REVIEW Plastic Pointers
Edited by Ann P. Murchison, MD, MPH
Putting Injectable Facial
Fillers to Their Best Use
Filler indications range from lip and cheek augmentation to
treatment of moderate to severe facial rhytids.
Ronald W. Milam Jr., MD, Matthew Zhang, MD, and Behin Barahimi, MD, Nashville, Tenn.
oss of volume in the face and perioc-
L ular region leads to rhytid formation
(exaggerated skin folds, creases and
wrinkles), giving individuals a more
aged appearance. Dermal fillers are
natural and synthetic materials that
are injected into the skin of the rhytids
to replace the loss of volume and ul-
timately diminish the appearance of
facial wrinkles and creases. The use of
dermal fillers for effacement of facial
rhytids has gained popularity since the
Food and Drug Administration ap-
proved the first collagen filler in 1981.1
In 2013, injection of soft-tissue fillers
was the second most common mini-
mally invasive cosmetic procedure per-
formed in the United States, account-
ing for 2.2 million procedures.2 The
number of injections increased by 243
percent from 2010 to 2013, which was
the second highest rate of increase,
behind botulinum toxin injection, for
all minimally invasive cosmetic proce-
dures performed in the United States.2
While there are numerous filler
types available to the clinician, hy-
aluronic acid is the most commonly
utilized today. Hyaluronic acid fill-
ers not only replace the volume loss
that is experienced with aging but
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also stimulate collagen production. A
study by Taihao Quan, MD, PhD, and
colleagues demonstrated increased fi-
broblast proliferation, expanded vascu-
lature and increased epidermal thick-
ness when hyaluronic acid was injected
into the skin of patients older than 70
years of age. They hypothesized that
fillers stiffen the extracellular matrix,
induce fibroblast elongation and acti-
vation, and upregulate the transform-
ing growth factor-beta pathway, lead-
ing to collagen synthesis.3
Currently, more than 20 dermal fill-
ers have FDA approval for use in the
United States. Filler indications range
from lip and cheek augmentation to
treatment of moderate to severe facial
rhytids (See Table 1).1 Here, we will
discuss the array of materials approved
for use as soft-tissue filler in the United
States, their ndications and known as-
sociated complications.
Types of Filler
Modern dermal/soft-tissue fillers
are made from various materials and
can be categorized into absorbable
fillers and non-absorbable fillers.
These are the FDA-approved filler
This article has no commercial sponsorship.
types available in the United States:
Absorbable Fillers
Collagen. Collagen is a protein
that is naturally occurring throughout
the human body and is found in the
skin, bones, tendons and numerous
other tissues. Collagen was the earliest
filler material used for the treatment
of rhytids and is primarily derived
from purified human or bovine colla-
gen products. Collagen fillers have the
shortest length of effect of all the filler
materials4-6 and their effects generally
last for about three to four months.7
Hyaluronic acid. Hyaluronic
acid is a polysaccharide that is naturally
occurring throughout the human body
and is found in numerous tissues, in-
cluding the skin, synovial fluid, certain
types of cartilage and other connective
tissues. Hyaluronic acid fillers are de-
rived from purified bacteria and avian
(rooster combs) products. Hyaluronic
acid is an excellent filler choice be-
cause it is biodegradable, biocompat-
ible and non-immunogenic (i.e., has
a very low potential for stimulating
allergic reaction). It has excellent vis-
coelastic and hygroscopic properties,
10/22/15 2:18 PM
 which create good volume expansion
for the effacement of facial rhytids.8
Poly-l-lactic acid. PLLA is a
biodegradable and biocompatible syn-
thetic polymer that has widespread
medical applications as absorbable
sutures, bone screws and soft-tissue
fillers.7 As a filler, PLLA is reconsti-
tuted with sterile water into a hydrogel
with a methylcellulose carrier. PLLA
achieves its effects by causing a for-
eign-body reaction that stimulates col-
lagen formation and dermal fibrosis.8
In order to achieve the desired amount
of volume replacement, PLLA is in-
jected in multiple treatment sessions
over a period of months.
Effects may not be seen for several
weeks to months but can last for years,
with periodic touch-ups.
Calcium hydroxylapatite. Figure 1. Methods for filler injection. A. Linear threading; B. Serial puncture; C. Radial
CaHA is a biocompatible and nonim- fanning; D. Cross hatching.
munogenic material that is naturally
occurring in human bones and teeth. loss due to disease or age. The FDA allergy to eggs or cow collagen;
CaHA fillers are synthetic bone micro- has approved most fillers for the treat- any history of allergy causing ana-
spheres suspended in a carboxymeth- ment of moderate to severe wrinkles phylactic shock;
ylcellulose carrier gel. Its effects last and localized fat loss (lipoatrophy) in allergy to lidocaine;
approximately 18 months.7 It should the face. Restylane, Restylane-L and history of or predilection for ke-
be noted that this filler type is visible Restylane Silk have also been approve loid formation; and
on radiographs and may obscure un- dfor lip augmentation in patients over actively inflamed or infected skin.
derlying structures on radiographic 21 years of age. As of October 2013,
images. Juvederm Volumna XC received ap- Injection Methods
proval for augmentation of the cheeks
Non-absorbable Filler in patients over 21 years of age (See Numerous methods have been dis-
Table 1). All other uses of fillers are cussed in regards to injecting dermal
Polymethylmethacrylate. considered off-label and should be dis- fillers. The depth of the injection de-
PMMA is a non-biodegradable, bio- closed as such to patients.1,7,9 pends on the properties of each prod-
compatible synthetic material that is Commonly utilized off-label appli- uct and the desired outcome. A few
used in bone cement, intraocular lens cations include volume replacement common methods utilized are dis-
implants and soft tissue fillers. As a and enhancement procedures such cussed below.
dermal filler, PMMA microspheres as cheek and chin augmentation, lip Linear threading. In linear
are suspended in a bovine-based col- enhancement, hand rejuvenation, tear threading, as the needle is withdrawn,
lagen and lidocaine solution and in- trough obliteration, nose reshaping, a tunnel of filler is injected to efface
jected over a period of several months. mid-facial volumization and correction the wrinkle. This technique is com-
PMMA microspheres are permanent of facial asymmetry. monly used to address isolated creases
and not absorbed by the body. such as nasolabial folds or marionette
Relative Contraindications lines. In this technique superficial in-
Indications & Uses jection of the filler can occur toward
The FDA recommends that patients the end of the needle withdrawal pro-
The main indications for injectable with the following conditions avoid the cess, resulting in the Tyndall effect
fillers include the filling of rhytids and use of facial fillers:9 (See Figure 1A).
folds, and the correction of soft-tissue history of bleeding disorders; Serial puncture. In this tech-

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 REVIEW Plastic
Pointers
nique serial injections are made along Table 1. Facial Fillers Available in the United States and their
the length of a wrinkle where small FDA Approved Indications1
aliquots of filler are deposited. There
is potential for more bruising with this Trade Name Material DOA FDA Approved Indications
technique (See Figure 1B). Belotero Balance HA 11/14/2011 Smooth facial rhytids
Radial fanning. The goal of Captique HA 11/12/2004 Moderate/severe facial rhytids
radial fanning is to fill the problem Elevess HA + Lido 12/20/2006 Moderate/severe facial rhytids
area with minimal skin punctures in Hylaform HA (avian) 4/22/2004 Moderate/severe facial rhytids
hopes of decreasing bruising. A needle Juvaderm 24HV
is inserted in the desired region and a Juvaderm 30 HA 6/2/2006 Moderate/severe facial rhytids
tunnel of filler is injected as the nee- Juvaderm 30HV
Juvederm Volumna 10/22/2013 Cheek
dle is withdrawn; however, before the augmentation for age-related
HA + Lido
XC volume loss (age > 21)
needle is completely removed from
Prevelle Silk HA + Lido 2/26/2008 Moderate/severe facial rhytids
the skin, it is redirected into a different
Restylane HA 12/12/2003 Moderate/severe facial rhytids
radial plane and more filler is injected
Restylane HA 3/25/2005 Moderate/severe facial rhytids
until the desired outcome is achieved
(See Figure 1C). Restylane HA 10/11/2011 Lip augmentation (age > 21)
Cross hatching. Cross hatching Restylane-L HA + Lido 8/30/2012 Moderate/severe facial rhytids and lip
builds on linear filling where a series augmentation (age > 21)
of parallel tunnels of filler is injected. Restylane Lyft with HA + Lido Moderate/severe facial rhytids;
Then perpendicular tunnels are in- 7/1/2015
Lidocaine Age-related volume loss (age > 21)
jected to create a cross hatching. This Lip augmentation & perioral rhytids
technique is meant for filling in broad- Restylane Silk HA + Lido 6/13/2014 (age > 21)
er areas (See Figure 1D). Cosmoderm 1 Collagen 3/11/2033 Correction of soft tissue deficiencies
Human-Based C such as wrinkles and acne scars
Evolence Collagen 6/27/2008 Moderate/Severe facial rhytids
Complications
Correction of depressed cutaneous
Fibrel Collagen 2/26/1988 scars
Several complications have been re-
Zyplast Collagen 6/24/1985 Correction of contour deficiencies
ported with the injection of soft-tissue
fillers. Complications from use of non- Zyderm Collagen 9/18/1981 Correction of contour deficiencies
absorbable fillers (PMMA) are more Radiesse CaHA 6/4/2015 Volume loss in dorsum of hands
difficult to manage: As they are not
absorbed they may need to be excised. Radiesse 1.3CC 12/22/2006 Moderate/severe facial rhytids;
This may result in unwanted scarring CaHA
Radiesse 0.3CC Facial lipoatrophy in HIV
and ultimately poor cosmetic results.
PMMA + collagen 10/27/2006 Use in facial tissue around the mouth
As a general rule, hyaulonic acid filler Artefill + lidocaine
complications may be reversed using
Sculptra PLLA 8/3/2004 Facial lipoatrophy in HIV
hyaluronidase, providing a distinct ad-
Sculptra-Aesthetic PLLA 7/28/2009 Shallow to deep facial rhytids
vantage for the clinician in the man-
agement of potential complications.10 HA = hyaluronic acid Lido = lidocaine
CaHA = calcium hydroxylapatite PMMA= polymethymethacrylate
Bruising. The most common PLLA = poly-l-lactic acid
complication seen with fillers is bruis-
ing of the injection site. This can oc-
cur regardless of the technique used. Use small-gauge needles and that can raise their blood pressure or
However, the following steps can be blunt cannulas. put strain on their head and face for 24
taken to minimize or prevent bruising: Minimize the number of punc- hours after injection (e.g., exercise and
Instruct patients to avoid using ture sites. activities that cause valsalva).
blood thinners (aspirin, warfarin, clopi- if bruising is noted or suspected Advise patients to keep their
dogrel, dabigatran, nonsteroidal anti- at the time of injection, immediately head elevated for 24 hours after injec-
inflammatory drugs, fish oil, vitamin E, hold pressure over the area and apply tion.
garlic, gingko or ginseng) for one week an ice pack. Over-filling. Overfilling may re-
prior to injection. Advise patients to avoid activities sult from injecting too much filler into

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 REVIEW Plastic
Pointers
a small area and may create lumps,
nodules or asymmetry. Treatment
includes: hyaluronic acidinjection of
hyaluronidase into area of over-filling;
other fillersincision and drainage of
the filler; and large volume nodules
injection of local anesthetic and aspira-
tion of filler with a larger-bore nee-
dle.10 Use caution when planning for
correction of multiple nodules within
vital anatomical structures.
Under-filling. Under-filling may
result from injecting too little filler into
a rhytid, and is treated by injecting
more filler in the area of under-filling.
Granulomatous inflammation.
Granulomatous inflammation may re-
sult from any type of filler. True granu-
lomas from fillers will likely involve
multiple sites of injections. Solitary
nodules are likely not true granuloma-
tous reactions. Treatment may include
graduated injections over period of
weeks to months with one of the anti-
inflammatory medications, kenalog,
triamcinolone or 5-fluorouracil.10
Tyndall effect. The Tyndall ef-
fect results from injecting hyaluroni-
dase fillers too superficially, which
places the filler close to the surface
of the skin. It causes a bluish discolor-
ation to the overlying skin, which looks
like a deep bruise. This complication
will not improve until the filler is re-
moved. Treatment entails injection of
15 to 50 IU of hyaluronidase, and gen-
tle massage by rolling a cotton-tipped
applicator over the area to disperse the
hyaluronidase.10
Infection at injection site. This
is an uncommon complication with fill-
ers. It may be caused by bacterial, viral
or Candida species. Herpes simplex
is the most common viral infection to
spread to an injection site, and is more
common in patients with a strong his-
tory of cold sores. Consider pretreating
with acyclovir, valacyclovir or famciclo-
vir to reduce the risk of complication.
Maintain a low threshold for complete
ophthalmologic evaluation if there is
any concern for ocular involvement of
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herpes simplex virus.10
In cases of abscess formation, treat-
ment involves incision and drainage
oral antibiotics to cover common skin
flora, gram positives if there is concern
for cellulitis. Hyaluronidase should al-
ways be avoided any time there is sus-
picion for infection, as it may allow for
further spreading of infection through
the surrounding soft tissue.
Biofilms. Biofilms may result
from any implantable device or foreign
material placed within the body. They
allow bacteria to lie dormant for a long
period, then awaken later in time to
cause granulomatous inflammation,
abscess formation or cellulitis. Treat-
ment includes:
Permanent fillers (PMMA)in-
cision and removal of filler. This is why
caution must be used when consider-
ing permanent fillers for use in vital
anatomical structures such as lips and
eyelids.
Hyaluronic acidinjection of hy-
aluronidase.
Broad-spectrum oral antibiotics
(fluoroquinolones or macrolides).
Avoid all steroids and NSAIDs.
If infection persists after above treat-
ment, consider laser lysis or incision
and drainage.1,10,11
Vascular necrosis.12 Vascular
necrosis is an extremely rare complica-
tion from filler use but still must be
discussed with patients. The risk for all
vascular complications increases with
deeper large bolus filler injections. It
results from accidental intravascular
injection of filler and may lead to local
or distant ischemic necrosis of soft tis-
sue. The local injection site necrosis is
most commonly seen in the glabella, a
potential vascular watershed region.
Clinical signs and symptoms include
blanching; mottled discoloration of
skin (livedo reticularis); pain; dusky
skin discoloration; and sluggish or ab-
sent capillary refill. Immediate treat-
ment is critical for recovery of vascular
supply and includes:
injection of hyaluronidase direct-
ly into the ischemic tissue (works if
injected filler is HA);
oral aspirin;
topical nitropaste over ischemic
tissue;
warm compress and massage of
the affected tissue; and
hyperbaric oxygen therapy, which
may be considered in persistent cases
failing initial treatment with above.
Central retinal artery occlu-
sion. CRAO is an extremely rare com-
plication from filler use but still must
be discussed with patients.12 It pres-
ents with sudden visual field defect or
vision loss. Funduscopy is warranted
and may show signs of CRAO. Treat-
ment includes ocular massage; hyper-
ventilation; oral aspirin; and hyperbaric
oxygen therapy. Treatment is widely
ineffective for CRAO related to filler
embolus.
Drs. Milam, Zhang and Barahini
are at the Vanderbilt Eye Institute,
Vanderbilt University Medical Center.
Contact Dr. Milam at 4505 Georgia
Ave. Nashville, Tenn. 37209. Phone:
(704) 929-8811; fax: (615) 936-4979;
Email: ronald.milam@vanderbilt.edu.
1. Soft tissue fillers approved by the center for devices and radio-
logical health. U.S. Food and Drug Administration website. www.
fda.gov/MedicalDevices/ProductsandMedicalProcedures/Cos
meticDevices/WrinkleFillers/ucm227749.htm. Updated 2015. Ac-
cessed 08/30/2015.
2. 2013 Plastic Surgery Statistics Report. American Society of Plas-
tic Surgeons.
3. Quan T, Wang F, Shao Y, et al. Enhancing structural support of the
dermal microenvironment activates fibroblasts, endothelial cells,
and keratinocytes in aged human skin in vivo. J Invest Dermatol
2013;133(3):658-667.
4. Narins RS, Brandt F, Leyden J, Lorenc ZP, et al. A randomized,
double-blind, multicenter comparison of the efficacy and tolerability
of restylane versus zyplast for the correction of nasolabial folds.
Dermatol Surg 2003;29(6):588-595.
5. Lindqvist C, Tveten S, Bondevik BE, Fagrell D. A randomized,
evaluator-blind, multicenter comparison of the efficacy and toler-
ability of perlane versus zyplast in the correction of nasolabial folds.
Plast Reconstr Surg 2005;115(1):282-289.
6. Baumann LS, Shamban AT, Lupo MP, et al. Comparison of
smooth-gel hyaluronic acid dermal fillers with cross-linked bovine
collagen: A multicenter, double-masked, randomized, within-sub-
ject study. Dermatol Surg 2007;33 Suppl 2:S128-35.
7. Soft tissue fillers (dermal fillers). U.S. Food and Drug Adminis-
tration website. http://www.fda.gov/medicaldevices/productsand
medicalprocedures/cosmeticdevices/wrinklefillers/default.htm.
Updated 2015. Accessed 08/30/2015.
8. Kontis TC. Contemporary review of injectable facial fillers. JAMA
Facial Plast Surg 2013;15(1):58-64. .
9. Filling in wrinkles safely. FDA Consumer Updates. Aug 2014.
10. DeLorenzi C. Complications of injectable fillers, part I. Aesthet
Surg J 2013;33(4):561-575.
11. Dayan SH, Arkins JP, Brindise R. Soft tissue fillers and biofilms.
Facial Plast Surg 2011;27(1):23-28.
12. DeLorenzi C. Complications of injectable fillers, part 2: Vascular
complications. Aesthet Surg J 2014;34(4):584-600.
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