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Aesth Plast Surg

https://doi.org/10.1007/s00266-018-1157-3

ORIGINAL ARTICLE NON-SURGICAL AESTHETICS

Muscle Insertion and Strength of the Muscle Contraction


as Guidelines to Enhance Duration of the Botulinum Toxin Effect
in the Upper Face
Antonio Carlos Abramo1

Received: 21 March 2018 / Accepted: 12 May 2018


Ó Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery 2018

Abstract Conclusion ‘‘BTA Codes’’ is a set of rules to apply botu-


Background In this series of patients the cutaneous inser- linum toxin supported by muscle anatomy and degree of
tion and strength of voluntary contraction of the muscles in voluntary contraction to enhance the duration of its effect.
the upper third of the face were used as guidelines for Level of Evidence IV This journal requires that authors
botulinum toxin application named ‘‘BTA Codes.’’ assign a level of evidence to each article. For a full
Method Anatomical dissection of fresh cadavers identified description of these Evidence-Based Medicine ratings,
the shape and cutaneous insertions of the muscles in the please refer to the Table of Contents or the online
upper third of the face. Patient voluntary contraction of the Instructions to Authors www.springer.com/00266.
muscles in the upper third of the face created different
patterns of skin lines classified by the 4-grade Facial Keywords Botulinum toxin  Injection points  Dose 
Wrinkle Scale. For botulinum toxin application injections Muscle insertion  Strength of voluntary contraction 
points followed the muscle cutaneous insertion and dose ‘‘BTA Codes’’
the 4-grade Facial Wrinkle Scale.
Results Injection points ranged from 3 to 23 points per
patient, average of 9.4 points. Dose per point varied from Introduction
2.5 to 7.5 U, ranging from 12.5 to 72.5 U per patient,
average of 33.82 U. Skin lines resulting from the voluntary The anatomy of the upper facial expression is complex, as
contraction of the muscle prior to toxin application were the muscles are very close together and interface at dif-
stated as baseline 1. The absence of skin lines and muscle ferent levels and depths, creating a network of hyperdy-
activity on day fifteen after toxin application defined namic skin lines. Despite having a single origin, the
baseline 2. Skin lines resulting from the recovered volun- corrugator supercilii originates several patterns of glabellar
tary contraction of the muscle after toxin application like skin lines due to three different cutaneous insertions [1].
those of baseline 1 established baseline 3. The botulinum Different patterns of skin lines are also created by muscles
toxin effect was the time elapsed between baselines 2 and with the same attachments and distinctive arrangements of
3, ranging from 171 to 204 days, average of 183.72 days, fibers, such as the frontalis muscle [2]. The number, length
greater than the 3 or 4 months reported in the literature. and depth of the skin lines depend on the strength of the
muscle contraction. Correction by using botulinum toxin
requires proper understanding of the anatomical shape and
insertion of the facial muscles [3]. Botulinum toxin action
& Antonio Carlos Abramo
acabramo@abramo.com.br; alessandra@abramo.com.br is more effective when applied by an objective muscle
identification approach [4]. Sundaram et al. [5] report that
1
Post-Graduate Course of Plastic Surgery of the Institute of inadequate injection points cause none or partial response
Assistance in Plastic Surgery of São Paulo, Endorsed by the
to the application of the botulinum toxin. Successful aes-
Brazilian Society of Plastic Surgery and Brazilian Medical
Association, General Hospital São Luiz – Jabaquara, Rua thetic outcomes have been reported by increasing injection
Afonso de Freitas, 641, São Paulo, SP 04006-052, Brazil points and reducing the dose per point of botulinum toxin

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Aesth Plast Surg

when combined with fillers [6]. However, duration of the


botulinum toxin effect is not described in the reports. The
typical duration of the botulinum toxin effect in the upper
third of the face is 3–4 months, depending on several
factors, including dose [7]. Low number of units by
injection point, regardless of the number of points, can
decrease duration of the botulinum toxin effect. Carruthers
et al. [8] reported that a higher botulinum toxin dose results
in greater efficacy and longer duration of effect. The
number, depth and length of the skin lines on the upper
third of the face are indicators of the botulinum toxin dose.
The 4-grade Facial Wrinkle Scale is a clinical tool for
assessing the depth and length of skin lines [9]. It is a
4-point scale of wrinkle severity that guides the appropriate
dose of botulinum toxin.
To enhance the duration of the botulinum toxin effect in
the upper third of the face, injection points into the muscle
cutaneous insertion and dose according to the strength of
its contraction are proposed. This system is named ‘‘BTA
Codes’’ because it represents a set of rules about how the
author applied botulinum toxin.

Anatomy

Frontalis muscle—Four types of muscle fiber arrangements


inserted along the forehead skin originate four muscle
shapes, establishing four patterns of cutaneous lines [2].
The full type (Fig. 1) creates horizontal straight lines across
the forehead (Fig. 2a); V-shaped type (Fig. 3), horizontal Fig. 2 a Forehead furrows caused for a frontalis full type. Injection
gull wing-shaped lines across the forehead (Fig. 4a); cen- points F1, F2, F4, F5 and F6 were distributed from line 2 to line 10 on
both sides of the forehead. Injection point F3 only on line 6. b Dose
tral type (Fig. 5), a column of short horizontal lines in the
for injection points was 2.5 U. At day 151 after baseline 2 a smooth
middle of the forehead (Fig. 6a); and lateral type (Fig. 7a), forehead during voluntary contraction of frontalis

Fig. 1 Cadaver dissection showing full type of frontalis and narrow Fig. 3 Cadaver dissection with V-shaped type of frontalis, and fan-
ribbon-shaped of both corrugator supercilii. The dotted line represents shaped for the right corrugator supercilii and rectangular-shaped for
the eyebrow location the left. Eyebrows marked by dotted line

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Aesth Plast Surg

Fig. 5 Cadaver dissection with central type of frontalis, and narrow


ribbon-shaped for the right corrugator supercilii and rectangular-
shaped for the left. Eyebrows marked by dotted line

Fig. 4 a A frontalis V-shaped type created severe horizontal gull


wing-shaped lines and excessive lift of eyebrows. Points F1, F2, F4
and F5 received 2.5 U, bilaterally. b At day 159 after baseline 2,
despite a few lines, a noticeable reduction in the gull wing-shaped
lines remains with natural eyebrows lift during the voluntary
contraction of the frontalis

two lateral columns of short horizontal lines on the fore-


head (Fig. 7b).
Corrugator supercilii muscle—A single origin in the
frontal process of the maxilla with three different insertions
underneath the medial half of the eyebrow creating three
muscle patterns [2]. Fan-shaped (Fig. 7a) along the medial
half of the eyebrow, causing vertical hockey stick-shaped
lines on the medial end of eyebrows (Fig. 8a); rectangular-
shaped (Fig. 9) in the lateral two-thirds of the medial half
of eyebrows causing vertical parallel straight lines on the
glabella (Fig. 9); and narrow ribbon-shaped (Fig. 1) at the
medial end of the eyebrows causing a single vertical line on
the glabella (Fig. 10a). Six patterns of lines can be found Fig. 6 a Voluntary contraction of central type of frontalis showing a
on both sides of the glabella, three symmetrical and three column of short horizontal lines in the middle of the forehead. Points
F2, F3, F4 and F5 received 2.5 U of botulinum toxin. b At day 138
asymmetrical, according to the muscle shape on each side after baseline 2 a smooth forehead is achieved during voluntary
[2]. contraction of the frontalis

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Aesth Plast Surg

Fig. 8 a Severe vertical hockey stick-shaped lines on the medial end


of eyebrows caused by fan-shaped corrugator supercilii. Injection
Fig. 7 a Cadaver dissection with lateral type of frontalis and fan- points C1, C2 and C3 received 7.5, 5.0 and 2.5 U, respectively, on
shaped of both corrugator supercilii. Eyebrows marked by dotted line. both eyebrows. b Glabellar skin lines or muscle activity is not
b Voluntary contraction of the frontalis lateral type shows two lateral observed during voluntary contraction at day 134 after baseline 2
columns of short horizontal lines on forehead

procerus muscles. Exclusion criteria included scars,


Orbicularis oculi muscle—In the upper eyelid, runs smokers, prior cosmetic procedures, soft tissue augmenta-
under the corrugator supercilii with the thick peripheral tion, pregnancy, lactation and neuromuscular disease.
fibers inserted at the lateral end of the eyebrow, and the Preparation of a botulinum neurotoxin type A from the
central thinner palpebral fibers spread around both eyelids same manufacturer was applied in all patients of this series.
[2]. Peripheral fibers shift the lateral end of the eyebrow Dilution of the botulinum neurotoxin type A in saline
downward, whereas the thinner palpebral fibers cause solution was established at 5 U per 0.1 mL of the solution.
crow’s feet (Fig. 11a). Injection points were distributed according to the cuta-
Procerus muscle—It is located between and below the neous insertion of the target muscle. The dose per injection
eyebrows [2]. Its activity creates horizontal lines on the point was established by the number, depth and length of
roof of the nose and ‘‘bunny lines’’ (Fig. 12a). the skin lines resulting from the voluntary contraction of
the muscle. The 4-grade Facial Wrinkle Scale measured
depth and length of the skin lines resulting from the muscle
Method contraction setting: FWS1 as none, FWS2 as mild, FWS3
as moderate and FWS4 as severe. The duration of the
Twenty-five females with age ranging from 41 to 59 years botulinum toxin effect was measured in days, considering
underwent application of botulinum neurotoxin type A in three assessments. Baseline 1: skin lines resulting from the
the frontalis, corrugator supercilii, orbicularis oculi and voluntary contraction of the muscle prior to toxin

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Aesth Plast Surg

Fig. 9 Rectangular-shaped of both corrugator supercilii. Voluntary


contraction of the muscles exhibited severe vertical lines on the
glabella

application. Baseline 2: day fifteen after toxin application


with the absence of skin lines and muscle activity. Baseline
3: skin lines resulting from the recovered voluntary con-
traction of the muscle after the toxin application, like those
exhibited in baseline 1. All patients signed an informed
consent form agreeing to the proposed treatment that was
performed according to the 1964 Declaration of Helsinki
and Medical Research Involving Human Subjects.

Dose
Fig. 10 a Severe single vertical line on the glabella during voluntary
contraction of a narrow ribbon-shaped corrugator supercilii muscle.
Dilution of botulinum toxin in saline solution was estab- Point C1 received 7.5 U of botulinum toxin. b No muscle activity
lished at 5 U per 0.1 mL of the solution, making easy during voluntary contraction at day 148 after baseline 2
application of fractional doses as 2.5 or 7.5 U. The dose per
injection point for FWS2 was 2.5 U, for FWS3 was 5.0 U needle toward the forehead. Point C1 was in compartment
and for FWS4 was 7.5 U. one; point C2 in compartment two; and point C3 in com-
partment three (Fig. 8a). Point C3 is an alternative appli-
Injection Points cation only for a fan-shaped muscle with severe contraction
strength, creating several vertical lines in the medial half of
Frontalis muscle—Eleven vertical parallel lines, with the the eyebrow associated with the vertical hockey stick-
same distance among them and numbered from the right to shaped line. At points C2 and C3, pressing with one finger
the left, split the forehead between both lateral ends of the inferior to the injection point helped to avoid dispersion of
eyebrows. Injection point F1 was marked on lines 2 and 10, the toxin to the levator palpebrae superioris muscle.
point F2 on lines 4 and 8 and point F3 on line 6, all of them Orbicularis oculi muscle—Lateral half of the eyebrow
2.0 cm above the eyebrow; point F4 on lines 3 and 9 and was split by four vertical parallel lines, the same distance
point F5 on lines 5 and 7, both 2.5 cm above the eyebrow; between them, resulting in three compartments numbered
and point F6 on lines 4 and 8, located 3.0 cm above the from the lateral end. Point O1 was in compartment one,
eyebrow (Fig. 2a). below the hair line of the eyebrow; point O2 in compart-
Corrugator supercilii muscle—The medial half of the ment one, 1.0 cm above the lateral canthus; point O3 in the
eyebrow was split by four vertical parallel lines, the same compartment two, at the level of the lateral canthus; point
distance between them, resulting in three compartments O4 in compartment two, 1.5 cm below the lateral canthus;
numbered from the medial end of the eyebrow. Injection and point O5 in compartment three, 2.0 cm below the
points were applied above the eyebrow hairline with the ciliary edge (Fig. 11a).

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Aesth Plast Surg

Fig. 11 a Voluntary contraction of orbicularis showing crow’s feet Fig. 12 a Severe bunny lines and horizontal lines on the root of the
on both eyelids. Lateral half of the eyebrow was split in 3 nose during voluntary contraction of the procerus. Nose was split in
compartments. Injections points O1, O2, O3, O4, O5 received four compartments. Injection points P1 received 5.0 U applied into
2.5 U each one. b Smooth eyelids during voluntary contraction of the the compartments 2 and 3 below the medial canthus. b Voluntary
muscle at day 140 after baseline 2 contraction at day 138 after baseline 2 without skin lines on the nose

Procerus muscle—The nose was split by five vertical patients, location of the injection points, dose per injection
parallel lines from one nostril to the other with the same point and duration of the botulinum toxin effect.
distance between them, numbered from the right to left.
Point P1 was applied on lines two and four, 1.0–1.5 cm Injection Points and Dose
below the medial canthus (Fig. 12a).
Injections points were performed at the intramuscular level
distributed according to the extension and location of the
Results cutaneous insertions of each muscle. Twenty-five female
patients received 236 injection points, ranging from 3 to 23
Twenty-five females with ages ranging from 41 to points per patient, average of 9.4 points. The dose followed
59 years, mean age of 48.43 years, had improvement of the FWS for each target muscle. A total of 848 U of
hyperdynamic skin lines on the forehead, glabella, nose botulinum toxin was applied, ranging from 12.5 to 72.5 U
and periorbital area after application of botulinum toxin. In per patient, average of 33.92 U. Thirteen points received
addition, the height and shape of the eyebrows recovered. 7.5 U, 76 points 5.0 U and 147 points 2.5 U.
The real-time duration of the botulinum toxin effect was Frontalis—Injection points improved forehead furrows,
established in days by the time elapsed between baselines 2 and height and symmetry of the eyebrows. Points F1, F2,
and 3, ranging from 171 to 204 days, average of F3, F4, F5 and F6 were used for full type muscles (Fig. 2a,
183.72 days. Table 1 summarizes the distribution of b); points F1, F2, F4 and F5 for V-shaped type muscles

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Aesth Plast Surg

Table 1 Patients distribution and outcomes


Age Frontalis Corrugator Orbicularis oculi Procerus Effect duration
Baseline
R* L* Center* R* L* R* L* R* L* 3 - baseline 2
(days)
F1 F2 F4 F5 F6 F1 F2 F4 F5 F6 F3 C1 C2 C3 C1 C2 C3 O1 O2 O3 O4 O5 O1 O2 O3 O4 O5 P1 P1

1 41 – – – – – – – – – – – – 5 – – 5 – – 5 2.5 2.5 – – 2.5 2.5 2.5 – – – 196 - 15 = 181


2 42 – – – – – – – – – – – 7.5 5 2.5 – 5 – – 5 – – – 5 5 – – – – – 188 - 15 = 173
3 41 2.5 2.5 – 2.5 – 2.5 2.5 – 2.5 – 2.5 5 2.5 – 5 2.5 – 5 2.5 2.5 2.5 2.5 5 2.5 2.5 2.5 2.5 2.5 2.5 191 - 15 = 176
4 45 – – – – – – – – – – – – 5 – – 5 – 5 2.5 2.5 – – 2.5 2.5 2.5 – – – – 201 - 15 = 186
5 59 – – – – – – – – – – – – – – – – – 5 – – – – 5 2.5 – – – – – 197 - 15 = 182
6 49 – – – – – – – – – – – 5 – – 5 – – – 5 2.5 – – – 2.5 2.5 2.5 2.5 – – 204 - 15 = 189
7 53 – – – – – – – – – – – – 5 – 7.5 5 – 5 – – – – 5 – – – – – – 199 - 15 = 184
8 57 – – – – – 2.5 5 5 2.5 2.5 – – – – – – – – – – – – – – – – – – – 199 - 15 = 184
9 47 – – – – – – – – – – – 5 2.5 – – 5 – – 5 2.5 – – – 2.5 2.5 2.5 2.5 2.5 2.5 199 - 15 = 184
10 44 – – – – – – – – – – – – 5 – – 5 – – 2.5 – – – – 2.5 – – – – – 199 - 15 = 184
11 42 – – – – – 2.5 2.5 2.5 – – – 5 2.5 – 5 2.5 – – 2.5 2.5 2.5 2.5 – 2.5 2.5 – – – – 194 - 15 = 179
12 58 – – – – – – – – – – – 7.5 5 2.5 – 5 – 2.5 – – – – 5 – – – – – – 204 - 15 = 189
13 52 – – – – – – – – – – – 7.5 5 – – 5 – 5 5 2.5 2.5 2.5 5 2.5 2.5 – – – – 219 - 15 = 204
14 52 – – – – – – – – – – – 7.5 5 – 7.5 2.5 – 5 – – – – 5 – – – – 2.5 5 186 - 15 = 171
15 57 2.5 2.5 2.5 2.5 – – – – – – 2.5 – – – – – – – – – – – – – – – – 200 - 15 = 185
16 53 – – – – – – – – – – – 7.5 5 2.5 – 5 – 5 – – – – 5 – – – – 5 5 212 - 15 = 197
17 44 2.5 2.5 2.5 2.5 – 2.5 2.5 2.5 2.5 – 2.5 7.5 – – 7.5 – – 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 195 - 15 = 180
18 46 – – – – – – – – – – – – 5 – – 2.5 – 2.5 2.5 2.5 – – 2.5 2.5 2.5 2.5 2.5 – – 195 - 15 = 180
19 52 – – – – – – – – – – – 5 2.5 – 5 5 – 2.5 – – – – 5 – – – – – – 194 - 15 = 179
20 54 2.5 2.5 – – – – – – – – 2.5 – 5 – – 5 – – 2.5 2.5 – – 2.5 5 2.5 – – – – 207 - 15 = 192
21 48 – 2.5 – 2.5 – – 2.5 – 2.5 – 2.5 7.5 5 2.5 7.5 5 2.5 5 2.5 2.5 2.5 – 5 2.5 2.5 2.5 – 2.5 2.5 192 - 15 = 177
22 46 – – – – – – – – – – – 5 5 2.5 5 5 2.5 – – – – – – – – – – – – 198 - 15 = 183
23 59 – – – – – – – – – – – 7.5 5 2.5 5 5 2.5 5 5 2.5 2.5 5 2.5 2.5 – – 2.5 2.5 196 - 15 = 181
24 49 – – – – – – – – – – – 7.5 5 2.5 – 5 – 2.5 – – – – 5 – – – – 198 - 15 = 183
25 58 – – – – – – – – – – – 5 – – – 5 – 2.5 – – – – 2.5 – – – – – – 205 - 15 = 190
*U international unit

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Aesth Plast Surg

(Fig. 10a, b); points F1, F2 and F4 for lateral type muscles; points F1, F2, F3, F4 and F5 weaken the frontalis muscle
and points F2, F3, F5 and F6 for central type muscles preserving its activity, minimizing forehead furrows with
(Fig. 11a, b). Thirty-four points on both sides of the fore- minimal downward displacement of the eyebrow. Injection
head received 2.5 U, and two points, F2 and F3, on left side point F6 is usually applied to residual furrows near the
of the forehead received 5.0 U. forehead hair line. The lack of antagonism resulting from
Corrugator supercilii—Injection points annulled the annulment of the eyebrow depressor muscles stimulates
glabellar vertical lines and resulted in adequate height of the automated movement of the frontalis, which reduces
the medial half of the eyebrow. Points C1, C2 and C3 were the expressiveness of forehead furrows, holding the eye-
applied to fan-shaped muscle (Fig. 4a, b); C2 to rectan- brow in a natural balanced position [14]. Injection points
gular-shaped muscle; and C1 to narrow ribbon-shaped C1, C2 and C3 for corrugator supercilii can be applied
muscle (Fig. 12a, b). Thirteen points C1 received 7.5 U separately or together according to the three distinct pat-
and thirteen 5.0 U; thirty-one points C2 received 5.0 U and terns of the muscle and the strength of the voluntary con-
eight 2.5 U; and ten points C3 received 2.5 U. traction. A single point in the center of the glabella has
Orbicularis oculi—Points O1 settled the lateral height of been reported to annul skin lines due to the activity of the
the eyebrow; and points O2, O3, O4 and O5 annulled the procerus muscles [15]. However, as the procerus muscles
crow’s feet (Fig. 11a, b). Twenty points O1 received 5.0 U are inserted into the skin between and below the eyebrows
and eleven 2.5 U; eight points O2 received 5.0 U and on either side of the glabellar midline, a single glabellar
twenty-one 2.5 U; twenty-four points O3 received 2.5 U; central injection point cannot annul the activity of both
fourteen points O4 received 2.5 U; and nine points O5 muscles. Injection point P1 is applied on either side of the
received 2.5 U. nose at the level of the medial canthus involving both
Procerus—Point P1 annulled horizontal lines on the roof procerus muscles to annul skin lines on the roof of the nose
of the nose and bunny lines (Fig. 12a, b). Three points and bunny lines. Duration of the botulinum toxin effect in
received 5.0 U and eleven 2.5 U. facial aesthetic applications has been reported as approxi-
mately 4 months. The treated muscles gradually regain
function, and generally, the skin lines return to their former
Discussion appearance 3–4 months after the treatment [16]. In this
series of patients, duration of botulinum toxin effect was 6
Injection points and dose per point of the botulinum toxin months or slightly more. It lasted from baseline 2, day
in the upper third of the face must be individualized [10]. fifteen after application, and not from baseline 1, day of
The morphology of each muscle, topographic relationship application, which establishes the real-time duration of
with surrounding muscles and the expressiveness of the effect. The dose per point in the ‘‘BTA Codes’’ is not
corresponding skin lines are relevant to optimize outcomes. standardized, changing with the number, depth and length
Classification of the facial skin lines, particularly in the of skin lines representing the strength of the voluntary
glabella, has been used as a guide for botulinum toxin contraction of the muscle. Although a very strong dosage,
injection points. However, application over the skin lines the association of 7.5, 5.0 and 2.5 U distributed in different
can recruit adjacent muscles besides the target muscle [11]. points of the same muscle extended the duration of the
To prevent recruitment of adjacent muscles, the ‘‘BTA botulinum toxin effect for about 6 months or more without
Codes’’ distributed the injection points along the cutaneous side effects, in this series of patients. There were two
insertions of the target muscle and not in the skin lines factors contributing to the elongated duration of the botu-
resulting from its voluntary contraction. Nevertheless, linum toxin effect in the ‘‘BTA Codes.’’ First, the injection
standardized injection techniques, when all the subjects points were distributed specifically along the cutaneous
receive the same injection points and equal doses per point, insertion of the target muscle, and second, the dose
regardless of the cutaneous insertion and contraction according to the strength of the muscle contraction.
strength of the muscle, are still being used for botulinum According to Maas et al. [17], the size of the field of effect
toxin [12]. Standard injection protocol techniques are is difficult to define and it is related to the volume applied.
unimportant as long as it remains standardized [13]. In the In this series of patients, 5.0 U of botulinum toxin in
‘‘BTA Codes’’ injection points are not standardized, 0.1 mL of the solution provided high doses, such as 7.5 and
changing among individuals and on each side of the same 5.0 U, with minimal volume, restricting its dispersion.
individual, attending the patterns of the muscle shape and/ Therefore, it limited the size of the effect field to the
or its cutaneous insertions. In the forehead, injection points cutaneous insertion of the muscle. This was particularly
follow the patterns of the frontalis muscle created by the important in the injection points C1, C2 and C3 of the
arrangement of its fibers, avoiding application of the toxin corrugator supercilii muscle, to avoid the drop of the upper
in the aponeurotic galea where it has no effect. Injection eyelid.

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Aesth Plast Surg

Conclusion 6. Carruthers J, Glogau RG, Blitzer A, Facial Aesthetics Consensus


Group Faculty (2008) Advances in facial rejuvenation: botulinum
toxin type A, hyaluronic acid dermal fillers, and combination
‘‘BTA Codes’’ is a practical strategy following the patterns therapies-consensus recommendations. Plast Reconstr Surg 121(5
of muscular dynamics in a selective manner. Duration of Suppl):5S–30S (quiz 31S-36S)
the botulinum toxin effect is dose dependent in relationship 7. Hexel DM, Klein AW (2010) Botulinum toxin. Section 51. In:
Baran R, Maibach HI (eds) Textbook of cosmetic dermatology,
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Does it matter? Dermatol Surg 33:S97–S104
Acknowledgements To the cadavers of selfless dedication. 9. Carruthers J, Rivkin A, Donofrio L et al (2015) A multicenter,
randomized, double-blind, placebo-controlled study to evaluate
Compliance with Ethical Standards the efficacy and safety of repeated onabotulinumtoxinA treat-
ments in subjects with crow’s feet lines and glabellar lines.
Conflict of interest The author has no financial interest or conflict of Dermatol Surg 41(6):702–711
interest to declare in relation to the content of this article. 10. Carruthers J, Fagien S, Matarasso SL, Botox Consensus Group
(2004) Consensus recommendations on the use of botulinum
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