Tiêm Botulinum Toxin Trong Thực Hành Thẩm Mỹ (Tập 2): Giải Phẫu Chức Năng Và Kỹ Thuật Tiêm

Botulinum Toxins in Clinical
Aesthetic Practice
Third Edition
Volume Two: Functional Anatomy and Injection Techniques

Series in Cosmetic and Laser Therapy
Series Editors
Nicholas J. Gary P. Lask, and David J. Goldberg
Anthony V. Benedetto, Botulinum Toxins in Clinical Aesthetic Practice, Third
Edition: Two Volume Set, ISBN 9781498716314
Robert Baran and Howard Maibach, Textbook of Cosmetic Dermatology,
Fifth Edition, ISBN 9781482223934
Philippe Deprez, Textbook of Chemical Peels, Second Edition: Superficial,
Medium, and Deep Peels in Cosmetic Practice, ISBN 9781482223934
Jenny Kim, Gary Lask, and Andrew Nelson, Comprehensive Aesthetic
Rejuvenation: A Regional Approach, ISBN 9780415458948
David J. Goldberg and Alexander L. Berlin, Disorders of Fat and Cellulite:
Advances in Diagnosis and Treatment, ISBN 9780415477000
Neil S. Sadick, Paul J. Carniol, Deborshi Roy, and Luitgard Wiest, Illustrated
Manual of Injectable Fillers: A Technical Guide to the Volumetric Approach to
Whole Body Rejuvenation, ISBN 9780415476447
Kenneth Beer, Mary P. Lupo, and Vic A. Narurkar, Cosmetic Bootcamp
Primer: Comprehensive Aesthetic Management, ISBN 9781841846989
Anthony Benedetto, Botulinum Toxins in Clinical Aesthetic Practice, Second
Edition, ISBN 9780415476362
Robert Baran and Howard I. Maibach, Textbook of Cosmetic Dermatology,
Fourth Edition, ISBN 9781841847009
Neil Sadick, Diane Berson, Mary P. Lupo, and Zoe Diana Draelos,
Cosmeceutical Science in Clinical Practice, ISBN 9780415471145
Paul Carniol and Gary Monheit, Aesthetic Rejuvenation Challenges and
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Avi Shai, Robert Baran, Howard I. Maibach, Handbook of Cosmetic Skin
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Botulinum Toxins in Clinical
Aesthetic Practice
Third Edition
Volume Two: Functional Anatomy and Injection Techniques
Edited by
Anthony V. Benedetto
Clinical Professor of Dermatology
Perelman School of Medicine
University of Pennsylvania
and
Medical Director
Dermatologic SurgiCenter
Philadelphia, Pennsylvania

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Library of Congress Cataloging-in-Publication Data
Names: Benedetto, Anthony V., editor.
Title: Botulinum toxins in clinical aesthetic practice / edited by Anthony V. Benedetto.
Description: Third edition. | Boca Raton, FL : CRC Press/Taylor & Francis Group, 2018. | Includes bibliographical references and index.
Identifiers: LCCN 2017024412| ISBN 9781138301849 (v. 1 : pack- hardback and ebook : alk. paper) | ISBN 9781138304802
(v. 2 : pack- hardback and ebook : alk. paper) | ISBN 9780203729847 (v. 1 : ebook) | ISBN 9780203729755 (v. 2 : ebook)
Subjects: | MESH: Botulinum Toxins, Type A--therapeutic use | Dermatologic Agents--therapeutic use | Skin--drug effects |
Cosmetic Techniques | Skin Diseases--drug therapy
Classification: LCC RL120.B66 | NLM QV 140 | DDC 615.9/5--dc23
LC record available at
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and the CRC Press Web site at

To Dianne, my loving wife of forty years, whose encouragement and support permitted me to accomplish that
which seemed at times insurmountable and unattainable.

Taylor & Francis Taylor & Francis Group

vii
Contents
Preface
ix
Acknowledgments
xi
12 Functional facial anatomy, proportions of beauty, and neuromodulation
105
Sebastian Cotofana
13 Cosmetic uses of botulinum toxin A in the upper face
113
Anthony V. Benedetto
14 Cosmetic uses of botulinum toxin A in the mid face
188
Anthony V. Benedetto
15 Cosmetic uses of botulinum toxin A in the lower face, neck, and upper chest
236
Anthony V. Benedetto
16 The use of botulinum toxin for the breast
293
Francisco Pérez Atamoros and Olga Macías Martínez
17 Aesthetic use of botulinum toxin in Asians
299
Kyle K. Seo
Appendix 2  Muscles of facial expression
310
Appendix 3  The preparation, handling, storage, and mode of injection of OnaBTX-A
315
Appendix 4  Patient treatment record
318
Appendix 5  Informed consent for the treatment of facial and body wrinkles with botulinum toxin
319
Appendix 6  Side effects and contraindications to injections with botulinum toxins
320
Index
323

Taylor & Francis Taylor & Francis Group

ix
Preface
Because of the exponential developments in the clinical use of botu­
linum toxins (BoNTs), the need for a third edition quickly became a
foregone conclusion. Maintaining the original mission of an instruc­
tional manual, this completely revamped and updated third edition
attempts to record the phenomenal progress that has evolved in the
use of BoNTs in clinical medicine over the past seven years. Updates
of the literature, expanded indications, improved clinical photo­
graphs and illustrations, and newer and innovative ways to utilize the
different BoNTs that are presently available worldwide are presented
in this newly formatted third edition. It also has become strikingly
obvious that BoNTs are injected in a variety of novel ways that differ
from East to West. Therefore, a concerted effort has been made to
include a profile of as many of the different BoNTs currently avail­
able around the world, including how they are utilized in a clinical
aesthetic setting in both Western and Eastern cultures.
In the United States, glabellar and lateral canthal lines remain the
only areas of the face that are approved by the FDA for the cosmetic
use of onabotulinumtoxinA (OnaBTX-A) or BOTOX Cosmetic.
The other BoNTs available in the United States, abobotulinumtoxinA
(AboBTX-A), incobotulinumtoxinA (IncoBTX-A), and rimabotulinum­
toxinB (RimaBTX-B), have their own similar, but very specific, FDA
indications. Consequently, except for glabellar and lateral canthal wrin­
kles, all the cosmetic injection techniques described in this third edition,
as in the previous editions, apply to non-approved, off-label indications,
which makes this book unlike most other textbooks in medicine.
It is sobering to realize that throughout human existence women
and men have always sought ways to improve their appearance. To
commence the in-depth and diverse discussions in this third edition
on beautification and rejuvenation with BoNTs, Nina Jablonski, PhD,
professor of anthropology at The Pennsylvania State University, and
a world-renowned biological anthropologist and paleobiologist, pro­
vides us in her Prologue with a brief introduction to the evolutionary
and anthropological perspectives on the importance of human facial
attractiveness and expressivity. She cautions both patients and treat­
ing physicians in the over-use of face altering procedures that can
effectively inhibit one’s ability to express oneself accurately and in a
completely natural manner.
Chapter 1 is written by Jean Carruthers, MD, to whom the world
is indebted for her prescient identification of the cosmetic uses of the
BoNTs. Dr. Jean Carruthers commences our venture through the
fascinating evolving world of the BoNTs by presenting a historical
account of the chronological events that led to the discovery, identi­
fication, isolation, and eventual synthesis of BoNTs for clinical use.
Included is her seminal work in the development and advancement of
the clinical uses of BoNT-A in ocular therapeutics, and her serendipi­
tous discovery of its cosmetic properties. Jean describes the role she
and her dermatologist husband, Dr. Alastair Carruthers, played in
their provocatively sensitive introduction and promotion of the cos­
metic uses of BoNT-A to the medical community.
Updates on the current advancements in the pharmacology and
immunology of the different BoNTs are discussed by world-renowned
scientists who are intimately involved in BoNT research and develop­
ment. These include Chapter 2 by Mitchell F. Brin, MD, neurologist
and one of the earliest clinical injectors of OnaBTX-A and now senior
vice president of global drug development and chief scientific officer
of BOTOX®, at Allergan Inc. (Irvine, CA). He presents an update on
the pharmacology, immunology, recent developments, and future
predictions on the use of BoNT-A. Chapter 3 by Juergen Frevert, PhD,
head of botulinum toxin research at Merz Pharmaceuticals GmbH,
(Potsdam, Germany), discusses the innovative pharmacology and
immunology of a noncomplexed BoNT-A, and the advantages of its
clinical uses.
Chapter 4 by the visionary dermatologist, Richard Glogau, MD,
discusses the fascinating emerging science, development, and effec­
tive clinical uses of a new topically applied BoNT-A. Chapter 5 by
Gary Monheit, MD, a dermatologist and leader in BoNT clinical
research, and dermatologist James Highsmith, MD, elaborates on the
recent advances of the different FDA approved BoNT-As and BoNT-B
with updates on the pertinent literature and details on recent devel­
opments in their clinical use. Chapter 6 by Andy Pickett, PhD, Senior
Program Leader & Scientific Expert, Neurotoxins for Galderma
Aesthetic and Corrective, and Director and Founder of Toxin Science
Limited, Wrexham, UK, identifies some of the different BoNTs used
in clinical practice currently available in other parts of the world.
Chapter 7 by Alastair and Jean Carruthers, MD, presents updated
and advanced clinical information on the adjunctive uses of the
BoNTs in conjunction with injections of soft tissue fillers, and light-
and energy-based devices for the aesthetic improvement of the face
and body.
In Chapter 8, Arthur Swift, MD, an otorhinolaryngologist, Kent
Remington, MD, a dermatologist, and Steve Fagien, MD, an oph­
thalmologist, add a new dimension to the aesthetic interpretation of
how to use injectables when rejuvenating the face, change to includ­
ing their explanation of facial proportions, geometrical Phi measure­
ments, aesthetics, and beauty as they relate to the use of BoNTs.
For Chapter 9, dermatologists David Pariser, MD, and DeeAnna
Glaser, MD, Secretary and President, respectively, of the International
Hyperhidrosis Society, have comprehensively revised and updated
the material on hyperhidrosis, discussing recent developments as well
as new and different areas of treatment.
Chapter 10 by dermatologist Kevin C. Smith, MD, the master of
novel injection techniques, along with dermatologists Irèn Kossintseva
and Benjamin Barankin continues to enlighten us on unique ways to
utilize BoNT-A for cosmetic and therapeutic purposes.
Chapter 11 by dermatologist and attorney David Goldberg, MD, JD,
concludes the first volume with a revision and update of his chapter
on the important medicolegal aspects of the cosmetic uses of BoNT.
Because of the ever-growing selection of the various BoNT prod­
ucts currently commercially available for clinical use in different
parts of the world, the new Appendix 1 written by dermatologist Alica
Sharova, MD, PhD, of Pirogov Russian National Research Medical
University, Moscow, presents thought-provoking results of her meta­
nalysis comparing consensus statements and recommendations for
injecting different BoNT products in the United States, Russia, and
different countries in Europe. She identifies and compares the falla­
cious recommendations of dose ratio equivalencies of the different
available BoNTs injected, including number of injection points and
dosaging for the different areas of the face and neck in males and
females.
In the second volume, Sebastian Cotofana, PhD, a quintessential
anatomist, has provided essential new material on functional facial
anatomy in Chapter 12.

Preface
x
The nuclear Chapters 13, 14, and 15 on the cosmetic treatment of
the face, neck, and chest with injections of BoNTs have been reor­
ganized and expanded, assimilating many improved injection tech­
niques by integrating updated information of recently published
clinical and anatomical studies. All the anatomical figures and illus­
trations have been revised and enhanced throughout the text. The
organization of these three chapters has remained the same. Each
clinical topic is subdivided according to its facial and functional
anatomy, and discussed in seven subheadings. The “Introduction”
of each topic identifies the different anatomical changes acquired
by men and women as they “age” and develop “wrinkles.” Normal
“Functional Anatomy” discusses the reasons these disconcerting
changes and wrinkles occur so that a suitable plan of correction with
a BoNT can be initiated. Functional anatomy is stressed and com­
plemented by clinical photographs and detailed illustrations because
the only way a physician injector can utilize any type of BoNT prop­
erly is to have an in-depth understanding of how to modify the nor­
mal and exaggerated movements of facial mimetic muscles and other
potentially treatable muscles elsewhere in the body. When injections
of a BoNT are appropriately performed, desirable and reproducible
results without adverse sequelae are created. In the “Dilution” sub­
heading, ­suggestions are given on how much diluent can be added
to reconstitute a 100-unit vial of OnaBTX-A in order to arrive at
various preferred concentrations per fluid volume dilutions when
injecting certain muscles at different anatomical sites. The U.S. FDA-
approved manufacturer’s recommendation for the reconstitution of
a 100-unit vial of OnaBTX-A is to add 2.5 mL of nonpreserved nor­
mal saline. This approved and recommended dilution is for inject­
ing glabellar and lateral canthal frown lines only, since these areas
on the face are the only approved indications for the cosmetic use
of OnaBTX-A. However, when treating other areas of the face and
body for cosmetic purposes, albeit in an off-label, unapproved man­
ner, higher or lower dilutions of OnaBTX-A have proven to be more
suitable and clinically more effective, depending on the muscles
being treated. Options for “Dosing” are presented, with an emphasis
placed on what to do and what not to do when injecting OnaBTX-A.
Precise dosing and ­accurate injections of OnaBTX-A will dimin­
ish muscle movements of the face and body in a safe and reproduc­
ible way. Fastidious injection techniques are necessary to correct a
particular aesthetic problem reliably, predictably, and for extended
periods of time with any BoNT. “Outcomes” and results of differ­
ent injection techniques are discussed to avoid “Complications” and
adverse sequelae. Finally, how to inject a particular anatomical site
and its projected results are summarized in the list of “Implications
of Treatment”.
Controversial and remarkable treatments for non-surgical breast
augmentation for women and men are practiced by dermatologists
Francisco Atamoros Perez and Olga Marcias Martinez and discussed
in detail in Chapter 16. Their accumulated clinical evidence of the
efficacy of BoNT-A injections of the pectoral area is clearly presented
with an abundance of clinical illustrations.
Chapter 17, by a prominent and internationally well-known Korean
dermatologist, Kyle Seo, MD, discusses the Asian perspective of the
use of the different BoNTs currently available in his part of the world.
Insight into the East and Southeast Asian cultural aesthetic needs and
the Asian perception of aesthetics and beauty, is emphasized. He also
presents a detailed description of the racial differences in the anatomy
between Asians and Caucasians, which call for different indications
and variations in appropriate dosing and injection points of BoNT-A
treatments, necessary when treating Asian patients. He also provides
some practical guidelines for the innovative use of BoNT-A in facial
skin redraping and body muscle contouring injection techniques that
are currently very popular in the East.
Many appendices supplying material for procedural reference con­
clude this second volume.
It is extremely fascinating and encouraging to understand that the
cosmetic use of OnaBTX-A was initiated by the insight and convic­
tions of two astute and courageous physicians, an ophthalmologist
wife and her dermatologist husband. If it were not for the persistence
of Jean and Alastair Carruthers in promoting their serendipitous
observations, many other perceptive and insightful physicians would
not have had the opportunity or the confidence to learn more about
BoNT and its use in clinical aesthetic medicine. The challenge now
being passed onto the reader is that with knowledge of how to inject
a few drops of BoNT appropriately and safely, while treating patients
with compassion and professionalism, additional innovative and
ingenious uses of BoNT can be discovered, be they for cosmetic or
therapeutic purposes.
We are all indebted to those physicians who have treated and con­
tinue to care for patients with BoNT for therapeutic and cosmetic
purposes. Their commitment to the improvement of their patients’
health and well-being through the advancement of sound and
­effective medical care is commendable and truly appreciated.
Finally, particular recognition and a special expression of gratitude
is due to Kelly Heckler for her organizational skills and secretarial
expertise that facilitated the completion of this book.
Anthony V. Benedetto, DO FACP
Philadelphia, PA

xi
Acknowledgments
Many of the anatomical drawings not otherwise attributed (e.g., Figure 10.1) have base artwork from the Shutterstock archives and are
­reproduced with permission under licence; the annotations and overlays have been developed by the lead author of each chapter.

Taylor & Francis Taylor & Francis Group

105
Functional facial anatomy, proportions of beauty, and neuromodulation
Sebastian Cotofana
DEVELOPMENT
The muscles of facial expression are derived from the second pha­
ryngeal arch during embryologic development and thus receive their
motor innervation from cranial nerve VII, the facial nerve. The pri­
mary function of these muscles is to protect the facial orifices and the
organs located in their proximity from mechanical damage (orbicu­
laris oculi), from ingestion of harmful substances (orbicularis oris),
and to aid the uptake of food (levator anguli oris, levator labii supe­
rioris, depressor anguli oris, and depressor labii inferioris muscles)
and air (nasalis, levator alaeque nasi, depressor septi nasi muscles).
Previously important muscles for the movement of the ears, which
were used, for example, during hunting or defense, can be still found
as rudiments (e.g., the auricularis muscles).
During phylogenetic development, however, these muscles are
progressively involved in the externalization of internal conditions
and feelings (lat.: movere = emotions [= to move something out]),
that is, for the expression of emotions. This was increasingly used
for communication between individuals and for the coordination of
social groups. A study in chimpanzees has shown1 that the size of
facial motor nucleus can be positively correlated to the group size
and to the amount of time spent grooming, that is, social activ­
ity; indicating that the role of the facial muscles has been changed
from rudimentary needs (food uptake and breathing) towards
social interaction and group coordination. With the development of
speech another important function of the muscles of facial expres­
sion was established: articulation. The perioral muscles are crucial
in the formation of sounds due to their movement of the lips. These
developments should be considered when trying to interfere with
their primary function and effects of applied treatments should be
also seen in the light of phylogenetic development. (See Prologue by
N Jablonski in Volume 1.)
GENERAL FUNCTION
The muscles of facial expression are unique in their morphology as
well as in their function. Regarding their macroscopic and histologic
characteristics, muscles of facial expression do not contain an envel­
oping fascial layer, that is, epimysium, like most of the muscles in
the human body. The absence of an epimysium enables these mus­
cles to have a strong interaction with their surrounding tissues as no
gliding plane is present, as opposed to having a gliding plane which
reduces shear forces between neighboring structures for a friction­
less and energy-efficient movement. Due to the strong interaction of
the facial muscles with their surrounding tissues, distinct muscular
contractions result in a minute movement of the neighboring tissues
and most importantly the overlying skin. This is important for the
delicate positioning of the skin during facial expressions and minute
differences in contraction can result in an almost opposite effect, for
example, smiling versus expression of disgust.
Another morphologic characteristic of these muscles is that they
do not insert to bones, ligaments, or span joints to produce move­
ments important for locomotion. They rather insert into the over­
lying skin or are of circular shape with origin and insertion being
closely related. Therefore, the actions of the mimetic muscles cannot
be described according to the general anatomic standards, that is,
extension/flexion or abduction/adduction, but by elevation/depres­
sion with vertical, horizontal or diagonal movements resulting in
facial expression on contraction.
Interestingly, histologic investigations have suggested that the
muscles of facial expression have a reduced quantity of stretch recep­
tors (as compared to regular skeletal muscles) and thus some authors
have suggested that this is one of the reasons why the muscles of facial
expression present with flaccid paralysis after a stroke rather than
with spasticity. Recent studies revealed also that with aging the mus­
cles of facial expression increase their muscular tone and have thus a
reduced contractility. Facial exercises or the application of facial mus­
cular training devices were less effective.2
ACTION MECHANISMS OF BOTULINUM TOXIN
The muscles of facial expression are classified as striated muscle
fibers and are organized histologically by sequentially arranged sub­
units called the sarcomeres. Each sarcomere is formed by thin and
thick myofilaments and receives its depolarizing signal from a cho­
linergic neuromuscular synapse. The ratio of recruited muscle fibers
by one single lower motor neuron is 1: <100 whereas this ratio is 1:
>1000 for thigh or back muscles. In regular neuromuscular trans­
mission, an action potential is transmitted distally to the axon ter­
minal, where neurotransmitter molecules (here acetylcholine) are
stored in vesicles. On ion shift in the axon terminal, synaptic vesicles
fuse with the presynaptic membrane and the vesicles’ contents are
released into the synaptic cleft. On the postsynaptic plate, specific
receptors are present with the ability to bind the released neurotrans­
mitter molecules and to generate a new postsynaptic potential which
is then distributed across the muscle fiber and ultimately leads to
muscle contraction.
The mechanism of vesicle fusion in the axon terminal requires
the binding of SNARE (soluble N-ethylmaleimide-sensitive factor
attachment protein receptor) proteins that are expressed on both the
vesicle (V-SNARE) and on the inner side of the presynaptic mem­
brane (T-SNARE). Binding of these proteins to one another induces
their fusion and the release of the vesicles’ content into the synaptic
cleft. Without the binding of the V-SNARES to the T-SNARES, the
vesicles will not fuse with the presynaptic membrane resulting in a
persistent but reversible inhibition of neurotransmitter release.
Botulinum toxins (BoNT) are the most potent toxins known
to humankind: the lethal dose for humans is 1 µg/kg by the oral,
10–13 ng/kg by inhalation, and 1–2 ng/kg by the intravenous or intra­
muscular routes. In detail, these toxins consist of a heavy chain and
a light chain and there are seven known serotypes (A–G) of which
toxin A (BoNT-A) is used in the majority of cosmetic procedures. The
toxin light chain will cleave both the V-SNARES and the T-SNARES
leading to a temporary flaccid paralysis as the incoming signal cannot
be transmitted via the synaptic cleft to the muscle fiber.3
The application of BoNT-A in the proximity of a muscle will lead
to the binding of the botulinum toxin to specific receptors at the
presynaptic axon terminal of the supplying nerve, internalization of
the toxin into the axon, and activation of its endopeptidase activity
against the V- and T-SNARE proteins. Thus, BoNT-A applications
have to be applied locally and in proximity to the intended muscle in
order to induce the blockage of its neuromuscular transmission. After
intramuscular injection, the dose-dependent paralytic effect of BoNT
can be detected within 2–3 days. It reaches its maximal effect in less
than 2 weeks, lasts somewhere between 3 and 6 months and gradu­
ally begins to decline in a few months due to the ongoing turnover of
synapses at the neuromuscular junction.4
12

Botulinum Toxins in Clinical Aesthetic Practice
106
GENERAL FACIAL ANATOMY
The anatomy of the face can be best described as a layered concept.
This concept is based on the fact that facial structures are arranged in
specific layers, that is, in a specific depth within the face with the sur­
rounding structures providing rigid or soft boundaries. From super­
ficial to deep these layers are: skin (layer 1), superficial (subcutaneous)
fat (layer 2), superficial musculo-aponeurotic system (SMAS) (layer
3), deep fat (layer 4), and deep fascia/periosteum (layer 5). Once this
concept is taken into consideration the third dimension is accessible
and the question: “Where is the muscle?” is not precise enough to tar­
get the respective muscle during treatment. Moreover, the additional
question: “In which layer is the muscle?” must be answered to achieve
the best possible outcome for botulinum toxin applications.
Having in mind that the facial musculature (like any other struc­
ture in the human body) is prone to variations in location, size, and
course, individualized application patterns are of crucial importance.
Rigid applications “according to the book” are outdated and indi­
vidualized application schemes need to be applied. Facial wrinkles,
independently if dynamic or static, are to be understood as muscular
contractions of underlying muscles (accompanied by social, environ­
mental, and demographic influences) and that the vector of contrac­
tion is perpendicular to the observed facial wrinkle.
MOTOR BRANCHES OF THE FACIAL NERVE
The motor component of the facial nerve emerges at the stylomastoid
foramen at the base of the skull and enters the parotid gland from deep
and posterior. Within the parotid gland the nerve divides into 3–7
branches and its divisions are called parotid plexus. At the anterior
boundary of the parotid gland the nerve emerges between the super­
ficial and the deep part of the parotid gland and its branches course
toward the temple (temporal branches), in proximity to the zygomatic
arch (zygomatic branches), horizontally across the cheek (buccal
branches), along the inferior margin of the mandible (marginal man­
dibular branches) and inferiorly and anteriorly toward the neck (cervical
branches) (Figure 12.1). The branches are deep to layer 5, that is, deep
to the parotideomasseteric fascia at the level of the masseter muscle, but
change planes toward superficial at the level of the anterior boundary of
the masseter muscle. There the branches can be identified superficial to
the facial vein and within the roof of the facial-vein canal. From there they
distribute toward the respective muscles of facial expression and provide
motor supply by entering into the muscles from inferior and posterior.
In the temporal region, the temporal branches can be located
within layer 4, that is, deep to the superficial temporal fascia but
superficial to the deep temporal fascia; superior to zygomatic arch
and inferior to the inferior temporal septum.
In the midface, the branches are located deep to the superficial
musculo-aponeurotic system (SMAS).
In the lower face, the marginal mandibular branch can be identi­
fied in 100% of the cases superficial to the facial artery and vein when
crossing the mandible.
ARTERIES OF THE FACE
The face is primarily supplied by branches of the external carotid
artery and only in minor parts (e.g., the upper face) by branches
of the internal carotid artery. The major supplying arteries of the
external carotid artery are: the facial artery, transverse facial artery,
buccal artery, lingual artery, superficial and deep temporal arteries.
Branches of the internal carotid artery are zygomaticofacial artery,
zygomaticotemporal artery, dorsal nasal, supraorbital artery, supra-
and infratrochlear artery, and medial and lateral palpebral arteries.
One must be aware that the arteries display a huge variation in terms
of course and presence as compared to facial veins (Figure 12.2).
The facial artery courses anterior to the facial vein and can be
identified within the buccal space after crossing the mandible. At the
angle of the mouth the artery is connected to the modiolus via mus­
cular and ligamentous adhesions and lies deep to the muscles of facial
expression but superficial to the buccinator muscle. After giving off
the superior labial artery, the name of the vessel changes toward the
angular artery. The angular artery gives off branches to anastomose
within the SMAS with branches of the transverse facial artery which
accesses the SMAS via the McGregor’s patch. The angular artery
courses in the depth of the nasolabial sulcus medially and superiorly
within the deep pyriform space. Deep to the levator labii superioris
alaequae nasi muscle it courses superiorly at the lateral margin of the
nose, gives off connecting branches to the infraorbital arteries, and
pierces in general the orbicularis oculi muscle around the medial
canthus. There it connects with branches from the supratrochlear,
dosal nasal, medial palpebral, and supraorbital arteries.
The upper lip is supplied by the superior labial artery whereas the
inferior lip receives arterial blood supply from the inferior labial
artery, the horizontal mental artery, and from the mental artery.
In the temporal region, an anterior and a posterior branch of the
superficial temporal artery can be identified. The superficial temporal
artery emerges from the depth 1 cm anterior and 1 cm superior from
the tragus and courses imbedded within the superficial temporal fas­
cial toward the temple.
VEINS OF THE FACE
The veins of the face are in course and variation much more stable
than the facial arteries and thus can serve as excellent landmarks
(Figure 12.2). The blood flow is in general directed as the facial
venous vessels have valves with the exception of the angular vein.
Here the blood flow is not directed and thus venous blood can drain
both superiorly toward the superior ophthalmic and into the cavern­
ous sinus or inferiorly toward the facial vein and into the external
jugular vein. The facial vein crosses the mandible posteriorly to the
facial artery and deep to the marginal mandibular branch. It enters
the facial-vein canal, which is formed by the anterior and the poste­
rior lamina of the parotideomasseteric fascia. The vein is found ante­
rior to the masseter muscle where it gives off the inferior and superior
labial vein and the deep facial vein, which drains into the pterygoid
plexus. The vein can be identified anteriorly to the parotid duct, deep
to the facial nerve branches, deep to the zygomaticus major muscle,
and lateral to the infraorbital foramen. At this level, the vein courses
more superficial and can be found superficial to the levator labii
superiors alaeque nasi muscle and forms there the lateral bound­
ary of the deep nasolabial fat compartment. It also has connections
to the infraorbital veins at this level. The angular vein then courses
medially and forms the medial boundary of the deep lateral cheek fat
and of the suborbicularis oculi fat (SOOF). The distance between the
inferior orbital rim and the vein was measured to be in mean 4 mm
and this course corresponds to the nasojugal groove which represents
the inferior boundary of the tear trough. It is important to note that
the vein courses inferior to the tear trough and deep to the orbicu­
laris oculi muscle and only at the level of the medial canthus does it
change toward a more superficial position. There it connects with the
dorsal nasal, the supra- and infratrochlear, the supraorbital and the
central forehead veins.
FACIAL MUSCLES
Upper Face Region (Figure 12.3) (See Appendix 2)
Frontalis muscle
Origin: Epicranial aponeurosis
Insertion: Orbicularis oculi muscle complex

12.  functional facial anatomy, proportions of beauty, and neuromodulation
107
Innervation: Temporal branches of facial nerve
Vascularization: Supraorbital artery, supratrochlear artery, lacrimal
artery, anterior branch of the superficial temporal artery
Function: Elevation of the supraorbital skin and eyebrow
Depth: Layer 3
Characteristics: The muscle is the anterior part of the occipitofron­
talis muscle. Together with the temporoparietalis muscle, this
muscle complex is also called epicranius muscle. Approximately
2–3 cm superior to the upper margin of the superior orbital rim
the muscle is connected to the periosteum via the middle frontal
septum. Movements of the overlying skin during muscle contrac­
tion converge toward this septum. Interestingly, the location of
this septum correlates well with the location of the central fore­
head line, that is, the deepest horizontal forehead wrinkle. In
some individuals, wavy (as opposed to straight) forehead lines can
be observed. This is due to an increased muscle fascicle angle and
due to the presence of a midline aponeurosis. Histological anal­
yses have revealed that even in the midline aponeurosis muscle
fibers can be identified, underscoring the importance of central
neuromodulator applications.
(a)
(c)
(b)
2
3
4
5
1
Figure 12.1  Nerves of the face. (a) Dissection. (b) The facial nerve, five motor branches: 1, zygomatic; 2, temporal; 3, buccal; 4, marginal mandibular; 5, cervical. (c) The
trigeminal nerve, sensory branches (each emerging from the corresponding foramen): 1,supraorbital; 2,infraorbital; 3,mental. ([a] Courtesy of Ross University; dissection
by Attila Molnar.)

Botulinum Toxins in Clinical Aesthetic Practice
108
Orbicularis Oculi Muscle
Origin: Frontal process of the maxilla, anterior lacrimal crest, medial
palpebral ligament
Insertion: Lateral palpebral ligament, lateral palpebral raphe
Innervation: Temporal branch of facial nerve, zygomatic branch of
facial nerve
Vascularization: Facial artery, anterior branch of superficial temporal
artery, supraorbital artery, lacrimal artery, supra- and infratroch­
lear artery, infraorbital artery
Function: Closure of the eye lids, depression of the eyebrow, drainage
of lacrimal fluid
Depth: Layer 3 (Change of layer in the medial canthus—described as
Horner’s muscle at this point)
Characteristics: The orbicularis oculi muscle consists of an orbital
part, septal part and a preseptal part. The latter is described as
Horner’s muscle at the medial canthus and facilitates the drainage
of the lacrimal sack. The differentiation between the orbital and
septal part is represented by the orbital margin and the separating
(a)
(c)
11
10
9
8
6
5
4
3
1
2
7
(b)
7
15
14
10
12
11
9
17
6
5
4
3
16
2
1
8
13
Figure 12.2  Arteries and veins of the face. (a) Dissection. (b) Arteries: 1, facial; 2, horizontal mental; 3, inferior labial; 4, superior labial; 5, alar branch of facial artery; 6,
angular; 7, supraorbital artery; 8, dorsal nasal; 9, supratrochlear; 10, transverse facial; 11, lingual; 12, maxillary; 13, infraorbital; 14, anterior branch of superficial temporal
artery; 15, posterior branch of superficial temporal artery; 16, mental; 17, infratrochlear. (c) Veins: 1, central forehead; 2, supraorbital; 3, dorsal nasal; 4, lateral nasal; 5,
angular vein; 6, superior labral; 7, inferior labial; 8, facial; 9, retromandibular; 10, anterior branch of superficial temporal vein; 11, posterior branch of superficial temporal
vein. ([a] Courtesy of Ross University; dissection by Attila Molnar.)

12.  functional facial anatomy, proportions of beauty, and neuromodulation
109
structure there is the orbicularis retaining ligament. The orbital
part, however, can reach laterally and inferiorly into the midface
and in dedicated cases muscular distentions (Figure 12.3) are
identified, where fat from deeper structures can protrude. The
laterally observed contraction at the level of the lateral canthus—
also called “Crow’s feet”—are arranged in perpendicular orienta­
tion to the muscular contractions in this area.
Depressor Supercilii Muscle
Origin: Frontal process of the maxilla
Insertion: Skin in the medial third of the eyebrow and into the orbicu­
laris oculi muscle complex
Innervation: Temporal branch of facial nerve
Vascularization: Supra- and infratrochlear artery, supraorbital artery
Function: Medial and inferior movement of the eyebrow
Depth: Layer 3 (moving superficially from the medial third of the eye­
brow and radiating into the skin [Layer 1])
Characteristics: The depressor supercilii muscle can be regarded as the
fourth part of the orbicularis oculi muscle. This muscle is located in
the same plane as the orbicularis oculi muscle and a clear separation
between these two is almost impossible during gross dissections.
Corrugator Supercilii Muscle
Origin: Superciliary arch of the frontal bone
Insertion: Skin in the medial third of the eyebrow and into the orbicu­
laris oculi muscle complex
Innervation: Temporal branch of facial nerve
Vascularization: Supra- and infratrochlear artery, supraorbital artery
Function: Medial movement of the eyebrow
Depth: Layer 5 (emerging from the bone and inserting into skin in the
medial third of the eyebrow)
Characteristics: The corrugator supercilii muscle originates from the
bone medial to the supraorbital foramen. However, its innervation
reaches from the lateral side the muscle.
Procerus Muscle
Origin: Nasal bone, transverse part of the nasalis muscle
Insertion: Skin between the eyebrows (glabella), frontalis muscle
Innervation: Zygomatic branch of the facial nerve
Vascularization: Dorsal nasal artery, supra- and infratrochlear artery,
anterior ethmoidal artery
Function: Depression of the skin superficial to the glabella between
the eyebrows
Depth: Layer 5 (originating from bone and moving superficially
toward the area of the glabella and radiating into the skin [Layer 1])
Characteristics: The procerus muscle originates from the bone and
crosses all layers. In the central part of the muscle the dorsal nasal
artery and vein can be identified, whereas in its lateral part branches
of the angular vein, as well as of the supra- and infratrochlear
artery, and supraorbital artery are coursing in a vertical direction.
Its fibers are radiating into the superficial fatty tissue, that is, the
glabellar fat body, and are anchored there. The most cranial fibers
connect with the central part of the frontalis muscle and can pull
the central part of the forehead inferiorly.
The interaction of the frontalis muscle, orbicularis oculi muscle,
procerus, depressor, and corrugator supercilii muscle can be classi­
fied as the orbicularis occuli muscle complex in the periorbital region.
All muscles show their effect on the movement of the eyebrows as well
as the skin movement in this area. Also, the orbicularis oculi muscle
complex must be balanced against the cranial pull of the frontalis
muscle, which in turn is the only elevator of the eyebrow.
Midface Region (Figure 12.4): Nose (See Appendix 2)
Nasalis Muscle
Origin: Alveolar canine jugum, canine fossa
Insertion: Aponeurosis of the dorsal nose, skin of the nasal wing
Innervation: Zygomatic branch of facial nerve
Vascularization: Internal carotid: dorsal nasal artery, external nasal
artery, anterior ethmoid artery; external carotid artery: facial
artery, maxillary artery, lateral nasal artery, superior labial artery,
septal artery, alar artery
Function: Elevation of the nasal wings and nasal tip, opening of nasal
nares
Layer: Dorsal nose (layer 3, part of the superficial musculo-aponeu­
rotic system)
(a)
(b)
2
5
3
1
4
Figure 12.3  Muscles of the upper face. (a) Dissection; (b) muscles: 1, frontalis; 2, orbicularis oculi; 3, depressor supercilii; 4, procerus; 5, corrugator supercilii (deep to
orbicularis oculi). ([a] Courtesy of Ross University; dissection by Attila Molnar.)

Botulinum Toxins in Clinical Aesthetic Practice
110
Characteristics: The nasalis muscle is composed of a transverse and
an alar part. Contraction of the nasalis muscle leads to the forma­
tion of nasal lines, also called “bunny lines.”
Depressor Septi Nasi Muscle
Origin: Processus alveolaris incisivus
Insertion: Nasal septum
Innervation: Zygomatic branch of facial nerve, buccal branch of facial
nerve
Vascularization: Superior labial artery, septal artery, alar artery
Function: Depression of the wings and nasal tip
Depth: Layer 5 (variation: layer 3)
Characteristics: The depressor septi nasi muscle originates in certain
cases from the orbicularis oris muscle. On contraction, the muscle
reduces the lip-nose distance and thus creates the impression of a
short upper lip.
Levator Labii Superioris Alaeque Nasi Muscle
Alternative name: Angular head of the quadratus labii superioris
muscle
Origin: Frontal process of the maxilla, medial infraorbital margin
Insertion: Skin of the nasal wings, lateral part of the nasolabial sulcus,
medial part of the modiolus
Vascularization: Infraorbital artery, superior labial artery, external
nasal artery, angular artery
Function: Elevation of nasal wings and upper lip
Innervation: Zygomatic branch of facial nerve
Depth: At its origin layer 5, the further caudally the more superficial
(layer 1)
Characteristics: The muscle can be subdivided into a labial part (alter­
native name: infraorbital head of the quadratus labii superioris
muscle) and an alaequae nasi part. The latter is located more medi­
ally toward the nose whereas the labial part is located more later­
ally with its fibers inserting into the modiolus. The angular vein
can be identified superfial to this muscle whereas the infraorbital
foramen is located deep to this muscle.
Zygomaticus Major Muscle
Origin: Zygomatic bone (anterior to the zygomaticotemporal suture)
Insertion: Modiolus, orbicularis oris muscle, skin of the nasolabial
sulcus
Innervation: Zygomatic branch of facial nerve
Vascularization: Zygomaticofacial artery, anterior branch of superfi­
cial temporal artery, angular artery, infraorbital artery
Function: Supero-lateral movement of the lip, causes a deepening of
the nasolabial sulcus
Depth: At its origin layer 5, the further inferomedial the more super­
ficial (layer 1)
Characteristics: The origin of the zygomaticus major can be found in
close proximity to the McGregor’s patch, which also represents
the beginning of the zygomatic ligament. The zygomaticus major
muscle forms with its broad-based origin the lateral boundary of
the deep lateral cheek fat compartment. In its medial third the
muscle can be identified superficial to the facial vein and may thus
cause compression during contraction. Its terminal muscle fibers
radiate into the skin of the nasolabial sulcus and form the floor of
the superficial (subcutaneous) nasolabial fat compartment.
Zygomaticus Minor Muscle
Alternative name: Zygomatic head of the quadratus labii superioris
muscle
Origin: Zygomatic bone, medial to the zygomaticus major muscle
Insertion: Modiolus, orbicularis oris muscle, nasolabial sulcus
Innervation: Zyomatic branch of facial nerve
Vascularization: Zygomaticofacial artery, anterior branch of superfi­
cial temporal artery, angular artery, infraorbital artery
Function: Supero-lateral movement of the lip, causes a deepening of
the nasolabial sulcus
(a)
(b)
1
8
6
2
3
7
5
4
Figure 12.4  Muscles of the midface. (a) Dissection; (b) muscles: 1, nasalis; 2, nasal part of the levator labii superioris alaeque nasi; 3, labial part of levator labii superioris
alaeque nasi; 4, zygomaticus minor; 5, zygomaticus major; 6, risorius; 7, buccinator; 8, levator anguli oris (deep to all others except buccinator). ([a] Courtesy of Ross
University; dissection by Attila Molnar.)

12.  functional facial anatomy, proportions of beauty, and neuromodulation
111
Depth: At its origin layer 5, the further inferomedial the more super­
ficial (layer 1)
Characteristics: The zygomaticus minor muscle originates from the
zygomatic bone and its fibers intermingle with the fibers of the
orbital part of the orbicularis oculi muscle, which can be found
in layer 3. As the orbicularis oculi muscle is discontinuous in
some anatomical variations, the zygomaticus minor muscle can
be listed as a part of the orbicularis oculi muscle or even as a part
of the levator labii superioris muscle.
Levator Anguli Oris Muscle
Alternative name: Caninus muscle
Origin: Canine fossa, inferior to the infraorbital foramen
Insertion: Modiolus, orbicularis oris muscle
Innervation: Zygomatic branch of facial nerve
Vascularization: Infraorbital artery, angular artery, superior labial
artery
Function: Supero-medial movement of the lip and of the labial angle
Depth: At its origin layer 5, the further inferomedial the more super­
ficial (layer 1)
Characteristics: The levator anguli oris muscle originates inferior to
the infraorbital foramen and forms the floor of the deep medial
cheek fat compartment and the deep pyriform space.
Risorius Muscle
Origin: Masseteric fascia, SMAS, skin (very variable)
Insertion: Modiolus
Innervation: Buccal branch of facial nerve
Vascularization: Facial artery
Function: Lateral movement of the labial angle
Depth: Layer 5 (when originating from the parotideomasseteric
­fascia), layer 3 (when originating from the SMAS), layer 2 (when
originating from the subcutaneous tissue)
Characteristics: The risorius muscle displays a high variation regard­
ing origin and course and in some dedicated cases, it is absent
during gross dissections.
Buccinator Muscle
Origin: Alveolar process of the maxilla, buccinator crest, pterygo­
mandibular raphe
Insertion: Modiolus, orbicularis oris muscle
Innervation: Buccal branch of facial nerve
Vascularization: Buccal artery, lingual artery, facial artery
Function: Assisting during chewing via creating tension of the cheeks
Depth: Layer 6 (muscle is covered by extension of buccopharyngeal
fascia, which can be regarded as deep fascia)
Characteristics: The buccinator muscle can be subdivided into three
main muscle fascicle bundles: upper, medial, and lower, which
crisscross each other at the modiolus and thus form the deep
component (layer) of the orbicularis oris muscle. The parotid duct
pierces the muscle anterior to the masseter muscle, but poste­
rior to the facial vein. In its covering fascia, the juxtaoral organ
is embedded, which is postulated to have a function either as a
stretch receptor or as a neuroendocrine organ.
Masseter Muscle
Origin: Deep aspect of zygomatic bone (deep part) and inferior aspect
of zygomatic bone (superficial part)
Insertion: Lateral aspect of the ramus of the mandible (deep part) and
mandibular angle (superficial part)
Innervation: Masseteric nerve of mandibular nerve of trigeminal nerve
Vascularization: Maxillary artery
Function: Elevation and protrusion of the mandible
Depth: Layer 6 (deep to the parotideomasseteric fascia, which is con­
sidered layer 5)
Characteristics: The masseter muscle plays an important role in the
lateral shaping of the face and its volume contributes significantly
to the overall facial appearance. The branches of the facial nerve
run on its surface medially.
Lower Face (Figure 12.5) (See Appendix 2)
Orbicularis Oris Muscle
Alternative name: Incisivus labii superioris muscle/incisivus labii
inferioris muscle for its part originating at the upper and lower
jaw
Origin: Alveolar jugum caninus of the maxilla (superiorly) and of the
mandible (inferiorly)
Insertion: Same as origin and skin of the upper and lower lip
Innervation: Zygomatic branch of facial nerve, buccal branch of facial
nerve, marginal mandibular branch of the facial nerve
(a)
(b)
6
4
8
7
3
1
2
5
Figure 12.5  Muscles of the lower face. (a) Dissection; (b) muscles: 1, mentalis; 2, depressor labii inferioris; 3, depressor anguli oris; 4, platysma; 5, sternal part of the sterno­
cleidomastoid muscle; 6, clavicular part of the sternocleidomastoid muscle; 7, orbicularis oris; 8, modiolus. ([a] Courtesy of Ross University; dissection by Attila Molnar.)

Botulinum Toxins in Clinical Aesthetic Practice
112
Vascularization: Superior labial artery, inferior labial artery, horizon­
tal mental artery
Function: Closure of the oral cavity, internal torsion of the vermilion
Depth: Layer 3
Characteristics: The orbicularis oris muscle consists of a superficial
and a deep part. The deep part is formed by the fibers of the buc­
cinator muscle, whereas the superficial part is formed by the fibers
of the muscles of facial expression. The modiolus is the hypomoch­
lion of the peri-oral musculature as here a total of three layers of
muscles merge together to form a muscular pillar of 1 × 1 × 2 cm
in extent. The modiolus can be found 0.7–1.5 cm laterally to the
labial angle and spans from layer 2–6. The facial artery is firmly
attached to the modiolus, but can vary in its course along the
upper and lower lips with three potential positions: subcutaneous,
intramuscular, and submucosal.
Depressor Anguli Oris Muscle
Alternative name: Triangularis muscle
Origin: Inferior mandibular margin
Insertion: Modiolus, lower lip (lateral end)
Innervation: Marginal mandibular branch of facial nerve, buccal
branch of facial nerve
Vascularization: Inferior labial artery, horizontal mental artery, men­
tal artery
Function: Depression of the lower lip and labial angle
Depth: Layer 3
Characteristics: The depressor anguli oris muscle originates from the
bone in layer 5 but becomes more superficial toward its course
to the modiolus. The muscle can be identified superficial to the
depressor labii inferioris muscle and its lateral fibers merge with
those of the platysma (layer 3).
Depressor Labii Inferioris Muscle
Alternative name: Quadratus inferioris muscle
Origin: Inferior mandibular margin, but cranial to the depressor
anguli oris muscle and inferior to the mental foramen
Insertion: Modiolus, lower lip (lateral third)
Innervation: Marginal mandibular branch of facial nerve
Vascularization: Inferior labial artery, horizontal mental artery, men­
tal artery
Function: Depression of the lower lip
Depth: Layer 3
Characteristics: The depressor labii inferioris muscle can be identi­
fied deep to the depressor anguli oris muscle having a fiber direc­
tion perpendicular to the orientation of those of the depressor
anguli oris muscle. Medial to a vertical line passing through the
angle of the mouth the depressor labii inferioris muscle and lat­
eral to this imaginary line, the depressor anguli oris muscle can
be identified.
Mentalis Muscle
Origin: Alveolar jugum of the mandible inferior to the transverse
mental septum
Insertion: Skin of the chin
Innervation: Marginal mandibular branch of facial nerve
Vascularization: Inferior labial artery, horizontal mental artery, men­
tal artery
Function: Cranial movement of the skin of the chin, creating a promi­
nent labiomental sulcus
Depth: Layer 5 to layer 1
Characteristics: The mentalis muscle can originate as a two-headed or
one-headed muscle from the mandibule, and the difference in the
muscle morphology can be inspected by the presence of a men­
tal fovea, which is more prominent if a two-headed variation is
present.
Platysma (Figure 12.6)
Origin: Modiolus, subcutaneous plane with adhesions at the level of
the inferior mandibular margin
Insertion: Skin of the neck
Innervation: Cervical branch of facial nerve
Vascularization: Superficial branch of transverse cervical artery,
mental artery
Function: Depression of the labial angle, movement of the skin of the
neck
Depth: Layer 3
Characteristics: The platysma is continuous with the SMAS in the
midface and with the superficial temporal fascia in the upper face.
It is discontinuous in the midline which can be observed in the
aging neck or during forced muscular contractions. The longitu­
dinal bands of the neck result from adhesions to the overlying skin
but also from projections of the mandibular ligament and from
the submental septum.
REFERENCES
1. Burrows AM, Li L, Waller BM, Micheletta J. Social variables exert
selective pressures in the evolution and form of primate mimetic
musculature. J Anat 2016; 228(4): 595–607.
2. Cotofana S, Fratila AA, Schenck TL, Redka-Swoboda W, Zilinsky
I, Pavicic T. The anatomy of the aging face: A review. Facial Plast
Surg 2016; 32(3): 253–60.
3. Kumar R, Dhaliwal HP, Kukreja RV, Singh BR. The Botulinum toxin
as a therapeutic agent: Molecular structure and mechanism of action
in motor and sensory systems. Semin Neurol 2016; 36(1): 10–9.

4. Dressler D, Benecke R. Pharmacology of therapeutic botulinum
toxin preparations. Disabil Rehabil 2007; 29(23): 1761–8.
Figure 12.6  Platysma: dissection. (By courtesy of Ross University; dissection by
Attila Molnar).

113
Cosmetic uses of botulinum toxin A in the upper face
Anthony V. Benedetto
INTRODUCTION
In the United States, injections of botulinum neurotoxin (BoNT) to
diminish horizontal forehead wrinkle lines, glabellar (central brow)
frown lines and lateral canthal rhytides (crow’s feet) are the only
cosmetic and aesthetic indications approved by the Food and Drug
Administration (FDA) in the United States of America (USA).1–3
Injecting BoNT for cosmetic purposes in any other part of the face
or body is not approved in the United States (US) by the FDA and
therefore is considered off label use.1–3 It remains to be seen whether
the FDA and other governmental regulatory agencies of other coun­
tries will ever approve every single indication for which the BoNTs
have proven to be effective in clinical practice. The fact remains that
BoNTs are extremely reliable, nontoxic, and safe.1–6 BoNTs provide
reproducible results when administered as prescribed. Consequently,
BoNTs have now become a major component of the armamentarium
of any physician who practices aesthetic medicine in any capacity and
who wants to produce the best cosmetic results for their patients.
In the early 1980s, botulinum neurotoxin serotype A (BoNT-A),
known at that time as OculinumTM, was found to be effective for the
treatment of strabismus in humans as an alternative to surgery.7 Soon
thereafter, OculinumTM was acquired by Allergan, Inc. and renamed
BOTOX®. In 1989, BOTOX® was approved by the FDA for the
therapeutic treatment of strabismus and blepharospasm.7 By 2000,
BOTOX® was approved by the FDA for the therapeutic treatment of
cervical dystonia. In April 2002, the FDA approved BOTOX® for the
cosmetic treatment of glabellar frown lines. This resulted in the man­
ufacturer’s redesignation of the additional brand name of BOTOX®
Cosmetic.1 Both BOTOX® and BOTOX® Cosmetic are exactly the
same product: they contain the same active ingredient in the same
formulation, are manufactured by identical methods, and are only
distributed under different names for different labeled indications
and usage. BOTOX® is to be used for therapeutic purposes, whereas
BOTOX® Cosmetic is to be used for cosmetic purposes.1,8
Subsequently, new and different formulations of BoNT-A other
than BOTOX® and BOTOX® Cosmetic were approved for use in the
US for both therapeutic and cosmetic purposes. The first of these was
DYSPORT®,2,9–11 which was approved by the FDA in May 2009 (see
Chapter 5 by Monheit and Highsmith). In July 2011, XEOMIN®, a
non-complexed BoNT-A was approved by the FDA for therapeutic
and cosmetic purposes3,12–14 (see Chapter 3 by Juergen Frevert).
To distinguish the current and future different formulations of
BoNT from one another without mentioning their trade names, the
FDA has assigned nonproprietary names, a type of “generic” name,
to the different formulations of the currently approved BoNTs.
(OnaBTX-A) was assigned to BOTOX® and BOTOX® Cosmetic, also
known as Vistabel® in certain countries in Europe, and Vistabex® in
Italy. AbobotulinumtoxinA (AboBTX-A) was assigned to DYSPORT®,
also known as Azzalure® in Europe and Reloxin® elsewhere.
IncobotulinumtoxinA (IncoBTX-A) was assigned to XEOMIN®, oth­
erwise known as XEOMEEN® in Belgium and Bocouture® in Europe
and elsewhere. Botulinum neurotoxin type B (BoNT-B) known
as Myobloc® in the United States and Neurobloc® in Europe was
given  the designation of RimabotulinumtoxinB (RimaBTX-B) (see
Chapter 5). Other BoNTs currently available for use in other parts of
the world are discussed in Chapter 6 by Andy Pickett.
Chapters 13 through 15 discuss cosmetic injections of BoNT for
the face and body. It is of particular importance to understand that
in order to avoid ambiguity and confusion with the injection of
appropriate and effective doses of BoNT, any reference to BoNT-A in
these three chapters will indicate specifically BOTOX® Cosmetic and
explicitly onabotulinumtoxinA or OnaBTX-A. The reason for this is
not preferential usage by the author, but because OnaBTX-A was the
first BoNT-A to be used for cosmetic purposes worldwide, and for
many years a multitude of patients have been treated with OnaBTX-A
before any of the other BoNT-As were available. Consequently, most
of the patients illustrated in these next three chapters were treated
with OnaBTX-A with the preferred dosages indicated. Therefore, for
the sake of clarity and uniformity, all dosage units specified through­
out Chapters 13 through 15 are expressed in units of OnaBTX-A.
Some may criticize the “cookbook” approach to Chapters 13
through 15. This systematic detailing of why, where, and how much
OnaBTX-A to inject in a particular area of the face and body, however,
is necessary to understand when correcting a certain aesthetic prob­
lem, and, therefore, was done intentionally. Moreover, it is important
to note that the face is the only area of the body where there is no deep
subcutaneous membranous fascia beneath the skin, thus allowing
slips of muscle fibers that are attached to the facial skeleton at their
origin to insert directly into the undersurface of the skin. But not all
facial muscles have their origins attached to bone. Some arise from
aponeuroses, but then they still insert onto the undersurface of the
skin. Consequently, when these muscles contract, they move the skin
of the face, producing folds and wrinkles always in a perpendicular
orientation to the direction of muscle contraction. Nowhere else in
the body are there similar types of muscles that contract voluntarily
or involuntarily, pulling on the skin and expressing an emotion.
The face can be divided topographically into three segments using
anatomical and cosmetic unit boundaries: the upper, mid, and lower
part of the face. In these segments of the face there are either single
or multiple muscles, that when contracted, move mostly in one direc­
tion. Depending on their location on the face and the anatomic posi­
tion of their fibers, these mimetic muscles can move the skin in an
upward, oblique, or downward direction. For example, this allows
one to either raise or lower the eyebrows, smile or frown, open or shut
the eyes, and so on. This difference in the direction of skin move­
ment is done by muscles in a complementary, opposing fashion, that
is, by elevating (levator) or lowering (depressor) muscles. These com­
peting movements by agonistic or antagonistic muscles contracting
intentionally or unintentionally cause horizontal, radial, or vertical
wrinkling of the face. Consequently, nonverbal communication can
be expressed with the slightest contraction of one or a combination
of facial muscles (hence the designation “mimetic facial muscles”).
The reader must never lose sight of the fact that every single indi­
vidual patient is different and he or she should never be treated in an
identical fashion without justification. These Chapters 13 through 15
strive to provide both the learning and experienced physician injec­
tor, the rationale for why and how a patient should be treated with
a particular dose of OnaBTX-A in one area or another for a distinct
and reproducible outcome. The reader also must understand that the
explicit injection techniques, described with their indicated preferred
dosages of OnaBTX-A, are only the author’s perception of a given aes­
thetic problem. The reason for the particular pattern of wrinkles and
the interpretation of a potential solution is this author’s approach to
the management of that specific problem for that particular patient,
who may or may not present again in the future in exactly the same
13

Botulinum Toxins in Clinical Aesthetic Practice
114
way. Therefore, when a physician is evaluating a patient prior to a treat­
ment with a BoNT, it does not matter if the patient has or has never
been treated previously with BoNT. The physician should approach
that patient as if he or she were receiving BoNT for the very first time.
Prior to commencing with injections of a BoNT, the physician must
evaluate the patient’s current aesthetic problem completely and have
a comprehensive understanding of the patient’s current concerns. The
physician injector should not necessarily rely on past treatment dos­
ing or on instructional photographs that address injection techniques
and dosing for similar problems. With a substantial understanding of
functional anatomy, the physician injector should be flexible enough
to evaluate correctly and treat appropriately the patient’s concerns and
specific offending changes which are visible at the time of presentation.
An expert injector utilizes BoNT to improve a patient’s excessively
dynamic muscle movements—thus treating the patient, not a picture.
The “before and after” clinical photographs of patients treated with
OnaBTX-A presented in Chapters 13 through 15 are pictures not of
study subjects, but of actual patients treated on a regular basis with
effective and different doses of OnaBTX-A in a long-standing der­
matologic clinical aesthetic practice. Hence, the reason for the lack
of standardization in the quality of the photographs. These before-
and-after clinical photographs are presented here only as examples
of reasonably acceptable clinical outcomes. The reader in turn, after
some personal experience with treating patients, should be able to use
these examples of injection techniques and treatment outcomes to
develop a preferred approach with his or her own personal injection
techniques and produce comparable results when treating patients
with similar clinical problems.
It is extremely important to understand that the specific units and
dosages of BoNT-A discussed in Chapters 13 through 15 are only for
OnaBTX-A (i.e., BOTOX® Cosmetic) unless explicitly stated oth­
erwise. The same number of units specified in detail in these chap­
ters for OnaBTX-A should absolutely not be used with an identical
unit dose of another source or manufacturer, to treat patients with
BoNT-A, even if a dose ratio of equivalency is provided as being
1:1.1 The confusion with dose equivalencies using OnaBTX-A as the
standard to which, regardless of serotype, all other BoNTs are mea­
sured, will only become more apparent and less reliable when differ­
ent formulations of BoNT-A or other BoNT serotypes are utilized in
the future.15,16 The reason for this interchangeable indecipherability
of dosing of the different brands of BoNTs is because currently the
proprietary cell-based potency assay used by Allergan is different
from other manufacturers’ proprietary potency assays of their own
BoNT and varies according to vehicle, dilution scheme, and labora­
tory protocols. Therefore, when using any type of BoNT including
OnaBTX-A (i.e., BOTOX® Cosmetic), it is imperative that one learns
how to administer that particular brand of BoNT independently of
any conversion ratio because individual muscles may respond in a
distinctly different manner to certain formulations and specific sero­
types of BoNT (see Appendix 1).15 Understanding the pharmacoki­
netics and pharmacodynamics of BoNT is still only in its early stages,
and the possibilities for future developments are limitless17–19 (see
Chapter 2 by Mitchell Brin).
In 2002, the muscles of the central brow or “glabellar complex”
were the first muscles of the face or body into which OnaBTX-A could
be injected for cosmetic purposes that were approved in the United
States (US) by the FDA.1 Then in 2013, the FDA approved injections
of OnaBTX-A for the cosmetic reduction of lateral canthal wrinkles
or “crow’s feet.”1 In 2017, OnaBTX-A was approved by the FDA for the
temporary reduction of moderate to severe forehead wrinkles lines.
Treatment of all other muscles in any other part of the face or body
with injections of OnaBTX-A or any other BoNT for cosmetic reasons
is done solely and expressly in an off-label, non-approved manner.
CENTRAL BROW (GLABELLAR) FROWN LINES
Introduction: Problem Assessment and Patient Selection
The area most frequently treated with BoNT is the central brow or
glabella and its frown lines.20–26 On the skin surface, the glabella is
the space between the eyebrows. There are four depressor muscles
of the brow that cause the horizontal and vertical creases of the gla­
bella (Figure 13.1). These muscles allow one to squint to protect the
eyes from projectiles, gusts of air, and the elements (i.e., glaring light,
wind, dust, sand) by lowering the eyebrows and ­adducting them medi­
ally. However, resting hyperkinesis of these depressor muscles can
cause persistent, unintentional adduction and lowering of the medial
aspect of the eyebrows, causing vertical and horizontal ­wrinkles
between the eyes. This central brow frowning during moments of
intense concentration, for example, can be misinterpreted by oth­
ers as a veritable frown, which usually expresses negative feelings of
concern, fatigue, disappointment, frustration, anger, pain, suffering,
advanced age, and so on. (Figure 13.2a). Weakening the four depres­
sors of the glabella with injections of BoNT can raise and slightly
abduct the eyebrows and virtually eliminate the frown lines of the
glabella. This allows a person to appear more relaxed, expressing a
positive demeanor, even when in reality one might be ­frowning and
attempting to convey a negative sentiment (see the Prologue from
Nina Jablonski) (Figure 13.2b and c). An elevated brow generally
expresses a positive attitude, whereas a depressed brow is indicative
of a negative one. In addition, low-set eyebrows that progressively
appear with age, eventuate in the formation of upper eyelid and
­lateral canthal hooding (Figure 13.3). Arched or peaked eyebrows
usually are more attractive in women (Figure 13.2c), whereas men
in general possess more horizontal eyebrows (Figures 13.4 and 13.5).
However, be aware of women who pluck or have had permanent tat­
tooing of their eyebrows, because the natural position of their brows
may be altered (see Figure 13.42).
The brow has both static qualities of beauty and dynamic quanti­
ties of expressiveness that change with advancing age. As one ages,
1
2
3
4B
4A
Figure 13.1  The upper third of the face consists of a single brow elevator (the fron­
talis) and four brow depressors: 1, procerus; 2, depressor supercilii; 3, corrugator
supercilii (its path underlying orbicularis oculi is shown here); 4A palpebral and
4B orbital fibers of orbicularis oculi. (See Appendix 2—muscle attachments.)

13.  cosmetic uses of botulinum toxin a in the upper face
115
the skin of the face and the rest of the body become inelastic and
redundant. In the periorbital area, the skin of the eyebrows and fore­
head becomes lax and can drop inferiorly to lie over the superciliary
bony ridge of the brows. This is recognized as brow ptosis of varying
degrees of severity. Brow ptosis can alter the shape and position of the
eyebrows, thereby compromising a person’s youthful appearance and
aesthetic attractiveness.
Trindade de Almeida et al. have classified glabellar frown lines into
five distinct patterns27 (see Figures 13.20 through 13.24). Although
the muscular anatomy is by and large alike in most patients, indi­
vidual skeletal morphology and idiosyncratic muscular movements
can produce unique variations in the pattern of wrinkles in the gla­
bellar area during intentional animation and spontaneous expres­
sion. The same is true anywhere else on the face for exactly the same
(a)
(b)
(c)
Figure 13.2  (a) A 53-year-old patient with unintentional frowning during intense concentration. An OnaBTX-A treatment was subsequently given. (b, c) 3 weeks after
OnaBTX-A injections in the forehead and glabellar area seen here (b) with and (c) without frowning.
Figure 13.3  Low set eyebrows and upper eyelid and lateral canthal hooding in a
59-year-old patient.
(a)
(b)
Figure 13.5  (a) A 28-year-old patient with relatively flat eyebrow arches before treatment. (b) After treatment with strategically placed OnaBTX-A, the eyebrows are
elevated and arched. Note the right eyebrow also is slightly lifted and more symmetrical with the left.
Figure 13.4  The ideal eyebrows for a man are less arched and lower set than a
woman’s.

Botulinum Toxins in Clinical Aesthetic Practice
116
reasons. The differences in glabellar wrinkle patterns indicate that
the strength of each of the four glabellar muscles are not identical
or uniform in size and strength in every patient and one set of mus­
cles may be stronger or weaker than its codepressor set of muscles.
Their response to neurostimulation also is uniquely different in every
individual. Therefore, the pattern of glabellar frowning is dependent
on which muscles are idiosyncratically stronger or weaker, and the
injected dose of OnaBTX-A must vary accordingly. Some glabellar
wrinkle patterns are observed more frequently than others according
to Trindade de Almeida et al.27
Functional Anatomy of the Central Brow (Glabella)
(See Appendix 2)
On the skin surface, the center of the brow, that is, the space between
the eyebrows is referred to as the glabella. In the area of the central
brow or glabella in some individuals, both vertical and horizontal
lines may develop, which frequently can project unintended nega­
tive social cues when one frowns. The bony glabella is the smooth,
flat, triangular elevation of the frontal bone superior to the nasal
radix positioned between the two superciliary ridges or arches.
Contracting any of the mimetic muscles of the face will cause wrin­
kling of the skin perpendicular to the orientation of those muscle
fibers and in the direction of their movement. The muscles that pro­
duce the vertical lines of the glabella do so because their fibers are
oriented more or less horizontally and they move in a horizontal
direction when contracted. They are the corrugator supercilii and
the adjacent medial horizontal fibers of the upper eyelid orbicularis
oculi.28–30 The horizontal lines between the eyebrows across the root
and bridge of the nose result from the contraction of the vertical
fibers of the “medial” brow depressors, which move in a vertical
direction when contracted. They are the procerus, depressor super­
cilii, and the adjacent medial vertical fibers of the orbicularis oculi
(Figure 13.1). All four brow depressor muscles, corrugator superci­
lii, orbicularis oculi, depressor supercilii, and procerus oppose the
contractions of the single brow levator muscle, the frontalis, in an
agonistic/antagonistic fashion which is functionally characteristic
of all the mimetic muscles of the face and anterior aspect of the neck
(Figure 13.1).
The corrugator supercilii is a small, pyramidal, deeply situated
paired muscle that arises from the frontal bone just inferior to the
medial aspect of the bony superciliary arch approximately 4 mm lat­
eral to the nasion31,32 (Figure 13.6). The nasion is the point of junc­
ture of the nasofrontal bony sutures with the internasal bony sutures
(Figure 13.7). Clinically, the nasion can be palpated as the center of
the concavity at the nasal radix (or root). The corrugator supercilii
lies directly against the frontal bone just beneath the interdigitating
muscle fibers of the superior orbicularis oculi, procerus, depressor
supercilii, and frontalis medially and travels upwardly and laterally
at an oblique angle of approximately 30°, to emerge from beneath the
interdigitating fibers of the frontalis and superior orbicularis oculi
and inserts underneath the skin into the soft tissue and dermis above
the middle of the eyebrow in the vicinity of the midpupillary line
and the supraorbital notch. The insertion point of the corrugator is
approximately 4.2–4.5 cm lateral to the midline and is often seen as a
dimple in the skin just above the medial brow (“corrugator dimple”)
(see Figure 13.8).
In anatomical dissections, the medial aspect of the corrugator
can be seen partially interdigitating with the frontalis superiorly,
procerus medially, and orbicularis oculi inferiorly.29,33 The bulk
of the corrugator supercilii usually is found overlying the inferior
aspect of the superciliary arch (Figure 13.7).31 Anatomic studies have
­demonstrated that the thickest portion of the belly of the corruga­
tor is at or just above a horizontal plane drawn through the mid­
dle of the eyebrow and approximately 2.0–4.0 cm from the nasion
(Figures 13.6 and 13.7).28,29,31–35 In some individuals the corrugator
can be shorter and more oblique or even bifid with a transverse and
an oblique head,33 which is one of the reasons why there are differ­
ent patterns of glabellar frown lines27 (see the frown lines in Figures
13.20 through 13.26). The supratrochlear neurovascular bundle
passes through the corrugator supercilii, while the supraorbital nerve
runs underneath the muscle and divides into two upward running
branches: the medial superficial and the lateral deep nerve branches.
1
(a)
(b)
1
Figure 13.6  (a) The corrugator supercilii lies on the bone and deep beneath the other glabellar muscles; its course is shown here. (See Appendix 2—muscle attachments.)
(b) The origin and insertion of the corrugators.

13.  cosmetic uses of botulinum toxin a in the upper face
117
The supraorbital artery and vein travel alongside the deep branch of
the supraorbital nerve.29
The orbicularis oculi is a thin, broad, flat muscle whose fibers
form a concentric ring over the eyelids and around the orbit. This
sphincteric muscle can be divided into three parts. The outermost
fibers of the orbicularis oculi are called the orbital portion of the
orbicularis oculi. The orbital orbicularis oculi arises from the
bony structures of the lateral nose and medial orbit, including the
medial canthal ligament. Its fibers then run superiorly and inferi­
orly, forming a wide sphincteric ring surrounding and extending
beyond the edges of the bony orbital rim and also into the eyelids
(Figure 13.9).28–30 A portion of the medial aspect of the orbital orbi­
cularis oculi, whose fibers have a more distinctly vertical orienta­
tion, is occasionally referred to as the “depressor supercilii” by some
authors (Figure 13.10).33,36 Contraction of the medial aspect of the
orbital orbicularis oculi lowers the eyebrow downward and medi­
ally and slightly depresses the lateral aspect of the brow. The inner
portion of the orbicularis oculi which overlies the eyelids is identi­
fied as the palpebral portion of the muscle. The palpebral orbicularis
oculi is further subdivided into the preseptal and pretarsal portions
(Figure 13.10).28–30 Contraction of the palpebral orbicularis oculi
approximates the upper with the lower eyelids, either deliberately
or involuntarily.
The horizontal lines of the glabella and nasal root are produced
by the contraction of the vertically oriented fibers of the procerus,
depressor supercilii, and the medial vertical fibers of the orbital
orbicularis oculi. These three muscles also are referred to as the
“medial brow depressors.”33
The procerus is a thin (≤1 mm thick), paired muscle, pyramidal
in shape and centrally located in the midline of the glabella between
the two eyebrows. It overlies the nasion and the bony origin of the
corrugator supercilii. Inferiorly at its origin, the paired muscle bellies
of the procerus are joined together but can separate in the form of a
V superiorly at their attachments into the skin.29 The shape, size, and
strength of the procerus will determine the different types of frown
lines that are created across the nasal radix (see de Almeida’s glabel­
lar frown lines, Figures 13.20 through 13.26). Its location 2–4 mm
beneath the surface of the skin makes it an easy target for injections
of BoNT32 (Figure 13.10). The procerus arises from the fascial apo­
neurosis attached to the periosteum covering the lower caudal part of
the nasal bridge (i.e., the upper portion of the nose overlying the nasal
bone), the perichondrium covering the upper cephalic part of the
upper ­lateral nasal cartilages, and the aponeurosis of the transverse
part of the nasalis. It inserts superiorly into the skin and subcutane­
ous tissue at the nasal radix and lower part of the forehead between
the two ­eyebrows. Superiorly, muscle fibers of the upper border of the
procerus also interdigitate with muscle fibers of the lower central fron­
talis. Inferiorly, muscle fibers of the procerus interdigitate with fibers
of the transverse nasalis. Laterally, the procerus interdigitates with
the corrugator supercilii, depressor supercilii, and the medial fibers
of the orbital orbicularis oculi. Contraction of the procerus pulls the
medial aspect of the eyebrows downward, creating the horizontal
O
B
(a)
(b)
I
X
O
B
I
X
Figure 13.7  The corrugator supercilii. (a) Skull with view of the corrugator supercilii superimposed with letters. The thickest part of the belly of the muscle is approximately
2.0 cm from the nasion. (b) A patient with representation of corrugator supercilii drawn in red with superimposed lettering. Abbreviations: X, naison; O, origin; B, belly;
I, insertion of corrugator supercilii.
(a)
(b)
Figure 13.8  (a) Injection just above the middle of the eyebrow where the lateral aspect of the corrugators insert into the undersurface of the midbrow, just medial to the
supraorbital notch or midpupillary line. (b) Note the obvious dimpling of the skin as the patient forcibly frowns.

Botulinum Toxins in Clinical Aesthetic Practice
118
frown lines across the root and bridge of the nose. Anatomic studies
also have demonstrated that the procerus can be longer in women
than in men and, at times, bifid similar to the frontalis.29,34
The depressor supercilii is considered by many a component
part of the medial, vertical fibers of the orbital orbicularis oculi
(Figure  13.10).28–30,34 Yet others consider it a separate and distinct
muscle from the orbicularis oculi and corrugator supercilii.33,36 The
depressor supercilii is a small, vertically oriented muscle that has been
found to originate directly from bone as one or two distinct muscle
heads from the frontal process of the maxilla roughly 2–5 mm below
the fronto-maxillary suture line, and the nasal process of the frontal
bone slightly posterior and superior to the posterior lacrimal crest.
Clinically, the depressor supercilii can be located approximately
10–15 mm above the medial canthal tendon.36 In cadaver dissec­
tions where the depressor supercilii originated as two separate heads,
the angular vessels passed in between the two bundles of muscles.
In cadavers where there was only one muscle head originating at the
medial canthus, the angular vessels were found coursing anteriorly
to the muscle before traveling deeper into the glabellar area.29 The
depressor supercilii then passed vertically upward and over the origin
of the corrugators to insert into the undersurface of the skin at the
medial aspect of the eyebrow, approximately 13–16 mm superior to
the medial canthal tendon. It overlies the corrugator supercilii and
the medial aspect of the orbital orbicularis oculi, but interdigitates
with some of the more superficial fibers of the orbital orbicularis
oculi.28,31,34 Not only does it help move the eyebrow downward and
close the eyelid, but the depressor supercilii also participates in the
functioning of the physiological lacrimal pump by compressing the
lacrimal sac (see page 174).
Opening and shutting the eyes is partially accomplished by the
contraction of the accessory muscles of the upper eyelid: one is a
cholinergic, striated muscle, the levator palpebrae superioris; the
other is an adrenergic, nonstriated, smooth muscle called the supe­
rior tarsal muscle of Müller. The levator palpebrae superioris is the
main retractor of the upper eyelid. It is a thin, flat, triangular sheet
of striated muscle originating at the apex of the bony orbit at the
common tendinous ring or annulus of Zinn on the lesser wing of the
sphenoid behind the globe and just above the origin of the superior
rectus (Figure 13.11a).28,30 The levator palpebrae superioris is posi­
tioned above the superior rectus as they both pass over the superior
aspect of the eyeball within the bony orbit. Approximately at the level
of Whitnall’s transverse suspensory ligaments, the superior rectus
attaches to the superior aspect of the globe at the level of the superior-
conjunctival fornix, while the levator palpebrae superioris continues
anteriorly as a wide aponeurosis. As the aponeurosis continues for­
ward, some of its tendinous fibers attach to the anterior surface of the
tarsus, and the rest of the fibers pass in between the muscle fibers of the
pretarsal orbicularis oculi and attach to the undersurface of the eyelid
skin.28,30 Its tendinous attachments in the upper eyelid are responsible
for the formation of the superior eyelid crease (Figure 13.11a).
Dilution for Injecting the Central Brow (Glabella)
(See Appendix 3)
Different clinicians have their favorite patterns of injecting the gla­
bella with varying doses of different concentrations of OnaBTX-A.
The manufacturer’s package insert recommends reconstituting
the 100 U vial of OnaBTX-A with 2.5 mL of unpreserved normal
saline, thus yielding 4 U of OnaBTX-A for each 0.1 mL of solution.1
However, since the brow depressors interdigitate with each other
in close proximity in a very small and confined area, it is extremely
important to inject accurately precise amounts of OnaBTX-A in this
area. Therefore, many seasoned injectors still reconstitute the 100 U
vial of OnaBTX-A with only 1 mL of normal saline. This provides 1 U
of OnaBTX-A in every 0.01 mL of solution, which is easily injected
using a 0.3 mL Becton-Dickinson insulin U-100 syringe with a
31-gauge needle directly attached (Becton, Dickinson and Company,
Franklin Lakes, NJ).37 The advantage of using an insulin syringe is
that the needle is directly swaged onto the hub of the syringe barrel,
so there is little or no additional wastage of product in the hub of the
needle or in the neck of the syringe (Figure 13.12). In addition, each
1
2
Figure 13.10  The depressor supercilii is the diminutive muscle of the glabella.
The procerus is the midline, deep muscle of the glabella. 1, procerus; 2, depressor
supercilii. (See Appendix 2—muscle attachments)
1
2
3
4
Figure 13.9  The orbicularis oculi has different subdivisions and interdigitates with
the other depressors and elevator of the glabella: 1, depressor supercilii; 2, orbicu­
laris oculi, orbital portion; 3, orbicularis oculi, palpebral portion preseptal; 4, orbi­
cularis oculi, palpebral portion, pretarsal. (See Appendix 2—muscle attachments)

13.  cosmetic uses of botulinum toxin a in the upper face
119
unit line marked on the syringe barrel corresponds to 0.01 mL or 1 U
of OnaBTX-A when a 100 U vial of OnaBTX-A is reconstituted with
1 mL of saline. In this way, only minimal volumes of OnaBTX-A will
be needed to produce the desired cosmetic results. Moreover, most
practitioners now have switched to using preserved saline with 0.9%
benzyl alcohol.38–41
Dosing: How to Correct the Problem (See Appendix 4)
(What to Do and What Not to Do) When Treating the
Central Brow (Glabella)
The pretreatment evaluation should include examining the patient at
rest and in full motion. Lightly palpate the muscles of the glabellar
area with the palmar surface of the fingertips of the nondominant
hand as the patient squints and frowns. This will help determine
the location, size, and strength of the individual muscles of the gla­
bella (Figure 13.1). A frequently used and standardized technique for
treating the glabella is to inject OnaBTX-A into five different sites
with doses that range anywhere from 4 to 10 U or more at each site
(Figure 13.13).16,41–43 Electromyographic guidance in this area has
not particularly improved treatment outcomes because these facial
muscles are superficial and easily localized by palpation and topo­
graphical landmarks.3,21,34,44
Patients who possess thinner, less sebaceous skin with finer wrin­
kles and shallower skin furrows and folds that can be spread apart and
reduced with the fingers (“glabellar spread test”) seem to have better,
longer-lasting results.45 There are, however, some patients who are
7
1
2
3
4
5
6
8
9
10
11
12
13
(a)
(b)
6
7
1
2
3
4
5
8
9
10
(c)
6
1
2
3
4
5
7
8
9
10
11
Figure 13.11  (a) Close-up view of the upper eyelid anatomy and muscle attachments. The levator palpebrae superioris is the main retractor of the upper eyelid; it is a striated
muscle. Mueller’s superior tarsal muscle is not striated, but a smooth muscle. 1, orbicularis oculi (orbital); 2, levator aponeurosis; 3, orbicularis oculi (preseptal); 4, orbi­
cularis oculi (pretarsal); 5, levator aponeurotic insertion into orbicularis; 6, levator aponeurotic insertion into superior tarsus; 7, Whitnall’s ligament; 8, levator palpebrae
superioris; 9, common sheath; 10, superior rectus; 11, superior conjunctival fornix; 12, superior tarsal muscle; 13, post-aponeurotic space. (b) Anterior view of the upper
orbit with the attachments of the levator aponeurosis and lower lid retractors. 1, pre-aponeurotic fat pad; 2, lacrimal gland; 3, lateral horn of levator aponeurosis; 4, leva­
tor aponeurosis inserting into superior tarsus; 5, lateral canthal tendon; 6, levator muscle; 7, Whitnall’s ligament; 8, medial horn of levator aponeurosis; 9, medial canthal
tendon; 10, lower lid retractors inserting into inferior tarsus. (c) Anterior view of the orbit showing the complexity of the vascular arcades and other vascular structures. 1,
supra-orbital artery and vein; 2, tarsal arcade upper lid; 3, lacrimal artery; 4, lateral palpebral artery; 5, tarsal arcade lower lid; 6, frontal vein; 7, supratrochlear artery; 8,
medial palpebral artery; 9, angular artery and vein; 10, facial artery and vein; 11, infraorbital artery and vein.

Botulinum Toxins in Clinical Aesthetic Practice
120
more difficult to treat because they are less responsive to the effects of
OnaBTX-A. In this group of patients who are more difficult to treat,
there is one type of patient who possesses thick sebaceous skin with
deep, intractable wrinkles whose furrows are difficult to pull apart with
the fingers. Usually these turn out to be men and sometimes women
who spend a lot of time outdoors or constantly in front of a computer
screen. The other type of patient is the one who possesses the inelas­
tic, redundant skin seen with dermatochalasis and whose furrows also
are deep but very easy to pull apart. These patients characteristically
are older (>65–70 years old) and unfortunately are not ideal candi­
dates for glabellar chemodenervation. Typically, in these patients, after
having OnaBTX-A injected with impeccable technique, the resultant
relaxation of the glabellar muscles causes a drop in the brow and in-
folding of the inelastic, redundant glabellar skin. Consequently, brow
ptosis and persistent frown lines and wrinkles are the only outcome,
even if higher doses of OnaBTX-A are subsequently injected.
Generally, glabellar frown lines in women can be satisfactorily
treated with a total dose of about 20–30 U of OnaBTX-A injected into
the standard five injection sites (Figure 13.14).46–48 Men, on the other
hand, usually require a significantly higher dose of OnaBTX-A (40–
80 U) injected at seven or more sites across the glabella and medial
brow to produce a reasonable effect that lasts at least 3–4 months
(Figure 13.15).49–53 When glabellar lines are deeper, longer, or thicker
on one side of the midline, that set of medial brow depressor muscles
(e.g., procerus, depressor supercilii, and medial aspect of the orbital
orbicularis oculi) should receive a slightly higher dose of OnaBTX-A
than the medial brow depressors on the contralateral side. Especially
when treating men and those patients who have the “V” and deep
“parallel lines” patterns of glabellar wrinkles (see Figure 13.21), the
two additional injection points can be given along with the standard
five injection points to reduce these deep glabellar lines effectively
(Figure 13.13). The two additional injections usually are given super­
ficially as one injection over the midpupillary line, bilaterally, which
is in the vicinity where the lateral fibers of the corrugator superci­
lii pass upward and through the interdigitating fibers of the fronta­
lis and orbicularis oculi and attach to the undersurface of the skin.
Superficial injections avoid weakening the interdigitating fibers of the
frontalis and orbital orbicularis oculi thereby avoiding brow ptosis,
while injections given at least 3–4 cm above the bony orbital rim or
2–3 cm superior to the superciliary arch or ridge at the midpupillary
line prevent, blepharoptosis (Figure 13.14).
At one time, there were some injectors who preferred treating the
glabella separately in one session first, before injecting the frontalis
in a different, later session, especially with first-time patients.41,54 This
concern might have been justified in the earlier years when injection
techniques were just being developed, especially since high doses of
Figure 13.12  A 3/10 mL Becton-Dickinson insulin U-100 syringe with a 31-gauge
needle swaged directly onto the syringe barrel. Note the absence of any dead space
between the hub of the needle and the neck of the syringe. Each unit notch on the
barrel corresponds to 0.01 mL or 1 U.
Figure 13.13  Standard five injection points for treating glabellar frown lines.
X
X
X
X
(a)
(b)
X
Figure 13.14  Standard five injection points for treating glabellar lines in a female frowning (a) before and frowning (b) 3 weeks after an OnaBTX-A treatment.

13.  cosmetic uses of botulinum toxin a in the upper face
121
OnaBTX-A were being injected into the forehead. By injecting both
the glabellar depressor muscles at the same time as the one brow ele­
vator muscle, overdosing with total immobility of the forehead and
glabella frequently was seen. At times, even brow ptosis was inevi­
table with those previously recommended doses.41 With the evolving
aesthetics and appeal of a “less frozen” look to the forehead, along
with the recent FDA approval of injecting OnaBTX-A into the fron­
talis to reduce the appearance of horizontal forehead lines and into
the lateral orbital orbicularis oculi to reduce the appearance of crow’s
feet, most injectors are now treating the entire upper one-third of the
face during the same session effectively and safely (Figure 13.1).42,55,56
Treating glabellar lines with OnaBTX-A and producing optimal
results are not simple tasks. There have been many injection patterns
reported in the literature over the years, and they all produce optimal
results when the ideal patient is treated appropriately with a given injec­
tion pattern. This leads one to believe erroneously that any injection pat­
tern will work and so injecting OnaBTX-A is easy. However, this is not
quite the case (see the glabellar patterns in Figures 13.20 through 13.26).
What is most important for a successful treatment outcome is for
the physician injector to evaluate the patient comprehensively prior
to treatment and to understand why certain wrinkles are formed and
which muscles are creating them. Once a sound assessment is made and
a justifiable treatment approach is designed, it does not matter which
of the injection patterns one uses. Patients should be treated individu­
ally according to their idiosyncratic pattern of muscle movements
and the resultant wrinkles they produce. A three, five, seven, or even
more injection-point pattern can be used if it is appropriate for that
particular patient.57,58 However, the novice injector needs a point of
reference; a standard of injection patterns to guide him or her dur­
ing their initial treatment sessions. As the neophyte injector acquires
a better understanding of the functional anatomy and its responses to
different patterns of injections with OnaBTX-A, then a more directed
and personalized approach to OnaBTX-A injections will automati­
cally develop. The physician injector should also not forget to identify,
photograph, and indicate to the patient prior to all OnaBTX-A injec­
tions any variation in the anatomy that might be present and cause
the patient’s eyebrows to be asymmetric. It appears that as much as
45%–65% of the general female and male population has some form
of brow asymmetry prior to ever being treated with a BoNT (author’s
personal observation). The patient’s permanent clinical record should
contain photographic documentation along with a written summary
of the physician’s clinical assessment and conversation with the patient
addressing any idiosyncrasies and asymmetries the patient may pos­
sess. It is absolutely necessary to include in the record, the patient’s
response to the conversation, including acknowledgment of any par­
ticular anatomical differences, in addition to a written and signed con­
sent for treatment before initiating treatment with any BoNT.
The pretreatment position and symmetry or asymmetry of the eye­
brows and eyelids will dictate the technique with which one will need to
treat the glabellar frown lines (Figure 13.16). In women whose eyebrows
X
X
X
X
X
X
X
(a)
(b)
Figure 13.15  Standard seven injection points for treating stronger glabellar muscles causing deeper furrows and frown lines in a 51-year-old male (a) before and (b) 1 month
after an OnaBTX-A treatment in a forced frown.
(a)
(b)
Figure 13.16  Woman with eyebrows barely arched (a) before strategically placed injections of OnaBTX-A were placed into the brow depressors. Same patient (b) after treat­
ment with eyebrows more highly arched.

Botulinum Toxins in Clinical Aesthetic Practice
122
are barely arched, strategically placed injections of OnaBTX-A into the
brow depressors can elevate the eyebrows by ­allowing the  untreated
lower fibers of the frontalis to raise the ­eyebrows ­unopposed by the
weakened interdigitating fibers of the corrugator supercilii, procerus,
orbicularis oculi, and depressor supercilii (Figures 13.17 and 13.18).
To treat the glabellar frown lines with optimal, reproducible results
and the least amount of complications, precise injections of relatively
concentrated doses and low volumes of OnaBTX-A must be used on
both sides of the midline whether the doses are equal. With the patient
sitting up or in the semireclined position, gently palpate the medial
aspect of the eyebrows as the patient squints and frowns. After locat­
ing the belly of the corrugator supercilii with the second and third
fingertip pads of the nondominant hand, ask the patient to raise the
eyebrows as high as possible, while keeping the tip of the index finger
positioned over the thickest part of the belly of the corrugator superci­
lii (Figure 13.17). Prior to inserting the needle, the index finger of the
nondominant hand should be advanced slightly cephalad and above
the point of maximal muscle thickness. This usually is just above the
eyebrow. The thumb is placed at the margin of the supraorbital bony
rim. The bore of the needle tip should be pointed upward and away
from the globe. The needle is inserted into the skin at a 60°–90° angle
and allowed to glide over the upper edge of the thumb between it and
the index finger. The needle is slowly advanced into the belly of the
corrugator supercilii in an oblique direction, slightly upward and
lateral, until penetration into the belly of the corrugator can be felt.
Entry into a muscle usually is detected when, after passing through
the dermis and subcutaneous tissue, an abrupt release of resistance is
felt as the needle penetrates fascia and muscle fibers. At this point, the
needle may or may not impinge on the bone. If it strikes a bone, the
patient will sense sharp pain. The needle should then be withdrawn
gently enough to move away from the bone, but not far enough to exit
the belly of the corrugator. The needle should always remain deep
within the muscle, medial to the supraorbital notch and approximately
2–2.5 cm superior to the supraorbital bony margin during injections
of the BoNT. The physician injector must refrain from striking the
frontal bone with the needle tip, so as not to inflict any additional pain
to the patient, which occurs when the periosteum is pierced. However,
this may not be avoidable when first learning how to find the deeply
seated corrugators and effectively inject them at the proper depth.
Placing the nondominant index finger and thumb on the brow just
above and below the eyebrow prior to injecting OnaBTX-A serves
many purposes. It prevents injecting OnaBTX-A too low and close to
the orbital rim. When direct pressure is applied with the thumb infe­
rior to the border of the supraorbital bony rim, Binder et al. felt they
could reduce the migration of OnaBTX-A behind the orbital septum
and avoid blepharoptosis.59 This maneuver also helps identify the loca­
tion and position of the corrugator supercilii because the muscle can
be felt between the index finger and thumb with light palpation. Slow,
deliberate, and gentle injections prevent OnaBTX-A from dispersing
into surrounding, nontargeted muscle fibers. While in position, inject
4–10 U of OnaBTX-A into the strongest portion of the muscle, which
is located approximately 10–15 mm superior and 15–20 mm lateral to
the nasion or the center of the concavity at the nasal radix.31–35,57–59
Next, watch as the patient frowns again, and notice to what extent
the midbrow adducts toward the glabella. Stronger corrugators will
visibly pull the skin medially toward the midline just above the eye­
brows in the vicinity of the mid-pupillary line. In some patients,
additional vertical corrugations along the brow parallel to the cen­
tral vertical glabellar lines also will be formed (see Trindade de
Almeida’s glabellar “converging lines” in Figures 13.24 through
13.27). These corrugations can be reduced by injecting 2–4 U of
OnaBTX-A intradermally into the skin just above the middle of the
eyebrow where the corrugators insert into the undersurface of the
midbrow, which is just medial to the supraorbital notch or midpu­
pillary line. This point is identified by an obvious dimpling (cor­
rugator dimple) of the skin as the patient forcibly frowns (Figure
13.8b). These more lateral injections over the midbrow should be
applied first by asking the patient to raise their eyebrows and then
physically raising the center of the eyebrow with the thumb of the
nondominant hand. Then approach the skin at a 45°–60° angle and
injecting superficially, confirmed by raising a wheal. The fibers of
the corrugators in this location are superficial and insert into the
under surface of the skin. These injections should reduce the adduc­
tion of the brow and eliminate brow corrugations adjacent to glabel­
lar frown lines and along the central brow (see Figures 13.25, 13.26a
and b). If the injections are too deep, then fibers of the frontalis also
will be affected and brow ptosis can result. If the injections are too
low and close to the bony orbital rim, blepharoptosis will result.
Next withdraw the needle out of the skin and redirect the tip of the
needle medially in the direction of the head of the eyebrow. Insert
the needle 60°–90° to the skin surface at, or adjacent to the most medial
aspect of the superciliary arch and eyebrow, approximately 2 cm
Figure 13.18  Technique of injecting the medial aspect of the orbicularis oculi and
depressor supercilii starting at the most infero-medial aspect of the superciliary
arch. Note the 60° angle and superficial placement of the needle, approximately
2 cm directly above the ocular caruncle.
Figure 13.17  Technique of injecting the medial corrugator supercilii (note the
position of the thumb and index finger of the nondominant hand).

13.  cosmetic uses of botulinum toxin a in the upper face
123
directly superior to the ocular caruncle at the inner canthus (Figure
13.18). Injections should be given superficially, and confirmed by raising
a wheal. Approximately 2–6 U of OnaBTX-A at this point of maximum
muscle contraction will treat the vertical muscle fibers of the medial
orbital orbicularis oculi and the depressor supercilii. Because the fibers
of the orbicularis oculi and depressor supercilii are closely adherent to
the overlying skin at this location, injections can be given either intra­
dermally or in the superficial subcutaneous plane. Superficial injec­
tions at this location also avoid puncturing the supratrochlear vessels
and nerve. A pleasing vertically upward lift to the medial brow can be
accomplished by this technique, if fibers of the frontalis are not inad­
vertently affected.60,61 Gentle massage in an upward and lateral direc­
tion for a few seconds immediately after the injection helps relieve the
typical acute pain of a transcutaneous injection. Heavy-handed mas­
sage will definitely disperse the OnaBTX-A beyond the target area and
into muscle fibers not intended for treatment, that is, into the fibers of
the lower frontalis, which can result in brow ptosis.
Next, treat the procerus with an injection of approximately 4–10 U of
OnaBTX-A given between the eyebrows at the nasal root into the belly
of the procerus (Figure 13.19). Some spread of the onaBTX-A into the
interdigitating fibers of the depressor supercilii and medial fibers of the
orbital orbicularis oculi often occurs, potentiating the weakening effect
on all three muscles. The dose needed for this injection of OnaBTX-A
will depend on the overall muscle strength and depth of the horizon­
tal glabellar wrinkles that are present. The strength of the procerus can
be determined by gently palpating the mid-glabellar area with the pads
of the second and third fingertips of the nondominant hand, while the
patient repeatedly squints and frowns. Glabellar wrinkles can be deeply
fixed in the skin, especially the horizontal ones. Those that are more
resistant to treatment with OnaBTX-A commonly are found in men
and women who spend a lot of time outdoors or in front of a computer
screen, because their glabellar muscles are significantly hypertrophied
from frequent squinting. Intramuscular instead of subcutaneous injec­
tions of OnaBTX-A into the procerus should be performed by gently
grasping the skin and soft tissue of the root of the nose between the
thumb and the index finger of the nondominant hand. Then elevate
the skin and muscle before placing the needle between the two fingers
and injecting OnaBTX-A into one or two sites in the center of the nasal
radix. This maneuver also will avoid the needle puncturing the nasal
bone and causing additional unwarranted pain on the patient. The
site of injection should be anywhere from 1 to 3 mm above or below
the center of the nasion. The weaker muscle fibers of the procerus are
injected with at least 2 U of OnaBTX-A, while the stronger ones usually
can be injected with up to 10 U and possibly even more in one, two, or
more injection points. The depressor supercilii already will have been
partially treated by the injections given at the medial aspect of the super­
ciliary arch and eyebrows when the medial orbital orbicularis oculi and
the depressor supercilii are treated. Likewise, gentle massage performed
in and around the nasal radix immediately after injecting the procerus
also will result in some spread of the OnaBTX-A into the interdigitating
fibers of the depressor supercilii and medial orbital orbicularis oculi.
Some patterns of glabellar frowning are seen more frequently than
others.27 The most common pattern observed by Trindade de Almeida
and colleagues were those produced by the simultaneous adduction
and depression of the skin of the glabella (64%). This occurs when the
corrugators contract and parallel vertical lines are formed in the cen­
ter of the glabella as the skin of the brow moves toward the midline. At
the same time, the procerus pulls the skin of the brow inferiorly, form­
ing horizontal lines across the root of the nose. There are two distinct
variations of this most commonly seen pattern of glabellar frowning.
The less frequently observed pattern (27%) of the two is what Trindade
de Almeida et  al. call the “U” pattern (Figure  13.20).27 In these
patients, the 5-point injection technique is corrective with 4–10 U of
OnaBTX-A given at each injection point.27 Stronger, more hyperki­
netic corrugators and procerus produce a similar pattern of glabellar
frown lines but they are deeper and more acute, resulting in a pattern
that better resembles a “V.” This was seen in 37% of the patients stud­
ied (Figure 13.21). Higher doses of OnaBTX-A in the 7-point injection
pattern are usually necessary to diminish these lines.27
Another, less frequently observed pattern, named the omega pat­
tern, was seen in only (10%) of patients. When these individuals
frown, their eyebrows initially adduct centrally and glabellar skin
drops slightly forming deep parallel vertical lines. Then with contin­
ued forceful frowning the upper part of the center of the glabella will
slide upward toward the frontal hairline, forming deep horizontal fur­
rows and folds. The medial end of the brows continues to move infe­
riorly producing slight horizontal lines along the lateral sides of the
nasal radix to create an overall wrinkle pattern that outlines the Greek
letter omega (Ω) (Figure 13.22).27 In these individuals the corrugators
and fibers of the medial brow depressors seem to contract in unison
with the muscle fibers of the lower to mid central frontalis. Injections
of 4–8 U or more of OnaBTX-A at multiple sites into the corrugators
and medial brow depressors, while 2–6 U of OnaBTX-A into the pro­
cerus and 2–6 U into the lower medial frontalis in divided doses at
multiple sites will diminish the omega pattern of glabellar frowning.27
The “inverted omega” pattern was the least encountered (6%) of
all the five patterns identified by the Trindade de Almeida group and
was attributed to individuals with a flat nasal radix, which is com­
monly found in the Asian population (Figure 13.23).27 When these
individuals frown the center of their glabella drops inferiorly along
with their eyebrows, creating deep horizontal wrinkle lines across
the nasal radix but minimal to no vertical glabellar lines.27,62 In such
individuals, treat the procerus with 6–10 U of OnaBTX-A and the
depressor supercilii and medial orbital orbicularis oculi with 4–8 U
of OnaBTX-A and the corrugators with 4–8 U of OnaBTX-A.
Another less commonly seen glabellar frown pattern (20%) is the
one where there is just adduction of the mid-to-lateral brow toward
the center of the glabella. There is minimal vertical movement of the
glabella either inferiorly or superiorly because there seems to be a neu­
tralizing balance of movements between the procerus and the frontalis
that produces barely perceptible or no horizontal glabellar frown lines
in this “converging arrows” (or “parallel lines,” the author’s preferred
term) pattern (Figure 13.24).27 In these individuals, the extent and
depth of the lateral-to-medial brow corrugations are dependent on the
Figure 13.19  Technique of injecting the procerus (note the position of the index
finger and the thumb of the nondominant hand).

Botulinum Toxins in Clinical Aesthetic Practice
124
4
4
4
4
4
(a)
(b)
(c)
(d)
Figure 13.20  (a) Mild to moderate approximation and depression of the medial brow forming the typical and one of the most commonly seen patterns of glabellar frown
lines (the “U” pattern). (b) Commonly seen “U” type of glabellar contraction and resulting pattern of frown lines. Muscles involved: predominantly the corrugators and
procerus (see Reference 26). (c) Five-point pattern of injection for this commonly encountered glabellar “U” pattern (see Reference 26). (d) Same patient frowning 2 weeks
after an OnaBTX-A treatment.
6
4
4
6
6
5
5
(a)
(b)
(c)
(d)
(e)
Figure 13.21  (a) Moderate to severe approximation and depression of the medial brow forming the more commonly seen pattern variation identified by very deep glabellar
frown lines (the “V” pattern) in a 62-year-old woman. (b) Vigorous glabellar contraction and resulting “V” pattern of frown lines. Muscles involved: strong corrugators,
procerus, and medial aspect of the orbicularis oculi (see Reference 26). (c) Seven-point pattern of injection for this exaggerated glabellar “V” pattern. Higher doses of
OnaBTX-A are usually needed for treatment (see Reference 26). (d) Same patient at rest and (e) frowning 2 weeks after an OnaBTX-A treatment.

13.  cosmetic uses of botulinum toxin a in the upper face
125
5
6
6
4
4
4
4
5
5
(a)
(b)
(c)
(d)
Figure 13.22  (a) Adduction of the medial eyebrows and elevation of the center of the glabella along with depression of the mid and lateral brow forms the “omega” pat­
tern of glabellar frowning. (b) This type of glabellar contraction results in the “omega” pattern of frown lines. Muscles involved: corrugators and lower central frontalis
(see Reference 26). (c) This eight-point pattern of injection is used for the glabellar “omega” pattern. Higher doses of OnaBTX-A are needed for the corrugators and lower
central frontalis and usually none for the procerus (blue, author’s modification). (d) Same patient frowning 2 weeks after an OnaBTX-A treatment. ([c] From Trindade de
Almeida AR et al. Dermatol Surg 2012; 38(9): 1506–15.)
6
6
6
6
6
6
8
(a)
(b)
(c)
(d)
Figure 13.23  (a) More depression than adduction of the medial brow forms the “inverted omega” pattern of glabellar frowning. Note the deep horizontal line at the root of
the nose. (b) Less frequently seen type of glabellar adduction producing an “inverted omega” pattern of frown lines. Muscles involved: mostly the procerus and depressor
supercilii (see Reference 26). (c) A different seven-point pattern of injection for this uncommon glabellar “inverted omega” pattern. Higher doses of OnaBTX-A are needed
for the procerus (see Reference 26). (d) Same patient frowning 2 weeks after an OnaBTX-A treatment.

Botulinum Toxins in Clinical Aesthetic Practice
126
person’s age and the amount of skin laxity present. Increased skin lax­
ity promotes an increased number of vertical corrugations along the
medial brow. Injections of a higher than usual dose (6–10 U or more)
of OnaBTX-A into the belly of the corrugator supercilii, along its body
and into the tail, will nicely relax the excess wrinkling across the brow
(Figures 13.25 and 13.26). The medial horizontal muscle fibers of the
upper orbital orbicularis oculi also may play a role in the brow corru­
gations, which would then require one or more intradermal injections
of 2–6 U of OnaBTX-A, approximately 2–3 cm above the supraorbital
bony rim at the midpupillary line and medially along the supercili­
ary arch if corrugations persist after treatment. The procerus also can
be treated with 4–10 or even more U of OnaBTX-A when indicated
(author’s ­preferred technique) (see Figures 13.22 and 13.24).27
Outcomes (Results) When Treating the Central Brow (Glabella)
(See Appendix 4)
A clear and accurate record of all the units and where they were
injected must be maintained of each treatment session on all patients.
Meticulously detailed clinical records facilitate reproducible results.
Consequently, when proper injection techniques are followed, results
are predictable and reproducible. The vertical lines between the eye­
brows and the horizontal ones across the root of the nose will dimin­
ish and eventually disappear. Glabellar and midbrow corrugations if
treated appropriately also will be reduced and temporarily eliminated.
There can be a noticeably high arching of the eyebrows of
­approximately 2–3 mm, caused by the levator action of the frontalis
in those patients whose glabellar depressors have been substantially
weakened, when the interdigitating muscle fibers of the frontalis imme­
diately above the brow have not (Figure 13.27).60–64 There also can be an
increase in the horizontal distance between the eyebrows along with
an elevation of the medial aspect of the eyebrows when glabellar frown
(a)
(b)
(c)
(d)
5
6
6
4
4
4
4
Figure 13.24  (a) Adduction and approximation mainly of the eyebrows form this “converging arrows” pattern of glabellar “corrugated” frowning. There is little to no
depression or elevation of the medial brow. (b) This is an uncommon type of glabellar contraction resulting in a “converging arrows” or “parallel lines” (author) pattern of
frown lines. Muscles involved: mainly the corrugators and the upper mid horizontal orbital orbicularis oculi. (see Reference 26). (c) This six-point pattern of OnaBTX-A
injections targets mainly the corrugators and the mid-section of the upper orbital orbicularis oculi (blue, author’s modification). (d) Same patient frowning 3 weeks after
an OnaBTX-A treatment. ([c] From Trindade de Almeida AR et al. Dermatol Surg 2012; 38(9): 1506–15.)
Figure 13.25  Converging arrows or parallel lines pattern of glabellar wrinkling
before treatment in a 48-year-old male. Note the strong procerus contraction pro­
ducing the deep horizontal line across the nasal radix.

13.  cosmetic uses of botulinum toxin a in the upper face
127
lines are treated with OnaBTX-A because of the dynamic relationship
between the brow depressors (corrugator supercilii, depressor superci­
lii, orbicularis oculi, and procerus) and their brow elevator (frontalis),
(Figure 13.28).60,62 Accentuated high arching eyebrows may be attrac­
tive in most women, but usually not in men. To avoid a high arch­
ing brow in men, an additional 2–6 U of OnaBTX-A can be injected
intradermally or intramuscularly into the frontalis 2.5–4.0 cm above
the supraorbital ridge at the midpupillary line. This maneuver should
straighten a high ­arching eyebrow without provoking a low-lying brow
ptosis, (see ­section on “horizontal forehead lines”).
Usually, one can expect the effect of an OnaBTX-A treatment of
glabellar frown lines to last at least 3–4 months. Patients who are
treated for the very first time with OnaBTX-A may experience some
asymmetry and therefore should return for an evaluation and possible
touch-up injections within 2–3 weeks after a treatment. Frequently,
the effects of OnaBTX-A may last longer with each subsequent treat­
ment session. Therefore, after the first 2–3 years of regularly sched­
uled treatment sessions every 3–4 months, some patients may prefer
to return for their next retreatment at 5- or 6-month intervals (see
Appendix 3).
(a)
(b)
Figure 13.26  (a) Converging arrows or parallel lines pattern of glabellar wrinkling before treatment in a 61-year-old female. Note the absence of procerus contraction and
horizontal line across the nasal radix. (b) Same patient 2 weeks after treatment with OnaBTX-A.
(a)
(b)
(c)
Figure 13.27  Arching of the eyebrows while frowning (a) before and (b) after OnaBTX-A treatment in a 52-year-old woman with a converging arrows pattern of glabellar
wrinkling. (c) Same patient at rest. Note the nicely arched eyebrows.
(a)
(b)
Figure 13.28  This 37-year-old patient had both the glabella and the forehead frown lines treated during the same session. (a) Frowning before OnaBTX-A treatment. (b)
Same patient frowning 2 weeks after treatment. Note the increase in interbrow distance after treatment and elevation of the medial brow.

Botulinum Toxins in Clinical Aesthetic Practice
128
Complications (Adverse Sequelae) When Treating the Central
Brow (Glabella) (See Appendix 6)
Ptosis of the upper eyelid is one of the most significant and frequently
occurring complications seen when injecting OnaBTX-A in and around
the glabella (Figure 13.29).8,54,64 It is felt by many that blepharoptosis
is caused by the migration of injected OnaBTX-A through the orbital
septum, weakening the levator palpebrae superioris (Figures 13.10
and 13.30). This can occur more frequently in older patients in whom
the barrier function of the orbital septum is attenuated, or when large
volumes of highly diluted OnaBTX-A are injected quickly, deeply,
low down and close to the bony supraorbital margin at the midpupil­
lary line. Occasionally at this location, some actual muscle fibers of
the levator palpebrae superioris can extend anteriorly into the levator
aponeurosis, allowing for easy access of the OnaBTX-A that has dif­
fused through the barrier of the orbital septum to weaken some of the
muscle fibers of the levator palpebrae superioris, and produce ptosis of
the upper eyelid (Figure 13.10). Unexpected blepharoptosis in a younger
patient is usually the result of forceful injections of OnaBTX-A placed
too deeply in the area of the midbrow, particularly with high volumes
of highly diluted OnaBTX-A. Another reason for inadvertent blepha­
roptosis is when OnaBTX-A is routinely injected at a fixed distance of
2 cm from the upper border of the eyebrows instead of 2 cm from the
bony superciliary arch or ridge. In most men and some women, their
eyebrows are situated low on the brow and directly over the bony orbital
rim (see brow positions below). Injecting OnaBTX-A just above the
eyebrows in these individuals puts their levator aponeurosis at risk of
contact with the BoNT as the aponeurosis exits the superior margin of
the bony orbit (Figure 13.10). OnaBTX-A then can easily weaken any
exposed levator muscle fibers contiguous with the aponeurosis, reduc­
ing the levator action of the upper eyelid and causing blepharoptosis.
Ramey and Woodward demonstrated by their cadaveric study
using injectable blue methylene dye that deep and forceful injections
of OnaBTX-A in the vicinity of the supraorbital foramen potentially
could allow the toxin to penetrate into the superior aspect of the bony
orbit, presumably through the foramen, and affect the levator palpe­
brae superioris.65 After injecting 1% methylene blue deep into the cor­
rugator supercilii just above the supraorbital foramen, they found, by
an anterior dissection approach, the anterior orbital septum and ante­
rior surface of the levator aponeurosis stained blue. They also found by
a posterior dissection approach the intraorbital surface of the perios­
teum and the periorbita stained with the blue dye. There also was blue
dye staining the superior surface of the levator palpebrae superioris
and adjacent tissues, including the superior ophthalmic vein and some
of its tributaries. From this study, they hypothesized two mechanisms
of blepharoptosis. First, BoNT may reach the levator palpebrae supe­
rioris as it traverses the pre-periosteal plane anteriorly after a forceful
injection. Second, BoNT may track along tributaries of the superior
ophthalmic vein, which travels along the levator palpebrae superioris
for part of its course. Consequently, blepharoptosis may be avoided by
carefully positioning the injection needle far away from the supraor­
bital foramen and using a gentle, slow injection technique with highly
concentrated, low volume BoNT. Deep injections, particularly those
overlying the bulk of the supraorbital nerve or near branches of the
superior ophthalmic vein, should be avoided to prevent perineural or
perivascular infiltration around the levator palpebrae superioris.65,66
To avoid injecting OnaBTX-A too close to the bony orbital rim, one
should inject superficially and at a point at least 3–4 cm superior to the
bony orbital rim or 2–3 cm superior to the superciliary ridge or arch.
Any injection less than 3 cm away from the bony orbital rim, regard­
less of where the eyebrow sits over the superciliary ridge, will allow
OnaBTX-A to reach the levator aponeurosis directly or indirectly and
weaken its proximal muscle fibers and cause blepharoptosis.
In female patients, the eyebrows commonly sit approximately 5 cm
above the upper eyelid crease. On the other hand, men’s eyebrows usu­
ally grow directly over or below the superciliary ridge. There are some
women, however, whose eyebrows rest just as low as men’s, that is, at or
below the superciliary ridge. Instead of using the eyebrows as a point
of reference from where to inject, the upper orbital bony margin or rim
should be the reference point. Therefore, injections should be placed
no lower than 3–4 cm above the upper margin of the bony orbit.
Blepharoptosis, when it occurs, is seen as a 1–2 mm or more drop in
the upper eyelid, obscuring the upper border of the iris (Figure 13.30).64
Ptosis can appear as early as 48 hours and up to 7–10 days after an
OnaBTX-A injection and usually can last 2–4 weeks or even longer. The
margin to reflex distance (MRD) is a way to measure and diagnose upper
lid blepharoptosis. MRD is defined as the distance from the mid-pupil
corneal light reflex to the lower cutaneous margin of the upper eyelid
with the eyes in forward primary gaze. A normal MRD should equal
approximately 4 mm in vertical height. Blepharoptosis is present when
an MRD is measured less than 2 mm. Moreover, an asymmetrical com­
parative height of more than 1-2 mm between both eyes indicates a cer­
tain degree of unilateral compensatory brow elevation67 (Figure 13.31b).
An antidote for blepharoptosis is apraclonidine 0.5% eye drops
(Iopidine®, Alcon Laboratories, Inc., Fort Worth, TX). The ocular
instillation of apraclonidine, an alpha-2-adrenergic agonist with mild
alpha-1 activity, causes Müller’s muscle (a nonstriated, smooth, sym­
pathomimetic levator muscle of the upper eyelid) to contract, tempo­
rarily raising the upper eyelid approximately 1–2 mm (Figures 13.10
and 13.30). One or two drops should be instilled into the affected eye.
If ptosis persists after 15–20 minutes, intraocular instillation of an
additional one or two drops may be required before the affected eye­
lid will elevate. This procedure can be repeated three to four times a
day. It is advisable to use apraclonidine eye drops only when abso­
lutely necessary because approximately 20% of patients can develop a
contact conjunctivitis with frequent use. The mydriatic and vasocon­
strictor phenylephrine (Mydfrin 2.5%, Alcon Laboratories, Inc., Fort
Worth, TX, or Neo-Synephrine® HCl, 2.5% Ophthalmic Solution,
USP, Paragon BioTeck, distributed by Bausch & Lomb [a division of
Valeant, Laval, Quebec, Canada] also known by other brand names:
AK-Dilate, AK-Nefrin, Isopto Frin, Neofrin) is an alpha-1 agonist
that also can be used when apraclonidine is not available.41 However,
there are more potential side effects associated with the use of phen­
ylephrine than with apraclonidine. Specifically, even when only the
2.5% ophthalmic solution is used, phenylephrine can increase intra-
ocular pressure, cause systemic allergic and urticarial reactions,
Figure 13.29  Eyelid ptosis in a 49-year-old patient. Note a drop of 1–2 mm of the left
upper eyelid that occurred approximately 10 days after an OnaBTX-A treatment.

13.  cosmetic uses of botulinum toxin a in the upper face
129
local contact and irritant dermatitis and acutely exacerbate narrow
angle glaucoma, cardiac arrhythmias, and hypertension. Because
it also is a mydriatic, even one drop of phenylephrine will prevent
the patient from accommodating as usual and visual acuity can be
compromised. Naphazoline (Naphcon-A®, Alcon Laboratories, Inc.,
Fort Worth, TX) is another ophthalmic decongestant containing
adrenergic properties that can be used to stimulate Műller’s muscle
to contract, temporarily lifting a ptotic upper eyelid.64 The different
brands of naphazoline (e.g., Vasocon-A®, [naphazoline HCl 0.05%,
antazoline phosphate 0.5%,], Novartis Ophthalmics, East Hanover,
NJ) also contain different antihistaminic additives, and because of
their multiple side effects profile, should be used infrequently and
with caution, strictly on an as-needed basis when utilizing them just
to elevate blepharoptosis. When a patient cannot tolerate any of the
topical anti-blepharoptosis medications, then additional injections
of OnaBTX-A into the palpebral orbicularis oculi, can be attempted
to  reduce the remaining strength of the upper eyelid depressor
(Figure 13.31a).64 For the expert, well-seasoned injector, subdermal
injections of low-dose, low-volume OnaBTX-A into the pretarsal
orbicularis oculi, the antagonist to the upper lid levator (levator pal­
pebrae superioris) can be performed. Similar injections are used to
treat various blepharospastic disorders. Depending on the severity
of the blepharoptosis, inject 0.5 unit and no more than 1.5 units of
OnaBTX-A subdermally into the extreme medial and lateral aspects
of the pretarsal orbicularis oculi just above the lid/lash margin, so as
to avoid any further exposure of the centrally located muscle fibers of
the levator palpebrae superioris with additional onaBTX-A. (Figure
13.31a).64 An obvious wheal should be produced with these injections.
Blepharoptosis also can be induced secondarily when the lower fibers
of the frontalis are weakened, producing a drop in the height of the
brow. The weight of the ptotic brow then impinges on the upper eyelid
and causes it to drop, narrowing the vertical palpebral aperture or fis­
sure. This secondary blepharoptosis seems to occur more frequently in
older patients who possess dermatochalasis of the skin of the eyelids and
brow. To compensate for a heavy, lax brow, some individuals, regard­
less of age, involuntarily use the lower fibers of their frontalis to lift the
soft tissue of the brow, which also maintains their upper eyelids in a
constantly raised position.64 When this compensatory brow lifting of
the frontalis is weakened by BoNT, a secondary blepharoptosis results.
Careful examination of the upper eyelids for the presence of a separa­
tion or weakness of the levator palpebrae superioris can be a preinjec­
tion method to identify individuals at risk for true blepharoptosis and
to avoid its occurrence after a treatment with any BoNT. The functional
strength of the levator palpebrae superioris is determined by measuring
the distance of the excursion of the upper eyelid margin from far down­
ward gaze to upward gaze while the frontalis muscle is held still with
the injector’s hand. A normal excursion is approximately 14 mm or
more.68 When the excursion is less than 14 mm, some degree of bleph­
aroptosis after any BoNT treatment of the glabella mostly likely will
occur (Figure 13.31c). Another way to predict the risk for unmasking
and intensifying the potential for blepharoptosis is to identify someone
with lash ptosis (LP). Individuals with either congenital or acquired
blepharoptosis can manifest LP, which is a generalized declination or
downward pointing of the eyelash follicles of their upper eyelids. The
presence of LP suggests laxity of the terminal fibers of the levator apo­
neurosis which weave through orbicularis oculi to insert into the sub­
cutaneous tissue and skin of the upper eyelid69 (Figure 13.31d).
In younger patients with taut skin and no compensatory brow lift­
ing, brow ptosis often can occur medially when there is an overzeal­
ous injection of a BoNT in the center of the forehead. Medial brow
ptosis is exhibited by the medial head of the eyebrows appearing
excessively lower than the lateral tail of the eyebrows. A bulge of skin
in the center of the glabella also can accompany this “medial brow
dip” of the eyebrows. This occurs because the lower central fibers of
the frontalis are overly weakened and there is some activity of the
fibers of the medial brow depressors, that is, the procerus, depressor
supercilii, and medial orbital orbicularis oculi, pulling down on the
center of the forehead and glabella (Figure 13.32).
Lagophthalmos or incomplete eyelid closure is another potential
complication that can occur particularly when overzealous injections
of a BoNT are given in the periorbital area. Lagophthalmos results
when there is a loss of the normal sphincteric function of the orbi­
cularis oculi, and the upper eyelid does not close and approximate
firmly against the lower eyelid. Loss of the sphincteric function of
the orbicularis oculi either with involuntary blinking or with delib­
erate forced eyelid closure can occur when BoNT diffuses into the
palpebral portion of the orbicularis oculi, causing undue eyelid weak­
ness. Lagophthalmos is seen more frequently in patients treated for
strabismus when extraocular muscles are injected with higher doses
of OnaBTX-A instead of the usual lower doses given for cosmetic pur­
poses in the periocular area. On the other hand, patients who have
an attenuated orbital septum because of age or other reasons may be
more prone to this adverse sequela. If incomplete eyelid approxima­
tion is present for extended periods of time, exposure of the cornea
can result in symptomatic dry eyes or exposure keratitis.70 There is
no antidote for lagophthalmos which can persist as long as the effects
of the OnaBTX-A are present. So, protecting the patient from devel­
oping secondary dry eyes is extremely important because excessive
corneal exposure will lead to desiccation of the cornea and superficial
punctate keratitis. Immediate consultation with an ophthalmologist
at the first sign of lagophthalmos will prevent any additional injury
to the eye.
(a)
(b)
Figure 13.30  (a) Eyelid ptosis in a 67-year-old patient. Note a drop of 1–2 mm of the right upper eyelid that occurred approximately 7 days after OnaBTX-A was used to treat
forehead and glabellar wrinkles. Patient is actively blinking. (b) Same patient 30 minutes after the instillation of 2 drops of apraclonidine into the right eye.

Botulinum Toxins in Clinical Aesthetic Practice
130
(a)
(b)
(d)
(c)
Figure 13.31  (a) The margin to reflex distance (MRD) is a way to measure and diagnose upper lid blepharoptosis. It is defined as the distance from the mid-pupil corneal
light reflex to the lower cutaneous margin of the upper eyelid with the eyes in forward primary gaze. A normal MRD, shown here in red, should equal approximately 4 mm
in vertical height. The palpebral fissure, shown here in green, is the distance between the upper and lower lid margins and normally measures between 7 and 12 mm. (b) A
69 year old male with lash ptosis and acquired blepharoptosis. Note the generalized declination or downward pointing of the upper eyelashes. (c) The functional strength
of the levator palpebrae superioris is determined by measuring the distance of the excursion of the upper eyelid margin from far downward gaze to upward gaze while the
frontalis muscle is held still with the injector’s hand. A normal excursion is approximately 14 mm or more. When the excursion is less than 14 mm, some degree of blepha­
roptosis after any BoNT treatment of the glabella mostly likely will occur. (d) To treat mild upper lid blepharoptosis OnaBTX-A is injected into the (far) medial and lateral
pretarsal orbicularis muscle fibers in the subdermal plane. (See further Reference 64.)

13.  cosmetic uses of botulinum toxin a in the upper face
131
Asymmetry is a minor adverse sequela that sometimes is unavoid­
able, particularly when a patient is treated for the first time with a
BoNT (Figure 13.33). There are three types of asymmetry that can
be corrected with injections of OnaBTX-A: iatrogenic, idiosyncratic,
and incidental or acquired. An example of incidental or acquired
asymmetry is Bell’s or facial (7th cranial) nerve palsy. Additional
examples are when one side of the face acquires a weakness because
of an event (e.g., cerebral vascular accident), or an accidental, trau­
matic, or surgical denervation injury. Idiosyncratic asymmetry
occurs when a person is born with the inability to control or move
a facial muscle to its fullest extent, while its counterpart muscle on
the contralateral side of the face is unaffected. This can result, for
example, in one eyebrow or one eyelid being higher than the other
(Figures 13.34 and 13.35) or in a crooked asymmetric smile (see
Chapter 15).
Iatrogenic asymmetry arises when an injection of OnaBTX-A
causes one side of the face to become weaker than the other (see Figure
13.34 and 13.39a). There are many reasons for this. The primary rea­
son is because the stronger side is not injected with an equivalent
dose of OnaBTX-A as the contralateral side. This could be the result
of the OnaBTX-A not diffusing as equally and completely through
all the fibers of a muscle or group of muscles. Another reason could
be that some of the fibers might have been physically resistant to the
OnaBTX-A, because those particular fibers were idiosyncratically
thicker or stronger than the rest of the area and may have required a
higher dose of OnaBTX-A. Another possibility is that the injections
were not given precisely symmetrically or in the thickest and stron­
gest part of the muscle, causing a particular section of muscle to retain
most or some of its strength. Iatrogenic asymmetry is probably the eas­
iest type of asymmetry to rectify. Generally, with a few additional units
4
6
6
4
4
3
3
3
3
3
2
2
3
(a)
(c)
(b)
(d)
Figure 13.32  The “medial brow dip” of the central glabella and eyebrows of this 40-year-old occurred after OnaBTX-A injections because the lower central frontalis was
overly treated. Patient is frowning (a) before and (b) after OnaBTX-A. Note the fullness of the medial brow skin after treatment. (c and d) The “medial brow dip” of the
central glabella of this other 45-year-old patient was avoided after OnaBTX-A injections because the central frontalis was not treated.
(a)
(b)
Figure 13.33  (a) Note the left eyebrow is higher than the right before and after treatment with OnaBTX-A. (b) Note the medial brow dip after treatment.

Botulinum Toxins in Clinical Aesthetic Practice
132
of OnaBTX-A injected into the appropriate area, iatrogenic asymme­
try can be expeditiously ameliorated (Figure 13.39b).
Another type of asymmetry is pseudoblepharoptosis. Many
individuals regardless of age possess, unbeknownst to them, an
idiosyncratic lower lying asymmetric brow on one side. They com­
monly will also possess a lower lying upper eyelid on the same side
and a smaller vertical palpebral aperture causing a narrower eyelid
fissure (i.e., a secondary blepharoptosis, see Figure 13.35). With age,
compensatory brow lifting will raise the affected lower lying brow
and upper eyelid to maintain unobstructed vision (Figure 13.36a).
When the frontalis of these patients is treated with injections of
OnaBTX-A, the patient’s compensatory brow lifting can be unin­
tentionally weakened. This inadvertent diminution of compensa­
tory brow lifting can occur even when only the higher upper fibers
of the frontalis are weakened with injections of OnaBTX-A. The
lower fibers of the frontalis do not necessarily have to be treated
directly with injections of OnaBTX-A to drop the brow a few mil­
limeters. With a drop in brow height comes a ­concomitant drop in
upper eyelid height and a narrowing of the palpebral fissure. Those
patients who already have an asymmetrically lower upper eyelid
(a)
(b)
(c)
Figure 13.35  (a) This 53-year-old woman at rest did not know that she had a naturally occurring brow ptosis on the right with an accompanying secondary blepharoptosis
of the right eyelid. (b) Same patient with an asymmetrical left brow elevation found with forced raising of the eyebrows before a treatment of OnaBTX-A. (c) Same patient
at rest and gazing forward, 8 weeks after an OnaBTX-A treatment.
(a)
(b)
(c)
Figure 13.36  A 70-year-old with compensatory brow lifting and an undetected left eyelid ptosis (a) at rest and (b) frowning before OnaBTX-A treatment. (c) Blepharoptosis
is seen at rest 1 month after OnaBTX-A. The patient and treating physician assumed the blepharoptosis was caused by OnaBTX-A until the before and after treatment
pictures were compared, which then prompted the diagnosis of “pseudoblepharoptosis”.
(a)
(b)
Figure 13.34  Patient is shown (a) before and (b) 2 weeks after OnaBTX-A treatment. Note the slightly higher elevation of the right eyebrow, which is seen as the patient
raises her eyebrows before and after treatment. Note also the medial brow dip and right “Mephisto” brow after treatment.

13.  cosmetic uses of botulinum toxin a in the upper face
133
on one side now appear to have developed blepharoptosis from the
OnaBTX-A injections (Figure 13.36). In reality, these patients more
accurately have pseudoblepharoptosis, which is simply an unmask­
ing of the secondary blepharoptosis they already possessed prior to
any BoNT treatment. At times, this can be enhanced because of an
age-related attenuation of the strength of the upper lid levator of
that eye (Figure 13.37). When the patient first realizes that one upper
eyelid is lower than the other, blame on the injector and OnaBTX-A
is a foregone conclusion.71 However, the astute physician will evalu­
ate the patient carefully prior to any treatment and document the
asymmetric clinical findings with pretreatment photographs. This
will enable the physician to discuss the actual problem with the
patient and graphically demonstrate the presence of the compensa­
tory brow lifting before embarking on a perilous course of inevitable
treatment failure (Figure 13.38). So, instead of the physician being
led to believe that the patient developed blepharoptosis because of a
poor ­injection technique, the physician will be able to identify that
the patient always had an idiosyncratic asymmetry and subclini­
cal upper eyelid ptosis that can be unmasked and even exaggerated
with injections of OnaBTX-A (Figure 13.39). This manifestation of
(a)
(b)
Figure 13.37  (a) A 57-year-old patient with a compensatory left brow lift before treatment with OnaBTX-A injections. (b) Same patient 2 weeks after OnaBTX-A demon­
strates a slight pseudoblepharoptosis on the left.
(a)
(b)
(c)
Figure 13.38  (a) Compensatory brow lifting raises the right eyebrow in this 60-year-old patient to correct a ptotic right eyelid. (b) Same patient, brows are fairly sym­
metrical with frowning, but the right upper lid is still ptotic before injections of OnaBTX-A. (c) Same patient, 1 week after injections of OnaBTX-A. The left brow was lifted
with OnaBTX-A and both eyebrows appeared fairly symmetrical. This paradoxically makes the upper eyelid appear ptotic even though the right brow was not treated with
OnaBTX-A.
2
(a)
(b)
Figure 13.39  An example of iatrogenic asymmetry. (a) A 42-year-old patient is seen at rest with a higher right eyebrow 2 weeks after OnaBTX-A injections of the glabella
and forehead and just before an additional 2 U of OnaBTX-A were given. (b) Same patient at rest 3 weeks after the additional 2 U of OnaBTX-A were given and 5 weeks
after her initial treatment with OnaBTX-A. Notice the relative symmetry of both eyebrows.

Botulinum Toxins in Clinical Aesthetic Practice
134
pseudoblepharoptosis frequently occurs in patients over the age of
60 years who are treated for forehead wrinkles and glabellar frown
lines with injections of BoNT. Correction of pseudoblepharoptosis
is not always completely successful but can be attempted by inject­
ing intradermally the extreme lateral and medial pretarsal orbicu­
laris oculi of the upper eyelid on the affected side with low doses
(0.5–1.0 units) of concentrated low volume OnaBTX-A.64,71
The best way to avoid additional difficulties with patient rapport
and confidence is to keep carefully documented written clinical notes
and before and after treatment photographs (see Appendix 4). Discuss
the physical findings with the patient and point out existing idiosyn­
cratic asymmetries, anatomical differences, and potential adverse
outcomes prior to treatment. Informing the patient of any atypical
findings before commencing with a treatment always is regarded by
the patient as an accurate diagnosis of a unique situation. Explaining
the circumstances and reasons for a particularly poor outcome after
treatment always, is considered by the patient as an excuse for an
improperly executed procedure.
Other untoward sequelae of more limited significance and dura­
tion can occur. These are the same adverse sequelae as those expe­
rienced with any type of subcutaneous or intramuscular injection.
They include ecchymoses, edema, and erythema at the injection sites
(Figure 13.40), headache, and flu-like malaise. Rarely, if ever, do any
of these side effects last beyond the day of treatment, except for ecchy­
moses which can last up to 10 days or more.
For some patients, a dull and transient headache with or without
general body malaise occurs after injections of OnaBTX-A that can
last beyond 24–72 hours.72 The occurrence of headache immediately
after an OnaBTX-A injection seems paradoxical since OnaBTX-A
injections are now FDA approved for treating tension and migraine
headaches.1,73 Headaches seem to occur more frequently in patients
after their first and subsequent 2 or 3 treatment sessions. They usu­
ally cease to occur with repeat treatments. Studies have documented
the incidence of patients who develop headaches after a treatment
of OnaBTX-A were similar to those receiving placebo.45 This seems
to indicate that the transient headaches which occur after a treat­
ment of BTX-A are due more likely to the physical act of injection
rather than to the actual BoNT-A itself.45 Other studies have found
that patients are more prone to headaches when the volume of
the injected BoNT-A is higher than usual. This also seems to sup­
port the opinion that headaches after injections of OnaBTX-A are
probably due to the trauma of the injection rather than to the actual
BoNT product.74
For the first-time recipient of a periorbital treatment of OnaBTX-A,
the presence of periorbital edema lasting a few hours to days may
occur. This can be attributed to lymph stasis, possibly produced by a
nondetectable attenuation of the sphincteric pumping action of the
inferior preseptal orbicularis oculi, reducing the efficiency of lymph
fluid clearance from the surrounding soft tissue.64 Moreover, when
there is a blatant reduction in lower eyelid tone, eversion of the punc­
tum and reduced blinking can compromise the action and efficacy of
the “lacrimal pump,” resulting in transient epiphora, until the lower
eyelid tone returns (see Figure 13.132).
For some women, habitual squinting and scowling are the result
of spending a lot of time outdoors, in front of a computer screen, or
suffering from constant and persistent headaches, or being plagued
with poor vision and refusing to wear corrective eyeglasses, among
many other things. Incessant contraction of the corrugator super­
cilii and orbicularis oculi, manifested by habitual scowling, causes
the medial end of the eyebrows to approach the midline. Sclafani
and Jung measured the difference in interbrow distance from
maximum elevation to maximum contraction of the brow, and it
was slightly greater than 4 mm. The average distance traversed by
the medial brow from frowning to repose was 3.26 mm in women
and 3.76 mm in men.75 Many women will pluck and shorten the
transverse length of their eyebrows by removing eyebrow hair from
the medial end of their brow. This will widen the glabellar inter­
brow space, so they do not look like they are habitually scowling,
when they actually are (Figures 13.39 and 13.41). After injections of
OnaBTX-A are given to reduce the number and extent of glabellar
frown lines, the corrugators are no longer constantly contracting
and adducting the eyebrows toward each other. Consequently, the
transverse width of the glabella returns to its normal anatomical
position because the corrugators now are more relaxed and less
hyperkinetic when they are in repose. However, those women who
have plucked the medial portion of their eyebrows now complain
after injections of OnaBTX-A that they look practically hyper­
teloric because their eyebrows appear widely separated. However,
it is only because the medial aspects of their eyebrows have been
excessively plucked that causes them to appear this way and not
the injections of OnaBTX-A. Such an adverse sequela is difficult
to predict, but warning patients who pluck their eyebrows of such
a potential side effect will prevent further disappointment on the
part of the patient and additional frustration on the part of the
physician. Also, be aware of the patients without any eyebrow hair
who need to color in, the shape of their eyebrows. The shape that
is chosen on the day of an OnaBTX-A treatment may not necessar­
ily correspond to the natural anatomical position of that person’s
brow. Injections of OnaBTX-A may return the area to its natural
anatomical position, which paradoxically may appear to be dis­
torting the glabellar area, when in reality it is not. Patients with
permanent eyebrow tattooing may present with similar challenges
and post-treatment confounding disappointments (Figure 13.42).
Serious reactions, particularly those of immediate hypersensitivity
such as anaphylaxis, urticaria, soft tissue edema, and dyspnea have
been extremely rare. When they occur, appropriate medical treat­
ment must be instituted immediately (see Appendix 6).76 However,
there has not been a confirmed serious case of spread of toxin effect
away from the injection site when OnaBTX-A has been used at the
recommended dose to treat glabellar frown lines.1
Figures 13.43 through 13.51 are some examples of different patients
treated with OnaBTX-A for glabellar frown lines. Note also those
who have had their forehead frown lines treated during the same
treatment session.
Figure 13.40  Note the erythema and edema in the pattern of the injections 10 min­
utes after a treatment of OnaBTX-A of the forehead and glabella.

13.  cosmetic uses of botulinum toxin a in the upper face
135
Treatment Implications When Injecting the Glabella

1. Precise amounts of accurately placed injections of minimal vol­
ume OnaBTX-A reduce the incidence of brow and eyelid ptosis.

2. Men may need higher doses of OnaBTX-A than women for
comparable results.

3. Women prefer arched eyebrows; most men prefer straighter,
non-arched eyebrows.

4. When injecting the corrugator supercilii with OnaBTX-A,
remain medial to the midpupillary line and 3–4 cm above the
supraorbital bony margin, and deep within the belly of the
muscle.

5. Blepharoptosis can be transiently reversed with alpha-­
adrenergic agonist eye drops, but brow ptosis cannot be reduced
and remits only when the effects of OnaBTX-A diminish.

6. Preexisting asymmetry of the brow and eyelids should be iden­
tified and discussed with the patient before treatment, and
might be corrected by accurately injecting appropriate doses of
OnaBTX-A on both the affected and non-affected sides.

7. Patients with inelastic, redundant skin of the brow who have
compensatory brow lifting because of a preexisting subclinical
secondary blepharoptosis can easily develop pseudoblepharop­
tosis when injections of OnaBTX-A decompensate their brow
lifting on the affected side.
HORIZONTAL FOREHEAD LINES
Introduction: Problem Assessment and Patient Selection
One of the easiest areas of the face to treat with injections of OnaBTX-A
is the forehead.57 Many individuals contract their ­frontalis constantly
for various and sundry reasons, and, in so doing, the skin buckles,
creating parallel furrows and folds transversely across their foreheads.
On the other hand, the presence of horizontal forehead lines seems to
be directly proportional to one’s age or time spent in the sun. Older
individuals generally have many forehead lines that become deeper
(a)
(b)
(c)
(d)
Figure 13.41  Note the widening of the glabellar interbrow space and the shortening of the transverse length of the brow (a) at rest and (b) frowning due to excessive pluck­
ing of the eyebrows. Same patient at rest (c) and frowning (d) after a treatment with OnaBTX-A. Note additionally the change in hair color after treatment.
Figure 13.42  This 58-year-old patient had her eyebrows permanently tattooed
prior to any OnaBTX-A treatments. Many years later, after regularly scheduled
OnaBTX-A treatments, her eyebrows are now permanently and widely spaced lat­
eral to the medial canthus.

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Figure 13.44  A 66-year-old patient at rest (a) before and (b) 4 weeks after OnaBTX-A treatment of the glabellar frown and forehead lines. The same patient is shown frown­
ing (c) before and (d) 4 weeks after OnaBTX-A treatment of the glabellar frown lines.
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Figure 13.45  A 43-year-old patient at rest (a) before and (b) 2 weeks after an OnaBTX-A treatment of the glabellar frown lines.
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Figure 13.43  A 56-year-old patient at rest (a) before and (b) 1 month after OnaBTX-A treatment of the glabellar frown lines. Note the different dosages for areas of stronger
muscle contraction.

13.  cosmetic uses of botulinum toxin a in the upper face
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Figure 13.48  A 43-year-old patient frowning (a) before and (b) 2 weeks after OnaBTX-A treatment of glabellar frown lines.
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Figure 13.47  A 52-year-old patient (a) before and (b) 2 weeks after an OnaBTX-A treatment of glabellar frown lines.
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Figure 13.46  A 57-year-old patient (a) before and (b) frowning 2 weeks after an OnaBTX-A treatment of the glabellar frown and forehead lines.

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Figure 13.51  A 49-year-old patient frowning (a) before and (b) 2 weeks after an OnaBTX-A treatment of glabellar frown lines.
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Figure 13.50  A 71-year-old patient frowning (a) before and (b) 2 weeks after an OnaBTX-A treatment of glabellar frown and forehead lines.
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Figure 13.49  A 59-year-old patient frowning (a) before and (b) 2 weeks after an OnaBTX-A treatment of glabellar frown lines.

13.  cosmetic uses of botulinum toxin a in the upper face
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with time. As one ages, the skin of the face, along with that of the rest
of the body, typically becomes more inelastic and redundant. When
this occurs in the upper face, not only do horizontal forehead lines
appear, but there also is a characteristic hooding of the brow that fre­
quently develops. Age-related brow hooding first develops commonly
over the lateral aspect of the brow, whereby brow skin extends over
the lateral aspect of the upper eyelids. This usually occurs in the sixth
or seventh decade in those individuals so predisposed (Figure 13.2).
For these individuals, a properly functioning frontalis is essential in
maintaining a normal unobstructed field of vision. It is the frontalis
that will keep the brow from dropping and causing the skin to drape
over the upper eyelids, which can interfere with their forward and
upward gaze.
Younger women who have horizontal forehead lines commonly
attempt to conceal their obtrusiveness by wearing their frontal hair
with a fringe or in bangs (Figure 13.52). Generally, the presence of
horizontal forehead lines causes one to appear stressed, worried,
tired, or old. Abruptly raising the eyebrows by acutely contracting
the frontalis also can express an emotion of surprise or even fear; a
social cue that one usually may not want to express too readily in
certain situations (Figure 13.53). When done properly, injections of
OnaBTX-A can diminish forehead wrinkling and replace one’s unin­
tended negative expressions with those that are more positive.
All too often it is the female rather than the male patient who is
more concerned about the presence of forehead lines. These women
are frequently quite determined to eliminate any vestige of the
appearance of a forehead wrinkle. A cautious and empathetic cos­
metic ­physician will remind such patients that the absolute absence
of forehead wrinkles, especially at full contracture or while express­
ing an emotion, may not be particularly attractive or appropriate.
It ­portrays an individual as too artificial and mask-like in appear­
ance, and thus should not be one’s ultimate goal. Because of the leva­
tor function of the ­frontalis, its antagonistic interaction with the
­depressor muscles of the glabella and periorbital area, and the poten­
tial risk of overtreatment causing brow ptosis, there are many who
believe treating the frontalis with OnaBTX-A is not as easy as one
might expect.41
Functional Anatomy of Horizontal Forehead Lines
(See Appendix 2)
The horizontal forehead lines are produced by the contraction
of the muscle fibers of the frontalis, the only levator muscle of the
upper third of the face (Figure 13.54). The function of the frontalis
is to elevate the eyebrows, the skin of the brow and forehead, and to
oppose the depressor action of the muscles of the glabella and brow.
Its superior aspect also retracts and lowers the scalp as a function of
its ­participation in the occipitofrontalis galea aponeurotic complex.
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Figure 13.52  (a) Note the fringe of hair concealing the forehead in a 52-year-old with deep forehead lines (b) before and (c) 2 weeks after a treatment with OnaBTX-A. (d)
A patient before and (e) 3 weeks after a treatment with OnaBTX-A. The bangs were pulled back to show the forehead rhytides.
Figure 13.53  Abrupt contraction of the frontalis expresses surprise or even fear.

Botulinum Toxins in Clinical Aesthetic Practice
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The frontalis is a pair of quadrilaterally shaped, distinct muscles
whose fibers are oriented vertically, contracting in a vertical direction
and producing the horizontal wrinkles of the forehead. The frontalis
lies beneath a thick layer of sebaceous skin and subcutaneous tissue
and has no attachment to bone. The frontalis is indirectly connected
to the occipitalis by the epicranial, membranous galea aponeurotica,
which attaches to both muscles on either side of the scalp vertex, the
occipitalis posteriorly and the frontalis anteriorly. The frontalis origi­
nates from the membranous galea aponeurotica superiorly and inserts
into the subcutaneous tissue and skin of the brow inferiorly at the level
of the superciliary ridge (or arch) of the frontal bone. The fibers of the
frontalis also interdigitate with muscle fibers of the brow depressors,
that is, the procerus, corrugator supercilii, depressor supercilii, and
orbicularis oculi. In some patients, there can be a downward exten­
sion of the membranous galea aponeurotica in the midline composed
of little or no muscle fibers (Figure 13.54). Injections of OnaBTX-A
into this area are ineffective and unnecessary when no muscle fibers
are present.77 However, in some men and even women, there are well-
developed muscle fibers in the center of the forehead (Figures 13.52b
and 13.55) which can be detected by light palpation over the area while
the patient actively raises and lowers the eyebrows. A study of cadav­
ers using punch biopsies to determine the location of frontalis muscle
fibers at three different locations along the vertical axis in the fore­
head midline, revealed a diminishing presence of muscle fibers in the
upper forehead.30 Fibers of the paired frontalis intersected and over­
lapped in the midline at the level of the eyebrows in 100% of cases. At
2 cm above the eyebrows the two bellies of the frontalis interdigitated
only in 40% of cases studied and at 4 cm above the eyebrow line no
intersecting frontalis fibers were found in the midline. However, when
functional muscle fibers of the frontalis can be detected in the center
of the forehead, injections of OnaBTX-A in the midline of the forehead
are needed to produce the desired effect (Figures 13.52b and 13.55e,f).
Dilution (See Appendix 3) When Treating Horizontal
Forehead Lines
Controlled widespread diffusion can be a desired effect when inject­
ing OnaBTX-A into the forehead. To avoid brow ptosis, the muscle
fibers of the frontalis must remain fully functional 1.5–2.5 cm above
the eyebrow, which is predicated on the resting position of the eye­
brows (i.e., 3–4 cm above the actual bony orbital margin). Then
higher dilutions and larger volumes of OnaBTX-A can be injected
into the upper forehead. Consequently, injectors will use anywhere
from 1 to 4 mL of non-preserved or preserved saline to reconstitute
a 100 U vial of OnaBTX-A when treating the forehead.39,78 The dilu­
tion recommended by the manufacturer and approved by the FDA
and specified in the OnaBTX-A product’s package insert is 2.5 mL
of nonpreserved sterile saline or 4 U of OnaBTX-A per 0.1 mL of
solution.
Dosing: How to Correct the Problem, (See Appendix 4), (What to
Do and What Not to Do) Whenx Treating Horizontal Forehead
Lines
Injections of OnaBTX-A into the frontalis for cosmetic purposes were
approved by the FDA in October, 2017. The intricate and essential
interaction of the frontalis with the brow depressors makes it virtu­
ally impossible not to treat the forehead when one is treating glabellar
frown lines.
A typical dose for injecting the forehead in women is approxi­
mately 8–18 U of OnaBTX-A. However, the FDA approved dose
for treating the forehead with Ona-BTX-A is 20 units. This can be
injected either subcutaneously or intramuscularly at four to six sites
across the forehead with 1–4 U of OnaBTX-A placed into each site at
intervals of approximately 1.5–2.5 cm apart on either side of a deep
crease (Figure 13.56).78,79 For men, the typical dose is approximately
16–32 U of OnaBTX-A and occasionally higher.80–82 These doses can
be injected at 4–12 or even more sites either subcutaneously or intra­
muscularly depending on the height and width of the forehead, with
up to 6–8 U of OnaBTX-A placed into each site, depending on the
strength of the frontalis (Figures 13.56b and 13.57).57,81 Some patients,
either men or women, can have many rows of fine to moderate fore­
head wrinkles, whereas others can have one or two rows of deeply set
folds and furrows. The number and dosage of the OnaBTX-A injec­
tions will depend on many ­factors, including the number and depth
of the wrinkles, the size, shape, and strength of the muscle and the
height, width, and shape of the forehead (Figure 13.57).41,57,81,82 More
often than expected, and unbeknownst to the individual, a patient
will present with asymmetrical eyebrows prior to their first treat­
ment with OnaBTX-A. Patients must be made aware of their idio­
syncratic anatomical differences which must be documented both
in the patient’s clinical chart and in his or her photographic record.
Sometimes the eyebrows can be made symmetrically level with each
other with carefully placed injections of OnaBTX-A (Figure 13.58)
and sometimes they cannot (Figure 13.59).
The patient usually is injected in an upright sitting or semire­
clined position. The pattern of injection across the forehead can
vary ­depending on the anatomical dimensions of the forehead and
the strength of the frontalis. To determine the overall muscular
strength of the frontalis, lightly palpate the forehead at rest and dur­
ing maximum eyebrow elevation. One can randomly inject 1–4 U of
­OnaBTX-A subcutaneously or intramuscularly at any point on the
forehead that is at least 2–2.5 finger breadths (i.e., 2.5–4.0 cm) above
the superior margin of the bony orbit (Figures 13.60 and 13.61).
Otherwise, one can use the on-label recommended technique and
total dose of 20 units of OnaBTX-A for treating horizontal forehead
lines for both men and women. To identify the recommended injec­
tion points one must first locate the superior extent of functionally
active frontalis, which is usually approximately 1 cm above the high­
est horizontal forehead crease. Then locate the lowest row of treatable
horizontal wrinkles, by identifying the midway point between the
superior margin of active frontalis and the eyebrows. This midway
1
Figure 13.54  Frontalis, the only levator muscle of the forehead.

13.  cosmetic uses of botulinum toxin a in the upper face
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Figure 13.55  (a, b) Men with deep forehead lines; the 58-year-old patient in (b) works outdoors. (c, d) Some women can have a well-developed frontalis in the middle of their
forehead. Neither of these women works outdoors. Note the on-label recommended injection points for treatment of the forehead on a patient (b) with a receding hairline
and (c) with a fixed hairline: (1) midline; (2) superior margin; (3) upper treatable row; (4) lower treatable row; (5) inferior margin at upper level of eyebrows, and see text
for location of injection points. (e, f) This 63-year-old man who spends a lot of time outdoors has a well-developed frontalis, seen here raising his eyebrows (e) before and
(f) 2 weeks after an OnaBTX-A treatment. Note the non-tanned skin in the base of the forehead furrows (f) after treatment.
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Figure 13.56  (a) Typical injection sites in a woman with an average sized forehead. (b) Typical injection sites in a man with an average sized forehead.