Hyaluronic acid
–based fillers: theory and practice
Marina Romagnoli, MD
a,c,d,
⁎
, Magda Belmontesi, MD
a,b
a
Superior Post Graduate School of Aesthetic Medicine, 20123 Milan, Italy
b
Plastic Surgery Department, University of Pavia, 27100 Pavia, Italy
c
Filler and Laser Advisory Board
’ of ISPLAD (International Italian Society of Plastic and Oncologic Dermatology),
Milan, Italy
d
Dermatology and Aesthetic Laser, Biomedical Clinic, Genoa, Italy
Abstract This article is aimed at providing information about the cross-linked hyaluronic acid marketing
at present. It is also aimed at helping the lectors improve their knowledge about injection modalities and
patient manage.
© 2008 Elsevier Inc. All rights reserved.
Hyaluronic acid
Terminology
Hyaluronic acid was isolated from the vitreous of a
bovine eye by Karl Meyer and his assistant John Palmer for
the first time in 1934. They found a substance containing
2 saccharide moieties, and one of them was uronic acid.
Therefore, they proposed the name hyaluronic acid,
combining the words hyaloid (vitreous) and uronic acid.
This polysaccharide is not physiologically present as an
acid but as a hyaluronate salt. The most represented cation
in tissues is sodium; thus, hyaluronic acid is generally
present as sodium hyaluronate. In 1986, the term hyalur-
onan was proposed, according to the modern nomenclature.
Sometimes, the official Pharmacopeia uses the term natrii
hyaluronas. The latter should not be confused with
hyaluronidase, which is an enzyme involved in the
degradation of hyaluronic acid. The following table depicts
the different terms cited above and their use in the
scientific literature:
Name
Comment
—field of use
Use (%)
Hyaluronic acid
Meyer and Palmer,
1934
—medicine
60
Na-hyaluronate
Neutral pH salt
—pharmaceuticals 10
Hyaluronan
Balazs et al
—scientific
30
Natrii hyaluronas Latin term
—pharmacopeia
Unique
Chemical structure
The chemical structure of hyaluronic acid is very simple:
disaccharide units containing glucuronic acid and N-
acetylglucosamine (
). It can be clearly defined as
a glycosaminoglycan with an unbranched polysaccharide
chain, derived from the aggregation of thousands of
disaccharide units composed of glucuronic acid residues
(glucose-derived) and N-acetylglucosamine.
“n” is the
number of repetitions of the disaccharide units. In vivo, all
carboxylic groups of glucuronic acid and of N-acetylgluco-
samine are fully ionized, making the hyaluronic acid
molecule highly polar and consequently highly water
⁎ Corresponding author. 16157 Genova, Italy. Tel.: +39 010 662631.
E-mail address:
(M. Romagnoli).
0738-081X/$
– see front matter © 2008 Elsevier Inc. All rights reserved.
10.1016/j.clindermatol.2007.09.001
Clinics in Dermatology (2008)
26, 123–159
soluble. Because of this property, hyaluronic acid can
complex to many molecules of water, reaching very high
levels of hydration. In all tissues and in all species,
hyaluronic acid contains only these 2 types of sugars; thus,
this molecule can be produced from nonanimal sources,
owing to modern biomedical technologies.
Molecular weight
The hyaluronic acid is a uniform, linear, tiled molecule
composed of the repetition of identical disaccharide units.
Different types of solutions based on hyaluronic acid differ
only in the length and the weight of the molecules contained.
For instance, the weight of hyaluronic acid molecules within
the synovial fluid is often decreased in a patient with articular
diseases. In healthy tissues the molecular weight of
hyaluronic acid is from 5 to 10 million. In some tissues or
species, especially in case of a disease, the molecular weight
can be less than 1 million. The molecular weight of
commercial products based on hyaluronic acid varies from
0.5 to 5 million. The typical molecular weight of proteins is
less than 100,000 compared to most vertebrate polysacchar-
ides that weigh approximately 10,000 and is linked to
different types of proteins.
Molecular length
The molecular length and the weight of hyaluronic acid
depend on the number of polysaccharide units present in the
chain. The length of a chain varies in different species and
tissues, but most variations depend on a tissue's condition.
One molecule of hyaluronic acid with a molecular weight of
10 million contains 25,000 disaccharide units linked to one
another to form a long linear chain composed of a repetition
of a 1 × 1-nm disaccharide unit. In normal tissues, a molecule
of hyaluronic acid weighing about 10 million is 1 nm thick
and 25
μm long. For a comparison, the diameter of an
erythrocyte is 7.5
μm.
Concentration in tissues
In all tissues, hyaluronic acid is an essential part of the
extracellular matrix. Very high concentrations are found in
tissues such as the umbilical cord (4 mg/g), synovial fluid
(3-4 mg/mL), and vitreous humor (0.1-0.4 mg/g). The mean
concentration of hyaluronic acid is 200 mg/kg (0.02%). A
human body weighing approximately 60 kg contains about
12 g of hyaluronic acid.
Tissue
Hyaluronic acid (mg/L)
Synovial fluid
3500
Vitreous humor
200
Extracellular space
Hyaluronic acid (mg/kg)
Cartilage
1200
Skin
200
Lung
150
Others
Hyaluronic acid (mg/L)
Serum
0.05
Intracellular
Absent
All tissues
200
Although a higher hyaluronic acid concentration is found
in connective tissues, the greater part of it (56%, 7 g) is
found in the skin. In its normal state in tissues, the hyaluronic
acid is present as a free polymer, although in some tissues
such as cartilage, it is linked to different structural
glycoproteins (proteoglycans) or in other tissues to specific
cell receptors.
Metabolism
The biosynthesis and catabolism (metabolism) of hya-
luronic acid are unique. The biosynthesis takes place through
an enzymatic complex within the cell membrane, and
scavenging as well as degradation processes are mediated
by the link to a receptor, followed by the intracellular
degradation. This process is very fast and effective.
Biosynthesis
The mechanism of synthesis of hyaluronic acid has been
explained only in recent years. The biomolecules are
synthesized inside the cells. The enzymatic complex that
produces hyaluronic acid is not located inside the cell but
inside the cell membrane. The 2 basic saccharide units are
added to the hyaluronic acid chain inside the cell, and the acid
itself is released directly in the extracellular matrix. Many
types of cells can synthesize the hyaluronic acid, for example,
fibroblasts, synovial cells, endothelial cells, adventitious
cells, and oocytes. The synthetase that produces hyaluronic
acid is identical in many species (human, chicken, frog, etc),
thus confirming the concept of a unique, uniform chemical
structure of this molecule in the animal kingdom.
Catabolism
Hyaluronic acid's turnover is very fast when compared to
other extracellular components such as collagen. In most
Scheme 1
Chemical structure of hyaluronic acid.
124
M. Romagnoli, M. Belmontesi
tissues, the half-life of hyaluronic acid varies from 12 hours
to a few days. In the skin, the half-life is less than 24 hours.
The daily turnover of hyaluronan is around one third of total
body content; thus, about 3 g of hyaluronic acid is
catabolized every day by a healthy human body. The big
hyaluronic acid molecules are degraded to their constituents
by intracellular lysosomial enzymes.
Residence time in tissues
The residence time of hyaluronic acid in tissues depends
only partly on the molecular weight. Hexogen and endogen
hyaluronic acids have a molecular weight of approximately 1
to 10 million. Many commercial products weigh approxi-
mately 1 million, but some of them, modified, can reach
10 million. Inflammatory processes favor a very fast
degradation. In most medical applications, the residence
time is around some weeks or months.
Functions
In the extracellular space, the functions of hyaluronic acid
are basic to the maintenance of a tissue's structure and
functions owing to its ability to:
• Create volume;
• Lubricate tissues;
• Affect cell integrity, mobility, and proliferation.
In the amorphous matrix of connective tissue, the
hyaluronic acid (approximately 1% of which is complexed
to other molecules forming bigger structures, the proteogly-
cans) is concerned in maintaining the moisture, turgidity,
plasticity, and viscosity. It can also act as a cementation agent
and as an antishock molecule, as well as an efficient lubricant
preventing cell damages induced in the tissues through
physical stresses. The very long length of the molecule
together with its high hydrating property allows many
hyaluronic acid polymers to organize in a reticular structure
having the following main functions:
• creation of a molecular framework that supports a
tissue's tone and shape;
• action as a filter to block the spreading in tissues of par-
ticular substances, and of bacteria and infectious agents.
Only quite low-molecular-weight substances will pass
through the meshes of this net, spreading in the tissues; all
higher-molecular-weight substances, such as bacteria or
viruses, will be trapped in the net. The hyaluronic acid,
furthermore, also plays a role when the cells need some space
for mobility and division, cooperating in cell differentiation,
migration, morphogenesis, embryogenesis, and wound repair.
Also, the articular tissues are lubricated by hyaluronic acid; the
high viscosity and elasticity of the solutions containing hya-
luronic acid create a fluid layer that protects moving tissues.
Biocompatibility
In general, biomolecules synthesized by different species
have different chemical content; when foreign substances get
in contact with the body, different responses are displayed,
such as immune responses or organ transplant rejection. In
contrast to other molecules, hyaluronic acid does not depend
on the source of its synthesis because its chemical structure is
invariable. All the cells synthesizing hyaluronic acid do it
following the same pattern. The same happens in some
bacteria that have acquired the ability to produce hyaluronic
acid from vertebrate.
Production process
Hyaluronic acid can be obtained by extraction from
tissue or produced with advanced biotechnological meth-
odologies. The hyaluronic acid obtained by extraction from
tissue can contain some impurities from the tissue where it
originates. The use of biotechnology allowed the isolation
of some bacteria that possess the enzymatic system for
hyaluronic acid production. These bacteria are grown in
media containing water and other nutrients, and the
hyaluronic acid these secrete is harvested and purified.
Residence time
The turnover of hexogen and endogen hyaluronic acid
is very fast but can be slightly modified by varying
molecule's size or concentration. Variation in molecular
weight only slightly increases the residence time. In a
healthy tissue, the extracellular ability to degrade
hyaluronic acid is very low. It probably depends on the
presence of free radicals cleaving the hyaluronic acid
molecules that later will be catabolized by linking to the
cell membrane and subsequent pinocytosis. The most
abundant degradation is through the lymphatic system
with partial depolymerization of hyaluronic acid and its
removal from the blood stream. The latter will be purified
by the degradation of hyaluronic acid to carbon dioxide
and water.
Uses
The are various possible uses. Hyaluronic acid injections are
used together with collagen protein injections in aesthetic
surgery and dermatology to eliminate wrinkles and to prevent
skin aging. In otologic surgery, hyaluronic acid is used as a
regenerator after perforation of the tympanic membrane. In
ophthalmic surgery it is used for the production of artificial
drops and in surgery of vitreous body of the eye. In orthopedics,
it is used as an antiphlogistic lubricant and a preserving agent of
joint's synovial fluid. Recent studies (not yet fully confirmed)
show that it can bind to CD44 receptors of the cells of hair
follicles, favoring their division and hair production.
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Hyaluronic acid—based fillers: theory and practice
Fillers
The most common definition for fillers is that these are
“materials injected in the face to fill wrinkles or depressions.”
These were introduced at the end of the 1960s as a remedy
for face imperfections in the form of silicone oil, a chemical
compound in a liquid, more or less viscous. Since 1980s, the
use of silicone is not allowed for the correction of skin aging.
The first filler, whose production and implantation techni-
ques were experimented in Palo Alto, Calif, in 1976, was the
injectable collagen. Since then, new molecules have been
studied and proposed as filler materials. Basically, we can
distinguish between 2 groups of fillers classified based on
their chemical composition:
1. Biological fillers: completely
“natural” molecules; they
undergo a more or less rapid skin resorption.
2. Synthetic fillers: they can be divided into:
▪ Totally synthetic;
▪ Partially synthetic.
Synthetic fillers show a very slow resorption or remain
permanently in the dermis. Among the fillers at our disposal,
some of them are indicated for wrinkle treatment and others
for depression filling.
Depending on the site of filler implant, we can distinguish:
▪ Superficial fillers: to be implanted in the superficial
dermis; they correct the
“mimic” wrinkle appearance.
▪ Deep fillers: to be implanted in the deep dermis, some
of them in the subcutaneous tissue; they correct
depressions, emptyings, or real
“furrows.”
The ideal filler
It is difficult to define a filler as ideal. Many opportunities
and solutions can be obtained within the wide variety of
materials at our disposal. The ideal filler should have the
following characteristics:
▪ Maximum result: both as percentage of imperfection
correction and as percentage of patient's satisfaction.
▪ Duration: namely, the persistence in time of the efficacy
of wrinkle correction. It is obvious that the biological
fillers have a limited duration (average of 3-6 months),
whereas synthetic materials show a longer duration (even
2 years), after which they also require some retouches.
▪ Safety: deriving from the possibility to avoid undesired
side effects.
▪ Minimal trauma: the chance to reduce to minimum the
trauma of a filler implies a better acceptance of the
treatment by patients; furthermore, it implies a lesser
persistence of evident signs (some small hematomas
could be present, resorbable in 3-4 days) as a
consequence of the implant itself.
▪ Costs: it is clear that an “acceptable cost” is a very
important point when choosing a filler. A good cost-
result ratio is the way to widen the number of patients
who can undergo these treatments.
Hyaluronic acid for fillers
Cross-linked or stabilized hyaluronic acid is nowadays
the most used resorbable filler. Since its first commercia-
lization in 1996, many molecules have been marketed.
These differ in the cross-linking or stabilization process,
necessary to lengthen their degradation by hyaluronidase.
The European laws classified it as a class III medical
device. Because hyaluronic acid is injectable, the medical
procedure for its use requires a premarketing controlled
clinical trial to attest the product's safety and efficacy with
respect to a reference gold standard. The trial should be
certified by a specific authorized agency. The producer
should also shoulder the burden of the product's tracking
and of device supervision regarding the potential post-
implant adverse and side effects, which should always be
notified to the Ministry of Health. The reference gold
standard in the category of resorbable fillers is bovine
collagen. A particular hyaluronic acid, the nonanimal
stabilized hyaluronic acid (NASHA), presently cited in
most scientific publications, has been shown to be more
durable and much safer compared to bovine collagen. The
ideal filler, in fact, should be nontoxic, nonmutagenic, non-
immunogenic, biocompatible, not migrating from the
implant site, naturally integrating within tissues, easy to
use, and with an acceptable duration with respect to costs
and expectations.
Characteristics of hyaluronic acidbased fillers
A number of fillers based on hyaluronic acid are
presently marketed. There are hyaluronic acids from animal
origin and rooster combs, but most are extracted from
bacteria, especially from Streptococcus equi, a bacterium
nonpathogenic to man. This is because the hyaluronic acid
molecule is identical in all organisms and species; its
biocompatibility and non-immunogenicity allow us to use it
without pretesting for sensitivity, such as in the case of
bovine collagen, even if it is not human derived. This was
one of the keys to success of this molecule; it reduced
the percentage of postimplant adverse events and made
the treatment feasible without waiting for the results of the
sensitivity test for 2 to 4 weeks (some authors suggest a
double test in case of collagen). After the extraction,
filtration, and purification processes, the structure of
hyaluronic acid is necessarily modified to remain in
tegument tissue for the 6 to 12 months certified from
producers. In fact, natural hyaluronic acid, used for instance
in biorevitalization, does not persist in tissues for more than
24 hours. The stabilization, or cross-linking, process is the
126
M. Romagnoli, M. Belmontesi
subsequent necessary step that defines the prolonged
duration of the material in the correction sites. Cross-linking
agents presently used are BDD butanedioldiglicioile and
vinyl sulfone. The product's safety is based on the process of
“washing” all the residues of these cross-linking agents to
obtain a pure, nontoxic, and biocompatible product. The
fight between
“duration” and “compatibility-safety” of
postimplant hyaluronic acid is then
“open.” It should be
ideal to have a molecule as identical as possible to the natural
one, although not assailable by degradation enzymes, that is,
hyaluronidases. Another key in this process is obviously the
hyaluronic acid purity after bacterial extraction.
Presently marketed fillers
The following sections list some of the molecules
presently used, as well as their bond characteristics.
Q-Med (Uppsala, Sweden)
The products are characterized by a different number
of spherical particles per milliliter and per different size
(
): this implies different clinical indications (
).
Restylane 1 mL/100,000
Restylane Perlane 1 mL/10,000 particle number
Fig. 1
Nonanimal stabilized hyaluronic acid.
Fig. 2
Nonanimal stabilized hyaluronic acid tissue-specific materials.
127
Hyaluronic acid—based fillers: theory and practice
Restylane Touch 1 mL/500,000 of gel per milliliter
Restylane Sub-Q 1 mL/1000
Restylane Lipp Gel dynamic and cohesive
Restylane Vital mild stabilization
Stabilized hyaluronic acid in gel (20 mg/mL) is produced
from S equi with a fermentation procedure. The hyaluronic
acid chains are chemically stabilized with a procedure that
modifies less than 1% of the chain sequence. Because it is
not animal-derived, it is named NASHA.
Teosyal: Teoxane Laboratories (Geneva, Switzerland)
First Line 20 mg/mL 30G or 32G
Global Action 25 mg/mL 30G
Deep Lines 25 mg/mL 27G
Kiss 25 mg/mL 27G or 30G
Ultra Deep 25 mg/mL 26G
These products differ in hyaluronic acid content and
cross-linking level. Based on these characteristics, their
indications are different (
). The levels of endotoxin
bacterial residue are less than 0.2 European Union (EU)/g;
these levels are fixed at less than 12.5 EU/g following
regulations. Protein levels are less than 5
μg/g.
Isogel: Laboratories Filorga (Paris, France)
Class 1
—14 mg/mL superficial dermis, thin wrinkles;
Class 2
—24 mg/mL middle dermis;
Class 3
—30 mg/mL lips, zygoma, volume, sculpturing of deep
dermis; 1.2 mL sterile syringes. High-molecular-weight
hyaluronic acid: 3 million daltons. PQ HP: quaternary
hyperreticulation process. The bonds are in the single
hyaluronic acid chain as well as among chains. In this way,
gel cohesion increases and the surface exposed to hyalur-
onidase degradation is limited. Residual protein index,
0.004
μg/g. Two milligrams of free hyaluronic acid is added
to the cross-linked product. This step makes the injection
easier because the product is more fluid and the cross-linked
chains are more protected against hyaluronidase.
Allergan
Hydrafill grade 1, Hydrafill grade 2, Hydrafill grade 3:
hyaluronic acids with increasing cross-linking levels;
SoftLine: 20 mg/mL of cross-linked hyaluronic acid + non
–
cross-linked hyaluronic acid;
SoftLine MAX: more cross-lined than the preceding product,
although fluid because of the presence of natural hyaluronic acid
with 20 mg/mL of cross-linked product;
Hylaform Plus, Hylaform Fine Line: from hyaluronic acid; both
derived from rooster combs;
Juviderm-Surgiderm: cross-linked with BDDE, biosynthetic
origin, 3-dimensional matrix of hyaluronic acid;
18 mg/g hyaluronic acid
—Surgiderm 18
24 mg/g of increasing reticulation level: 24 xP;
30;
30 xP;
Surgilips: single phase hyaluronic acid cross-linked with BDDE;
Voluma: biosynthetic hyaluronic acid, 20 mg/g with 3-dimen-
sional reticulation.
Belotero: Merz Aesthetik (Frankfurtammain, Germany)
Biosynthetic hyaluronic acid with double BDDE reticulation,
cohesive gel with differentiated density; cohesive polydensified
matrix technology;
Basic: 22.5 mg/mL, higher gel percentage with elevated
viscosity;
Belotero Soft: 20 mg/mL, higher gel percentage with moderate
viscosity.
Fig. 3
Summary table
—Teosyal range. Reprinted with permission from the Teoxane Laboratories.
128
M. Romagnoli, M. Belmontesi
FDP (Naples, Italy)
High fill: 20 mg/mL of cross-linked hyaluronic acid, viscosity,
6500 m/Pascal;
High fill AV: 24 mg of cross-linked hyaluronic acid, viscosity,
9000 m/Pascal.
These are synthetic hyaluronic acids obtained from
bacterial fermentation and cross-linking with BDDE. Both
contain 2.5 mg of free hyaluronic acid in addition to the
cross-linked one.
Bio-Polymer GmbH and Co KG (Montabaur, Germany)
Matrigel:
Hyaluronic acid sodium salt, 25 mg;
Cross-linked hyaluronic acid (high viscosity), 25 mg;
Carboxymethyl cellulose, 15 mg.
Matridur (thin wrinkles, superficial use):
Hyaluronic acid sodium salt, 25 mg;
Cross-linked hyaluronic acid, 25 mg;
Carboxymethyl cellulose, 15 mg.
Presently replaced by:
Covalent Reticulated Matrix (CRM) DUR
Cross-linked sodium hyaluronate (BDDE), 14 mg;
Biotechnological poly
–cross-linked hyaluronic acid with
CRM technology (linking agent, BDDE); superficial dermis
implant, 30G needle
—for superficial, perilabial, and ocular
wrinkles.
CRM GEL
Sodium hyaluronate, 4 mg;
Cross-linked sodium hyaluronate (BDDE), 16 mg;
Biotechnological poly
–cross-linked hyaluronic acid
with CRM technology; middle-deep dermis implant;
29G needle
—for volume augmentation of malar area,
deep wrinkles, nasolabial folds, glabellar furrows, and
lip augmentation.
Rofil Medical (Breda, The Netherlands)
Rofilan Forte, double
–cross-lined hyaluronic acid with
vinyl sulfone and hydroxypropylmethyl cellulose, from
bacterial fermentation, 9 mg, 30G needle
—for horizontal
wrinkles in forehead, crow's feet, perioral wrinkles, acne
scars, lip augmentation.
MacDermol from MacDermol SarGenopole d’Evry
(Paris, France)
MacDermol S, hyaluronic acid from rooster combs, 2.1%;
superficial or middle dermis implant
—for superficial,
perioral, and periocular wrinkles.
MacDermol R, hyaluronic acid from rooster combs,
3.4%; middle-deep dermis implant
—for deep wrinkles,
nasolabial folds, lip augmentation.
Mentor
Puragen: biotechnological double
–cross-linked hyaluro-
nic acid with DXL technology (double reticulation of both
hydrophobic and hydrophilic esteric bonds).
Hyaluronic acid in aging face: when and where
The presence on the market of a variety of hyaluronic acids
allows a real whole facial restructuring, by restoring the
volumes lost during the chronoaging processes in sites such
as those of the mid-third of the malar region, the
subcommissural furrow, the inferior third, and the chin area.
This first step that can be accomplished with basic hyaluronic
acid requires high quantities of product. For this reason, it is
preferable to use hyaluronic acids specifically studied for
deep implants (subcutaneous or subperiosteal) with better
results with the same implanted volume. These can be used
for the filling of deep wrinkles alone or to create the base of
the wrinkle that will then be refined superficially with other
acids, with a technique named composed flooring. The areas
more prone to this technique are the nasolabial fold, the
subcommissural angle, and the labial-chin furrow. The tear
trough is sometimes very marked and gives a tired and older
appearance. To obtain a
“fresh” look, a deep implant at the
periosteal level is required. This is technically difficult; thus,
this is only for the skilled hands and can be done possibly with
products of medium viscosity and using few drops of material
injected medially in the inferior orbital rim. The first
indication in case of single or double, horizontal or vertical
glabellar wrinkles, of horizontal wrinkles on the forehead,
and of periocular radial wrinkles (chick's crows) in the upper
third of the face is botulinum toxin. This does not mean that
these areas are prohibited to fillers. On the contrary, highly
marked wrinkles and very thick skin, such as in man, often
require a filling subsequent to botulinum toxin treatment to
cancel wrinkle memory. The combination of the 2 techniques
is more durable. This should be done about 2 weeks later,
when the toxin effect is complete. Much attention should be
paid when the upper third of the face also suffers from
gravitational effects, that is, in old patients, in patients with
blepharochalasis and subpalpebral bags, or in supraciliar
ptosis. In these cases, botulinum toxin treatment could be
contraindicated and anyway reserved to the very skilled
hands because it could inhibit the compensatory muscular
movements, highlighting the defects. Thus, the filler can
appropriately be used to project the lateral third of the
eyebrow, raising it, to correct the horizontal wrinkles on the
forehead located 1 to 1.5 cm from the supraciliar arch, the thin
wrinkles of the inferior eyelid, and to fill the temporal fossa
when it loses its natural fat. The nasal pyramid can also be
slightly improved, filling the small
“minuses” that appear
near the small humps, especially near the glabella, obtaining a
more linear profile without surgery. The mid-third region of
the face can undergo the most significant treatments.
Zygomatic and nasolabial areas can undergo multiple types
129
Hyaluronic acid—based fillers: theory and practice
of implants. Only the lips and the perioral area can have the
same number of techniques.
Products’ sites and uses
Restylane, Hydrafill grade 2, SoftLine, Hydroform,
Teosyal Global Action, Belotero Isogel class 2, Hyfill,
Surgiderm 24 xP, Matridur, Matrigel, Rofilan Forte, and
Puragen are the basic products; they can be used in all
indications. The unskilled should be particularly careful in the
areas of thin wrinkling, that is, the periocular and
“bar code”
areas, where the implant can be too visible (Tyndall effect).
When acting on volumes and lips, the duration could be less
than what obtained with more specific hyaluronic acids.
Restylane Perlane, Teosyal Deep Line, Ultra Deep, Isogel
class 3, Hydrafill grade 3, Soft line Max, Juviderm-
Surgiderm 30 XP, High fill HV, CRM gel, and MacDermol
R are used to correct deep furrows and wrinkles, at the level
of the mid-deep dermis.
Restylane touch, Hydrafill grade 1, Hylaform Fine Line,
Teosyal first line, Isogel Class 1, Surgiderm 18, MacDermol
S, and CRM DUR are the most fluid products with less
reticulation and/or concentration of hyaluronic acid. Their
use is very superficial, intended for refining of the above
implants or in areas of thin skin, such as in periocular,
subpalpebral, and perioral regions, especially for filling of
the vertical lines of bar code.
VITAL (Q-Med) is different because it belongs to the
group of modified hyaluronic acids. Its optimal use is in the
mid-deep dermis to reduce dehydration of the thin wrinkled
regions; for example, the use on the actinic wrinkles in a
patient with thin skin gives optimal results. It can be used on
the neck, back of the hands, neckline, knees, and arms and,
also differently from others, in the rejuvenation of tissues.
Lip correction: specific products:
Volume: Lipp Q-Med
Volume and perioral region: Teosyal Kiss, Surgilips.
The specific products for lip correction are characterized
by a higher reticulation that should give them a longer
duration in a site known to be subjected to a rapid resorption
(3-4 months) because it is much vascularized and particularly
mobile. In the case of Lipp, the conformation of hyaluronic
acid allows an adaptation of the product to the particular
anatomy of the submucosa, avoiding unaesthetic masses and
giving the correction a very natural appearance, soft to the
touch. Its limit resides in the fact that it can be used in the
submucosa only and not in the perioral area.
Sub-Q (Q-Med) and Voluma (Allergan) are used for the
filling of volumes and for the sculpturing of deep implants.
Indications
Among the wide therapeutic choices at a physician's
disposal to correct the defects of skin aging, the fillers have an
irreplaceable role in the restoration of volume, both of wide
and small areas. No other treatments give such an immediate
result with such a rapid resumption of social life. The
restoration of lacking volumes can be superficial (wrinkles),
more deep (furrows), or concern a real volume
“sculpturing”
in tissues that, after aging, have lost natural turgidity. This
phenomenon is observed especially in sites exposed to
resorption of adipose (ie, zygoma) and bone tissue (ie,
submandibular region). The hyaluronic acid is used also in
congenital and posttraumatic hypoplasia, often to give
patients in advance an idea on the effect of the correction in
place of more surgical procedures (such as cheek prosthesis).
Defects to be corrected by fillers as a first choice
(see the face with the implant sites)
– Nasolabial wrinkles and folds;
– Marionette and oral commissural wrinkles;
– Subcommissural furrows;
– Sleep wrinkles (creases);
– wrinkle on chin;
– Zygoma;
– Temporal area (depressions);
– Chin;
– Lips;
– Philtrum;
– Auricular lobe;
– Tear trough.
Defects to be corrected by fillers as a second
choice (easier and more immediate method,
although less effective)
– Dynamic wrinkles, especially in the upper third of the
face (first choice: botulinum toxin), eyebrow raising;
– Vertical wrinkles of inferior and superior lip (peeling,
ablative laser);
– Periocular wrinkles (botulinum toxin, laser);
– Subpalpebral wrinkles (laser);
– Mandibular arch region;
– Small “minus” in the pyramid and nose tip;
– Actinic wrinkles of labial region (laser, peeling);
– Extensible depressed scars (laser, peeling, surgery).
Sites where hyaluronic acid use is not indicated
– Nonextensible scars (eg, ice pick);
– Neck, neckline, and other sites different from the face,
with the exception of the back of the hands;
– Sites previously implanted with permanent or unknown
fillers, still palpable.
Contraindications
Absolute:
– Reported previous reactions to cross-linked hyaluronic
acid;
130
M. Romagnoli, M. Belmontesi
– History of multiple allergies;
– Previous anaphylaxis;
– Implants in incongruous sites (breast, muscles, vessels);
– Collagen diseases;
– Psychic patients;
– Presence of permanent fillers.
Temporary:
– Herpes or other diseases in the implant site (acne,
dermatitis);
– Intake of drugs that facilitate the onset of ecchymoses
(NSAID, anticoagulants, vitamins C and E,
ω-3 and
ω-6);
– Coagulation deficiencies;
– Pregnancy and lactation;
– Immediate sun exposure or postimplant exposure to
heat sources;
– Important social life events in the subsequent 72 hours.
Relative:
– Presence of other resorbable material in the correction
site;
– Autoimmune diseases;
– Diabetes;
– Predisposition to infections and to keloid scars;
– Unreal expectations;
– Diseases subject to Koebner's phenomenon.
Schematic correction sites
Fair physician-patient approach
The correction of a defect, linked or not linked to aging,
should provide for a careful attention to patient's requests to
evaluate whether or not these requests can be technically
satisfied with hyaluronic acid or with other methods (better if
combined) (
). Physician-patient approach
should follow the procedure:
1. Complete history: chronic diseases, patient's allergies,
and so on, help the physician in the choice of the filler.
2. Skin checkup: with particular attention to the examina-
tion of imperfections. It could be a wrinkle, a fold, a
depression, or a pseudodepression (not as a thinning of
subcutaneous tissues, but as a relaxation with excessive
folding of the area above).
3. Evaluation of the patient's needs and expectations:
which are the less accepted imperfections, not only
physically but also psychologically?
Fig. 4
Mouth: details.
Fig. 5
Sites of implant.
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Hyaluronic acid—based fillers: theory and practice
Written informed consent
An informed consent is not mandatory in the written form,
although important orally. It should sum up everything about
potential advantages and risks:
– Therapeutic alternatives (other fillers, lypofilling, etc);
– Side effects: differentiating between probable and rare
ones;
– Pre- and postintervention precautions;
– Cost estimate, evaluation of the duration of results;
– Subsequent follow-up and corrections.
Preparation for the implant
Preparations are as follows:
– The patient should be skin-cleansed;
– The patient should be disinfected;
– The patient should be under a good light;
– The patient should be seated or in a position that
facilitates the observance of the gravitational effect on
tissues to treat;
– It is useful to take a preimplant picture;
– Evaluation with patient of possible defects or asymme-
tries with the aid of a mirror;
– Evaluation with patient of the most appropriated
implant sites. Patient's requests should always be
taken into consideration, but physician's opinion
should always be given about the areas to correct,
even if not highlighted by the patient;
– Time planning: it is preferable for an optimal correction
in a single site rather than a massive distribution of
material, with the risk of unsatisfactory results.
The patient should clearly know that duration and efficacy
of correction depend also on the quality of the material used.
Tips and tricks
In any case, suggest a check in 2 weeks to correct possible
imperfections or to follow up a global result. If this is the
patient's first session, it is not advisable to implant great
volumes. Hyaluronic acid attracts water; thus, the edema that
can develop in the days after the implantation may worry the
patient, making the patient hesitate to undergo this procedure
again or in the future. Patients used to the procedure are a
different case: on the contrary, they may be interested in time
optimization. In case of an implantation of great quantities
(more than 2-3 mL of product), a pharmacologic therapy may
be helpful immediately after the intervention to reduce the
discomfort in the following days (betamethasone 4 mg, 1
ampule, IM, after the implantation, or Arnica 9 ch/Apis 6 ch,
5 + 5 sublingual granules from the day before up to 20 days
after implantation). Aside from the number of planned
sessions, the physician should estimate in advance the
quantity of material to use. It is important to give the patient
all useful elements, also the economic considerations,
needed not only to obtain the expected result but also for
maintenance. Inform the patient that checks at 3 to 4 months
will be necessary once the optimal results have been
reached, allowing maintenance without excessive expenses
at the patient's charge. The areas that undergo dynamic
stress and are very vascularized such as lips show more
rapid resorption times. On the contrary, zygoma, tear
trough, nasal pyramid, and scars show long duration
corrections, often more than 6 months.
The session
Pain management
Pain threshold for implants as well as for all other
aesthetic procedures of correction is strictly personal: bear in
mind that the patient will want to come back. A traumatic
treatment often removes this wish. The first step is the
creation of an empathic, relaxed atmosphere. Confidence in
the physician is of great help. The physician should decide
with the patient how to manage not only the
“discomfort” of
the small needle (32G or 26G) but also of the hyaluronic acid
gel not combined with an anesthetic, thus bruising a little.
There are many solutions:
▪ Ice packs before and after implantation;
▪ Topical anesthetic: very useful in sites of very thin skin
(periocular area, labial mucosa), yet avoiding the
discomfort of the needle only, not of the gel;
▪ Infiltrating anesthesia, avoiding to deform the implant
area (useful in the commissures);
▪ Anesthetic block: surely the most effective, but we
personally find it useful for lips and perioral area only.
The treatment is started after an ice pack, followed by
anesthesia only if the patient asks for it, especially if this is
the first implantation. In fact, anesthesia is often useful in the
first implantation; then the patient gets used to the method
and
“patiently” tolerates a few-minutes discomfort, avoiding
the inconvenience due to the block in the subsequent hours.
When the patient can consciously choose to use an anesthetic
or not, his or her compliance greatly increases and he or she
does not experience the discomfort as something unavoid-
able or, worse, imposed.
Correction techniques
The following are basic techniques:
Nasolabial wrinkles and folds;
Glabellar wrinkles;
Wrinkles on the forehead;
132
M. Romagnoli, M. Belmontesi
Lip contour, definition;
Philtrum;
Subcommissural wrinkles and furrows;
Commissural wrinkles;
Zygoma, chin, endodermal correction.
These are advanced techniques requiring more manual
skill, to be performed by a well-experienced specialist.
Lip: volume;
Periorbital region;
Supraciliar region and temporal fossa;
Vertical perioral wrinkles;
Zygoma-chin: over-periosteal correction;
Mandibular contour;
Nose tip
—nasal bridge;
Tear trough.
Basic techniques
The first step is the right choice of hyaluronic acid. In
case of doubts, it is preferable to use the basic product of
the line whose unique limit could be the efficiency and
the lower duration, without the risk of imperfections. For
the same reason, when choosing the depth of the implant,
it is preferable to stay at a very deep level, deep dermis
or subcutaneously, to avoid visible translucent blue
masses (Tyndall effect). The needle should create a 30°
to 45° angle to the skin, 45° angle in case of highly
viscose material and/or less number of particles per
milliliter. The orientation of needle bevel is not important,
even if we prefer it to be directed to the operator rather
than to the skin's deep layers, except in case of porous
and thin skin.
The infiltration technique can be (
– Linear
– Retrograde: when the infiltration is done during needle
extraction. This is the most used technique.
– Anterograde (advanced technique): infiltrating infinite-
simal quantities of material during the introduction of
the needle in skin layers. The small quantity of
hyaluronic acid infiltrated before needle passage shifts
the small vessels, avoiding causing minor traumas. This
is a useful technique in the sites more exposed to
ecchymoses and bleeding risks, such as lips, tear trough,
and periocular region.
Fig. 6
Infiltration techniques.
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Hyaluronic acid—based fillers: theory and practice
– Serial puncture: the easier technique because it does not
require particular skills when moving the needle in the
skin layers. It is more traumatic because the number of
skin access is higher, but the risk of vascular traumas is
decreased. It is used depending on personal preferences. It
can be useful for small superficial corrections in the tech-
nique of superimposed layers, in periocular and perioral
areas, and in the white part of upper and lower lips.
Fanning and cross-linking techniques
These are both linear techniques used in the treatment of
important volumes and wide areas.
Nasolabial wrinkles and folds
Together with the labial area, these are the sites where a
correction with a filler is often requested. When the depression
is not so evident, it may be enough to inject 1 mL of basic
product, but it may also be necessary to inject filling in
superimposed layers with 2 to 3 mL of material, combining the
basic product with other fillers at higher density, to be
implanted deeply if folds are present. The correction of this
area gives generally satisfying results and can also be done by
neophytes once some principles are fully understood. We
distinguish between the accentuation of the nasolabial fold
linked to the ptosis of the superficial muscolo aponeurotic
system, typical of chronoaging, which is easier to correct if not
too evident and perfectly visible in a sitting or standing patient
(not laying) at rest, from the one possibly present in a young
subject, which is more difficult to correct with the filler alone
and is linked to hypertonicity of the elevator muscle of the
upper lip. In this second case, the fold will be more evident,
especially in the upper part (wing furrow) of the triangle among
the nose wing, nose, and cheek when the patient is asked to turn
up the nose. In this case the correction will be more effective if
combined with botulinum toxin use on corresponding muscles.
Good practice includes the analysis of the more depressed
areas, to start from these with a mid-deep dermal implant. The
needle should not be visible, but the gel should be palpable
during the infiltrating phase. This first phase is followed by the
implant in the less depressed part with the same material or
with a more fluid one, with this latter case to be implanted more
superficially. In the second case, the needle can be seen through
easily, but no whitening of tissue should be present during
infiltration because this may cause the implant to be visible.
This risk is more elevated in thin skins, where it is possible that,
in case of an implant that is too superficial, a red-brownish sign
appears, lasting for some days, due to the trauma of needle
track (
).
Tips and tricks
Keep medially to the wrinkle's depression to avoid
prolapse accentuation of labial area with lateral dislocation
of the material. The triangle in the upper-mid position of the
fold, in correspondence to the nose wing, is highly
sensitive: a topical anesthesia may be useful, as well as a
fanning infiltration with inferior-lateral cone apex with
respect to the medial wing, to limit the number of needle
skin access. The correction of this area is important because
the permanence of this depression greatly reduces the final
Fig. 7
Correction lines of the subcommissural furrow and nasolabial fold.
134
M. Romagnoli, M. Belmontesi
effect. In case of infiltration in 2 layers during the same
session, try to use the same cutaneous access routes to
reduce to a minimum the trauma and the risk of ecchymoses
by limiting to the second, more superficial layer, forming a
30° angle.
Glabella and forehead horizontal wrinkles
When using fillers in the glabella, some considerations
should be done: botulinum toxin is highly indicated for
correction of wrinkles in this area. In some situations the
filler has an indication that may be exclusive or comple-
mentary. Wrinkles in this area are mostly due to the
contraction of frontal muscle (forehead horizontal wrinkles),
corrugator muscle of the eyebrow (vertical wrinkles,
glabella), and procerus muscle (horizontal wrinkle of
glabella). Sometimes the reduction of the contraction
strength of the muscle after botulinum toxin is not enough
or not advisable to obtain an optimal correction. The use of
the filler is the first choice when absolute or relative
contraindications to botulinum use are present, such as the
presence of significant blepharochalasis. Wrinkles are
worsened in thick, redundant skin or in those with high
level of elastosis, often in man. In these cases, the correction
using the toxin alone may be incomplete and must be
completed with the filler. To identify this chance, the
maneuver of stretching the glabellar wrinkles between the
fingers can be helpful. If the wrinkles are still visible, filler
use will be surely necessary for a complete correction. The
filler should be used 2 weeks after the first treatment for a
better analysis of the areas that still need a correction. The
same concept applies in the case of forehead horizontal
wrinkles, where 2 alternatives are possible:
– Frontal wrinkles, seborrheic thick skin, or sun elastosis;
– Frontal wrinkles at less than 2 cm from supraciliar arch,
particularly those lateral to the temporal fusion line: an
area that is off limits for the toxin, due to the high risk of
palpebral and eyebrow ptosis.
The particular terminal vascularization of the glabellar
area and of the underlying bone layer advise against the use
of materials that are too thick or of excessive volumes in
this area. In fact, even if extremely rare, some cases of
glabella necrosis are described in the literature. The risk
could be connected either to a direct intravasal infiltration
of a terminal arteriole or to a compression of the tissue
between the underlying bone and great and dense quantities
of material.
Tips and tricks
If possible, prefer a previous correction with botulinum
toxin, implant small quantities at a time, and use basic
material of with low viscosity. The implant should be done in
the mid-deep dermis, with the needle bevel downward,
because the high concentration of sebaceous glands in this
site can cause the extrusion of the material through follicles
during the implantation. In case of whitening of the tissue
during the process, immediately suspend the procedure,
vigorously massage the area, and apply warm packs on the
area to facilitate restoration of vascularization; follow up
during the following days. Some authors suggest the
application of topical nitroglycerine also.
In forehead horizontal wrinkles, it is advisable to use
fillers that are not too viscous because the immediate
nearness of the underlying bone may make the implants
visible. We prefer to correct this area with 3 to 4 monthly
sessions using highly moisturizing hyaluronic acid (Hydro-
reserve), obtaining a more gradual, but natural, correction. In
both sites, we prefer to use the
“serial puncture” technique
with very small quantities of product in each infiltration site.
Stabilized, moisturizing hyaluronic acid should be inserted in
the mid-deep dermis with a short, linear, or elongated serial
puncture technique, interrupting the infiltration much before
needle extraction.
Eyebrow and temporal areas
A woman's eyebrow should be positioned slightly above
the orbital arch. The highest bend should be in the junction
between the mid two thirds and the lateral third. The mid and
lateral poles must be on the same horizontal line. The mid
pole limit is on the line that from the nose wing passes near the
Fig. 8
Proportion and position of the supraciliar arch in men and women.
135
Hyaluronic acid—based fillers: theory and practice
internal side of the eye. The lateral pole stays on the line that
from the nose wing passes near the external side of the eye. In
men, the position is slightly lower, in correspondence to the
orbital rim, and more horizontal. Supraciliar arch position has
a primary role in the aesthetic of the upper two thirds of the
face (
). Shape, thickness, and position of this area
influence facial harmony and express one's mood such as
astonishment, anger, and sadness. Eyebrow position varies in
men and women and tends to lower with aging due to
gravitational effects and to the reduction of the support given
by soft tissues and mostly by orbital arches. The filler can act
by increasing the rising of this latter and of supraciliar fat, in
case of congenital hypoplasia or chronoaging resorption. The
possible changes in this area are only in the order of
millimeters; it is possible to raise and slightly project the
eyebrow in all its length or only in its lateral third with a slight
lifting effect (
). This method does not replace surgery
(brow lift), but can be usefully combined with the action of
the botulinum toxin to obtain a fresher and happier
appearance, characteristics associated to supraciliar ptosis.
In this method, basic or slightly more viscous hyaluronic
acids can be used. Usually, the lateral and mid part of eyebrow
underneath the hair area are infiltrated. In the temporal area, a
small depression can appear, linked to the resorption of
adipose tissue present here, in young subjects. In this case, the
depression can be flattened using a basic filler in superficial
dermis, preferably with the fanning technique.
Tips and tricks
To avoid infiltrations in underlying tissues or a downward
migration of the implant (with consequent palpebral burden-
ing), it is important to keep a finger on the inferior supraciliar
rim. The infiltration area can be held between the fingers. The
implant should be deep supraperiosteal or deep dermal.
Always verify the presence of preexisting asymmetries. The
temporal area is characterized by superficial vessels: a good
light will help in avoiding them. For the unskilled, it may be
good to start with a micropuncture infiltration: the risk of
hematoma should be reduced. In this site, as well in all thin
skin sites and in superficial implants, it is mandatory to
massage the area to obtain a homogeneous correction.
Lip correction
Lip correction may be necessary for congenital reasons or
after facial aging. Manifestations are as follows:
1. Lack of volumes: thin lip;
2. Turgidity and hydration loss:
“shriveled” lip;
3. Loss of lip's contour;
4. Loss of Cupid's bow, that is, the mid part of the upper
lip that limits, with the philtrum lines, a sort of an
enlarged
“M” that during aging gets flatter;
5. Loss of labial tubercle;
6. In the part called
“white lip” in contrast to the mucosal
and transition ones, also called
“red lip,” the aging
process causes the onset of:
– Vertical or radial wrinkles in upper and lower lips,
defining, when maximally present, the so-called
bar code;
7. Descending of lip's corners and formation of commis-
sural wrinkles, also called
“marionette” lines, and of
labial-chin and subcommissural furrows;
8. Loss of the ascending philtrum, that is, of the 2 down-
ward divergent lines that from the columella go to right
and left labial cusps.
Fig. 9
Eyebrow correction: injection along the eyebrow in the medium dermis.
136
M. Romagnoli, M. Belmontesi
The lip undergoes in time to different aesthetic reference
criterions. There are anatomical proportions to refer to, but
considering the variability in time of aesthetic preferences, it
is recommended to use a resorbable product.
The well-proportioned lip
The height ratio between upper and lower lips should be
0.6:1; thus, the inferior lip should be higher than the upper
lip. Instead, lateral limits of the lip should be within 2 lines
tangential to the mid part of right and left iris (
). The
lip can be classified into:
– Short lip, when clearly within lateral limits;
– Long lip, when it exceeds such limits (
In these cases, the correction can aim not only at volume
augmentation but also at the restoration of proportions.
Obviously, there exist a request regarding upper and lower
lip proportions, as well as a restoration of a
“thin lip,”
probably the most difficult to be satisfactorily obtained.
The easier lip to treat is the one that has lost its natural
turgidity, although still proportionate, or the young
proportionate one, for which volume augmentation is
requested (
Fig. 10
Correction areas in the proportionate lip.
Fig. 11
Aesthetic correction morphology.
137
Hyaluronic acid—based fillers: theory and practice
Labial philtrum
Labial philtrum is composed of two crests in relief
that from the columella go downward to the upper labial
cusp apex.
Technique
With the retrograde linear technique, an increasing volume
of product is injected downward. The same infiltration may
be used to augment the volume of labial cusps (
Fig. 12
Volume augmentation of a lip with minus in the vestibular part of upper lip and consequent volume augmentation to
avoid disproportions.
Fig. 13
Infiltration in a thin lip of Restylane Lipp in the submucosal vestibular part of the lip to obtain projection. In such cases, avoid the
treatment of the skin-mucosal rim. Nasal philtrum corrected with Restylane.
138
M. Romagnoli, M. Belmontesi
Tips and tricks
It is important to guide the needle and the material emitted
by shrinking the philtrum lines between the first and second
finger of the nonoperating hand to concentrate the correction
along the line that tracks the philtrum lines, avoiding
product's enlargement. Also, in this site, the implantation is
painful, but it may be sufficient to inject 2% lidocaine in a
small puncture laterally to the labial philtrum, and then in the
mucosa, and to wait 10 minutes to anesthetize the area.
Correction of lip volume
Specially formulated hyaluronic acids should be used for
this type of correction because their structure confers them a
higher resistance to hyaluronidase (major cross-linking) and
to the stresses typical of this site (cohesive and dynamic gel),
with a more natural result. Nowadays, the more up-to-date
look for a perfect lip is this one:
“the correction has been done,
but no one can see it.
” The most used techniques are the
mixed, anterograde, and retrograde, and the serial puncture
technique. The lip is particularly sensitive; thus, the use of a
topical anesthesia is preferred, to be administered 15 to
20 minutes preimplantation. Type and extent of correction
should be discussed in advance with the patient, bearing in
mind that more material can always be added later, if
requested. It is important to inform the patient that in the first
4 to 5 days, the correction will look bigger because of the
edema that always appears in this site and that the final effect
will be clear about 7 days after implantation. When correcting
volumes, the implantation must be done strictly in the ver-
million portion of the lip, at the submucosal level. The needle
will be placed parallel to the labial rim, about 2 mm in its
internal side. A linear, anterograde, and retrograde infiltration
will be performed, slowly injecting small quantities of
product to avoid the risks of hematoma and pain, higher in
this site than in others, when treated without anesthesia. In
this way we can proceed along the perimeter of the upper and
lower lips, if we are only augmenting lip volume.
Thin lip: technique
In the case of very thin lip, it may be useful to implant the
material in the mucosal part of the vestibular side. In this
way, we can obtain a higher vermillion projection. The
implant in the vestibular part of the mucosa may be felt by a
patient as small nodules. The correction may be completed
with a serial puncture infiltration of the 2 upper lip cusps.
Short lip: technique
This is the lip that develops mainly vertically. In this case,
it will be important to infiltrate in the lateral rims, implanting
Fig. 14
Correction of the short lip. Slow antero-retrograde injection in the submucosa of the internal lip, in its lateral part, with an increase of
the projection.
Fig. 15
Correction of a young lip with disproportion between upper and lower lips. Correction done with Restylane Lipp.
139
Hyaluronic acid—based fillers: theory and practice
in the portion that includes the lateral third of upper and
lower hemilip in the vestibular submucosa. The opening of
lateral commissures may also be useful (
).
Long lip: technique
The long lip develops horizontally, with no vertical
projection. In this kind of lip, it is necessary to emphasize the
Cupid's bow with an elongated serial puncture infiltration in
the cusps and tubercle. The inferior lip can be corrected only
medially (
).
Complications
Complications include edema, hematoma, persisting
nodules, higher evidence in salivary glands in the mucosal
part, and asymmetries.
Lip contour
It is a useful correction to emphasize lip contour when the
demarcation line between the white and the red lip is not
sharp. This often happens in the aging lips, when the vertical
wrinkles of upper and lower lips elongate to the vermillion.
The virtual channel between the white and the red lip can be
reconstructed to avoid in these cases the overflowing of
lipstick within vertical lines. This correction must be done
first if a volume augmentation has also been planned.
Technique
The needle has to be inserted in the virtual channel
between the mucosal (red) and the white part. The hemilip is
usually divided into 3 parts: lateral (A), mid (B), and medial
(C) that ends with the apex of Cupid's bow. To complete the
correction, the last segment will be the one between the apex
of Cupid's bow and the inferior part of the
“M” of Cupid's
bow (D), near the labial tubercle. It is important not to use
highly viscose hyaluronic acid, to avoid important edema
and a
“duck's beak” appearance. The infiltration will be
linear, retrograde, and very slow, trying to confer symmetry
to the 2 hemilips. This correction will greatly improve the
lip's vertical wrinkles, obviously only in the part near the
vermillion (
).
Tips and tricks
Lip correction will be more comfortable with the use of
infiltrating anesthesia. Some authors prefer the block of
infraorbitary and chin nerves, whereas others suggest small
punctures in the vestibular part of labial mucosa. The linear,
anterograde injection reduces bleeding and hematoma,
especially in volume augmentation. It is advisable to suggest
an anti
–herpes prophylaxis with acyclovir 400 mg, 5 times a
day, before the implantation in subjects with herpes recidivism.
Using ice packs for 10 minutes after implant will help in
reducing the edema that usually reaches its peak in the
following 24 hours, spontaneously regressing in 5 to 7 days.
Vertical wrinkles of upper and lower lips
The optimal correction of this imperfection can be
obtained with mid to deep peelings and with ablative lasers,
but the results obtained with these techniques require months
to be evident, in addition to a downtime period of 4 to 5 days.
The risk of side effects is also present, such as scars and
hyperpigmentations. For these reasons, a hyaluronic acid
treatment in this site is often preferred, even if the wrinkles
do not completely disappear.
Technique 1
This technique is useful in case of scattered, deep wrinkles.
The wrinkle is filled along its course using the micropuncture
technique. It is important to avoid overcorrection, particularly
in thin skin. This technique is often combined with the
definition of labial rim, to be performed in advance to
eliminate the part of wrinkle that contacts vermillion.
Technique 2
This is useful in the classic bar code, when there are lots of
wrinkles. It is preferable to infiltrate wrinkles perpendicu-
larly, following the labial rim and departing toward the upper
limit of the white lip (
).
Tips and tricks
In both techniques, use fluid material and thin needles to
avoid overcorrection and a duck's beak appearance. Infiltrate
and whiten the white lip at the level of the first millimeter
Fig. 16
Vertical lines.
140
M. Romagnoli, M. Belmontesi
from the vermillion, reaching a nice projecting effect of the
red lip; this is feasible also in patients who do not desire
lip augmentation.
Correction of commissural and subcommissural
or labial chin furrow
Commissural lines, also called marionette lines, give a sad
look and define an arch-like conformation, with an upward
convexity instead of being in line with the lip (
Hypertonicity of depressor angulis oris muscle, whose
treatment requires botulinum toxin use, can be partly
responsible of this imperfection, mostly due to perioral tissues
relaxation and to mandibular bone resorption. Edentulism,
even partial of the fourth or fifth teeth of the inferior arch,
makes this imperfection more evident, even worsened by a
real labial-chin groove. Another condition that can induce this
problem is a significant weight loss. The treatment with fillers,
by integrating the lost tissues, is of primary importance in this
site and in the fold that often appears immediately under the
labial commissure and the chin region.
Commissural wrinkles or marionette lines
Technique 1
Infiltrate for no more than 4 to 5 mm in the track of the
virtual channel, established between the white and the red lip
with an open
“V” toward the lip whose apex corresponds to
lip lateral limit (
). It is important not to infiltrate too
much material: 0.1 mL on each side should be enough.
Technique 1
An alternative of the preceding one, it is more useful when
tissue sagging is strong due to the concomitant presence of a
chin-labial fold (
). It consists of a crossed technique. The
first passage is the infiltration in the first 3 to 4 mm of upper
and lower lips, in the region of the virtual channel between the
white and the red lip, by a single needle injection, starting
from either the upper or the lower part. The second passage is
slightly more medial and shorter than the first one, going in
the opposite direction with respect to the first passage.
Subcommissural or labial-chin furrow
Technique
Depending on imperfection severity, the correction
(
) can be done as follows:
1. Infiltrating along the depression's course, linearly, with
the retrograde technique.
2. Often, near the commissure, a depression in the
shape of a triangle with upward direction becomes
evident. In this case, it will be necessary to do a
fanning correction, infiltrating the material perpendi-
cularly to the depression.
3. Very deep grooves often require the deposition of
the material on 2 superimposed layers. The first
correction should be done in a deeper level, with
viscous material and fanning technique. Then, even
during the same session, the correction can be
refined superficially, with a linear technique, using
a basic compound.
Zygoma augmentation by hyaluronic
acid concentration
Indications
Cheekbone volume augmentation is indicated when
facial aging caused a progressive flattening of zygo-
matic eminence. This happens during the aging pro-
gression, which induces not only the reduction of
dermis but also of the Bichat bulla, as well as pro-
gressive bone tissue resorption. The aesthetic conse-
quence is less protrusion of zygoma, more accentuation
of nasolabial fold, often an accentuation of labial-chin
fold, and the folding of the cutaneous fold along the
mandible: the final effect is a general facial flattening
and falling of the upper third of the face. Therefore,
these conditions can be corrected by a filler implant of
hyaluronic acid. The temporary zygomatic correction is
one of the other indications, as a presurgery before
zygomatic prosthesis implantation.
Hinderer’s technique
To identify the correct site of filler implant in the
zygomatic area, the Hinderer's technique is advisable. The
patient should be examined while sitting at a 90° position.
The drawing, to be executed with a dermographic pencil,
traces 2 lines on the face: the first one starts from the lateral,
external corner of the eye, going downward to the labial
commissure; the second line, perpendicular to the first one,
starts from the nasal wing and ends to the tragus. In the
intersection point, an ellipse is drawn, within the drawing
upper quadrants: in that area, the zygomatic eminence is
found (
).
Patient’s preparation
A thorough case history should be done to ascertain the
absence of a previous implant with permanent material (a
contraindication); the presence of other contraindications,
such as above; a general healthy condition; and the patient
141
Hyaluronic acid—based fillers: theory and practice
warning not to take acetil salycilic acid, NSAID or
anticoagulant drugs for at least 5 days before treatment (to
reduce hematoma or bleeding risk). After that, a clinical
evaluation is done, first with the patient seated, then with the
patient lying, staying behind his or her head to evaluate
possible asymmetries. After a clear and complete informa-
tion about treatment, results, and possible side effects,
the patient should read and sign the informed consent.
The pictures should be taken frontally and in a three-
fourths profile, to highlight eminence and roundness of the
zygoma. Before treatment, the skin should be cleansed,
removing any makeup and drying with some Kleenex. Then,
with the patient seated, the implant can begin, following
Hinderer's technique.
Correction by intradermal implant
No local anesthesia is necessary in this implant, only a
topical anesthetic cream 20/30 minutes before the procedure.
This correction is indicated if a filling effect of the zygomatic
area is desired but not a lifting and remodeling of face contour.
In the intradermal correction, a highly viscous hyaluronic acid
is preferred, cross-linked or stabilized, injected with a 27G
needle. The implant should be inserted in the mid-deep
dermis. The material can be implanted with the fanning tech-
nique, starting from a single injection point, and completely
filling the designed area. Mean quantity in each treatment can
vary with cases, from 0.5 to 1 mL on each side. After the
implantation, a modeling massage is suggested. It is important
to inject the same quantity on both sides, except if preexisting
asymmetries have been noticed. In this case, the correction
should reduce the asymmetry. During posttreatment, the
application of cold packs for a few minutes is advisable,
followed by creams based on vitamin K and/or arnica gel.
This latter can be continued at home for 24 to 72 hours.
Correction by supraperiosteal deep
implanttransdermal technique
This correction is a
“lifting” of the zygomatic area,
partially reducing the nasolabial fold, giving firmness to the
inferior third of the face. A hyaluronic acid gel created for
face sculpturing (Restylane Sub-Q and Voluma) should be
chosen; we prefer to inject this gel using a smooth cannula
(Coleman's type) with 16/18G, which is less traumatic than a
needle. The implant should be deep, subcutaneous, and
supraperiosteal. The anesthesia can block the infraorbital
nerve with 2% lidocaine, about 2 mL on each side. The
anesthetic should also be infiltrated in the point of the scalpel
puncture, near the terminal part of posterior zygomatic arch,
indispensable for cannula introduction. The superficial
incision is done with an 11-blade scalpel. The treatment
must be performed in sterile conditions (sterile gloves,
gauzes, scissors, cloths, and disposable scalpel and cannulas,
steril-strip). After the incision, a cannula is inserted directing
it to the bone surface, then tangentially, sliding on the bone,
to the treatment area. Always be sure to avoid the orbicular
septum of the eye and not to implant in the inferior
zygomatic region, near the buccal septum (too thin, it cannot
support the weight of the gel). It is suggested to use a tunnel
technique, with retrograde infiltration in the area to fill,
creating about 6/8 pouches where to inject the gel. Once
filling is complete, do not inject material while withdrawing
the cannula (to avoid a too superficial deposition of gel
residues in the dermis). Then, disinfect the microincision and
apply steril-streep. A sweet and modeling massage of treated
area is suggested. Mean quantity on each side can vary, from
a minimum of 1 mL to a maximum of 3 to 4 mL on each side.
On average, 2 mL is necessary for one correction. If
asymmetries are present, the correction should be balanced.
Once the treatment on one side is completed, repeat the
procedure on the other side. In the immediate postimplanta-
tion, we suggest the application of ice packs, vitamin K, and
arnica creams, also in the following 3 to 4 days. No systemic
antibiotic treatment is necessary. After about 24 hours, steril-
streep is removed, without any suture stitch or obvious scars.
Correction by supraperiosteal deep
implanttransvestibular technique
The same type of correction can be done by transves-
tibular technique. After having blocked the infraorbital
Fig. 17
Hinderer's technique.
142
M. Romagnoli, M. Belmontesi
nerve, a drop of anesthetic is injected near the superior canine
fossa (between II and III), then a scalpel puncture with an 11-
blade scalpel. The cannula is inserted through the incision,
sliding on the bone surface to the zygomatic area; the
hyaluronic acid gel is injected with the same technique as
above. Once the implantation has been completed, a sterile
gauze impregnated with disinfectant (eg, iodine, Germany) is
left for a few minutes, then it can be removed without
suturing. A light massage is suggested, modeling in the
upward direction. Then, repeat the same procedure on the
other side.
Posttreatment home care
In the following 7 days, at home, the patient can still
locally apply an arnica cream/gel and should avoid causing
traumas to the inherent area, especially during the first 48/72
hours, and sleeping with the face pressing on the pillow (a
supine position is suggested). Avoid exposure to heat sources
or to direct hot steam (hair dryers, sauna, steam bath,
professional face cleansing with heating, aerosol, etc). Avoid
sudden temperature excursions. There should be no UV lamp
and no sun exposure in the following 15 days. In this case,
we prefer to administer a single dose of azithromycin 500
mg/d, starting from the preceding day, for 3 days.
Immediate side effects and their management
The immediate side effects are related to the implant
injection; mild to mid edema, pain, mild to mid erythema,
and ecchymoses can occur. Such reactions will sponta-
neously disappear in some hours or few days. A dose of
nonsteroidal anti-inflammatory drug (eg, nimesulide) can be
administered for a couple of days to eliminate subjective
aching. Hematoma is rare, when the treatment has been done
with a good technique. The patient can follow his or her
normal social life, without leaving work.
Posttreatment side effects and their management
When the technique has not been correctly performed and
the implant is too superficial, gel palpability and gel
migration are possible events (particularly in the incision
site). In this case, 2 kinds of interventions are possible. If the
gel is superficial and mobile, an incision with a mesotherapy
needle can be done, squeezing out the gel. If the nodule is
more localized and not mobile, an intralesion microinjection
of hyaluronidase can be done, releasing hyaluronic acid
mass. Some cases of persistent edema lasting approximately
8 to 10 days have been reported; in this case, we suggest the
intake of systemic cortisone, 2 mg/d, for 8 days. The possible
onset of some palpable and mobile small nodules in the eye
socket is due to an error of implantation causing septum
breaking and internal implant of material. An intralesion
microinjection of hyaluronidase is suggested. No permanent
outcomes have been reported.
Retouches and duration
Should retouch be necessary to confer symmetry to the
implant, we suggest to repeat treatment after about a month.
The duration of an intradermal implant can be evaluated at
approximately 5 to 6 months. A deep supraperiosteal implant
can last a maximum of approximately 8 to 9 months.
Obviously, the response is variable, and the subject's habits
can influence the duration of results.
Correction of the chin by hyaluronic
acid infiltration
Indications
Chin correction or augmentation is indicated in case of
congenital hypogenia or as a presurgical treatment. Such
Fig. 18
Lines of facial profiles. The Frankfurt horizontal axis connects the lowest point of the orbital margin to the higher point of the
external acoustic meatus.
143
Hyaluronic acid—based fillers: theory and practice
correction is indicated also when the patient shows a marked
disproportion, at the lateral profile, between the nose tip and
chin tip, to create a more harmonic appearance. Many
requests come from patients with Asiatic somatic feature that
desire chin augmentation, lightening the protruding zygoma
to obtain an occidental look.
Patient evaluation
The patient should be evaluated in a seated position, at
90°. One should consider the ratio between the lines of
facial profile (nose-lip-chin) following the
“Frankfort axes”:
the Frankfort horizontal axis connects the lowest point of
the orbital margin to the higher point of the external
acoustic meatus.
Lines of facial profile
The nose-lip-chin ratio is depicted in
.
Patient’s preparation
A thorough case history should be done to ascertain the
absence of a previous implant with permanent material (a
contraindication); a general healthy condition; and the
patient warning not to take acetyl salicylic acid, NSAID, or
anticoagulant drugs for at least 5 days before treatment (to
reduce hematoma or bleeding risk). After that, a clinical
evaluation is done with the seated patient. Then, evaluate the
face in frontal as well as in right and left lateral projections to
identify possible asymmetries. After a clear and complete
information about treatment, results, and possible side
effects, the patient should read and sign the informed
consent. The pictures should then be taken frontally and
laterally (both sides). The drawing for chin augmentation is
done with the patient seated to find the chin dimple, which is
due to the presence, in the midline, of a fibroelastic lamella
extending from chin symphysis to the deep skin layer. Near
the dimple, one can find the 2 inferior lateral parts of the
chin, the sites of implantation. Bear in mind that the tender
parts of the chin should be divided into 3 layers, thick skin,
muscle and fat layer, and periosteum, to differentiate layers
of injection depending on the material chosen.
Correction by intradermal implant
No local anesthesia is necessary for this implant, only a
topical anesthetic cream 20/30 minutes before the procedure.
In the intradermal correction, a highly viscous hyaluronic
acid is preferred, cross-linked or stabilized, injected with a
27G needle. The implant should be inserted in the mid-deep
dermis. The material can be implanted with the fanning
technique, starting from a single injection point and
completely filling the designed area. Mean quantity in
each treatment can vary with cases, from 0.5 to 1 mL on
each side. After the implant, a modeling massage is
suggested. It is important to inject the same quantity on
both sides, except if preexisting asymmetries have been
noticed. In this case, the correction should reduce the
asymmetry. During posttreatment, the application of cold
packs for a few minutes is advisable, followed by creams
based on vitamin K and/or arnica gel. This latter can be
continued at home for 24/72 hours.
Correction by supraperiosteal deep
implanttransdermal technique
This kind of correction is indicated to
“fill and move
forward
” the chin area, partly reducing the disproportion
between nose tip and chin tip, giving the inferior third of
the face a tighter look. A hyaluronic acid gel created for
face sculpturing should be chosen; we prefer to inject this
gel using a smooth cannula (Coleman's type) with 16/18G,
which is less traumatic than a needle. The implant should
Fig. 19
Lines of the aesthetic profile according to Gonzalez-Ulloa (1968). The line perpendicular to the Frankfurt horizontal axis lowered
from the nasion that continues downward should cross chin pogonion.
144
M. Romagnoli, M. Belmontesi
be deep, subcutaneous, and supraperiosteal. The anesthesia
can block the infraorbital nerve with 2% lidocaine, about 2
mL on each side. The anesthetic should also be infiltrated
in the point of the scalpel puncture, near the chin dimple,
indispensable for cannula introduction. The superficial
incision is done with an 11-blade scalpel. The treatment
must be performed in sterile conditions (sterile gloves,
gauzes, scissors, cloths, and disposable scalpel and
cannulas, steril-strip). After the incision, a cannula is
inserted directing it to the bone surface, then tangentially,
sliding on the bone, to the treatment area. Always be sure
to avoid the area of chin vessels, and of muscle and nerve
bundles. It is suggested to use a tunnel technique, with
retrograde fanning infiltration in the area to be filled,
creating about 3/5 pouches where to inject the gel. Once
filling of the half is complete, do not inject material while
withdrawing the cannula (to avoid a too superficial
deposition of gel residues in the dermis). Then, the same
procedure is done in the other half, using the same
entrance incision. Then, disinfect the microincision and
apply steril-streep. A sweet and modeling massage of the
treated area is suggested, onward and upward. Mean
quantity on each side can vary, from a minimum of 1 mL
to a maximum of 2 mL on each side. On average, 2 mL is
necessary for one side. If asymmetries are present, the
correction should be balanced. In the immediate posttreat-
ment, we suggest the application of ice packs, vitamin K,
and arnica creams, also in the following 3 to 4 days. No
systemic antibiotic treatment is necessary. After about
24 hours, steril-streep is removed, without any suture
stitch or obvious scars (
Correction by supraperiosteal deep
implanttransvestibular technique
The same type of correction can be done by transves-
tibular technique. After having blocked the infraorbital
nerve, a drop of anesthetic is injected near the superior
canine fossa (between V and VI), then a scalpel puncture
with an 11-blade scalpel. The cannula is inserted through
the incision, sliding on the bone surface to the chin area; the
hyaluronic acid gel is injected with the same technique as
above. Once the implant has been completed, a sterile
gauze impregnated with disinfectant (eg, iodine, Germany)
is left for a few minutes, then can be removed without
suturing. A light massage is suggested, modeling in the
upward and onward direction. Then, repeat the same
procedure on the other side.
Posttreatment home care
In the following 7 days, at home, the patient can still
locally apply an arnica cream/gel and should avoid causing
traumas to the inherent area, especially during the first
48/72 hours, and sleeping with the face pressing on the
pillow (a supine position is suggested). Avoid exposure to
heat sources or to direct hot steam (hair dryers, sauna,
steam bath, professional face cleansing with heating,
aerosol, etc). Avoid sudden temperature excursions. There
should be no UV lamp and no sun exposure in the
following 15 days. In this case, we prefer to administer an
antibiotic, such as described in the transvestibular treat-
ment of zygoma.
Posttreatment side effects and their management
See the section on transvestibular augmentation of the
chin under the heading correction by supraperiosteal deep
implanttransvestibular technique on this page.
Retouches and duration
Should a retouch be necessary to confer symmetry to the
implant or if the patient desires more volume, we suggest to
repeat the treatment after about a month. The duration of an
intradermal implant can be evaluated at approximately 5 to
6 months. A deep supraperiosteal implant can last a
maximum of approximately 9 to 10 months. Obviously, the
response is variable, and the subject's habits can influence
the duration of results.
Fig. 20
Implant sites.
145
Hyaluronic acid—based fillers: theory and practice
Correction of the mandibular contour by
hyaluronic acid infiltration
Indications
The correction of mandibular profile is indicated in case of
progressive facial flattening, with the formation of a
nasolabial fold that continue with the labial-chin furrows,
creating a fold in the mandibular contour (para-chin area). In
such cases, marionette lines and emptying of chin dimple are
also present, conferring a sharp chin. This correction should
always be combined with a correction of nasolabial and
labial-chin furrows, and often to a correction of the marionette
fold and labial commissures (
“Pierrot” expression). In this
way, there is a clear improvement of the inferior third of the
face and of facial profile. Therefore, for these corrections,
midlevel of aging is indicated, when the skin is still compact
and tonic. This correction could also be combined with chin
correction for a better definition of the inferior third of the
face. It is not indicated in advanced aging, with marked skin,
subcutaneous fat, and bone relaxation, where other kinds of
aesthetic corrections are more indicated.
Fig. 21
Correction with Teosyal Deep. After filling of the subcommissural furrow, nasolabial fold, and lip contour.
Fig. 22
Correction of the nasolabial fold and wrinkle, and lip commissural wrinkle with hyaluronic acid.
146
M. Romagnoli, M. Belmontesi
Patient evaluation and preparation
A thorough case history should be done to ascertain the
absence of a previous implant with permanent material (a
contraindication); the presence of other contraindications,
such as above; a general healthy condition; and the patient
warning not to take acetyl salicylic acid, NSAID, or
anticoagulant drugs for at least 5 days before treatment (to
reduce hematoma or bleeding risk). After that, a clinical
evaluation is done, first with the patient seated, then
analyzing the patient's profile by making him or her slowly
rotate to evaluate possible asymmetries. After a clear and
complete information about treatment, results, and possible
side effects, the patient should read and sign the informed
consent. The pictures should be taken frontally and in a three-
fourths profile. Before treatment, the skin should be cleansed,
removing any makeup and drying with some Kleenex. Then,
with the patient seated, the implantation can begin, following
Hinderer's technique. Then, with the patient seated in a 90°
position, the drawing of treatment site is traced. The chin
dimple is highlighted, then an elongated ellipse is drawn,
about 1 to 2 cm high, starting from para-chin fossa along the
jawbone for approximately 8 cm, on both sides.
Correction by intradermal implant
No local anesthesia is necessary in this implant, only a
topical anesthetic cream 20/30 minutes before the procedure.
This correction is indicated when a final effect of zygomatic
area filling is desired and not the lifting and remodeling of
facial profile. In the intradermal correction, a highly viscous
hyaluronic acid is preferred, cross-linked or stabilized,
injected with a 27G needle (with low fluidity in case of
correction of deep layers) or with a 30G needle (with high
fluidity in case of correction of superficial layers). The
implant should be inserted in the mid-deep dermis. The
technique we suggest is the linear retrograde, following
the entire area along the jawbone to the chin region. Mean
quantity in each treatment can vary with cases, from 1 to
1.5 mL on each side. After the implantation, a modeling and
relaxing massage is suggested. Then, proceed contralaterally
in the same manner. It is important to inject the same quantity
on both sides, except if preexisting asymmetries have been
noticed. In this case, the correction should reduce the
asymmetry. During posttreatment, the application of cold
packs for a few minutes is advisable, followed by creams
based on vitamin K and/or arnica gel. This latter can be
continued at home for 24/72 hours.
Correction by supraperiosteal deep
implanttransdermal technique
This kind of correction is indicated to
“fill and stretch”
the zygomatic contour, partly reducing the labial-chin fold,
giving the inferior third of the face a tighter look. A
hyaluronic acid gel created for face sculpturing should be
chosen; we prefer to inject this gel using a smooth cannula
(Coleman's type) with 16/18G, which is less traumatic than
a needle. The implant should be deep, subcutaneous, and
supraperiosteal. The anesthesia can block the chin nerve
with 2% Xylocaine, about 2 mL on each side. The anesthetic
should also be infiltrated in the point of the scalpel puncture,
near the inferior part of chin dimple (under jawbone),
indispensable for cannula introduction. The superficial
incision is done with an 11-blade scalpel. The treatment
must be performed in sterile conditions (sterile gloves,
gauzes, scissors, cloths, and disposable scalpel and cannulas,
steril-streep). After the incision, a cannula is inserted
directing it to the bone surface, then tangentially, sliding
on the mandibular bone, to the final treatment area. Always
be sure to avoid the area of chin vessels, and of muscle and
nerve bundles: proceed slowly and delicately, guiding the
smoothed tip of the cannula from the outside. It is suggested
to use a tunnel technique, with retrograde linear infiltration
in the area to be filled with the gel. Once filling of the half is
complete, do not inject material while withdrawing the
cannula (to avoid a too superficial deposition of gel residues
in the dermis). Then, the same procedure is done in the other
half, using the same entrance incision. In the end, disinfect
Fig. 23
Nasolabial wrinkle.
147
Hyaluronic acid—based fillers: theory and practice
the microincision and apply steril-streep. A sweet relaxing
and modeling massage of treated area is suggested. Mean
quantity on each side can vary, from a minimum of 1 mL to a
maximum of 2 mL on each side. On average, 2 mL is
necessary for one side. If asymmetries are present, the
correction should be balanced. In the immediate posttreat-
ment, we suggest the application of ice packs, vitamin K,
and arnica creams, also in the following 3 to 4 days. No
systemic antibiotic treatment is necessary. After about
24 hours, steril-streep is removed, without any suture stitch
or obvious scars.
Posttreatment home care
See the section on transvestibular augmentation of the
zygoma under the heading posttreatment home care.
Posttreatment side effects and their management
See the section on transvestibular augmentation of the
chin under the heading posttreatment side effects and their
management.
Retouches and duration
Should a retouch be necessary to confer symmetry to the
implant or to complete the correction of the inferior third of
the face with more volume, we suggest to repeat treatment
after about 3 weeks. The duration of an intradermal implant
can be evaluated at approximately 5 to 6 months. A deep
supraperiosteal implant can last a maximum of approxi-
mately 8 to 9 months. Obviously, the response is variable,
and the subject's habits can influence the duration of results.
Fig. 24
Nasolabial wrinkle.
Fig. 25
Volume correction of the upper lip.
148
M. Romagnoli, M. Belmontesi
The result can last longer if this correction is combined with
other corrections of the inferior third, such as para-chin area,
labial-chin folds, and marionette lines.
Tips and tricks
We think that the choice of the transvestibular technique
in zygoma, chin, and mandibular contour is particularly
indicated in patients with a tendency to develop postin-
flammatory keloids and hyperpigmentation, allowing a for
faster recovery.
Nose correction: profile
Indications and contraindications
The superficial correction of the nose profile by
subcutaneous implant of hyaluronic acid allows a temporary
remodeling of the nasal bridge, in case of light to mild hump
and of a slight hollow of the bridge, near the tip. This
temporary correction is only aesthetic and does not imply
any intervention on possible septal deviations or respiratory
impairments, which need a surgical correction. Therefore,
the implant is indicated in patients with aesthetic defects only
who do not want to undergo surgery or as a presurgery. In
case of previous rhinoplasty, 6 months should have passed
from the intervention at least.
Patient evaluation and preparation
A thorough case history should be done. After that, a
clinical evaluation is done, first with the patient seated, then
analyzing the patient's profile by making him or her slowly
rotate to evaluate possible existing asymmetries. After a clear
and complete information about treatment, results, and possible
side effects, the patient should read and sign the informed
Fig. 26
Before botulinum toxin, after botulinum toxin, and after botulinum toxin plus hyaluronic acid.
Fig. 27
Correction of glabellar wrinkle with basic hyaluronic acid.
149
Hyaluronic acid—based fillers: theory and practice
consent. The pictures should be taken frontally and laterally.
Before treatment, the skin should be thoroughly cleansed,
removing any makeup and drying with some Kleenex.
Correction by subcutaneous implant
Such a method has been introduced only recently; thus,
the techniques are still under testing. No local anesthesia is
necessary in this implantation, only a topical anesthetic
cream 20/30 minutes before the procedure. In the sub-
cutaneous correction, a midviscous hyaluronic acid is
preferred, cross-linked or stabilized, injected with a 30G
needle. The implant should be subcutaneous. For hump
correction, the injection is performed with the area above the
hump kept between the fingers, then a slow injection in the
subcutaneous region is done, avoiding to hypercorrect and
always massaging with a slight and modeling pressure. To
obtain a straight and uniform nasal bridge along the entire
area to be treated, we suggest the retrograde linear technique,
keeping the skin and the nose edges between the fingers to
check the quantity of gel injected and at the same time to
model the implant. Mean quantity in each treatment can vary
from 0.5 to 1 mL, usually no more than 0.5 mL along nose
bridge. After the implantation, a modeling and relaxing
massage is suggested. Preexisting asymmetries should be
carefully evaluated and eventually corrected in another
session, to better highlight the final result, avoiding edema.
During posttreatment, the application of cold packs for a few
minutes is advisable, followed by creams based on vitamin K
and/or arnica gel. This latter can be continued at home.
Posttreatment home care
In the following 7 days, at home, the patient can still
locally apply an arnica cream/gel and should avoid causing
traumas to the inherent area, especially during the first 48/
Fig. 28
Correction of glabellar wrinkles and crow's feet with
BTX botulinum toxin, and of tear trough with hyaluronic acid.
Fig. 29
Correction of the nasolacrimal trough.
150
M. Romagnoli, M. Belmontesi
72 hours, and sleeping with the face pressing on the pillow
(a supine position is suggested). Avoid exposure to heat
sources or to direct hot steam (hair dryers, sauna, steam
bath, professional face cleansing with heating, aerosol, etc).
Avoid sudden temperature excursions. There should be no
UV lamp and no sun exposure in the following 15 to
20 days.
Immediate side effects and their management
The immediate side effects are related to the implant
injection; mild to mid edema that can extend to nose sides or,
rarely, to the periocular area; pain; mild to mid erythema; and
ecchymoses can occur. Such reactions will spontaneously
disappear in some hours or few days. A dose of nonsteroidal
Fig. 30
Correction of a depressed surgical scar.
Fig. 31
Hypogenia correction. Supraperiosteal implant with transdermal technique using hyaluronic acid for face sculpturing.
151
Hyaluronic acid—based fillers: theory and practice
anti-inflammatory drug (eg, nimesulide) can be administered
for a couple of days to eliminate subjective aching. Hematoma
can appear if many injections have been done. The patient can
follow his or her normal social life, without leaving work.
Posttreatment side effects and their management
When the technique has not been correctly performed and
the implant is too superficial, palpability and possible
hypercorrection can manifest. Usually, a reduction of the
hypercorrection is obtained by massaging and remodeling the
area. After a wrong correction technique, if the gel is still
persistent, we suggest an intralesion microinjection of
hyaluronidase. In case of persistent edema lasting more
than 2 days, we suggest the intake of systemic cortisone,
betamethasone 2 mg/d, for 8 days. No permanent outcomes
have been reported.
Retouches and duration
Should a retouch be necessary to confer symmetry to the
implant or to complete the correction, we suggest to repeat
treatment after about 3 weeks. The duration of an intradermal
implant can be evaluated at approximately 7 to 9 months.
Fig. 32
Correction of nasal profile in an Asian woman.
Fig. 33
Correction of nose hump.
152
M. Romagnoli, M. Belmontesi
The result is better and lasts longer when combined with
other corrections, such as the glabella correction and,
possibly, combination to type A botulinum toxin treatment
of septum. Obviously, the response is variable, and the
subject's habits can influence the duration of results.
Correction of nasolacrimal trough and
of orbital rim
Indications and contraindications
A superficial correction of the nasolacrimal trough and of
the orbital rim by hyaluronic acid intradermal implant allows
a temporary mild/moderate to deep correction of both the
nasolacrimal trough and of, when present, the well-marked
orbital rim that confer the deep-seated eye of mild-moderate
to marked degree. This correction is not indicated in case of
marked, dark, and hyperpigmented eye socket because the
result would be a more dark and hyperpigmented socket. In
case of previous blepharoplasty, it advisable to wait 4 to 6
months at least and that no postinflammatory residual edema
is present. The presence of marked bags under the eyes and
the tendency for palpebral swelling (eg, water retention) are
contraindications because the hyaluronic acid implant
attracts water, emphasizing the edema and the swelling,
worsening the patient's look.
Fig. 34
Supraperiosteal volume augmentation with transdermic technique using hyaluronic acid for face sculpturing.
Fig. 35
Transvestibular correction of the zygoma with hyaluronic acid for sculpturing.
153
Hyaluronic acid—based fillers: theory and practice
Patient evaluation and preparation
A thorough case history should be done, particularly
about bleeding susceptibility. After that, a clinical evaluation
is done, with the patient seated, then analyzing the patient's
profile making him or her open and close the eyes to evaluate
the presence of bags under the eyes. After a clear and
complete information about treatment, results, and possible
Fig. 36
Correction of the mandibular contour and chin area.
Fig. 37
Correction of the bar code using a combined technique.
154
M. Romagnoli, M. Belmontesi
side effects, the patient should read and sign the informed
consent. The pictures should be taken frontally and laterally.
Before treatment, the skin should be thoroughly cleansed,
removing any makeup and drying with some Kleenex.
Correction by mid- to deep-dermis implant
Such a method has been introduced only recently; thus, the
techniques are still under testing. For this implant, only a topical
anesthetic cream 20/30 minutes before implantation and the
application of ice to induce vasoconstriction are necessary. In
the deep intradermal correction, a low-viscous hyaluronic acid
is preferred, cross-linked or stabilized, injected with a 30G
needle. The implant should be in the mid-deep dermis or
supraperiosteal. For the correction of nasolacrimal trough, the
injection is slow and gradual, avoiding hypercorrection and
always massaging with a slight and modeling pressure. Gel
quantity varies, but we suggest to inject no more than 0.5 mL.
For periorbital trough correction, we suggest the retrograde
linear technique along the entire area, or the serial puncture
technique. If the furrow is deep, a fanning technique can be
performed, avoiding to hypercorrect and checking the quantity
of gel injected, while modeling the implant. Mean quantity in
each treatment can vary from 0.5 to 1 mL, usually no more than
0.5 mL. After the implantation, a modeling and slight
pressuring relaxing massage is suggested. Preexisting asym-
metries should be carefully evaluated and eventually corrected
in another session to better highlight the final result, avoiding
edema. During posttreatment, the application of cold packs for a
few minutes is advisable, followed by creams based on vitamin
K and/or arnica gel. The latter can be continued at home.
Tips and tricks
It is important to avoid hypercorrection and accidental
injection in the orbital septum. Therefore, it may be useful
Fig. 38
Nodules from a wrong implantation site.
Fig. 39
Hypercorrection of periocular wrinkles.
155
Hyaluronic acid—based fillers: theory and practice
to put a finger on the orbital arch and keep it inferiorly
while infiltrating.
Posttreatment home care
In the following 7 days, at home, the patient can still
locally apply an arnica cream/gel and should avoid causing
traumas to the inherent area, especially during the first 48/72
hours, and sleeping with the face pressing on the pillow (a
supine position is suggested). Apply cold packs of
chamomile and witch hazel to decongest the edema. Avoid
exposure to heat sources or to direct hot steam (hair dryers,
sauna, steam bath, professional face cleansing with heating,
aerosol, etc). Avoid sudden temperature excursions. There
should be no UV lamp and no sun exposure in the following
15 to 20 days.
Immediate side effects and their management
The immediate side effects are related to the implant
injection; the patient should be notified in advance that
edema and hematoma can appear due to the thin and well-
vascularized skin in this region.
Retouches and duration
Should a retouch be necessary to complete the correction,
it is advisable to repeat treatment after about 3 weeks. The
duration of an implant can be evaluated around a maximum of
4 to 6 months. Obviously, the response is variable, and the
subject's habits can influence the duration of results. The
result is better and lasts longer when combined with other
corrections, such as the treatment of periocular wrinkles with
type A botulinum toxin.
Hyaluronic acid: side effects and their
management
The problems linked to this kind of method, even if
possible, are fortunately rare; usually they have a short
duration and an early onset after the implantation, from few
hours to some months. These features differ from the side
effects induced by permanent fillers. It has been reported that
these latter can induce adverse events setting on years later
from the implantation, which last for years, are difficult to
manage, both from a medical and surgical point of view, and
are often associated with permanent sequelae.
Foreseeable side effects
These are linked to the minor trauma induced by the
needle, to anesthesia, and to the hyaluronic acid's ability to
attract water within tissues. These appear within few hours
after the implant to a maximum of 48 hours later, lasting no
more than 2 weeks.
Edema
It is more evident where the thin skin undergoes a
gravitational effect or in the mucosa (lips, subcommissural
Fig. 40
Nodule element that has been absorbed without abscessing.
Fig. 41
The nodule has been totally absorbed after 3 months.
Fig. 42
Cold abscess with spontaneous drainage on the mucosal
side after 2 months.
156
M. Romagnoli, M. Belmontesi
furrows). It will be more evident the more hyaluronic acid has
been implanted. Heat exposure (UV lamps, sauna) in the
48 hours after the implantation should be avoided and cold
packs before and after the procedure to limit spreading and
duration should be used. As a preventive treatment, a
single dose of 4 mg betamethasone immediately after the
implant is suggested; also, single dose of 250 ch/Apis and
arnica is useful.
Erythema
Predisposing factors are thin skin, sensitive skin, and
presence of telangiectasia. The use of thermal water with
bicarbonate and magnesium and a light camouflage after the
implant are sufficient to cope with the discomfort of the
first days.
Pain-itch-palpability and higher sensitivity to
the implant
These are consequences of the edema and of the trauma
caused by needle. In these cases, the application of cold
packs may be sufficient. In sites of high tactile sensitivity,
such as the lip, implant perceiving can last more: the patient
should be informed in advance.
Ecchymosis
It is a consequence of the trauma induced by the needle on
the small vessels, often in predisposed patients. The presence
of erythrosis and telangiectasia entails a particular attention
to limit such an event. Prevention is fundamental. We
suggest all the following preventive measures: a good light
to avoid superficial vessels; the withdrawal of antiplatelets
and anticoagulants at least 5 days before; cold or ice packs
before and after the implantation; and a thorough analysis
excluding blood crisis. The application of gel heparinoids
helps in the recovery. A camouflage is also useful, using the
yellow for masking the violet part and the green for masking
the reddish one.
Herpetic reactivation
It involves mainly the lip. In case of a history of recurrent
herpes, a prophylaxis with 400 mg acyclovir (or another
antiviral drug) can be established, 4 to 5 times a day, for
5 days.
Side effects caused by malpractice
Fortunately, these side effects are always reversible, often
before the product has been completely resorbed. It is
important to keep in touch with the patient and assure him
that these effects are only temporary. In more visible cases,
small quantities of intralesion hyaluronidase can be used to
speed up the resorption.
Excessive palpability of the implant, nodules
These are connected with the use of inadequate material in
that site, for example, a high-viscosity filler in the thin skin of
the periocular area or to the use of fillers in unsuitable sites
such as the neck.
Hypercorrection
This is due to the use of too much material or an implant
that is too superficial.
Bluish coloring of the implant
It is mostly due to a correction that is too superficial and
to the optical effect induced by the accumulation of
hyaluronic acid in some sites (Tyndall effect). The optical
effect is given by small accumulations some millimeters
thick, with a gray to blue coloration, easily present in the
labial area, in the subcommissural fold or labial-chin
wrinkle, and in the nasolabial triangle. We think that the use
of excessive as well as of superficial quantities of product
may induce this effect, especially in the thinnest area. If
this occurs in the first days after the implantation, it is
possible to prick and empty the accumulation with a
30G needle. If this occurs later, it will be necessary to
wait for the natural resorption of the product or to use
the hyaluronidase.
Whitening of the treated area
This usually happens while implanting. It happens
rarely in the areas with terminal vascularization, such as in
the lip, glabella, and nose tip. It can be due to an
intravasal infiltration of hyaluronic acid in a terminal
arteriole, to a too highly viscous hyaluronic acid, or to an
excessive quantity of hyaluronic acid with compression of
the tissue (glabella) against the underlying bone. In all
cases, the infiltration should be immediately stopped,
massaging the area and following up in the following
days. The extreme consequence of this rare occurrence is
tissue necrosis (2 cases of necrosis with more than
250,000 ampoules in the dermatosurgery of the glabella
in 2006).
Infection
It is linked to a wrong preimplant preparation of the skin
and to an inadequate disinfection. In this case, a proper
antibiotic therapy should be designed, with tetracycline or
amoxicillin and clavulanic acid.
157
Hyaluronic acid—based fillers: theory and practice
Unpredictable side effects
These are probably linked to a particular reactivity of the
subject to the presence of protein residues of bacterial or
avian origin in the filler and/or of impurities from the cross-
linking process. The studies on hyaluronic acid safety are
numerous and were performed on significant samples of
implanted population, although most of all these studies show
the limit of considering only the events spontaneously
reported by patients or by patients coming back for a new
implant. This fact could lightly underestimate the side effects,
which are described to be between 0.8% and 0.06%.
Erythema/recurrent edema
In some patients, the sites of infiltration can show
mild recurrent edema lasting as long as the correction is
present. The mechanism is not clear, perhaps a difficult
lymphatic drainage, present only in particular cases such
as after intensive training, sun exposure, hearty meals,
and alcohol intake. It does not last for more than
24 hours.
Cold abscesses
These are different from septic abscesses because the
appear later (more than 2 weeks later) and are sterile.
The usual onset is erythematic or edematous papules or
plaques, painful at palpation and spontaneously evolving
in the following days/weeks or evolving in abscesses
that can become fistulas, both on the mucosal and skin
side. From personal experience, their evolution is self-
limiting and without permanent outcomes. It is advisable
to drain the abscesses and start an anti-inflammatory
therapy with prednisone 25 mg for 5 days and an
antibiotic therapy with clavulanic acid and amoxicillin
1 g BID for 6 days.
Granuloma from foreign body
This is the most feared side effect, fortunately; the rarest.
In the most serious cases, it may need a steroid therapy,
although its nature (self-limiting) avoids the need of
surgical excision.
The case of persistent granulomatous reactions after
hyaluronic acid correction in sites previously treated with a
different filler, often permanent, is different. These 2 latter
occurrences have been reduced in number since the market-
ing of more pure hyaluronic acids.
Sensitizing test?
Some authors suggest the use of the sensitizing test such
as for collagen. It is a common experience that these
reactions can also present in patients who have undergone
numerous procedures. The same patients subsequently
retreated (a behavior we do not suggest) do not always
develop new adverse events. These data rule out that the test
could protect them against the onset of adverse events, which
still remain unpredictable.
Clinical cases are depicted in
Adverse events are depicted in
.
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2. Friedman PM, Mafong EA, Kauvar ANB, et al. Safety data of injectable
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Dermatol Surg 2002;28:491-4.
3. Andre P, et al. Adverse reactions to dermal fillers: a review of European
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tissue augmentation. A clinical and histological study. Dermatol Surg
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Hyaluronic acid—based fillers: theory and practice
Document Outline
- Hyaluronic acid–based fillers: theory and practice
- Hyaluronic acid
- Fillers
- The “ideal” filler
- Hyaluronic acid for fillers
- Characteristics of hyaluronic acid–based fillers
- Presently marketed fillers
- Q-Med (Uppsala, Sweden)
- Teosyal: Teoxane Laboratories (Geneva, Switzerland)
- Isogel: Laboratories Filorga (Paris, France)
- Allergan
- Belotero: Merz Aesthetik (Frankfurtammain, Germany)
- FDP (Naples, Italy)
- Bio-Polymer GmbH and Co KG (Montabaur, Germany)
- Rofil Medical (Breda, The Netherlands)
- MacDermol from MacDermol Sar—Genopole d'Evry (Paris, France)
- Hyaluronic acid in aging face: when and where
- Schematic correction sites
- The session
- Correction techniques
- Nasolabial wrinkles and folds
- Glabella and forehead horizontal wrinkles
- Eyebrow and temporal areas
- Lip correction
- Labial philtrum
- Correction of lip volume
- Lip contour
- Vertical wrinkles of upper and lower lips
- Correction of commissural and subcommissural or labial chin furrow
- Commissural wrinkles or marionette lines
- Subcommissural or labial-chin furrow
- Zygoma augmentation by hyaluronic acid concentration
- Indications
- Hinderer's technique
- Patient's preparation
- Correction by intradermal implant
- Correction by supraperiosteal deep implant—transdermal technique
- Correction by supraperiosteal deep implant—transvestibular technique
- Posttreatment home care
- Immediate side effects and their management
- Posttreatment side effects and their management
- Retouches and duration
- Correction of the chin by hyaluronic acid infiltration
- Indications
- Patient evaluation
- Lines of facial profile
- Patient's preparation
- Correction by intradermal implant
- Correction by supraperiosteal deep implant—transdermal technique
- Correction by supraperiosteal deep implant—transvestibular technique
- Posttreatment home care
- Posttreatment side effects and their management
- Retouches and duration
- Correction of the mandibular contour by hyaluronic acid infiltration
- Nose correction: profile
- Correction of nasolacrimal trough and of orbital rim
- Hyaluronic acid: side effects and their management
- Foreseeable side effects
- Edema
- Erythema
- Pain-itch-palpability and higher sensitivity to the implant
- Ecchymosis
- Herpetic reactivation
- Side effects caused by malpractice
- Excessive palpability of the implant, nodules
- Hypercorrection
- Bluish coloring of the implant
- Whitening of the treated area
- Infection
- Unpredictable side effects
- Erythema/recurrent edema
- Cold abscesses
- Granuloma from foreign body
- Sensitizing test?
- Further reading
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