Cosmet Surg 2000; 17(3).
10.1177/074880680001700302
Carruthers J, Carruthers A. A prospective,
randomized, parallel group study analyzing
the effect of BTX-A (Botox) and nonanimal
sourced hyaluronic acid (NASHA,
Restylane) in combination compared with
NASHA (Restylane) alone in severe
glabellar rhytides in adult female subjects:
treatment of severe glabellar rhytides with
a hyaluronic acid derivative compared with
the derivative and BTX-A. Dermatol Surg
2003; 29(8):802–809.
Carruthers J, Carruthers A, Maberley D.
Deep resting glabellar rhytides respond to
BTX-A and Hylan B. Dermatol Surg 2003;
29(5):539–544.
Kadunc BV, Trindade De Almeida AR,
Vanti AA, Di Chiacchio N. Botulinum toxin
A adjunctive use in manual chemabrasion:
controlled long-term study for treatment of
upper perioral vertical wrinkles. Dermatol
Surg 2007; 33(9):1066–1072; discussion 72.
Kenner JR. Hyaluronic acid filler and
botulinum neurotoxin delivered
simultaneously in the same syringe for
effective and convenient combination
aesthetic rejuvenation therapy. J Drugs
Dermatol 2010; 9(9):1135–1138.
Alam M, Dover JS, Klein AW, Arndt KA.
Botulinum a exotoxin for hyperfunctional
facial lines: where not to inject. Arch
Dermatol 2002; 138(9):1180–1185.
Gunter JP, Antrobus SD. Aesthetic analysis
of the eyebrows. Plast Reconstr Surg 1997;
99(7):1808–1816.
Pham S, Wilhelmi B, Mowlavi A. Eyebrow
peak position redefined. Aesthet Surg J
2010; 30(3):297–300.
Lietzow MA, Gielow ET, Le D, et al.
Subunit stoichiometry of the Clostridium
botulinum type A neurotoxin complex
determined using denaturing capillary
electrophoresis. Protein J 2008; 27(7–8):
420–425.
Schantz EJ, Johnson EA. Properties and use
of botulinum toxin and other microbial
neurotoxins in medicine. Microbiol Rev
1992; 56(1):80–99.
Naumann M, Carruthers A, Carruthers J,
et al. Meta-analysis of neutralizing
antibody conversion with
onabotulinumtoxinA (BOTOX®) across
multiple indications. Mov Disord 2010;
25(13):2211–2218.
Xeomin [package insert]. Frankfurt,
Germany: Merz Pharmaceuticals; 2011.
Dressler D. Comparing Botox and Xeomin
for axillar hyperhidrosis. J Neural Transm
(Vienna) 2010; 117(3):317–319.
Jost WH, Blumel J, Grafe S. Botulinum
neurotoxin type A free of complexing
proteins (XEOMIN) in focal dystonia.
Drugs 2007; 67(5):669–683.
Roggenkamper P, Jost WH, Bihari K, et al.
Efficacy and safety of a new botulinum
toxin type A free of complexing proteins in
the treatment of blepharospasm. J Neural
Transm (Vienna) 2006; 113(3):303–312.
Kane MA, Gold MH, Coleman WP 3rd,
et al. A Randomized, double-blind trial to
investigate the equivalence of
incobotulinumtoxinA and
Botulinum Toxins
onabotulinumtoxinA for glabellar frown
lines. Dermatol Surg 2015; 41(11):
1310–1319.
Durif F. Clinical bioequivalence of the
current commercial preparations of
botulinum toxin. Eur J Neurol 1996; 2:
17–18.
Karsai S, Raulin C. Current evidence on the
unit equivalence of different botulinum
neurotoxin A formulations and
recommendations for clinical practice in
dermatology. Dermatol Surg 2009; 35(1):
1–8.
Lowe P, Patnaik R, Lowe N. Comparison of
two formulations of botulinum toxin type
A for the treatment of glabellar lines: a
double-blind, randomized study. J Am
Acad Dermatol 2006; 55(6):975–980.
Sampaio C, Costa J, Ferreira JJ. Clinical
comparability of marketed formulations of
botulinum toxin. Mov Disord 2004;
19(Suppl 8):S129–S136.
Trindade de Almeida AR, Marques E, de
Almeida J, et al. Pilot study comparing the
diffusion of two formulations of botulinum
toxin type A in patients with forehead
hyperhidrosis. Dermatol Surg 2007;
33(1 Spec No.):S37–S43.
Lowe NJ, Shah A, Lowe PL, Patnaik R.
Dosing, efficacy and safety plus the use of
computerized photography for botulinum
toxins type A for upper facial lines.
J Cosmet Laser Ther 2010; 12(2):106–111.
de Almeida AT, De Boulle K. Diffusion
characteristics of botulinum neurotoxin
products and their clinical significance in
cosmetic applications. J Cosmet Laser Ther
2007; 9 Suppl 1:17–22.
Hsu TS, Dover JS, Arndt KA. Effect of
volume and concentration on the diffusion
of botulinum exotoxin A. Arch Dermatol
2004; 140(11):1351–1354.
Cliff SH, Judodihardjo H, Eltringham E.
Different formulations of botulinum toxin
type A have different migration
characteristics: a double-blind, randomized
study. J Cosmet Dermatol 2008; 7(1):50–54.
Hexsel D, Dal’Forno T, Hexsel C, et al. A
randomized pilot study comparing the
action halos of two commercial
preparations of botulinum toxin type A.
Dermatol Surg 2008; 34(1):52–59.
Carruthers A, Carruthers J. Prospective,
double-blind, randomized, parallel-group,
dose-ranging study of botulinum toxin type
A in men with glabellar rhytids. Dermatol
Surg 2005; 31(10):1297–1303.
Ascher B, Talarico S, Cassuto D, E et al.
International consensus recommendations
on the aesthetic usage of botulinum toxin
type A (Speywood Unit) – Part I: Upper
facial wrinkles. J Eur Acad Dermatold
Venereol 2010; 24(11):1278–1284.
Matarasso A, Shafer D. Botulinum
neurotoxin type A-ABO (Dysport): clinical
indications and practice guide. Aesthet
Surg J 2009; 29(6 Suppl):S72–S79.
Ozsoy Z, Genc B, Gozu A. A new
technique applying botulinum toxin in
narrow and wide foreheads. Aesthet Plast
Surg 2005; 29(5):368–372.
Ozsoy Z, Genc B, Gozu A. A new
technique for the application of botulinum
toxin in short and tall foreheads. Plast
Reconstr Surg 2005; 115(5):1439–1441.
Hsu TS, Dover JS, Kaminer MS, et al.
Why make patients exercise facial muscles
for 4 hours after botulinum toxin
treatment? Arch Dermatol 2003; 139(7):
948.
Huang W, Foster JA, Rogachefsky AS.
Pharmacology of botulinum toxin. J Am
Acad Dermatol 2000; 43(2 Pt 1):249–259.
Carruthers J, Carruthers A. Botulinum
toxin type A treatment of multiple upper
facial sites: patient-reported outcomes.
Dermatol Surg 2007; 33(1 Spec No.):
S10–S17.
Jacobs LC, Liu F, Bleyen I, et al. Intrinsic
and extrinsic risk factors for sagging
eyelids. JAMA Dermatol 2014; 150(8):
836–843.
Ferreira JJ, Colosimo C, Bhidayasiri R, et al.
Factors influencing secondary
non-response to botulinum toxin type A
injections in cervical dystonia.
Parkinsonism Relat Disord 2015; 21(2):
111–1115.
Treatment of the Periocular Area – Crow’s Feet, Brow, and Bunny Lines
Girish S. Munavalli, MD (MHS, FACMS),1 Anthony V. Benedetto, DO (FACP, FCPP),2,3
Brian S. Biesman, MD (FACS),4 and Carolee M. Cutler Peck, MD5
1Medical Director, Dermatology, Laser, and Vein Specialists of the Carolinas, PLLC, Charlotte, USA
2Clinical Professor of Dermatology, Perelman School of Medicine, University of Pennsylvania, PA, USA
3Medical Director, Dermatologic SurgiCenter, Philadelphia and Drexel Hill, PA, USA
4Assistant Clinical Professor Ophthalmology, Dermatology, Otolaryngology, Vanderbilt University Medical Center, Nashville, TN, USA
5Ophthalmic and Plastic and Reconstructive Surgeon, SouthEast Eye Specialists, Knoxville, USA
Introduction
The eyes have long been appreciated as cen-
trally important to the cosmetic appearance
of the face. Indeed, long before Cicero noted
“The eyes are the window to the soul”, in the
book of Matthews in the Old Testament, it
is quoted, “The light of the body is the eye:
if therefore thine eye be single, thy whole
body shall be full of light.” (Matthew 6:22–
23). A single or complex interplay of fac-
tors can cause one’s eyes to look less than
desirable. It is critically important to under-
stand exactly what feature of the periocular
region is of most concern to the patient before
making therapeutic recommendations. Some
patients blame a chronic lack of sleep on
“looking tired” when in fact they are con-
cerned about extrinsic aging factors such as
loss of skin tone, excessive eyelid skin (der-
matochalasis), eyebrow ptosis, or dark cir-
cles under the eyes, hollowness in the tear
trough area (medial lower eyelid below the
orbital rim). Some patients will be concerned
about lower eyelid bags, festooning or bulging
orbital fat pads. Certain other less struc-
turally severe conditions, such as “hyper-
trophic” pretarsal orbicularis oculi muscle,
and/or deep lateral canthal rhytids can also be
concerning. These rhytids can be effectively
addressed with readily available neuromodu-
lators such as botulinum toxin.
Considered to be an off-label treatment,
botulinum toxin types A and B have both
been employed for the reduction of perioc-
ular rhytides with excellent clinical results
[1–4]. The best candidates for periocular
botulinum toxin injections are those with
mild to moderately deep lateral canthal
rhytids and/or those who develop a “roll or
mound” of pretarsal orbicularis muscle, just
inferior to the lid margin, as they smile. There
are very few absolute contraindications to
periocular botulinum toxin injection. Cau-
tion should be employed in patients with true
dry eye syndrome or systemic diseases that
may produce dry eyes such as Sjogren’s syn-
drome and severe rheumatoid arthritis, and
lastly, patients with ocular myasthenia gravis
or other conditions that may affect extraoc-
ular muscle function. It should be used with
great caution in patients with lagophthalmos
(inability to completely close the eyes) due
to previous 7th nerve palsy, thyroid eye dis-
ease, or previous blepharoplasty [5]. More
recently, Goldman described a case report of
new-onset festooning of the lower lids after
botulinum injection in a male patient who
had a history of transcutaneous lower lid ble-
pharoplasty [6].
Botulinum Toxins: Cosmetic and Clinical Applications, First Edition. Edited by Joel L. Cohen and David M. Ozog.
© 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.
Companion Website:
Botulinum Toxins
Anatomic Considerations
Effective botulinum toxin treatment of the
periocular area involves a though under-
standing of facial anatomy, with special atten-
tion to periorbital anatomic structures and
their functional correlation to ocular and
facial aesthetics. Eyelid skin is among the
thinnest in the body with little underlying
subcutaneous tissue. By its very nature, it is
dynamic and moves frequently with gaze and
blinking. It is also located in an anatomic
region that receives extensive exposure to
sunlight. All these factors predispose eye-
lid and periocular skin to actinic injury with
thinning, loss of elasticity, dyspigmentation,
and the development of fine wrinkling [7].
Downward movement of the eyebrows is
another common occurrence with aging. Eye-
brow ptosis may present as “hooding” of the
upper eyelids, horizontal forehead rhytids
from chronic brow elevation, horizontal
rhytids at the nasion, and even headache and
fatigue. Brow ptosis develops insidiously and
many affected patients fail to recognize this
change themselves. A history of “looking bet-
ter” when a towel has been wrapped around
the head after showering is highly suggestive
of brow ptosis. Significant brow ptosis can
also accentuate superiorly located lateral can-
thal “crow’s feet” lines. Failure to recognize
brow ptosis can have disastrous conse-
quences if Botulinum toxin injections are
administered in an effort to treat horizontal
forehead rhytids. In this scenario, relaxation
of the frontalis muscle will prevent elevation
of the brows leaving an uncompensated pto-
sis. This is referred to as latent brow ptosis
and can be identified by manually holding the
brows in a fixed position as the patient gazes
straight ahead. This simple, but important
maneuver is performed by asking the patient
to hold their head parallel to the floor while
they fixate their gaze on an object across
the room (not too close) at eye level. The
forehead is then observed for the presence
of horizontal rhytids and frontalis muscle
activation. Gentle palpation of the skin
overlying the forehead rhytids will allow the
examiner
to
detect
underlying
frontalis
muscle activity.
Brow configuration varies widely from
patient to patient. In many cases it is impos-
sible to determine whether the brows have
actually fallen or whether they were always
low. When asked, most patients provide an
unreliable history of this. The good way eval-
uate if brow position has changed is to exam-
ine old photographs of the patient, prefer-
ably looking at multiple photos over a period
of time per decade starting back with high
school pictures. Repositioning of brows via
surgical or chemical techniques can be highly
rewarding but can also change a patient’s fun-
damental appearance. This must be carefully
discussed prior to treatment.
Eyelid position relative to the eye itself
must also be carefully assessed. The eyelids
should be studied both at rest and while ani-
mating. Normally the upper eyelid margin
covers the superior 1–2 mm of the cornea
while the lower eyelid margin rests at the cor-
neoscleral limbus. The white colored sclera
should not be visible at either the 6:00 or
12:00 positions. The distance between the
edge of the upper and lower eyelids while the
patient gazes straight ahead in primary posi-
tion is referred to as the palpebral fissure or
palpebral aperture. Barring normal variations
in the population, the normal palpebral fis-
sure is 8–11 mm [7]. The palpebral fissure
normally narrows with smiling. Failure of this
subtle change to occur with facial animation
may be interpreted by others as unnatural
or insincere. Upper eyelid position is usually
judged relative to the pupil or superior lim-
bus. There is a wide range of “normal” with
some patients having naturally low upper lids
while others have a wide palpebral fissure.
Blepharoptosis is the term used to describe
a lid that is in a lower than desirable posi-
tion. Ptosis is thus a relative as opposed to
an absolute condition. A ptotic upper eyelid
may occlude some, none, or even the entire
pupil [8]. Many patients are highly sensi-
tive to changes in their upper eyelid posi-
tion although most do not become aware of
their eyelid position until after undergoing a
12 Treatment of the Periocular Area – Crow’s Feet, Brow, and Bunny Lines
periorbital procedure such as botulinum
toxin injection or blepharoplasty surgery. The
value of preoperative photographs and iden-
tification of pretreatment asymmetry cannot
be overstated.
Lower eyelid position is also somewhat
dependent on the position of the eye rel-
ative to the orbital rim. With increasing
laxity, the lid will sag visibly exposing the
sclera below the inferior corneoscleral lim-
bus. This condition is best known as ectro-
pion. Many patients have enough residual
canthal tendon tone that the lower eye-
lid position remains acceptable from func-
tional and aesthetic standpoints; however,
there isn’t enough structural integrity to avoid
ectropion formation when additional stresses
such as botulinum toxin injections or surgery
are introduced. Lower eyelid integrity may
be assessed with the “snap” or “pinch” tests.
The snap test is performed by pulling the lid
downward and letting the lid return to its
resting position. A brisk return is considered
normal. A slow, gradual response is abnormal
and suggestive of excessive laxity and thereby,
increased risk for ectropion formation or
tearing following botulinum toxin injections.
The pinch test, somewhat less popular than
the snap test, is performed by pinching the
lower eyelid between the thumb and forefin-
ger and distracting it from the globe. Less
than 6 mm is considered normal. If the lid
stretches further than 6 mm, caution should
be undertaken when performing lower eye-
lid procedures. While upper eyelid position
is highly variable, lower eyelid position is less
so. Rounding of the lateral canthus or tempo-
ral ectropion can be interpreted as a sad or
artificial look and should be avoided. Poten-
tial changes in lower eyelid position must be
discussed prior to botulinum toxin injection.
Beneath the eyelid skin is found the orbic-
ularis oculi muscle, which forcibly closes
the eyelids when contracted. The orbicu-
laris oculi muscle is divided into three com-
ponents: pretarsal, preseptal, and orbital.
The pretarsal component overlies the tarsal
plates, the collagenous “backbone” of the eye-
lid while the preseptal portion overlies the
orbital septum, a fibrous membrane separat-
ing the orbital contents from more superficial
structures. If the pretarsal orbicularis mus-
cle is rendered inactive while the preseptal
portion of the muscle is allowed to contract,
the preseptal portion of the muscle can move
upward in an “overriding” fashion, turning
the eyelashes and lid margin in against the
globe, a condition known as entropion. Rel-
ative hypertrophy of the pretarsal orbicularis
muscle produces “bunching” of the lower eye-
lids that occurs with smiling. If this condition
is treated with botulinum toxin, the injections
should be administered into the pretarsal and
superior preseptal muscle. The orbital por-
tion of the orbicularis oculi muscle overlies
the orbital rim and blends with the frontalis,
procerus, depressor supercilii and corruga-
tor supraciliaris muscles of the eyebrow supe-
riorly and the temporalis and zygomaticus
major and minor muscles laterally and infe-
riorly. The temporal portion of the orbital
orbicularis oculi muscle is the primary eye-
brow depressor [9].
The orbital portion of the orbicularis mus-
cle is highly variable in size and shape, espe-
cially laterally and inferiorly. Temporally the
orbicularis oculi muscle fans out from the lat-
eral canthus toward the ear. In some patients,
the muscle extends only as far as the outer
aspect of the orbital rim while in others it
extends almost to the tragus [7]. The mus-
cle also extends to a variable degree supe-
riorly and inferiorly. The distribution of the
orbicularis oculi muscle is assessed by asking
the patient to forcibly close their eyes. Dig-
ital palpation is then used to determine the
muscle’s size and shape. Asymmetry of the
orbicularis oculi muscle is common so the
muscle should be assessed on each side prior
to botulinum toxin injection. The dose and
distribution pattern of the toxin is entirely
dependent on the orbicularis oculi muscle
size and shape. Although general guidelines
can be created, the concept of a “standard”
dose and distribution pattern of botulinum
toxin does not apply in the periorbital region.
Lines emanating from the lateral can-
thal region in a fan shaped distribution are
Botulinum Toxins
commonly referred to as “crow’s feet” lines.
These lines can be one of the first signs of
aging. Depending on a person’s skin type, his-
tory of sun exposure, and muscle strength,
crow’s feet can appear in someone as young
as 20 years of age [10]. The natural thinness
and abundance of the skin in the lateral peri-
orbital area make this site prone to wrinkling.
These lateral canthal lines initially appear
only during animation, they soon accentu-
ate while smiling, laughing, or squinting and
become increasingly noticeable with time.
Their presence causes a perpetually tired and
fatigued appearance, which can make the per-
son look even older than their actual cur-
rent age. Presence of these lines may have a
slightly different societal perception depend-
ing on gender, in the sense that lines in
women are considered undesirable, especially
when make-up accumulates in the depths of
the creases. For men, crow’s feet may be per-
ceived as a masculine, rugged feature [10].
These lines may be caused by contrac-
tion of the orbicularis oculi muscle alone
but skin laxity and contraction of zygomati-
cus major may contribute to varying degrees
as well. Some patients have deep rhytids in
repose while others only demonstrate deep
lines with animation. These types of wrin-
kles are always present whether or not a per-
son is actively animating and therefore are
referred to as static wrinkles. When the bulk
of crow’s feet are the result of long-term static
wrinkles, injections of botulinum toxin A will
be less effective but will improve the static
appearance over time (Figure 12.1a, b). In
this case, a resurfacing procedure or a soft
tissue filler may help minimize static wrin-
kling of the lateral canthus. When the bulk
of crow’s feet are produced by the hyperactiv-
ity of the lateral orbital orbicularis oculi, then
injections of botulinum toxin A can play a
significant role in diminishing the wrinkling.
Lastly, it is extremely important to distinguish
between lines caused by orbicularis contrac-
tion versus those produced by a wrinkling
effect as contraction of the zygomaticus mus-
cles “pushes” skin into the periorbital region
(a)
(b)
Figure .Before and after treatment of early static lines of 36 year old female with 8 U onabotulinumtoxin.
12 Treatment of the Periocular Area – Crow’s Feet, Brow, and Bunny Lines
(a)
(b)
Figure .Before and after treatment of moderate crows feet of 50 year old male with 12 U of
incobotulinumtoxin. Note the zygomaticus muscles “pushes”skin into the periorbital region in both the before
and after photo and is not improved with toxin injection.
(Figure 12.2a, b). The latter phenomenon is
difficult to treat without risking facial droop
or an unnatural appearance as overtreat-
ment of the zygomaticus muscle will decrease
the natural cheek elevation and fullness that
occurs with smiling. Again, a resurfacing pro-
cedure or a soft tissue filler may help in this
instance.
Patient Selection/Pretreatment
Evaluation
It is critically important to understand
exactly what feature of the periocular region
is of most concern to the patient before
making therapeutic recommendations. Some
patients complain of “looking tired” when
in fact they are concerned about loss of skin
tone, excessive eyelid skin (dermatochalasis),
eyebrow ptosis, dark circles under the eyes,
hollowness in the tear trough area (medial
lower eyelid below the orbital rim), bulging
orbital fat pads, “hypertrophic” pretarsal
orbicularis oculi muscle, and/or deep lateral
canthal rhytids. Periocular rejuvenation is
a complex topic and addressing only one
of many needs may or may not provide a
satisfactory result.
Evaluation of the patient begins from the
time the person first walks into the exami-
nation room. The patient’s facial features are
assessed for typical facial stigmata of aging
including lentigenes, erythema, fine wrin-
kling, loss of skin laxity, eyebrow and/or eye-
lid ptosis (or chronic eyebrow elevation to
correct latent brow or lid ptosis), midfacial
ptosis, jowling, loss of facial volume, and deep
dynamic rhytids in the glabellar, perioral, and
periocular regions. It is particularly impor-
tant to view the patient as a whole before
concentrating on the periocular (or any other
individual) region as the goal of any treatment
is to create a harmonious facial appearance.
Any pre-existing asymmetry should be noted
and documented prior to treatment.
Botulinum Toxins
The patient is then evaluated from a frontal
perspective. Particular attention is paid to the
presence of rhytids at rest, eyebrow contour
and position, horizontal forehead rhytids that
may be indicative of chronic brow elevation,
extent of photoaging, presence of derma-
tochalasis (excess skin laxity) in the upper
eyelid, position of the upper eyelid margin
relative to the pupil, and lower eyelid posi-
tion. If white sclera is visible above the supe-
rior limbus or below the inferior corneoscle-
ral limbus, additional ophthalmic evaluation
is warranted. The presence of horizontal
forehead rhytids may either indicate overac-
tive use of the muscles or facial expression or
a compensatory response to eyebrow ptosis.
One must make this distinction as weakening
the frontalis muscle in the latter setting
will uncover a previously latent eyebrow
ptosis. Patients who have been unknowingly
compensating by elevating their eyebrows
continuously
to
prevent
impairment
of
their superior visual field will no longer
be able to do so if their frontalis muscle is
weakened.
The examiner can identify the patient with
latent brow ptosis by studying the patient
when the frontalis muscle is completely
relaxed (instruct the patient to relax their
forehead). If the eyebrows assume a lower
position when the frontalis muscle relaxes,
botulinum toxin should not be injected into
the forehead. These patients need eyebrow
and/or eyelid surgery to correct their under-
lying problem. Next, the patient is asked
to gently (not forcibly) close the eyes to
ensure complete apposition of the upper and
lower lids. Some patients who have had prior
surgery, trauma, or thyroid disease may be
able to forcibly close their eyes but have an
incomplete blink that leaves them highly vul-
nerable to symptomatic dry eyes if the orbicu-
laris oculi muscle is weakened. The patient is
then instructed to forcibly close the eyes. This
permits evaluation of the pretarsal orbicularis
oculi muscle in its dynamic state. The appear-
ance of a prominent “bulge” in the pretarsal
region is suggestive of “hypertrophic” orbicu-
laris oculi muscle. Importantly, this condition
must be differentiated from a “bunched”
lower eyelid occurring as a result of cheek tis-
sue recruitment with contraction of the zygo-
maticus major and minor muscles.
Horizontal rhytids in the lateral canthal
region should be evaluated in both frontal
and lateral views. The patient is viewed from
each side first at rest, then with gentle eyelid
closure and finally during forced closure. This
series of maneuvers permits the examiner
to differentiate between fine skin wrinkles
due to loss of elasticity and rhytids caused
by action of the orbicularis oculi muscle.
Next, a “map” of the orbicularis oculi muscle
should be constructed by asking the patient
to repeatedly squeeze their eyes tightly while
the examiner palpates the lateral canthal
region with the tip of the index finger. The
orbicularis oculi muscle may be relatively
small and confined to the region overlying
the lateral orbital rim or may extend nearly to
the tragus laterally, into the lateral extent of
the temporal region superiorly, and into the
upper region of the midface inferiorly. It is
important to map the orbicularis oculi mus-
cle on both sides as its distribution may be
asymmetric.
Finally, the position of the eye is assessed
relative to the orbital rim. Patients with
prominent eyes due to high myopia (a condi-
tion in which the globe is actually longer than
normal), thyroid eye disease, or shallow orbits
should be treated with greater care as they
are more prone to lagophthalmos and change
in lower eyelid position after botulinum toxin
injection.
Treatment Goals
Botulinum toxin may be used in the perior-
bital region to diminish dynamic rhytids in
the lateral canthal region, to weaken eyebrow
depressors and thereby elevate or contour the
brows, and to treat “hypertrophic” orbicu-
laris oculi muscle in the lower eyelid. In any
given patient, it may be desirable to accom-
plish one or more of these goals. They are not
mutually exclusive and should be considered
independently.
12 Treatment of the Periocular Area – Crow’s Feet, Brow, and Bunny Lines
Figure .Complete treatment of
hypertrophic orbicularis oculi muscle
will reduce the muscle bulk upon
smiling but will also make the eyes
appear to be open wider. Patient also
had upper blepharoplasty contributing
to outstanding aesthetic outcome.
When treating lateral canthal rhytids, the
injector must distinguish between those lines
due to the action of the orbicularis oculi
muscle, those caused by contraction of zygo-
maticus major and minor muscles (causing
upward movement of the cheek with smil-
ing) and those due to photoaging of the skin.
Only those lines clearly caused by contrac-
tion of the orbicularis oculi muscle should be
treated with botulinum toxin [11–13]. Treat-
ment at the most inferior-medial orbicularis
may produce an unnatural appearance when
smiling, facial asymmetry or, in the most
extreme circumstance, facial drooping. The
safest approach is to use the least amount
of toxin necessary to produce the desired
clinical effect while still providing adequate
efficacy. One can start conservative and add
more in subsequent weeks as needed. Use
of too much toxin will minimize the action
of the orbicularis oculi muscle to the point
where the lateral canthus does not wrinkle at
all with smiling and other facial expression.
This can signal the appearance of insincer-
ity in some patients, and thus over aggressive
injection in the crow’s feet region should be
avoided.
Careful documentation should be kept and
first-time patients are usually followed up 2
weeks after their injection. At the follow up
visit, the treatment goals should be reviewed
and compared to the clinical results. If addi-
tional injections are needed, this is a good
timepoint to intervene, as all the neuromod-
ulatory effect should be present. If the patient
isn’t satisfied with the results, careful notes
should be made about adjustments that need
to be made in dosage, placement, or both.
As another subtle, yet effective periocu-
lar treatment, botulinum toxin can also be
used to weaken the pretarsal orbicularis oculi
muscle. This can reduce the prominent “roll”
that appears with smiling in patients with
“hypertrophic” orbicularis muscle and can
also increase the size of the palpebral fis-
sure (the distance between the upper and
lower eyelids). While these goals are separate,
they are indistinct as it is difficult to accom-
plish one objective without the other; that is,
treatment of hypertrophic orbicularis oculi
muscle will not only reduce the muscle bulk
upon smiling but will also make the eyes
appear to be open wider. (Figure 12.3).
Further, some patients who complain of
“bunching” of their lower eyelid with smiling
or animation have either excess eyelid skin or
a normal amount of eyelid skin that is com-
pressed into a small area by the upward move-
ment of the cheek associated with strong con-
traction of the zygomaticus muscles. These
patients will not benefit significantly from
botulinum toxin injection into the lower eye-
lid. Thus, a careful examination and discus-
sion about realistic goals is needed prior to
treatment.
The dosage of botulinum toxin A injected
into the periorbital region should be deter-
mined by the treatment goal, the size and
strength of the orbicularis oculi muscle, and
the position of the globe relative to the orbit.
With regards to dosage amounts, it should be
noted that one size definitely does not fit all.
The size and distribution of the orbicularis
oculi muscle may vary dramatically from
patient to patient and even within individuals
from one side of the face to the other.12 Addi-
tionally, distinct crow’s feet patterns were fur-
ther identified and quantified by Kane et al. in
a recent retrospective photographic review
[13]. The looked retrospectively at 2,699
photographs from 1,392 subjects who had
previously participated in neuromodulator
Botulinum Toxins
Figure .Full-fan pattern as described by Kane
et al. [14] (crinkling of lateral canthal skin from lower
lateral brow across the upper eyelid, through the
lateral canthus, and across the lower eyelid/upper
cheek junction).
studies. Full-fan pattern (crinkling of lateral
canthal skin from lower lateral brow across
the upper eyelid, through the lateral canthus,
and across the lower eyelid/upper cheek junc-
tion) (Figure 12.4), lower-fan pattern (wrin-
kling in both the lower lid and upper cheek
area), central-fan pattern (severe wrinkles
only in the skin immediately surrounding the
lateral canthus) (Figure 12.5), and upper-fan
pattern (wrinkles only in the upper eyelid skin
down to the lateral canthus were quantified at
rest and animation. The incidence of full fan,
lower fan, and central fan patterns at rest and
animation was approximately one third for
each, while upper fan was quite uncommon,
seen in only 4.2% of patients at maximum
smile and 6.4% of patients at rest. Individuals
with muscle distributed over a large area
or with relatively hypertrophic muscle will
require larger doses of toxin than may be con-
sidered “standard”. Similarly, patients with
smaller muscles that do not contract as force-
fully should receive relatively lower doses
Figure .Central-fan pattern as described by Kane
et al. [14] (severe wrinkles only in the skin
immediately surrounding the lateral canthus).
of toxin. The dosage should also be reduced
when injecting the lower eyelid and inferior
lateral canthal region of patients with promi-
nent globes due to shallow orbits, thyroid eye
disease or myopia (extreme near-sightedness
due to a longer than normal eye) as these
patients are at higher risk for ectropion or
incomplete eyelid closure [12].
The authors recommend that when dosing
this area, it may be helpful to think in terms
of number of units per injection site than the
total dose required to treat the entire region.
As a general rule, 2.5–5.0 U of onabotulinum
or incobotulinum toxin per site is adequate
in the lateral canthal area. When treating
the inferior pretarsal orbicularis oculi muscle
only 1–2 U should be used per site.
Injection Technique
It is impossible to construct an injection site
map or scheme that can be applied to patients
in a generic manner. While some general
12 Treatment of the Periocular Area – Crow’s Feet, Brow, and Bunny Lines
Figure .Relaxation of the temporal
brow depressor (orbicularis oculi)
leading to brow elevation. The patient
also had her glabellar complex treated.
guidelines can be applied, it is not feasible or
appropriate to recommend a fixed number of
injection sites, total dose of toxin, or the exact
location of injection sites; treatments must
be individualized to each patient. Asymme-
try in orbicularis oculi muscle distribution
does occur [13]. This often necessitates vary-
ing the dose of toxin between the 2 sides of
the face. When injecting in the lateral can-
thal region, the risk of toxin diffusion into the
orbit increases with proximity to the canthal
angle as well as depth. While there has yet
to be a study to address this issue directly, it
seems that injecting 1–1.5 cm from the lateral
canthal angle minimizes the risk of clinical
effects of toxin on the extraocular muscles.12
Because this can be a sensitive area for
treatment, pain management techniques for
periorbital botulinum toxin injections are
often employed. Topical anesthetic agents,
such as 4–6% topical lidocaine can be used
with appropriate incubation times. Addition-
ally, some have used of ice packs imme-
diately prior and after injection for pain
control, vasoconstriction of periocular ves-
sels, and containment of new-onset purpura.
Extremely anxious patients may very rarely
request oral sedation prior to injection. Of
course, transportation arrangements must be
made as driving while sedated cannot be per-
mitted. If a topical anesthetic agent such as
4% lidocaine cream, is applied, it should be
thoroughly removed before injection. Resid-
ual cream can occlude the small caliber 30–
32 G needles and result in lost time and
wasted product.
Regarding brow contouring/shaping with
botulinum toxin, some of the finer points
of treatment should be discussed. The ratio-
nale for using botulinum toxin A to change
eyebrow position is based on the selective
relaxation of brow depressors [16]. Centrally
the corrugator, depressor supercilii, and pro-
cerus muscles are all important brow depres-
sors. Temporal to the papillary midline, the
orbicularis oculi muscle is the sole brow
depressor. The orbicularis oculi is opposed
by the frontalis muscle medial to the tem-
poral line of fusion (conjoined tendon) and
is unopposed temporal to this landmark (in
the region overlying the temporalis mus-
cle). Therefore, relaxation of the tempo-
ral brow depressor leads to brow elevation
(Figure 12.6).
For placement of these injections, anec-
dotal reports suggest a variety of options
including directly into the tail of the brow,
above the tail, and below the lateral brow.
Providing the orbital orbicularis oculi muscle
is affected by the toxin, the exact placement
of the injection is probably not critical.
Avoiding
unintended
diffusion
into
the
inferior aspect of the frontalis muscle is to
be strictly avoided. Those injectors using
a higher dilution (e.g. 4 cm3 of saline) and
thus a greater volume may be well advised
to inject relatively more superiorly to avoid
unexpected diffusion of toxin into the levator
muscle. Another option is to utilize a more
potent/less diluted injection solution. The
authors have found that a 1 cm3 dilution gives
very precise control over the treatment area.
Injections given along the superior orbital
rim should be performed with care. In this
manner, injections can be safely performed
in this area. As an example, the authors
Botulinum Toxins
routinely
treat
patients
with
intractable
blepharospasm,
injecting
5 U
of
onabo-
tulinumtoxinA each of three positions along
the superior orbital rim (a total of 15 U) along
with an additional 2.5–5.0 U in the medial
and lateral portions of the upper eyelid itself
(a total of 5–10 U), without adverse sequelae
(Dr.
Biesman,
personal
communication).
Always direct the needle away from the orbit
as directing the toxin toward the eye may
result in diffusion of toxin into extraocular
muscles or even serious injury if the patient
were to move suddenly during the injection.
The novice injector may wish to either sta-
bilize their injecting hand against the patient
or “smart” hand as it rests on the patient.
This will prevent inadvertent perforation of
veins or the eye in the event of an unexpected
movement. When injecting into the perior-
bital region, always point the needle away
from the eye itself. To minimize the risk of
ecchymosis in the lateral canthal region, it
is helpful to identify the vessels when possi-
ble. Visualization with good overhead room
lighting, a dermatoscope, transillumination,
or use of a cross-polarized light source can
help with this. This is easier with type I–III
patients and atrophic skin. The authors rec-
ommend very superficial intradermal injec-
tions, akin to a superficial bleb (Figure 12.7).
When possible, injecting immediately over-
lying an obvious vessel should be avoided.
Figure .Superficial blebs demonstrating
placement depth of neuromodulator in periocular
area will minimize all potential complications.
Finally, injections should be administered
from the side and never from in front of the
patient to avoid having the needle directed
towards the orbit. If immediate bleeding or
bruising does occur, holding point pressure
with a fingertip or cotton-tipped applicator
for 1–2 minutes will help minimize spread.
Additionally, use of the pulsed dye laser can
hasten the clearance of new-onset purpura.
Although it is generally true that absolute
rules about dosage and number of injection
sites should not be made, great care should be
taken when injecting the pretarsal orbicularis
oculi muscle. This muscle can be injected in
its central portion (immediately below the
pupil) or alternately, may be injected in two
sites, roughly corresponding to the medial
and lateral corneoscleral limbus. If a single
central injection is planned, a dose of no more
than 2 U of onabotulinumtoxinA should
be injected initially. Additional injections
can be administered as needed at the 2-week
follow up visit. If two separate sites are used,
no more than 1.0–1.5 U should be delivered
at each site. Excessive delivery of toxin in this
region can impair eyelid closure and may lead
to tearing, ectropion, and even inward turn-
ing of the eyelid against the eye (entropion).
Entropion can occur when the preseptal
orbicularis oculi muscle contracts forcefully
in the setting of an immobile pretarsal mus-
cle. In this situation, the preseptal muscle
moves
upward
overriding
the
pretarsal
muscle and pushing the pretarsal muscle
and eyelid margin inward toward the eye.
This usually produces severe ocular pain and
irritation. When administering lower eyelid
injections, it is advisable to deliver the toxin
subcutaneously to avoid diffusion into the
inferior oblique muscle which occupies a rela-
tively anterior position in the orbit. If the infe-
rior oblique muscle is affected, vertical and/or
torsional diplopia can result.
The final area of treatment to be dis-
cussed in this chapter is treatment of the
oblique lines overlying the nasal root and dor-
sum, the so-called “bunny lines.” This pat-
tern of dynamic rhytides can be elicited by
scrunching the nose, or with expressions of
12 Treatment of the Periocular Area – Crow’s Feet, Brow, and Bunny Lines
displeasure or a forced smile. Additionally,
this pattern can often be seen in concert with
the appearance of crow’s feet, because both
are elicited by chronic squinting. These lines
should be differentiated from transverse lines
resulting from procerus activity.
Bunny lines can result from contracting the
transverse portion of the nasalis. This portion
arises from the maxilla and runs diagonally
across the bridge of the nose. It expands into a
thin aponeurosis and is continuous with that
of the muscle of the opposite side and with the
aponeurosis of the procerus [14]. The nasalis
muscle has two main parts, the transverse
or compressor part (also known as compres-
sor naris), which constricts the nostril, and
the alar or dilator part (also known as dilator
naris), which flares the nostril [15]. An alter-
nate etiology of these lines is due to contrac-
tion of the levator labii superioris alequae nasi
in some patients, analogous to zygomaticus
causing lateral canthal lines.
Injection technique
When treating this area, it is imperative that
injections avoid the levator labii superioris
alaeque nasi and the levator labii superioris to
prevent drooping of the upper lip. A series of
one to three injection points along the mid-
line nasal dorsum and along the upper nasal
sidewall, superficially in the nasalis muscle,
should be sufficient to soften or eliminate
these lines. Performing the injections super-
ficially is critical to avoid bruising in this
highly vascular area [16,17]. Typically, 1–3 U
of onabotulinumtoxinA per injection point
is sufficient to achieve the desired effect. The
injector can also consider including an injec-
tion of 1–2 U per side of the upper nasalis
when treating the glabellar area, to pre-
vent recruitment. As previously noted, the
authors recommend a 1 cm3 dilution to avoid
diffusion in this area, which could result in lip
ptosis.
In summary, enhancement of the perioc-
ular area of the face with botulinum toxin
can be challenging and technique-dependent.
Careful evaluation of the area, with atten-
tion to any pre-existing asymmetry, underly-
ing compensatory muscle action, and natural
brow positioning is critical to achieving good
treatment outcomes. Using the approach and
techniques described in this chapter can facil-
itate reproducibly good results for rejuvena-
tion of this cosmetically sensitive region.
References
Frankel AS. Botox for rejuvenation of the
periorbital region. Facial Plast Surg 1999;
15(3):255–262.
Flynn TC. Periocular botulinum toxin. Clin
Dermatol 2003 Nov–Dec;21(6):498–
504.
Matarasso A, Glassman M. Effective use of
botox for lateral canthal rhytids. Aesthet
Surg J 2001 Jan;21(1):61–63.
Matarasso SL, Matarasso A. Treatment
guidelines for botulinum toxin type A for
the periocular region and a report on
partial upper lip ptosis following injections
to the lateral canthal rhytids. Plast Reconstr
Surg 2001 Jul;108(1):208–214.
Biesman, B. Periorbital rejuvenation. In
Hirsch R., Sadick N., and Cohen JL (eds),
Aesthetic Rejuvenation – A Regional
Approach. New York, McGraw Hill, 2008:
100–115.
Goldman MP. Festoon formation after
infraorbital botulinum A toxin: a case
report. Dermatol Surg 2003 May;29(5):
560–561.
Schwartz RJ, Burns AJ, Rohrich RJ, et al.
Long-term assessment of CO2 facial laser
resurfacing: aesthetic results and
complications. Plast Reconstr Surg 1999;
103(2):592–601.
Biesman BS. Anatomy of the eyelid,
forehead, and temporal region. In Biesman
BS (ed), Lasers in Facial Aesthetic and
Reconstructive Surgery. Baltimore. Williams
and Wilkins 1999:15–27.
Botulinum Toxins
Aguilar GL, Nelson C. Eyelid and anterior
orbital anatomy. In Hornblass AH (ed.)
Oculoplastic, Orbital and Reconstructive
Surgery. Baltimore, Williams and Wilkins
1988;4–22.
Benedetto AV. Botulinum Toxins in
Clinical Aesthetic Practice, 2nd ed. New
York: Informa Healthcare, 2011:64.
Fagien S. Botox for the treatment of
dynamic and hyperkinetic facial lines and
furrows: adjunctive use in facial aesthetic
surgery. Plast Reconstr Surg 1999;103:
701–708.
Biesman BS, Arndt KA. Periocular
treatment. In Carruthers A and Carruthers
J (eds). Botulinum Toxin. Procedures in
Cosmetic Dermatology. 2005 Elsevier,
Inc.:45–57.
Kane MAC. Classification of crow’s feet
patterns among caucasian women: the key
to individualizing treatment. Plast Reconstr
Surg:2003 Oct 112(5);33S–39S.
Kane AC, Cox SE, Jones D, et al.
Heterogeneity of crow’s feet line patterns in
clinical trial subjects. Dermatol Surg 2015
Apr;41(4):447–456.
Carruthers J, Fagien S, Matarasso SL.
Consensus recommendations on the use of
botulinum toxin type a in facial aesthetics.
Plast Reconstr Surg 2004 Nov;114(6 Suppl):
1S–22S.
coursepages/m1/anatomy2010/html/
anatomytables/muscles_head_neck.html
Maas CS, Kim EJ. Temporal brow lift using
botulinum toxin A: an update. Plast
Reconstr Surg 2003 Oct;112(5 Suppl):
109S–112S.
Contouring of the Lower Face and of the Lower Leg and Calf
Mee young Park, MD (PhD),1 Dennis A. Porto, MD,2 and Ki Young Ahn, MD (PhD)3
1Department of Neurology, Yeungnam University, College of Medicine, Daegu, South Korea
2Department of Dermatology, Henry Ford Hospital, Detroit, USA
3Director, Dr. Ahn’s Aesthetic & Plastic Surgical Clinic, Daegu, South Korea
Contouring of the Lower Face
Introduction
In 1994, Smyth [1] first reported the medi-
cal utility of botulinum toxin type A (BoNTA)
in benign masseter hypertrophy (BMH).
BoNTA injection was suggested as a poten-
tial aesthetic procedure for lower face con-
touring by von Lindern et al. in 2001 [2] and
was simultaneously being employed by early
physician adopters in Korea and elsewhere in
Asia [3,4].
The mechanism of lower facial contour-
ing by BoNTA differs from that of treat-
ment of dynamic rhytides and various facial
neuromuscular disorders [3, 5] such as ble-
pharospasm and hemifacial spasm. Facial
contouring, instead, relies on the temporary
but significant effects of muscle atrophy and
partial muscle paralysis due to acetylcholine
blockade at the neuromuscular junction.
The facial muscles (which are traditional
targets of BoNTA injection for treating
rhytides) are relatively thin and if atrophy
occurs after repeated injections, it may not be
clinically apparent. In contrast, the masseter
muscle is thicker, making it an ideal target for
facial contouring and amenable to treatment
for BMH.
Body contouring with neurotoxins contin-
ues to be refined, and investigators have made
forays into calf, shoulder, and neck sculpting
as well. More research is necessary to fully
define the role of neurotoxins in this blossom-
ing discipline.
Contouring
Some women tend to prefer oval and almond-
shaped faces and dislike a square jaw, which
they believe is more masculine. Differences
in facial preferences between Caucasians and
Asians derive in part from ethnic differences
in the craniofacial shape, with those of Euro-
pean origin often having a long, narrow face
compared to shorter, wider faces among some
Asian women [6]. Many Asian women tend to
dislike a square shaped jaw as it can accen-
tuate a wider face. Men tend to prefer a
defined jaw and therefore masseter injections
are rare in this group; however, we are happy
to accommodate men who are seeking a slen-
derer appearance or those interested in gen-
der confirmation procedures.
Contouring of the mandible is a rela-
tively common aesthetic procedure in Asia,
although it is rare among Caucasians. At
present,
operative
treatment
is
limited
to resection of the angle or body of the
mandible, masseter resection, and liposuc-
tion. These surgical procedures have many
disadvantages, including risks of persistent
swelling, hematoma, and postoperative pain.
Botulinum Toxins: Cosmetic and Clinical Applications, First Edition. Edited by Joel L. Cohen and David M. Ozog.
© 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.
Companion Website:
Botulinum Toxins
In addition to these immediate complica-
tions, prominent scars may occur on the neck
with the extraoral approach, and partial palsy
of the facial nerve has been reported [2,7].
Patients who desire neurotoxin facial con-
touring are generally 20–40 years old and
often have social responsibilities that make
surgical procedures difficult. Therefore, the
use of botulinum toxin type A (BoNTA) for
contouring of the lower face could offer a sim-
ple alternative to the risks of surgery.
BoNTA injections are gaining acceptance
for lower facial contouring in Korea. This
procedure is beginning to be used as fre-
quently as surgical mandiblectomy and some-
times the two are used in combination.
The goal has been to establish a procedure
that avoids the risks of surgery while offer-
ing a predictable and clinically significant
improvement. Since 2001, we have worked to
achieve this goal and the remainder of this
chapter delineates our findings.
The Anatomy of the Masseter Muscle
The masseter is the most superficial and one
of the strongest muscles of mastication. The
masseter is a thick, somewhat quadrilateral
muscle, consisting of two heads: superficial
and deep. The fibers of the two heads are
continuous at their insertion. The superficial
head is larger and originates with thick and
tendinous aponeuroses from the zygomatic
process of the maxilla and from the anterior
two-thirds of the inferior border of the zygo-
matic arch. Its fibers pass inferior and poste-
rior and insert into the angle of the mandible
and inferior half of the lateral surface of the
ramus of the mandible. The deep head is
much smaller, yet more muscular. It origi-
nates from the posterior third of the lower
border of the zygomatic arch and from the
whole of the medial surface of the zygomatic
arch. Its fibers pass ventral and inferior, to be
inserted into the upper half of the ramus as
high as the coronoid process of the mandible.
The deep head of the muscle is partly con-
cealed, anteriorly, by the superficial portion.
Posteriorly, it is covered by the parotid gland.
Along with the other three muscles of
mastication (temporalis, medial pterygoid,
and lateral pterygoid), the masseter is inner-
vated by the mandibular division (V3) of the
trigeminal nerve.
The action of the muscle during bilateral
contraction of the entire muscle is to elevate
the mandible, raising the lower jaw. Elevation
of the mandible occurs during the closing of
the mouth. The action of the masseter par-
allels the medial pterygoid muscle, but it is
stronger.
We performed a cadaveric dissection to
better characterize landmarks and other
properties of the masseter to refine our tech-
nique. The masseter is approximately 8 cm
and its thickness varies along its length with
a maximum of about 1 cm (Figure 13.1) The
majority of the masseter volume is below the
line from the subnasale to the tragus (Fig-
ure 13.2).
We recruited 12 women between the ages
of 20 and 40 without masseter hypertrophy in
order to study the masseter with ultrasound
and CT scans. The mean (SD) thicknesses
of masseter muscles in these normal control
subjects by ultrasound were 12.1 (±1.0) mm
on the left side and 12.1 (±1.1) mm on the
right side. By CT scans, these figures were
12.1 (±1.2) and 12.5 (±1.8) mm, respectively.
These data are also similar to the results of
Qingfeng Li et al. in China, published in the
2014 [8].
These are the only published measure-
ments of masseter thickness, and therefore
are the reference when establishing whether
a patient has BMH.
Preinjection Considerations
It is important to review with patients the
possible causes of masseter hypertrophy.
These include chewing gum or cuttlefish,
bruxism, various dental treatments, and tem-
poromandibular joint pain. If bony protuber-
ance of the mandibular angle is instead sus-
pected, this can be confirmed with xray. If
TMJ is suspected, this should be confirmed
with TMJ X-rays, CT and/or MRI. BoNTA
13 Contouring of the Lower Face and of the Lower Leg and Calf
Figure .A cross-sectional view of the masseter muscle along its length.
injection may lead to adverse effects among
these patients.
Injection Technique
As with other neuromodulator use, there
is considerable variability among authors
on
neuromodulator
type,
dose,
volume,
injection points, and intervals for repeat
injections.
We reconstitute 100 U vials of onabo-
tulinumtoxin (Botox®) with 2 ml of normal
saline to yield 5 U per 0.1 ml. We then ask the
patient to clench their jaw so that the bor-
ders and volume of the masseter muscle can
be palpated. We define a safe area of injec-
tion by drawing a line from the subnasale to
the tragus and connecting this to the palpated
anterior, inferior, and posterior margins of the
masseter. Percutaneous intramuscular injec-
tions of the masseter are performed without
electromyographic guidance. Between 25 and
30 U are injected into each masseter, divided
between five to six points. In male patients,
up to 40 U are sometimes used. We inject
deep into the masseter itself with a 29 gauge,
12.7 mm BD insulin syringe. Most patients
were injected with a total of 50 U to 60 U
(Figure 13.3).
It is important to inject both masseter
muscles, even in patients with asymmetric
hypertrophy, because both muscles contract
simultaneously; however, an additional 5–
10 U can be injected into the hypertrophic
side (Figure 13.4).
A
B
C
(a)
(b)
(c)
Figure .The topographic relationship
between the masseter and nose, lips, ear.
The majority of the masseter volume is
below the line from the columella to the
tragus in Frankfort horizontal position.
(a) Subnasale; (b) the highest point of the
upper vermillion border; (c) the lateral
oral commissure.
Botulinum Toxins
(a)
(b)
Figure .Injection points. A checkerboard pattern is used to create five or six injection points for each
masseter.
(a)
(b)
Figure .A 34 year old female patient, treated with 25 U of Botox® on the left masseter and 30 U on the right
masseter. (a) Preinjection; (b) 3 months after injection.
13 Contouring of the Lower Face and of the Lower Leg and Calf
Reduction in Hypertrophy Measured by
Ultrasound and CT
To better evaluate the reduction in mas-
seter volume after BoNTA injections, CT
and ultrasound imagining were performed at
follow-up. Due to the variable thickness of the
masseter along its length, it was necessary to
use well-defined landmarks and patient posi-
tioning to make meaningful measurements.
Serial measurements of the thickness of
the masseter were made by ultrasound and
CT scans before the injections and at 1
and 3 months thereafter. Two males and 43
females participated in the study. Ages ranged
between 24 and 48 years, with a mean of 35.
Among the total of 45 patients, 15 under-
went all three ultrasound scans, whereas
14 received all three CT scans. The mean
masseteric thickness before injection was
14.0 (1.9) mm on the left side and 14.4
(2.2) mm on the right side, as measured by
ultrasound. Using CT, these measurements
were 14.9 (2.2) and 15.5 (3.3) mm, respec-
tively. Mean masseteric thicknesses at 1 and
3 months after injection by ultrasound were
11.2 (1.6) and 11.5 (1.4) mm on the left side
and 11.5 (1.6) and 11.9 (1.4) mm on the right
side, respectively. By CT scan, these respec-
tive figures were 13.3 (2.1) and 12.0 (1.7) mm
and 14.2 (2.6) and 12.7 (2.2) mm (Table 13.1).
In this study, the average amount of thick-
ness change of masseter in ultrasound and
CT measurement studies was approximately
2.8–2.9 mm, and these changes were equiv-
alent to approximately 18–20% of the mus-
cle thickness of the masseter at preinjection.
This change was statistically significant. In an
extreme case, one patient who was excluded
from the quantitative analysis of the thickness
change showed an approximate 30% masseter
thickness change.
In 2001, several studies attempted to quan-
tify the change in masseter thickness after
BoNTA. A report by von Lindern et al. [2]
found that seven patients with unilateral or
bilateral hypertrophy of the masseter and
temporalis muscles that were treated with an
average of 100 U of Dysport® showed a 50%
reduction in masseter thickness. That result
was considered to be aesthetically satisfac-
tory after a single injection in four of the
seven patients. To et al. [7] described five
patients with unilateral and bilateral hyper-
trophy of the masseter who were treated with
200–300 U of Dysport® per side, and demon-
strated improvement confirmed by ultra-
sound. Three of five patients needed a sec-
ondary injection within 1 year. Mandel and
Tanakan [9] reported that one patient with
unilateral hypertrophy of the masseter was
treated with 5 U of Botox, and the effect lasted
approximately 4 months, although no long-
term results were reported.
Table 13.2 is a summary of other recent
reports that attempt to quantify masseter
improvement with neuromodulator use.
Outcomes Measured by Serial Photography
The outcome most important to our patients
is the improvement in their clinical appear-
ance. This can be easily, inexpensively, and
accurately measured by anterior-posterior
(A-P) photography. We collected serial pho-
tographs of multiple patients and measured
Table .Descriptive analysis of observed data for the masseter thickeness in both sides (mean [SD]).
Preinjection
Postinjection
Month
Postinjection
Months
Controls
(N = )
Time methods
Lt
Rt
Lt
Rt
Lt
Rt
Lt
Rt
CT (N = 14)
14.9 (2.2)
15.5 (3.3)
13.3 (2.1)
14.2 (2.6)
12.0 (1.7)
12.7 (2.2)
12.1 (1.2)
12.5 (1.8)
SONO (N = 15)
14.0 (1.9)
14.4 (2.2)
11.2 (1.6)
11.5 (1.6)
11.5 (1.4)
11.9 (1.4)
12.1 (1.0)
12.1 (1.1)
Lt, Left; Rt, Right; Mo, Month; SONO, Ultrasound; CT, Computerized tomography.
Botulinum Toxins
Table .Comparison of several reports of botulinum toxin for masseter hypertophy.
Reference
Aesth Plast
Surg (2011)
35:452–455
Plast
Reconstr Surg
134:209e,
2014
Plast
Reconstr
Surg, March
2005 115:919
Dermatol
Surg 2015;41:
S101–S109
Dermatol
Surg 2003;29:
484–489
Corresponding
author
C. S. Chang
et al. [10]
Qingfeng Li
et al. [8]
Nam Ho Kim
et al. [11]
Chuanchang
Dai et al. [12]
Kyle Seo et al.
[4]
Type of BoNTA
Dysport®
HengLi®
(similar to
Botox®)
Dysport®
BTX-A
(unspecified
type)
Botox®
Concentration
and dilutent
200 U/cm3 in
sterile
distilled water
unknown
125 U/cm3 in
sterile
distilled water
unknown
100 U/cm3 in
sterile saline
Injection
points per
masseter
6
unknown
3–4
4
6
Total injected
dose per
masseter
120 U
20–40 U
based on
masseter
thickness
100–140 U
based on
masseter
volume
35 U
30 U
Approximate
measured
improvement
30%
decreased
volume
32%
decreased
thickness
31%
decreased
thickness
31%
decreased
thickness
22%
decreased
volume
their improvement using a standardized tech-
nique. To quantify improvement, the width of
the lower face at the level of the oral commis-
sure (A) was measured and compared to the
unchanging width between the left and right
ala (B). With these values, the percent reduc-
tion in width of the lower face can be deter-
mined using this formula:
The reduction rate of the width of the
lower face at oral commissure level (%) =
A/B (preinjection) −A/B (postinjection)
A/B (preinjection)
× 100
This ratio is also demonstrated in Fig-
ure 13.5.
We used this method of measurement for
a patient and found a 3.7% reduction in
facial width 1 month after injection. Maxi-
mum efficacy was at 3 months with a 6.9%
improvement before eventuating in a 4%
improvement at 1 year postinjection (Fig-
ure 13.6). This is in keeping with our clinical
experience, in that maximal efficacy is noted
at month 3 or 4 with a gradual return to base-
line over many months. In this way, improve-
ment from BoNTA injection is more dynamic
and reversible when compared to a procedure
like mandibulectomy or liposuction.
Our patients were very satisfied after treat-
ment with a single injection. At 10 months’
postinjection, 37 of 45 patients were either
very satisfied or satisfied. These numbers are
similar to other published reports.
Repeat injections
Improvements in masseter hypertrophy after
BoNTA injection tend to subside over the
proceeding months and years, so repeat injec-
tions are often necessary. Some authors allow
patients to decide when they require reinjec-
tion while others have a structured reinjec-
tion schedule. Further, some authors adjust
the dose of the BoNTA injection based on
masseter size while others use the original
dose for all subsequent injections.
13 Contouring of the Lower Face and of the Lower Leg and Calf
(a)
(b)
B
A
B′
A′
Figure .Pre- and post-treatment comparison of the static distance between the left and right nasal ala, and
the improved width of the lower face at the level of the oral commissure.
We studied a group of patients that were
reinjected every 6–12 months at the same
dose as their initial injection (typically 25–
30 U per masseter, as described above). We
then used serial photographic measurements
to track facial width. We followed 13 patients
over several years during which they received
at least three injections. On average, patients
completed 5.5 sessions and returned about
every 11.5 months. We analyzed patients in
two groups: those with irregular reinjection
intervals between 7 and 12 months, and those
(a)
(b)
(d)
(e)
(c)
Figure .Serial photography over the course of one year post-injection with maximum efficacy at three
months.
Botulinum Toxins
(a)
(b)
(c)
Figure .Significant improvement of masseter hypertrophy in a patient treated every six months with
botulinum toxin.
with regular reinjections every 6 months. The
mean reduced width of the lower face in
the former group was 8.15% and in the lat-
ter group was 12.42%. Further, duration of
improvement after cessation of injections was
longer in the 6 month group compared to the
7–12 month group (Figure 13.7).
There are few reports that examine the
durability of improvement after repeat injec-
tion.
Kim et al. [13] studied 121 patients treated
for more than 1 year with BoNTA, receiv-
ing anywhere from two to eight injections.
At each visit, masseter thickness was mea-
sured with ultrasound. Patients were injected
with 100–140 U of Dysport in each masseter,
based on thickness. Average masseter mus-
cle thickness was reduced from 13.32 mm at
the baseline visit to 9.94 mm at the last visit
on average (a 25.4% improvement). The dose
of Dysport was adjusted downward at return
visits as the masseter’s thickness decreased.
In a randomized control trial of 98 patients,
Jiao Wei et al. [14] found that patients
instructed to exercise their masseter early
after BoNTA injection had the effect of delay-
ing the return of masseter hypertrophy.
Effect on the mandible and other muscles
of mastication
Chang et al. [10] examined the mandible
with three dimensional CT before and three
months after BoNTA injection of bilateral
masseter muscles. They evaluated ten female
patients and measured mandibular cortex
thickness, bone thickness, and mandibu-
lar volume and found that there were no
significant changes during this time interval
preinjection and postinjection. They believed
that these results supported the continued
practice of BoNTA masseter injection com-
bined with mandibular surgery in selected
patients. Further, Chung-Chih Yu et al. [15]
used CT to confirm no significant changes
in other mastication muscle volume of after
masseter injection.
Side effects
Patients may notice an ache at the site
of injection, difficulty with hard food, and
speech disturbances 1–4 weeks after injec-
tion; these complaints are transient. There
are also reports of visible masseter fascicu-
lation, dry mouth, and asymmetry including
a prominent zygoma or sunken cheek. Kim
et al. [13] have suggested that sunken cheeks
may be attributed to injections that are too
high or too anterior on the masseter and may
be more common in those with poor skin
elasticity.
The most common side effect is a transient
and mild masticatory weakness with easy
fatigue while chewing, or weakened bite with
tough food. Such changes are mild and toler-
able and should be anticipated with BoNTA
injection into the masseter.
Using a bite-force transducer, we quanti-
fied this reduction in masseter strength [15].
We measured bite force prior to injection of
BTX-A 25 U bilaterally, and at 2, 4, 8, and
12 weeks’ postinjection. While the maximum
bite force was significantly reduced after
injection, it slowly recovered by 12 weeks.
Chung-Chih Yu [16] completed a similar
13 Contouring of the Lower Face and of the Lower Leg and Calf
study that found that bite force was decreased
1 week postinjection and that it reached its
lowest point in week 3. But by month 3, bite
force completely recovered despite improve-
ments in masseter hypertrophy. This discrep-
ancy is thought to be due to compensation by
the other muscles of mastication.
Other side effects are similar to BoNTA
injections elsewhere on the body and include
headache, body ache, and rare allergy. Fur-
ther, there are rare reports [17] of antibody-
induced
therapy
failure
with
multiple
injections.
Ideal
facial
contouring
with
BoNTA
maximizes reduction in masseter hypertro-
phy while minimizing masseter weakness.
Reports of temporomandibular joint distur-
bances or antibody formation are thought
to be related to high doses of administered
BoNTA. As in Sloop’s dose–response curve
[18], beyond a certain point, additional units
of BoNTA do not lead to additional efficacy.
Therefore, it is preferable to use the lowest
necessary dose while scheduling appropriate
reinjections to prevent complications.
Contouring of the Lower Leg
Introduction
More and more women are interested in con-
touring and slimming of the lower leg, in
part due to popular clothing styles that high-
light this area (e.g., high-heeled shoes, shorts,
skirts, capris). Often, women requesting this
are former professional or amateur athletes or
those with jobs that require a lot of standing
(including professional models), leading to
calf hypertrophy. Men rarely request calf con-
touring. In fact, the authors have not treated
a male patient with this procedure, although
it could feasibly be part of a gender confirma-
tion procedure.
Over the past 15 years, many surgi-
cal approaches to calf slimming have been
attempted, but most require invasive proce-
dures with inherent risks. These include lipo-
suction, endoscopic partial resection of the
hypertrophic calf, and severing branches of
the tibial nerve that innervate the medial
head of the gastrocnemius. In addition to the
usual surgical risks of ecchymosis, swelling,
hematoma, scarring, and infection, there are
also reports of long postoperative recoveries
and gait disturbances [19].
The surface appearance of the calf is influ-
enced not only by the underlying muscle,
but also the abundance or paucity of sub-
cutaneous fat, the exposed Achilles’ tendon,
and the shape of the tibia and fibula. Large
calves can be divided into three etiologic
groups: lipodystrophic (often with a slim
ankle), hypertrophic (often with visible fas-
ciculation when walking), and combined
lipodystrophic and hypertrophic (often with
a larger ankle circumference and “radish-like”
appearance).
Patients in the lipodystrophic group bene-
fit most from liposuction. In the past, patients
in the hypertrophic group have been treated
with endoscopic resection of the hyper-
trophic parts of the calf and severing of
branches of the tibial nerve that innervate the
medial head of the gastrocnemius. Patients
in the mixed lipodystrophic/hypertrophic
group have been treated with a combination
of these modalities.
Calf contouring with BoNTA began in the
past 15 years in Korea among physicians
who had positive experiences using these
injections for lower face contouring. BoNTA
injection was thought to be potentially a safer,
temporary but effective alternative to the
invasive surgical procedures used previously.
As expected, patients with large calves due
primarily to muscular hypertrophy stand to
benefit most from BoNTA injection.
Anatomy
The target muscles of calf reduction and con-
touring procedures with BoNTA are the gas-
trocnemius and soleus muscles located on the
posterior surface of the low leg. The primary
action of these muscles is plantar flexion (i.e.,
“tip-toeing”) [21]. Among these, the soleus is
the more important postural muscle, and is
persistently active during ordinary standing
to prevent the person falling forward; thus,
Botulinum Toxins
(a)
(b)
(c)
Figure .The various types of muscular hypertrophy calf. the prominent medial head (a), the prominent
medial and lateral heads (b), and the diffusely prominent calf (c).
soleus paralysis is likely to disturb gait and
stability.
The gastrocnemius muscle is more super-
ficial and thus contributes more to the super-
ficial contour of the calf. The lateral head of
the gastrocnemius originates from the lateral
condyle of the femur and the medial head
originates from the medial condyle of the
femur. Together with the soleus muscle, the
gastrocnemius forms the Achilles’ tendon
which inserts onto the posterior surface
of the calcaneus. While the gastrocnemius
also contributes to plantar flexion, it plays
a lesser role and therefore is unlikely to dis-
turb gait if weakened. Therefore, the target
muscle for BoNTA (at least initially) is the
gastrocnemius.
Injection Technique
Prior to injection, the most hypertrophic por-
tions of the calf are identified and marked
with the patient in plantar flexion. Patients
are injected with 100 U of Botox® reconsti-
tuted in 10 cm3 of normal saline, yielding
10 U/cm3. The gastrocnemius is a relatively
thick and dense muscle, so we use a 23G,
1.25 inch, 10 cm3 Profi syringe® for injection.
Among patients with muscular calf hyper-
trophy, we find that their anatomy most often
falls into one of three categories: the promi-
nent medial head, the prominent medial and
lateral heads, and the diffusely prominent calf
(Figure 13.8a–c).
We inject 50–100 U per each calf, divided
between 5 and 10 injection points with 5–
10 U of BoNTA per point. The injections
should be deep within the substance of the
muscle, thus requiring a 1.25 inch syringe.
Most patients are injected with a total of 100–
200 U each session. To limit the risk of gait
abnormality, it is sometimes advisable during
the patient’s first session to limit injections
only to the medial gastrocnemius.
Clinical effect
Calf contouring with BoNTA remains a rel-
atively rare procedure due to expense and
comparatively short duration of effect. Fur-
thermore, objectively measuring improve-
ment with CT or ultrasound have proven
13 Contouring of the Lower Face and of the Lower Leg and Calf
(a)
(b)
(c)
Figure .(a) Pre-injection; (b) injection points; (c) attenuation of the medial head of the gastrocnemius.
difficult and cost prohibitive. For these rea-
sons, there is very little published on this
technique. We will review several demonstra-
tive cases below.
Case 1
A 28-year-old patient with hypertrophy of
the medial head of the gastrocnemius was
injected with 50 U of Botox® in each calf,
divided among the medial head as shown in
Figure 13.9. Eight weeks after injection, the
border of the medial head of the gastrocne-
mius was softened.
Case 2
A 41-year-old patient with prominent medial
and
lateral
heads
of
the
gastroctemius
received yearly injections of 50 U Botox®
per side for a total of four sessions. She
returned 3 years after her fourth injection
with persistent slimming of the lower legs
(Figure 13.10).
Case 3
A 56-year-old patient with diffusely promi-
nent calves was injected with Xeomin® 100 U
per calf every 6 months. Both the gastroc-
nemius and soleus were injected. Six months
after the second injection, the lower legs are
slimmer with attenuated surface contouring
(Figure 13.11).
In
the
authors’
experience,
clinical
improvement
in
calf
hypertrophy
tends
to be evident at 3–4 weeks’ postinjection
and from month 6 to 12 begins to return to
baseline. This course is similar to our expe-
rience in lower face contouring. Park et al.
[19] have found that 50–150 U of BoNTA
per calf led on average to a decrease in calf
circumference of 0.7–1.58 cm (12.5–24.8%
improvement)
6
months’
postinjection.
According to Park et al. [19], 50–150 U of
BoNTA on each calf region and followed up
for 6 month. This percent improvement is
also similar to what can be expected with
masseter injection. Apart from changes in
calf circumference, many patients also are
pleased with improvement in calf contour.
Side effects
The most common side effects were minor
ecchymosis or dull and transient discomfort
at the sites of injection. Uncommonly, stand-
ing instability or fatigue (especially with high
heels) were noted. This instability also tends
to subside within a month and is related to
higher administered doses and injections
Botulinum Toxins
(a)
(b)
(c)
Figure .(a) Pre-injection; (b) just prior to the fourth injection; (c) 3 years after the fourth injection.
(a)
(b)
(c)
Figure .(a) Pre-injection; (b) injection points; (c) 6 months after the second injection.
13 Contouring of the Lower Face and of the Lower Leg and Calf
outside the gastrocnemius. The authors have
not observed gait disturbance or antibody
formation
leading
to
BoNTA
inefficacy,
although these are theoretical risks. To
reduce the likelihood of antibody formation
(especially considering the high doses of
BoNTA required), injection intervals of
6 months or longer are recommended. To
limit side effects and cost, efforts should be
made to use the minimal dose of BoNTA
necessary to achieve the desired clinical
endpoint.
Concluding Remarks: Masseter
and Calf Contouring
Basic principles of BoNTA injection apply to
both masseter and calf injection, and prin-
ciples in one muscle group can help inform
the other. Calf muscles, for example, are
much larger than the masseter and therefore
100 U of Botox® are diluted in 10 cm3 of nor-
mal saline for the calf and we only dilute
with 2 cm3 for the masseter. For both mus-
cle groups, injections should be distributed
evenly over the body of the muscle, includ-
ing origins and insertions. Failure to ensure
even distribution can result in compensatory
hypertrophy or fasciculation.
In
the
authors’
experience,
clinical
response to BoNTA varies considerably
among individuals based on a myriad of
factors including gender, age, anatomy, and
ethnicity. Further, reduction in hypertrophy
tends not to be as idealized as Sloop’s curve.
Instead, from our experience and from the
available literature, the reduction of both
masseter and calf hypertrophy seems to
approximate 20–30% regardless of the maxi-
mal dose injected. Thus, every effort should
be made to use as little BoNTA as necessary
to achieve an excellent clinical outcome.
Both muscle groups require regular repeat
injections for sustained improvement. The
high doses of BoNTA required in these
procedures put the patient at increased
risk for antibody development leading to
treatment failure, so repeat injections are not
recommended more frequently than every
6 months. As BoNTA treatment of larger
muscle groups (trapezius, deltoids, thighs)
gain popularity, this concern is even greater.
Critically, the most desirable clinical end-
point is typically not the greatest reduction
in muscle mass; instead, the goal should be
beauty. Beauty is in part related to principles
like symmetry and the golden ratio, but in
part is beyond objective definition and relies
on the artistic acumen of the physician.
References
Smyth AG. Botulinum toxin treatment of
bilateral masseteric hypertrophy. Br J Oral
Maxillofac Surg 1994;32:29–33.
von Lindern JJ, Niederhagen B, Appel T,
Berge S, Reich RH. Type A botulinum toxin
for the treatment of hypertrophy of the
masseter and temporal muscle: an
alternative treatment. Plast Reconstr Surg
2001;107:327–332.
Park MY, Ahn KY, Jung DS (2003)
Botulinum toxin type A treatment for
contouring of the lower face. Dermatol
Surg 29:477–483; discussion 483.
Kim HJ, Yum KW, Lee SS, Heo MS, Seo
Kyle Effects of botulinum toxin type A on
bilateral masseteric hypertrophy evaluated
with computed tomographic measurement.
Dermatol Surg 2003;29:484–489.
Park, MY, Ahn KY. Follow-up; Botulinum
toxin A for the treatment of facial
hyperkinetic wrinkle lines in Koreans. Plast
Reconstr Surg 2003;105:148(s).
Satoh K. Mandibular contouring surgery by
angular contouring combined with
genioplasty in Orientals. Plast Reconstr
Surg 1998;101:461–472.
To EW, Ahuja AT, Ho WS, et al. A
prospective study of the effect of botulinum
toxin A on masseteric muscle hypertrophy
with ultrasonographic and
Botulinum Toxins
electromyographic measurement. Br J Plast
Surg 2001;54:197–200.
Yun Xie, Jia Zhou, Haizhou Li, Cheng
Cheng, Tanja Herrler, Qingfeng Li.
Qingfeng Li Classification of masseter
hypertrophy for tailored botulinum toxin
type A treatment. Plast Reconstr Surg 2014;
134:209e–217e.
Mandel L, Tanakan M. Treatment of
unilateral masseteric hypertrophy with
botulinum toxin: case report. J Oral
Maxillofac Surg 1999;57:1017–9.
Chang. CS, Bergeron L, Yu CC, Chen PKT,
Chen YR. Aesth Plast Surg
2011;35:452–455.
Kim NH, Chung JH, Park RH, Park JB. The
use of botulinum toxin type A in aesthetic
mandibular contouring. Plast Reconstr
Surg 2005;115:919–929.
Yun Xie, Jia Zhou, Haizhou Li, Cheng
Cheng, Tanja Herrler, Qingfeng Li.
Classification of masseter hypertrophy
for tailored botulinum toxin type A
treatment. Plast Reconstr Surg
2014;134:209e–218e.
Kim NH, Park RH, Park JB. Botulinum
toxin type A for the treatment of
hypertrophy of the masseter muscle. Plast
Reconstr Surg 2010;125:1693–1705.
Jiao Wei, Hua Xu, Jiasheng Dong, Qingfeng
Li, Chuanchang Dai. Prolonging the
duration of masseter muscle reduction by
adjusting the masticatory movements after
the treatment of masseter muscle
hypertrophy with botulinum toxin
type A injection. Dermatol Surg 2015;41:
S101–S
Ahn KY, Kim ST. The change of maximum
bite force after botulinum toxin type A
injection for treating masseteric
hypertrophy. Plast Reconstr Surg 2007;
120:1662–1666.
Chung-Chih Yu, Philip Kuo-Ting Chen,
Yu-Ray Chen. Botulinum toxin A for lower
facial contouring: A prospective study.
Aesth Plast Surg 2007;31:445–451.
Lee HH, Kim ST, Lee KJ, Baik HS. Effect of
a second injection of botulinum toxin on
lower facial contouring, as evaluated using
3-dimensional laser scanning. Dermatol
Surg 2015;41:439–444.
Sloop RR, Escutin RO, Matus JA, Cole BA,
Peterson GW. Dose–response curve of
human extensor digitorum brevis muscle
function to intramuscularly injected
botulinum toxin type A. Neurology
1996;46:1382–1386.
Park JM, Ha JS, Lee KC, Kim SK, Lee GN,
Lee MJ, Lee KH. The effect of botulinum
toxin A on calf reduction. J Korean Soc
Plast Reconstr Surg 2005;32:85–92.
Suh IS. Neurectomy of nerve branch to
medial gastrocnemius muscle for calf
reduction. J Korean Soc Aesth Plast Surg
2007;13;95–104.
Lee HJ, Lee DW, Park YH, Cha MK, Kim
HS, Ha SJ. Botulinum toxin A for aesthetic
contouring of enlarged medial
gastrocnemius muscle Dermatol Surg
2004;30:867–871.
Han KH, Joo YH, Moon SE, Kim KH.
Botulinum toxin A for lower leg
contouring. J Dermatol Treat 2006;17:
50–254.
Treatment of the Perioral Area
Shawn Allen, MD (FAAD, FACMS),1,2 Roberta Sengelmann, MD,3 and Rachel Simmons,
MD (FAAD)4
1Director and Founder, Dermatology Specialists, Boulder, USA
2Assistant Clinical Professor, University of Colorado, Department of Dermatology, Boulder, USA
3President and Owner, Santa Barbara Skin Institute, Associate Clinical Professor, UCI Dermatology, Santa Barbara, USA
4Dermatologist, Dermatology Specialists, Boulder, USA
Introduction
Rejuvenation of the aging face can take on
many different forms and methods ranging
from laser and surgical approaches, injectable
fillers and topical cosmeceuticals. Much of
the aging of the central face may be attributed
to the chronic use of the perioral muscles
as well as loss of bony and structural sup-
port around the mouth. Minimally invasive
procedures to address these concerns such
as soft tissue filler and neurotoxin injections
have grown in popularity due to the minimal
downtime, good safety profile, increased effi-
cacy, and reproducibility of results. Chemi-
cal denervation with botulinum toxins plays
an important role in minimally invasive facial
rejuvenation, particularly in the perioral area.
Although current FDA-approved cosmetic
indications for botulinum toxins do not
include treatment of the perioral area, this is
a common location where experienced injec-
tors can take advantage of the muscle relaxing
effects of neurotoxins to reduce facial lines,
wrinkles, and folds as well as to reshape the
face. Some of the perioral uses of botulinum
toxins include treating hyperfunctional ver-
tical lip lines, reshaping the face by lower-
ing the upper lip or elevating the corners
of the mouth, smoothing the dimpled skin
of the chin, as well as restoring symmetry.
Because the mouth is critical to many daily
activities, care should be taken to have a thor-
ough understanding of muscular anatomy
and neurotoxin properties to avoid complica-
tions when attempting to rejuvenate this area.
In general, due to the important functional
considerations around the mouth, injection
doses in the lower face tend to be lower than
those in the upper face. The need to main-
tain normal function of the mouth for eat-
ing, speaking, drinking, and daily activities
makes overdosing in this area more than just
a cosmetic concern. Therefore, special cau-
tion should be used when injecting patients,
especially those who make a living from
using their mouths professionally such as
wind instrument musicians, singers, speech
therapists, and public speakers. In contrast
to treating the glabellar complex where the
goal of treatment is to minimize or eliminate
movement, the goal of treating the perioral
region is to weaken the muscles while pre-
serving function. Patients must therefore be
educated that more subtle results (than those
achieved in the glabella) are to be expected
when treating this area.
In this chapter we review the common
uses of neurotoxins in the perioral area. We
will focus on improvement of hyperdynamic
Botulinum Toxins: Cosmetic and Clinical Applications, First Edition. Edited by Joel L. Cohen and David M. Ozog.
© 2017 John Wiley & Sons Ltd. Published 2017 by John Wiley & Sons Ltd.
Companion Website:
Botulinum Toxins
vertical lip lines, relaxing the upper lip to
alleviate a “gummy smile”, lifting the down-
turned corners of the mouth and correcting
the dimpling of the chin. When available,
we will provide consensus recommendations
as well as author preferences for dosing
and injection location. Please note that
recommended dosing will vary depending
on the choice of neuromodulator used. For
the purposes of this chapter, we will limit the
dosage discussion to the botulinum toxins
FDA-approved for cosmetic use on the face at
the time of publication: abobotulinumtoxinA
(Dysport®), onabotulinumtoxinA (hereafter
referred to as Botox®), and incobotulinum-
toxinA (Xeomin®). Other neurotoxins that
become available for cosmetic use will need
to be dosed according to product-specific
published studies or guidelines. Please note
that botulinum toxin units may not be
interchangeable between different products
as one must consider the different diffusion
characteristics, units of measurement, onset
of action, duration, potency, and side effects
associated with each commercially available
product; however, it is generally agreed that
Botox and Xeomin may be compared at a 1 : 1
ratio. As the authors have more clinical expe-
rience with Botox/Dysport, the reader may
comfortably substitute Xeomin doses when
only Botox doses are stated.
Lip Area: Vertical Lip Lines
Upper and lower radiating vertical lip lines
are primarily caused by the large sphincter
muscle called the orbicularis oris. This mus-
cle contracts to purse the lips and results in
radial lip lines when fully contracted. Its func-
tion is critical in daily activities such as eat-
ing and drinking, the use of straws, the abil-
ity to enunciate letters such as “p” and “q”
and the ability to whistle. The goal in treat-
ing the orbicular oris is to weaken (rather
than immobilize) the muscle to decrease lip
pursing and the formation of vertical lines.
Overdosing this area can lead to difficulty in
phonation, eating, drinking, and kissing [1].
Some predisposing factors to the early onset
of static radiating vertical lip lines include
daily practices that cause frequent pursing
of the lips. For example, smokers, athletes
who frequently drink from water bottles, and
professional wind instrument musicians will
have an increased risk of developing pre-
mature vertical lip lines due to their fre-
quent pursing motion of their lips. The pri-
mary author has noted a significant trend for
women, far greater than men, to have early or
late signs of vertical lip lines.
Vertical lip lines may be dynamic or static
in nature. The end result of a chronic
untreated dynamic line, resulting from mus-
cle contraction, is a static line. Once static
lines are created, they may be softened by
neurotoxin injections but usually not erased.
This will usually require the addition of soft
tissue fillers and/or chemical or laser resur-
facing procedures. Therefore, early treatment
with botulinum toxins may help to prevent
and/or delay the creation of these static lines.
In addition to relaxing vertical lip lines, it has
been reported that injection into the vermil-
ion border of the lip may also result in the
appearance of slight lip pseudoaugmentation
due to the decreased centripetal sphincter
tone with subsequent eversion of the lip [1].
Treatment of the vertical lip lines in con-
junction with other aesthetic procedures can
have a synergistic beneficial effect. When
toxin in the perioral area is combined with
soft-tissue fillers, the presence of toxin in this
highly dynamic area can increase the dura-
tion of the filler. Toxin can also improve the
outcome of perioral laser resurfacing as the
healing time is decreased with minimized
muscular contraction theoretically [2].
Injection points for vertical lip lines will
vary from individual to individual based upon
the shape of the mouth, the strength of the
orbicularis oris, and the location and severity
of the vertical lines with animation. Injections
of botulinum toxins for vertical lip lines can
be administered to the upper or bottom lip
alone or both simultaneously. Many patients
will benefit from injections at the vermil-
ion border only while others will need the
14 Treatment of the Perioral Area
Figure .Pursing the lips will assist in determining
the amount and location of the injections. Typical
injection points along the vermilion border of
2.5-5 DU or 1-2BU/XU per site are identified by white
circles. Additional injection points are located in red
but may increase risk of oral incompetence.
vermilion and focal areas of the cutaneous lip
injected to best address their concerns. Hav-
ing the patient animate by pursing their lips
will help to assess where, how much, and how
many injections are needed (see Figure 14.1).
Several scales for classifying severity of
aging in the perioral area are available. An
aesthetic rating scale which classifies perio-
ral lines at maximal contracture (POLM) is
particularly relevant to the treatment of this
area with neurotoxin. Patients can typically
expect one grade of improvement in POLM
score with successful treatment of botulinum
toxin to the vertical lip lines. Reference to
severity scales in clinical practice can be use-
ful in patient consultation as education about
anticipated improvement can help temper
patient expectations and gauge patient satis-
faction [3].
Published
consensus
recommendations
and author preferences for vertical lip line
injections include the following for Dysport®
and Botox®/Xeomin®. Locations of injec-
tions of Dysport units (DU),Botox units (BU),
and Xeomin units (XU) are essentially the
same. Volume dilution should be modified to
patient needs and desired effects. For moder-
ate dynamic lip rhytides, the vermilion border
of the upper lip should be injected at 2–4
injection points within 2–5 mm of the ver-
milion border with 2–4 DU and 1–2 BU/XU
per site. Two additional injection points
with similar doses in the mid cutaneous
lip can be performed for patients with long
radiating lines; however, these injections
may have a higher likelihood of impairing lip
function and should be performed cautiously.
Because of its less dynamic lines, the lower lip
is usually injected at only two points located
just below the vermilion border with 2–3 DU
or 1–2 BU/XU per site. The dose range in the
upper lip is 2.5–16 DU and 4–6 BU/XU and
the range for the lower lip is 2.5–7.5 DU and
2–3 BU/XU [4,5].
Cohen et al. compared the dose response
of onabotulinumtoxinA (BU) 7.5 BU to 12 BU
for injection in the upper and lower lips to
minimize perioral lines. The authors found
that the 7.5 BU dosing (two injection points
per lip with 5 BU in the upper lip and 2.5 BU
in the lower lip) was optimal for most patients
as it was highly effective for up to 16 weeks
with lower potential for AEs. Examples of
treatment-related AEs in this study included
lip weakness, lip numbness, difficulty eat-
ing, lip dryness, lip fullness, lip swelling, and
inability to kiss [1]. Care should be taken
to avoid overdosing in this area [2]. Options
to minimize the risk of lip ptosis and func-
tional compromise include treating at the
lower range and having the patient return
in 2 weeks for reassessment and additional
units as needed. Some injectors may also
choose to treat the upper lip only to maintain
the integrity of the lower lip’s pursing effect.
Keeping injections superficial [6] and within
5 mm of the vermilion border will also help
to avoid further excessive effect. Having the
patient purse their lips prior to injecting will
help to gauge the strength and integrity of
the muscle and to adjust toxin doses accord-
ingly (Figure 14.2). Some other key points
to consider include avoiding injections too
laterally as this can cause drooping of the
mouth and drooling if the integrity of the oral
Botulinum Toxins
Figure .Having the patient pucker the lips will
help to assess where along the vermilion border to
place your injection of 2.5-5 DU or 1-2BU/XU per site.
A 32 gauge needle with a 1cc no waste syringe is
used.
commissure is compromised. Also, avoid
injections too medially as this may cause soft-
ening or loss of the cupids bow shape.
Lastly, in the authors’ experiences the low
doses typically used as well as the constant
activity of the large underlying sphincter
muscle contributes to a shorter duration
of action of botulinum toxins in this area.
Therefore, realistic expectations and counsel-
ing regarding the possible need for frequent
treatments as well as adjunctive modalities
such as laser or chemical resurfacing pro-
cedures and or soft tissue fillers should be
discussed prior to treatment in this area.
Chin Area: Chin Dimpling and
Mental Crease
Chin dimpling, also referred to as “peach pit
chin,” “apple dumpling chin“ or “golf ball chin”
is caused mainly by the activity of the men-
talis muscle. The muscles originate from the
incisive fossa near the apex of the chin and the
paired muscles ascend in opposite superolat-
eral directions toward the lower lip to insert
into the skin of the chin [7]. The chin dim-
pling occurs with the dynamic contraction of
the muscles but typically does not result in
static changes.
The mentalis muscles are the main con-
tributors not only for dimpling of the chin
but also for the creation of the mental crease,
along with the depressor labii inferioris mus-
cles. Once a mental crease or groove has been
formed, it may be softened by neurotoxin
injections but usually not erased. This may
require the addition of soft tissue fillers
or other chin implant procedures for full
correction. Therefore, early treatment with
botulinum toxins for chin dimpling may also
help prevent and/or delay the creation of the
mental crease.
Injections of botulinum toxins for chin
dimpling can be done as a single injection
centrally or in 2 separate symmetrical sites.
Palpating the mentalis muscles while having
the patient animate by pushing the lower lip
up toward the top lip or pulling the lower lip
in towards the lower teeth will help assess
where to place the injections. The mentalis
muscles are the deepest muscles in the chin
and should be targeted deeply just above the
level of the periosteum. Injections should be
placed in a caudal location within 10 mm of
the bony rim of the chin (Figure 14.3). Alter-
natively, more superficial injections may tar-
get the more superficial fibers of the men-
talis but may carry a higher risk for involving
the depressor labii inferioris and may risk oral
compromise. Care must also be taken to avoid
injecting too laterally or superiorly as this can
cause oral incompetence and drooling of the
mouth due to involvement of the depressor
labii inferioris.
Published
consensus
recommendations
and author preferences for mentalis injec-
tions include the following. Locations of
injections of both products are essentially
the same. Depending all toxins on the volume
dilution and desired effect they should be
modified accordingly. For mild to moderate
mentalis muscle volume and strength, a sin-
gle injection point within 5 to 10 mm of the
chin apex with 5–10 DU and 2.5–5 BU/XU
is recommended. Alternatively, two separate
injection points may be more effective for
14 Treatment of the Perioral Area
Figure .Patient animating to help identify the
mentalis muscles. Single injection point of 10 DU or
5 BU/XU located in white. Alternatively, 2 separate
injection points of 2.5-5 DU or 2.5-5 BU/XU each,
identified by red circles.
wider stronger mentalis muscles. Each site
receives 5- 10 DU or 2.5–5 BU/XU (See
Figure 14.3). The dose range is 5–20 DU and
2.5–10 BU. It may be helpful to lower the
dose and bring the patient back at 2 weeks
and touch up the area as needed. Some
experienced injectors may choose to try to
treat the dimpled chin and mental crease
with a more cephalad injection. This can be
done, but again risks some degree of oral
incompetence if the depressor labii inferiors
is inadvertedly injected.
Care should be taken to avoid overdosing
and injecting too cephalad in this area as
this may lead to oral functional compro-
mise. Options to minimize this risk include
treating at the lower range and having the
patient return in 2 weeks for reassessment
and additional units as needed. Keeping
injections deep and caudal within 5 to 10 mm
of the bony chin border will also help to
avoid further unwanted side effects. Having
the patient animate prior to injecting will
help to gauge the strength and integrity of
the muscle and help in adjusting doses and
location accordingly.
Downturned Commissures:
Mouth Frown
Downturned corners of the mouth can create
a frowning appearance at baseline. The sad
or angry appearance is caused mainly by the
activity of the depressor anguli oris (DAO)
muscles. The lateral fibers of the depressor
labii inferioris (DLI) muscles and platysmal
bands also play a more minor role in this
effect. The DAO muscles originate from the
oblique line of the bony rim of the mandible
and are intercalated with the platysma at
their origin. The paired muscles ascend in
an arcuate and superolateral then superome-
dial direction toward their respective corners
of the mouth where they then intercalate with
the orbicularis oris and the risorius muscles.5
The down turning of the mouth corners
occurs by unopposed or hyperactive down-
ward pull of the muscles and typically does
not result in static changes although there
can be some accentuation of the oral com-
missure crease and marionette lines. Once an
oral commissure crease or groove has been
formed, it may be softened by neurotoxin
injections but usually not erased. The addi-
tion of soft tissue fillers are often most help-
ful for full correction. Early treatment with
botulinum toxins for downturned mouth cor-
ners may help prevent and/or delay the cre-
ation of the oral commissure crease.
Injections of botulinum toxins for down-
turned oral commissures are usually done
as a single injection per side. Palpating the
DAO muscles while having the patient ani-
mate by showing their lower teeth will help
assess where to place the injections. The DAO
muscles are superficial muscles in the lat-
eral chin and should be targeted intramuscu-
larly and in a caudal location within 5 mm
of the bony rim of the chin. Alternatively,
more superficial injections may target the
more superficial fibers of the DAO, but may
carry a higher risk for involving the depressor
Botulinum Toxins
labii inferioris which would lead to oral
incompetence. Injections located too high
along the lateral chin will likely cause some
functional compromise by either denervat-
ing more muscle mass than desired and or
inadvertently involving the DLI muscles and
ascending platysmal fibers.
Published
consensus
recommendations
and author preferences for DAO injections
include the following. Locations of injec-
tions are essentially the same. Depending
on the volume dilution and desired effect,
they should be modified accordingly. For
mild to moderate DAO muscle volume and
strength, a single injection point within
5 mm of the bony rim of the chin with 5–
10 DU or 2.5–5 BU/XU is usually adequate
(See Figure 14.4). The total dose range is
10–20 DU and 5–10 BU/XU. Advanced
injectors may choose to try to treat the DAO
with a more cephalad injection. This can be
done as a second site with low doses with
2.5 DU and 1 BU/XU but may risk functional
compromise with drooling.
Care should be taken to avoid overtreat-
ment in this area which may lead to oral
incompetence. It is also important to avoid
injecting too cephalad as this can also lead
Figure .Injection of the DAO at the mandible
border (white dot) with 5-10 DU or 2.5-5 BU/XU will
allow for upturned corner of the mouth.
to oral incompetence and drooling due to
inadvertent denervation of the DAO and DLI.
Options to minimize this risk include treat-
ing at the lower range and having the patient
return in 2 weeks for reassessment and addi-
tional units as needed. Keeping injections
caudal and within 5 mm of the bony chin bor-
der will help to avoid unwanted side effects.
Having the patient animate prior to injecting
will help to gauge the strength and integrity
of the muscle and aid in adjusting doses and
location accordingly.
Gummy Smile
A gummy smile is defined as excessive
gingival show (greater than 3 mm) [8] when
smiling, and is caused mainly by the over
activity of the levator labii superioris alaeque
nasi (LLSAN) muscles. The other lip levators
such as the levator labii superioris (LLS), lev-
ator anguli oris (LAO), risorius, zygomaticus
minor (ZMi) and zygomaticus major (ZMa)
may also play a role in creating a gummy
smile. Mazzuco and Hexsel further classified
the gummy smile into 4 categories based
on the contraction of the specific above
listed muscle(s) responsible for the gingival
show [9].
In addition, genetic or acquired changes in
gingival tissue and maxillary bone formation
can play a role in accentuating the gummy
smile [10]. Although botulinum toxins may
be ideal for treating many patients [11], surgi-
cal lip repositioning, gingival laser treatments
and other procedures performed by oral sur-
geons, orthodontists or periodontists may
also be considered. The LLSAN muscles orig-
inate from the bony aspect of the nasal side-
wall and frontal process of the maxilla and
insert at the deep border of the orbicularis
oris of the upper lip [7]. The muscles travel
from the nasal sidewall, along the edge of the
alar crease below the LLS, and then interca-
late with the orbicularis oris. Early descend-
ing fibers assist in dilating the nares, while
the longitudinal fibers assist in elevating
the lip. The excess gummy show of the smil-
ing mouth occurs by unopposed upward pull