Current Concepts in The Use of Small-Particle Hyaluronic Acid

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FILLERS

Current Concepts in the Use of Small-Particle


Hyaluronic Acid
Vince Bertucci, MD, FRCPC
Background: Soft-tissue augmentation with hyaluronic acid (HA) fillers has
Carrie B. Lynde, MD, FRCPC
become one of the most popular cosmetic procedures performed. HA fillers
Toronto, Ontario, Canada represent safe and commonly used fillers. Several different HA fillers are avail-
able. The differences lie in the manufacturing process, allowing for tailored
uses. A small-particle HA with lidocaine (SP-HAL; Restylane Silk; Galderma,
Uppsala, Sweden) was approved by the US Food and Drug Administration in
June 2014 but has been available for many years in Canada as Restylane Fine
Lines and in Europe as Restylane Vital.
Methods: Relevant articles were reviewed relating to the composition, effec-
tiveness, and safety of SP-HAL. We also discuss the author’s extensive clinical
experience in the use of this product in Canada.
Results: SP-HAL has demonstrated proven benefits for lip fullness, augmen-
tation, and treatment of perioral rhytides. Although off-label in the United
States, SP-HAL is also well suited for the treatment of superficial fine lines,
including periorbital, forehead, marionette, and smile lines. In addition, it
has also been used in the tear trough region. A novel application for SP-HAL
includes use as a skinbooster with intradermal micropuncture. In this tech-
nique, small aliquots of product are injected so as to gradually rejuvenate the
skin in areas such as the face and hands. Side effects of SP-HAL were generally
transient and mild. The most common side effects were swelling, tenderness,
bruising, pain, and redness.
Conclusion: SP-HAL is an effective and safe HA filler with varied clinical
uses.  (Plast. Reconstr. Surg. 136: 132S, 2015.)

S
oft-tissue augmentation with hyaluronic acid Multiple HA fillers are available in different
(HA) fillers has become one of the most markets, each with their own unique characteris-
popular cosmetic procedures performed in tics. Nonanimal stabilized hyaluronic acid fillers
the United States.1–3 A member survey conducted are one example of commonly used HA fillers
by the American Society for Dermatologic Surgery with favorable clinical characteristics. Some other
revealed that 1.01 million soft-tissue filler treat- fillers available in different parts of the world
ments were performed in 2014, making injectable include the Juvederm, Emervel, Belotero, and
fillers the second most popular of all cosmetic Teoxane families of products. In the nonanimal
procedures performed by dermatologists, second stabilized hyaluronic acid family, a new small-par-
only to neuromodulator treatments.4 HA dermal ticle HA with lidocaine (SP-HAL, Restylane Silk;
fillers have become the material of choice, given Galderma, Uppsala, Sweden) was approved by the
their ease of use, low immunogenicity, reversibil- US Food and Drug Administration in June 2014
ity, and longevity.5 The better the ability of the gel and is indicated for submucosal implantation for
to resist deformation, the higher the lifting capac- lip augmentation and dermal implantation for
ity of the HA filler.6 The cross-linking process correction of perioral rhytides in patients over the
used to manufacture HA fillers serves to preserve age of 21.8,9 The same SP-HAL has been available
the entanglements of natural HA and to prolong in Canada and Europe for many years, marketed
product persistence in tissue.7
Disclosure: Dr. Bertucci has been an investigator,
From the Division of Dermatology, University of Toronto. speaker, and consultant for Allergan, Galderma,
Received for publication April 3, 2015; accepted June 25, Merz, and Valeant. Dr. Lynde has no financial
2015. ­interest in any of the products, devices, or drugs
Copyright © 2015 by the American Society of Plastic Surgeons ­mentioned in this article.
DOI: 10.1097/PRS.0000000000001834

132S www.PRSJournal.com
Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
Volume 136, Number 5S • Use of Small-Particle Hyaluronic Acid

under different names (Restylane Fine Lines and to Gram-positive bacteria such as streptococcus,
Restylane Vital, respectively), and is indicated bleeding disorders, or hypersensitivity to amide
there for facial tissue augmentation and correc- local anesthetics.8 Safety has not been established
tion of thin, superficial lines.10 It is a transparent, in patients who are pregnant, breast-feeding, wish-
viscous, and sterile HA gel isolated from a Strepto- ing to become pregnant, or under the age of 22
coccus species. years or over 65 years.8 Anecdotally, SP-HAL has
HA fillers from different manufacturers vary been safely used in an off-label fashion in individ-
in characteristics, such as total HA concentra- uals under the age of 21.
tion, modulus, particle size, degree of cross-linking, Products that are somewhat comparable to
percentage of cross-linked HA, the amount SP-HAL include, among others, Belotero Bal-
of unmodified HA present, and the extrusion ance (Merz Pharmaceuticals, Greenboro, N.C.),
force.11–13 HA gel is stabilized during the manu- a soft-tissue filler that has been available in the
facturing process to create a molecule that is United States since 2011. It may be used for sim-
resistant to mechanical and enzymatic degrada- ilar indications, but it differs in that it does not
tion,14 as tissue half-life is only 1–2 days without contain Lidocaine. Outside the United States,
cross-linking.1 The stabilization process varies other products such as Juvederm Volbella
according to manufacturer and explains differ- (Allergan, Irvine, Calif.) compete with SP-HAL.
ences in product longevity and viscosity.15 SP-HAL The latter product has a lower HA concentra-
is chemically cross-linked with 1,4-butanediol tion (15 mg/mL) than SP-HAL and an even less
diglycidyl ether and stabilized and suspended viscous consistency. Its rheological properties
in phosphate buffered saline at pH = 7 and a make it appropriate for very superficial injec-
concentration of 20  mg/mL.8 It contains 0.3% tions such as for subvermilion sheeting in the
lidocaine and is commercially available in a 1-mL lips to efface lip rhytides and to improve fine
disposable glass syringe.8 perioral rhytides.
The particle size or calibration of this prod-
uct family is set during the manufacturing pro- CLINICAL USE
cess by passing stabilized HA gel through screens
with a specific pore size, producing well-defined Lips
gel particles that are uniform in both shape The effectiveness of SP-HAL for lip fullness
and diameter.16 Each form of HA has a differ- augmentation and treatment of perioral rhytides
ent gel particle size (Table 1) (Fig. 1).15 SP-HAL was evaluated in a randomized, evaluator blinded,
is a low-density, less viscous filler indicated for no treatment–controlled study.17 Two hundred
more superficial dermis, whereas another prod- twenty-one subjects with very thin or thin lips
uct in the product range, small gel–particle HA based on the Medicis Lip Fullness Scale (MLFS)
with lidocaine (Restylane-L; Galderma), is com- were randomized 3:1 to SP-HAL or no treatment.17
posed of medium-density particles and is more Subjects randomized to treatment at baseline were
viscous and better suited for augmentation of retreated at 6 months and subjects randomized to
the mid-dermis.1 Finally, a third product in the no treatment at baseline received their first treat-
line, large gel–particle HA with lidocaine (Per- ment at 6 months. Treatment success was defined
lane; Galderma), is a high-density, longer-lasting as at least a 1-grade increase from baseline in the
HA filler that is useful for deep dermal injection MLFS for the blinded evaluator assessment at
and can be clinically used for deep subcutane- week 8 compared with the baseline assessment.17
ous and supraperiosteal injection such as in the A total of 76.1% of subjects who received SP-HAL
mid-cheek.1 were assessed as combined upper and lower lip
Contraindications include patients who MLFS responders by the blinded evaluator at 8
have severe allergies with a history of anaphy- weeks compared with 11.6% of subjects who were
laxis, multiple severe allergies, severe allergies not treated (P < 0.001)17; 90.1% of treated subjects
assessed themselves as improved or better from
baseline at 8 weeks and 75.6% at 24 weeks. Fifty-
Table 1.  Particle Size of Nonanimal Stabilized two subjects with Fitzpatrick types IV and V skin
Hyaluronic Acid Family of Products
were enrolled in the study with results similar as
Product Gel Particles/mL the overall study.17
Small-particle HA (Restylane Silk) 200,000 Clinically, SP-HAL is effective in lip augmenta-
Small gel–particle HA (Restylane) 100,000 tion, reducing perioral lines and effacing super-
Large gel–particle HA (Perlane) 8000
ficial rhytides within the vermilion of the lip

133S
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Plastic and Reconstructive Surgery • November Supplement 2015

Fig. 1. Schematic representation of nonanimal stabilized hyaluronic acid (NASHA) filler manufac-
turing process with respective particle sizes. Reprinted with permission from Galderma. Copy-
right 2015, Galderma Laboratories, L.P.

(Figs. 2–4). Thus, SP-HAL may be described as a As with many HA fillers, care should be taken
refining and defining soft-tissue filler. to avoid superficial injection so as to reduce the
risk of developing a blue hue, often referred to as
Superficial Fine Lines the Tyndall effect.
Although indicated for lips and perioral lines
in the United States, SP-HAL is also well suited for Nasojugal Groove/Tear Trough
superficial fine lines, including periorbital, fore- In the author’s experience (V.B.), SP-HAL
head, marionette, and smile lines. In some clinical may be used to improve the appearance of valleys
practices, it may be injected in a layered fashion, and shadows in the so-called tear trough region.
in combination with other HA products that are Treatment of this area requires deeper injection,
injected more deeply, so as to address not only super- below the plane of the orbicularis oculi muscle.
ficial lines but also improve contour and structure. This can be accomplished using the needle pro-
In the premarket US trial, there was a statisti- vided or with a cannula, such as a 27-gauge, 1.5-
cally significant and clinically meaningful improve- inch cannula.
ment in perioral rhytides as assessed by the blinded A prospective, randomized, split-face clinical
evaluator at weeks 8–24. A total of 56.5% of study produced excellent and safe results in 10
patients in the perioral rhytides treatment group subjects with prominent nasojugal grooves. SP-
were responders, while only 20.9% of those whose HAL was injected into one nasojugal groove using
upper lip only was treated were responders (P < serial puncture intradermally with a specialized
0.001). Seventy-two percent of treated subjects injector (Restylane injector) that dispensed 10
assessed themselves as improved or better from μL per injection. Normal saline was injected into
baseline at 8 weeks and 64% at 24 weeks.17 the other side. Blinded evaluators’ mean score

134S
Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
Volume 136, Number 5S • Use of Small-Particle Hyaluronic Acid

Fig. 2. A 32-year-old woman before (above) and after (below) treatment with 2  mL of SP-HAL
in the lips, perioral lines, and commissures and 1 mL of small gel–particle HA with lidocaine in
the nasolabial folds. Note improved lip projection, enhanced lip size, and reduced rhytides while
maintaining natural contours. Reprinted with permission from Galderma. Copyright 2015, Gal-
derma Laboratories, L.P. Photographs by Ava Shamban, MD.

on the treated side was statistically higher than Kerscher et al19 injected 19 subjects with SP-
control side at both 4 and 8 weeks, while at 24 HAL into the lower part of the cheeks bilaterally in
weeks, it remained higher but was not statistically 3 sessions: week 0, week 4, and week 8. Intradermal
significant. At 24 weeks, 50% of subjects reported injections approximately 1 cm apart using a serial
satisfaction compared with their status before puncture technique were utilized, with each subject
treatment.18 Use of a standard needle or cannula receiving approximately 1 syringe per session. The
is also effective for the nasojugal groove. The ben- vast majority of subjects (85%) rated the outcome
efit of a cannula is that the risk of intravascular as “very good” or “good,” with the remaining sub-
injection may be diminished if the cannula is used jects rating the treatment outcome as “moderate.”
gently, taking care to avoid advancing the cannula There was statistically significant improvement in
when significant resistance is met. both skin elasticity and roughness.19
Williams et al20 compared the effect of micro-
Skinboosters and Microinjection injections of SP-HAL on the hands with nonsta-
Injections of SP-HAL as skinboosters have bilized HA. Twenty-five subjects were injected at
been shown to be efficacious and well toler- weeks 0, 4, and 8 with random assignment of left
ated.19–23 SP-HAL skinboosters involves delivery of and right hands to either SP-HAL or nonstabi-
HA using intradermal micropuncture with small lized HA (ie, native HA). There was a significant
aliquots of product. This technique is designed to improvement in skin elasticity, surface roughness,
gradually rejuvenate the appearance of the skin hydration, and transepidermal water loss at week
in areas such as the face, hands, neck, and décol- 12 compared with baseline.20
letage with a series of treatments.22 Although less Microinjections for discrete depressed “ice
commonly utilized in North America, this tech- pick” acne scars have also been shown to be effec-
nique is more popular in parts of the world such tive. Twelve patients who responded well to laser
as Europe. treatment, but who still exhibited scattered deep

135S
Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
Plastic and Reconstructive Surgery • November Supplement 2015

“thread.” Threading is usually accomplished as


retrograde such that the needle is fully inserted
and is being withdrawn as one injects the filler;
however, it may also be done while advancing
the needle in an antegrade approach.8 Although
some injectors prefer the retrograde threading
technique to enhance the vermilion of the lip
and nasolabial folds, others prefer the antegrade
approach; product flow with the latter technique
may help to “push” vessels out of the way, theoreti-
cally reducing the risk of intravascular injection.

Serial Puncture
Serial puncture is accomplished by multiple,
closely spaced injections along wrinkles, folds,
or lips. The injection sites are close together to
ensure the material merges into a smooth, con-
tinuous line that ultimately lifts the wrinkle or
fold.1 Serial puncture allows for tight control
and precise product placement. This technique
is often used for fine superficial rhytides and
nasolabial folds.1 Serial puncture for treating lips
was found to have fewer adverse events, includ-
ing pain, swelling, bruising, and tissue mass, than
the linear anterograde technique in one random-
ized, evaluator-blinded study.16 These data may
indicate that despite multiple injections, serial
puncture may cause less tissue trauma than the
submucosal tunneling of the lip that occurs with
linear techniques.25 Having said that the author
(V.B.) anecdotally finds the linear threading
Fig. 3. A 59-year-old woman before (above) and after (below)
technique less traumatic as there are less needle
treatment with 1.0  mL of small gel–particle HA with lidocaine
puncture sites.
in the nasolabial folds and 2.8 mL of SP-HAL in the lips, perioral
lines, and oral commissures. Note improvement in perioral rhyt-
Fern Pattern Technique
ides and restoration of lip volume and contour. Reprinted with
permission from Galderma. Copyright 2015, Galderma Labora-
The fern pattern technique involves injecting
tories, L.P. Photographs by Ava Shamban, MD.
along the fold, in a linear fashion using a series
of punctures. The needle is inserted perpendic-
ular to the fold and advanced a few millimeters
ice pick scars, were treated with intradermal
away from the fold, and the product is injected
microinjections of SP-HAL via the Restylane injec-
in a retrograde fashion.26 This is repeated along
tor. All subjects were satisfied with the procedure
the length of the fold alternating between the left
and exhibited visible improvement in scars.24
and right sides of the fold. Modifications of this
technique employ antegrade product injection.
INJECTION TECHNIQUE This technique is especially helpful for dynamic
In the authors’ experience and as substantiated facial lines, such as smile lines, superficial nasola-
in the literature, SP-HAL may be injected utilizing bial lines, and marionette lines.26 This technique
a number of different techniques depending on is not effective for deep injection.
patient characteristics and the treating physician’s
experience and preference. Fanning
With the fanning technique, the needle is
Linear Threading inserted similar to linear threading; however,
Linear threading involves fully inserting the before it is withdrawn, its direction is changed
needle into the middle of the wrinkle, fold, or and product is injected along a new line creat-
lip and injecting the filler along the track like a ing linear deposits in a wheel spoke pattern.1 This

136S
Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
Volume 136, Number 5S • Use of Small-Particle Hyaluronic Acid

effects reported in the subject diaries included


swelling (98%), tenderness (91%), bruising
(81%), pain (77%), and redness (70%), all of
which are typical of lip injections.8 Seven percent
of subjects had abnormal lip firmness, almost all
of which were mild and 99% of which resolved
by 2 weeks after the first treatment.27 There were
no cases of severe abnormal lip firmness at any
point in the study, and none of the lip assess-
ments (texture, firmness, symmetry, movement,
function, mass formation, and device palpability)
were remarkable or presented safety concerns.8,17
Five serious adverse events were reported in 3
subjects; however, none were related to treat-
ment with SP-HAL. In addition, given the similar-
ity of the chemical compositions of SP-HAL and
other products in this family, studies previously
conducted support conclusions of the safety and
effectiveness of SP-HAL.8

CONCLUSIONS
SP-HAL is effective and well tolerated for lip
augmentation and for the correction of perioral
rhytides. In addition, SP-HAL has been clinically
used for the correction of other fine lines, such
as periorbital, forehead, marionette, and smile
lines. SP-HAL has a proven safety record, and side
Fig. 4. A 25-year-old woman before (above) and after (below) effects are generally mild and transient in nature.
treatment with 0.8 mL of SP-HAL in the lips. Enhanced lip con- Some of the novel uses of SP-HAL include micro-
tour and partial effacement of superficial rhytides within the puncture techniques as a skinbooster to gradu-
vermilion are evident. Copyright 2015, Dr. Vince Bertucci. ally rejuvenate the skin in areas such as the face,
hands, neck, and décolletage.
technique can be used submucosally to efface ver- Vince Bertucci, MD, FRCPC
tical wrinkles in the lip proper. Division of Dermatology
University of Toronto
8333 Weston Road, Suite 100
Specialized Injector Devices Woodbridge, Ontario L4L 8E2, Canada
Specialized injectors are devices designed vince.bertucci@utoronto.ca
to allow precision control of quantity of HA dis-
pensed. They generally allow the operator to con- patient consent
centrate solely on the placement of the gel and
Patients provided written consent for the use of
facilitating an even distribution of the gel across
their images.
the injected area.18,22 These devices may be espe-
cially useful for novice injectors as they become
familiar with product characteristics such as flow REFERENCES
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Copyright © 2015 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.
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