Atlas Phẫu Thuật Thẩm Mỹ (Tập 2) – Atlas of Cosmetic Surgery

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Tập 2 của bộ Atlas Phẫu thuật thẩm mỹ kinh điển, trình bày minh họa sắc nét các thủ thuật tạo hình khuôn mặt và định hình cơ thể. Tài liệu hỗ trợ tra cứu nhanh các bước tiến hành phẫu thuật chuẩn y khoa.


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256
Chapter 17
Cosmetic surgery procedures and techniques
two applications or coats followed by a 14–18-hour i­ncubation
time. However, this application was subsequently found to be
associated with significant discomfort during the lengthy illu­
mination process.39 It was discovered that short incubation
(3 h) was as effective as long (14–18 h) for AK clearance when
used with LP PDL.15 This finding was reproduced for ALA
in conjunction with blue light.41,42 As a result, ALA applica­
tion is currently recommended for a short 1-hour incubation
followed by blue light for the treatment of AK and photo­
damage. In cases of severe photodamage, topical lidocaine
and prilocaine (EMLA cream) may be applied following ALA
application and for 1 hour prior to blue light irradiation in
order to minimize discomfort.41 Though it is the author’s pref­
erence that patients incubate in low-light environments, many
clinicians do not shield patients from light during incubation
and there are no studies evaluating this aspect of the PDT
protocol. The affected area is subsequently washed prior to
the blue light step.
Blue light irradiation.  Blue light is applied with the Blu-U
(BLU-U® Blue Light Photodynamic Therapy Illuminator
DUSA pharmaceuticals) at 10 W per cm2 for 1000 seconds or
16 minutes and 40 seconds for the treatment of AK.40 Typi­
cally, one to two treatments at monthly intervals are required
for AK treatment. It is important to note that alternative blue
light sources yielded distinct irradiances and time of exposure
needs to be adjusted accordingly.
Acne
Aminolevulinic acid application.  For acne treatment with
ALA and blue light, topical ALA is recommended for 45–60
minutes incubation since shorter incubation times in the 15–30
minute range demonstrated lower reported efficacy.43,81 The
comparative efficacy of ALA blue light versus blue light alone
awaits further investigation, as blue light is effective in treat­
ing acne independent of ALA application.43,64 The patient
may wash the ALA prior to blue light irradiation; however,
the author recommends performing the blue light step prior
to washing in order to augment the response.
Blue light irradiation.  Following ALA incubation, patients
are irradiated with blue light (Blu-U) at 10 W per cm2, initially
for an exposure time of 8 minutes and 20 seconds. During
subsequent treatments, the exposure time may be increased to
16 min 40 sec depending upon the side effect profile from the
initial treatment. The frequency, timing and long-term efficacy
of this protocol has yet to be determined, and upcoming trials
will clarify this treatment regimen. The treatment frequency
has varied among investigators from weekly to monthly.
• Once the clinical trials for ALA and blue light
for treatment of acne are completed, patient
­selection will be refined to choose patients
most likely to respond to ALA and blue light,
as ­opposed to other light sources.
Pearls
• The most significant postoperative complica­
tion is the excessive erythema and edema often
referred to as the ‘phototoxic reaction’ or
‘PDT reaction.’ The reaction is exemplified by
marked erythema and crusting. For AK or photo­
damage treatment, this occurs more commonly
with blue light than with newer light sources.14
The phototoxic reaction occurs almost exclusively
in patients who have significant photodamage
and/or who inadvertently receive too much light
exposure following treatment. Avoidance of this
complication in susceptible individuals may be
achieved by decreasing incubation and expo­
sure times, selecting a newer light source such
as the LP PDL (below), and by advising patients
as to strict light avoidance during the first 2
postoperative days. When this reaction occurs,
it may prolong recovery time to 2–3 weeks.
• Postoperative corticosteroid ointments, such
as fluocinolone acetonide 0.025% ointment
(Synalar), two to three times daily are recom­
mended. In addition, advising the patient to
sleep with head elevated on pillows to minimize
facial edema and further light avoidance are
helpful to speed resolution.
pitfalls
• For very fair, type I skinned women with signifi­
cant photodamage, a single coat of topical ALA
for shorter incubation times is advised to mini­
mize risk of postoperative erythema and edema.
Keratotic AK may be curetted or pretreated with
acetone or urea so that the ALA can penetrate
to the basal layer.41Alternatively, one may apply
a third or fourth application coat of ALA and
additional passes with the laser or light source
to individual lesions.
• It is advisable to check on the patient during
the illumination process, and if a patient is expe­
riencing significant discomfort, to decrease the
exposure time.
• For patients with a history of marked discomfort
during PDT, a topical anesthetic cream, such as
EMLA, may be applied after ALA application for
the 1 hour prior to illumination.41
• Make certain the patient has brought their
broad-brimmed hat and cleared their schedule
the day of treatment. If the patient forgot their
hat or has an appointment the same day that
precludes light avoidance, it is best to reschedule
the treatment rather than risk a phototoxic
reaction.
PEARLS

257
Photodynamic therapy  •  Chapter 17
Aminolevulinic acid and long-pulsed pulsed
dye laser
Actinic keratosis and photodamage
Aminolevulinic acid application.  For AK treatment with
ALA and PL PDL, topical ALA may be applied for 1–3
hours’ incubation. Since 3-hour incubation was found to be
as effective as 14–18-hour long incubation, 3 hours is rec­
ommended to achieve high (>80%) clearance rates for AK
following a single treatment with ALA and LP PDL.15 When
this incubation time is decreased to 1 hour, efficacy rates
diminish to the >60% range, thus requiring an additional
re-treatment at 1 month to achieve further clearing. For
keratotic lesions, the ALA solution may be applied in three
successive applications to the individual lesions to enhance
penetration. Curettage, acetone scrubs, or pretreatment with
urea may be performed to keratotic lesions prior to ALA
application.
Long-pulsed pulsed dye laser irradiation.  Immediately
following ALA incubation and without cleansing the skin,
LP PDL (V beam laser, Candela, Wayland, MA) is applied
at 595 nm, with a fluence of 7–7.5 J/cm2, pulse duration of
10 ms, spot size of 10 mm and dynamic cooling spray (DCD)
of 30 ms with 30 ms delay. For distinct lesions, double or triple
pulses or passes are recommended. Immediate application of
cool compresses is recommended during the treatment process
and greatly minimizes any transient discomfort generated by
the laser pulses. In most cases with 3-hour incubation, a sin­
gle treatment is required, though resistant cases may require
a second treatment 1 month later. Recalcitrant, nonrespond­
ing lesions may be evidence of SCC; therefore, skin biopsies
may be necessary.15 For recalcitrant AK, adjuvant treatment
with imiquimod twice weekly for 4 months may be utilized
to achieve complete clearance. Once patients are clear, re-
­treatment may be necessary, as clinically indicated, on the
order of once per 1–2 years.
Actinic cheilitis
Aminolevulinic acid application.  For AC, topical ALA is
applied to in two or three successive coats for 2 hours’ incuba­
tion.68 The entire mucosal lip and vermillion borders should
be covered by the application and allowed to air dry. It is
recommended that the patient incubate in a low-light envi­
ronment or the area be covered using a nonstick gauze pad
(Telfa).
irradiation.  Long-pulsed PDL at 595 nm, fluence of 7–
7.5 J/cm2, pulse duration of 10 ms, spot size of 10 mm,
and DCD of 30 ms with 30 ms delay should be applied in
two to three passes.64 Postoperatively, petrolatum or Aqua­
phor Healing Ointment is applied twice daily until 1-month
follow-­up. Patients are still required to wear a broad-brimmed
hat the day of treatment and for 2 postoperative days and
to adhere to bright light avoidance for that period of time.
Complete clearance is achieved in most patients in one to
three monthly treatments, and re-treatment is expected to be
necessary every 1–2 years.68
• Adults with acne should be examined for signs
of photodamage and the necessary precautions
taken to avoid the phototoxic reaction discussed
above.
• A transient worsening of acne may occur during
the first postoperative week.
Pitfalls
• Following ALA application, patients’ lips are
shielded from light using light-impervious
dressings.
• Patients are not allowed to eat or drink during
the 2-hour incubation period.
• Light avoidance postoperatively is much less
critical than it is with AK and photodamage; if a
patient forgets to bring a hat, nonstick dressings
that are light occlusive may be easily applied.
Pearls
• As discussed in preoperative considerations
above, patients with a history of herpes labialis,
staphylococcal infections, immunosuppression,
or evidence or erosive or ulcerative AC should
be premedicated with antiviral and/or antibacte­
rial antibiotics to avoid postoperative herpes
simplex or impetigo.
Pitfalls
• Three to four coats of ALA solution and three
to four pulses or passes of the laser may be
applied to individual lesions to enhance
efficacy.
Pearls
• Rarely does a patient experience significant
erythema or edema with this light source, and
usually in the setting of severe photodamage
and excessive postoperative sun exposure.
• Even more rare is postoperative infection;
should a patient complain of worsening redness
or pustulation suggesting impetigo, treatment
with dicloxacillin is recommended (see below).
• While the settings used here are subpurpuric, it
is still possible that a patient on anticoagulation
may experience ecchymosis, which is self-
­limited and rapidly resolving.
Pitfalls

258
Chapter 17
Cosmetic surgery procedures and techniques
Acne
Aminolevulinic acid application.  Patients clean the face
with a non-soap cleanser as aforementioned, followed by ALA
application in one to two coats. ALA solution is applied in one
coat for the initial treatment and two coats for all subsequent
treatments. An incubation time of 45 minutes to 1 hour is rec­
ommended for LP PDL-mediated PDT.74 Patients are allowed
to incubate in a dimly room for the specified time.
Long-pulsed pulsed dye laser irradiation.  Long-pulsed
PDL is applied to the unwashed ALA-incubated skin at
595 nm, a starting fluence of 7 J/cm2, pulse duration of 10 ms,
spot size of 10 mm, and DCD of 30 ms with 30 ms delay. For
individual acne lesions or erythematous scars, a second pass
or double pulse may be performed. Immediate ­application of
cool compresses to the treated areas as the treatment is per­
formed greatly minimizes discomfort. Patients then wash the
treated areas with cool water and non-soap cleanser (Cetaphil,
Galderma). The skin is not treated with any postoperative
dressing. Patients are instructed to discontinue topical medica­
tions for approximately 5 days post-treatment. At that point,
any residual desquamation has resolved and patients may
restart their topical regimen. The fluence should be increased
to 7.5 J/cm2 upon the second treatment session and main­
tained at this level. A range of one to six treatments at monthly
intervals may be necessary for complete clearance.74
Aminolevulinic acid and intense pulsed light
Actinic keratosis and photodamage
Aminolevulinic acid incubation.  As above, patients are
instructed to clean the skin with a non-soap cleanser and
ALA is applied in one to two coats. For type I skin photo­
damaged women, one application is recommended for the
initial treatment. For IPL PDT of AK, short incubation of
45 minute to 1 hour is recommended based on published
findings.75–77
Intense pulsed light settings.  The standard photorejuvena­
tion settings for the particular IPL device should be employed.
The lowest starting fluence should be used for the initial
t­reatment with a single pass. Based on published findings,
at least two treatments at monthly intervals are necessary to
achieve high efficacy of AK clearance.75–77
Acne
Aminolevulinic acid application.  For acne treated with
ALA and IPL, the incubation times of ALA have ranged from
15 minutes to 1 hour, with greater reported efficacy at longer
• The postoperative course of long-pulsed PDL
PDT is normally cosmetically well accepted, with
minimal erythema resolving within 2–3 days.
However, rarely a patient may report significant
erythema or desquamation. This tends to occur
in adult acne patients with concurrent photo­
damage or those who expose themselves to
excessive sun; therefore, such patients should
be advised as to stricter light avoidance.
• As stated earlier, if the patient forgets to bring
a hat, it is better to reschedule the treatment to
avoid excessive erythema. In cases where such
erythema occurs, it typically resolves within
5–7 days.
Pitfalls
• The treatment interval is important, as recru­
descence may be observed if re-treatment is
delayed to 6 weeks or more. Thus, treatment
intervals should be limited to 3–5 weeks for
optimal rates of clearing.74
• A bonus of long-pulsed PDL PDT for acne is the
marked improvement that is achieved in
active erythematous acne scars.74 A second
pulse or pass to scars further speeds their
resolution, making this light source the ideal
choice for PDT of acne.
Pearls
• For individual AKs, a second pass with the
IPL may be performed to theoretically achieve
higher activation of photosensitizer and greater
clearance, though this approach awaits research
confirmation.
Pearls
• The unexpected phototoxic reaction is relatively
harder to predict when using IPL PDT for a first-
time patient.
• For patients with type I skin and extensive AK
or photodamage, a single application coat of
ALA with shorter incubation of 45 minutes,
followed by IPL at the lowest settings, and strict
bright light avoidance should be utilized.
• Should this complication occur, application of
topical fluocinonide 0.025% ointment two to
three times daily is helpful to speed resolution.
Pitfalls
• Though skin type VI patients have been suc­
cessfully treated with long-pulsed PDL PDT
without dyspigmentation,74 these patients are
still counseled about sun avoidance prior to and
following treatment.
• In dark-skinned patients, transient hyperpig­
mentation may occur in treated areas that are
sun-exposed postoperatively. This is wholly
preventable with strict bright light avoidance, but
nevertheless resolves within days to weeks.

259
Photodynamic therapy  •  Chapter 17
incubation times.80,81 It is thus recommended that ALA is
incubated for 45 minutes to 1 hour. Though it is the author’s
preference that patients incubate in low-light environments,
many clinicians do not shield patients from light during incu­
bation, as discussed earlier.
Intense pulsed light settings.  Once again, following ALA
incubation, the IPL is generally employed at standard photo­
rejuvenation settings for the specified device, using the lowest
fluence for the first treatment and limiting to one pass. A dou­
ble pulse or second pass may be performed on visible lesions.
Multiple treatment sessions are required, though ­further stud­
ies are needed to determine optimal treatment frequency and
range.
Methyl aminolevulinic acid and red light
Actinic keratosis
Methyl aminolevulinic acid application.  For the FDA-
approved indication of treating AK with MAL and red
light, the AK surface is curetted first to remove scales and
crusts. MAL (160 mg/g methyl aminolevulinate hydrochlo­
ride equivalent to 16.0%) cream is subsequently applied in
a 1 mm thick layer by using a spatula to each lesion and to
the surrounding 0.5–1.0 cm of normal skin. The area is then
covered with an occlusive dressing for a 3-hour incubation
time. At this point, the dressing is removed and the area is
cleansed with saline.
Red light.  Red light (Aktilite, Photocure) with a continuous
spectrum of 570–670 nm, a light output of 350 mA/light
emitting diode (LED) and a total light dose of 75 J/cm2 is
applied to the treated areas. The light dose is determined by
the size of the light field, distance between the skin and lamp,
and illumination time. One should refer to the user manual,
as two Aktilite lamps with LEDs are used for PDT and each
has a different light field size. The distance of the lamp from
the skin surface should be 5–8 cm. The average illumination
period is 10 minutes. Treatment of AK requires one to two
treatments spaced at monthly intervals.
Basal cell carcinoma
Methyl aminolevulinic acid application.  The use of MAL
PDT to treat BCC is still undergoing FDA phase III trials and
is not FDA-approved. The process of curettage and MAL
cream application for BCC is similar to that described for AK,
above. The concentration of MAL and the incubation time
are the same at 160 mg/g and 3 hours, respectively.
Red light.  The irradiation dose and time is the same as for
AK, above. One to two treatment sessions are required for
complete response of BCCs, though two sessions are currently
recommended. Superficial BCC respond at slightly higher
rates as compared to nodular BCC, though final trials are
pending.83
• Intense pulsed light PDT for the acne patient
may be the preferred choice for the adult acne
patient who is also suffering from signs of photo­
damage or fine lines, since the IPL has demon­
strated efficacy in these conditions.
Pearls
• The phototoxic reaction is very unusual in this
patient population, and is most likely to occur
in the photodamaged adult acne patient or one
who inadvertently is exposed to excessive sun.
The same treatment protocol should be em­
ployed to speed resolution. Prompt intervention
with topical corticosteroids is usually adequate
in ameliorating this side effect.
• Dyspigmentation is a potential complication in
darker skinned or tanned individuals, as it is for
the IPL alone, and is best handled by avoiding
treatment in these cases.
• Should postinflammatory hyperpigmentation
occur, routine treatment with hydroquinone,
other topical bleaching agents, or chemical
peels may be necessary.
Pitfalls
• During the initial curettage, the crusts and scales
should be removed, but normal tissue should
not be damaged.
• No reports have evaluated this treatment for
pigmented or hyperkeratotic AK.
Pearls
• Contact dermatitis may occur with MAL. This
has been attributed to the excipient cetostearyl
alcohol and methyl- and propyl parahydroxy­
benzoate.82 Any report of pruritus, excessive
redness or other unanticipated reaction at the
site of application should alert the clinician to the
possibility of this diagnosis. Treatment with topi­
cal corticosteroids is recommended.
• Local phototoxicity remains the most common
side effect, and it is generally mild and self-
limited. Burning or stinging sensation in the
skin (up to 80%), erythema (50–60%), edema
(14–17%), crusting (5–38%), and blister forma­
tion (7–19%) are the most commonly reported
complications.83 Throughout the clinical trials
consisting of up to 800 patients, one case of
intense pain was reported which occurred
during the second treatment, and which
resolved.83
Pitfalls

260
Chapter 17
Cosmetic surgery procedures and techniques
Postoperative clinical
considerations
Actinic keratosis/actinic cheilitis/
photodamage
Immediately postoperatively, the patient should wash the
treated area with a gentle non-soap cleanser and lukewarm to
cool water, and pat dry with paper towels. The most important
aspect of postoperative care is strict bright light avoidance. The
patient should put on the broad-brimmed hat immediately af­
ter washing. If the area treated was for actinic keratosis, actinic
cheilitis, or photodamage, petrolatum, such as Aquaphor Heal­
ing Ointment, should be applied twice daily. Patients are dis­
charged home and advised to stay in a low-light environment,
pulling the blinds in their office or home if it is a sunny day.
They are also advised to minimize going ­outdoors on sunny
days, and to wearing the broad-brimmed hat at all times except
while asleep during the first 2 postoperative days. If the treated
area is off the face and the patient can shield the areas easily
by wearing clothing, these instructions do not apply. If patients
adhere to this regimen of strict bright light avoidance for the
first 2 postoperative days, it is generally assured that they will
emerge on the third day with minimal erythema that resolves
by the fifth day. On the other hand, patients who do experience
bright light exposure during the first 2 postoperative days may
develop significant erythema that prolongs recovery to 7–10
days. Very rarely do patients develop significant erythema and
edema from the LP PDL protocol. Should such side effects oc­
cur, Synalar 0.05% ointment twice to three times daily suffices.
Acne
Once again, the patient should cleanse the treated area imme­
diately postoperatively with a gentle, non-soap cleanser and pat
dry. If the patient is treated for acne, nothing is applied postop­
eratively. The patient is advised to put on a broad-brimmed hat
and avoid bright light for the successive 2 postoperative days. If
it is a sunny day, they are advised to pull the shades in the home
or office. There is no need to be absent from school or work, but
the patient should wear the hat during these exposures. Patients
are advised to stay indoors for 2 consecutive days and wear
their hat during daylight hours. If they must go outdoors, they
should minimize the time period and wear the broad-brimmed
hat throughout that time. If patients adhere to this regimen of
strict bright light avoidance for the first 2 postoperative days, it
is generally assured that they will emerge on the third day with
minimal to no erythema. Some desquamation is anticipated. In
a minority of acne cases, a transient worsening of the acne may
occur during the first postoperative week, followed by improve­
ment during the second and third weeks.
Photorejuvenation
Depending upon the degree of actinic damage, the extent of
risk of phototoxicity is variable. Most patients may wear a wide-
brimmed hat and avoid bright light environments, but do not
need to stay indoors for the first 2 postoperative days unless ex­
tensive actinic damage is present. Postoperative petrolatum (Aq­
uaphor Healing Ointment) is advisable in most cases, excepting
patients who have a history of acneiform eruptions. However,
patients with extensive actinic damage should follow, at least the
first treatment, the postoperative instructions for AK.
• Curettage of BCC requires removal of the soft
tumor material, once again leaving the
surrounding normal skin and tissue intact.
• The use of this treatment for infiltrating,
morpheaform or variant forms of BCC has not
been reported.
Pearls
• The side effects and complications for treatment
of BCC are similar to those of AK (see above).
Pitfalls
Table 17-1  Algorithm of PDT
AK
AC
Acne
Photoaging
BCC
I. Application of photosensitizer
A. 5-ALA
1–3 h
1–2 h
0.75–1 h
1 h
3 h-overnight
B. MAL
3 h occluded
ND
ND
ND
3 h occluded
II. Laser or light irradiation
A. Blue
16’40”
ND
8’20”
16’40”
ND
B. LP PDL
7–7.5 J/cm2, 10 ms, 10 mm, DCD 30 ms/30 ms, 1 pass AK, acne, 2–3 pass AC, ND for BCC
C. IPL
Standard photorejuventaion settings, start lowest fluence AK, photoaging, ND for AC and BCC
D. Red
10’
ND
ND
ND
10’
H, hour; ND, not determined; ALA, aminolevulinic acid; MAL, methylated aminolevulinate; AK, actinic keratosis; AC, actinic cheilitis; BCC, basal cell carcinoma; Blue,
blue light; LP PDL, long-pulsed pulsed dye laser; IPL, intense pulsed light; Red, red light.
M. Alexiades-Armenakas, unpublished data.

261
Photodynamic therapy  •  Chapter 17
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30. Dougherty TJ, Kaugman JE, Goldfarb A, et al. Photoradiation therapy
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31. McCaughan JS, Guy JT, Hawley P, et al. Hamatoporphyrin-derivative
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32. Szeimies RM, Hein R, Baumler W, et al. A possible new incoherent
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33. Collins P, Robinson DJ, Stringer MR, et al. The variable response of
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34. Morton CA, Whitehurst C, Moseley H, et al. Comparison of
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35. Wolf P, Rieger E, Kerl H. Topical photodynamic therapy with
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36. Lui H, Salasche S, Kollias AT, et al. Photodynamic therapy of
nonmelanoma skin cancer with topical aminolevulinic acid: a clinical
histologic study. Arch Dermatol 1995; 131:737–738.
37. Orenstein A, Kostenich G, Tsur H, et al. Photodynamic therapy of
human skin tumors using topical application of 5-aminolevulinic acid,
DMSO and EDTA. In: Brault D, Jori G, Moan J, eds. Photodynamic
therapy of cancer II. Proc SPIE, 1995: 2325:100–105.
38. Fijan S, Honignsmann H, Ortel B. Photodynamic therapy of epithelial
skin tumours using delta-aminolevulinic acid and desferrioxamine.
Br J Dermatol 1995; 133:282–288.
39. Jeffes EW, McCullough JL, Weinstein GD, et al. Photodynamic therapy
of actinic keratoses with topical aminolevulinic acid hydrochloride and
fluorescent blue light. J Amer Acad Dermatol 2001; 45:96–104.
40. Piacquadio DJ, Chen DM, Farber HF, et al. Photodynamic therapy
with aminolevulinic acid topical solution and visible blue light in
the treatment of multiple actinic keratoses of the face and scalp:
investigator-blinded, phase 3, multicenter trials. Arch Dermatol 2004;
140(1):41–46.
41. Touma D, Yaar M, Whitehead S, et al. A trial of short incubation,
broad-area photodynamic therapy for facial actinic keratoses and diffuse
photodamage. Arch Dermatol 2004; 140(1):33–40.
42. Smith S, Piacquadio D, Morhenn V, et al. Short incubation PDT versus
5-FU in treating actinic keratoses. J Drugs Dermatol 2003; 2(6):
629–635.
43. Goldman MP, Boyce S. A single-center study of aminolevulinic acid and
417 nm photodynamic therapy in the treatment of moderate to severe
acne vulgaris. J Drugs Dermatol 2003; 2:393–396.
44. Tarstedt M, Rosdahl I, Berne B, et al. A randomized multicenter study
to compare two treatment regimens of topical methyl aminolevulinate
(Metvix)-PDT in actinic keratoses of the face and scalp. Acta Derm
Venereol 2005; 85(5):424–428.
45. Parisar DM, Lowe NJ, Steward DM, et al. Photodynamic therapy
with topical methyl aminolevulinate for actinic keratosis: results of a
prospective randomized multicenter trial. J Am Acad Dermatol 2003;
48:227–232.
46. Freeman M, Vinciullo C, Francis D, et al. A comparison of
photodynamic therapy using topical methyl aminolevulinate (Metvix)
with single cycle cryotherapy in patients with actinic keratosis: a
prospective, randomized study. J Dermatol Treatment 2003; 14(2):
99–106.

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47. Szeimes RM, Karrer S, Radakovic-Fijan S, et al. Photodynamic therapy
using topical methyl 5-aminolevulinate compared with cryotherapy for
actinic keratosis: a prospective, randomized study. J Am Acad Dermatol
2002; 47(2):258–262.
48. Soler AM, Warloe T, Berner A, et al. A follow-up study of recurrence
and cosmesis in completely responding superficial and nodular
basal cell carcinomas treated with methyl 5-aminolaevulinate-based
photodynamic therapy alone and with prior curettage. Br J Dermatol
2001; 145:467–471.
49. Rhodes LE, de Rie M, Enstrom Y, et al. Photodynamic therapy using
topical methyl aminolevulinate vs. surgery for nodular basal cell
carcinoma: results of a multicenter randomized prospective trial. Arch
Dermatol 2004; 140(1):17–23.
50. Vincullo C, Elliot T, Francis D, et al. Photodynamic therapy with topical
methyl aminolaevulinate for ‘difficult-to-treat’ basal cell carcinoma.
Br J Dermatol 2005; 152(4):765–772.
51. Lui H, Anderson RR. Photodynamic therapy in dermatology: recent
developments. Dermatol Ther 1993; 11(1):1–13.
52. Bandieramonte G, Marchesini R, Melloni E, et al. Laser phototherapy
following HpD administration in superficial neoplastic lesions. Tumori
1984; 70:327–334.
53. Lui H, Hobbs L, Tope W, et al. Photodynamic therapy of multiple
nonmelanoma skin cancers with verteporfin and red light-emitting
diodes: two-year response and cosmetic outcomes. Arch Dermatol 2004;
140(1):26–32.
54. Warloe T, Peng Q, Moan J, et al. Photochemotherapy of multiple
basal cell carcinoma with endogenous porphyrins induced by topical
application of 5-aminolevulinic acid. In: Spinelli P, Fante MD,
Marchesini R, eds. Photodynamic therapy and biomedical lasers.
Amsterdam: Elsevier Science Publishers BV; 1992:436–440.
55. Warloe T, Peng Q, Heyerdahl H, et al. Photodynamic therapy with
5-aminolevulinic acid induced porphyrins and DMSO/EDTA for basal
cell carcinoma. In: Cortese DA, 5th edn. International Photodynamic
Association Bienniel Meeting. Proc SPIE 1995; 2371:226–235.
56. Svanberg K, Andersson T, Killander D. Photodynamic therapy of
human skin malignancies and laser-induced fluorescence diagnostics
utilizing Photofrin and delta-aminolevulinic acid. In: Spinelli P, Fante
MD, Marchesini R, eds. Photodynamic therapy and biomedical lasers.
Amsterdam: Elsevier Science Publishers BV, 1992: 436–440.
57. Svanberg K, Andersson T, Killander D, et al. Photodynamic therapy
of non-melanoma malignant tumors of the skin using topical delta-
aminolevulinic acid sensitization and laser irradiation. Br J Dermatol
1994; 130:743–751.
58. Calzavara-Pinton PG. Repetitive photodynamic therapy with topical
delta-aminolaevulinic acid as an appropriate approach to the routine
treatment of superficial non-melanoma skin tumors. J Photochem
Photobiol B 1995; 29:53–57.
59. Jeffes EW, McCullough JL, Weinstein GD, et al. Photodynamic therapy
of actinic keratoses with topical 5-aminolevulinic acid: a pilot dose-
ranging study. Arch Dermatol 1997; 133:727–732.
60. Peng Q, Warloe T, Berg K, et al. 5-aminolevulinic acid-based
photodynamic therapy: clinical research and future challenges. Cancer
1997; 79(12):2282–2308.
61. Oseroff A, Shieh S, Frawley NP, et al. Treatment of diffuse basal cell
carcinomas and basaloid follicular hamartomas in nevoid basal cell
carcinoma syndrome by wide-area 5-aminolevulinic acid photodynamic
therapy. Arch Dermatol 2004; 141(1):60–67.
62. Hongcharu W, Taylor CR, Chang Y, et al. Topical ALA-photodynamic
therapy for the treatment of acne vulgaris. J Invest Dermatol 2000;
115:183–192.
63. Pollock B, Turner D, Stringer MR, et al. Topical aminolaevulinic
acid-photodynamic therapy for the treatment of acne vulgaris: a study
of clinical efficacy and mechanism of action. Br J Dermatol 2004;
151:616–622.
64. Papageorgiou P, Katsambas A, Chu A. Phototherapy with blue (415 nm)
and red (660 nm) light in the treatment of acne vulgaris. Br J Dermatol
2000; 142:973–978.
65. Itoh Y, Ninomiya Y, Tajima S, et al. Photodynamic therapy for acne
vulgaris with topical 5-aminolevulinic acid. Arch Dermatol 2000;
136:1093–1095.
66. Itoh Y, Ninomiya Y, Tajima S, et al. Photodynamic therapy of acne
vulgaris with topical delta aminolevulinic acid and incoherent light in
Japanese patients. Brit J Dermatol 2001; 144:575–579.
67. Alam M, Dover JS. Treatment of photoaging with topical
aminolevulinic acid and light. Skin Therapy Lett 2004; 3(5):548–551.
68. Alexiades-Armenakas MR, Geronemus RG. Laser-mediated
photodynamic therapy of actinic cheilitis. J Drugs Dermatol 2004;
3(5):548–552.
69. Lee WL, Shalita AR, Poh-Fitzpatrick MB. Comparative studies of
porphyrin production in Propionibacterium acnes and Propionibacterium
granulosum. J Bacteriol 1978; 133:811–815.
70. Arakane K, Rya A, Hayashi C, et al. Singlet oxygen (1 delta g)
generation from coproporphyrin in Propionibacterium acnes on irradiation.
Biochem Biophys Res Commun 1996; 223:578–582.
71. Divaris DX, Kennedy JC, Pottier RH. Phototoxic damage to sebaceous
glands and hair follicles of mice after systemic administration of
5-aminolevulinic acid correlates with localized protoporphyrin IX
fluorescence. Am J Pathol 1990; 136:891–897.
72. Alexiades-Armenakas MR, Bernstein L, Chen J, et al. Laser-assisted
photodynamic therapy of acne vulgaris and related conditions. Amer
Soc Las Surg Med Abstracts, Anaheim, April 2003.
73. Alster TS, Tanzi EL. Photodynamic therapy with topical aminolevulinic
acid and pulsed dye laser irradiation for sebaceous hyperplasia. J Drugs
Dermatol 2003; 2(5):501–504.
74. Alexiades-Armenakas MR. Long pulsed dye laser-mediated
photodynamic therapy combined with topical therapy for mild-to-severe
comedonal, inflammatory and cystic acne. J Drugs Dermatol 2006;
5(1):45–55.
75. Avram DK, Goldman MP. Effectiveness and safety of ALA-IPL in
treating actinic keratoses and photodamage. J Drugs Dermatol 2004;
3(1 Suppl):S36–S39.
76. Gilbert DJ. Treatment of actinic keratoses with sequential combination
of 5-fluorouracil and photodynamic therapy. J Drugs Dermatol 2005;
4(2):161–163.
77. Kim HS, Yoo JY, Cho KH, et al. Topical photodynamic therapy using
intense pulsed light for treatment of actinic keratosis: clinical and
histopathologic evaluation. Dermatol Surg 2005; 31(1):33–36. discussion
36–37.
78. Alster TS, Tanzi EL, Welsh EC. Photorejuvenation of facial skin with
topical 20% 5-aminolevulinic acid and intense pulsed light treatment:
a split-face comparison study. J Drugs Dermatol 2005; 4(1):35–38.
79. Hall JA, Keller PJ, Keller GS. Dose response of combination
photorejuvenation using intense pulsed light-activated photodynamic
therapy and radiofrequency energy. Arch Facial Plast Surg 2004;
6(6):374–378.
80. Gold MH, Bradshaw VL, Boring MM, et al. The use of a novel
intense pulsed light and heat source and ALA-PDT in the treatment of
moderate to severe inflammatory acne vulgaris. J Drugs Dermatol 2004;
3(6 Suppl):S15–S19.
81. Taub AF. Photodynamic therapy for the treatment of acne: a pilot study.
J Drugs Dermatol 2004; 3(suppl 6):S10–S14.
82. Wulf HC, Philipsen P. Allergic contact dermatitis to 5-aminolaevulinic
acid methlester but not to 5-aminolaevulinic acid after photodynamic
therapy. Br J Dermatol 2004; 150(1):143–145.
83. Kernland K, Karrer S, Szeimes RM, et al. Clinical photodynamic
therapy in dermatology. 2006;

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Photodynamic therapy  •  Chapter 17
Appendix A
Photodynamic Therapy Instructions
Description of treatment
• Photodynamic therapy is a treatment that has been successfully used for actinic keratoses (precancerous skin growths), acne, and
other skin conditions.
• A solution called Levulan is applied to the affected areas for anywhere from 1 hour to overnight depending upon the condition
treated.
• The solution makes the condition sensitive to light destruction or amelioration. A light source (blue light) IPL, red light or laser
(long-prised dye laser) is then applied to the affected areas. This step takes from 5 to 15 minutes.
Pretreatment instructions
• The day of treatment, you must bring a broad (4 inch) brimmed hat to shield your face from light if this is the area to be treated.
• Plan your treatment for a time when you are not expected to be in outdoor midday sunlight or bright indoor light for a period of
approximately 2–5 days after treatment depending upon the condition treated. Do not plan sunny vacations for at least 10 days after
treatment.
• Please instruct the physician of any medications you are taking, since they may make you more light sensitive, and of any history of
cold sores so that you may be pretreated with antiviral medications.
Post-treatment instructions
• Immediately following treatment, your skin will appear reddened. For most patients, the degree of redness is mild to moderate.
• Wash twice daily with Cetaphil cleanser (or another non-soap cleanser that you tolerate) and apply Aquaphor Healing Ointment (or
another emollient that agrees with you).
• The redness usually lasts from 2 or 5 days, though in unusual instances as long as 2 weeks, depending upon the degree of sun
damage or other factors.
• You should avoid sunlight or bright indoor light particularly the first 3 days after treatment. If you must go out, wear your hat and
keep exposure to a minimum. If stinging or burning occurs, this signifies too much light exposure and you should go into a darker
environment. When indoors, keep lighting low and blinds pulled. Most patients tolerate the procedure well.
Follow-up and ongoing treatments
• You will be instructed as to the appropriate follow-up interval following your photodynamic treatment. This typically ranges from
2 to 4 weeks, depending upon the condition.
• Depending upon the type and severity of your skin condition, you may require a series of ongoing treatments spaced at defined
intervals apart. This is necessary to safely and effectively treat the skin condition at hand. It is important to keep your follow-up
appointments in order to be properly evaluated and to achieve the best possible results.
When to call the office
• If you develop pain, pus-filled bumps, or redness extending beyond the treated area, this may signify on early infection. Call the
office so that you may be evaluated promptly by the physician and considered for antibiotic treatment.
Appendix B
Treatment of Photodynamic Therapy Consent Form
I hereby authorize Dr. ___________________and his/her associates to perform upon the named patient or me the following surgical/
medical procedure(s), invasive test(s), and/or treatment(s) for my condition which has been explained to me:
Procedure(s)/Test(s)/Treatment(s)_________________________________________________________________________
______________________________________________________________________________________________________
Diagnosis/Condition(s)_________________________________________________________________________________
______________________________________________________________________________________________________

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Background information
Photodynamic therapy involves the application of a substance onto the skin which is absorbed by specific skin cells and makes
them sensitive to light. The second step to this process involves application of light or laser to the treated area in order to acti­
vate the process. Photodynamic therapy has been developed over the past century and is currently used most commonly for the
treatment of: precancerous lesions of the skin (actinic keratoses) and lip (actinic cheilitis), skin cancers (basal cell carcinoma and
squamous cell carcinoma), sun-damaged skin, and acne. It is also used for photorejuvenation. Several light sources or lasers may
be used, including the blue light, red light, pulsed dye laser, and intense pulsed light.
Nature, purpose, risks and benefits of procedure(s)/test(s)/treatment(s)
The nature and purpose of the procedure(s), test(s), and/or treatment(s) have been explained to me. The expected benefits and
possible complications or risks have also been explained. I understand that there is no guarantee of a specific result or cure,
and that discomforts, risks and complications may arise. Results of laser treatment of vascular lesions vary from person to person
depending upon the type, size, and depth of the blood vessels in the skin and the color of my skin. The possible alternatives to
proposed treatment, including no treatment, have been explained to me. I have been given the opportunity to ask questions and
all of my questions have been answered fully and to my satisfaction.
Possibility of additional unplanned procedures(s)/test(s)/treatment(s)
I understand that during the course of the procedure/test/treatment, unforeseen conditions may require that different and/or
additional procedures/tests/treatments be performed. I therefore consent to the above-named physician and assistants to perform
such additional procedures/tests/treatments, as they consider necessary.
Risks and complications
• I understand that I must avoid sunlight or direct bright light exposure for 2 to 3 days following treatment. I must wear a
broad-brimmed hat or cover the treated area during this time and stay indoors in a dimly lit environment during this time. If I
do not follow these instructions, I understand that I will prolong and worsen the side effects below.
• I understand that I will experience redness of the skin at or around the treatment site and may notice some crusting or scabbing.
This usually fades in 5 to 14 days for actinic keratosis or sun-damaged skin, and 1 to 3 days for actinic cheilitis, acne, and photoreju­
venation. If I do not follow the postoperative instructions, I increase the risk of blistering, redness or scabbing and will prolong the
duration of redness. I will experience some stinging or burning, and understand that protecting the treated areas from light will
lessen these sensations. Some patients may develop a temporary brown discoloration of the treated areas of skin following treat­
ment. I understand that this discoloration usually fades in several months.
• I understand that laser procedures may result in scars, hyperpigmentation (darkening of skin), hypopigmentation (lightening
of skin), or localized hair loss in hair-bearing areas that are treated. I confirm that the areas to be treated have been delineated in
advance of the procedure with my approval. I understand that scars, hyperpigmentation, and hypopigmentation may be amenable
to additional procedures or treatments in the future in order for them to be improved.
• I understand that laser procedures may result in a burn. I have informed my physician of any recent tanning or prior history of
laser procedures.
• I understand that other common side effects or complications from surgical procedures/tests/and/or treatments include bleeding,
bruising and infection. I understand that the risk of bleeding or bruising either during or after the procedure is increased when
taking certain medications or supplements, and I have informed my doctor as to which medications and supplements I am taking.
The risk of infection is increased in individuals with certain medical problems, and I have informed my doctor as to my medical
conditions.
• I understand that uncommonly allergic reactions may occur, which may manifest as a red bump at the site of injection, incision,
procedure, test or treatment; theoretically, an extreme, severe form of allergy may result in anaphylaxis, which manifests as itch­
ing, skin swellings, difficulty breathing, and exceedingly rarely, even death. I have informed my physician of any allergies that I am
known to have.
• Other risks include blood clot formation in a superficial (thrombophlebitis) or deep (deep venous thrombosis) vessel; bruising,
swelling or tenderness at the treated areas; or delayed wound healing, which may require additional procedures/tests/treat­
ments. Such risks are increased in smokers and, if I am a smoker, I understand that I should discontinue smoking for at least two
weeks following the procedure, test, or treatment.
• Unusual risks include superficial nerve damage at the treated sites, which may result in prolonged pain, disturbed sensation, or
impaired movement at the treated areas.
• I understand that the treatment(s) may result in incomplete removal of the lesion. Photodynamic therapy typically requires
multiple treatments.

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Photodynamic therapy  •  Chapter 17
Cosmetic tattoo information
I understand that tattoos that are red, flesh-toned, white, or brown in color may permanently darken following laser treatment. I
have informed my doctor of any cosmetic tattoos I may have.
Post-treatment instructions
I understand the postoperative instructions given to me on the postoperative instruction sheet. I understand that in order to
­minimize the chances of side effects or complications, it is important that I follow all the postoperative instructions carefully.
Contraindications
I hereby confirm that I am not pregnant or breastfeeding, nor have I taken isotretinoin (Accutane) in the past year nor
gold therapy. I am not taking hydrochlorothiazides, tetracyclines or other medicines that may make me sun-sensitive. I
understand that I should inform my physician of any medical conditions, allergies, medications, smoking history, or recent sun
exposure.
Photography
I also agree to having photographs taken. These photographs will be used for educational purposes and may be used for
publication.
Consent
I have read the above information regarding the procedure(s)/test(s)/treatment(s), pre- and post-treatment information and in­
structions, risks and complications, and contraindications. I have asked my physician any questions I may have and am satisfied by
the answers to these questions. I accept the risks and potential complications resulting from the procedure(s)/test(s)/treatment(s),
deny any contraindications in my medical history, and hereby give my informed consent to the procedure(s)/test(s)/treatment(s).
___________________________________________________________________________
Patient/Healthcare Agent/Next-of-Kin Signature
Printed Name
Date
___________________________________________________________________________
Relationship Interpreter
___________________________________________________________________________
Witness
Physician/practitioner certification
I hereby certify that the nature, purpose, benefits, risks, and alternatives to (including no treatment and associated risks), the sur­
gical procedure(s)/test(s)/procedure(s), and/or treatment(s) have been explained to the patient. Any and all questions have been
answered in full. I believe that the patient/health care agent/guardian/next-of-kin fully understands what has been explained.
___________________________________________________________________________
Physician Signature

Date

HISTORY AND SCIENCE
Background and history
Botulinum toxin is a naturally occurring protein produced
by the bacteria Clostridium botulinum. Clostridium botulinum is
also responsible for botulism, the food poisoning that begins
as blurred vision, dry mouth, dizziness, and nausea and may
progress to a deadly, flaccid paralysis. Early outbreaks were
believed to be caused by sausage, thus the name was derived
from the Greek word for sausage, botulus. Although botulism
was well known in historical legend, the organism causing bot­
ulism was not identified until 1895 by Professor Emile Pierre
Marie van Ermengem. It is an anaerobic, spore-forming
bacterium that, under the proper conditions, can germinate
and create a toxin.
C. botulinum bacteria produces seven serologically distinct
types of botulinum neurotoxin (designated as types A, B, C,
D, E, F, and G).1 All subtypes of botulinum neurotoxin act
by preventing the release of acetylcholine at the neuromus­
cular junction of striated muscle fibers, creating a flaccid
paralysis of the muscle. Type A, which was purified in 1946 by
Dr. Edward Shantz, is the most potent of the seven subtypes
and is also the most potent neurotoxin known.2 Dr. Vernon
Brooks first suggested its therapeutic use on hyperfunctional
muscles in the 1950s. The initial batch of botulinum toxin
A (BTX-A), made by Dr. Alan Scott, was not prepared for
­human experiments until 1979. That 150 mg batch, labeled
79-11, was the source for all BTX-A used in the United States
until December 1997.3 Since 1997 a new FDA-approved
BTX-A source with less protein load has been widely used in
clinical practice (Allergan, Irvine, CA).
Botulinum A exotoxin (Botox, Botox Cosmetic, Allergan,
Irvine, CA) is approved by the US Food and Drug Admini­
stration (FDA) for the treatment of hyperfunctional muscles
affected by conditions such as blepharospasm, ­spastic muscle
activity, treatment of hyperhidrosis, and glabellar rhytides.
Many facial skin rhytides form when skin folds together per­
pendicular to the direction of underlying muscular contrac­
tions. When skin loses its elasticity with age and photoaging,
it does not rebound as well from the constant forces of stress
placed upon it, and wrinkles activate. A good example of this
is the pattern of horizontally oriented lines on the forehead.
Forehead rhytides form perpendicular to the vertically con­
tracting frontalis muscle. When the facial muscles responsible
for creating the wrinkles are not functionally necessary, BTX
may be injected to temporarily weaken them and ameliorate
the lines.
The use of BTX-A for cosmesis dates to 1988 when Drs.
Jean Carruthers and Alastair Carruthers noted resolution of
periorbital wrinkles in patients treated with Botox for benign
essential blepharospasm.4 The seminal work by Carruthers led
to Botox having an FDA-approved indication for ­treatment
of glabellar lines. Although officially off-label, BTX-A is now
used to treat many areas of the face including the forehead,
periorbital region, midface, perioral areas, and the neck. It
also has an excellent role in the treatment of palmar and
axillary hyperhidrosis, and certain types of headaches.
Basic science
In a normal nerve ending at the neuromuscular junction (NMJ),
there exist numerous small preformed vesicles containing the
neurotransmitter acetylcholine. As an action potential travels
down a nerve and reaches the nerve ending, it causes the vesi­
cles to dock to the terminal membrane of the junction. The
membranes fuse and acetylcholine from the vesicles is released
into the synaptic cleft. Acetylcholine is bound to the postsynap­
tic muscle and a muscular contraction is initiated. What allows
the preformed acetylcholine vesicles to dock and fuse to the
membrane is a structure termed the synaptic fusion complex.
The synaptic fusion complex is made up of a group of proteins
known as the SNARE (soluble N-­ethylmaleimide-sensitive
Botulinum Type A Toxin
Injections for Cosmetic Use
and Hyperhidrosis
Timothy C. Flynn, and
Thomas E. Rohrer
C H A P T E R
18
p a r t 2

268
Chapter 18
Cosmetic surgery procedures and techniques
factor attachment protein receptors) proteins. This SNARE
core complex is the location of action for botulinum toxins. If
one or more of the SNARE proteins are damaged, the acetyl­
choline vesicles are not able to dock and fuse and acetylcholine
will not be released. This results in a nonfunctional muscle.
BTX-A functions by interfering with acetylcholine release
at the NMJ (Fig. 18-1).5 The toxin exists in its native state com­
plexed with nontoxic proteins. The active toxin itself makes
up only 150 kilodaltons (kDa) of the total 900 kDa molecular
weight of the BTX-A complex structure. The remainder of
the structure is made up of large protective proteins, ­primarily
hemagglutinins, held together by covalent bonds that are very
stable in acidic environments. This clever structure serves to
protect the ingested toxin in the harsh acidic environment
of the gut. As the toxin is released into the bloodstream and
the pH rises, the bonds dissociate and the free neurotoxin is
released to have its effect on striated muscles.
The 150 kDa toxin is composed of two chains, light
(50 kDa) and heavy (100 kDa), linked by disulfide bonds.6 The
heavy chain has the C-terminus on it and is responsible for
the high-affinity docking on the presynaptic nerve membrane.
This binding is rapid and irreversible. In vitro, it is felt to oc­
cur in approximately 32–64 min. The toxin is then ­enveloped
by the cell membrane and internalized through energy-
dependent endocytosis. Once inside the cell, the disulfide
bonds are broken and the light chain of BTX-A is released
into the cytoplasm. Inhibition of acetylcholine release oc­
curs by it acting as a zinc-dependent metalloendoprotease
that deactivates specific components of the neuroexocytic
mechanism.7 Numerous proteins are required for the release
of acetylcholine, and botulinum toxin cleaves one or more of
these proteins as its mechanism of action. Botulinum toxins
A, C, and E cleave the 25 kDa synaptosomal associated pro­
tein SNAP-25. Types B, D, F, and G cleave a vesicle-associated
membrane protein.8
Botulinum toxin does not damage the nerve or alter the pro­
duction of acetylcholine. Only the structure responsible for the
transmission of the signal across the NMJ is damaged. Once the
synaptic transmission is inhibited, the target structures no longer
function. In the case of skeletal muscle, this means contraction
ceases. Clinically, muscle weakness becomes apparent 2–3 days
following BTX-A injection, with complete paralysis seen after
8–14 days.9 Histologically, the injected muscle atrophies with
individual muscle fibers becoming smaller.10–12 After 1 month
the atrophy stabilizes. Over time, the terminal nerve ending be­
gins to form new smaller unmyelinated nerve endings, termed
peripheral sprouts. Peripheral sprouting begins to occur within
28 days and activity returns to the nerve muscle complex in
approximately 3 months. Peripheral sprouts may originate from
the terminal node of Ranvier, the unmyelinated terminal axon
just retrograde to the end plate, or the terminal axon site itself.
Although it was originally thought that the peripheral sprout­
ing resulted in new normal NMJs, recent evidence13 suggests
that the SNAP-25 proteins eventually regenerate in the origi­
nal NMJ and re-establish the initial connection. The peripheral
sprouts then retract over time and disappear. Muscles paralyzed
by BTX-A return to function approximately 2–5 months after
injection, depending on the dose administered and the individ­
ual patient. Repeated injections are typically performed at this
interval to keep facial rhytides from reforming.
BTX-A is capable of inducing the formation of neutraliz­
ing antibodies. Once formed, the antibodies make the patient
relatively resistant to additional toxin injections. Antibody for­
mation seems to be dose dependent. Patients receiving mean
doses of 200 U are at increased risk for the development of
neutralizing antibodies.14 Such high doses are rarely used for
Botulinum toxin
Heavy chain
Light chain
Disulfide bond
Synaptotagmin
Syntaxin
SNAP 25
VAMP
Acetylcholine
Synaptic
vesicles
VAMP
Ach
Ach
Ach
Ach
Ach
Ach
Ach
Ach
Ach
Ach
Ach
Ach
Ach
Ach
Ach
S25
S25
Ach
S25
Ach
Fig. 18-1  Mechanism of action for botulinum toxin A at the
presynaptic neuron.

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Botulinum type A toxin injections for cosmetic use and hyperhidrosis  •  Chapter 18
cosmetic purposes but may at times be used for the ­treatment
of hyperhidrosis. There are very few reports of clinically
significant antibody formation occurring at cosmetic doses.
Botulinum toxin type B is available as Myobloc (Solstice
Pharmaceuticals). The dose finding study published in 2007
showed that the effect does not last as long as in available forms
of botulinum toxin type A. Significant numbers of units of
type B toxin (>100×) are needed to approach the effect of the
type A toxins. There is no cross-reactivity between the different
subtypes, which could be a clinical consideration for patients
who might develop neutralizing antibodies to BTX-A.15
Clinical studies
Each vial of Botox contains 100 U of lyophilized botulinum
A exotoxin, 0.5 mg of human albumin, and 0.9 mg of sodium
chloride (Box 18-1). It is kept refrigerated or frozen until recon­
stitution with normal saline. A study by Alam et al.16 demon­
strated significantly reduced pain on injection when Botox was
reconstituted with saline containing preservative. It is thought
that the benzyl alcohol used as preservative acts as an anes­
thetic and decreases pain on injection. Once reconstituted, the
package insert states that it should be used within 4 hours.
This is an FDA position on any reconstituted material and has
to do with sterility, not a decrease in efficacy. In terms of ef­
ficacy, Garcia and Fulton demonstrated continued potency of
solution kept refrigerated up to 4 weeks after reconstitution.17
Similarly, Hexsel et al. found no difference in efficacy between
Botox reconstituted up to six weeks prior to injection.18
The amount of saline used to reconstitute BTX varies
widely between practitioners. Placing anywhere between
1 and 10 mL of saline into the 100-unit vial, with correspond­
ing dilutions of 100 to 10 units/mL, have been published.
Although this has been a somewhat controversial point for
several years, recent glabellar studies19 suggest within the
range of 100–10 u/mL there was no noted difference in ef­
ficacy. Dilution had no effect on outcome in a study of lateral
orbital rhytids.20 These authors recommend finding a dilution
and remaining consistent with it. Botulinum toxin injections
should be thought of and discussed in terms of units and not
in terms of volume. This will help reduce confusion and po­
tential over- or underdosing. Whether injecting comparable
units, in higher or lower volumes, produces a more pleasing
cosmetic result remains a question.
Another form of botulinum toxin A is available as Dysport
(Speywood Pharmaceuticals, Maidenhead, Berkshire, United
Kingdom) in Europe and will be known as Reloxin in the
United States. Botox is roughly 2.5–4 times more potent
than Dysport/Reloxin, so that 2.5–4 times as many units of
Dysport/Reloxin are needed to achieve equivalent clinical ef­
fects.21,22 In a published dose finding study by Asher et al.,23
50 U of Dysport (Reloxin) was found to be the optimal dose
for treatment of glabellar rhytides. The package insert for
Botox suggests 20 U of Botox for glabellar treatment.
Rhytides
Original work published by Alastair and Jean Carruthers4,22–28
has opened the way for many other investigators to report their
experience with Botox. The Carruthers have used a delivery
of 100 U/1 mL of preservative-containing normal saline. This
allows the use of small volumes into the targeted muscles. Cur­
rent standard practice expresses treatment as a ‘number of
units’ placed in an area rather than expressing dose as volume.
Recent publication has shown that the dilution used does not
have any effect on the clinical result or the duration.
Many physicians tell their patients that the effects of Botox
last 3–4 months. Examination of the data from the FDA study
on Botox shows that approximately 25% have a persistence
of effect beyond 4 months.29 While the package insert recom­
mends 20 U be used for glabellar complex treatment, many
physicians use doses in the glabellar above this dose.30 Guyuron
and Huddelston found that they needed a Botox dose of 25 U
per glabellar complex to achieve muscle paralysis lasting for
­several months.31 Lower doses had an effect as short as 2 weeks.
Lowe et al. performed a double-blind, placebo-controlled
study of Botox for rhytides.32 They injected 10 U of Botox
or normal saline into each corrugator muscle of 30 subjects
under EMG guidance. The subjects who received the Botox
injection had a statistically significant reduction in their gla­
bellar frown line depth and length compared with the placebo
control 12 weeks after the injection.
Frankel and Kamer found, in a study of 30 patients, that
injecting 20 U of Botox into the glabellar muscle complex
achieved a modest brow elevation in 62% of patients.33 In
a collaborative study, 1500 patients were treated with Botox
for platysmal bands and neck wrinkles.34 Most patients were
treated with 50–100 U of Botox. Among patients with mild to
moderate platysmal bands and rhytides, 98.5% were judged
to have achieved good to excellent results. The treatment of
patients with severe platysmal bands was far less effective. One
percent of patients reported temporary neck weakness, and
one patient experienced dysphagia lasting 2 weeks.
Hyperhidrosis
Botox has also been used recently with success to treat ­axillary,
palmar, and plantar hyperhidrosis. An initial report by ­Bushara
et al. showed that injecting 50 U of Botox into the ­subdermal
tissue of the axilla achieves anhidrosis lasting 6–8 months
before wearing off.35 Glogau reproduced these results in 10
patients with axillary hyperhidrosis, with the anhidrosis lasting
4–7 months in his patients.36 Odderson blocked axillary sweat­
ing with 100 U per axilla in two patients; sweating started to
Box 18-1  Botox (botulinum exotoxin A, Allergan,
Irvine, CA)
Botulinum A exotoxin
100 U (lyophilized)
Human albumin
0.5 mg
Sodium chloride
0.9 mg

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Chapter 18
Cosmetic surgery procedures and techniques
return after 2–4 months.37 In two randomized, double-blind,
placebo-controlled trials of botulinum A exotoxin for severe
axillary hyperhidrosis, 13 patients received 200 U of Dysport
into one axilla with the other one being injected with normal
saline. Ninhydrin staining showed a 30% sweat reduction in
the Dysport-treated side compared with the placebo-treated
side at 3 months after injection. Subjectively, the Dysport side
had 60% less sweating compared with the placebo side.38
Shelley et al. achieved effective treatment of palmar hyper­
hidrosis in four patients by injecting 100 U of Botox into each
palm, 50 subdermal injections of 2 U. The anhidrosis lasted
4–12 months, and one patient experienced mild thumb weak­
ness for 3 weeks after injection.39 Naumann et al. injected
3 U of Botox per 4 cm2 into the axillae, palms, or soles of 11
patients with hyperhidrosis of those areas. Hyperhidrosis was
effectively blocked for the entire 5-month follow-up ­period.40
Lowe et al.41 performed a 52-week multicenter study of ef­
ficacy and safety of botulinum toxin injections for primary
axillary hyperhidrosis. They found a two-point improvement
on a four-point scale in the 50 U and 75 U BTX-A treatment
groups. The median duration of effect was around 200 days.
Frey’s syndrome, or gustatory sweating onto the cheek,
can be a fairly common side effect of parotid gland surgery.
Injecting Botox intracutaneously into the area of ­ gustatory
sweating has been shown to block the unwanted ­ sweating.
Bjerkhoel and Trobbe injected Botox into the cheeks of 15 pa­
tients with Frey’s syndrome and found abolition of sweating for
up to 13 months.42 In another study of 45 patients, Botox injec­
tion blocked gustatory sweating during the entire 6-month fol­
low-up period.43 Laskawi et al. treated 19 patients with severe
Frey’s syndrome and found the sweating effectively blocked
with one Botox injection for a mean of 17 months.44 Gustatory
sweating recurs anywhere from 8 months to 30 months after
Botox injection, but the recurrent sweating is always less severe
than initially and responds to additional Botox injections. On
the basis of these studies, Botox has become the nonsurgical
treatment of choice for severe Frey’s syndrome.45
Headaches
Botox injections into certain pericranial muscles has been
reported to be effective in a reduction in tension as well as
migraine-type headaches. Schulte-Mattler et al. injected a
total of 200 U of Dysport into the frontal, temporal, occipital,
and sternocleidomastoid muscles of nine patients with tension
headaches.46 The frequency and severity of headaches was
reduced by 50%. Wheeler achieved similar improvement in
four patients suffering from tension headaches.47 A review of
the use of BTX-A for migraine has recently been published48
and more studies are underway.
Discussion
The use of botulinum A exotoxin has evolved dramatically
over the past decade. Use of BTX-A in the treatment of hyper­
dynamic rhytides has become the leading cosmetic ­procedure
as reported by the American Society of Plastic Surgeons
(ASPS).49 Prior to the use of BTX-A, rejuvenation of the up­
per face was performed primarily with surgical interventions
such as forehead lifts or ablative laser resurfacing. The mor­
bidity of those procedures made them at times an unattractive
alternative for those patients seeking a subtle enhancement in
their appearance. With the advent of BTX-A, improvement
in dynamic rhytides of the glabella, forehead, and periocular
region became available to a much broader range of patients.
In addition, the simplicity of the BTX-A procedure made it
much more accessible to physicians. Doctors became comfort­
able treating rhytides with this injection technique due to its
relative ease of use and superb safety margin.50
Use of BTX-A in the dermatology community has
­exploded. While there continue to be many subtly different
approaches to the clinical use of BTX-A, the end goal is the
same: elimination of wrinkles or sweating for a period of 3–6
months. Some patients experience a prolonged period of clin­
ical efficacy greater than the average 3–6 months, but that is
the exception rather than the rule. Treatment of facial wrinkles
with botulinum toxin type A is often the patient’s introduction
to what can be achieved with dermasurgery, with many satis­
fied individuals partaking of additional procedures.
BTX-A is now routinely used to treat the upper one-third
of the face. Improvement in the appearance of forehead
wrinkles, glabellar folds, and periocular crow’s feet is remark­
able with only a few injections. Physicians who have gained
experience with the upper face often move to treatment of
the mid and lower face. Platysmal bands, previously treatable
only through surgical platysmaplasty, can now be addressed
for many patients in a 10-minute injection procedure instead
of a 1–2-hour surgical procedure.51 Surgical platysmaplasty is
still the definitive treatment of choice, but clearly the recovery,
cost, and risk profile for BTX-A can be much more attractive
to the prospective patient.
Botulinum A exotoxin injection is a safe, reproducible,
­office-based method for treating the aging face as well as
hyperhidrosis. Its role has evolved rapidly and will likely
­continue to do so. Newer uses for the toxin are almost certain
to be explored and new toxins will be coming to market.
PROCEDURES AND TECHNIQUES
Preoperative clinical considerations
Botox is reconstituted with preservative-containing normal
saline immediately before injection. Bacteriostatic normal sa­
line contains 0.9% benzyl alcohol, which is a mild anesthetic
and decreases the pain of injection. Common reconstitution
volumes include 1–5 mL per vial of 100 U of Botox or Botox
cosmetic. Again, the number of units injected into an area is
the most important factor in efficacy and duration of action.

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Botulinum type A toxin injections for cosmetic use and hyperhidrosis  •  Chapter 18
Authors have used anywhere from 0.5 mL to 10 mL of saline
to dilute the toxin, with no definitive difference in therapeutic
efficacy demonstrated (Box 18-2).17,52 Use of the 10 U/0.1 mL
concentration allows for use of the U-100 0.3 mL ultrafine II
needle insulin syringe which allows a direct reading of the
number of units off the barrel of the syringe.53 Using very
small amounts per injection site makes exact placement possi­
ble and has less tissue disruption and edema (Box 18-3). More
dilute concentrations allow for slightly greater and more even
spread of the toxin. This may lead to a more natural appear­
ance of the treated areas since there a more gradual transition
between treated and nontreated areas or a less noticeable line
of demarcation. The authors recommend choosing a concen­
tration that works for each physician and sticking with it.
Regardless of the concentration chosen by the treating
physician, dosing is recorded in the patient’s chart as number
of units injected. The reconstituted toxin is stable up to
6 weeks when stored in the refrigerator with no loss of efficacy
(Box 18-4).
Injection for facial rhytides can usually be accomplished
with anywhere from a few units up to 100 units in males. The
duration of action for BTX-A appears to lengthen to some
degree in a dose-dependent fashion up to a point. The higher
the number of units injected per muscle, the longer the clini­
cal effect. However, at a certain point, complication rates may
increase as well. Injection of the palms, soles, or axillae for
hyperhidrosis can require as much as 100–200 U per session,
and physicians should exercise caution when deciding how
many areas to treat at one time.
The issue of antibody development to the toxin has been
raised in several publications, but to date, anti-BTX-A anti­
bodies have not been identified when injections are ­performed
at the recommended doses for rhytide improvement. It is ad­
visable to remain under 200 U per session in order to reduce
the risk of neutralizing antibody formation.14 In the past for
noncosmetic treatments, it has been recommended that re-in­
jection be deferred for at least 30 days after the previous injec­
tion.54 However, the authors routinely use 2–20 U of Botox
for small touch-up procedures 2 weeks after the initial treat­
ment session without any apparent antibody formation when
patients are seen for a follow-up visit to evaluate the results.
Pretreatment preparation is minimal. Our patients are
asked to avoid aspirin, vitamin E, and nonsteroidal anti­
inflammatory drugs (NSAIDs) before treatment (Box 18-5).
However, BTX-A injection can safely be performed in indi­
viduals who have recently used agents that interfere with the
coagulation cascade. In individuals who have minor bleeding
at the point of injection, firm pressure with gauze or a cot­
ton-tipped applicator can be applied to the treated area until
bleeding is reduced. BTX-A injection is contraindicated dur­
ing pregnancy or nursing. It should be avoided in those with
a known hypersensitivity to human albumin and in patients
with neurological or muscular diseases such as amyotrophic
lateral sclerosis.
Hyperdynamic rhytides
BTX-A is widely used to treat hyperdynamic wrinkles of the
upper face. The forehead, glabella, and periorbital regions are
especially well suited to this treatment modality (Box 18-6). Since
Box 18-2  Dilution options for Botox
Diluent (ml of 0.9%
saline)
Concentration (units
of Botox per 0.1 mL)
1
10
2
5
2.5
4
5
2
Box 18-5  Pretreatment instructions
• Avoid aspirin-containing products for 1–2 weeks before
treatment.
• Avoid NSAIDs and other platelet inhibitors for 3 days
before treatment.
• Contraindications to treatment:

• Neuromuscular disease

• Allergy to human albumin

• Pregnancy or lactation
Box 18-4  Botox storage
• In refrigerator or freezer prior to reconstitution.
• Refrigerate after reconstitution. Package insert
recommends use in less than 4 hours. Clinical experience
suggests Botox can be stored and used for up to 6 weeks
without loss of effectiveness.
Box 18-3  Dilution technique
• Clean Botox bottle top with alcohol and allow to thoroughly
dry before adding diluent.
• Use preservative-containing 0.9% bacteriostatic normal
saline with preservative.
• Add diluent to Botox bottle through an 18–23-gauge needle.
• Insure complete dilution of Botox before withdrawing for
injection.
• Gently swirl it to mix.
Box 18-6  Muscle groups
Glabellar complex:
Corrugator supercilii, procerus,
depressor supercilii
Forehead:
Frontalis
Crow’s feet:
Lateral portion of orbicularis oculi

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Chapter 18
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BTX-A acts to inhibit the muscle actions that are the primary
causes of wrinkles of the upper third of the face, it is particu­
larly well suited to use in these locations. Additional treatment
options for wrinkles in this area include filler substance injec­
tions, resurfacing techniques such as erbium or carbon dioxide
lasers, ablative and nonablative fractional devices, as well as
surgical muscular denervation or excision. While all of these
options have selected advantages and disadvantages, BTX-A,
in general, is superior to each when used to treat dynamic wrin­
kles. BTX-A can consistently and effectively treat large areas
of the upper face with a few well-placed injection sites. It can
also be performed on an outpatient basis with rapid recovery
and very little associated morbidity, and patients can return
to their normal activities almost immediately after treatment.
Filler substances are often used in conjunction with BTX-A
therapy, and hyaluronic acid when used in combination with
BTX-A has been show to significantly improve results in the
appropriate patient.55 Resurfacing lasers can improve rhytides
and tighten skin. They can yield particularly impressive results
in the periorbital area where tightening of the thin eyelid skin
can be most dramatic. Unfortunately, glabellar and forehead
rhytides, even when significantly improved with resurfacing
devices, tend to recur fairly rapidly given the constant motion
in these dynamic areas. Botulinum toxin injection just prior
to the procedure has been shown to enhance and prolong the
effects of laser resurfacing. Resurfacing procedures carry with
them significant risks (outlined in other chapters) and have
prolonged recovery times. When other signs of photoaging
such as increased vascularity, lentigines, textural changes, and
fine rhytides are the patient’s primary concern, combination
techniques such as vascular and pigmented lesion lasers or an
intense pulsed light device can be used. The ideal patients for
BTX-A injections alone are those with hyperdynamic wrinkles
of the forehead, glabella, and crow’s feet with little associated
pigmentary or textural changes. Those with additional signs
of photoaging may benefit from using BTX-A in combination
with other therapies.
BTX-A injections are also used to treat wrinkles of the peri­
oral area and lower face, as well as platysmal bands. Although
more severe rhytides may require laser resurfacing, BTX-A in
small doses is helpful alone or in collaboration with filler sub­
stance of the lips. Vertical platysmal bands can be effectively
treated with BTX-A injections, and some correction of hori­
zontal rhytides has been reported.56 Patients with thin necks
and well-defined muscular bands are likely to achieve better re­
sults than those with advanced photoaging, submental fat, and
jowl formation. Those with advanced photoaging are likely
to benefit more from liposuction of the neck and jowls with
surgical repair of the platysma muscle. Full or partial face-lift
procedures are also options for treatment of the aging neck.57
Hyperhidrosis
The axillae, palms, and soles are areas of the human body that
are particularly susceptible to the condition hyperhidrosis. Ex­
cessive sweating in these areas has clear social ­implications for
those affected by it, and patients will often go to great lengths
to try to improve it. Topical therapy such as 20% aluminum
chloride hexahydrate (Drysol, Delasco, Council Bluffs, IA) has
little associated morbidity, but patients often find this relatively
ineffective. Iontophoresis which acts by creating keratin plugs
of eccrine gland ostia can be effective in selected patients, but
the improvement is relatively short lived, requiring continued
iontophoresis. Surgical sympathectomy can achieve excellent
results. However, there is a high percentage of recurrence fol­
lowing the procedure and patients often are reluctant to ex­
pose themselves to the associated morbidity of the surgery.
BTX-A injections can be performed on an outpatient basis
with a high degree of efficacy for hyperhidrosis and therefore
have quickly become the treatment of choice for excessive
sweating of the palms, soles, and axillae.
While some patients experience sweating of just the palms,
many have sweating that involves the fingers as well. This can
be a debilitating problem for them, dramatically interfering
with social interactions. These patients are typically reluctant
to shake even the physician’s hand at the time of the initial
consult due to being self-conscious about their sweating prob­
lem. While most patients are interested in having treatment
of both hands, some are uneasy about the prospect of having
injections into the hands, and the authors offer to them uni­
lateral injection of the right hand. This allows them to experi­
ence the benefits of BTX-A injection during post-treatment
social interactions, and many of these patients return to have
the left hand treated in the future.
Procedural techniques
Once reconstituted, BTX-A is injected directly into striated
muscle to produce its effects for the treatment of dynamic
rhytides of the face. It is injected in the superficial subdermal
subcutaneous space for hyperhidrosis.
Injections are performed with 1 mL Luer-Lok syringes (BD,
Franklin Lakes, NJ), which have clear markings on the bar­
rel to allow easy observation of injection volumes (Box 18-7)
or with the 0.3 cc U-100 ultrafine II BD insulin syringe. The
amount of BTX-A to be injected is calculated ahead of time,
and the exact amount to be used is slowly drawn up into the
syringe. An 18–23-gauge needle can be used with the Luer-
Lok syringe. Upon removing the needle from the vial, the
BTX-A left in the needle bevel is drawn into the syringe to re­
duce wasting any of this very expensive material. A 30-gauge,
half-inch needle is routinely used for injection, although some
physicians prefer a 31- or 32-gauge needle. Many ­physicians
• Injecting into or as close to the targeted muscle
will improve results and decrease complications.
• Some physicians prefer to mark the points of
injection prior to treatment.
Pearls

273
Botulinum type A toxin injections for cosmetic use and hyperhidrosis  •  Chapter 18
using the insulin syringe withdraw the reconstituted solution
directly into the ‘no dead space’ syringe. Use of these syringes
decreases waste of botulinum toxin.
Topical or local anesthesia is not generally required for cos­
metic injections, but some patients prefer preparation with a
topical anesthetic. The area to be treated should be cleaned
with an alcohol wipe, and the alcohol allowed to dry com­
pletely before commencing therapy to prevent denaturation
of the protein. While not necessary, some physicians prefer to
mark the exact points of injection prior to treatment.
Glabellar region
A thorough knowledge of the anatomy of the glabellar
region is critical to understanding proper injection techniques
for BTX-A (Fig. 18-2). The midline procerus muscle is a
­pyramidal-shaped muscle that originates on the nasal bone
in the superior nasal dorsum and inserts on the underside
of the dermis in the inferior forehead just superior to the
medial head of the eyebrows. The procerus also interdigitates
with the medial superior fibers of the orbicularis oculi mus­
cle and the medial inferior fibers of the frontalis muscle. The
procerus is thin (about 1 mm) and is approximately 1–4 mm
below the surface of the skin. The procerus muscle is slightly
longer in females (19.1 mm) than males (16.4 mm). Because
procerus contraction depresses the medial head of the brows,
it is categorized as a brow depressor and is responsible for the
horizontal rhytides in the nasal root area.
The corrugator supercilii muscle lies deep to the ­frontalis
muscle and superficial to the periosteum. It originates on the
frontal bone in the superior portion of the nasal dorsum, and
inserts on the underside of the dermis just above the eyebrow
bilaterally as well as the orbicularis oculi and frontalis mus­
cles. It has an oblique course, approximately 30 degrees above
horizontal and lies inferior to the superciliary arch. Its thickest
portion is found directly above the medial canthus, approxi­
mately 8 mm from the nasion (4 mm superior, and 6 mm
lateral to it). The bulk of the muscle is found at or above the
mid eyebrow level. There are two distinct patterns noted in
cadaver dissections of the corrugator muscles: a short pyrami­
dal shape and a long narrow straight shape extending along
the supraorbital ridge to or just beyond midbrow position. By
having a patient scowl it is easy to see where the lateral inser­
tion is and then make the injection just medial to that point.
Due to its orientation, the corrugator muscle is categorized as
both a brow apposer and depressor and is responsible for the
oblique and vertical rhytides in the glabellar region.
The depressor supercilii muscle is a thin muscle purported
to lie superficial to the corrugator muscle bilaterally. It is said
to originate on the superior nasal dorsum and inserts in the
dermis 13–14 mm superior to the medial canthal tendon. Its
vertical orientation and vector of action allows it to be catego­
rized as a brow depressor. There is, however, some question as
to this muscle’s existence. Although it has been described and
documented,58 two recent cadaver dissection studies involving
71 different cadavers, could not find the depressor supercilii in
any of the specimens.
Treatment of the glabellar complex must include inactivation
of procerus, corrugator, and perhaps the depressor supercilii
to achieve the desired effects (Fig. 18-3). Failure to completely
relax all of the musculature leads to less-than-optimal results.
Since the three muscles of the corrugator complex are the
only known brow depressors, a positive effect of therapy, in
­addition to elimination of glabellar rhytides, can be elevation of
the ­mediolateral brow. This is due to unopposed action of the
frontalis muscle, an elevator of the brow.
The authors use five to seven injection sites to treat the
­glabellar complex and have standardized their patient po­
sitioning to allow for reproducible results. All injections are
­performed with the needle and syringe barrel perpendicular
to the skin surface. The patient is positioned so that she or he
is upright or slightly reclined in the treatment chair, with the
head resting against the headrest. The end result is a posture
and needle position that allows for direct perpendicular injec­
tion into the skin (Fig. 18-4). All injections are performed by
placing the needle into the muscle and injecting the desired
number of units of BTX-A.
Box 18-7  Injection tools and tips
• Allow the alcohol on the patient’s skin to dry thoroughly
before injection to prevent toxin denaturation.
• Use of the 0.3 cc U-100 BD insulin syringe with ultrafine II
needle as well as a 1 mL/100 U vial dilution allows use
of the individual syringe marks which correlate with the
number of units injected.
• Patients’ injection sites can be marked with an eyebrow
pencil or a red dry eraser marker.
• Use a 30–32-gauge half-inch needle for injection.
Procerus m.
Corrugator
supercilii m.
Depressor
supercilii m.
Fig. 18-2  Glabella anatomy. The procerus muscle is a vertical
midline muscle (light pink). Corrugator supercilii fibers are oriented
horizontal/oblique bilaterally in a position at or just above the
eyebrow. Depressor supercilii is a narrow bilateral muscle vertically
oriented just lateral to procerus.

274
Chapter 18
Cosmetic surgery procedures and techniques
The five to seven injection sites are the following (Fig. 18-5):

• Into the center of the procerus, found by drawing lines
between the medial brow origin and the contralateral inner
canthus. The intersection marks the center of the muscle
in the majority of patients. This injection is made into the
belly of the procerus at a depth of approximately 2–4 mm.

• Two or three injections on each side to treat the corruga­
tor muscle. These injections are in line with the medial
canthus 1 cm above the orbital rim at the superciliary arch.
The superciliary arch may be palpated and generally lies
at the mid eyebrow position at its most medial point. Since
the corrugator muscle originates in the frontal bone, the
injection is made deep in this area closer to the perios­
teum. The most lateral injections are the most varied from
patient to patient and depend on the shape and length of
the corrugator being treated. The lateral most injection
point is made a centimeter above the orbital rim at the
point a little medial to where the patient’s lateral fibers of
the corrugator insert into the skin. By having the patient
scowl, this point is generally quite apparent. This injec­
tion is often in a vertical alignment with the ­lateral limbus
(outer edge of the iris with the patient in a ­neutral posi­
tion). The middle injection of the corrugator is ­halfway
between these two in patients with the long, straight, nar­
row shaped corrugators. Patients who have short narrow
straight muscles will often not require these midcorrugator
injections.
The first injection inactivates the procerus muscle, and
the other four to six injections inactivate the corrugator and
depressor supercilii muscles. A starting dose of 10–30 U of
Botox is common to treat the glabellar complex in females
and achieve good duration. Males and those females with very
strong glabellar complexes require more BTX-A, while those
with smaller weaker muscles may do well with smaller doses.
Persistent muscle activity following Botox injection of the
glabellar complex is not uncommon and can have one of sev­
eral causes. As stated above, there are some patients who need
higher doses of BTX-A and this alone may be sufficient to
accomplish the goals. Men typically need higher doses, and
starting doses of up to 40 U/glabella for males are often used.
Patients who have a very long narrow corrugator muscle may
simply have been injected too medially to inactivate the lateral
A
B
Fig. 18-3  A 28-year-old woman before (A) and two weeks after (B) BTX-A treatment of the glabella. Twenty-eight units was used and resulted
in a nice reduction in frown lines.
B-D
.1
.2
.3
.5
.6
.7
.8
.9
1
Fig. 18-4  Horizontal syringe position for BTX-A injection.

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Botulinum type A toxin injections for cosmetic use and hyperhidrosis  •  Chapter 18
Fig. 18-5  Glabella injection sites. Pink ‘x’ marks denote individual
injection points.
aspect of the muscle. By having the patient scowl, a small su­
perficial injection may be made into these lateral fibers. Some
individuals are able to furrow the glabellar area in the absence
of corrugator or glabellar muscular activity by recruiting the
lateral aspect of the orbicularis oculi muscle (Fig. 18-6). The
horizontal superolateral portion of orbicularis oculi, when it
contracts, can produce apposition of the medial head of the
brows. Small superficial doses of BTX-A can be useful to ­
relax this portion of orbicularis.
Proximal nose rhytides (so-called bunny lines) can also be
effectively treated.50.1 The patient is asked to furrow the proxi­
mal nose and medial cheek, and bilateral 2–4 U injections are
placed into the proximal obliquely oriented nasal rhytides to
weaken the muscles and produce the desired effect (Box 18-8).
Periorbital region
The lateral canthus region (crow’s feet) responds quite well
to BTX-A injections. The duration of action is shorter than
for other parts of the face. Three 2–5 U injections are per­
formed bilaterally to paralyze the lateral, vertically oriented
fibers of the orbicularis oculi muscle (Box 18-9). The muscle
lies deep to the subcutaneous tissue, but this layer is quite thin
lateral to the eye and there are numerous blood vessels in this
area that could potentially be disturbed and cause bruising.
Therefore, injection of toxin is generally performed just be­
low the skin to obtain good results. Some authors have even
reported using intradermal injections in this area. They feel
that administering BTX-A as a ‘wheal’ injection decreases
the risk of ­bruising even further. The three injection sites are
spaced approximately 1 cm apart in an arcuate orientation
around the crow’s feet area approximately 1 cm lateral to the
bony orbital rim (Fig. 18-7). It is helpful to have the patient
smile and squint before the injection to localize the muscle.
The orbicularis oculi varies significantly in its size and dis­
tribution around the eye. Some patients have a very broad,
more laterally based muscle that requires a more laterally
placed injection.
Injection of small amounts of BTX-A into the infe­
rior ­ horizontal fibers of orbicularis oculi below the lower
Fig. 18-6  Recruitment of lateral, horizontally oriented fibers of
orbicularis oculi to frown glabella. Pink arrows denote motion vectors.
Box 18-8  Injection techniques for glabellar complex
• Have patient contract muscles to identify corrugator
position and insertion.
• Use five to seven injection sites.
• Needle should remain parallel to floor and perpendicular
to muscle groups/face.
• All injections of glabellar region are performed by injecting
into the musculature.
• Central injection is between medial head of eyebrows
to treat procerus.
• Three symmetrical injections per side can be used to treat
corrugator supercilii.
Box 18-9  Injection techniques for lateral canthus region
(crow’s feet)
• Inject at approximately 45-degree angle directed away
from the globe directly into the thin subcutaneous space.
• Have patient squint or smile slightly to accentuate the
muscle.
• Stay 1 cm lateral to the orbital rim.
• Observe and avoid the veins that typically run in these
areas.
• For patients with prominent infraorbital rhytides and
crepe-like skin, 2-unit injections can be performed into the
inferior horizontal portion of the orbicularis oculi muscle.

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Cosmetic surgery procedures and techniques
eyelashes decreases infraorbital folds and widens the eye
slightly (Fig. 18-8). An injection of one to 2 U of BTX-A is
placed in the superficial subcutaneous space approximately
0.3 cm ­below the lash line bilaterally in the midpupilary line.
In some patients, this can help to improve fine lines and the
‘crepe-like’ texture of the skin in this region. A dose finding
study60 found doses greater than 4 U in the lower eyelid were
associated with complications such as an inability to com­
pletely close the eye and photophobia. Some patients may
experience infraorbital puffiness at even smaller doses and all
should be warned of this possibility prior to treatment.
Brow-lift
For many patients, a subtle elevation of the mid and lateral
eyebrow helps to improve the appearance of the upper one-
third of the face, and in particular the eyes. Patients com­
ment that they look younger when the brow is elevated.
Surgical techniques for brow elevation include coronal and
endoscopic brow-lifts. It is also possible, however, to achieve
a temporary but substantial elevation of the brows with
BTX-A (Fig. 18-9).
By weakening the superior lateral orbicularis oculi and
the glabellar complex, the two brow depressors, the fronta­
lis is able to act unopposed and elevate the brow. Injections
of BTX-A are placed in the subdermal space around the lat­
eral superior periocular area and in the glabellar complex.
A simple injection at the tail of the brow of 2–4 U will relax
vertical fibers of the orbicularis occuli. Complete treatment
of the crow’s feet area will result in lateral brow elevation.
Injections into the entire glabellar complex or even just the
medial aspect of the complex will produce central brow eleva­
tion. Carruthers has reported a technique for producing brow
elevation ­chemically with BTX-A.61 Three injection sites are
Fig. 18-7  Standard periorbital BTX-A injection sites. Pink ‘x’ marks
denote individual 4–5-unit injections.
A
B
C
Fig. 18-8  Supplemental periorbital and infraorbital BTX-A
injection sites. (A) Pink ‘x’ mark denotes individual 2-unit injection.
(B) (shaded rectangle) denotes risk zone for eyebrow depression if
this area is treated with BTX-A. (C) (shaded rectangle) highlights risk
zone for eyelid ptosis if this area is injected with BTX-A.
Fig. 18-9  Brow-lift technique. Note treatment of lateral brow
region, as well as glabella and standard periorbital injection sites.
This technique treats the brow depressor muscles. Pink ‘x’ marks
denote individual injection points.

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Botulinum type A toxin injections for cosmetic use and hyperhidrosis  •  Chapter 18
used, all in an attempt to eliminate or reduce activity of the
brow depressors (Fig. 18-10):

• Central glabella between the medial head of the brows

• Bilateral symmetrical injection sites approximately 0.5 cm
below the lateral head of the brow (two injections, one on
either side).
Forehead
Forehead rhytides can also be improved with injection of
BTX-A. Although longevity of muscle paralysis can be longer
in this region than with other areas of the face, flaws in tech­
nique are readily apparent to even the casual observer. The
area most prone to problems is the lateral forehead. Under­
treatment can result in isolated activity of the forehead over
the lateral brow, producing an unnatural expression. Over­
treatment of the inferior forehead can result in eyebrow de­
pression and inability to elevate the brow, with a resultant sad,
heavy appearance. In some patients, it is advisable to treat the
forehead 2–3 weeks after the initial treatment to the glabellar
region. Care should be taken not to overtreat the ­forehead
and to remember that the lower 2 cm of the frontalis is re­
sponsible for brow position.
The frontalis and occipitalis muscles are connected via the
fibrous galea, and therefore both act as the only elevators of
the eyebrows. However, in many individuals the occipitalis
contribution to eyebrow elevation is minimal to nonexistent,
and the authors prefer to plan the surgical technique with the
assumption that frontalis is the sole brow elevator. On exami­
nation, patients are asked to elevate their brows. There are
basically two patterns of forehead elevation (Fig. 18-11). In
the first, individuals have muscle activity beyond the lateral
limbus of the iris, and in some beyond the lateral head of the
brows. In the second, patients have rhytides that remain cen­
tral on the forehead between a vertical line drawn between the
two pupils. In the latter group there is less of a concern with
altering lateral brow shape and position with BTX-A, since
there is little if any muscle activity in that region. However, the
former group is at risk for alteration in eyebrow motion follow­
ing BTX-A injection. The physician should note the pattern
and mark treatment areas to aid in symmetry. Many patients
have wrinkles superiorly near their hairline. Failure to treat
these areas will allow movement to persist. If injections are
placed too low in the frontalis, brow depression can occur. If
treatment is low and lateral, the lateral eyebrows can droop.
The frontalis muscle is a bifid, fan-shaped muscle that
originates and merges with the galea superiorly and in­
serts into the skin of the eyebrow inferiorly (Fig. 18-12). In
many ­patients, the midline fibers overlap considerably, so for
­practical purposes it is best to think of frontalis as a single
Fig. 18-10  Carruthers brow-lift technique. Pink ‘x’ marks denote
individual injection points.
B
A
Fig. 18-11  Two types of forehead wrinkles. (A) Rhytides extend
beyond the lateral portion of the eyebrow. (B) Rhytides remain
central in the forehead.

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Chapter 18
Cosmetic surgery procedures and techniques
muscular sheet across the forehead. Injections of 2–4 U are
placed approximately 2 cm apart into the body of the muscle,
using caution to remain 2 cm above the eyebrows (Box 18-10).
A good rule of thumb is to inject only above the inferiormost
horizontal forehead rhytide, knowing that if necessary addi­
tional injections may be used to treat some remaining lower
forehead wrinkles (Fig. 18-13).
The vertically oriented fibers of the frontalis muscle con­
tract to elevate the brow. The lateral portion of the muscle,
if left untreated, will continue to elevate the brow when con­
tracted, but if the central frontalis is paralysed, only the lateral
brow will elevate. This can produce a dramatic change in eye­
brow shape often referred to by patients as the ‘Jack Nicholson
look’ (Fig. 18-14), referring to a similarity with the eyebrow
shape of the well-known actor. Some patients may like and
prefer this, but careful preoperative discussion and counseling
are ­essential to determining the patient’s objectives. The main
goal of treatment of the lateral forehead region is to always
leave some frontalis muscle activity to prevent brow ­depression.
To accomplish this, the authors tend to perform bilateral
Box 18-10  Injection techniques for forehead
• Have patient elevate brows to show where frontalis is
causing skin rhytides.
• Inject directly into the muscle belly.
• Use caution in the lower lateral forehead.
• Maintain some lower frontalis muscle action to prevent
eyebrow ptosis.
• One can treat the lateral forehead if one stays high in the
forehead (superior).
• The brow can be elevated laterally by leaving the lateral
forehead untreated.
• If lateral brow elevation is too severe or unnatural following
injection, add a small amount of botulinum toxin high on
the lateral forehead.
• Consider treating the forehead 2–3 weeks after the
glabella for a precise effect.
Fig. 18-13  Midline persistent forehead rhytides following BTX-A
injection. This patient did not have the central forehead treated.
A
B
Fig. 18-14  A 31-year-old man before (A) and 2 months after (B) BTX-A injection of the forehead. Treatment did not relax lateral frontalis,
producing a compensatory lateral brow elevation.
Fig. 18-12  Frontalis muscle anatomy and location.

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Botulinum type A toxin injections for cosmetic use and hyperhidrosis  •  Chapter 18
2–4 cm BTX-A injections high on the lateral forehead 3–4 cm
above the brow at the point of lateralmost frontalis muscle
activity (assessed by having the patient contract the muscle)
(Fig. 18-15). This helps to preserve activity of the inferior part
of the lateral frontalis muscle and is sufficient to keep the brow
elevated. In those patients who are interested in adding some
arch to their brows, the authors will omit the higher lateral
forehead injection site. The authors tell their patients that they
may not like the appearance of their brows when the BTX-A
effect takes place in 3–4 days, and if so they can return for a
small touch-up procedure where the authors will perform 2 U
injections to the high lateral forehead bilaterally.
There are a handful of patients who have extremely active
lateral frontalis muscle fibers (Fig. 18-16). They note persistent
arching of the lateral brow and will often return for retreat­
ment despite the fact that the authors have already treated the
high lateral forehead. For these patients, the authors perform
additional 2–4 U injections of BTX-A to the lower lateral
forehead approximately 1–2 cm above the brow. These pa­
tients are counseled that they run the risk of developing eye­
brow ptosis and depression with this technique. Some choose
to have the additional treatment performed, while others elect
to forgo it. In many cases, persistent arching of the brows fol­
lowing high lateral forehead injection with BTX-A will soften
with time as the treatment effect evolves, avoiding the need
for lower lateral forehead injection. Filler substances such as
hyaluronic acid can be used in the lateral brow in combina­
tion with BTX-A. The fillers serve to elevate the lateral brow
while the BTX-A treatment of the forehead relaxes the lines
in motion.
Upper lip
Vertical rhytides of the upper lip are currently treated with
techniques such as filler substances, ablative laser resurfacing,
or fractionated resurfacing, or careful use of filler substances.
Ablative laser resurfacing techniques are superb at eliminat­
ing cutaneous rhytides and contracting the underlying tissue,
but do not treat the muscle activity that can contribute to the
formation of these wrinkles.
BTX-A injections can be performed to the upper lip re­
gion to reduce the ability to contract the horizontal fibers of
the circumferential orbicularis oris muscle. The result of this
muscle paralysis is decreased motion of the upper lip. Mild
weakness should be the treatment goal, as complete paralysis
may interfere with normal speech. The net gain from treat­
ment is a reduction in wrinkle size and appearance. Injection
technique varies, but in general three to four injections of 1 U
Fig. 18-15  A frequent forehead injection technique. Pink ‘x’ marks
denote individual 2–4-unit injection sites.
B
A
Fig. 18-16  A 30-year-old woman before (A) and 3 weeks after (B) BTX-A treatment of forehead.

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Chapter 18
Cosmetic surgery procedures and techniques
are performed at equal intervals along the cutaneous upper
lip Injections should be placed within the muscle at the ver­
milion border. BTX-A injections alone are often not sufficient
to reduce the perioral rhytides, but BTX-A in combination
with filler substances produces an excellent result. This com­
bination of fillers plus BTX-A is standard technique in many
clinics.
Mentalis
An overactive mentalis can produce a ‘wiggling chin’ when
animated and is known as a ‘pruny chin’ or ‘peach pit chin.’
While patients do not often present desiring treatment of this
area, when patients have their overactive mentalis treated
they are quite pleased. One or two injections of 4–10 U into
the mentalis can produce an excellent result. Treatment of
the mentalis can also give the chin slightly more protrusion
with the relaxation of the musculature contracting it in. Care
should be taken to keep these injections low and central in the
mentalis. If toxin is injected laterally, it can affect the depres­
sor labii inferioris and produce lower lip weakening and an
asymmetrical smile.
Depressor anguli oris
The depressor anguli oris (DAO) muscle is a triangular muscle
originating from the mandible and inserting in the corner of
the mouth. Its function is to turn the mouth corners down
when frowning. Treatment of the depressor anguli oris muscle
elevates the corner of the mouth. This effect is seen at rest
where the mouth corners lift and at full smile where the pa­
tient is able to produce a more attractive expression. Relaxa­
tion of the depressor anguli oris is accomplished by injecting
2–6 U into the DAO in its posterior edge. This point is chosen
so as to decrease the chance of weakening the muscle more
medial to depressor anguli oris, the depressor labii inferioris.
The point of injection is at the mandibular angle 1 cm lateral
to the corner of the mouth.
The DAO is injected commonly when the marionette lines
are treated with filler substances such as collagen or hyaluronic
acid. Treatment of the DAO is complimentary to the desired
result.
Neck
In the continuing quest for low-morbidity cosmetic surgical
alternatives to the face-lift, treatment of the aging neck with
BTX-A has evolved. There are three primary features of the
aging neck:

• cutaneous photoaging rhytides, lentigines, telangiectasias

• skin laxity

• muscle (platysmal) bands.
BTX-A injections can be used to produce improvements
in prominent platysmal banding. In addition, thorough treat­
ment of the neck can yield an improvement in skin laxity and
in some cases the horizontal rhytide component of photoaging.
It will obviously not change pigmented or vascular lesions that
are seen with neck photoaging (poikiloderma of Civatte).
For treatment of platysmal bands, patients are asked to grim­
ace and tighten the platysma muscle. The physician will then
grasp the visible bands of muscle between the thumb and forefin­
ger of the nondominant hand and inject 2 U of BTX-A directly
into the muscle band, approximately 1 cm apart. Most patients
with platysmal bands have two distinct bands near the midline;
however, some will have a broader, less distinct band lateral to
the two central bands. All can be treated with BTX-A.
If the physician is attempting to improve skin laxity, jowls,
and horizontal neck rhytides, then a more thorough and dif­
fuse treatment of the neck is indicated. Many patients with
cutaneous aging of the neck will have deep, prominent
horizontal rhytides that are in part the result of years of
­contraction of the platysma muscle and motion of the neck.
Treatment of the entire neck with small amounts of BTX-A
at 1 cm subcutaneous injection intervals surrounding the
horizontal rhytides can substantially decrease activity of the
platysma muscle (Fig. 18-17). Treatment of vertical platysmal
bands is also performed in these patients as described above.
The net effect is to produce unopposed action of the muscles
of facial expression above the jawline and a tightening of the
neck skin. This can produce a reduction in the appearance of
fine and medium horizontal rhytides of the neck, as well as in
some patients a tightening of skin along the jawline and eleva­
tion of the jowls to reduce their appearance.
Neck results vary greatly from patient to patient, as well as
physician to physician. Controlled trials documenting efficacy
are lacking for BTX-A treatment of the neck, and further
study is clearly needed to standardize treatment parameters
and efficacy standards. Whereas therapy of the upper third
of the face tends to produce uniform and predictable results,
neck therapy with BTX-A is less predictable. For this reason,
the authors counsel each of their patients that results may
vary, and therefore the authors are unable to make any assur­
ances as to outcomes following BTX-A therapy of the neck.
Some of the best neck results have been seen with EMG-
directed guidance for platysmal band treatment. Complications
have been reported, such as excessive neck weakness and
­dysphagia.
Fig. 18-17  Platysma muscle injection technique. Pink ‘x’ marks
denote individual 2–4-unit injection points.

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Botulinum type A toxin injections for cosmetic use and hyperhidrosis  •  Chapter 18
Nasolabial fold
Some published reports have discussed treatment of nasola­
bial fold rhytides with BTX-A injection.62 The intended tar­
gets of muscle paralysis are the levator labii superioris alaeque
nasi (LLAN), which act to move the nasolabial fold and upper
lip medially. Treatment of these muscles theoretically would
reduce the appearance of nasolabial fold rhytides. Care must
be taken when treating this muscle as there is a high tendency
to create a droop of the upper lip. Treatment of the LLAN is
often used in conjunction with filler treatments of the nasola­
bial fold. Care should be taken when considering this use of
BTX-A for improving the nasolabial fold.
Therapy of hyperhidrosis
When used to treat hyperhidrosis, BTX-A is injected into the
dermis where it inhibits acetylcholine release from choliner­
gic nerve fibers associated with eccrine and apoeccrine sweat
glands (Box 18-11). Intradermal wheals are used to treat all
areas of hyperhidrosis. Areas to be injected can be identified
by one of several methods, but the overall goal is to inject
areas of excess sweating. Because the areas to be injected
are significantly larger in surface area than those injected for
rhytides and the sweat gland nerve fibers are less sensitive to
BTX-A, substantially larger amounts of toxin are used to treat
hyperhidrosis in any given session.
Many patients with hyperhidrosis have only localized areas
of increased sweating. The hyperactive areas can be localized
with Minor’s starch-iodine test. An iodine solution is painted
over the area and allowed to dry. At this point, starch pow­
der is sprinkled on the area. Sweat causes the mixture to turn
dark blue. By injecting only the positive areas, effective sweat
reduction is achieved while reducing the total dose needed.
Repeating the starch-iodine test can also be useful to quantita­
tively assess success of treatment, and identifying areas which
are still active.
Clinical effects begin to appear 2–4 days after injection,
and longevity of sweat reduction varies from 2 to 8 months.
The authors typically use a concentration of 2 U/0.1 mL, and
inject 0.05–0.1 mL per needle site. If patients have persistent
sweating after the BTX-A effects have begun, the authors will
perform a small touch-up procedure to these areas. Patients are
asked to wait at least 2 weeks following the initial session before
the authors are able to fully assess efficacy of treatment.
A total of approximately 30–50 injections are done per
hand or foot, for a total dose of 60–100 U of botulinum A
­exotoxin. The authors use a standard terminology of one
hand, for example, being one hyperhidrosis ‘site.’ When either
both hands or both feet are treated in one session, 120–200 U
of toxin are injected. Similar doses are used to treat the axillae
or feet as well. Therefore, the authors prefer to treat only two
‘sites’ per session.
For treatment of the axillae, often no anesthesia is used.
For treatment of the palms and soles, a number of techniques
­including, ice, cold air, and nerve blocks may be used to
reduce the pain of intradermal injections.
At the time of treatment, ice cubes may be used to preanes­
thetize the area about to be injected. An assistant holds an ice
cube over the intended injection site for 10–15 seconds prior
to needle insertion. This technique has been found to greatly
improve patient comfort, particularly on the hands. The au­
thors have also employed the use of a Zimmer air cooling
device that blows very cold air over the treatment area and
decreases pain.
Palms
Injection is accomplished with the needle held at approxi­
mately a 45-degree angle, and the needle advanced until a
slight decrease in resistance is felt when it enters the dermis.
Injection sites are approximately 1 cm apart, since botulinum
A exotoxin is thought to migrate nearly 1 cm from its site of
injection (Fig. 18-18). A pattern of approximately 24 injection
sites can be marked on the palm with a gentian violet surgical
marker when treating the first few patients. The authors also
inject each palmar interphalangeal (IP) region, approximately
midway between the IP creases, as well as the fingertips. There
are a total of 14 IP and fingertip injection sites. Some patients
have lateral palmar sweating as well, and therapy should be
tailored to fit the individual patient, as focal hyperactive sites
may vary.
Axillae
The axillae are treated by injecting 50 U of BTX-A at 1 cm in­
tervals intradermally. The area is identified using the ­Minor’s
starch-iodine test prior to treatment to define the extent of
sweating, and the entire area is treated. Performing a ring of
injections around the outer margin of the sweating areas is
useful to delineate the extent of injections. Hair in the axilla
does not need to be trimmed prior to treatment, but trimming
it can make injections easier. For this reason, care must be
taken to use a consistent pattern within the axilla to maintain
an efficient injection technique.
Plantar foot
The plantar surface of the foot is a very challenging area to
inject with BTX-A. Injection sites can be extremely painful,
and many patients choose to avoid treatment of this area.
For those who decide to have treatment performed, adequate
anesthesia is essential. Topical anesthesia with EMLA and
ice may be adequate for the minority of patients, but for the
rest nerve blocks or other forms of regional anesthesia are
Box 18-11  Injection techniques for hyperhidrosis
• Inject at 1–2 cm intervals.
• Inject BTX-A intradermally.
• Inject lateral palms and soles when affected.
• Inject volar (palmar) interphalangeal joints of fingers,
including fingertips.

282
Chapter 18
Cosmetic surgery procedures and techniques
­essential. A Bier block is helpful. Some patients may even
­benefit from conscious intravenous sedation in collaboration
with an anesthesiologist.
Injections are performed in a time-efficient manner at 1 cm
intervals on the plantar surface of the foot, with care taken to
inject the lateral soles. The toes are not often injected. It is es­
sential to have a physician who is skilled in obtaining regional
anesthesia involved in the patient’s care if the physician
performing the BTX-A injections does not have significant
experience.
Postoperative clinical considerations
Following injection, light pressure may be applied to the treated
area for a few seconds to aid in hemostasis and decrease the
chances of bruising. An added benefit of firm pressure held
to the treated area appears to be even distribution and migra­
tion of the injected BTX-A within the locally treated area.
Cosmetic patients are instructed to contract injected ­muscles
occasionally for an hour or two to theoretically increase
presynaptic uptake of the toxin (Box 18-12). Although there
is a study showing benefit to this type of activity in a monkey
hand model, there are no published studies in humans to show
this is beneficial.
Although effects can be documented as early as 24 hours
using careful standard photography, clinical effects generally
begin to appear within 2 to 3 days of injection (Box 18-13).
Even though muscle weakening is noted this early, final
­effect occurs at 2–4 weeks. Data suggest that clinical wrinkle
­improvement continues to increase with repeat treatments.
The duration of clinical efficacy is related to several fac­
tors, including units of BTX-A, injection technique, and indi­
vidual patient variation (Box 18-14). On average, the effects of
BTX-A injection remain apparent for 3–4 months following
injection of dynamic muscles. Clinical efficacy is in part dose
related, so that the more toxin one uses, the greater the like­
lihood of inducing long-term effects. Therefore, in patients
who do not achieve long-term correction at standard doses,
the physician can choose to increase the concentration or dose
of toxin injected at subsequent sessions to potentially increase
therapeutic efficacy.
It remains unclear whether there is a point at which in­
creasing concentration does not improve results but rather
only serves to increase the risk of complications. The most
common complications are pain at the injection site (Fig.
18-19) and ecchymosis. The incidence of eyelid ptosis from
glabellar treatment is now well below the rate quoted in
the Botox package insert. A rare side effect of BTX-A in­
jection is diplopia. Both diplopia and ptosis are temporary
and usually resolve spontaneously within 2–4 weeks. During
this difficult time, patients are reassured that no interven­
tion is warranted. In some instances of upper eyelid ptosis,
Box 18-12­  Post-treatment instructions
• Contract treated muscles for the first hour or so after
treatment.
• Avoid aspirin, nonsteroidal antiinflammatory agents,
alcohol, and vitamin E supplements for 24 hours after
treatment.
Box 18-13  Clinical action
• Onset of effects is usually within 3–4 days.
• Initial injection for dynamic rhytides will last on average
3 months.
• Repeat injections will often cause continued improvement
in rhytides.
• Injections for hyperhidrosis last on average 6 months.
Box 18-14  Botox longevity
• Forehead appears to last longer than other areas on the
face.
• Periorbital Botox tends to wear off faster than other regions
of the face.
• Palms and axillae will remain sweat-free for approximately
6 months.
Fig. 18-18  Palm hyperhidrosis injection technique. A total of up
to 50 sites are injected on each palm, with care to inject the lateral
thenar and hypothenar eminences. Pink ‘x’ marks denote individual
2-unit injections, for a total of 100 U per palm.

283
Botulinum type A toxin injections for cosmetic use and hyperhidrosis  •  Chapter 18
­midriatic agents such as apraclonidine hydrochloride 0.5%
or phenylephrine can be used to temporarily elevate the up­
per eyelid by causing contraction of Müller’s muscle.63,64
More commonly, the so-called complications of Botox injec­
tion are not true complications at all, but rather cosmetic
or efficacy-related concerns. These often take the form of
persistent rhytides within days of treatment, persistence of
muscle action, and change in eyebrow shape and position.
These can often be addressed either by reassuring the pa­
tient or by a small touch-up procedure.
Patients on occasion will complain of a change in their fa­
cial expression and smile following injection of the periorbital
region. In particular, they note that their mouth does not move
the same as it did prior to treatment. Often, this is due to inad­
vertent injection of the zygomaticus major or minor muscles
that have their origin on the upper cheek near the malar emi­
nence. Toxin migration can affect these muscles and reduce
the ability of the patient to elevate the corner of the mouth.
There is no treatment for this condition, and patients must be
reassured that this effect is temporary.
Complications are uncommon with BTX-A injection for
­hyperhidrosis. Sweating that continues 1–2 weeks after injection
can be treated with additional BTX-A injected at a touch-up
procedure. Patients are able to drive a car, write, and lift small
objects without difficulty. Hand grip weakness can occur but is
often mild and transient, lasting less than 3–4 weeks, and gen­
erally does not interfere with daily function. Weakness is likely
due to action of the toxin on the thenar and hypothenar emi­
nences and muscles, inhibiting apposition of the thumb and
little finger. Intervention is not needed. Patients are instructed
to use caution when lifting small objects with their hands.
Finger weakness is very rare since, other than the lumbricals,
the majority of the muscles that control finger ­motion are in
the forearm, with only their tendinous insertions coursing
through the palm. Similar concerns for the soles and ­axillae
do not exist.
Botulinum injection for aesthetic improvement of ­dynamic
rhytides has rapidly become the most popular cosmetic
­procedure in the country for several very simple reasons. It is
safe, it is predictable, and it gives excellent results in appropri­
ate patients without any significant ‘downtime.’ As we have
learned more about the cosmetic use of botulinum toxin, we
have seen a shift away from creating an expressionless face
and towards creating a more balanced and relaxed face. By
understanding the interplay of the dynamic muscles of the
face, it is possible to help shape a more youthful face.
Acknowledgments
Drs. Michael Kaminer and George Hruza contributed sig­
nificantly to the first edition of this text. Their superior work
has been added to as newer experience and data has become
available.
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B
A
Fig. 18-19  Eyelid ptosis following BTX-A injection. (A) Obvious right eyelid ptosis. (B) Subtle right eyelid ptosis.

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Cosmetic surgery procedures and techniques
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21. Lowe NJ. Botulinum A toxin type A for facial rejuvenation: United
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23. Ascher B, Zakine B, Kestemont P, et al. A multicenter, randomized,
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25. Carruthers A, Kiene K, Carruthers J. Botulinum A exotoxin use in
clinical dermatology. J Am Acad Dermatol 1996; 34:788–797.
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27. Carruthers J, Carruthers A. The adjunctive usage of botulinum toxin.
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28. Carruthers A, Carruthers J. Cosmetic uses of botulinum A exotoxin. In:
Klein AW, ed. Tissue augmentation in clinical practice: procedures and
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29. Carruthers A, Lowe N, Menter MA, et al. Botox glabellar lines study
group. A multicenter, double blind, randomized, placebo controlled
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treatment of glabellar lines. J Am Acad Dermatol 2002; 46:840–849.
30. Guerrissi J, Sarkissian P. Local injection into mimetic muscles of
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31. Guyuron B, Huddelston SW. Aesthetic indications for botulinum toxin
injection. Plast Reconstr Surg 1994; 93:913–918.
32. Lowe NJ, Maxwell A, Harper H. Botulinum A exotoxin for
glabellar folds: a double-blind, placebo-controlled study with an
electromyographic injection technique. J Am Acad Dermatol 1996;
35:569–572.
33. Frankel AS, Kamer FM. Chemical browlift. Arch Otolaryngol Head
Neck Surg 1998; 124:312–323.
34. Matarasso A, Matarasso SL, Brandt FS, et al. Botulinum A exotoxin
for the management of platysma bands. Plast Reconstr Surg 1999;
103:645–652.
35. Bushara KO, Park DM, Jones JC, et al. Botulinum toxin – a possible
new treatment for axillary hyperhidrosis. Clin Exp Dermatol 1996;
21:276–278.
36. Glogau RG. Botulinum A neurotoxin for axillary hyperhidrosis: no
sweat Botox. Dermatol Surg 1998; 24:817–819.
37. Odderson IR. Axillary hyperhidrosis: treatment with botulinum toxin A.
Arch Phys Med Rehabil 1998; 79:350–352.
38. Schnider P, Binder M, Kittler H, et al. A randomized, double-blind,
placebo-controlled trial of botulinum A toxin for severe axillary
hyperhidrosis. Br J Dermatol 1999; 140:677–680.
39. Shelley WB, Talanin NY, Shelley ED. Botulinum toxin therapy for
palmar hyperhidrosis [see comments]. J Am Acad Dermatol 1998;
38:227–229.
40. Naumann M, Hofmann U, Bergmann I, et al. Focal hyperhidrosis:
effective treatment with intracutaneous botulinum toxin. Arch Dermatol
1998; 134:301–304.
41. Lowe NJ, Glaser DS, Eadie N, et al. North American Botox in primary
axillary hyperhidrosis clinical study group. Botulinum toxin type A in
the treatment of primary axillary hyperhidrosis: 952 week multicenter
double blind, randomized, placebo controlled study of efficacy and
safety. J Am Acad Dermatol 2007; 56:604–611.
42. Bjerkhoel A, Trobbe O. Frey’s syndrome: treatment with botulinum
toxin. J Laryngol Otol 1997; 111:839–844.
43. Naumann M, Zellner M, Toyka KV, et al. Treatment of gustatory
sweating with botulinum toxin. Ann Neurol 1997; 42:973–975.
44. Laskawi R, Drobik C, Schonebeck C. Up-to-date report of botulinum
toxin type A treatment in patients with gustatory sweating (Frey’s
syndrome). Laryngoscope 1998; 108:381–384.
45. Laccourreye O, Muscatelo L, Naude C, et al. Botulinum toxin type A
for Frey’s syndrome: a preliminary prospective study. Ann Otol Rhinol
Laryngol 1998; 107:52–55.
46. Schulte-Mattler WJ, Wieser T, Zierz S. Treatment of tension-type
headaches with botulinum toxin: a pilot study. Eur J Med Res 1999;
26:183–186.
47. Wheeler AH. Botulinum toxin A, adjunctive therapy for refractory
headaches associated with pericranial muscle tension. Headache 1998;
38:468–471.
48. Aurora S. Botulinum toxin type A for the treatment of migraine. Expert
Opin Pharmacother 2006; 7:1085–1089.
49. American Society of Plastic Surgeons, 2000/2005/2006 National
Plastic Surgery Statistics: Cosmetic and Reconstructive procedure
trends, pdf publication from surg.org.
50. Hruza GJ. Botulinum toxin. J Watch Dermatol 1999; 7:59–62.
51. Kane MA. Nonsurgical treatment of platysmal bands with injection of
botulinum toxin A. Plast Reconstr Surg 1999; 103:656–665.
52. Hankins CL, Strimling R, Rogers GS. Botulinum A toxin for glabellar
wrinkles: dose and response. Dermatol Surg 1998; 24:1181–1183.
53. Flynn TC, Carruthers A, Carruthers J. Surgical pearl: the use of the
UltraFine II short needle 0.3cc insulin syringe for botulinum toxin
injections. J Am Acad Dermatol 2002; 46:931–3.
54. Scott A, Kennedy E, Stubbs H. Botulinum A toxin injection as a
treatment for blepharospasm. Arch Ophthalmol 1985; 103:347–350.
55. Coleman KR, Carruthers J. Combination therapy with Botox and
fillers. The new rejuvenation paradigm. Dermatol Ther 2006; 19:
177–188.
56. Brandt FS, Bellman B. Cosmetic use of botulinum toxin type A exotoxin
in the aging neck. Dermatol Surg 1998; 24:1232–1234.
57. Jimenez G, Spencer JM. Erbium:YAG laser resurfacing of the hands,
arms, and neck. Dermatol Surg 1999; 25:831–835.

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58. Cook BE, Lucanelli MJ, Lemke BN. Depressor supercilii muscle:
anatomy, histology, and cosmetic implications. Ophthal Plast Reconstr
Surg 2001; 17:404–11.
59. Tamura BM, Odo MY, Chang B, et al. Treatment of nasal wrinkles
with botulinum toxin. Dermatol Surg 2005; 31:271–275.
60. Flynn TC, Carruthers JA, Carruthers JC, et al. Botulinum A toxin in the
lower eyelid: dose finding study. Dermatol Surg 2003; 29:943–950.
61. Huilgol SC, Carruthers A, Carruthers JDA. Raising eyebrows with
botulinum toxin. Dermatol Surg 1999; 25:373–376.
62. Fagien S. Botox for the treatment of dynamic and hyperkinetic facial
lines and furrows: adjunctive use in facial aesthetic surgery. Plast
Reconstr Surg 1999; 103:701–713.
63. Edelstein C, Shorr N, Jacobs J, et al. Oculoplastic experience with the
cosmetic use of botulinum A exotoxin. Dermatol Surg 1998; 24:
1208–1212.
64. Matarasso SL. Complications of botulinum A exotoxin for
hyperfunctional lines. Dermatol Surg 1998; 24:1249–1254.

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Appendix A
BOTULINUM TOXIN Consent Form
Patient
Age
Date

1.  I hereby authorize Dr. ________________________ and those he or she may designate as assistants to perform upon myself
a Botox injection of the skin. I am aware that possible complications of Botox injection include, but are not limited to, need
for touch-ups, as well as occasional temporary eyelid droop (for frown lines/forehead treatment), eyebrow droop (for forehead
treatment), double vision (for crow’s feet treatment), and grip weakness (for palm treatment).

2.  The nature and purpose of the procedure has been explained to me. I am aware that the practice of medicine and surgery
is not an exact science and I acknowledge that no guarantees have been made to me concerning the results of the operation,
treatment, or procedure.

3.  I understand and have been so informed there are risk(s) and consequences associated with the operation(s) described
in Paragraph 1.

4.  I hereby authorize Dr. _______________________ to use my case materials, including photos and/or motion pictures,
in teaching, medical publications, and exhibits.
I certify that I have read or have had read to me and fully understand the above consent to the procedure, that the explanations
therein referred to were made, and that all blanks or statements requiring insertion or completion were filled in.
Signature of Witness
Signature of Patient

HISTORY AND SCIENCE
Soft tissue augmentation has been utilized for cosmetic en­
hancement for over 100 years. The first attempts to correct
volume loss and contour deformities involved products such
as paraffin and autologous fat. Paraffin injections were ini­
tially greeted with enthusiasm and the product was embraced
as a safe, inexpensive way to rejuvenate the face. The use of
paraffin rapidly decreased as experience demonstrated that
it ­produced paraffinomas and could migrate. Autologous fat
continued to be used as a filling material. However, following
an initial surge of enthusiasm, use of fat for facial rejuvenation
abated. Recently, newer methods of harvesting and injecting
fat have rekindled interest in its use. The next major para­
digm shift in soft tissue augmentation began in the 1950s and
1960s when silicone was introduced as a safe, inexpensive, and
permanent way to fill folds and creases. Unlike either fat or
paraffin, silicone was believed to be the perfect soft tissue aug­
mentation product. Unfortunately, experience dampened the
initial enthusiasm and silicone was also marred by what has
been referred to as ‘the psychopathic’ usage which includes
the use of nonmedical-grade product, the use of large vol­
umes of silicone, and the injection of this material by ­injectors
lacking any formal training.1
The modern era of soft tissue augmentation began in 1982
with the approval of bovine collagen. Since that time, mate­
rials and methods used to provide soft tissue augmentation
have expanded as has the experience of injecting materials for
cosmetic enhancement. This renaissance has been embraced
by physicians and patients alike and, according to the most
recent data, there were approximately 1 194 222 hyaluronic
acid soft tissue augmentation procedures performed in the US
in 2005, making these procedures second only to injections of
botulinum toxin as the most common cosmetic nonsurgical
procedure.2 The 2005 numbers represent a 35% increase from
2004 and it is likely that as newer fillers including additional
hyaluronic acid products become approved, this number will
increase. At the present time, the hyalurons collectively ac­
count for approximately 80% of the soft tissue augmentation
market.
Within the past few years there has been an explosion of
products approved for soft tissue augmentation in the US,
­Canada, and Europe, and there is every reason to believe that
this trend is likely to continue. While it is beyond the scope of this
chapter to provide a comprehensive list of agents, Table 19-1
lists some of the most relevant products as well as their at­
tributes. An overview of several of them is also provided and
it is hoped that while this will not afford the reader with an en­
cyclopedic knowledge of filling agents, it will insure that one
has enough background to understand the risks, benefits, and
indications of newer products as they emerge. At the present
time, the hyalurons are responsible for the majority of soft tis­
sue augmentation procedures and, although new ones appear
to be on the cusp of approval by the US Food and Drug Ad­
ministration (FDA), the basic science and many of the techni­
cal considerations discussed for the materials mentioned will
be applicable to newer products as they come into usage.
PROCEDURES AND TECHNIQUES
Hyaluronic acids
Whether they are animal or synthetic in origin, all hyaluronic
acids are polysaccharides with the same fundamental struc­
ture. Each molecule is comprised of a repeating chain of
d-glucuronic acid and n-acetyl-d-glycosamine monosach­
arides. These polysaccharide chains must be cross-linked
to have any tissue persistence or utility as a dermal fillers.
Soft Tissue Augmentation
Kenneth R. Beer and
Rhoda Narins
C H A P T E R
19
p a r t 2

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Chapter 19
Cosmetic surgery procedures and techniques
Table 19-1  Some of the most relevant soft tissue augmentation products and their attributes
Product
FDA
­approved
Source material
Expected duration
of correction
Approved for ­aesthetic
indication in the US/EU
or Canada
Aquamid
No
Cross-linked polyacrylamide
More than two years
No/Yes
Artefill/Artecoll
Yes
Bovine collagen with
­methylmethacrylate beads
Permanent
Yes/Yes
Bioplastique
No
Silicone particles in a gel carrier
Permanent
No
Captique
Yes
Synthetic hyaluronic
acid
2–4 months
Yes/Yes
Cosmoderm/
Cosmoplast
Yes
Collagen derived from human
fibroblastic cells
2–4 months
(Cosmoderm)
2–6 months
(Cosmoplast)
Yes/Yes
Cymetra
Yes
Cadaveric dermis
(micronized Alloderm)
Months
No
Dermalive/Dermadeep
No
Acrylic hydrogel in a HA vehicle
Semipermanent
No/Yes
Evolence
No
Porcine collagen
9 months
No/Yes
Hyacel
no
Hyaluronic acid
Months
No
Hylaform/Hylaform Plus
Yes
Rooster combs
2–4 months
Yes/Yes
Isolagen
No
Autologous collagen and
fibroblasts
Unclear
No/UK only
Juvederm
Yes
Synthetic hyaluronic acid gel
6–9 months
Yes/Yes
Matridex/Matrigel
No
Cross-linked HA (25 mg/mL)
and sephadex
Unclear
No/Yes
Puragen
No
Double cross linked HA
8–12 months
No/Yes
Radiesse
Yes
Calcium hydroxyapatite
9–18 months
Yes
Restylane
Yes
Synthetic hyaluronic acid
6 months
Yes/Yes
Rofilan
No
Hyaluronic acid, cross-linked
No/Yes
Sculptra
Yes
Poly L lactic acid
12–22 months
Expected in 2007/Yes
Silicone
Yes
Synthetic
Permanent
No
Surgiderm
No
Cross-linked HA
Unclear
No/Yes
Teosyal
No
Cross-linked HA
Unclear
No/Yes
Viscontour
No
Hyaluronic acid, presently ­available
as noncross-linked product
in Europe, cross-linked under
­development
2–4 months
No/Yes
Zyderm/Zyplast
Yes
Bovine Collagen
Uncross-linked/cross-linked
3–4 months/
3–5 months
Yes/Yes
The degree to which the molecules are cross-linked greatly
affects the stability of the products in vitro. Absent the cross-
linkage, the molecules would be rapidly digested and have a
longevity measured in hours rather than months. Each of the
cross-linking agents is present to a small degree as an unbound,
free molecule and one safety consideration is the concentration.
For Restylane™, the concentration of 1,4-butandiol diglyci­
dylether (BDDE) is not greater than 2 ppm (in reality, it is fre­
quently not measurable) (Medicis Pharmaceuticals, Scottsdale,
AZ, personal communication).
Many factors other than cross-linkage affect the degree
and duration of soft tissue augmentation obtained following

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Soft tissue augmentation  •  Chapter 19
­injection. For instance, the particle size and concentration both
have a significant impact on tissue correction. For a given mo­
lecular structure, variations in the size of the particle or, if it is
a homogeneous gel, the concentration of the gel have signifi­
cant bearing on the interaction of the material with the skin.
Product flow and stiffness are affected by several character­
istics. In general, larger molecules tend to flow with more diffi­
culty. However, the hyalurons are lubricants and when present
in a free (not cross-linked form) they increase flow. The degree
to which each of the presently approved hyaluronic acid prod­
ucts is cross-linked and what percentage of each is unbound is
at present controversial. Whatever the concentration present
in each product it is clear that an noncross-linked product will
not contribute to any lasting correction and should be sub­
tracted from the stated total hyaluronic in order to attain a
‘tissue effective’ hyaluronic acid concentration.
Since product stiffness is affected by many attributes it will
be useful to have an objective measurement of this character­
istic. In order to understand the concept of flow resistance it
is helpful to picture two metal plates separated by a layer of
filler. The resistance to lateral movement of the two plates of­
fered by the filler between them is measured as its flow resist­
ance number. A higher flow resistance number implies more
resistance to movement of the plates which translates to the
clinical property of hardness. Measured product stiffness is af­
fected by several factors including the degree of cross-linkage.
The size of the gel particle also impacts this measurement,
with smaller particles of the same physical characteristics hav­
ing more stiffness than larger ones (a longer chain has more
potential to move in different directions). Finally, the amount
of free hyaluronic acid (HA) affects the resistance to flow with
more free HA providing less flow resistance.
The Restylane™ family of products maintains the same
chemical formula and concentration of hyaluronic acid across
each of its products including Touch, Perlane, Sub Q, and
Restylane. Each product varies the size of the particle to
­create fillers with different characteristics. Restylane utilizes
a Streptococcus fermentation manufacturing process to produce
hyaluronic acid. Cross-linkage for this family of products is
obtained using 1,4-butandiol diglycidylether (BDDE). The
degree of cross-linking of Restylane molecules is 1%.3
Traditional Restylane has a particle density of 100 000 par­
ticles per milliliter. Restylane has a gel particle size of 400 μm.4
Variations on this theme include Restylane Touch which has
a particle density of 200 000 gel particles per milliliter, and
Restylane Perlane has a particle density of 10 000 particles per
milliliter. Other iterations of this molecule include Restylane
Sub Q, designed as a deep filler that might be a substitute
for autologous fat. By manipulating the particle density (even
while maintaining identical molecular and chemical struc­
tures), a wide range of filler characteristics may be obtained.
As of 2006, Restylane has approximately 74–79 % of the
­hyaluronic acid filler market in the US.
Other types of hyaluronic acids alter the physical properties
of their products by altering the concentration of hyaluronic
acid rather than altering the size of the gel particle. Juvederm
is a hyaluronic acid made with a homogeneous gel rather than
a particulate one. The technology utilized to manufacture this
product has been termed ‘Hylacross’™ and it is best visual­
ized by imagining a gel placed into a blender until the mixture
obtained became homogeneous.
Juvederm is available in gel concentrations ranging from
18 mg/mL to 24 mg/mL to 30 mg/mL. These products are
indicated for superficial, mid, and deep dermal injections. Ad­
ditional concentrations will be manufactured to enhance the
range of locations and indications treated with these products.
Alterations in the structure will likely affect tissue persistence
as well.
A third category of hyaluronic acid products is the Hyla­
form series of products which utilize hyaluronic acid with a
concentration of 5.5 mg/mL. The cross-linking agent in this
molecule is divinyl sulfone (DVS). Although the degree of
cross-linkage in this family is high (20%) it is limited by its
relatively low concentration, and a clinical trial comparing
Restylane with Hylaform Plus demonstrated the superiority
of Restylane when treating the nasolabial creases.5
The manufacturing process for this molecule initially relied
upon rooster combs. The inaugural product in this family was
Hylaform and it has a particle size of 500 μm. When the size
of the particle was altered to 750 μm it received the appela­
tion Hylaform Plus. In an effort to minimize the allergenic
potential, the manufacturing source was changed from rooster
comb to a bacterial fermentation process, creating a product
known as Captique. The particle size for Captique is the same
as Hylaform, 500 μm.4 At the present time, the Hylaform fam­
ily of molecules has not gained a significant share of the US
hyaluronic acid filler market.6
There are numerous other hyaluronic acid molecules that
are presently approved for use in several countries (see Table
19-1 for a partial listing). Technologies employed to manufac­
ture these has differs from that discussed above. It remains to
be seen whether these differences translate into differences in
clinical indications and applications or are simply marketing
nuances. Clinical trials comparing the safety and efficacy of
these molecules with existing ones already approved will help
to answer this question.
Indications
The hyaluronic acids presently approved for use in the United
States are presently approved for ‘mid-to-deep dermal implan­
tation for the correction of moderate to severe facial wrinkles
and folds, such as the nasolabial folds.’7–9 Information in the
package insert for Juvederm states that it is indicated for ‘in­
jection into the mid to deep dermis for correction of moderate
to severe facial wrinkles and folds (such as nasolabial folds).’
Although the various package inserts mention treatment of
the nasolabial crease, utilization is not limited to this narrow
indication. Other areas frequently treated with HA include
the marionette lines and perioral rhytides. Lip augmentation
with hyaluronic acids is also popular. Less common uses of the

290
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Cosmetic surgery procedures and techniques
hyalurons include the ear lobes, zygomatic arch augmenta­
tion, scars, the dorsal aspects of the hands, the glabella, and
the tear trough.
Contraindications
There are several contraindications to injections with hy­
alurons. Although not specifically mentioned, one should
consider pregnancy and lactation with respect to medicolegal
rather than purely medical reasons and there is no such speci­
fied contraindication in either the Restylane or Juvederm pack­
age inserts. Absolute contraindications to injections with the
hyalurons vary with each product but they include a history of
severe anaphylactic reactions to any of the components con­
tained within the product in question. For Restylane, allergy to
any of the ingredients (including the BDDE used to cross-link
the molecules) contained in the product is an absolute con­
traindication. Patients with allergies to any of the ingredients
(including the DVS used for cross-linking) in the Hylaform
family or with allergies to chicken proteins should avoid using
these products. Potential patients for Juvederm should not be
injected if they are allergic to any component of this prod­
uct and it must be avoided in patients with a history of aller­
gies to ‘gram positive bacterial proteins.’9 A similar warning
is present in the package insert for Restylane (and most likely
will appear in any future products that rely upon bacterial
fermentation for manufacturing. The package insert for Juve­
derm also cautions that following ‘laser treatment, chemical
­peeling, or other procedure based on active dermal response …
there is a possible risk of eliciting an inflammatory reaction
at the implant site.’9 Finally, injection of any product into the
blood vessels should be avoided. If blanching is observed dur­
ing the injection of any soft tissue augmentation product, the
injection should immediate cease and patient care should fol­
low the protocol elaborated by Glaich et al.10
Pretreatment considerations
As with any proposed soft tissue augmentation procedure, the
physician needs to assess the patient from a multitude of per­
spectives. As previously discussed, patients expecting to erase
moderate nasolabial creases with 1 mL of any filler need to
have a realistic discussion of the limitations of the proposed
procedure. When discussing correction of any area using the
hyalurons, it is helpful to ask the patient to use a mirror and
discuss what issues are significant to him or her. The expected
duration of the correction achieved as well as the cost per
treatment is also important aspects of the consultation.
Hyaluronic acid molecules are inherently hygroscopic and
absorb water upon injection. Thus, it is imperative to con­
sider the patient’s schedule before injections commence. Dur­
ing the preoperative consultation, it is essential to discuss the
potential for bruising and swelling that may follow treatment.
Patients who have significant social or business events should
allow for approximately 1 week of time following an injection
with hyaluronic acid. Certain areas (such as the lips and tear
troughs) may require longer than this.
Other preoperative considerations include the interac­
tions of the material as well as the needle with the patient’s
medications, medical history and implanted devices. As with
any injection, particularly around the lips, the trauma to the
skin from the needle or the product may induce an outbreak
of herpes in patients that are so predisposed. It is essential
to elicit this history and, if applicable, to treat patients sus­
ceptible with an antiviral such as famciclovir or valacyclovir.
Famciclovir should be dosed at 500 mg, three times per day
for approximately 5–7 days. Valacyclovir may be given at 2 g
given twice daily for 1 day. Treatment may be initiated on the
day of the procedure.
Patients with active infections in the areas being injected
should not be treated until the infection has been adequately
treated. Infection with HIV is not a contraindication (although
immunosuppression is a consideration mentioned in several
package inserts) for treatment with hyaluronic acids and many
patients with lipoatrophy have been effectively treated with
these molecules.11
The list of medications and supplements known to increase
bruising and bleeding is expanding with the number of medi­
cations and herbal supplements used to decrease the risk of
strokes and heart attacks (Table 19-2). Patients taking these
drugs and supplements should stop them in advance of any
proposed treatment. In addition, many other substances can
significantly impair blood clotting. Among the more common
agents are: nonsteroidal antiinflammatory agents including
ibuprofen, naproxyn, aspirin, and all of the products that
contain these ingredients. In addition to these various prod­
ucts, many people consume alcohol on a daily basis and some
will even have alcohol prior to their visits. Alcohol will inhibit
platelet function, and ideally it should be avoided for approxi­
mately 1 week prior to injections. If patients has consumed
alcohol prior to a treatment, they should be advised that many
hyaluronic acid products are prone to bruising and that their
treatment may be more likely to bruise. The reality of patient
care is that many patients choosing to undergo soft tissue aug­
mentation are likely to have consumed some alcohol within a
week of treatment and the treating physician must reconcile
oneself with this reality.
In reality, many injections of HAs result in bruising and
since, to date, there is no study comparing the relative bruis­
ing risks of the various agents in patients who have ceased
using these agents prior to treatment, it is impossible to quan­
titate the relative risk for bruising associated with the agents
mentioned in Table 19-2. There is, however, a publication
that documents adverse effects associated with cessation of
antiplatelet and anticoagulant drugs and one may infer that
there may be a similar type of risk for certain patients who
stop these types of medications prior to undergoing soft tissue
augmentation.12
Implanted devices such as Gore-tex or silicone implants
may cause injections of hyaluronic acid to be lumpy or dis­
crete rather than homogeneous since either of these can im­
pede flow of materials injected. Scarring surrounding either

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Soft tissue augmentation  •  Chapter 19
of these materials may also affect the flow of any filler as it
penetrates the tissue space. Liquid injectable silicone also im­
pacts the flow of subsequent fillers and each of these should
be addressed during the preoperative consultation since re­
sults from hyalurons injected near any of these products will
not be as smooth as if it had been injected into untreated
areas.
Informed consent is an important facet of one’s pre­
operative considerations. The informed consent can vary but
should ­ include several basic components. Among these are
the ­potential complications that can occur; these should be as
complete as possible and many skilled injectors list everything
from bruising, swelling, bleeding, exacerbation of cold sores,
infections, hyperpigmentation, hypopigmentation, necrosis of
the skin, blindness, anaphylaxis, allergies, asymmetry, lumps,
bumps, and a host of other potential complications to the fact
that there is a charge for each syringe used and that a perfect
correction is not guaranteed.
Anesthetic considerations are also an intrinsic part of the
preoperative plan. The various options for managing the dis­
comfort associated with injection of HA range from none to
topical anesthetic to injection with various anesthetic com­
pounds. Discussion of the risks, benefits, and duration of an­
esthetic associated with each of these methods is an important
aspect of the preoperative plan.
After considering the patient’s anatomy and goals, it is
worthwhile to use a mirror to discuss the treatment with the
patient. This helps to insure that the physician does not ­correct
something aesthetically significant to the doctor but irrelevant
to the patient.
When assessing a particular area, one needs to consider
how much hyaluron and which hyaluron will produce the best
outcome for a given patient. Assessment of the adjunctive use
of botulinum toxin should be considered as there is evidence
that these combinations of hyalurons and botulinum toxins
may be synergistic in certain areas.13 Deep nasolabial creases
will be best treated with thicker molecules such as Restylane,
Perlane or Juvederm 24 HV or 30 HV. Typical women with
moderate nasolabial creases will require 2–4 mL of ­material.
Small injections of botulinum toxins in this area (into the leva­
tor labii superioris alaeque nasii) may improve the ­appearance
of the correction but the potential complications of this
­injection should be carefully considered and discussed with
the patient. Fine perioral lines can be corrected with a softer
molecule such as Hylaform or Captique or with one contain­
ing smaller-sized particles (Restylane Touch) or lower concen­
trations (Juvederm 18). Small amounts of botulinum toxin
(e.g. 1–2 U of botulinum type A) may be injected in conjunc­
tion with perioral hyaluronic acid injections with a dramatic
outcome. The risks attendant with this addition must be dis­
cussed with the patient prior to adding this treatment.
The second most popular site for injections of hyaluronic
­acids is the lips and selection of the appropriate ­ material
depends on the desired outcome of the patient and the
­experience of the injector.
Anesthetic considerations
Several advances in pain management have made injections
of hyaluronic acids more comfortable for the patient. One
needs to consider that, depending on the density of material
selected and the volume of material injected, there may be
considerable tissue pressure. Certain areas such as the lips will
require anesthetic injections in most patients. Failure to obtain
patient comfort during the procedure will result in a patient
that is unlikely to return for additional treatments and a mov­
ing target during injections. Although none of the presently
approved HA products incorporates anesthetic, it is likely
that some of these anesthetic/HA combinations will be intro­
duced in the near future. Another source of discomfort during
injection of HA comes not from the material itself but from
the needle used to introduce the material. It is important that
one use a needle that is extremely sharp and able to puncture
the skin without significant tissue trauma. When using a serial
puncture technique to inject HA, it is likely that one will dull
the needle and it is important to change the needle frequently
if the tissue resists puncture.
Certain areas, such as the lips, are more heavily inner­
vated and warrant special attention prior to treatment with
HA. These areas are best treated with injectable anesthesia in
order to provide the patient with a good experience and the
physician with a stationary target for injection and sufficient
time to perform a methodical assessment and treatment.
Table 19-2  Some agents that may increase bruising with soft tissue augmentation injections
Common agents that increase
bruising
Duration of effect
Method of action
Aspirin
About 10 days
Inhibit platelet function
NSAIDs
About 3 days
Inhibit platelet function
Gingko biloba
‘Prior to surgery’
Inhibit platelet function and aggregation
Garlic
Weeks
Inhibit platelet function and aggregation
Vitamin E
‘Prior to surgery’
Inhibit platelet function and aggregation
Ginger
‘Prior to surgery’
Inhibit platelet function and aggregation
Source: Chang L, Whitaker D. The impact of herbal medicines on dermatologic surgery. Dermatol Surg 2001; 27:759–763.

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In the perioral and lip area, the use of either infraoral
blocks or gingival ‘miniblocks’ can be safely and easily per­
formed. One technique helpful when performing either of
these blocks is to apply topical dental anesthetic gel for a
few second prior to infiltration with the needle. This makes
the initial injection more tolerable and puts the patient, who
frequently fears any needle, at ease. Another method that is
helpful when injecting is to use a dental pump such as ‘the
wand’ (made by Compudent). This pump is pedal activated
and it infiltrates with a slow, constant rate that most patients
appreciate. If one injects anesthetic with a syringe, it is helpful
to gently vibrate the lip with the nondominant hand in order
to utilize the anesthetic effect afforded by the gate theory of
pain, which posits that a vibratory stimulation in a given area
is likely to minimize the transmission of pain by interfering
with transmission along the pain fiber pathways.
The choice of anesthetic utilized prior to HA injection has
a great bearing on the patient experience. Certain anesthetics
such as artecaine (Septocaine) have a rapid onset that in many
patients is within 5–7 minutes. Another benefit of using this
product is that it has a relatively rapid offset, typically 1.5–2
hours. Other anesthetics may also be injected depending on
the patients allergies, sensitivity to epinephrine (present in
Septocaine and many other products), and duration of an­
esthesia desired. Certain patients may benefit from a longer-
acting anesthetic but the expected duration of any of these
products should be discussed prior to their use. Among the
injectable anesthetics commonly used for preoperative treat­
ment, 1% lidocaine with epinephrine (1:100 000), 1% lido­
caine without epinephrine, 2% lidocaine, and carbocaine are
all viable alternatives. Although some have advocated the use
of the collagens for anesthetic (due to their lidocaine content),
a more comfortable experience is insured when anesthesia
is utilized in a manner and quantity suitable to produce the
­desired results.
Other areas, including the zygomatic arch and nasolabial
creases, may be treated with either no or minimal ­anesthetic.
For many patients treatment of these areas is adequately
managed with a topical anesthetic such as a compounded
­betacaine/lidocaine/tetracaine mixture, applied for 15–30
minutes. Topical anesthetic options include prepared prod­
ucts such as LMX 4, LMX 5, and EMLA. Finally, there are
patients who will do well with the application of ice to the area
being injected.
Procedural techniques
General technical considerations
In general, the hyalurons are placed in the dermis at a level
(Fig. 19-1) such that they produce the desired result (etching
out fine lines, providing support, or adding volume) without
resulting in lumps, bumps, or blue blebs. Optimal patient out­
comes require that each product be placed into the plane for
which it was designed, but this is not sufficient to insure opti­
mal patient treatment outcomes. This requires that sufficient
volume of the filler be injected; perfect placement without
adequate volume will produce suboptimal results as will poor
placement of optimal quantities of material.
A multitude of injection techniques may be used to inject
the hyalurons (Fig. 19-2). Crosshatching involves using the nee­
dle to inject in a grid-like manner. Serial puncture techniques
make several, serial punctures through the skin as adjacent ar­
eas are injected. Linear threading utilizes injection of material
as the needle is removed from a single insertion point. Fanning
injections deposit material in a radial manner from a single
insertion point. The fanning technique has been shown in a
phase 4 clinical trial to cause the most bruising and should be
avoided if possible.14 As with any cosmetic technique, the best
results are used when one is not wed to a single style but rather
adapts each to a particular contour defect and situation. Most
experienced injectors rely on combinations of these as well as
the ‘eversion’ technique (described in the above pearl) when
injecting soft tissue augmentation materials.
Selection of a particular HA for treating a given area de­
pends partly on the differing chemical and physical attributes
Line
Wrinkle
Epidermis
Dermis
Subcutis
Fold
Fig. 19-1  Diagram showing hyalurons placed in the dermis at
a level such that they produce the desired result (Hylaform, Captique
and Restylane Touch and Juvederm 18 for upper dermis Hylaform
Plus, Restylane, Juvederm 24 for mid-dermis Perlane, Juvederm
30 for deep dermis).
• When injecting fillers, visualize the potential
space that one are filling in three dimensions
and use the nondominant hand to contour the
skin into the shape that one wish to produce.
For instance, when injecting the marionette lines,
use the nondominant hand to flex the ­concavity
into a convexity and guide the product into
place.
Pearls

293
Soft tissue augmentation  •  Chapter 19
of each and partly on the experience and preferences of the
injector. Restylane is a denser molecule than is Captique or
­Hylaform but it is not as dense as Juvederm 24 or 30. Since it is
a homogeneous gel, Juvederm may give a smoother ­correction
initially than the particulate molecules such as Restylane.
The cross-linking of each molecule also contributes to the
physical characteristics of each of these HAs. When injecting
the deep dermal planes in an effort to reverse moderate to
­severe creases, it is reasonable to select Juvederm, ­Restylane,
or ­Perlane. For more superficial lines (those limited to the mid
to upper dermis), Restylane, Juvederm, Captique, or ­Hylaform
may be utilized.
After the area has been cleaned and anesthesia (if utilized)
obtained, the injection of material begins. When injecting a
crease, grasping both sides of the crease between the non­
dominant thumb and forefinger (Fig. 19-3) will help to guide
the product into the exact location to which it is intended to
go. Once this is done, the needle is placed into the mid dermis.
If one can see the outline of the needle, it is probable that
placement will be too superficial and the needle should be re­
positioned. If, after injecting about 0.1 mL of product, there
is no visible difference in the area treated, it is possible that
the needle is too deep and it should be moved more superfi­
cially. Although various authors posit that needle placement
A. Linear threading technique
B. Serial puncture technique
C. Fan technique
D. Cross-hatching technique
Fig. 19-2  Diagram showing injection techniques.

294
Chapter 19
Cosmetic surgery procedures and techniques
should be at a particular location (e.g. the mid-dermal plane
or the dermal–subcutaneous junction) it is more reasonable to
guide ones injections by the anatomic response to the material
injected rather than attempt to blindly place a product in a
location that is a fraction of a millimeter in size.
Area-specific technical considerations
Nasolabial crease
The nasolabial (NL) location (Fig. 19-4) is the most frequent
area injected and it is very amenable to treatment with the
HA family (Fig. 19-5). Outstanding results (Fig. 19-6) may be
obtained with several products and clinical trials to compare
efficacy and duration of various cross-linked hyalurons will
clarify the duration and texture over time of each. When
injecting the nasolabial crease, one should begin at the in­
ferior aspect of the crease and gradually proceed superiorly
(Fig. 19-7). This enables the physician to gauge the interac­
tion of the product with the tissue and the patient to ad­
just to the process of being injected in an area that is less
painful than the perinasal sulcus. The needle is inserted into
the skin about 0.1 mm deep and the orifice of the needle
should be oriented either medially or towards the dermis. A
­serial puncture technique is preferred in this area by one of
the authors while a linear threading technique is preferred
by the other, but blending other techniques such as linear
threading will help to produce a homogeneous correction.
It is useful to grasp the NL crease as previously described
because this enables one to palpate the product as it goes in
and to guide it into the actual crease rather than allowing it
to ­extravasate ­laterally. While injecting, care should be taken
Fig. 19-3  Injection into a fold.
Fig. 19-4  Nasolabial crease.
A
B
Fig. 19-5  Before (A) and after (B) photographs demonstrating results obtained with Restylane. (Courtesy of Kenneth Beer, MD)

295
Soft tissue augmentation  •  Chapter 19
to avoid increasing the bulk of the cheek. As one approaches
the superior aspect of the crease, the orientation of the ­needle
should be adjusted such that instead of it ­ paralleling the
crease, it should be slightly horizontally oriented. ­Gradually
changing the orientation of the needle enables one to ‘bridge’
the cosmetic units of both sides of the nasolabial crease. This
helps to blur the line of demarcation that serves to draw
­attention to the crease. There is an embryologic ­fusion plane
at the superior aspect of the nasolabial crease that is an area
of decreased tissue resistance to flow. In some patients, injec­
tions near the ala will cause filler to flow into this potential
space and result in a ridge between the nasal ala and the
upper lip. If one notices this ridge forming, use one finger to
provide a physical barrier to product flow and inject with less
pressure. Slower flows using less pressure may be associated
with less bruising.
Correction of the nasolabial creases requires consideration
of three different contributing factors that most injectors are
intuitively aware of and they include: facial ptosis, local vol­
ume loss, and loss of epidermal support. Facial ptosis causes
the face to sag and, although it is partly manifested in the
nasolabial creases, unless the underlying cause is addressed
its contribution can not be addressed. Methods of reversing
midface descent are beyond the scope of this chapter but they
are advancing rapidly and include: injections of Sculptra,
­insertion of cogged threads, lights, lasers and radiofrequency
energy sources, and surgery. Local loss of deep tissue may be
reversed by placement of fillers including the HAs into this
plane. Among the products capable of producing an improve­
ment are Perlane, Restylane, Restylane Sub Q, ­ uvederm,
and Hylaform Plus. Finally, each nasolabial crease has a su­
perficial component visible as an ‘etched-in’ line that must be
addressed by placement of product superficially enough to
­elevate the epidermis. Injections for this latter indication may
utilize Restylane, Captique, Juvederm, and Hylaform. In this
area, the technique rather than the product is critical.
The amount of material needed for treatment of the NL
creases depends on the depth of the crease, the material cho­
sen, and the degree of correction desired. Not all patients want
or can afford what the injector considers an ‘ideal’ correction.
In general, an average woman with moderately deep nas­olabial
creases will require 2–3 mL of Restylane, Perlane, or Juvederm.
As with other areas, failure to inject adequate volume will ­result
in a treatment that fails, and there is nowhere that this is more
noticeable than the NL crease. Men with moderately deep
creases will require more volume than women and they will
also tend to tolerate the thicker ­ molecules better. ­ Anatomic
considerations for injections in this location include the angular
A
B
Fig. 19-6  Correction of the NL Crease with Juvederm. Approximately 1 mL was used in each crease of this patient. (Courtesy of Kenneth Beer, MD)
• In order to inject at a superficial plane, it may
be helpful to use a needle that is smaller than
the one provided with the product. For instance,
although many of these products include a 30 g,
half-inch needle, it is helpful to use a 32 g,
half-inch needle when injecting superficially.
Pearls
Fig. 19-7  Needle placement for nasolabial injection. (Courtesy
of Kenneth Beer, MD)

296
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Cosmetic surgery procedures and techniques
artery and vein which should be avoided. If one sees blanching
during an injection, one should immediately stop injecting and
follow protocols elucidated by Glaich et al.10
Lips
The lips are the second most popular area treated with the
hyalurons. As this area tends to be more sensitive to pain and
more technique dependent than NL creases, it is ­recommended
that injected anesthetic be considered for those patients with
low pain thresholds (Fig. 19-8). Perhaps more than any other
area, the esthetic proportions of the lip are subjective and
one needs to have a clear understanding of the patient’s goals
­before injecting (Fig. 19-9).
While there are several differing constructs regarding the
functional anatomy of the lip as it relates to soft tissue aug­
mentation, it is useful to consider two overriding aspects: vol­
ume and definition. Quite simply, volume relates to the ­desire
to have lips that are bigger while definition refers to the shape
of the lip. Obviously, neither volume nor shape exists in isola­
tion and injections intended to alter the volume will ­obviously
alter the shape but it is useful initially to consider each of these
types of injections separately. Once one has mastered the ­basic
concepts and techniques of lip augmentation, it is worthwhile
to consider other constructs including those ­ espoused by
­pioneers in lip augmentation.15
To help visualize the ideal shape and volume of the lip, one
only needs to pick up the latest women’s magazine. Typically,
these magazines feature lips that are full in volume and ­sharply
defined. While this may not be what most patients desire for
their own corrections, it is something that factors into their
expectations. The proportional size of these archetypal lips
usually features a lower lip that is approximately 33% larger
than the upper lip.
Injections intended to restore volume to the lip are prima­
rily placed into the body of the lip whereas those designed to
shape them are placed at the junction of the vermilion and
the surrounding epidermis. In many patients who have not
had prior injections or foreign bodies placed (and thus do not
have any fibrosis) there is a potential space at the rolled border
of the lip (Fig. 19-10). By placing a 30 g needle into this space,
it is possible to run a small amount of material across the bor­
der of the lip much the way collagen was injected in this area.
This serves two useful functions: it restores a boundary to the
lip thereby defining the lip and it also helps to minimize the
‘bleeding’ of lipstick that many women find troubling. Most
women require about 0.25–0.5 mL of material for each lip
to be effectively treated in this manner. The serial puncture
technique is the preferred method for this area and it is easy to
visualize where the leading edge of the material is and to use
this as the insertion point for the next injection.
Volume restoration is obtained by injecting the body of the
lip. The site of insertion is at the line where the Fordyce glands
begin (easily visualized as the ‘wet–dry’ junction of the lip) (Fig.
19-11). A serial puncture technique is preferred when treating
this area and it is imperative to use a low pressure, slow injec­
tion. If one creates a bleb of material, withdraw the needle
and stop injecting. Insert in an adjacent area and proceed with
the augmentation while making sure that one removes the bleb
with a no. 11 blade or 18 g NoKor needle. Lip augmentations
Fig. 19-8  Injection into the lip.
Fig. 19-9  Proportional and youthful appearing lips, following
­injections of Restylane into the body and border. (Courtesy
of Kenneth Beer, MD)
Fig. 19-10  The rolled border is delineated. (Courtesy of Kenneth
Beer, MD)

297
Soft tissue augmentation  •  Chapter 19
need to consider the contour of the lip as well as the propor­
tions and if the injector simply places product where it will
most easily flow, the results will be large, unattractive lips. Most
of the lip volume for the upper and lower lips should be cen­
trally located but it is important to avoid ‘fading lips’ that look
great in the middle but disappear at the margins. Increasing
the volume of the lips may also cause the lips to evert and as
one is injecting, the needle should be reoriented to avoid creat­
ing duck-bill lips that stick out and evert. The lower lip has two
central prominences that should be injected with additional
material, and placing 0.1 mL into each of these results in an
aesthetically pleasing outcome. In general, the average women
seeking lip augmentation will require 1–2 mL of product for an
adequate outcome and many patients are content with 1 mL.
It is important to counsel patients with very thin lips that
these may never be made very large. Unlike other areas, the lips
tend to swell and patients need to be counseled regarding this
prior to the procedure. The homogeneous gels may cause less
swelling than the particulate products and clinical trials com­
paring these products should determine the degree to which this
is true. Significant swelling may be treated with oral steroids and
some physicians also find diuretics such as furosemide helpful.
Marionette lines/oral commissures
Loss of soft tissue from the lateral chin and lower lateral lip
may result in deep marionette lines and an angle of the mouth
that is oriented inferiorly. These defects are among the most
simple to correct with HAs and are frequently the most pleas­
ing for the patient.
As with the crease of the nasolabial area, it is beneficial to
begin injections of this area by grasping the crease between
the thumb and forefinger or securing the area with firm coun­
tertraction. Using a serial puncture technique at the inferior
aspect of the crease, small amounts of material are inserted
into the dermis. If one uses the grasping technique, it is pos­
sible to palpate the material as it flows into the area and to
confirm that it is not drifting into an unintended area. As one
approaches the lip, a fanning technique should be used to but­
tress and provide support for the corner of the mouth. One
author (RN) uses linear threading technique with retrograde
injection rather than the fanning technique. Adequate volume
placed in this area will restore the corner of the mouth to a
horizontal, neutral position and make a significant cosmetic
difference.
Glabella
Perhaps more than any other area, this area should be ap­
proached with caution because of the risk of necrosis associ­
ated with injections at this location. Despite this caveat, there
are few areas as rewarding to treat either with hyaluronic acid
in isolation or in conjunction with botulinum toxins. The
combination of HA and botulinum toxin in this area has been
demonstrated to be synergistic and it results in a high degree
of patient satisfaction when performed well (Fig. 19-12).16,17
Injections of the glabella have resulted in necrosis with
­hyaluronic acids as well as with most other soft tissue augmen­
tation products. Whether the risk of necrosis results from intra­
vascular injections or compression of the vascular structures in
the area is not known but if one injects fillers into this area, it is
wise to keep materials such as nitroglycerin paste nearby.
The injection of HA into the area should proceed more
slowly than in any other and minute amounts of material
should be introduced while watching for any signs of blanch­
ing. Using a serial puncture technique, the HA may be gently
introduced. It is helpful to tent the skin upwards, away from
the glabella in order to guide the product into the furrow and,
more significantly, to distract the injection site from the un­
derlying blood vessels. One author (RN) uses a linear thread­
ing technique that also serves to subcise the tissue. The needle
is placed into the dermis while HA is injected with minimal
Fig. 19-11  The junction between the epithelial and mucosal
­surfaces where many volume injections should be initiated.
(­Courtesy of Kenneth Beer, MD)
The addition of a minute amount of material into
the lower lip will provide a significant difference when
treating the marionette lines
An average amount of material that is used for this
indication is about 0.5 mL per side. Anatomic consid­
erations in this area include the angular artery and
vein, and one needs to avoid intravascular injection
and try to avoid injuring these vessels when injecting
in this location.
Pearls
• When injecting the lips, save a small amount of
volume to buttress the lateral aspects. Although
this will not be adequate to reposition the
­corners of the mouth to a neutral position,
patients will appreciate even a slight
­improvement in this area.
Pearls

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­pressure on the plunger. On average, not more than 0.25 mL
of HA should be introduced in any given session and, when
using a thicker product such as Juvederm or Perlane, it may be
wise to inject even less. In many patients who get this area in­
jected with fillers, a botulinum toxin is used concurrently, and
it is helpful to place the toxin after the augmentation material.
This has the theoretical advantage of reducing the risk of toxin
migration secondary to the pressure of the filler introduction.
Periorbital
The periorbital area is an area that is frequently treated with
botulinum toxins but is also amenable to soft tissue augmenta­
tion with the hyalurons. Whereas the toxins are ideally ­suited
for treatment of the dynamic rhytides of the orbicularis, hy­
aluronic acids may be used for the tear trough and perhaps in
the crow’s feet. As with any injection in this location, augmen­
tation may produce significant bruising and edema. A discus­
sion of this possibility must ensue prior to any treatment and
the potential duration should be discussed and documented.
Treatment of the dynamic component of the crow’s feet
can usually be easily accomplished with botulinum toxins.
In many patients, this treatment does not afford the patient
the degree of resolution desired because of the residual static
component and it is this latter aspect that HA may be utilized
to address. In contrast with many other areas, the soft, low-
concentration HAs such as Captique and Hylaform may be
suited for this indication. The use of thicker products may
result in bumps and should be avoided in most patients. Injec­
tions of fillers in the crow’s feet should utilize a low-pressure,
slow-injection technique that places small amounts of mate­
rial into the dermis. Massaging the material into a smooth
configuration is essential to optimal outcomes. The back of
ones fingernail is useful for this technique.
When injecting the tear trough, it is vital to asses the extent
of the trough. Some patients will have a relatively small (e.g.
1 cm) area on the medial aspect of the infraorbital rim while
others will have a trough that extends to the lateral canthal
margin and can span 2–2.5 cm. In either instance, the most
important aspect of the injection is to protect the globe. This
is accomplished with one finger placed on the inferior orbital
rim such that the orbit is protected. It is also helpful to insure
that the needle is oriented in a manner that directs the sharp
end away from the eye and also to keep the injecting hand
planted on the patient’s face. By doing so, any sudden move­
ment by the patient will not result in jabbing the needle into
the orbit, which can be upsetting for all concerned.
The injection begins with placement of the needle in the
submuscular plane (just above the periosteum). Before inject­
ing, it is important to aspirate so that there is no chance of in­
travascular injection of material. Small amounts of material,
each approximately 0.05–0.1 mL may be placed and gently
massaged so that a homogeneous zone of correction (rather
than a series of discrete nodules) is obtained. Caution should
be taken to avoid superficial placement of material which
can result in bluish papules that are readily apparent through
the thin skin of the eyelids. Injections should span the entire
trough for a given individual and not be arbitrarily terminated
at any given location (e.g. the midpupillary line).
Zygomatic arch
Volume restoration to the zygomatic arch provides two essen­
tial functions. The first is to reposition the midface in a more
youthful, anatomically correct position. This effect is achieved
by the direct upwards pull of the material. The ­second ben­
eficial effect of zygomatic injections is by filling this area the
skin, which typically has lost its elasticity and has begun to
sag, is ‘re-inflated’ and tightened. Small volumes of materials
­injected in this location can have a profound ­cosmetic impact.
Injections of the zygomatic arch are placed at the deep der­
mal or subcutaneous level. Material selected should be dense
(such as Perlane, Restylane Sub Q, Juvederm, Restylane).
The volume required for this injection depends on the age,
bone structure (high or low cheekbones), and degree of tis­
sue loss. On average, many patients benefit from 0.25–0.5 mL
of material. When injecting the zygomatic areas, it is better
to undercorrect and subsequently enhance the effect than to
overcorrect.
By grasping the proposed injection area between one’s
thumb and forefinger, placement of product is directing into
the areas desired. In general, a fanning technique with the
A
B
Fig. 19-12  Before (A) and after (B) photographs of deep static and dynamic rhytides treated with Restylane and Botox. (Courtesy of Kenneth
Beer, MD)

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Soft tissue augmentation  •  Chapter 19
insertion radius at the inferomedial aspect (see Fig. 19-2)
will be best suited for this treatment. Alternative methods
­include injections that are directed along the zygomatic arch,
proceding laterally and superiorly in order to direct the vector
of correction in the same directions. Molding of the implant
following the injection will help to reduce any asymmetry and
to create a contour that best suits the individual patient.
One study of Restylane Sub Q injected into the submuscu­
lar plane of the zygoma demonstrated an improvement when
evaluated by the physicians and all were satisfied with the
­results obtained.18 The average amount of Restylane Sub Q
used in this study was 3.9 mL for the malar areas, and the aver­
age duration of response was reported to be ‘up to 64 weeks.’
Hands
One of the cardinal signs of aging is the atrophy that occurs
on the dorsal aspects of the hands. Renewed attention to this
cosmetic area has followed the availability of various new
products that are able to replace volume in the hands and one
of the most versatile of these options is the hyalurons.
In order to improve the appearance of the hands, it is
­necessary to conceal the ‘stringy’ appearance afforded by the
extensor tendons as they show through an atrophic epidermis
and dermis. As has been accomplished with autologous fat,
this may be accomplished with hyaluronic acids. Juvederm 24,
Juvederm 30, Restylane, and Perlane are products that may
be used in this location. Because of its increased particle size,
Restylane Sub Q may also be a good filler for this site.
Large volumes of hyaluronic acid will be required for cor­
rection of most patients with dorsal hand atrophy and it is
important to discuss the approximate number of syringes (and
attendant cost) with the patient prior to beginning the treat­
ment. Average patients may require up to 3–4 mL of product
for a significant improvement.
Topical anesthetic may be applied to the dorsal hands prior
to the injection or a small amount (e.g. 1–2 mL of 1% lido­
caine with 1:100 000 epinephrine) may be injected. Needle
insertion should begin at the proximal aspect of the hand,
adjacent to the tendons (Fig. 19-13). Small boluses of mate­
rial (0.1–0.25 mL) may be placed and massaged forward in
order to obtain an even plane of correction. An alternate ap­
proach is the use a linear threading technique and gently in­
ject product as one advances the needle forwards. Since this is
a vascular area, care must be taken to avoid intravascular in­
jections. After injecting the space adjacent to the first tendon,
one should proceed in the same manner with the adjacent
area until the entire atrophic area has been corrected. Once
this is accomplished, it is useful to address the epidermal signs
of aging with topical retinoids, chemical peels, lasers, or light
sources in order to obtain optimal cosmetic results.
Post-treatment considerations
Following injections of hyaluronic acids, there are a multitude
of potential complications. There are several instructions that
patients should follow and it is worthwhile to have a printed
postoperative sheet for patients so that they are not alarmed
at routine occurrences. Among the potential postoperative
complications, the following were noted to occur for Restylane
during the FDA trials: bruising (52.2%), redness (84.8%), swell­
ing (87%), pain (57.2%), tenderness (77.5%), itching (30.4%).
and other (24.6%).7 It should be noted that although these
statistics seem higher than one might expect, they were self-
reported by the patients and were short lived, with 70–90%
disappearing in 3–4 days and/or mild in extent.
In clinical practice, as the hyaluronic acid implants interact
with local tissues, they swell as they imbibe water and they also
cause adjacent swelling due to an inflammatory response. The
degree of swelling depends on the product (Restylane swells
more than Hylaform), the location injected (lips tend to swell
more than nasolabial creases), the amount of material injected,
and the inflammatory reaction mounted by the patient.
Different strategies have been utilized to manage postoper­
ative swelling. These may include administration of oral ster­
oids begun the day of the procedure and continuing for 2 or 3
days afterwards. A tapering dose of steroids such as a Medrol
Dose Pack™ or prednisone dosed at 20–40 mg per day may
be used and can be especially helpful managing postoperative
swelling from lip augmentation procedures. Diuretics such as
furosemide may alleviate some postoperative edema follow­
ing injections into the tear trough regions. Typical doses are
20–40 mg per day.
Postoperative analgesia may consist of acetaminophen or a
nonsteroidal antiinflammatory drug (NSAID) such as ibupro­
fen or naproxen. The analgesia and antiinflammatory actions
of NSAIDs is partially offset by their potential to increase the
extent and duration of bruising.
As previously mentioned, postoperative instructions for pa­
tients prone to herpetic outbreaks should include an antiviral
agent which should be continued for several days.
The application of ice or other cooling agents may be quite
helpful following injections of any soft tissue ­ augmentation
product. Application of ice, frozen peas, or a frozen gel pack
will help to decrease swelling and discomfort. Regimens may
Fig. 19-13  Needle insertion should begin at the proximal aspect
of the hand, adjacent to the tendons. (Courtesy of Kenneth Beer,
MD)

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consist of application of the cool product for 3–5 minutes
every hour while the patient is awake.
One final postoperative tip is to have prepared bags ready
for each patient who receives an injection. These bags should
include a postoperative information and care sheet that
­includes the physician’s contact information, cover makeup
(typically, a green tint works well) to mask any bruising that
may occur and, if NSAIDs are recommended, individually
packaged Motrin™, Advil™, or similar product.
Future directions
At the present time, there are many hyaluronic acid products
available in the US and Europe. It is likely that many of the
products approved in Europe will appear in the US market
over the next few years. Among the improvements likely to
be incorporated into the hyaluronics is the addition of an
­anesthetic, which will greatly enhance patient comfort. Other
changes likely to occur are modifications of the cross-linking
which could increase the duration of correction. Additions to
the hyalurons, which could include synthetic molecules, have
occurred and these products are being utilized in Europe and
there is every reason to believe that this type of hybrid mate­
rial will be refined as injectors gain experience with them.
Conclusion
The hyalurons offer a major improvement over previously ap­
proved soft tissue augmentation products. The ranges of con­
centrations offered, molecule sizes available, and cross-­linking
variations afford the dermatologic surgeon exciting new pos­
sibilities. Newer versions of these molecules including ones
incorporating anesthetic and semipermanent molecules are
likely to ensure that this category of filler remains significant
and relevant for years to come.
Collagen
In the two decades that followed FDA approval of Zyderm in
1981, bovine collagen dominated the soft tissue augmentation
market by default. The introduction of other products, such
as hyaluronics, shifted this landscape and newer products as­
sumed the majority of the injectable market. Poly L lactic, cal­
cium hydroxylapatite, methylmethacrylate beads immersed in
various carriers have now become part of the soft tissue aug­
mentation landscape, yet collagen remains a viable product.
Newer versions of collagen are expected to be introduced into
the United States and it is anticipated that these products will
offer a long-lasting version of collagen.
The first collagen product approved for soft tissue augmen­
tation was Zyderm. This product is 35 mg/mg of bovine col­
lagen in phosphate buffered saline and it contains lidocaine as
an anesthetic. Unfortunately, initial enthusiasm for this prod­
uct was dampened by the need for more durable and more
substantive corrections. It was noted early on that Zyderm
tended to disappear rapidly and a second collagen product,
Zyderm II, was created. Zyderm II contained collagen in the
same lidocaine and buffered saline but it has collagen at a con­
centration of 60 mg/mL. Zyderm II was an improvement and
it was rapidly accepted but a desire for a more durable cor­
rection led to a cross-linked collagen. This product, Zyplast,
was cross-linked with glutaraldehyde in an effort to inhibit the
degradative processes that digest injected collagen. As an ad­
ditional improvement, Zyplast was offered in larger (2.5 mL
instead of 1.0 mL) syringes that proved to be more economical
and better suited for areas such as the nasolabial creases.
Allergic reactions to collagen tempered the initial enthusi­
asm for the products and skin testing, which had been recom­
mended as a single test, was increased to two tests.19 While
this decreased the incidence of allergic reactions, it also meant
that patients had to assume the burden of two visits to the
physician, each approximately 1 month apart. The double vis­
its precluded any patient treatments at the time of initial con­
sultation and this, combined with the attendant costs of two
physician visits, curbed enthusiasm for collagen treatments
with these products.
In an effort to facilitate patient treatments and decrease the
number of visits required, human versions of collagen were
developed. These have included cadaveric, autologous, and
collagen derived from cultured human fibroblast cells. Cadav­
eric collagen enjoyed a brief period of popularity but never
obtained significant market share and the product (Dermalo­
gen) was withdrawn from the market. Other cadaver-derived
products, including Fascian, are still in existence but none has
been widely used. Autologous collagen has been in the plan­
ning and testing phases for several years and one product, Iso­
lagen, is presently in FDA approval trials. Collagen derived
from cultured human fibroblasts eliminated the need for skin
testing as well as the delay required for autologous cultures and
it avoids the stigma of cadaveric products. However, problems
with the degree and duration of corrections obtained have
limited patient acceptance of these products.
Newer versions of collagen include porcine collagen cross-
linked with different technology.
Three versions of human fibroblastic collagen are pres­
ently available and each corresponds to a previously available
bovine product. Cosmoderm I is analogous to Zyderm I and it
contains 35 mg/mL of collagen. Cosmoderm II is analogous
to Zyderm II and contains 60 mg/mL of collagen. Cosmo­
plast is made from cross-linked collagen and it is used the same
way that Zyplast is used. Neither of the Cosmoderm products
nor Cosmoplast requires prior skin testing and each may be
injected at the time of initial patient consultation. Cosmoplast
is used for areas including the nasolabial creases, Cosmoderm
I is used for superficial placement, and it can be used in the
perioral and periorbital regions. Cosmoderm II is used in a
variety of areas including the lips.
In an effort to increase the duration of collagen corrections,
modifications of various molecules have been created. One such
molecule has utilized a different method of cross-­linking the
collagen fibrils. Evolence™ cross-links porcine collagen fibers
using ribose moieties instead of the glutaraldehyde technology

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Soft tissue augmentation  •  Chapter 19
used by Cosmoplast and Zyplast. In addition, the use of por­
cine collagen may present a less antigenic stimulus, thereby
enabling the collagen to persist without significant antigenic
degradation. Evolence is in an FDA phase 3 clinical trial in
the USA that is nearly completed and is already approved in
­Canada and Europe. One benefit of this product is that is sup­
posed to last for at least 12–15 months (Solish N, personal com­
munication.). It is likely that if the product gains market share
and leads to resurgent interest in collagen for soft tissue aug­
mentation, other versions of the product will be introduced.
Technical considerations
In the two decades that collagen dominated the soft tissue
augmentation market, there have been numerous publica­
tions discussing its use and the reader is referred to these for
an in-depth discussion of the technical considerations of the
collagens.20 The thicker, cross-linked collagen molecules (Zy­
plast and Cosmoplast) are best utilized for structure. They are
injected into the nasolabial creases with good short-term re­
sults that last approximately 4 months. Anesthetic for Zyplast
or Cosmoplast usually consists of either none or topical an­
esthetic because the products contain lidocaine. For patients
who require additional anesthesia, infraorbital nerve blocks or
miniblocks can provide additional anesthesia.
Nasolabial creases
On average, approximately 2.5–3 mL of collagen is required
for correction of an average middle-aged woman’s nasolabial
crease. Injections should be made into the mid-deep dermis.
If they are placed more superficially, they will appear yellow
and impart a peau d’orange texture to the overlying epider­
mis. Typically, the needle is oriented with the bevel pointed to­
wards the deep or medial aspect. Many injectors find the linear
threading and serial puncture techniques helpful in this area.
Lips
Since their approval, collagens made a significant impact in lip
augmentation and this area has been the second most popu­
lar area for implantation (after the nasolabial creases).2 Non­
cross-linked materials are used to increase the size of the lips
and to etch out fine perioral rhytides. In the past few years,
the adjunctive usage of botulinum toxins to minimize the
­activity of the orbicularis oris muscle has greatly improved these
­treatments.21 Cosmoderm I and II and Zyderm I and II are
well suited for this indication. Cross-linked collagens including
Zyplast and Cosmoplast are useful for increasing the size and
contour of the lips. One indications for which collagens remain
especially useful is for the correction of perioral rhytides (most
commonly referred to as ‘smoker’s line’ (Fig. 19-14).
Typically, there is both a static and a dynamic component
to these rhytides and addressing the static component with col­
lagen will produce dramatic improvements. A typical patient
with lines such as those pictured will do well with Cosmoderm
I placed into each rhytide with either a serial puncture or lin­
ear threading technique. When utilizing the latter method, it
is helpful to grasp the individual rhytide between one’s fingers
and cannulate the fold, injecting as one withdraws the needle.
Adjunctive use of 2 units of Botox on each side of the upper
and lower lips will help to minimize the dynamic component
of these lines and will produce dramatic results. As with any
injection of Botox around the mouth, a discussion of the rela­
tive risks and benefits is warranted before proceeding.
Marionette lines
Deep marionette lines may be treated with Cosmoplast or Zy­
plast and more superficial rhytides in this area are treated with
noncross-linked products. When injecting the marionette lines
with collagens, the techniques discussed for the hyalurons are
largely applicable. One difference is the potential for using
different thicknesses of collagens at different places. Following
volume restoration in this area using a cross-linked collagen,
the fine lines that are etched into the epidermis may be treated
with a noncross-linked collagen. Treatment of the marionette
lines may be combined with injections of botulinum toxin into
the depressor anguli oris to enhance the outcomes. However,
this latter injection must be made by injectors with a great
degree of experience because of its relatively high rate of
complications.
Glabella
Furrows in the glabella are commonly treated with botulinum
toxins but in many patients the static component persists after
this treatment. Cosmoderm I, Cosmoderm II, Zyderm I, and
Zyderm II may all be used to fill this component and they pro­
duce dramatic results when combined with the toxins. There
have been reports of necrosis in this area following injections
of Zyplast and the use of this product (and by extension,
­Cosmoplast) in this area should be avoided.
Zygomatic arch and hands
The collagens have not had significant impact on ­treatment
for zygomatic arch/malar augmentation nor have they
­impacted the dorsal hands. To date, they have made their best
Fig. 19-14  Example of etched-in smoker’s lines. (Courtesy of
­Kenneth Beer, MD)

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­contributions to nasolabial creases and lips. Some have advo­
cated their use as ‘structural’ fillers, comparing their fibrillar
structure to scaffolding upon which one can layer hyalurons.
Others have espoused the collagens as fillers that can impart
anesthesia. Since there are no data to support either of these
contentions, and the collagens are presently fairly costly ad­
ditions to patient treatments, it seems reasonable to use them
within the scope discussed here.
Conclusions
Despite the advent of newer fillers, collagen retains a portion
of the filler market. The collagens offer the advantage of hav­
ing minimal post-treatment bruising and for this reason will
most likely remain popular with some patients. For physicians
and patients comfortable with its long safety record, collagen
will continue to have a role. Future collagen-based products
will incorporate newer cross-linking technology that will en­
able them to persist for greater lengths of time. In addition,
it is likely that the addition of various materials to collagen-
based carriers will cause these materials to be relevant for the
foreseeable future.
Poly l lactic acid (sculptra)
Basic science
Sculptra™ was FDA approved in 2004 for facial lipoatrophy
and is expected to gain approval for cosmetic indications in
2007. It is polymerized L lactic acid (PLLA) that must be
reconstituted prior to injection. Optimal dilution for recon­
stitution of this product has yet to be determined and at
the present time many injectors prefer to reconstitute with
4–6 mL of sterile water and an additional 1–2 mL of either
1% lidocaine, 2% lidocaine, or 1% lidocaine with epine­
phrine. Inclusion of epinephrine may decrease the incidence
of bruising. Clinical trials performed in Europe demonstrated
a high rate of subcutaneous papules when less diluent was
utilized.22 Although the package insert states that the product
should be used within 24 hours of dilution most physicians
have now begun to allow the product to saturate for at least
24 hours and many are keeping the product refrigerated for
up to 3 weeks.23 Pre-mixing of material eliminates the need to
either bring patients back for a second visit in the event that
they elect to have treatment following a consultation or risking
the wasting of an expensive product that was diluted but not
injected. To date, there are no studies defining what the maxi­
mal duration of product stability following reconstitution is.
Unlike traditional soft tissue augmentation products, PLLA
is not a direct volume substitute. Rather, it is a ‘volumizer’ that
stimulates the body to produce collagen and other connective
tissues in response to it. The degree of volume produced by
any given individual is difficult to predict and injecting 2–3 mL
of PLLA in an individual will not produce a 2–3 mL direct
­tissue augmentation. Unlike other agents, PLLA is ­injected as
a series of injections, each spaced ­approximately 4–6 weeks
apart. The optimal number of treatment sessions depends on
the patient’s ability to produce collagen, the degree of correc­
tion required, and the amount of PLLA injected (Fig. 19-15).
The duration of correction obtained with PLLA may span
18 months or more.22 This duration is one of the strengths
of this material. Another is its ability to tighten the skin in a
­manner that traditional volume replacement products can not.
For instance, injections of PLLA into the zygomatic arch are
able to lift the face, and injections of the jaw area can help to
tighten the ‘jowls.’ Optimal dilutions, intervals, and volumes
for injections are being evaluated with clinical trials and it is
likely that this product will obtain a niche in the filler arena.24
A clinical trial using PLLA for the treatment of acne scarring
has been conducted and it would seem that this ­product will
be useful for this indication.25
Technical considerations
Unlike many other materials, injected PLLA is neither a gel
nor a solution. Rather, it is a suspension of material whose
theoretical concentration is determined by the injector rather
A
B
Fig. 19-15  Before (A) and after (B) photographs demonstrating Sculptra’s ability to add volume in the cheek area. (Courtesy of Kenneth Beer, MD)

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Soft tissue augmentation  •  Chapter 19
than the manufacturer. The theoretical concentration of the
suspended PLLA is the concentration that would be obtained
if the product remained homogeneous throughout its usage.
Unfortunately, this is not the case and the product precipitates
as it is being injected. This precipitation means that certain
areas will be injected with more-concentrated PLLA. It also
means that when injecting the product, one should try to keep
the material agitated and evenly suspended and inject with
some degree of haste.
When injecting the product, one should use a 25- or
26-gauge needle because any smaller size will result in ­constant
needle clogging. Needles ranging from 0.5 inch to 1.0 inch may
be used (longer needles are better for fanning techniques but
incur more resistance to flow). For most patients, the anesthetic
contained in the reconstituted product is adequate. Patients
who require more than this may benefit from topical anesthetic
or nerve blocks in addition. Techniques that can be utilized for
injecting Sculptra include the fanning, ­serial ­puncture, cross-
hatching, and linear threading techniques and most ­experienced
injectors use a combination of these to increase the probability
of obtaining homogeneous product placement.
Injections of the zygomatic arch, jaw area, temporal area,
nasolabial crease, and mental crease should be at the ­border
of the subcutis or within the subcutis. Tear trough injections
should be at the submuscular region, just above the peri­
osteum. PLLA is less forgiving than many other products and
its ­placement into the superficial dermis will result in ­visible
and palpable nodules at relatively high frequencies. Other
areas that are amenable to treatment with Sculptra ­include
the dorsal hands. When injecting the dorsal hands, it may be
beneficial to use more-dilute product (9–10 mL per bottle).
In addition, care should be taken to avoid injections into the
vasculature of the hands and to avoid injecting the product
immediately adjacent to the tendons.
Because the product does not directly replace lost tissue
volume, the amount used for a given situation is difficult to
precisely estimate. In general, an average 50-year-old woman
with moderate-depth nasolabial creases will benefit from
three 4-injection session of PLLA with each session using 1–
2 bottles of Sculptra. Other areas such as temporal wasting
and zygomatic arches typically require three to four sessions
with the amount of material required dictated by the sever­
ity of tissue loss present as well as the degree of correction
desired.
It is important to emphasize to patients that the degree
of correction obtained with PLLA is not predictable and
this statement should be clear in the written consent forms.
Undercorrection following three injections may produce pa­
tients with low satisfaction while overcorrection that may oc­
casionally follow two injections may also produce dissatisfied
patients.
Nasolabial creases
The use of PLLA as a treatment for the nasolabial creases has
two technical components.
Restoration of the volume lost in the actual nasolabial
creases may be accomplished with PLLA injections. PLLA
diluted to 6–8 mL per bottle should be injected into the
deep dermis with a 0.5 or 1.0 inch, 25- or 26-gauge needle
oriented towards the deep tissue. A combination of serial
puncture and fanning techniques should be utilized. Since
it may take two bottles per session to restore volume in a
moderate or deep crease, the patient should be cautioned
regarding the increased cost associated with this treatment.
Although the original paradigm for this product was to use
the diluted product as a gauge of correction, the use of
more-dilute PLLA as well as experience with this material
has changed this perspective and it is now recognized that
there are no useful physical predictors of correction during
the injection.
A second technical component for treating the nasolabial
creases with PLLA relies upon the injection of adjacent areas.
This mechanism relies upon the collagen-induced skin tight­
ening associated with PLLA injections. By injecting PLLA into
the zygoma and cheek area, the laxity and ptosis associated
with moderate nasolabial creases may be corrected. A fan­
ning technique is used to place PLLA into these areas. Each
side should be injected with approximately 1 mL of PLLA at
a 6–8 mL dilution.
Zygomatic arches
Facial descent is one hallmark of the aging face. Although
face-lifts have long sought to correct this by pulling the face
laterally, the restoration of volume and reversal of skin laxity
to the midface is better at addressing the root causes of facial
descent. Injection of PLLA into the zygomatic and cheek areas
is best made using a 0.5 or 1.0 inch, 25- or 26-gauge needle.
Using a fanning technique, approximately 1 ml of material
should be deposited into each side. When approaching the eye
area, it is best to aspirate prior to injections in order to avoid
retrograde injections into the ocular vasculature.
After waiting a minimum of 4 weeks to gauge the degree
of volume correction, this technique may be repeated. One
caveat for injecting the midface is that it is better to err on the
side of waiting longer than to inject more frequently because
overcorrection of the midface will make the patient look like a
chipmunk and, since this is caused by the formation of innate
collagen, there is no easy way to reverse this.
Cheeks
Drawing upon the experience with HIV lipoatrophy patients,
injections of PLLA have been used to restore cheek ­volume
lost during normal aging.26 Treatment of this area can
­produce dramatic results that are rewarding for physician and
patient alike.
To inject these areas, a cross-hatching technique that
places material in the deep dermis/subcutis is used. When
­injecting this site, it is worth noting the desired degree of
­convexity ­desired and moving the needle to different levels as
one progresses to different areas of the cheeks. As with other

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areas of the face, this site is best treated with a 0.5 or 1.0
inch, 25- or 26-gauge needle. Average amount used in this
location is ­approximately 1–4 mL per side (using a 6–8 mL
dilution).
Postoperative care
Following injections of any of these areas, it is important to
vigorously massage the material. One commonly utilized pro­
tocol is to have the patient massage the injected sites for 5 min­
utes per session five times per day for 5 days. To date, there is
no evidence-based literature to prove that this ­methodology
reduces the incidence of papule formation but it makes intui­
tive sense.
Silicone
No soft tissue augmentation product has generated more con­
troversy than silicone. Several well-respected physicians have
enjoyed decades of experience with this product, having a low
incidence of complications. Other well-respected physicians
consider this product unfit for cosmetic injections.27 Often lost
in any discussion of silicone is the fact that there are totally
disparate experiences. One experience involves the use of
pharmaceutical silicone injected in a microdroplet technique
by dermatologists and plastic surgeons that are judicious injec­
tors. The second experience, termed ‘psychopathic’ by David
Duffy, MD, involves the use of silicone of varying degrees of
purity by people with varying degrees of knowledge, experi­
ence, and ethics.1
Silicone is a compound derived from silicon, oxygen,
and methane. It was first formulated in the early 1900s and
since then has been used in a variety of medical applica­
tions including breast implants, intravenous tubing, and as
an injectable material for intraocular injections.28 At the
present time, a 1000-centistoke silicone has been used for
the treatment of HIV-associated lipoatrophy with impressive
results.29 In addition, recent evidence supports the safety and
efficacy of using 1000-centistoke silicone in the treatment
of nasolabial folds and marionette lines. A small series of
eight patients followed over a 3-year period revealed supe­
riority to Zyplast collagen, near 100% patient and physi-
cian satisfaction, as well as the absence of any significant
side effects (Michael Kaminer 2006, personal ­communica-
tion). Although the sample size is small and follow-up only
3 years, this scientific work taken with the body of experi­
ence in the physician community suggests that silicone may
indeed have a prominent role in soft tissue augmentation in
years to come.
­Although there was a ban on its usage, at the present time
silicone is approved by the FDA for the treatment of ­intraocular
retinal hemorrhage. This approval allows physicians to inject
this product in an off-label indication. Prior to injecting this
product, however, it is recommended that one obtain written
approval from one’s malpractice carrier to cover the use of this
product.
Indications
Silicone is indicated for soft tissue augmentation in patients
desiring a permanent soft tissue correction. Among the in­
dications for which silicone is ideal is distensible acne scars.
According to Duffy, this product can produce outstanding
aesthetic correction for patients with these types of scars and,
unlike other filling agents, the correction of these scars is per­
manent.28
Other areas that experienced injectors use silicone in­
clude the glabella, nasolabial folds, marionette lines, cheek
­hollows, cheek bones, chin, prejowl sulcus, and tear troughs.30
Silicone has also been used with good results for lip augmen­
tation.
Contraindications
The major contraindications to silicone injections are the
use of nonmedical-grade silicone, injection techniques other
than the microdroplet method, and injections performed by
­physicians who are not properly trained in the correct meth­
odology. Other contraindications include injections into
the breast and penis (both of which have been performed
with disastrous complications). Injections into areas that are
­infected are also to be avoided, as are injections into horizon­
tal creases of the forehead and mental area which may result
in beading.
Patients lacking any prior soft tissue augmentation with a
temporary implant should be considered a relative contrain­
dication to injections with silicone. Since the product is per­
manent, injection of silicone into a filler-naive individual may
result in a patient changing his or her mind following observa­
tion of the correction obtained.
Pregnancy and lactation are relative contraindications
­because of the medicolegal implications of any pregnancy or
infancy complication. Prior injection of silicone by another
individual is also a relative contraindication because patients
will associate any complication with the last, most easily
­located injector.1 Collagen vascular diseases are also a relative
contraindication to injections with silicone.
Anesthetic considerations
Most patients receiving silicone injections require topical
anesthesia but nothing more. Several prescription-strength
products such as LMX 4 (Ferndale Laboratories, MI) or com­
pounded products using betacaine, tetracaine, and lidocaine
are also effective. As with any topical anesthetic, the longer the
agent is applied, the more effective the anesthetic obtained,
and most patients do well with a 15–30 minute application. For
patients who are undergoing lip augmentation, injections with
lidocaine or artecaine provide sufficient analgesia to ­provide
a comfortable experience for both physician and patient.
Injections with these agents are best accomplished with gingi­
val ‘miniblocks’ rather than infraorbital and mental regional
blocks. The experience may be made more ­comfortable by
application of a dental anesthetic gel.

305
Soft tissue augmentation  •  Chapter 19
Technical considerations
The single most important technical consideration for silicone
is to insure that medical-grade material is injected using the
microdroplet technique. This technique requires patience
on the parts of both physician and patient and represents
a treatment regimen different from other fillers such as the
­hyalurons. Microdroplet silicone injections employ very small
(0.01–0.03 mL) of silicone injected into the deep dermis/
upper subcutaneous space.31 A 27-gauge needle is required
to inject the material and several experienced injectors use
the Becton Dickinson 0.3 cc insulin U-100 Syringes (Becton
Dickinson, US). Whatever needle is selected, it is important
to make sure that it is secured using a Luer lock mechanism
so that the pressures required for injection do not separate the
needle from the syringe. Correct placement of the needle is
crucial to successful treatments. Product placed too superfi­
cially will result in ‘beading’ of the product which becomes
visible and palpable as an unsightly row of papules. Place­
ment too deeply is not as significant and results in a less effec­
tive correction.
Injection sessions typically consist of injections of 0.5–1.0 mL
with total treatment usually not exceeding 3–5 mL.32 To obtain
a complete correction, patients must return for several visits
over the span of several months.
Nasolabial crease
When injecting the nasolabial creases, the needle should be ori­
ented medially to avoid lateral placement. Smiling and other
facial expressions have a tendency to pump the product later­
ally and postoperative movement should be minimized. Some
physicians advocate using tape until a fibroblastic capsule
has secured the microdroplet of silicone in place (Fig. 19-16).
As demonstrated in Figure 19-17, silicone offers the patient a
cost-effective, cosmetically pleasing, long-term correction in
this area when it is injected by a skilled injector who under­
stands the unique characteristics of this product.
Glabella
Glabella furrows may be corrected using silicone and it is
likely that the miniscule volumes required by microdroplet
techniques are better suited for this location than the injec­
tions of larger volumes used with other materials. Another
facet of this location that is amenable to treatment with sili­
cone is the frequency with which it is immobilized with Botox.
B
A
Fig. 19-17  Before (A) and after (B) photographs of
acne scars treated with silicone. (Courtesy of David
Duffy, MD)
B
A
Fig. 19-16  Before (A) and after (B) ­photographs
of nasolabial creases after treatment with silicone.
(Courtesy of David Duffy, MD)

306
Chapter 19
Cosmetic surgery procedures and techniques
This latter treatment creates an ideal environment for silicone
­encapsulation.
Lips
Injections of silicone for lip augmentation will remain one of
the most popular uses for this material. Although any place­
ment of permanent fillers should be thoroughly discussed and
documented prior to inception, this holds especially true for lip
augmentation. Since the lips are a major facet of the patient’s
appearance, silicone should be injected even more gradually
in this location than in others. Adjunctive use of botulinum
toxins to minimize the pumping actions of the orbicularis oris
musculature may also be helpful in this locale. When injecting
silicone into the lips, one needs to exercise caution and avoid
fashion trends that are soon outdated. One example of such
a trend was the ‘Paris Lip’ briefly in vogue during the early
1990s. Imparting a permanent look using a transitory fashion
phenomenon as a guide is a recipe for a chronically unhappy
patient.
Scars
Perhaps the aesthetic indication that is most amenable to treat­
ment with silicone is acne scarring. These scars have a signifi­
cant impact on a patient’s appearance and self-image. When
they are distensible scars, they can have profound changes
­following correction with silicone (see Fig. 19-17). Treatments
should be limited to distensible scars and should err on the
side of undercorrection.
Future directions
The silicones have been part of the soft tissue augmenta­
tion landscape for over five decades and it is likely that they
will remain viable filling products for the foreseeable future.
Versions that enabled physicians to alter the product with
­radiofrequency or lasers might be engineered and these would
offer permanent fillers that could be altered or removed if re­
quired. Pure silicones are already available and these are likely
to gain market share if they prove to be utilized in a manner
consistent with the microdroplet techniques espoused by those
injectors skilled in its usage.
Calcium hydroxyapatite (Radiesse)
Product overview
Calcium hydroxyapatite has been used in medicine for sev­
eral years and its usage as a soft tissue augmentation product
has been expanding in recent years. The reasons for its popu­
larity include its relatively long duration (in many patients it
lasts for over 1 year) and its relative profile of safety. Adverse
reactions to this product consist largely of nodule formation
and these are thought to be related to technical issues includ­
ing placement rather than to any intrinsic properties of the
material.
Radiesse™ has been approved for use in craniofacial de­
fects and for laryngoplasty in the US. The material is sup­
plied in syringes that are either 1.3 mL or 0.3 mL, and it does
not require refrigeration. It is radiopaque, and this should be
­considered prior to its injection.
Indications
Radiesse™ is indicated in instances for lines of moderate to
severe depth. Among the areas that Radiesse™ may be used
for are the nasolabial creases, marionette lines, and zygomatic
arches. The product may also be used, albeit with a great deal
of caution, in the glabella and the perioral areas.
Contraindications
Radiesse™ is contraindicated in patients with a known sensi­
tivity to any of its ingredients. It is also relatively contraindi­
cated in patients who do not desire a long-term correction. In
addition, it should be used with caution in the body of the lips
as it has a tendency to form bumps in this location.
Anesthetic considerations
There is no anesthetic present in Radiesse™ and, since it is
a dense filler, injections without anesthetic may be unpleas­
ant. When injecting the nasolabial creases, the use of infraor­
bital nerve blocks and adjunctive injections into the angle of
the mouth will help to make the injection more comfortable.
Injections in other parts of the face (such as the zygomatic
arch) should follow the application of topical anesthetic or ice.
Mental nerve blocks will help to make injections into the mari­
onette lines more tolerable.
Techniques for selected areas
In general, Radiesse™ injections are made into the deep der­
mis, the superficial subcutaneous space, or deep into muscle
or near periosteum. Injections placed higher than these levels
will increase the likelihood of granuloma and lump formation.
The syringes are compatible with a Luer lock needle and for
most injections a 0.5 inch, 25-, 26- or 27-gauge needle is rec­
ommended for injections. Certain areas, such as the zygomatic
arch, are amenable to treatment with 1.0 or 1.25 inch needles.
Nasolabial crease
The nasolabial creases and marionette lines are perhaps the
best area treated by Radiesse™. For creases that are moder­
ate to severe in nature, this product may be used to restore
lost volume. Following cleansing of the skin and anesthetic
(if used), injections are made using a combination of serial
puncture and linear threading techniques. The fold should be
grasped between the thumb and forefinger of the nondomi­
nant hand while material in injected. Palpation of the mate­
rial as it flows into place diminishes the risk of its wandering
into unintended places. Injection depth should be deep der­
mis or subcutaneous. For an average woman in the mid-50s,
1.3–1.6 mL of material injected into both creases should
­provide an excellent correction. As with other fillers, it is

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