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Alluzience Consensus

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0% found this document useful (0 votes)
39 views11 pages

Alluzience Consensus

Uploaded by

IoanaStoenica
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd

Cosmetic Medicine

Aesthetic Surgery Journal


Special Topic 2024, Vol 44(2) 192–202
© The Author(s) 2023. Published by
Oxford University Press on behalf of The
International Consensus Recommendations Aesthetic Society.
This is an Open Access article
on the Aesthetic Usage of Ready-to-Use distributed under the terms of the
Creative Commons Attribution License

AbobotulinumtoxinA (Alluzience) (https://creativecommons.org/licenses/


by/4.0/), which permits unrestricted
reuse, distribution, and reproduction in

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any medium, provided the original work
is properly cited.
https://doi.org/10.1093/asj/sjad222
Benjamin Ascher, MD; Berthold-Josef Rzany, MD; www.aestheticsurgeryjournal.com

Philippe Kestemont, MD; Alessio Redaelli, MD; Benoit Hendrickx, MD, PhD;
Ivano Iozzo, MD; Christoph Martschin, MD; Alicia Milotich, MD;
Beatriz Molina, MD; Hugues Cartier, MD; Philippe Picaut, PharmD;
and Inna Prygova, MD

Abstract
Alluzience (abobotulinumtoxinA RTU; Ipsen, Paris, France and Galderma SA, Lausanne, Switzerland) is the first ready-
to-use (RTU) botulinum toxin type A liquid solution approved for the treatment of glabellar lines in Europe. In this article,
the authors provide consensus recommendations on the aesthetic usage of abobotulinumtoxinA RTU. Members of the
International Board on Alluzience convened to develop consensus on the treatment of glabellar lines as well as other facial
wrinkles based on their own extensive experience. Consensus recommendations were developed to provide practical
guidelines for injection of abobotulinumtoxinA RTU. General guidance on proper assessment, treatment planning, and
patient education is provided, as well as specific injection guidelines per indication. Indications covered include glabellar
lines, crow’s feet, horizontal forehead lines, lateral eyebrow lift, lower eyelid wrinkles, bunny lines, drooping nasal tip, perio­
ral wrinkles, drooping mouth corners, masseter hypertrophy, hollow cheek lines, dimpled chin, and platysmal bands. These
guidelines provide a practical framework to support routine injection of facial muscles with Alluzience.

Level of Evidence: 5

Editorial Decision date: June 12, 2023; online publish-ahead-of-print July 25, 2023.

physician, Plastic and Aesthetic Surgery Department, Hospital la


Dr Ascher is a plastic surgeon in private practice in Paris, France and Salud, Valencia, Spain. Dr Molina is a cosmetic physician in private
an international editor for Aesthetic Surgery Journal. Dr Rzany is a practice in Somerset, UK. Dr Cartier is a dermatologist in private
dermatologist in private practice in Berlin, Germany. Dr Kestemont is practice in Arras, France. Dr Picaut is a pharmaceutical consultant in
a plastic surgeon in private practice in Nice, France. Dr Redaelli is a Paris, France. Dr Prygova is head of medical affairs, Galderma,
professor, Cosmetic Medical Department, Visconti di Modrone Uppsala, Sweden.
Medical Center, Milan, Italy. Dr Hendrickx is a plastic surgeon,
Department of Plastic and Reconstructive Surgery, University Corresponding Author:
Hospital Leuven, Leuven, Belgium. Dr Iozzo is a plastic surgeon in Dr Benjamin Ascher, 8 rue Foucault, 75116 Paris, France.
private practice in Bologna, Italy. Dr Martschin is a dermatologist in E-mail: [email protected];
private practice in Lisbon, Portugal. Dr Milotich is a cosmetic Twitter: @dr_ascher
Ascher et al 193

Facial aging is a multifactorial process that involves gravity, Table 1. The AbobotulinumtoxinA Ready-to-Use Formulation
muscular facial hyperactivity, soft tissue aging, skeletal
Ingredient Function
remodeling, and skin aging.1 With aging, dynamic wrinkles,
especially around the central areas, the eyes, forehead, Clostridium botulinum toxin type A protein Active agent
and mouth, eventually become more prominent. Since their complex

introduction more than 30 years ago,2 botulinum neurotox­ Histidine Buffer


in type A (BoNT-A) injections into the facial muscles have
become the most common minimally invasive cosmetic Sucrose Stabilizer

procedure worldwide. In 2021, the International Society of Polysorbate-80 Stabilizer


Aesthetic Plastic Surgery (ISAPS) reported over 7 million
BoNT-A procedures (up 45% since 2017), with 35- to Sodium chloride Isotonic agent

50-year-olds accounting for 47.2% of procedures.3 When Hydrochloric acid pH adjustment to neutral

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injected into the appropriate facial muscles, BoNT-A inhib­ level
its the release of acetylcholine thereby diminishing muscle
Water for injection Diluent
contraction, and smoothing hyperkinetic wrinkles (eg,
mainly glabellar lines, crow’s feet, and forehead) and/or
correcting facial muscle hyperactivity (eg, gummy smile,
as “none” or “mild”) already at Day 8 (80% vs 2.5% with pla­
masseter etc).
cebo), with peak effect at Day 29, and a significant proportion
Of the several available preparations of BoNT-A products,
of patients were still considered as responders at 6 months.
ready-to-use (RTU) abobotulinumtoxinA (Alluzience; Ipsen,
The proportion of responders at maximum frown (as deter­
Paris, France and Galderma SA, Lausanne, Switzerland)
mined by the investigator) was maintained over repeated in­
was the first RTU liquid solution to be made available in
jection cycles (between 82.2% and 87.8%). Importantly for
Europe for the treatment of moderate-to-severe glabellar
patients, patient satisfaction was very high at peak effect
lines.4 This RTU liquid formulation was developed to provide
(85.2% vs 9% with placebo) and a significant proportion of pa­
several practical benefits over existing lyophilized powder
tients remained satisfied with their wrinkle appearance at 6
formulations, not only in terms of convenience of injection
months (49% vs 11% on placebo). Based on the validated
and prevention of reconstitution errors, but also in terms of
FACE-Q patient- reported outcome measure scales for satis­
consistency and precision of dosing because it is provided
faction with facial appearance overall, significant improve­
at a single RTU concentration that does not require any cal­
ments were observed for psychological well-being and
culations and is optimized for facial aesthetic use in terms of
aging appearance.6-8 Further investigations of subject satis­
onset, effect, and duration of effect. The liquid formulation
faction have been made in the open-label STAR study, which
was specifically designed to avoid using any excipients or in­
supported high satisfaction through 6 months posttreat­
gredients from animal or human origin, including lactose and
ment.9 As of today, AboBoNT-A RTU is the sole commercial­
human serum albumin. Indeed, it is the first BoNT-A commer­
ized BoNT-A for which the authorities have granted a
cialized product in Europe to successfully remove the need
6-month duration effect into the SmPC (Alluzience summary
for this human protein, which is used to stabilize other
of product characteristics [SmPC]).
BoNT-A products and prevent adsorption of BoNT-A onto
In 2010, experts convened an international consensus
the vial. The aboBoNT-A liquid RTU formulation uses the
meeting on the practical use of aboBoNT-A in its powder
same purified neurotoxin type A complex (Hall strain) as pre­
form (Dysport/Azzalure; Ipsen and Galderma SA) for facial
vious lyophilized powder formulations and contains 0.9% so­
aesthetic indications.10,11 Although the core neurotoxin
dium chloride, small amounts of polysorbate 80, histidine to
(aboBoNT-A) remains the same, the upgrades in formula­
buffer the formulation, and hydrochloric acid to maintain the
tion as well as the RTU presentation of Alluzience necessi­
pH constant at 6.5 (to prevent premature dissociation of the
tate specific guidance for the new product that also
nontoxic neurotoxin-associated proteins and the toxin)
consider recent important advances in injection technique.
(Table 1). Dissociation of the complex is immediate once
The following consensus-led guidelines were developed to
the product is injected in the targeted tissue.
provide practical guidance on how to optimize aesthetic
In Phase III studies,5-7 aboBoNT-A RTU (50 U) was as­
outcomes when injecting aboBoNT-A RTU.
sessed as providing high levels of efficacy in the treatment
of moderate-to-severe glabellar lines by both the investiga­
tors and patients. With precision dosing, visible effects are METHODS
seen as early as 24 hours postinjection, with most patients
reporting improvement in their wrinkles within 1 to 3 The International Board on Alluzience (IBA) comprised
days.6-8 A high proportion of patients were considered treat­ 10 dermatologists/plastic surgeons who have extensive ex­
ment responders (glabellar line severity rated by investigator perience in the aesthetic usages of aboBoNT-A RTU. Three
194 Aesthetic Surgery Journal 44(2)

board members were leading members of the Glabellar realistic patient expectations. It is important to consider if
Lines Study Group for Alluzience.6,7 Board members con­ the proposed treatment plan will benefit from combining
vened face-to-face on May 14, 2022, to update/develop treatments (eg, with dermal fillers or other minimally inva­
consensus recommendations on various upper face indica­ sive procedures) and patients should be clearly informed
tions, based on their own experience during clinical prac­ if they are about to receive injections for an off-label indica­
tice and based on the results of large clinical studies if tion. Anesthesia is rarely required, and patients should be
available. counselled about the possibility of any expected discom­
Considering the “average” patient, members indicated fort as well as the number of injection sites expected for
their preferred injection points on provided anatomic imag­ the procedure. Finally, injectors must ensure they remain
es and discussed the techniques they find useful in clinical compliant with all mandatory legal requirements. For exam­
practice. High-risk injection points were considered out of ple, from October 2021 it is a criminal offence to administer
scope, as were indications requiring extensive injector ex­ botulinum toxin or a dermal filler by way of injection for a

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perience. Consensus recommendations were developed cosmetic purpose to a person aged under 18 in England,
to provide simple guidelines for the safe injection of even if they have the permission of someone over 18.14
aboBoNT-A RTU and reflect the real clinical practice of aes­ In most fields of medicine, shared decision-making is ad­
thetic providers. Board members considered aspects such vocated as the preferred model of patient-physician interac­
as the recommended injection points, dose, and the cor­ tion to engage patients in the process of deciding about
rect injection technique. A strong consensus was defined treatment when more than one reasonable option is avail­
as approval from at least 8 of 10 members. It is important to able.15 Although often not properly implemented in cosmetic
note that the dosing recommendations provided here medicine,16 the IBA considered shared decision-making to
refer to aboBoNT-A Speywood Units, which includes be an essential part of the consultation process as it helps de­
Alluzience, as well as the formulations Azzalure and termine which products best match the patient’s individual
Dysport, and cannot be compared to any other formula­ characteristics and preferences and forms the basis for
tions or preparations of BoNT-A. true informed consent.15 When introducing the aboBoNT-A
RTU liquid formulation to patients, the IBA considered that
it is important to mention to the patients that the upgraded
GENERAL PREPARATION AND RTU formulation contains the same, proven, well-studied
CONSULTATION neurotoxin as the powder formulations (Azzalure/Dysport).
This enables a thorough discussion of the proven mode of
The IBA confirmed that the general principles of ensuring action, long history of usage, and good safety record of
proper patient education and counselling from the previ­ aboBoNT-A. In line with patient expectations for an aesthetic
ous consensus paper10 still stand. It remains essential for product, the innovative formulation has also enabled a switch
patients to have a realistic expectation of the treatment out­ to plant-based and synthetic excipients. Some patients may
come as this significantly influences their level of satisfac­ also be reassured that the formulation makes it possible to
tion with treatment.12 Recent surveys have also shown increase the precision of the dosing by not going through a
that patients who feel they are well informed and provided reconstitution phase and uses novel syringes with the units
with sufficient information are more likely to be satisfied and volume already calibrated. In the recent open-label
with treatment. Information should be provided in an STAR study, investigators reported multiple benefits with
easy-to-understand manner, avoiding overuse of compli­ the RTU product, including precision of the injection and
cated medical terminology.13 the possibility to spend more time on patients.9
During the initial consultation, injectors should discuss in Patients should be made aware of the estimated onset of
detail the patient’s requests and be attentive to the differ­ action and duration of effect of aboBoNT-A RTU. Of note,
ence between objective and subjective perceptions. the large pivotal studies conducted to gain approval in
Injectors should probe for patient preferences and priori­ Europe support a distinctly favorable time course of action.
ties such as a natural look, or full control of wrinkles, with Up to a quarter of patients experience improvements within
a risk of fixity. The IBA recommended a static then dynamic the first day of injection, and the median onset was within 3
approach for mapping and treatment planning. A full holis­ days. AboBoNT-A RTU has also demonstrated a long dura­
tic assessment of the facial anatomy, during rest and during tion of action of up to 6 months postinjection and with main­
movement, should be performed and any pre-existing tained efficacy over repeated cycles.7 Injectors should also
asymmetry documented and discussed. A series of photo­ explain how the treatment will be delivered (eg, number of
graphs and/or videos with and without muscle movements injection points), potential adverse events (eg, headache
are crucial before any injection. Injectors may then set out and/or injection site reactions9,17), and, if necessary, the
a proposed treatment plan that considers the patient’s re­ treatment to correct any undesired outcomes. While
quest, facial anatomy, and skin status while maintaining some injection site pain can be expected, it is typically
Ascher et al 195

A B

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C D

Figure 1. Treatment of (A) glabellar lines, (B) crow’s feet, (C) horizontal forehead lines, and (D) lateral brow lift. For the treatment of
glabellar lines, a 5-point injection is recommended for most patients, with 1 point in the procerus and 2 points in each corrugator.
For the treatment of crow’s feet, an injection pattern of 3 points per side (ie, 6 points in total) surrounding the canthal region is
recommended for most patients. For the treatment of horizontal forehead lines, the International Board on Alluzience
recommended 4 to 8 points for the total frontalis depending on patient presentation (gigure shows 8 points). For the lateral brow
lift, 1 injection point should be placed at each eyebrow tail into the pars orbicularis, 1 cm above the orbital rim. An additional
injection point should be placed at the external part of the frontalis, at a minimum of 4.5 cm up from the eyebrow (depending on
hairline) and 4 to 5 cm from the midline. Created by and published with permission from Virginie Denis.

transient (gone within seconds) and was reported as an ad­ the labelling guidelines, a 5-point injection is recommend­
verse event in only 1% to 5% of patients in the clinical tri­ ed for most patients, with 1 point in the procerus and 2
als.5,7 In the STAR study, 91% of surveyed patients said points in each corrugator (Figure 1A). In the case of a long
they “felt comfortable with the injection procedure.”9 and/or strong procerus, the IBA recommended that a sec­
Patients should also be counseled that because the effects ond injection point along the same procerus crease can
of aboBoNT-A RTU are potentially longer lasting than those be made. In the case of long corrugators (extending be­
of other BoNT-A products, there needs to be full agree­ yond the midpupillary line) a third injection point per corru­
ment on their treatment goals and expectations. A follow- gator can be added laterally.
up appointment may be scheduled, the benefits of which Injections should be perpendicular (keeping the distance
have been shown to be another significant contributor to between skin and target as short as possible to encounter
patient satisfaction.13 All patients should provide docu­ fewer blood vessels and free nerve endings, thereby induc­
mented informed consent before treatment commences. ing less bruising and pain), 0.5 to 1 cm from the upper orbit­
al rims and internal to the midpupillary lines and never in
the direction of the orbital rim. IBA members recommended
CONSENSUS GUIDELINES injecting deep medially and more superficial laterally. The
recommended total aboBoNT-A RTU dose is 50 U, with
Glabellar Lines
10 U in the procerus, 10 U in the head of each corrugator,
AboBoNT-A RTU is indicated for the improvement in ap­ and 10 U in the tail of each corrugator. If a third injection
pearance of moderate to severe glabellar lines (vertical per corrugator is required, IBA members recommended
lines between the eyebrows) and its efficacy and safety administering 2.5 U lateral to the midpupillary line (intra­
has been established in recent randomized, controlled muscularly or subdermally depending upon muscle size).
studies.5,6,8 For the treatment of glabellar lines, as per Some of the IBA board members preferred to consider
196 Aesthetic Surgery Journal 44(2)

this “extra” injection at a touch-up visit conducted 2 to 4 Unwanted effects include pain, aggravation of malar
weeks after the initial injection. There was consensus that edema and under-eye wrinkles, and effects on neighboring
the final dosage for each individual patient depends on muscles such as the inferior region of the zygomaticus
their muscle structure and mass, the wrinkle severity, and major, which can lead to drooping mouth corners and
patient’s preference of a more natural or a more static look. asymmetry if injected. To avoid these problems, the IBA
IBA members noted that the need for procerus injection recommended performing a snap test to confirm the pa­
may decrease over time, but 70% of members said they tient has adequate skin elasticity and to avoid injecting
continue to inject because it elevates the medial part of the canthal region in patients with prominent malar edema.
the brow. Some advisors noted they preferred to inject Treatment of crow’s feet can be combined with lower eye­
within skin pores because this helps avoid nerves and lid wrinkles if they are present. In this case, the same injec­
blood vessels. As with prior formulations, injection site re­ tion points should be used with a slightly lower dose per
actions, including transient injection site pain (typically last­ point. Eyelid ptosis is avoided by injecting superficially

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ing a few seconds) and hematoma, remain the main safety with posterior directionality.
concerns for this indication.10,11 Injection site reactions can
mostly be mitigated with proper injection technique as can
Horizontal Forehead Lines
eyelid ptosis (caused by unwanted involvement of the leva­
tor palpebrae).18 Adverse events such as headache or eye­ Often treated alongside the glabellar region, horizontal
lid ptosis rarely occur and usually subside within days or a forehead lines are another commonly treated indication
few weeks.7 Patients with a history of eyelid ptosis follow­ for BoNT-A injections. For the treatment of horizontal fore­
ing treatment should be counseled that their individual head lines, the IBA recommended 4 to 8 points for the total
anatomy might be predisposed to the diffusion of toxin frontalis depending on patient presentation. In view of the
into the levator palpebrae superioris.19 anatomy of the frontalis muscles and thin skin of this loca­
tion the injections should be superficial (ie, subdermal/in­
tramuscular), and perpendicular to the skin. To avoid any
Dynamic and Static Periorbital Wrinkles brow ptosis, the IBA recommended injecting relatively
high on the forehead (at least 2 cm from the upper orbital
(Crow’s Feet)
rim and avoiding the inferior frontalis), in a slightly curved
Lateral canthal rhytids (crow’s feet) are a common indica­ V-shape for women and more horizontally in men
tion where injections are used to compensate for overacti­ (Figure 1C). A total aboBoNT-A RTU dose range of 20 to
vation of orbicularis oculi during animation. The injection 40 U (2.5-5 U per point) was recommended. The higher
technique may also be part of a nonsurgical brow lift. For the number of injection points, the lower the dose per point
the treatment of crow’s feet, the IBA recommended inject­ should be used.
ing 3 points per side (ie, 6 points in total) surrounding the IBA members also recommended an injection (2.5 U) into
canthal region (Figure 1B). For some patients with long the orbicularis point, 1 cm above the orbital rim, to protect
and severe crow’s feet the number of injections can be in­ the effect. Half of the IBA board members recommended
creased to 6 points per side adapted to the location of the starting with a smaller dose followed by a touch-up visit,
wrinkles. All points should be at the lateral part of the orbi­ while the other half only performed a touch up if needed.
cularis oculi, 1 to 2 cm from the external orbital rim. Some Board members noted that movement of the lateral fronta­
board members recommended that the inferior point lis can sometimes lead to fine wrinkles (WIFI lines) above
should be a bit more internal and/or a lower dose to avoid the lateral part of the eyebrows. This can be treated with
any diffusion to the zygomatic muscles. Injections should a subdermal/intradermal injection of 2.5 U in the WIFI
be slow and controlled, lateral (30-45° angle to the skin), line, during the full injection or during the touch up.
and superficially into the dermal plane. It is recommended
that the needle always points away from the patient’s eyes.
Lateral Eyebrow Lift
The injector should stretch the skin slightly to visualize
superficial veins and avoid bruising. A total aboBoNT-A Usually performed in women and in combination with other
RTU dose of 30 to 60 U is recommended, with 5 to 10 U upper face treatments, BoNT-A treatment is often used to
per point (15-30 U per side); dosage considerations include correct dropping of the lateral part of the brow. For this in­
the strength of the muscle, depth of wrinkles, and the thick­ dication, the IBA recommended a 4-point injection with 2
ness/firmness of the skin and subcutaneous tissue. Doses points per side (Figure 1D). One injection point should be
should be reduced (mainly in the inferior part) for patients placed at each eyebrow tail into the pars orbitalis, 1 cm
with signs of malar edema. As with previous aboBoNT-A above the orbital rim. Treatment with aboBoNT-A RTU
formulations, the minimal injection dose should be adopted blocks the depressor while the frontalis functions normally
to avoid a frozen look when smiling. to elevate the lateral part of the eyebrow. An additional
Ascher et al 197

A B

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Figure 2. Treatment of (A) lower eyelid wrinkles and (B) bunny lines. For the treatment of lower eyelid wrinkles, board members
recommended 1 to 3 injections about 2 to 3 mm below the lash line. For the treatment of bunny lines, 1 to 3 injection points in the
nasalis pars transversa are recommended (figure shows 2 points per side). Created by and published with permission from
Virginie Denis.

injection point should be placed at the external part of the Open Eye Technique
frontalis, at a minimum of 4.5 cm and an average of 4 cm
from the midline. Injection in this part of the frontalis boosts Treatment with BoNT-A reduces the inferior wrinkles, in­
the levator activity of the inferior part of the frontalis, and creases the palpebral aperture, and thus widens the
can further drop the medial brow, reshape the entire eye­ eyes. The open eye technique is used where there are
brow, and accentuate the lateral arch. asymmetries of the eyelids or to treat narrow eyes on smil­
The recommended dose is 5 to 10 U/point and the total ing and facial palsy. For this technique, the IBA recom­
dose range is 20 to 40 U. Injection into the pars orbicularis mended 2 to 3 superficial injection points (1-2 U per point
should be of medium depth (6 mm) and the injection into for a total dose of 4-6 U) on the lower lid, close to the
the frontalis should superficial, intramuscular, and perpen­ lash line in the lateral and tarsal parts of the orbicularis oc­
dicular to the skin. Eyelid and brow ptosis occur only rarely uli. In some cases, when the patient has small eyes or wants
when the injection sites are too close to the orbital rim. to elevate their eyebrows, an additional 3 injections in the
lateral canthus can help improve symmetry.
As with lower eyelid wrinkles, unwanted effects include
Lower Eyelid Wrinkles ectropion and exacerbating dry eye. Patient exclusion cri­
teria are like those for crow’s feet. Injectors should ensure
Lower eyelid wrinkles (external and inferior eyelid orbicula­ patients have sufficient skin elasticity using a snap test
ris oculi bands) occur because of overactivity of the tarsal (<2 seconds), and should avoid injecting patients with dry
and lacrimal portions of orbicularis oculi. For the treatment eyes, prominent malar edema, scleral show, or morning
of lower eyelid wrinkles, board members recommended eyelid edema.
1 to 3 injections about 2 to 3 mm below the lash line.
Injections can be made at the sand, “owwee,” and midpu­
pillary points20 (Figure 2A). Board members recommended
Bunny Lines
injecting tangentially and very superficially (with papule)
1 to 2 U per point for a total dose of 5 to 6 U (2.5-3 U per Bunny lines refer to dynamic wrinkles (from the levator labii
side). Treatment of lower eyelid wrinkles may be synergis­ superioris alaeque nasi and the transverse nasalis muscles,
tic with treatment of the lateral periorbital wrinkles (“crow’s together with the medial portion of the orbicularis oculi
feet”) to obtain optimal results. IBA members agreed that muscle) on the side of the nose. In some patients, dynamic
treatment is not suitable for treating the static wrinkles wrinkles may extend to the lower eyelids and cheeks. If
caused by photodamage or eye bags caused by muscle bunny lines appear in addition to glabellar lines when pa­
laxity; in these cases, combination therapy with fillers, peel­ tients frown, they should be treated together. Weakening
ing, lasers, or surgery is usually more appropriate. of the lateral portion of the orbicularis oculi muscle for re­
Unwanted effects for both indications include ectropion duction of lateral canthal lines often results in compensato­
and exacerbating dry eye. Injectors should ensure patients ry hyperactivity of the medial portion, accentuating the
have sufficient lid elasticity using a snap test (<2 seconds), bunny lines. For the treatment of bunny lines, 1 to 3 injection
and should avoid injecting patients with dry eyes, promi­ points in the nasalis pars transversa are recommended
nent malar edema, scleral show, or morning eyelid edema. (Figure 2B). In case of wider lines, additional injections
198 Aesthetic Surgery Journal 44(2)

into the alae nasi part of the levator labii alaeque nasi the size of nostril aperture) are only recommended for ex­
(LLAN) are also recommended. Injections should be deep perienced injectors.
(close to the periosteum), the orientation of the injection
should be perpendicular, with an angle of about 90° to
Perioral Wrinkles
the nasal bone. The consensus recommendation is to use
aboBoNT-A RTU 2.5 to 10 U per injection point for a total The perioral area is a complex area due to its function and
dose of 10 to 20 U. the interplay of muscles. Aging, heliodermy, and smoking
can result in substantial changes in the appearance of
the lips including vertical perioral wrinkles. The normal ac­
Injecting for the Upper Face and Overall tions of the orbicularis oris accentuate these lines. For the
Facial Enhancement treatment of perioral wrinkles, 4 to 6 injection points are
recommended, with four symmetric points just above the
Treatment planning should consider whether the patient’s

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vermilion border and, if necessary, 2 points on the lower
goals and preferences are for one specific area or for over­
lip (Figure 3A). Injections should be perpendicular to the
all facial shaping and enhancement. Facial muscles do not
skin and intradermal, and injection sites should be adjusted
act in isolation but have complex interactions, and the treat­
to the pattern of perioral lines. The IBA advised that lateral
ment plan must consider the interdigitation of muscle fibers
points should be at least 1.5 cm away from the mouth cor­
and the degree to which their activities are antagonistic to
ners to avoid incompetence, which may cause drooling
each other to ensure the desired aesthetic effect is
as well as difficulties in speaking, drinking, and eating.
achieved. For example, the most common indications of
A total dose of 4 to 12 U is recommended, with 1 to 2 U
glabellar, lateral canthal, or forehead lines can all alter eye­
per point. The dose depends on the muscle strength, se­
brow shape and position, and this should be considered
verity of the hyperkinetic lines, and the degree of elastosis.
when planning and discussing treatment plans with the pa­
However, higher doses should be avoided in the cupid’s
tient.21,22 In addition, facial muscles with different functions
bow. Due to the complexity of the area, the IBA recom­
and orientations often overlap and cross various planes,
mended a conservative approach to treatment because
making the depth of injection an important consideration.
overcorrection can cause significant mouth dysfunction.
Injections made too superficial or too deep can lead to in­
A reasonable approach is to begin with 1 site per quarter
advertent injection of the wrong muscle, potentially caus­
lip and reassess in 2 weeks when a touch up or additional
ing an opposite effect from the desired outcome.23
injection sites can be added. Combination treatment with
Finally, facial asymmetry can occur if injections are admin­
dermal fillers is often indicated in older patients to preserve
istered unequally between both sides of the face.
the shape of the philtrum. Injections may be painful, and ap­
plication of a numbing cream is recommended. Finally, pa­
tients should be counseled that complete wrinkle removal
Drooping Nasal Tip
is not realistic and that combined therapy with dermal fil­
A drooping nasal tip when smiling often involves increased lers, laser, peelings, and/or energy-based devices can be
activity of the depressor septi nasi or hypertonia of the LLAN. necessary. Even in the best hands, patients should be pre­
To prevent the nasal tip from drooping with animation, 1 in­ pared to expect some difficulty of speech, drinking with a
jection in the middle of the columella is recommended. straw, or excessive pouting of the lips in the first few
The aboBoNT-A RTU dose should be 10 U, and the injection days. It is therefore recommended to start with low doses
should be perpendicular to the skin and deep in the region and to gradually increase the dose upon repeated
of the nasal spine, as both muscle bellies cross the midline at treatments.
this point. If there is hypertonia of the LLAN muscle with a
clear lift of the nasal sides and rotation of the tip downwards,
Drooping Mouth Corners
some IBA members recommended injecting an additional
point on each side at the sides of the alae nasi part of the Drooping mouth corners can make a face appear sad or an­
LLAN. In this case, the aboBoNT-A RTU dose should be gry and are also commonly associated with marionette lines
10 U per point. that run down from the corners of the mouth. A 1- to 2-point
Pain is the most common adverse event and topical injection into the depressor anguli oris is recommended
numbing creams are recommended. Patients should not (Figure 3B). The major injection points should be 1 cm lateral
be treated for nasal tip if the nose does not droop when to the commissure and 1 cm down. The injector should pinch
smiling and talking. Injections into the LLAN should be the muscle slightly to prevent its movement and inject intra­
made with caution because it is possible that the length muscularly. The needle should point towards the side with a
of the upper lip can increase, resulting in ptosis. Other indi­ posterior flow to avoid the depressor labi inferioris which
cations in the nasal area (eg, in the alar nasalis to decrease could cause labial incompetence. A total dose of 5 to 10 U
Ascher et al 199

A B

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Figure 3. Treatment of (A) perioral wrinkles and (B) drooping mouth corners. For the treatment of perioral wrinkles, 4 to 6 injection
points are recommended, with 4 symmetric points just above the vermilion border and, if necessary, 2 points on the lower lip. For
the treatment of drooping mouth corners, a 1- to 2-point injection into the depressor anguli oris is recommended. The major
injection points should be 1 cm lateral to the commissure and 1 cm down. If additional hyperkinetic wrinkles appear lateral to the lip
corner, the International Board on Alluzience recommended also injecting the fascial platysma (inferior point). Created by and
published with permission from Virginie Denis.

is recommended, with 2.5 to 5 U per point depending on the to possible effects on crunching power and mastication capa­
strength of the depressor. If additional hyperkinetic wrinkles bility, it is important to assess the muscle mass and adjust
appear lateral to the lip corner, the IBA recommended also doses accordingly. Finally, the IBA noted that the temporalis
injecting the fascial platysma using an additional 2 injection works in synergy with the masseter, and in some cases of
points (5 U per point). bruxism, some IBA members prefer to simultaneously inject
For this indication, the IBA noted that injections will not im­ the upper temporalis (above the hairline) using an additional
prove severely depressed oral commissures and will not el­ 4 injection points (5 U per point) close to the temporal crest.
evate the marionette lines. It is therefore important to inform This is not required for facial contouring unless there is visible
the patient that only a subtle improvement is likely. For these hypertrophy of the temporalis muscle.
patients, a combination strategy with aboBoNT-A RTU and a Hollow lines of the cheek are a relatively rare indication
dermal filler can augment the quality of the result. caused by hypertonus of the risorius. The IBA recommend­
ed injecting 1 to 2 points per side, at least 1 cm behind the
Masseter Hypertrophy and Hollow Cheek modiolus (Figure 5A). Injections should be intradermal and
have a posterior flow following the wrinkle, and the recom­
Lines mended aboBoNT-A dose is 1 to 2 U per point. Treatment is
The masseter is a large, strong muscle in an active area of usually combined with a dermal filler. Injections should be
the face. AboBoNT-A RTU injections can be used to tempo­ superficial to avoid the buccinator muscle, and injectors
rarily weaken the masseter, resulting in a smoother and slim­ should be careful to address any asymmetries.
mer lower face contour. This procedure is common mainly in
Asian patients and good results can be achieved with re­
Dimpled Chin
peated injections. In Caucasians, masseter hypertrophy is
more often associated with bruxism, which also responds A dimpled chin is caused by contraction of the mentalis
well to treatment by toxin following an adapted protocol. muscle, and the IBA noted they prefer to inject only patients
For masseter hypertrophy, the IBA recommended 3 to 5 in­ with active dimpling (eg, they dimple while speaking).
jection points (in a pyramid) per side (Figure 4). Injections Combination therapy with fillers is often appropriate be­
should be perpendicular, injecting first deep and then super­ cause loss of collagen and subcutaneous fat in this region
ficially into the 2 portions of the muscle. The total dose should is a significant contributor to the formation of a dimpled
be 40 to 80 U (5-10 U per point) per site depending on mas­ chin.
seter strength. Higher doses of aboBoNT-A (100-140 U) have The IBA recommended a 1- to 3-point injection at the
been reported in Asian patients.24 Injections should be avoid­ bony jaw line close to the central midline (Figure 5B).
ed above the line from the lip corner to tragus. Injection just Injections should be deep with an aboBoNT-A RTU dose
beneath the zygomatic bone should be avoided to prevent of 5 to 10 U per injection point adjusted according to
unwanted effects in the zygomatic muscles which can lead the mentalis muscle mass. Injecting laterally and at a
to awkward facial expression, especially when smiling. Due higher-than-recommended dose may affect the depressor
200 Aesthetic Surgery Journal 44(2)

there is no muscle in this region and there is a risk of spread to


the subhyoid muscle which can cause significant problems
with breathing or swallowing. The posterior part of the platys­
ma should be avoided in high doses due to the risk of toxin
spread to the sternocleidomastoid muscle with the risk of
causing a posterior tilt of the head. The IBA recommended
scheduling a follow-up visit at 2 weeks for touch up or treat­
ment if new smaller bands appear.
The IBA did not typically recommend treatment with
BoNT-A for the décolleté region where aging is usually caused
by photodamage. Instead, they preferred alternatives such as
mesotherapy, lipofilling, dermal fillers, and/or lasers, which are

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often more effective. When used (in rare cases) the IBA recom­
mended a maximum total dose of 120 U with 2.5 to 5 U per
point. Injections should follow the distribution of wrinkling in
the pectoralis muscle. When necessary, platysmal bands
should be treated together with the décolleté wrinkles.

SUMMARY AND ADDITIONAL POINTS FOR


CONSIDERATION
Figure 4. Treatment of masseter hypertrophy. For masseter
hypertrophy, a pyramid of 3 to 5 injection points per side is These guidelines provide a practical framework for the
recommended (figure shows 3 points per side). Created by routine injection of facial muscles with aboBoNT-A RTU
and published with permission from Virginie Denis. (Alluzience). The guidelines were prepared to address the
initial approach for each indication based on the IBA’s exten­
sive experience with the product and its characteristics and
labii inferioris, causing mouth asymmetry. Injections can be knowledge on anatomy and physiology. A thorough under­
supplemented with some subdermal injections into the standing of static and dynamic facial anatomy is a prerequi­
dimples as required. The IBA noted that when the dimpled site for anyone undertaking aesthetic procedures with
chin and drooping mouth corners (depressor anguli oris) aboBoNT-A RTU to maximize efficacy, and minimize the
are treated together, 1 central injection point of 5 to 10 U risk of adverse events. Board members considered thor­
might be sufficient. Safety concerns mainly relate to using ough assessment and a proper discussion of treatment
higher-than-recommended doses which may affect the de­ objectives as fundamental to treatment success. This is be­
pressor labii inferioris and the orbicularis oris, causing cause doses and injection techniques (eg, depth of injection)
drooling, speech impairment, and mouth asymmetry. should be optimized to the individual patient, considering
their unique facial anatomy, and based on the size and
shape of the muscle, the severity of the wrinkles, and the de­
Platysmal Bands and Décolleté Wrinkles
gree of immobilization required by the patient.
Visible active platysmal bands on the neck may be appar­ The IBA recommends that injectors should always aim to
ent in some slim patients and become more prominent start with the lowest recommended effective dose per mus­
when they speak or smile. Patients should be seated up­ cle for the first injection, and to work in an iterative manner;
right, and the injector should pinch each band and inject some patients will benefit from a touch-up visit 2 to 4 weeks
laterally with a superficially intramuscular injection. As after the initial injection. Using lower-than-recommended
with all aesthetic indications, there is usually no need for doses may result in suboptimal efficacy or duration of ef­
topical anesthesia. fect. Once the patient has achieved their goal, the injector
The total number of injection points depends on the num­ will need to consider maintenance treatment, taking into
ber and length of platysmal bands; it is recommended to start consideration that, although the efficacy of injection does
the first point at the jawline and go down every 2 cm to the not change with repeat treatment, the original muscle bal­
middle of the bands (Figure 5C). The total maximum dose rec­ ance has been modified. The minimum injection interval is
ommended for this indication is typically 100 U, with a total of 3 months; however, the efficiency of the Alluzience formu­
20 U per treated band (5-10 U every 2 cm depending on neck lation typically allows for a longer duration of benefit. Other
length). Injections can be perpendicular to lateral in an exter­ maintenance considerations include aspects such as stabi­
nal direction. There is no need to inject at the midline because lization of the eyebrow position and the prevention of new
Ascher et al 201

A B

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C

Figure 5. Treatment of (A) hollow cheek lines, (B) dimpled chin, and (C) platysmal bands. For the treatment of hollow cheek lines,
the International Board on Alluzience recommended injecting 1 to 2 points per side, at least 1 cm behind the modiolus. Injections
should be intradermal and have a posterior flow following the wrinkle. To treat the dimpled chin, a 1- to 3-point injection at the bony
jawline close to the central midline is recommended. For platysmal bands, it is recommended to start the first point at the jawline
and go down every 2 cm to the middle of the bands. Created by and published with permission from Virginie Denis.

wrinkles appearing (eg, injection into new faint lines). For Iozzo, Martschin, Milotich, and Molina report consultancy and/
patients with significant volume loss due to aging, injectors or speaker fees for Galderma. Dr Cartier reports participation
can consider combination treatments to correct for volume in clinical trials for Fillmed (Paris, France), Vivacy, and
loss.25,26 For younger patients whose goals are preventa­ Galderma. Dr Picaut reports consultancy for Galderma and
tive, the IBA recommended a similar treatment approach Ipsen. Dr Prygova is employed by Galderma.
considering whether patients can use a slightly lower
dose or have a longer interval between treatments. As for Funding
all patients, there is a duty for injectors to ensure that the
This work was funded by ThinkIn (Paris France), supported by
younger patient has a good understanding of what can an Unrestricted Educational Grant from Galderma (Lausanne,
be achieved with such treatment. Sweden). Authors received expenses for meeting attendance.
No author received specific renumeration for participation in
Acknowledgments the writing of this paper. One author (I.P.), employed by the
The authors thank Dr A. Chadha-Patel (ACP Clinical sponsor (Galderma), participated in the meeting where she
Communications, Buckinghamshire, UK) for editorial assistance provided formulation details of Alluzience and commented
and Virginie Denis Greiss for artwork, both funded by ThinkIn on the licensed indication for glabellar lines.
(Paris, France).

Disclosures
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