Ứng Dụng Laser Trong Da Liễu Và Y Học (Lasers In Dermatology – 2018)

139
light-based sources capable of improving fine
facial rhytides, dyspigmentation, and telangiec-
tasia associated with cutaneous photodamage.
The armamentarium of lasers and light-based
sources currently available to treat cutaneous
photodamage is larger than ever before
(Table  9.1). The most appropriate technique
depends upon the severity of photodamage and
rhytides, the expertise of the laser surgeon, and
the expectations and lifestyle of the individual
patient.
Ablative Laser Skin Resurfacing
Indications and Contraindications
The ideal patient for ablative laser skin resur-
facing has a fair complexion (skin phototype I
or II), exhibits cutaneous lesions that are ame-
nable to treatment, and has realistic expecta-
tions of the resurfacing procedure. Adequate
preoperative patient evaluation and education
are absolute essentials to avoid pitfalls and
optimize the clinical outcome (Table  9.2).
Proper patient selection is paramount as abla-
tive laser resurfacing can be complicated by a
prolonged postoperative ­recovery, pigmentary
alteration, or unexpected scarring. The patient’s
emotional ability to tolerate an extended con-
valescence is an important factor in determin-
ing the most appropriate choice of laser.
Although CO2 and modulated Er:YAG lasers
often produce the most dramatic clinical
results, some patients may be unable to tolerate
the intensive recovery period. For patients
unable or unwilling to withstand extended
postoperative healing, a short-pulsed Er:YAG
laser or application of a non-ablative or frac-
tional laser procedure may be a more suitable
choice.
Table 9.1  Lasers and light sources for skin resurfacing
Laser type
Wavelength (nm)
Ablative
CO2 (pulsed)
Er:YAG (pulsed)
10,600
2940
Non-­
ablative
Pulsed dye
Nd:YAG, Q-switched
Nd:YAG, long-pulsed
Diode, long-pulsed
Er:glass, long-pulsed
Intense pulsed light
source
585–595
1064
1320
1450
1540
515–1200
Fractional
Er-doped fiber
1550
Er erbium, Nd neodymium, Q-switched quality-switched,
YAG yttrium-aluminum-garnet
Summary Box
• Indications
–– Mild-to-moderate rhytides, preferably
in non-movement-associated areas
–– Other signs of photodamage (e.g.,
dyspigmentation and keratoses)
–– Shallow atrophic scars
–– Superficial skin lesions
• Contraindications
–– Patients
with
unrealistic
expectations
–– Patients with perpetual sun exposure
–– Active bacterial, viral, fungal infec-
tion or inflammatory skin conditions
involving the skin areas to be treated
–– Patients with prior lower blepharo-
plasties using an external approach
are at greater risk of ectropion forma-
tion after infraorbital ablative laser
treatment
–– Patients with darker skin tones
(skin phototype IV–VI) have a
high incidence of postoperative
hyperpigmentation
–– Concomitant isotretinoin use could
potentially lead to an increased risk
of hypertrophic scarring
–– Patients with a propensity to scar will
be at greater risk for postoperative
scarring
9  Lasers for Resurfacing

140
Techniques
Preoperative Management
There is no consensus among laser experts
regarding the most appropriate preoperative regi-
men for ablative laser skin resurfacing. The use
of topical retinoic acid compounds, hydroqui-
none bleaching agents, or α-hydroxy acids for
several weeks before laser treatment has been
touted as a means of speeding recovery and
decreasing the incidence of postinflammatory
hyperpigmentation
[11].
Topical
tretinoin
enhances penetration of chemicals through the
skin and has been shown to accelerate postopera-
tive re-epithelialization after dermabrasion or
deep chemical peels [12]. However, because
ablative laser-induced wounds are intrinsically
different from those created by physically
destructive methods, laser skin penetration is not
typically affected by the topical application of
any of these medications. In addition, being that
postinflammatory hyperpigmentation is rela-
tively common after ablative cutaneous laser
resurfacing, many laser surgeons originally
believed that the prophylactic use of topical
bleaching agents would reduce the incidence of
this side effect, but investigators subsequently
demonstrated that the preoperative use of topical
tretinoin, hydroquinone, or glycolic acid had no
effect on the incidence of postablative laser
hyperpigmentation [13].
Due to the moist, de-epithelialized state of
ablative laser-resurfaced skin and the possibility
of bacterial contamination and overgrowth, many
laser surgeons advocate oral antibiotic prophy-
laxis; however, this practice remains controver-
sial due to the results of a controlled study that
demonstrated no significant change in post-laser
resurfacing infection rate in patients treated with
prophylactic antibiotics [14]. The most common
Table 9.2  Ablative laser resurfacing: patient selection, risks, and precautions
Preoperative patient evaluation
• Are the lesions amenable to ablative laser skin resurfacing? All suspicious lesions require biopsy before
treatment.
• Has the patient ever had the areas treated before? Ablative laser resurfacing can unmask hypopigmentation or
fibrosis produced by prior dermabrasion, cryosurgery, or phenol peels. Patients with prior lower blepharoplasties
using an external approach are at greater risk of ectropion formation after infraorbital ablative laser treatment.
• What is the patient’s skin phototype? Patients with paler skin tones (skin phototype I or II) have a lower
incidence of postoperative hyperpigmentation than do patients with darker skin tones.
• Does the patient have a history of herpes labialis? All patients should be treated with prophylactic antiviral
medication before perioral treatment, because reactivation and/or dissemination of prior herpes simplex
infection can occur. The de-epithelialized skin is also particularly susceptible to primary inoculation by herpes
simplex virus.
• Does the patient have an autoimmune disease or other immunologic deficiency? Intact immunologic function
and collagen repair mechanisms are necessary to optimize the tissue-­healing response due to the prolonged
recovery associated with ablative resurfacing.
• Is the patient taking any medications that are contraindicated? Concomitant isotretinoin use could potentially
lead to an increased risk of postoperative hypertrophic scar formation due to its detrimental effect on wound
healing and collagenesis. A safe interval between the use of oral retinoids and ablative laser skin resurfacing is
difficult to determine; however, most advocate a delay in treatment for at least 6 months after discontinuation of
the drug.
• Does the patient have a tendency to form hypertrophic scars or keloids? Patients with a propensity to scar will
be at greater risk of scar formation after treatment, independent of the laser’s selectivity and the operator’s
expertise.
• Does the patient have realistic expectations of the procedure and adhere to postoperative instructions? Patients
who can not physically or emotionally handle the prolonged postoperative course should be dissuaded from
pursuing ablative laser skin treatment.
Summary Box
• Adequate preoperative patient evalua-
tion and education
• Oral antibiotic prophylaxis as indicated
R. Wanitphakdeedecha and T. S. Alster

141
infectious complication is a reactivation of labial
herpes simplex virus (HSV), most likely caused
by the thermal tissue injury and epidermal dis-
ruption produced by the laser [15, 16]. Any
patient undergoing full-face or perioral ablative
resurfacing should receive antiviral prophylaxis
even when a history of HSV is denied. It is
impossible to predict who will develop HSV
reactivation, because a negative cold sore history
is an unreliable method to determine risk and
many patients do not remember having had an
outbreak or are asymptomatic HSV carriers. Oral
antiviral agents, such as acyclovir, famciclovir,
and valacyclovir are effective agents against HSV
infection, although severe (disseminated) cases
may require intravenous therapy. Patients should
begin prophylaxis by the day of surgery and con-
tinue for 7–10 days postoperatively.
Description of the Technique
Carbon Dioxide (CO2) Laser
The Ultrapulse (Lumenis Corp, Yokeam, Israel),
one of the first high-energy, pulsed CO2 laser sys-
tems developed, emits individual high energy
pulses (peak energy densities of 500 mJ in 600 μs
to 1  ms). Its earliest competitor, the SilkTouch
(Lumenis Corp, Yokeam, Israel), was a continuous-­
wave CO2 system with a microprocessor scanner
that continuously moved the laser beam so that
light did not dwell on any one area for more than
1  ms. The peak fluences delivered per pulse or
scan ranged from 4 to 5  J/cm2, which were the
energy densities determined to be necessary for
complete tissue vaporization [7, 17–19]. Studies
with these and other pulsed or scanned CO2 laser
systems showed that after a typical skin resurfac-
ing procedure, water-containing tissue was vapor-
ized to a depth of approximately 20–60  μm,
producing a zone of thermal damage ranging
20–150 μm [7, 18, 20–22].
The depth of ablation correlates directly with
the number of passes performed and usually is
confined to the epidermis and upper papillary
dermis; however, stacking of laser pulses by
treating an area with multiple passes in rapid suc-
cession or by using a high overlap setting on a
scanning device can lead to excessive thermal
injury with subsequent increased risk of scarring
[15, 23, 24]. An ablative plateau is reached with
less effective tissue ablation and accumulation of
thermal injury. This effect is most likely caused
by reduced tissue water content after initial desic-
cation, resulting in less selective absorption of
energy [24]. The avoidance of pulse stacking and
incomplete removal of partially desiccated tissue
is paramount to prevention of excessive thermal
accumulation with any laser system.
The objective of ablative laser skin resurfac-
ing is to vaporize tissue to the papillary dermis.
Limiting the depth of penetration decreases the
risk for scarring and permanent pigmentary
alteration. When choosing treatment parame-
ters, the surgeon must consider factors such as
the anatomic location to be resurfaced, the skin
phototype of the patient, and previous treat-
ments delivered to the area [17, 25]. In general,
areas with thinner skin (e.g., periorbital) require
fewer laser passes and non-facial (e.g., neck,
chest) laser resurfacing should be avoided due
to the relative paucity of pilosebaceous units in
these areas [25]. To reduce the risk of excessive
thermal injury, partially desiccated tissue
should be removed manually with wet gauze
after each laser pass to expose the underlying
dermis [24].
The clinical and histologic benefits of cutane-
ous laser resurfacing are numerous. With the CO2
laser, most studies have shown at least a 50%
improvement over baseline in overall skin tone
and wrinkle severity (Fig. 9.1a, b) [10, 26–30].
The biggest advantages associated with CO2 laser
Summary Box
• Areas with thinner skin (e.g., perior-
bital) require fewer laser passes
• Non-facial (e.g., neck, chest) areas
should be avoided due to paucity of
pilosebaceous units with diminished
capacity for re-epithelialization.
• Avoidance of pulse stacking in order to
decrease risk of scarring
9  Lasers for Resurfacing

142
skin resurfacing are the excellent tissue contrac-
tion, hemostasis, prolonged neocollagenesis and
collagen remodeling that it provides. Histologic
examination of laser-treated skin demonstrates
replacement of epidermal cellular atypia and
dyplasia with normal, healthy epidermal cells
from adjacent follicular adnexal structures [7,
21]. The most profound effects occur in the papil-
lary dermis, where coagulation of disorganized
masses of actinically-induced elastotic material
are replaced with normal compact collagen bun-
dles arranged in parallel to the skin’s surface [31,
32]. Immediately after CO2 laser treatment, a
normal inflammatory response is initiated, with
granulation tissue formation, neovascularization,
and increased production of macrophages and
fibroblasts [21].
Persistent collagen shrinkage and dermal
remodeling are responsible for much of the
continued clinical benefits observed after CO2
resurfacing and are influenced by several fac-
tors [33, 34]. Thermal effects of laser irradia-
tion of skin produce collagen fiber contraction
at temperatures ranging from 55  °C to 62  °C
through disruption of interpeptide bonds result-
ing in a conformational change to the colla-
gen’s basic triple helical structure [35, 36]. The
collagen molecule is thereby shortened to
approximately one third of its normal length.
The laser-induced shrinkage of collagen fibers
may act as the contracted scaffold for neocol-
lagenesis, leading to subsequent production of
the newly shortened form. In turn, fibroblasts
that migrate into laser wounds after resurfacing
may up-regulate the expression of immune
modulating factors that serve to enhance con-
tinued collagen shrinkage [37].
The CO2 resurfacing laser is a most effective
tool for improving photo-induced facial rhytides;
however, dynamic rhytides are not as amenable
to laser treatment. Many patients experience
recurrence of movement-associated rhytides
(particularly in the glabellar region) within
6–12  months postoperatively. Thus, cosmetic
denervation with intramuscular injections of bot-
ulinum toxin type A is often used concomitantly
with laser resurfacing to provide prolonged clini-
cal improvement [38].
Absolute contraindications to CO2 laser skin
resurfacing include active bacterial, viral, or fun-
gal infection or an inflammatory skin condition
involving the skin areas to be treated. Isotretinoin
use within the preceding 6-month period or his-
tory of keloids also are considered contraindica-
tions to CO2 laser treatment because of the
unpredictable tissue healing response and greater
risk for scarring [39, 40].
In an attempt to address many of the difficul-
ties associated with the use of multiple-pass CO2
laser skin resurfacing, refinements in surgical
technique were subsequently developed. Single-­
pass CO2 laser treatment was shown to effect
faster re-epithelialization and an improved side
effect profile [41]. Rather than remove partially
desiccated tissue (as was typical with multiple-­
pass procedures), the lased skin was left intact to
a
b
Fig. 9.1  CO2 laser resurfacing (a) before and (b) after
R. Wanitphakdeedecha and T. S. Alster

143
serve as a biologic wound dressing. Additional
laser passes could then be applied focally in areas
with more severe photodamage in order to limit
unnecessary thermal and mechanical trauma to
uninvolved skin. Subsequent reports have sub-
stantiated the improved side effect profile of this
less aggressive procedure [42–44].
Erbium: Yttrium–Aluminum–Garnet
(Er:YAG) Laser
The Er:YAG laser is a more ablative tool that
emits light at 2940 nm, corresponding well to the
3000 nm absorption peak of water. The absorp-
tion coefficient of the Er:YAG is 12,800  cm−1
(compared with 800  cm−1 for the CO2 laser),
making it 12–18 times more efficiently absorbed
by water-containing tissue than is the CO2 laser
[45]. The pulse duration (averaging 250  μs) is
also much shorter than that of the CO2 laser,
resulting in decreased thermal diffusion, less
effective hemostasis, and increased intraopera-
tive bleeding which can hamper deeper dermal
treatment. Because of limited thermal skin injury,
the amount of collagen contraction is also
reduced with Er:YAG treatment (1–4%) com-
pared to that observed with CO2 laser irradiation
[11, 46].
The erbium’s efficient rate of absorption, short
exposure duration, and direct relationship
between fluence delivered and amount of tissue
ablated leads to 2–4 μm of tissue vaporization per
J/cm2, producing a shallow level of tissue abla-
tion. Much narrower zones of thermal necrosis,
averaging only 20–50 μm, are therefore produced
[45, 47–49]. Laser-induced ejection of desiccated
tissue from the target site typically produces a
distinctive popping sound. Thermal energy is
confined to the selected tissue, with minimal col-
lateral thermal damage. Because little tissue
necrosis is produced with each pass of the laser,
manual removal of desiccated tissue is often
unnecessary.
The short-pulsed erbium laser fluences used
most often range from 5 to 15 J/cm2, depending
on the degree of photodamage and anatomic
location. When lower fluences are used, it is often
necessary to perform multiple passes to ablate
the entire epidermis. The ablation depth with the
short-pulsed Er:YAG does not diminish with suc-
cessive passes, because the amount of thermal
necrosis is minimal with each pass. It takes three
to four times as many passes with the short-­
pulsed Er:YAG laser to achieve similar depths of
penetration as with one pass of the CO2 laser at
typical treatment parameters [3, 11]. To ablate
the entire epidermis with the short-pulsed
Er:YAG laser at 5  J/cm2, at least two or three
passes must be used which increases the possibil-
ity of uneven tissue penetration. Deeper dermal
lesions or areas of the face with extreme photo-
damage and extensive dermal elastosis may
require up to nine or ten passes of the short-­
pulsed Er:YAG laser, whereas the CO2 laser
would effect similar levels of tissue ablation in
two or three passes [7, 18, 45].
Pinpoint bleeding caused by inadequate
hemostasis and tissue color change with multiple
Er:YAG passes can impede adequate clinical
assessment of wound depth. Irradiated areas
whiten immediately after treatment and then
quickly fade. These factors render it far more dif-
ficult for the surgeon to determine treatment end-
points and thus requires extensive knowledge of
laser–tissue interaction.
Conditions amenable to short-pulsed Er:YAG
laser resurfacing include superficial epidermal or
dermal lesions, mild photodamage and subtle
dyspigmentation. The major advantage of short-­
pulsed Er:YAG laser treatment is its shorter
recovery period. Re-epithelialization is com-
pleted within an average of 5.5 days, compared
Summary Box
• Typical fluences range from 5 to 15 J/
cm2, depending on the degree of photo-
damage and anatomic location
• When lower fluences are applied, it is
often necessary to perform multiple
passes to ablate the entire epidermis
• Shorter pulse durations are used for tis-
sue ablation and longer pulses are used
to effect coagulation and expand zones
of thermal injury
9  Lasers for Resurfacing

144
with 8.5 days for multiple-pass CO2 procedures
[18, 47]. Postoperative pain and duration of ery-
thema are reduced after short-pulsed Er:YAG
laser resurfacing, with postoperative erythema
resolving within 3–4 weeks. Because there is less
thermal injury and trauma to the skin, the risk of
pigmentary disturbance is also decreased, mak-
ing the short-pulsed Er:YAG laser a good alterna-
tive in patients with darker skin phototypes [3,
50]. The major disadvantages of the short-pulsed
Er:YAG laser are its limited ability to effect sig-
nificant collagen shrinkage and its failure to
induce new and continued collagen formation
postoperatively [3, 47, 51]. The final clinical
result is typically less impressive than that pro-
duced by CO2 laser skin resurfacing for deeper
rhytides. However, for mild photodamage,
improvement of approximately 50% is typical
(Fig.  9.2a, b). Although clinical and histologic
effects are less impressive than those produced
with the CO2 laser, short-pulsed Er:YAG laser
skin resurfacing still affords modest improve-
ment of photodamaged skin with a shorter recov-
ery time [17, 47].
To address the limitations of the short-pulsed
Er:YAG laser, modulated Er:YAG lasers systems
were developed to improve hemostasis and
increase the amount of collagen shrinkage and
remodeling effected. The Er:YAG-CO2 hybrid
laser system delivers both ablative Er:YAG and
coagulative CO2 laser pulses. The Er:YAG com-
ponent generates fluences up to 28 J/cm2 with a
350 μs pulse duration, while excellent hemostasis
is provided by the CO2 component which can be
programmed to deliver 1–100  ms pulses at
1–10 W power. Zones of thermal necrosis mea-
suring as much as 50  μm have been observed
depending on the treatment parameters used and
significant increase in collagen thickness has
been noted 3 months after four passes with this
hybrid technology [52]. Another modulated
Er:YAG device is a dual-mode Er:YAG laser that
emits a combination of short (200–300 μs) pulses
and long coagulative pulses to achieve tissue
ablation depths of up to 200 μm per pass. The
output from the two Er:YAG laser heads are com-
bined into a single stream in a process called
optical multiplexing [53]. The desired depth of
ablation and coagulation can be programmed by
the laser surgeon into the touch-screen control
panel. Several investigators have studied the his-
tologic effects of dual-mode Er:YAG laser resur-
facing and found a close correlation between the
programmed and actual measured depths of abla-
tion [54, 55]. The actual zones of thermal injury
correlate well to the first pass with decreasing
coagulative efficiency on subsequent passes. The
variable-pulsed Er:YAG laser system delivers
pulse durations ranging 500 μs to 10 ms. Shorter
pulse durations are used for tissue ablation and
a
b
Fig. 9.2  Erbium:YAG laser resurfacing (a) before and (b) after
R. Wanitphakdeedecha and T. S. Alster

145
longer pulses are used to effect coagulation and
zones of thermal injury similar to the CO2 laser
[53, 56].
Since the modulated Er:YAG lasers were
developed to produce a greater thermal effect and
tissue contraction than their short-pulsed prede-
cessors, investigators compared collagen tighten-
ing induced by the CO2 laser with that of the
CO2–Er:YAG
hybrid
laser
system
[57].
Intraoperative contraction of approximately 43%
was produced after three passes of the CO2 laser,
compared with 12% contraction following
Er:YAG irradiation. At 4  weeks; however, the
CO2 and Er:YAG laser treated sites were con-
tracted to the same degree, highlighting the dif-
ferent mechanisms of tissue tightening observed
after laser treatment. Immediate thermal-induced
collagen tightening was the predominant response
seen after CO2 irradiation, whereas modulated
Er:YAG laser resurfacing did not produce imme-
diate intraoperative contraction but instead
induced slow collagen tightening [53, 57].
Postoperative Management
Wound care during the immediate postoperative
period is vital to the successful recovery of ablative
laser-resurfaced skin. During the re-­epithelialization
process, an open- or closed-wound technique can
be prescribed. Partial-thickness cutaneous wounds
heal more efficiently and with a reduced risk of
scarring when maintained in a moist environment
because the presence of a dry crust or scab impedes
keratinocyte migration [58]. Although there is con-
sensus on this principle, disagreement exists
regarding the optimal dressing for the laser-­ablated
wound. The ‘open’ technique involves frequent
application of a thick healing ointment to the de-
epithelialized skin surface; whereas occlusive or
semi-occlusive dressings are placed directly on the
lased skin in the ‘closed’ technique. While the open
technique facilitates easy wound visualization, the
closed technique requires less patient involvement
and may also decrease postoperative pain. Proposed
advantages of a closed wound care regimen include
increased patient comfort, decreased erythema and
edema, increased rate of re-epithelialization, and
decreased patient involvement in wound manage-
ment [58, 59]. On the other hand, additional expense
and a higher risk of infection have been associated
with the use of these dressings [3, 60, 61].
In addition to postoperative wound care, ice
pack application and anti-inflammatory medica-
tions should be prescribed during this time.
Furthermore, pain medication is particularly
important for ablative laser-resurfaced patients dur-
ing the first few postoperative days.
Adverse Events
Summary Box
• Side Effects/Complications
–– Mild: Prolonged erythema, milia,
acne, contact dermatitis
–– Moderate: Infection (bacterial, viral,
fungal), hyperpigmentation
–– Severe: Hypopigmentation, hyper-
trophic scarring, ectropion
• Prevention and Treatment
–– Adequate preoperative patient evalu-
ation and education are absolute
essentials to avoid pitfalls and opti-
mize clinical outcomes
–– Preoperative examination to deter-
mine eyelid skin laxity/elasticity to
prevent ectropion
–– Avoidance of pulse stacking, scan
overlapping, and incomplete removal
of partially desiccated tissue to pre-
vent hypertrophic scarring
Summary Box
• During the re-epithelialization process,
an open- or closed-wound technique can
be used
• Ice pack application, anti-­inflammatories
and
pain
medications
should
be
prescribed
• Early recognition and treatment of side
effects (e.g., topical bleaching creams
for hyperpigmentation)
9  Lasers for Resurfacing

146
Side effects associated with ablative laser skin
resurfacing vary and are related to the expertise of
the laser surgeon, the body area treated, and the
skin phototype of the patient (Table 9.3). Certain
tissue reactions, such as erythema and edema, are
expected in the immediate postoperative period
and are not considered adverse events. Erythema
can be intense and may persist for several months
after the procedure. The degree of erythema corre-
lates directly with the depth of ablation and the
number of laser passes performed [3, 16]. It may
also be aggravated by underlying rosacea or der-
matitis. Postoperative erythema resolves spontane-
ously but can be reduced with the application of
topical ascorbic acid which may serve to decrease
the degree of inflammation [62, 63]. Its use should
be reserved for at least 4 weeks after the proce-
dure in order to avoid irritation. Similarly, other
topical agents such as retinoic acid derivatives,
glycolic acid, fragrance-containing or chemical-
containing cosmetics and sunscreens should be
strictly avoided in the early postoperative period
until substantial healing has occurred [16].
Adequate preoperative patient evaluation and
education are absolute essentials to avoid pitfalls
and to optimize clinical outcomes.
Mild side effects of laser resurfacing include
milia formation and acne exacerbation which
may be caused by the use of occlusive dressings
and ointments during the postoperative period,
particularly in patients who are prone to acne [15,
16, 25, 60]. Milia and acne usually resolve spon-
taneously as healing progresses and the applica-
tion of thick emollient creams and occlusive
dressings ceases. Oral antibiotics may be pre-
scribed for acne flares that do not respond to topi-
cal preparations [16, 30, 60]. Contact allergies,
irritant or allergic, can also develop from various
topical medications, soaps, and moisturizers used
postoperatively. Most of these reactions are irri-
tant in nature due to decreased barrier function of
the newly resurfaced skin [16, 64].
Wound infections associated with ablative
laser
resurfacing
include
Staphylococcus,
Pseudomonas, or cutaneous candidiasis and
should be treated aggressively with an appropriate
systemic antibiotic or antifungal agent [61]. The
use of prophylactic antibiotics remains controver-
sial [14]. After CO2 resurfacing, approximately
7% of patients develop a localized or dissemi-
nated form of HSV [16]. These infections develop
within the first postoperative week and can pres-
ent as erosions without intact vesicles because of
the denuded condition of newly lased skin. Even
with appropriate prophylaxis, a herpetic outbreak
Table 9.3  Side effects and complications of ablative laser skin resurfacing
Expected side effects
Complications
Mild
Moderate
Severe
Erythema
Edema
Pruritus
Prolonged erythema
Milia
Acne
Dermatitis
Infection (bacterial, viral, fungal)
Transient hyperpigmentation
Permanent hypopigmentation
Hypertrophic scarring
Ectropion
–– Topical agents such as retinoic acid
derivatives, glycolic acid, salicylic
acid,
fragrance-containing
or
chemical-­containing cosmetics and
sunscreens should be strictly avoided
in the early postoperative period until
substantial healing has occurred
–– Oral antibiotics may be prescribed
for acne flares that do not respond to
topical preparations
–– Any patient undergoing full-face or
perioral ablative resurfacing should
receive antiviral prophylaxis, even if
a history of HSV is denied
–– Postinflammatory
hyperpigmenta-
tion can be hastened with the postop-
erative use of a variety of topical
agents, including hydroquinone, reti-
noic, azeleic, and glycolic acid.
–– Regular sunscreen use is important
during the healing process to prevent
further skin darkening.
R. Wanitphakdeedecha and T. S. Alster

147
still can occur in up to 10% of patients and must
be treated aggressively [17]. In order to prevent
this complication, patients should begin prophy-
laxis by the day of surgery and continue for
7–10 days postoperatively.
The most severe complications associated
with ablative cutaneous laser resurfacing include
hypertrophic scar and ectropion formation [15,
16]. Although the risk of scarring has been sig-
nificantly reduced with pulsed laser technology
(compared to the continuous wave systems),
inadvertent pulse stacking or scan overlapping,
as well as incomplete removal of desiccated tis-
sue between laser passes can cause excessive
thermal injury that could increase the develop-
ment of fibrosis. Focal areas of bright erythema,
with pruritus, particularly along the mandible,
may signal impending scar formation [25, 65].
Ultrapotent (class I) topical corticosteroid prepa-
rations should be applied to decrease the inflam-
matory response. A pulsed dye laser also can be
used to improve the appearance and symptoms of
laser-induced burn scars [65].
Ectropion of the lower eyelid after periorbital
laser skin resurfacing is rarely seen, but if
encountered, usually requires surgical correction
[25]. It is more likely to occur in patients who
have had previous lower blepharoplasty or other
surgical manipulation of the periorbital region.
Preoperative examination is essential to deter-
mine eyelid laxity and skin elasticity. If the infra-
orbital skin does not return briskly to its normal
resting position after a manual downward pull
(snap test), then ablative laser treatment near the
lower eyelid margin should be avoided. In gen-
eral, lower fluences and fewer laser passes should
be applied in the periorbital area to decrease the
risk of lid eversion.
Hyperpigmentation is one of the more com-
mon side effects of cutaneous laser resurfacing
and occurs to some degree in all patients with
darker skin tones (Fig. 9.3) [16, 25]. The reaction
is transient, but its resolution can be hastened
with the postoperative use of a variety of topical
agents, including hydroquinone, retinoic, azeleic,
and glycolic acid. Regular sunscreen use is also
important during the healing process to prevent
further skin darkening. The prophylactic use of
these products preoperatively, however, has not
been shown to decrease the incidence of post-­
treatment hyperpigmentation [13]. Postoperative
hypopigmentation, on the other hand, is often not
observed for several months and is particularly
difficult because of its tendency to be intractable
to treatment. The use of an excimer laser or topi-
cal photochemotherapy to stimulate repigmen-
tation has proven successful in some patients
[66, 67].
Side effects and complications following
Er:YAG laser irradiation are similar to those
observed after CO2 laser treatment, but they dif-
fer in respect to duration, incidence, and severity
[50, 68, 69]. Although greater postoperative ery-
thema is seen after modulated Er:YAG laser
treatment than is usually produced with a short-­
pulsed Er:YAG system, the side effect profile and
recovery period after modulated Er:YAG laser
irradiation remain more favorable than after
multiple-­pass CO2 laser treatment. In an extended
evaluation of 50 patients, investigators reported
complete re-epithelialization in an average of
5 days after dual-mode Er:YAG laser skin resur-
facing with only three patients having prolonged
erythema beyond 4  weeks [68]. In a split-face
comparison of 16 patients after pulsed CO2 and
variable-pulsed Er:YAG laser skin resurfacing,
other investigators reported decreased erythema,
less edema, and faster healing on the Er:YAG
laser-treated facial half [70].
Postinflammatory hyperpigmentation is not
uncommon after any cutaneous laser resurfac-
ing procedure. While hyperpigmentation fol-
lowing modulated Er:YAG laser skin resurfacing
Fig. 9.3  Postinflammatory hyperpigmention following
ablative laser resurfacing
9  Lasers for Resurfacing

148
(mean, 10.4  weeks) can last longer than after
treatment with a short-pulsed Er:YAG laser, it is
not as persistent as that observed after multiple-
pass CO2 laser resurfacing (mean, 16  weeks)
[69]. However, when comparing the most cur-
rent trends in ablative cutaneous laser resurfac-
ing—single-pass CO2 versus multiple-pass,
long-­ulsed Er:YAG laser skin resurfacing—
postoperative healing times and complication
profiles are comparable, even in patients with
darker skin phototypes. In a retrospective review
and analysis of 100 consecutive patients, Tanzi
and Alster [44] showed average time to re-epi-
thelialization was 5.5 days with single-pass CO2
and 5.1  days with long-pulsed Er:YAG laser
resurfacing.
Postoperative
erythema
was
observed in all patients, lasting an average of
4.5 weeks after single-pass CO2 laser treatment
and 3.6 weeks after long-pulsed Er:YAG laser
treatment. Hyperpigmentation was seen in 46%
of patients treated with single-pass CO2 and
42% of patients treated with the long-pulsed
Er:YAG laser ­(average duration 12.7 weeks and
11.4  weeks, respectively). Delayed-onset per-
manent hypopigmentation—a serious complica-
tion that has been observed several months after
multiple-­pass CO2 laser skin resurfacing—has
not yet been reported following single-pass
treatment. To date, only three cases of hypopig-
mentation after modulated Er:YAG laser skin
resurfacing have been reported [71, 72]. Since it
is possible for hypopigmentation to present sev-
eral years postoperatively, clinical studies are
ongoing to determine its true incidence follow-
ing either single-­pass CO2 or modulated Er:YAG
laser skin resurfacing.
Non-ablative Laser Skin
Resurfacing
Indications and Contraindications
Proper patient selection is critical to the success
of non-ablative laser skin remodeling. Patients
with mild-to-moderate facial photodamage or
atrophic scars with realistic expectations of treat-
ment are the best candidates for non-ablative pro-
cedures. Patients seeking immediate improvement
in photodamaged skin or those who desire a dra-
matic result may be less than satisfied with the
overall clinical outcome.
Techniques
Preoperative Management
Adequate preoperative patient evaluation and
education are absolute essentials (Table 9.4). For
patients with a strong history of herpes labialis,
prophylactic oral antiviral medications should be
considered when treating the perioral skin.
Reactivation of prior herpes simplex infection
can occur after non-ablative laser treatment due
to the intense heat produced by the laser or light
source.
Prior to non-ablative laser procedures, sun
exposure should be avoided, particularly when
using shorter-wavelength systems such as the
Summary Box
• Indications
–– Mild facial rhytides, atrophic scars,
and photodamage
• Contraindications
–– Patients
with
unrealistic
expectations
–– Patients with darker skin tones
(skin phototype IV–VI) have a high
incidence
of
postoperative
hyperpigmentation
–– Patients with perpetual sun exposure
–– Patients with history of herpes labia-
lis may require prophylactic oral
antiviral medications.
Summary Box
• Adequate preoperative patient evalua-
tion and education
• Oral antiviral prophylaxis in patients
with history of herpes labialis
R. Wanitphakdeedecha and T. S. Alster

149
pulsed dye laser or intense pulsed-light source.
Unwanted absorption of irradiation by activated
epidermal melanocytes can increase the risk of
side effects, including crusting, blistering, and
dyspigmentation.
Description of the Technique
Most of the non-ablative laser systems emit light
within the infrared portion of the electromagnetic
spectrum (1000–1500 nm). At these wavelengths,
absorption by superficial water-containing tissue
is relatively weak, thereby effecting deeper tissue
penetration [73]. Since non-ablative remodeling
involves creation of a dermal wound without epi-
dermal injury, all of these laser systems employ
unique methods to ensure epidermal preservation
during treatment. These methods typically
include contact cooling handpieces or dynamic
cryogen devices capable of delivering variable
duration spray cooling spurts either before, dur-
ing, and/or after laser irradiation. Since laser
beam penetration and dermal wounding must be
targeted to the relatively superficial portion of the
dermis, contact cooling devices that theoretically
lead to excessive dermal cooling may affect the
level or degree of energy deposition in the skin.
As such, there remains no general consensus con-
cerning which method of cooling is most effica-
cious during treatment.
In general, treatment of facial photodamage
with non-ablative technology does not produce
results comparable to those of ablative CO2 and
Er:YAG lasers; however, many patients are will-
ing to accept modest clinical improvement in
exchange for fewer associated risks and shorter
recovery times.
Pulsed Dye Laser (PDL)
Clinical studies have demonstrated the ability of
585 nm and 595 nm pulsed dye laser (PDL) to
reduce mild facial rhytides with few side effects
[74]. The most common side effects of PDL treat-
ment include mild edema, purpura, and transient
postinflammatory hyperpigmentation. Although
increased extracellular matrix proteins and types I
Table 9.4  Non-ablative laser resurfacing: patient selec-
tion, risks, and precautions
Preoperative patient evaluation
• Is the amount of photodamage amenable to
non-ablative laser skin remodeling? Patients with
mild-to-moderate facial photodamage are the best
candidates for non-ablative procedures. Patients
with severe rhytides and skin laxity may be
disappointed with the overall clinical outcome.
• Does the patient have a history of herpes labialis?
Reactivation of prior herpes simplex infection can
occur with perioral non-ablative laser skin
modeling due to the intense heat produced by the
laser. Patients with a strong history of herpes
simplex labialis may require prophylactic oral
antiviral medication to avoid a postoperative
outbreak.
• What is the patient’s skin phototype? Although the
majority of current non-ablative systems used are
within the mid-infrared range of the
electromagnetic spectrum and not avidly absorbed
by epidermal melanin, patients with darker skin
phototypes may develop postinflammatory
hyperpigmentation after non-ablative treatment.
This temporary reaction may develop due to
inflammation created by concomitant cryogen
spray epidermal cooling.
• Does the patient have realistic expectations?
Patients seeking immediate gratification after a
single non-ablative treatment are not good
candidates as clinical improvement typically occurs
after multiple sequential treatments (usually three
to five) and is often delayed 3–6 months after the
final session. Moreover, patients seeking dramatic
results following non-ablative laser skin techniques
should be dissuaded from treatment as clinical
improvement may be subtle.
Summary Box
• Infrared light (1000–1500 nm) creates a
dermal wound without epidermal injury
• Epidermis is preserved during treatment
by tissue cooling
Summary Box
• 585  nm and 595  nm pulsed dye laser
(PDL) can reduce mild facial rhytides
with few side effects
• Side effects include mild edema, pur-
pura, and transient postinflammatory
hyperpigmentation
9  Lasers for Resurfacing

150
and III collagen and procollagen have been
detected after PDL treatment, the exact mecha-
nism whereby wrinkle improvement is effected
remains unknown [75]. One theory states that vas-
cular endothelial cells damaged by the yellow
laser light release mediators that stimulate fibro-
blasts to produce new collagen fibers [76].
Intense Pulsed Light (IPL) Source
Several investigators have shown successful reju-
venation of photodamaged skin after intense
pulsed light (IPL) treatment [77, 78]. The IPL
source emits a broad, continuous spectrum of light
in the range of 515–1200 nm. Cut-off filters are
used to eliminate shorter wavelengths depending
on the clinical application, with shorter filters
favoring heating of melanin and hemoglobin.
Bitter [78] showed improvement in wrinkling,
skin coarseness, irregular pigmentation, pore size,
and telangiectasia in the majority of 49 patients
treated with a series of IPL treatments (fluences
30–50  J/cm2). In a retrospective review of 80
patients with skin phototypes I–IV, Weiss and col-
leagues [79] reported signs of photoaging, includ-
ing telangiectasias and mottled pigmentation of
the face, neck, and chest, improved by a series of
IPL treatments. While substantial clinical improve-
ment of dyspigmentation and telangiectasia asso-
ciated with cutaneous photodamage is often seen,
neocollagenesis and dermal collagen remodeling
with subsequent improvement in rhytides follow-
ing IPL treatment has been minimal. The effect on
dermal collagen is thought to be induced by heat
diffusion from the vasculature with subsequent
release of inflammatory mediators stimulated by
vessel heating [80].
1064 nm Q-Switched (QS) Neodymium:
YAG (Nd: YAG) Laser
The
1064
nm
quality-switched
(QS)
neodymium:YAG (Nd:YAG) laser was the first
mid-infrared laser system used for non-ablative
cutaneous remodeling. Although absorption of
energy by tissue water is relatively weak at the
1064 nm wavelength, it was possible to achieve
dermal penetrative depths that could potentially
induce neocollagenesis. The nanosecond range
pulse duration of the QS Nd:YAG laser was also
determined to limit significant thermal diffusion
to surrounding structures, thereby making it suit-
able for non-ablative rejuvenation.
In 1997, Goldberg and Whitworth [81] pub-
lished their experience using a 1064  nm
Nd:YAG laser for facial rhytide reduction.
Eleven patients (skin phototypes I, II) with mild
to moderate periorbital or perioral rhytides
underwent treatment on one side of the face
with a QS Nd:YAG laser at a fluence of 5.5 J/
cm2 (3 mm spot size) and CO2 laser ablation on
the contralateral side for comparison purposes.
Pinpoint bleeding was used as the clinical end-
point of QS Nd:YAG treatment. Not unexpect-
edly, all of the CO2-laser irradiated sites
demonstrated significant rhytide improvement,
Summary Box
• Although absorption of energy by tissue
water is relatively weak at the 1064 nm
wavelength, it was possible to achieve
dermal penetrative depths that could
potentially induce neocollagenesis.
• The nanosecond range pulse duration of
the QS Nd:YAG laser was also deter-
mined to limit significant thermal diffu-
sion to surrounding structures, thereby
making it suitable for non-ablative
rejuvenation.
• Treatment is delivered by using the flu-
ences of 2–6 J/cm2 with 3–7 mm spot
size and pulse duration, ranging 6–20 ns.
Summary Box
• The IPL source emits a broad, continu-
ous spectrum of light in the range of
515–1200 nm
• Cut-off filters are used to eliminate
shorter wavelengths depending on the
clinical application, with shorter filters
favoring heating of melanin and
hemoglobin.
• Treatment is delivered by using the flu-
ences of 30–50 40 J/cm2.
R. Wanitphakdeedecha and T. S. Alster

151
whereas only three QS Nd:YAG laser-treated
patients demonstrated improvement. These
patients
also
developed
prolonged
post-­
treatment erythema (lasting up to one month),
suggesting that the amount of dermal wounding
(with subsequent collagen remodeling) was
directly related to the degree of cutaneous
injury. Another study using the QS Nd:YAG
laser for rhytide reduction in 61 patients (242
sites) was conducted using a topical carbon
solution for improved optical penetration of the
1064 nm light [82]. Patients underwent a series
of three monthly QS Nd:YAG laser treatment
sessions at a fluence of 2.5 J/cm2, 7 mm spot
size, and pulse durations, ranging 6–20 ns. At
least slight improvement was seen in 97% of
class I rhytides and 86% of the class II rhytides.
Side effects of treatment were mild and limited,
including transient erythema, purpura, and
postinflammatory hyperpigmentation.
Long-pulsed Nd:YAG laser treatment has more
recently been advocated for skin photorejuvena-
tion. Lee [83] evaluated a combination technique
using a long-pulsed 1064 Nd:YAG laser and long-
pulsed 532 nm potassium-titanyl-­phosphate (KTP)
laser, both separately and combined, for non-inva-
sive photorejuvenation in 150 patients with skin
phototypes I through V. Patients treated with the
combined laser approach showed at least 70%
improvement in erythema and pigmentation and
30–40% improvement in fine rhytides. In the
patient groups treated with monotherapy, patient
satisfaction was greater with KTP laser treatment
than with the Nd:YAG laser primarily due to a
reduction in dyspigmentation and telangiectasias.
1320 nm Nd: YAG Laser
A long-pulsed 1320 nm Nd:YAG laser was the
first commercially available system marketed
solely for the purpose of non-ablative laser skin
remodeling. The 1320 nm wavelength is associ-
ated with a high scattering coefficient that allows
for dispersion of laser irradiation throughout the
dermis. Later models are capable of delivering
energy densities up to 24 J/cm2 with a pulse dura-
tion of 350 μs through a 10-mm handpiece. The
1320 nm Nd:YAG laser handpiece contains three
portals: the laser beam itself, a thermal feedback
sensor that registers skin surface temperature,
and a dynamic cryogen spray apparatus used for
epidermal cooling. When skin surface tempera-
tures are maintained at 40–45  °C, dermal tem-
peratures reach 60–65 °C during laser irradiation,
thereby effecting collagen contraction and neo-
collagenesis. In order to prevent unwanted
sequelae (e.g., blistering) from excessive heat
production, it is imperative that epidermal tem-
peratures be kept lower than 50 °C. A series of
three or more treatment sessions are scheduled at
regular intervals (typically once a month) for
optimal mitigation of fine rhytides [73]. Side
effects of treatment are generally mild and
include transient erythema and edema.
Menaker et al. [84] reported effective rhytide
reduction in an early study using a prototype
1320 nm Nd:YAG laser. Ten patients with peri-
ocular rhytides received three consecutive laser
treatments at bi-weekly intervals. Triple 300 μs
pulses were delivered at 100 Hz and fluence of
32 J/cm2 with a 5 mm handpiece. Epidermal pro-
tection was achieved with application of a 20 ms
cooling spray after a 10 ms preset delay. Patients
were evaluated at 1 and 3 months post-treatment.
Although four of the ten patients showed clinical
improvement in rhytide severity by end-study,
these findings were not statistically significant.
Summary Box
• The 1320 nm wavelength is associated
with a high scattering coefficient that
allows for dispersion of laser irradiation
throughout the dermis.
• A thermal feedback sensor should be used
intraoperatively to select appropriate treat-
ment fluences delivered to the individual
patient’s cutaneous temperature, thereby
maximizing dermal temperatures that
effectively lead to collagen reformation.
• In order to prevent unwanted sequelae
(e.g., blistering) from excessive heat
production, it is imperative that epider-
mal temperatures be kept lower than
50 °C.
9  Lasers for Resurfacing

152
Similarly, the slight homogenization of collagen
noted on histology at 1 and 3 months following
treatment was not statistically significant and
inconsistent with the clinical findings.
In another study, Kelly et al. [85] treated 35
patients with mild, moderate, and severe rhytides
using a 1320 nm Nd:YAG laser. Three treatments
were delivered at 2-week intervals using fluences
ranging 28–36  J/cm2 with a 5  mm spot size.
Cryogen spray cooling was applied in 20–40 ms
spurts with 10 ms delays. Patients were evaluated
at 12 and 24 weeks following treatment with sta-
tistically significant improvement noted in all
clinical grades after 12  weeks. Only the most
severe rhytides; however, showed persistent
improvement 24 weeks following treatment.
Goldberg devised two similar studies to exam-
ine the effectiveness of the 1320 nm Nd:YAG laser
for the treatment of facial rhytides. In the first
study, ten patients with skin types I–II and class I–
II rhytides in the periorbital, perioral, and cheek
areas were treated [86]. Four treatments were
administered over a 16-week period using fluences
of 28–38 J/cm2 with a 30% overlap and a 5 mm
spot size. One or two laser passes were applied to
achieve the treatment endpoint of mild erythema.
Skin surface temperatures were limited to 40–48 °C
using the aforementioned dynamic cooling spray in
order to provide epidermal protection, whilst
effecting
dermal
temperatures
ranging
60–70 °C. Six months after treatment, two patients
showed no clinical improvement, six showed
‘some’ improvement, and two showed ‘substantial’
improvement. This study emphasized several key
points in non-­ablative laser resurfacing. It sug-
gested a thermal feedback sensor is best used intra-
operatively with this technology in order for
appropriate treatment fluences to be selected based
upon the individual patient’s cutaneous tempera-
ture, thereby maximizing dermal temperatures that
effectively
lead
to
collagen
reformation.
Furthermore, longer follow-up periods are usually
required to fully appreciate the effect of serial treat-
ment sessions on dermal collagen stimulation. In
the second study, ten patients underwent full-face
treatments with the 1320  nm Nd:YAG laser at
3–4  week intervals [87]. As with the first study,
treatment results were inconsistent—four patients
showed no improvement, four showed some
improvement, and two showed substantial improve-
ment in facial rhytides and overall skin tone.
Others also studied the 1320 nm Nd:YAG laser
for treatment of facial rhytides in ten women [88].
Full-face treatment was administered to three
patients, whereas two patients had periorbital
treatment, and five patients received perioral
treatment. Laser fluences of 30–35  J/cm2 were
delivered in triple 300 μs pulses at a repetition rate
of 100 Hz. Dynamic cryogen spray cooling was
used with a 30 ms spurt and a 40 ms delay between
cryogen delivery and laser irradiation. A thermal
sensor was also used to maintain peak surface
temperatures in the range of 42–45 °C in order to
avoid excessive tissue heating. Treatments were
administered twice a week over a period of
4  weeks for a total of eight treatment sessions.
Only two out of ten patients expressed satisfaction
with their final result despite clinician evaluations
showing significant improvement in five of ten
patients and fair improvements in another three.
Moreover, there was no correlation between his-
tologic changes and the degree of subjective clini-
cal improvement as judged by the patients.
A more recent study by Fatemi et  al. [89]
demonstrated that the 1320  nm Nd:YAG laser
produced mild subclinical epidermal injury that
could potentially lead to enhanced skin texture
and new papillary collagen synthesis by stimula-
tion of cytokines and other inflammatory media-
tors. Thus, the long-term histologic improvement
seen in photodamaged skin may not be based
solely on direct laser heating of collagen, but
through stimulation of cytokine release by heat-
ing the superficial vasculature. In addition, the
histologic findings suggested that multiple passes
with fluence and cooling adjusted to a Tmax of
45–48 °C can yield improved clinical results, as
compared to those specimens in which epidermal
temperatures above 45 °C were not achieved.
1450 nm Diode Laser
Summary Box
• The fluences ranging 10–20  J/cm2
should be applied in a single nonover-
lapping pass with 6-mm spot size.
R. Wanitphakdeedecha and T. S. Alster

153
The 1450  nm mid-infrared wavelength diode
laser targets dermal water and penetrates the skin
to an approximate depth of 500 μm. This low-­
power laser system achieves peak powers in the
10–15 W range with relatively long pulse dura-
tions of 150–250 ms. Because of these long expo-
sure times, epidermal cooling must be delivered
in sequence during the application of laser energy
in order to avoid excessive thermal buildup
within the superficial layers of the skin.
Goldberg et al. [90] reported on the effects of
1450 nm diode laser irradiation in 20 patients with
class I–II rhytides. Two to four treatment sessions
were delivered with 6-month follow-up evaluation.
Patients were treated with laser and cryogen spray
cooling on one facial half and cryogen spray cool-
ing alone on the contralateral side. On the laser-
treated facial halves, seven did not demonstrate any
improvement, ten showed mild improvement, and
three had moderate improvement. None of the sites
treated with cryogen alone showed any improve-
ment after 6 months. Side effects of treatment were
mild and included transient erythema, edematous
papules, and one case of postinflammatory hyper-
pigmentation persisting for 6 months. The authors
concluded that the 1450 nm diode laser was effec-
tive for treatment of mild to moderate facial rhytides
with minimal morbidity. Additionally, their study
demonstrated that non-ablative laser treatment
alone was responsible for the clinical improvements
and that the non-specific injury induced by cryogen
spray cooling could not effect the changes seen.
Hardaway and colleagues [91] demonstrated
statistically significant mean wrinkle improve-
ment of 2.3 (range 0–4, with four representing
severe wrinkling) at baseline to 1.8 at 6 months
following a series of three 1450 nm diode laser
treatments. They concluded that although the
1450 nm diode laser is capable of targeting der-
mal collagen and stimulating fibrosis, clinical
improvement of rhytides was mild and did not
correlate well with the degree of histologic
change noted in previous studies.
In a controlled clinical and histologic study,
Tanzi and Alster [92] demonstrated improvement
in mild to moderate perioral or periorbital rhytides
in 25 patients treated with four consecutive
1450  nm diode laser treatments using fluences
ranging 15–20 J/cm2 with a 4 mm spot size. Peak
clinical improvement was seen 6 months after the
series of laser treatments. The periorbital area was
more responsive to laser treatment than the perioral
area—a finding consistent with results obtained
using other non-ablative laser systems (Fig. 9.4a,
b). Side effects were limited to transient erythema,
edema, and postinflammatory hyperpigmentation.
In a separate controlled study performed by the
same group, 20 patients with transverse neck lines
received three consecutive monthly treatments
using a long-pulsed 1450  nm diode laser [93].
a
b
Fig. 9.4  1450 nm
long-pulsed diode laser
(a) before and (b) after
9  Lasers for Resurfacing

154
Modest improvements in appearance and texture of
the transverse neck lines was reported, as measured
by blinded clinical assessments and through three-
dimensional in  vivo microtopography (PRIMOS
Imaging System; GFM, Germany). Mean fluences
of 11.6 J/cm2 were used with a 6 mm spot size and
50 ms total cryogen.
Due to the marked dermal remodeling effect
of the long-pulsed 1320-nm Nd:YAG and 1450-­
nm diode lasers, Tanzi and Alster [94] reported
the long-term clinical and histologic results of
these systems on atrophic facial acne scars in 20
patients. Facial halves were randomly assigned to
received three consecutive monthly treatments
with a 1320-nm Nd:YAG laser (CoolTouch;
CoolTouch Corp., Auburn, CA) on one side and a
1450-nm diode (SmoothBeam; Candela Corp.,
Wayland, MA) on the contralateral. The 1450-nm
diode laser was used at fluences ranging 9–14 J/
cm2 (average 11.8  J/cm2, 6-mm spot size) in a
single nonoverlapping pass; whereas, the 1320-­
nm Nd:YAG laser was used of fluences ranging
12–17  J/cm2 (average 14.8  J/cm2, 10-mm spot
size) in two passes. Mild to moderate clinical
improvement was observed in the majority of
patients. Patient satisfaction scores and in  vivo
microtopography measurements paralleled the
photographic and histopathologic changes seen
without significant side effects or complications.
The 1450-nm diode laser showed greater clinical
scar response at the parameters studied.
1540 nm Erbium: Glass Laser
The 1540  nm erbium-doped phosphate glass
laser is another mid-infrared range laser that has
been used for amelioration of fine facial rhytides
and atrophic facial scars. Similar to other infrared
laser systems, the erbium:glass laser targets intra-
cellular water and penetrates tissue to a depth of
0.4–2 mm [73]. The 1540 nm wavelength exerts
less effect on epidermal melanin as do the
1320 nm and 1450 nm lasers—a potential advan-
tage of this system when treating tanned or
darker-skinned patients. Mordon et al. [95] stud-
ied the 1540 nm erbium:glass laser on hairless rat
abdominal skin with pulse train irradiation (1.1 J,
3 Hz, 30 pulses) and varying cooling tempera-
tures (+5  °C, 0  °C, −5  °C). Biopsies obtained
after 1, 3, and 7 days following treatment dem-
onstrated fibroblast proliferation and new colla-
gen synthesis as early as the third day. The
authors concluded that the erbium glass system
held promise for treating facial rhytides because
of its high water absorption and reduced tissue
scattering effect that limits energy deposition to
the upper dermis where most solar elastosis is
evident.
Ross et  al. [96] studied the effect of the
1540 nm erbium:glass laser with a sapphire cool-
ing handpiece on the preauricular skin of nine
patients. A 5 mm collimated beam was used to
deliver fluences of 400–1200 mJ/cm2. Epidermal
necrosis and scar formation were noted at the
highest pulse energies. Several key points were
illustrated by this study; namely, that denatured
collagen located deep in the dermis (more than
600 μm) is associated with granuloma formation
and that the peaks of heating and cooling with
non-ablative laser remodeling are in proximity,
by necessity, since maximum wrinkle reduction
may be achieved by a zone of thermal injury
100–400 μm beneath the skin surface.
Lupton et  al. [97] reported their use of a
1540 nm erbium:glass laser to treat 24 patients
with fine periorbital and perioral rhytides.
Patients underwent a series of three treatments on
a monthly basis using a 4 mm spot size, 10 J/cm2
fluence, and 3.5  ms pulse duration. Epidermal
protection was achieved with concomitant appli-
cation of a contact sapphire lens cooled to
5  °C.  Histologic specimens demonstrated
increased dermal fibroplasia at 6 months after the
Summary Box
• The treatment should be performed on a
monthly basis for three to five sessions
using a 4  mm spot size, 10  J/cm2 flu-
ence, and 3.5 ms pulse duration.
• Epidermal protection was achieved with
concomitant application of a contact
sapphire lens cooled to 5 °C.
R. Wanitphakdeedecha and T. S. Alster

155
series of laser treatments. Average clinical scores
were improved at 1 and 6 months following the
third treatment session with slightly better results
observed in the periorbital regions. Side effects
of treatment were mild and included transient
erythema and edema.
Fournier and colleagues [98] subsequently
treated 42 patients (skin phototypes I–IV) with
five consecutive 1540 nm diode laser treatments
at 6-week intervals. Patients were evaluated using
clinical data, patient satisfaction surveys, digital
photography, ultrasound imaging, and profilom-
etry data from silicone imprints. The majority of
patients demonstrated modest improvement in
objective and subjective measurements which
remained stable throughout the 14-month evalua-
tion period.
Radiofrequency (RF) Device
A monopolar radiofrequency device (ThermaCool
TC; Thermage Inc., Hayward, CA) has also been
studied for deep dermal heating with subsequent
tightening of photodamaged skin. Unlike a laser
in which light energy is converted into heat, the
radiofrequency device generates electric current
which produces heat through dermal resistance.
The energy is delivered to the skin through a spe-
cialized treatment tip with a capacitive coupling
membrane which allows for uniform delivery of
heat over the entire treatment area. Epidermal
protection is provided by simultaneous cryogen
cooling within the contact treatment tip. Using
this technique, a reverse thermal gradient is gen-
erated. The depth of heat penetration is depen-
dent upon the size and specifics of the detachable
treatment tip and can be changed according to the
clinical application. Preliminary animal studies
demonstrated selective dermal heating at the lev-
els of the papillary dermis and as deep as the sub-
cutaneous fat [80]. Ruiz-Esparza and Gomez [99]
reported facial tissue tightening in 14 of 15
patients 3 months after a single radiofrequency
treatment with minimal side effects.
Alster and Tanzi [100] demonstrated signifi-
cant improvement in cheek and neck skin laxity
in 50 patients received one treatment with a
radiofrequency device (ThermaCool; Thermage
Corp., Hayward, CA) at fluences ranging
97–144 J/cm3 (level of 13.6–16; average of 130 J/
cm2) on the cheeks and 74–134 J/cm3 (average
110 J/cm3) on the neck in a single, nonoverlap-
ping pass. Patient satisfaction scores paralleled
the clinical improvement observed with side
effects limited to transient erythema, edema, and
rare dysesthesia. The tightening continued to be
evident 6 months after a single treatment.
Another RF device, Polaris WR™ (Syneron
Medical Ltd., Israel), which combines bipolar RF
and diode laser energies has been developed in an
attempt to address both facial rhytides and skin
laxity. Doshi and Alster [101] demonstrated mod-
est clinical improvement of facial rhytides and
skin laxity in 20 patients by using optical ener-
gies of 32–40 J/cm2 (mean 36.4 J/cm2) and radio-
frequencies of 50–85 J/cm3 (mean 67.4 J/cm3) for
three treatments at 3-week intervals. Side effects
were mild and limited to transient erythema and
edema. No scarring or pigmentary alteration was
seen.
Postoperative Management
Since the epidermis remains intact following
non-ablative laser skin remodeling, postoperative
care is minimal. Some patients experience mild
erythema and edema lasting less than 24 h.
Summary Box
• The treatment should be delivered at the
fluences ranging 90–150 J/cm3 in a sin-
gle, nonoverlapping pass.
• When combining treatment with other
lasers or light sources, the fluences of
RF can be reduced.
Summary Box
• Minimal to no care except sun
avoidance
9  Lasers for Resurfacing

156
Adverse Events
Rarely, postoperative hyperpigmentation can
develop several weeks after non-ablative skin
remodeling and is more likely to be experienced
by patients with darker skin tones and/or tans. In
some cases, investigators demonstrated an asso-
ciation of post-treatment hyperpigmentation with
excess intraoperative epidermal cryogen cooling
[92]. Although always transient, topical bleach-
ing agents and light glycolic acid peels can has-
ten
the
resolution
of
postinflammatory
hyperpigmentation.
In the weeks following a series of non-ablative
laser procedures, in-office visits can help identify
patient concerns and increase the overall satisfac-
tion with treatment. Clinical improvements after
a series of non-ablative laser procedures may
take weeks to realize, thus reassurance by the
laser surgeon regarding the patient’s progress can
be particularly important.
Fractional Laser Skin Resurfacing
Indications and Contraindications
Over the past decade, a novel approach in skin
resurfacing termed fractional photothermolysis
has been developed to address the shortcomings
associated with skin rejuvenation using pulsed
and scanned ablative and non-ablative lasers
and light sources [102]. Although dramatic clin-
ical improvement can be achieved with these
ablative lasers, patients are often hesitant to pur-
sue this treatment option because of the extended
postoperative recovery period and inherent risks
of the procedure. Non-ablative lasers and light
sources, on the other hand, have demonstrated
modest efficacy in the non-invasive treatment of
mild facial rhytides and atrophic scarring with
minimal side effects, but require multiple treat-
ments with delayed and often inconsistent clini-
cal results. Due to a need for more noticeable
clinical improvement than these latter nonabla-
tive systems could provide, fractional photo-
thermolysis was introduced into the skin
resurfacing market to treat patients with rhyt-
ides, dyspigmentation, and atrophic scars [103–
108] (see Chap. 10). Currently, a variety of
ablative and nonablative fractionated lasers
have been developed and are being used to treat
a wide range of conditions. Fractionated tech-
nology has virtually replaced pulsed and
scanned ablative and nonablative systems due in
large part to their excellent clinical effects and
low risk profiles [109].
Summary Box
• Side Effects/Complications
–– Transient postinflammatory hyper-
pigmentation in patients with darker
skin phototypes or tans
• Prevention and Treatment
–– Topical bleaching agents and light
glycolic acid peels can hasten the
resolution
of
postinflammatory
hyperpigmentation.
Summary Box
• Indications
–– Mild to moderate facial rhytides and
photodamage
–– Atrophic scars
–– Superficial epidermal/dermal lesions
–– Melasma
• Contraindications
–– Patients with unrealistic expectations
–– Patients with darker skin tones (skin
phototype IV–VI) at greater risk of
postoperative hyperpigmentation
–– Patients with perpetual sun exposure
–– Patients with active bacterial, viral,
fungal infection or inflammatory
skin conditions involving treatment
areas
–– Patients with history of herpes labia-
lis may require prophylactic oral
antiviral medications.
–– Concomitant isotretinoin use could
potentially lead to an increased risk
of hypertrophic scarring.
R. Wanitphakdeedecha and T. S. Alster

157
Nonalative Fractional Skin Resurfacing
Nonablative fractional skin resurfacing (NAFR),
typically involves the use of mid-infrared wave-
lengths (1440 nm, 1550 nm, 1927 nm) emitted
by a variety of laser sources (e.g., erbium, thu-
lium) to create microscopic non-contiguous col-
umns of thermal injury in the dermis (referred to
as microscopic thermal zones or MTZ) at depths
of 200–500 μm surrounded by zones of viable
tissue at 200- to 300  μm intervals [102]. The
spatially precise columns of thermal injury pro-
duce localized epidermal necrosis and collagen
denaturation at 125 or 250  MTZ/cm2 [110].
Because the tissue surrounding each MTZ is
intact, residual epidermal and dermal cells con-
tribute to rapid healing. Maintenance of the stra-
tum corneum ensures continued epidermal
barrier function. Histologic evaluation of the
MTZ demonstrates ­homogenization of the der-
mal matrix and the presence of epidermal
necrotic debris (MEND), representing the extru-
sion of damaged epidermal keratinocytes by
viable keratinocytes at the lateral margin of the
MTZ [102]. Microscopic epidermal necrotic
debris exfoliates over the next several days, pro-
ducing a bronzed appearance to the skin. The
wound healing response differs from that after
ablative laser techniques because the epidermal
tissue that is spared between thermal zones con-
tains viable transient amplifying cells capable
of
rapid
re-epithelialization.
Furthermore,
because the stratum corneum has a low water
content, it remains intact immediately after
treatment. Therefore, the wound created by
fractional resurfacing is unique—not simply
that of an ablative laser used to make “holes” in
the skin. In addition, fractional resurfacing can
provide an advantage over purely non-ablative
laser treatments due to the gradual exfoliation of
the epidermis with resultant improvement in
superficial dyspigmentation (Fig.  9.5a, b).
Because only a fraction of the skin is treated
during a single session, a series of fractional
resurfacing treatments is required to achieve
optimal clinical improvement.
Ablative Fractional Skin Resurfacing
Although the NAFR system is patient-friendly
and is associated with minimal recovery, its
clinical outcomes in the treatment of rhytides
and scars are often less impressive than that
achieved after ablative fractional resurfacing
(AFR) [109, 111, 112]. AFR systems, including
carbon dioxide (CO2) [113], erbium-doped
yttrium aluminum garnet (Er:YAG) [114], and
erbium-doped yttrium scandium gallium garnet
lasers [115], were developed in an attempt to
achieve the clinical results provided with full-
field ablative resurfacing lasers with greater
safety profiles. These devices cause micro-
scopic treatment zones (MTZs) of complete
epidermal ablation with variable amounts of
dermal coagulation. As with the NAFR sys-
tems, fractional delivery of an ablative laser
source results in a microscopic pattern with
spatial separation of columns of thermally
a
b
Fig. 9.5  Fractional photothermolysis (a) before and (b) after
9  Lasers for Resurfacing

158
affected epidermal and dermal tissue. Although
the results are not as effective as with full-field
(pulsed/scanned) ablative laser resurfacing, sig-
nificant improvement in rhytides, atrophic
scars, and laxity of the skin has been demon-
strated after one or two treatments with the
fractional ablative lasers [116–118].
Techniques
Preoperative Management
Adequate preoperative patient evaluation and
education are essential. Sun exposure should be
avoided prior to treatment in order to decrease
risk of postoperative dyspigmentation. For
patients with a history of herpes labialis, prophy-
lactic oral antiviral medications should be con-
sidered when treating perioral skin. Reactivation
of prior herpes simplex infection can occur
despite absence of an external wound due to the
intense dermal heat produced by the laser.
Description of the Techniques
The treatment areas should be cleansed free of
debris (including dirt, makeup, and powder)
using a mild cleanser and 70% alcohol. A topical
anesthetic cream is often applied to the treatment
sites for 60 min before treatment. While the first
generation NAFL device required that a water-­
soluble blue tinted tracking dye solution be
applied to the skin during treatment, current
NAFL systems do not. NAFL treatment is deliv-
ered with concomitant forced air cooling at
energy settings ranging 25–70 mJ. Total energies
of 2–6 kJ are typically applied for full face treat-
ment. Re-treatments with gradually higher flu-
ences should be performed at 4  week intervals
until patients are satisfied with clinical outcomes
(typically three to five sessions are necessary to
produce substantial clinical improvement). For
AFR, the fractional CO2 laser is typically used
with a 950 μs pulse duration and 12.5 mJ energy,
creating average vaporization and coagulation
depths of 160 and 350 μm, respectively. The frac-
tional Er:YAG laser is often applied at a 350 μs
pulsed duration and 14  mJ energy, producing
average vaporization and coagulation depths of
65 and 100 μm, respectively. Retreatment using
identical treatment techniques and parameters
can be performed at 6–8 week intervals as needed.
Postoperative Management
Summary Box
Description of the techniques: NAFR
• Laser treatment is delivered with con-
comitant forced air cooling. Energy set-
tings of 25–70  mJ at densities of
125–250 MTZ/cm2 are applied to treat-
ment areas in 8–10 passes (total energy
applied per session: 2–6 kJ)
Summary Box
• Adequate preoperative patient evalua-
tion and education
• Oral antiviral prophylaxis in patients
with history of herpes labialis
• Topical anesthetic cream application
(60 min) prior to NAFL
• Additional anesthesia (e.g., oral analge-
sics, IV or IM medications) for AFL
Summary Box
• Mild cleanser, thermal spring water spray
mist, and moisturizer several times daily
for the first few postoperative days
Description of the techniques: AFR
• Fractional CO2 laser with 950  μs pulse
duration and 12.5 mJ energy creates aver-
age depths of vaporization and coagula-
tion of 160 and 350 μm, respectively
• Fractional Er:YAG laser with 350  μs
pulsed duration and 14 mJ energy pro-
duces average depths of vaporization
and coagulation of 65 and 100  μm,
respectively
R. Wanitphakdeedecha and T. S. Alster

159
Patients are instructed to use a mild cleanser,
thermal spring water spray mist, and moisturizer
several times daily for the first few days after
each treatment session (or as long as bronzing/
xerosis is apparent).
Adverse Events
Side effects of fractional resurfacing are typically
mild and transient, including erythema, periocu-
lar edema, xerosis, and slight darkening of the
skin (bronzing) during desquamation of the
microscopic epidermal necrotic debris [112,
113]. Erosions are uncommon and can be man-
aged by liberal application of a healing ointment
or plain petrolatum with cool wet compresses
every 2–3 h. While permanent pigmentary altera-
tion and scarring have not been reported after
NAFR treatment, use of an aggressive treatment
protocol with high density microscopic thermal
zones increases the risk of visible epidermal
ablation and its associated side effects.
In clinical practice, the factors in choosing a
particular treatment are based not only on the
anticipated treatment efficacy, but also on the
risk of adverse effects, recovery time, and pain
acceptability. A clinical study of patients with
darker skin [118] demonstrated that fractionated
Er:YAG laser treatment produced one-third the
coagulation depth of fractionated CO2 laser
treatment, but provided equivalent clinical out-
comes and healing processes. In addition, the
fractionated CO2 laser was associated with more
pain during treatment. Although non-significant
differences in post-inflammatory hyperpigmen-
tation (PIH) rates were seen between the two
systems, there was a trend toward higher PIH
risk with the fractionated CO2 laser. Taking all
risks and benefits into account, the fractionated
Er:YAG laser is often reported as a better treat-
ment choice for Asian patients. The prevention
of PIH includes the application of topical bleach-
ing agents before and after laser treatment, the
use of a cooling device during treatment to pro-
tect the epidermis from laser heat, and the dili-
gent application of sunscreen after treatment
[119, 120]. Additional research is ongoing to
determine optimal treatment parameters and the
long-term benefits and sequelae of fractionated
laser resurfacing in a variety of conditions and
skin phototypes.
Conclusion
Ablative laser skin resurfacing has revolution-
ized the approach to photodamaged facial
skin. Technology and techniques continue to
evolve, further enhancing the ability to achieve
substantial clinical improvement of rhytides,
scars, and dyspigmentation with reduced post-
operative morbidity. Utilizing proper tech-
nique and treatment parameters, excellent
clinical results can be obtained with any one
or combination of CO2 and Er:YAG laser sys-
tems available. Therefore, the best choice of
laser ultimately depends on the operator’s
expertise, clinical indication, and individual
patient characteristics. Regardless of the type
of ablative resurfacing laser used, the impor-
tance of careful postoperative follow-up can-
not be overemphasized.
For those patients who desire a less aggres-
sive approach to photorejuvenation than abla-
tive laser skin resurfacing, non-ablative
dermal remodeling or fractional laser photo-
thermolysis represent viable alternatives for
patients willing to accept modest clinical
improvement in exchange for ease of treat-
ment and a favorable side-effect profile.
Treatments are typically delivered at monthly
intervals with progressive clinical improve-
ment observed after each session. Recent
Summary Box
• Side Effects/Complications
–– Erythema, periocular edema, xerosis,
and slight darkening of the skin
(bronzing)
–– Post-inflammatory hyperpigmenta-
tion in patients with darker skin tones
• Prevention and Treatment
–– Ice pack application for first 48 h
–– Keep skin well-hydrated/moisturized
for 48–72 h (or until xeroxis/bronz-
ing disappears).
–– Strict ultraviolet light avoidance and
daily use of sunscreen
9  Lasers for Resurfacing

160
advances in fractional laser technology, in par-
ticular, have resulted in clinical effects approx-
imating those of ablative laser treatment
without its associated complications and risks.
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165
© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Fractional Photothermolysis
Dieter Manstein, Hans-Joachim Laubac,
Sofia Iglesia, Alaleh Dormishian,
Ali Rajabi-­Estarabadi, and Keyvan Nouri
Abstract
Traditional Resurfacing techniques are well
established treatments for modifying appear-
ances and characteristics of the skin, but their
drawbacks include prolonged procedural
downtime, scarring risk and long-lasting hyper-
pigmentation. Fractional Photothermolysis
(FP) overcomes these drawbacks through the
generation of patterns of microscopic treatment
zones (MTZs), while leaving the surrounding
skin undamaged, allowing for quick healing
and limits the development of inflammation
and fibrosis. The ability of delivering multiple
FP treatments and with the manipulation of the
laser parameters allows the physician to choose
between the two types of FP and customize the
treatment regime that is best fit for the patients’
needs and expectations. Non- Ablative gener-
ates MTZs by thermal coagulation while
Ablative FP generates MTZs by vaporizing
microscopic zones of tissue which results in
immediate tissue loss and a surrounding zone
of coagulated tissue. FP techniques include a
wide spectrum of dermatological diseases that
could be treated through the facilitation of drug
and cell delivery into the skin. FP demonstrates
to be an effective home-use product for self-
treating wrinkles, 87% of patients have reported
improvement in the appearance of wrinkles in a
1–3 months period. The future for FP may
include specialties beyond dermatology.
Keywords
Fractional Photothermolysis · Microscopic
Treatment Zones · Ablative Fractional
Photothermolysis · Non-Ablative Fractional
Photothermolysis · Dermatological Laser
Therapy · Fractional resurfacing ·
Microdermal Treatment Zones · Optical
penetration depth · Thermal coagulation ·
Vaporizing microscopic zones
Abbreviations
FP
Fractional photothermolysis
FR
Fractional resurfacing
MEND
Microscopic epidermal-necrotic-debris
MTZ
Microthermal treatment zone
OPD
Optical penetration depth
D. Manstein (*)
Wellman Center for Photomedicine, Massachusetts
General Hospital, Harvard Medical School,
Boston, MA, USA
e-mail: dmanstein@partners.org
H.-J. Laubac
Dermatologische Abteilung, Universitäre Krankenhäuser
von Gen, Genf, Schweiz
S. Iglesia · A. Dormishian · A. Rajabi-Estarabadi
K. Nouri
Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine,
Miami, FL, USA
10

166
Introduction and Background
• Traditional resurfacing techniques have their
drawbacks
Traditional ablative resurfacing techniques
and non-ablative laser and light procedures are
well-established treatment modalities for modi-
fying the appearance and characteristics of skin
[1–3]. However, patients have become hesitant to
accept the side effects and risks associated with
traditional ablative techniques [4]. The main con-
cerns of ablative resurfacing are prolonged pro-
cedural downtime, risk of scarring, and the
incidence of delayed, long-lasting hypopigmen-
tation, also known as ‘alabaster skin’ [5, 6].
Further, traditional non-ablative techniques for
collagen remodeling have shown inconsistent
and often unpredictable results, frequently lead-
ing to unsatisfied patients and treating physicians
[7]. For a detailed description of the advantages
and disadvantages of traditional resurfacing tech-
niques, see Chaps. 9, 12, and 13 of this volume.
• Fractional photothermolysis’ (FP) is a rela-
tively new concept introduced by Manstein
et al. in 2004.
• FP is based on generating patterns of micro-
scopically small lesions, also called ‘micro-
scopic treatment zones’ (MTZs).
• FP has become an established treatment—
technique in dermatological laser therapy.
To overcome the drawbacks of these tradi-
tional resurfacing approaches, fractional photo-
thermolysis (FP) was developed by Manstein
et  al. [8]. In contrast to traditional laser tech-
niques, which provide laser exposure to the entire
skin surface, FP creates a pattern of microscopi-
cally small, 3-dimensional treatment zones
(microscopic treatment zones or MTZs) while
leaving the skin surrounding each of these MTZs
substantially undamaged (Fig.  10.1). The term
“fractional photothermolysis” was selected to
express that only a fraction (lat: frangere, to break
into pieces) of the skin is exposed to light (photo)
to thermally damage or destroy (thermolysis)
small treatment zones. FP procedures have been
demonstrated to successfully treat a wide variety
of aesthetic and dermatological indications.
There is a broad range of possible treatment set-
tings that may be used to generate the resulting
wound healing response. FP can be delivered in
multiple treatments, each providing incremental
improvement within the limits of individual
patient’s tolerance for downtime and side effects.
Therefore, FP gives the physician additional
options to provide a customized treatment regime
that is suited to fit their patient’s needs and expec-
tations. FP procedures have become increasingly
popular over the past few years and have become
an established concept in dermatological laser
therapy. The rapid proliferation of publications in
the dermatological literature related to FP is an
indication of the significant impact that FP had
on the field (Fig. 10.2). The success of FP is also
documented by the wide variety of commercially
available FP devices; virtually all dermatological
laser device companies currently have at least
one FP device in their product portfolio (Tables
10.1 and 10.2).
Fig. 10.1  Concept of fractional photothermolysis. An
array of microscopically small zones of thermal injury, so
called MTZs (microscopic treatment zones, gray arrows),
is generated by multiple, focused laser pulses. Each of the
MTZ is surrounded by undamaged skin (orange, circular
arrow), allowing for fast repair (Laubach and Manstein [9])
D. Manstein et al.

167
• Individual MTZs are typically so small that
they induce neither extended inflammation
nor fibrosis.
• MTZs heal quickly due to their small cross
section and the presence of adjacent unharmed
tissue.
• MTZs can extend down to the deep reticular
dermis for certain laser parameters.
350
300
250
200
150
100
Annual Citations
50
0
1980
1985
Sum of SP Citations Per Year
Sum of FP Citations Per Year
Citations of Selective and Fractional photothermolysis
1990
1995
2000
Year
2005
2010
2015
2020
Fig. 10.2  Annual citations of the original article for frac-
tional photothermolysis (FP) and selective photothermol-
ysis (SP). Data obtained from ‘ISI Web of Knowledge™’,
Thompson Reuters. The rapid proliferation of FP related
publications indicates an increasing impact of this concept
in the field of dermatology. The annual citations of FP
have already reached a level comparable to that of
SP. Further analysis reveals that recently SP citations are
increasingly for non-dermatological indications, e.g., in
ophthalmology or otorhinolaryngology. In contrast, FP
citations are so far generally limited to dermatological
indications (SP: Anderson and Parrish [10]; FP: Manstein
et al. [8])
Table 10.1  Characteristics of selected, commercially available non-ablative fractional photothermolysis (nFP)
devices, including manufacturer, device name, laser type, emitted wavelength, nominal spot size and range of energy/
MTZ. This table is not comprehensive, the pulse duration listed device parameters were obtained by manufacturer sur-
vey and are also subject to change
Company
Device
Laser type
Wavelength
[nm]
Delivery
Spot size [μm/
MTZ]
Energy [mJ/
MTZ]
Pulse duration
[ms]
Cynosure
Affirm
Nd:YAG
1440 ± 1320
Stamping
100–150
up to 4.1
1, 1.5, 2
Lutronic
Mosaic
Erbium
1550
Scanned
240 mJ
4–40
0.5–4.5
Stamping
Palomar
Lux1540
Erbium
1540
Stamping
70 mJ per
microbeam
up to 100
5, 10
Palomar
Lux 1440
Nd:YAG
1440
2–240
0.25–5
Quanta
Matisse
Er:Glass
1540
Stamping
up to 20
4–14
Sellas
Sellas
1550
Erbium
1550
Scanned
312–1000
1–30
0.5
Stamping
Solta
Fraxel
re:fine
Erbium
1410
Rolling
4–70
5–20
Solta
Fraxel
Er:Glass
1550/1927
Rolling
135/up to 600
4–70, 5–20
0.015–3
re:store
(Former
SR 1550)
Erbium
1440
Clear+
Brilliant
Diode
DUAL
Erbium+
thulium
10  Fractional Photothermolysis

168
Table 10.2  Characteristics of selected, commercially available ablative fractional photothermolysis (FP) devices, including manufacturer, device name, laser type, emitted
wavelength, average optical emission power, nominal spot size and range of energy/MTZ. This table is not comprehensive, the pulse duration listed device parameters were
obtained by manufacturer survey and are also subject to change
Company
Device
Laser
Wavelength [nm]
Delivery
Power (W)
Spot size [μm/
MTZ]
Energy [mJ/MTZ] Pulse duration [ms]
Alma
Pixel CO2
CO2
10,600
Scanned stamping
40, 70
250
2500 mJ/p
50–300
Harmony (2940)
Er:YAG
2940
Pixel Omnifit
CO2
10,600
AMT
Touch Cell
CO2
10,600
Scanned stamping
30
200
Candela
QuadraLase
CO2
10,600
Scanned stamping
20
Cutera
Pearl Fractional
YSGG
2790
Scanned stamping
300
60–320
600
Cynosure
Smart Skin
CO2
10,600
Scanned stamping
30
0.2–20
Affirm CO2
Deka
SmartXide
CO2
10,600
Scanned stamping
50
300
0.2–80
DOT HP
Ellipse
Juvia
Fractional
CO2
10,600
Scanned stamping
0.1–15
500
5–15
5–7
Focus Medical
NaturalLase Er
Er:YAG
2940Up to 24 J/
cm2
350
Fotona
SP Pulse
Nd: YAG/
Er:YAG
1064/2940
35–80
Up to 600 J/cm2
0.1–300
SP Dualis
Nd: YAG/
Er:YAG
1064/2940
35–80
Up to 400 J/cm2
5–200
XS Dualis
Er: YAG
2940
Up to 3000 mJ
0.1–1.5
XS Fidelis
Er: YAG
2940
Up to 1000 mJ
0.1–1.5
Lasering USA
Mixto SX
CO2
10,600
Scanned stamping
0.5–30
180, 300
2.5–16
Velure S5 MiXto
VX
Diode
10,600
0.1–5
10–1000
Lumenis
Active FX
CO2
10,600
Scanned stamping
60
1300
5–225
0.04–2
DeepFX
60
120
5–50
0.04–0.2
TotalFX
–
–
1–225 mJ
<1 ms
Lutronic
eCO2
CO2
10,600
Scanned stamping
30
120, 180, 300
4–120
D. Manstein et al.

169
Company
Device
Laser
Wavelength [nm]
Delivery
Power (W)
Spot size [μm/
MTZ]
Energy [mJ/MTZ] Pulse duration [ms]
Palomar
Lux2940
Er:YAG
2940
Stamping
80–125
up to 25
Lux1540
1540
LuxDeepIR
850–1350
Infrared
light
up to 175 J
Quanta
youlaser CO2
CO2
10,600
Scanned stamping
30
0.05–20
Quantel
BuraneFX
Er:YAG
2940
Scanned stamping
30
150
0.7–32
0.35–250
EXELO2
CO2
10,600
40
350
Up to 2 J
1–100
Sandstone
Medical
Technologies
Matrix LS-25
CO2
10,600
25
100
UltraFine-FS
Scanner
CO2 lasers
10,600
Sciton
ProFractional
Er:YAG
2940
250
4–70
Halo™
Solta
Fraxel re:pair
CO2
10,600
Scanned stamping
40
136, 600
5–70
0.15–3
10  Fractional Photothermolysis

170
One of the key concepts of FP is that the
individual damaged tissue regions (MTZs) are
so small in at least one dimension that the dam-
aged or destroyed tissue is rapidly repaired
without any significance, the close proximity
of surrounding viable tissue facilitates the
wound healing. Although the individual MTZs
induce a guaranteed wound healing response,
the extent of inflammation is limited and con-
fined to their close proximity. The overall
wound healing response is primarily deter-
mined by the shape of individual MTZs and
their distribution (density) within the treatment
area. This “fractional” approach contrasts with
thermal wounds having larger dimensions and
longer healing times, which are typically
generated using conventional resurfacing pro-
cedures or the like. Another advantage of gen-
erating lesions on a microscopic scale is that
the individual lesions are so small that typi-
cally they cannot be resolved with the naked
eye under clinical conditions, thereby ensuring
a homogenous appearance of the treated area.
MTZs heal quickly due to their small cross
section and the presence of unharmed tissue.
They can extend down to the deep reticular
dermis and still be well-tolerated in terms of
rapid healing. Such deep tissue destruction has
to be carefully avoided with traditional abla-
tive resurfacing techniques, as confluent dam-
age to such depth levels would impair the
skin’s ability to regenerate, and would most
likely result in scarring similar to that seen in
third-degree burns [11–13].
• Two distinct types of FP exist: non-ablative
FP (nFP) and ablative FP (aFP).
• Non-ablative FP (nFP) generates MTZs char-
acterized by thermal coagulation.
• Ablative FP (aFP) generates MTZs exhibiting
some degree of immediate tissue removal
(vaporization) and a surrounding zone of
coagulated tissue.
• A distinction between superficial, medium
and deep FP procedures may facilitate descrip-
tion of the procedure, but is somewhat
arbitrary.
At present, two distinct types of FP exist—
non-ablative FP (nFP) and ablative FP (aFP)
(Fig.  10.3). Non-ablative FP (nFP) generates
MTZs having a small-diameter zone of thermally
damaged epidermis and dermis extending down
to a particular depth. The shape of such MTZs is
either an inverted cone or a tapered column
extending into the dermis. The degree of thermal
damage within an MTZ is typically sufficient to
cause cell necrosis and to coagulate collagen.
traditional
ablative
a
b
c
d
superficial
fractional
ablative
non-ablative
non-ablative
fractional
ablative
fractional
Fig. 10.3  Schematics of different resurfacing modalities.
Traditional ablative procedures generate a confluent layer
of tissue removal and with thermal coagulation to the
adjacent remaining tissue (a). Mainly, two distinct types
of FP procedures exist, ablative (aFP) and non-ablative
(nFP) photothermolysis. nFP creates multiple micro-
scopic treatment zones (MTZs) consisting of coagulated
tissue. Despite of the thermal damage, the physical integ-
rity of the skin remains intact (c). AFP vaporizes some
tissue, creating multiple MTZs which consist of a cavity
lined by a thin layer of eschar and surrounded by a cuff of
coagulated tissue (d). Further differentiation of FP proce-
dures according to the depth of individual MTZ is possi-
ble, e.g., superficial FP, but somehow arbitrary (b)
D. Manstein et al.

171
The physical integrity of the skin remains intact,
in spite of the marked localized thermal damage
[8]. Ablative FP (aFP), on the other hand, creates
MTZs by vaporizing microscopic zones of tissue
up to a particular depth. This depth is primarily
dependent on pulse energy and may extent into
the deep reticular dermis. The resulting tapered
cavity is lined by a thin layer of eschar and sur-
rounded by a cuff of thermal denaturation, which
is sufficient to destroy cells and coagulate colla-
gen. Ablative FP results in immediate tissue loss
due to the physical removal of portions of the
skin by vaporization, and the physical integrity
and barrier function of the skin is locally compro-
mised [14]. As the depth of MTZ can vary greatly,
it appears reasonable to further distinguish
between FP procedures generating MTZs of dif-
ferent depths, e.g., superficial, medium and deep.
While such a classification may serve to better
describe a FP process, classification by damage
depth is somewhat arbitrary [15].
• The laser wavelength determines primarily if
an FP procedure is ablative or non-ablative.
• Ablative FP procedures are performed with
lasers emitting at wavelengths corresponding
to strong absorption bands of water.
• The depth of an MTZ for nFP is limited by the
optical penetration of the particular wave-
length into skin tissue.
FP procedures generate a 3-dimensional pat-
tern of MTZs in the skin and the wound healing
response is primarily determined by the charac-
teristics of individual MTZs and their spatial dis-
tribution. The laser tissue effects generated
within individual MTZs depend primarily on
applied wavelength, pulse energy, focused beam
diameter and pulse duration. The laser wave-
length plays an important role in the characteris-
tics and results of an FP procedure. The main
chromophore absorbing the laser energy, either
for nFP or aFP, is water. Wavelengths that are
very strongly absorbed can result in local volu-
metric energy densities sufficient to vaporize tis-
sue [16]. Therefore aFP procedures are performed
with lasers emitting at wavelengths correspond-
ing to strong absorption bands of water. The
approximate optical penetration depth (OPD) in
water for such lasers is minimal, e.g., 1 μm for
the Er:YAG laser(λ = 2940 nm) and 10 μm for the
laser (λ  =  10,600  nm) [17]. High volumetric
energy densities are reached virtually instanta-
neously within the focus of the laser beam, and
therefore such lasers can quickly advance a cav-
ity deep into the tissue during the pulse. Due to
this process, it is possible that the resulting depth
of an MTZ can greatly exceed the optical
­penetration depth of any particular laser wave-
length. Once the local energy density exceeds the
vaporization threshold, the depth of the laser cre-
ated cavity is primarily related to the total energy
delivered for a given spot size, and relatively
independent of the applied wavelength. It should
be noted, that the Er:YAG typically produces less
thermal damage in the residual tissue as com-
pared to the CO2 laser due to the stronger absorp-
tion by water. As nFP procedures do not
physically remove tissue, the maximum depth of
MTZs in nFP procedures is limited by the optical
penetration depth of any particular laser wave-
length. Variation of the applied laser energy
allows some adjustment of the thermal injury
depth within this physically imposed limit.
However, several points should be considered
when applying this concept to real procedures.
The optical penetration depths provided are
approximations of the penetration depth in water
provided by Hall [17]. The water content of tis-
sue can vary substantially and is approximately
30% for the epidermis and 70% for the dermis
[18]. As the optical properties of water are also
temperature dependent, it has been reported that
the rapid change of tissue temperature during a
laser pulse can dynamically alter the penetration
depth substantially [19]. Also, other factors such
as scattering, phase transitions (e.g., collagen
denaturation), and non-linear phenomena should
be taken into consideration for a more detailed
analysis of the wavelength dependent effects on
the shape of MTZs. The following are examples
of lasers that can be used for nFP, together with
their respective wavelengths (λ) and approximate
optical penetration depth (OPD) : Er:YAG
(λ  =  1440  nm, OPD  ≈  300  μm) Er:Glass
(λ = 1540 and 1550 nm, OPD ≈ 1000 μm), and
Thulium
fiber
laser
(λ 
= 
1927 
nm,
OPD  ≈  100  μm). These differences in optical
penetration lengths indicate why the Thulium
laser, with a relatively shallow penetration depth,
10  Fractional Photothermolysis

172
is often used to treat superficial lesions within the
epidermis and papillary dermis, and why the
Er:Glass laser with a relatively larger optical
penetration depth can generate MTZs extending
down into the mid to deep reticular dermis.
Because these provided numbers are estimates
that which can be affected by various factors,
they should serve only as a general guideline,
and not as a specific reference.
• The pulse duration and temporal pulse profile
can affect the amount of thermal damage in
the surrounding tissue.
The pulse duration for FP systems is typically
in the range of up to a few milliseconds, but var-
ies with the preset energy applied per MTZ. The
MTZ energy is controlled for most FP systems
by adjustment of the pulse duration used to create
individual MTZs. In a first approximation, such
short pulse durations are within the thermal
relaxation time of individual MTZs and minor
variation of pulse duration should have limited
effects on lesion shape. However, variation of
pulse duration over an extended range of pulse
profiles will affect the MTZ shape, e.g., ablation
depth and/or extent of residual thermal damage.
Tissue effects related to pulse duration and/or
temporal pulse profile have not yet been charac-
terized in detail, but these parameters are likely
to be the focus of future studies for optimizing
FP procedures. The available average power of
an FP laser system is a critical factor that limits
the maximum overall coverage rate. For exam-
ple, a laser that delivers a higher average optical
power can be capable of faster treatment of larger
areas.
• Coverage of a treatment area can be achieved
by the ‘stamping’ or ‘rolling’ technique.
• Typically, multiple passes are necessary to
provide sufficient treatment coverage.
• Variation of the number of passes and expo-
sure settings in different areas can be used to
adjust the clinical outcome in specific loca-
tions, e.g., ‘feathering’ at the edges of the
treatment area.
• Excessively high treatment densities should
be avoided as they can result in undesirable
side effects.
There are two general techniques currently
available for generating the desired density of
MTZs (number per unit area) within the treat-
ment area: the ‘stamping’ technique and the ‘roll-
ing’ technique. The ‘stamping’ technique is
performed by forming a preset pattern of multiple
MTZs on a skin region within a well-defined
exposure area of the fixed handpiece, and then
moving the handpiece to another skin region and
repeating until the entire treatment area is cov-
ered. The density of MTZs at the end of a treat-
ment session depends on the preset density within
the exposure area of the handpiece and the num-
ber of passes performed over each skin region. A
pass is defined as the coverage resulting from a
single application of the hand-piece to a particu-
lar area of the skin. The ‘rolling’ technique is per-
formed by continuously rolling the handpiece
across the entire treatment area. It is also referred
as ‘brushing’ technique, because the movements
of the operator are similar to using a paint brush.
As the velocity of the handpiece relative to the
skin varies during treatment, the delivery rate is
adjusted automatically in order to maintain a
defined, preset MTZ density per pass. The total
density of MTZs at the end of a treatment session
can be estimated as the density of MTZs per pass
multiplied by the number of passes performed.
However, this presents only an estimate as with
each pass the remaining undamaged skin surface
decreases and therefore the effective amount of
tissue that is newly damaged with each subse-
quent pass decreases. Some MTZs formed on
subsequent passes may overlap or coincide with
MTZs already formed during prior passes. A
more detailed description of the determination of
coverage in terms to number of passes is pro-
vided by Manstein et al. [20]. There appears to be
no single best technique for delivering the desired
density of MTZs. The ‘rolling’ technique can
facilitate treatment of larger areas, while the
‘stamping’ technique can facilitate the precise
treatment of smaller areas, in particular areas
having an irregular surface profile. It is the opin-
ion of the authors that a reasonably well-defined
MTZ density can be achieved with both tech-
niques, and the choice between stamping and
brushing ultimately comes down to a personal
preference of the operator. FP systems generally
allow the operator to adjust both MTZ density
D. Manstein et al.

173
and MTZ characteristics independently within
the treatment area. The MTZ density can be
adjusted by varying the preset number of pulses
per area and/or number of passes, while the
dimensions of individual MTZs can be modified
by adjustment of the MTZ energy, energy beam
focal characteristics, etc. Such control allows, for
example, formation of a decreased MTZ density
at the periphery of a treatment area to avoid
demarcation lines between treated and untreated
areas (feathering), or an increased MTZ density
or applied energy density within particular areas
that can benefit from an enhanced treatment out-
come. The overall extent of the wound healing
response, and thus the extent of both clinical
improvement and side-effects appear to be related
to the total amount of thermal injury or total
energy delivered per treatment area. Treatment
densities that result in confluent thermal injury
can result in blistering or even scarring.
• Bulk heating is the temperature rise of the tis-
sue between individual MTZs by thermal con-
duction as each MTZ acts as a local heat
source.
• Limited bulk heating may be desirable in FP
procedures.
• Excessive bulk heating can result in confluent
tissue damage and severe side effects includ-
ing scarring.
• Excessive bulk heating can be avoided by lim-
iting MTZ densities, extending the time inter-
val between passes and application of
cooling.
• Changes in tissue temperature effect the shape
of individual MTZs.
While FP procedures are designed to deliver
localized thermal injury within individual MTZs,
it should be taken in consideration that energy
deposited into the tissue may accumulate under
certain conditions. The temperature gradient
tends to be very high within a single MTZ, often
resulting in a very sharp demarcation between
coagulated
and
non-coagulated
collagen.
However, each MTZ represents a small heat
source within the surrounding tissue. This heat-
ing effect has two principal consequences. First,
although there is typically a very sharp demarca-
tion at the perimeter of an individual MTZ, ther-
mal effects on the tissue immediately surrounding
an MTZ have been observed. For example, apop-
totic cell death and induction of various heat
shock proteins can be seen close to individual
MTZs. Although the effects of such events on the
clinical outcome have to be further investigated,
it can be speculated, that up to a certain extent,
these local heating effects around the MTZs may
enhance wound healing and clinical outcome.
Second, as each of the MTZs acts as a local
heat source, forming many MTZs within a short
time period can lead to an increase in the average
tissue temperature of the treated region due to
heat conduction. Such tissue heating is described
by the term ‘bulk tissue heating.’ Bulk tissue
heating can become a significant problem when
the local average tissue temperature rises above a
critical temperature such that confluent areas of
tissue are damaged or destroyed, rather than lim-
iting such damage to discrete small microscopic
zones. Such gross thermal injury mimics that of a
third degree burn, which can lead to substantial
side effects including scarring.
The following precautions should be taken
into consideration in order to avoid excessive
bulk heating during FP procedures:
(a) For higher individual MTZ formation ener-
gies, the spatial density of MTZs formed in
the treatment region should be decreased.
(b) When multiple passes are performed on a
treatment region, the time interval between
passes should be long enough to allow the
tissue to cool down between consecutive
passes.
(c) External cooling, e.g., forced air cooling, can
be used to remove some heat from the tissue
region being treated.
Changes in tissue temperature have been
shown to affect the geometry of individual
lesions. Reduction of MTZ dimension due to
decrease of tissue temperature have been shown
to be more marked for nFP [21] as compared to
aFP [22]. Skin cooling before, during and/or after
FP treatments is often desirable because it can
alleviate pain during treatment and also reduce
the risk of bulk heating. Because skin cooling can
also decrease the MTZ lesion size resulting from
particular system settings during an nFP
10  Fractional Photothermolysis

174
procedure, it is important to perform such proce-
dures under standardized cooling conditions to
control the thermal damage within individual
MTZs. It should be noted that during aFP proce-
dures, a substantial part of the laser energy is
removed from the tissue with the hot laser plume.
This is in contrast to nFP procedures, and there-
fore it is reasonable to conclude that for the same
applied energy per MTZ energy and MTZ den-
sity, the overall (bulk) heating of tissue is greater
for nFP as compared to aFP. Although, no studies
have been carried out to either confirm or quan-
tify this effect, the operator should be aware of
such potential interrelated effects that are based
on principles of laser tissue interaction.
• FP procedures are typically performed as mul-
tiple treatments.
• Treatment outcome is typically incrementally
enhanced after additional FP treatments.
• Typically, a series of approximately 3–5 nFP
or 1–3 aFP treatments are performed.
• There is some controversies regarding whether
the clinical improvement of an aggressive
treatment can be achieved by repetition of less
aggressive treatments.
• FP treatments allow distribution of the ther-
mal wounding resulting from individual
MTZs at different densities and over distinct
treatment sessions.
FP treatment of a particular skin region can be
delivered in single or multiple treatment sessions.
Typically, 3–5 nFP or 1–3 aFP treatment sessions
are performed, but the number of treatments can
vary within a wider range depending on indica-
tions, treatment settings and patient response.
Each treatment is customized to a patient’s
individual condition to best manage side effects
and downtime. The treatment is repeated until
either the desired outcome is achieved or no fur-
ther relevant improvement can be achieved. It
should be remembered that some of the effects,
e.g., collagen remodeling, can progress over a
period of weeks or months after a treatment.
Multiple treatments are generally performed at
intervals of approximately 4–8 weeks. However,
there are no studies currently known that com-
pare the outcomes achieved based on variation in
treatment intervals. The current intervals of sev-
eral weeks are generally preferred because they
allow sufficient time for side effects to subside
and also arguably because such intervals are con-
venient for the appointment scheduling of most
offices and patients. There is some controversy
regarding the effect of multiple treatments ses-
sions on enhancement of treatment outcomes.
While it is generally accepted that multiple treat-
ments sessions can improve the overall outcome,
it is not clear exactly how the number of treat-
ments sessions is related to the overall improve-
ment. Also, it is still not known whether multiple
treatments performed at well-tolerated settings
can mimic the outcome of fewer or single treat-
ments sessions performed with more aggressive
settings that are associated with a marked wound
healing response and prolonged downtime. FP
treatments provide the possibility of obtaining
particular degree of thermal wounding within
individual MTZs and varying just the density of
such MTZs and/or adjusting the number of ses-
sions. In contrast, conventional treatments that
cover the entire treatment area continuously do
not allow for this freedom. These full surface
procedures only allow for adjustment of the treat-
ment level by varying the fluence applied over the
entire area.
• Several factors beyond the laser parameter set-
tings can affect the thermal damage.
• Mechanical manipulation of the skin such as
compression, stretching and contraction can
affect the shape and density of MTZs.
A variety of factors beyond an FP system’s
preset MTZ exposure/energy and density settings
can affect the thermal injury of the tissue. The
operator should be aware of such factors, as they
can impact the wound healing response, clinical
outcome, and side effects experienced by the
patient. For example, mechanical factors such as
tissue stretching, contraction, or compression can
affect MTZ lesion dimension and MTZ density.
Stretching of the skin during exposure can lead to
an increased actual density of MTZs. The density
per pass is typically preset by the system for a
fixed exposure area, but skin stretching during
the exposure can actually result in relatively
D. Manstein et al.

175
higher MTZ density. This can occur because as
the skin is able to retract after the stretching is
relieved, any number of delivered pulses is
located within a relatively smaller area. MTZs of
smaller cross section can also result from stretch-
ing of the skin prior to treatment, as the MTZs
that are formed in the stretched skin may shrink
in size when the skin is allowed to retract. Point
compression can distort the skin dimensions
locally during exposure, and relatively deeper
MTZs with smaller cross sections can result from
such mechanical tissue manipulation. Also,
because skin may contract as a result of localized
thermal injury to the collagen, the dimensions of
the skin can change during the delivery of a series
of passes to generate individual MTZ patterns.
Ablative FP procedures performed, particularly
when performed with higher MTZ energies, tend
to exhibit such shrinkage of the tissue during
multiple FP passes over a particular treatment
area.
• In addition to the shape and density of indi-
vidual MTZs, the number of treatment ses-
sions and intervals can be chosen by the
operator.
• The broad variety of possible combinations
allows tailoring patient treatment protocols to
specific needs.
• The multivariate complexity of FP procedures
represents a challenge to obtain comparative
clinical data.
• Most FP treatments result in varying degrees
of clinical improvement for appropriate
indications.
• The three basic rules of any FP treatment are:
–– Individual MTZs should induce wound
healing but not fibrosis.
–– Confluent damage and bulk heating should
be avoided.
–– The cumulative MTZ density should be
sufficiently high to result in clinical
improvement after the completion of a
treatment course.
As discussed herein, many factors can affect
thermal damage patterns generated in the skin
and subsequent wound healing responses. Such
factors include laser exposure parameters (e.g.,
energy per MTZ and focal spot size), the number
of passes and time interval between them,
mechanical tissue manipulation, use of skin cool-
ing procedures, and others. The treatment inter-
val between individual passes within a single
treatment session and the number of sessions can
also be varied. This virtually unlimited number of
possible treatment combinations provides the
possibility of tailoring patient treatment proto-
cols to specific needs. However, this flexibility
also leads to some complexity and uncertainty
associated with the choice and control of all pos-
sible parameters and factors. The multivariate
complexity of FP procedures explains in part the
current lack of clinical studies comparing the
effect of many specific FP parameters on patient
outcomes. In spite of this complexity, it turns out
that most FP treatment regimes result in some
kind of clinical improvement for appropriate
indications. Also, the fundamental principles of
FP that guide the selection of treatment parame-
ters are relatively simple and can be summarized
by three basic rules. First, the dimensions of indi-
vidual MTZs should not exceed certain dimen-
sions, such that the induced wound healing
results in tissue repair rather than inducing fibro-
sis. Second, the overall density of MTZs should
not be excessively high to maintain sufficient
undamaged tissue between the MTZs and facili-
tate tissue repair. In particular, thermal damage to
confluent tissue via bulk heating should be
avoided. Third, the cumulative density of MTZs
should be sufficiently high to induce sufficient
clinical improvement after a completed course of
FP treatments.
When the concept of FP was first intro-
duced, the laser was used as the energy source
to generate fractional damage to the skin. The
laser is still the most common energy source
used in FP procedures. Its ability to quickly
deliver energy in the form of focused optical
radiation with high precision into small con-
fined zones makes the laser a modality well
suited for FP. Recently, other energy sources
have emerged for generating fractional dam-
age patterns. For example, radiofrequency
(RF) and ultrasound devices are now commer-
cially available that generate a pattern of small
and confined thermal damage zones in skin
10  Fractional Photothermolysis

176
tissue. The shape and anatomical location of
MTZs generated using such modalities typi-
cally differ from those induced by focused
optical radiation because of a different energy
distribution within the tissue. As RF energy
quickly diverges with increasing distance from
the delivering electrode, it is possible to gener-
ate a spatially confined RF generated thermal
injury only within the tissue directly adjacent
to the tip of a needle electrode. Depending on
the location of the tip of such RF electrode,
damage can be generated either at the skin sur-
face [23], or virtually at any depth by inserting
needle electrodes into the skin [24], The use of
stamping techniques with arrays or linear
arrangements of multiple needle electrodes
allows for coverage of a treatment area within
a reasonable time. Focused ultrasound non-
invasive generation of confined lesions [25], in
skin layers such as, e.g., the deep reticular der-
mis or even the superficial musculoaponeurotic
system (SMAS) without causing any surface
damage [26]. The MTZ cross section of RF or
ultrasound generated MTZs is typically larger
than that of laser generated MTZs because
laser radiation can be more focused. However,
the ability to focus optical radiation decreases
with increasing skin depth due to scattering
and absorption of optical radiation. Further
investigations are needed to investigate how
the size and location of thermal lesions gener-
ated using RF and ultrasound sources affect the
clinical outcome as compared to laser-gener-
ated MTZs.
• aFP and nFP can treat a wide variety of clini-
cal conditions including some that have been
traditionally the domain of selective photo-
thermolysis (SP).
• The relative benefits and disadvantages of
ablative and non-ablative FP approach are
being investigated.
Both aFP and nFP target water-containing
tissue and, unlike selective photothermolysis
procedures [10], there is no significant selectiv-
ity of specific components because virtually all
cells of the skin are composed primarily of
water. Nevertheless, FP can be used to treat cer-
tain conditions that traditionally have been a
domain of selective photothermolysis, includ-
ing treatment of pigmented and vascular
lesions. FP targets aqueous tissue that contains
such target lesions and therefore can affect a
variety of lesions. Both, aFP and nFP have been
applied successfully to a variety of clinical
indications, including collagen remodeling and
treatment of vascular and pigmented lesions.
Further details of indications and the wound
healing process are described in the following
sections. The balance between improved clini-
cal efficacy of aFP for selected indications as
compared to nFP and the additional risks and
side effects of aFP associated with a impaired
epidermal barrier function and removal of
entire columns of tissue in aFP is still being
explored.
Non-ablative Fractional
Photothermolysis (nFP)
• A variety of nFP devices are available in the
marketplace.
• Principal treatment parameters for nFP are
applied energy per MTZ and density of MTZs
(number per square centimeter).
• To keep the areal fraction of damaged skin
surface constant the MTZs density should be
decreased when higher MTZ energies are
applied.
An overview of certain systems currently
available commercial systems for nFP proce-
dures is presented in Table 10.1. These systems
use various lasers emitting in the near IR range.
Spot sizes in these systems are all in the sub-­
millimeter range, and the depth of the generated
MTZs is mainly wavelength dependent, varies
widely, and can extend into the deep reticular
dermis for some systems. The depth and diameter
of individual MTZs is positively correlated with
energy [27].
Variation of the focusing optics can also affect
MTZ shape [28]. An example of the effects of
different energies on the thermal damage and
shape of MTZs is exhibited in Fig. 10.4. Primary
treatment parameters for nFP include the energy
D. Manstein et al.

177
applied per MTZ and the areal density of MTZs
(e.g., the number per square centimeter). It is
therefore necessary to decrease the MTZ areal
density if higher energies are applied per MTZ to
keep the areal fraction of damaged skin surface
constant.
• Histologically, a column of necrotic, coagu-
lated tissue is generally observed within the
skin after formation of a MTZ via nFP.
• The skin barrier is preserved in nFP and the
dam- aged epidermis is quickly replaced.
• Oval balls of microscopic epidermal necrotic
debris (MEND) on the skin surface are often
observed within 24 h of an nFP treatment.
• The ‘MENDs shuttle’ allows for controlled
removal of epidermal and dermal content,
e.g., melanin and elastin.
• nFP is well-suited for treatment of ‘low con-
trast’ superficial pigmented lesions.
• The remodeling of the damaged dermis can
take several weeks and occurs without forma-
tion of fibrosis.
Histological analysis immediately after nFP
treatment shows a column of thermally denatured
dermis and epidermis that constitutes a micro-
scopic treatment zone (MTZ) (Fig.  10.5a). In
addition, subepidermal clefting may be observed
in the area of the MTZ. This destruction of the
dermal-epidermal (DE) junction corresponds to a
microscopic blister, the size of which generally
increases with the energy per MTZ. The tissue
surrounding the MTZs appears microscopically
undamaged. Further, the stratum corneum over-
lying the MTZ often appears unaltered, thus, pre-
serving an intact skin barrier is preserved after
nFP
treatment.
This
is
consistent
with
the early studies of Manstein et  al. [8] who
reported an absence of any significant change in
a
b
Fig. 10.4  Skin histology resulting from a nFP device at
different energy levels. NitroBlueTetrazolium stain was
used to monitor for thermal damage. Lack of blue staining
indicates thermal cell injury. Lesions were produced with
Fraxel re:store, Solta, λ = 1550 nm within excised human
skin. The depth and diameter of the MTZs vary with energy,
40 mJ (a) vs. 100 mJ (b). Note, the unstained part of the
lesion consist of thermally damaged tissue rather than a cav-
ity. Also, the commercial version of this laser is limited to a
maximum energy of 70 mJ/MTZ (Thongsima et al. [28])
10  Fractional Photothermolysis

178
trans-­epidermal water loss after nFP. Due to the
typically small (sub-millimeter) cross section of
the MTZ, a rapid repair of the thermally damaged
epidermis is generally observed. Within 24 h fol-
lowing an nFP procedure, necrotic cells in the
epidermis are replaced by viable keratinocytes
migrating to the damaged areas from the
unharmed
tissue
surrounding
the
MTZ
(Fig.  10.5b) pushing the cellular debris of
necrotic cells upwards towards the skin surface.
Due to the excretion of the necrotic debris via the
upper portion of the MTZs, oval balls of tissue
may appear within about 24  h after nFP treat-
ment. This tissue is referred to as microscopic
epidermal necrotic debris (MEND) [8]. Immuno-­
histochemical staining has revealed that MEND
is mainly composed of necrotic epidermal tis-
sue (including, e.g., melanin) but may also
include portions originating from of dermal tis-
sue (e.g., elastin) [30]. In the days following an
FP procedure, MEND migrates through the stra-
tum corneum and can produce a small flaked
shedding. The term ‘MEND shuttle’ describes
the release of dermal and epidermal material
through the MEND migration and shedding.
During the migrational period of the MEND
through the epidermis and stratum corneum, the
number of dyskeratotic cells is reduced within
the epidermis. About 1 week after the nFP treat-
ment, the epidermis usually appears normal
again. The MEND shuttle primarily facilitates
controlled elimination of epidermal pigment, but
it also allows for the removal of dermal content.
The removal of pigment and dermal content by
the MEND shuttle can be well-controlled by
selection of the overall MTZ density formed dur-
ing an nFP procedure. In contrast to laser proce-
dures that utilize selective photothermolysis, the
relative amount of pigment removed by the
MEND shuttle is independent of the pigmenta-
tion of the treated tissue, because the wavelengths
utilized to form the MTZs are primarily absorbed
by water.
This feature allows for a gradual removal of
pigment of all skin colors by adjusting the den-
sity of MTZs. The pigment is also laterally redis-
tributed during the MEND shuttle process, so
that a relative homogeneous removal of epider-
mal pigment can be achieved. As this process
does not rely on the chromophore properties of
melanin, all skin types can be effectively treated
by the nFP process. Therefore, nFP is a proce-
a
b
Fig. 10.5  Skin histology at different time points after
nFP treatment. H&E stain, 200×. Lesions were produced
with Solta prototype, λ = 1500 nm, 5 mJ/MTZ. (a) 1 h
after treatment a column of denaturated collagen (black
arrow) can be seen within the MTZ (black outline). The
entire stratum corneum remains intact, even above the
MTZ. There is no inflammatory infiltrate around the MTZ
yet. (b) Day 1 after nFP.  MTZs (black outline) contain
microscopic epidermal necrotic debris (MENDs, black
arrows), which represent the elimination of thermally
damaged keratinocytes. MENDs are loaded with melanin.
Subepidermal clefting is evident from 1 h after FP and
lasts up to 5 days (stars). The dermal part of the MTZs
appears the same as immediately post treatment and shows
thermally altered collagen and a lack of nuclear staining.
Subtle perivascular inflammatory infiltrate begins to form
in the dermis (white arrow) (Laubach et al. [29])
D. Manstein et al.

179
dure of choice for removing pigment that pres-
ents as a ‘low contrast lesion’, i.e., where the
difference in pigmentation levels between the
lesion and the surrounding skin are relatively
small. While the epidermal damage produced by
nFP is quickly repaired, the dermal (deeper) por-
tion of the MTZs is still well distinguishable for
several weeks as a column of thermally coagu-
lated collagen surrounded by minor perivascular,
inflammatory infiltrate. Histological analyses
performed 3  months after an nFP procedure
­indicate that the dermal portions of the MTZs are
no longer distinguishable by standard H&E stain-
ing. However, overall dermal remodeling and
restoration of a more undulated DE junction have
been reported after nFP procedures [8].
• nFP can also affect fine vessels, particularly
for higher MTZ energies.
The effects of nFP are not limited to removal
of epidermal pigment (Fig. 10.6a) and collagen
remodeling (Fig. 10.6b). It has been shown both
histologically and clinically that nFP can also
affect small vessels (Fig. 10.6c) [29]. Although
there is no significant selective absorption of
energy by vascular targets in nFP procedures, it
has been shown that small vessels having cross-­
section areas comparable to those of the MTZ
lesions can be coagulated in a statistical manner,
e.g., based on random intersection of the MTZs
and vascular lesions. While selective photother-
molysis remains the technique of choice for
removal of vascular lesions, nFP can also have a
beneficial effect on small vascular lesions. This
vascular effect generally requires application of
higher nFP energies to reach the tissue depth
where the vascular targets are present. The clear-
ance of vascular targets in the treatment region by
using an nFP treatment with a high energy
applied per MTZ was achieved (Fig. 10.7a, b),
whereas a similar region of the same patient that
was treated with the same total energy applied
per unit area of the treatment region—but using a
lower energy per MTZ formed—did not show
any significant clearance of vascular lesions
(Fig. 10.7c, d). The authors are not aware of any
published clinical studies that have been per-
formed to date on the treatment of vascular
lesions with nFP, and further research is war-
ranted in this area.
• The risk of bulk heating can be reduced by
con- current use of cooling.
• Cooling may alter the MTZ shape.
Forming relatively deep MTZs can be benefi-
cial due to an increase in the local volume of ther-
mally altered or destroyed tissue within the skin.
However, increasing the diameter of the MTZs
and/or the areal MTZ density ultimately results
in unwanted side effects arising from increased
damage to the dermoepidermal junction (DEJ)
and a stronger wound healing response. Although
the optimal diameter and depth of MTZs formed
during nFP to produce the greatest clinical effi-
cacy and fewest side effects are yet to be deter-
mined, some limitations on these parameters
a
b
c
Fig. 10.6  Histological summary of the main effects of
nFP procedures. (a) Pigment removal (arrow) by MENDs
shuttle process (Fontana Masson stain). (b) Dermal
remodeling as evidenced by positive colla gen type III
engulfing MTZs (arrow). (c) Coagulation of small blood
vessels by statistical co-location of the MTZ and vessel
(arrow)
10  Fractional Photothermolysis

180
have already been established. For example, it is
well known that too much thermal damage per
unit area of skin tissue (e.g., resulting from a
large number of MTZs formed per unit area of
tissue) can result in a loss of dermoepidermal
integrity and generation of severe unwanted side
effects, such as blistering. Furthermore, creating
too many MTZs within a region of skin in too
short a time period can inhibit thermal relaxation
of the tissue in between passes and result in bulk
heating of the entire treatment area. The thermal
energy in such nFP procedures is no longer con-
fined to the MTZs but instead diffuses into the
surrounding tissue, leading to a thermal alteration
of the entire tissue rather than limiting such ther-
mal effects to the well-defined MTZ volumes.
a
b
c
d
Fig. 10.7  Energy dependent response of telangiectasias
to nFP treatment. A study patient with rosacea and acne
scars had similar distribution of fine telangiectasias in
contra-lateral areas of the face. 3 nFP treatments were per-
formed at 1  month intervals with Fraxel re:store,
λ = 1550 nm. A similar Fluence (average energy per area)
was delivered at each side per treatment (approximately
13 J/cm2) and outcome assessed 1 month after last treat-
ment. The side treated with a lower MTZ energy (6 mJ/
MTZ, ≈2200 MTZ/cm2) did not show any reduction of
telangiectasias (a) and (b). The side treated with higher
MTZ energy (70 mJ/MTZ, ≈200 MTZ/cm2) showed sig-
nificant reduction of telangiectasias (c) and (d)
D. Manstein et al.

181
This spreading of the thermal energy ultimately
may lead to unwanted side effects, including
scarring of the treatment area. The combination
of areal density of MTZs, energy used to form
each MTZ, and the time interval in which they
are created that can generate beneficial effects
without introducing significant bulk heating to
the treatment area remains an area in which more
studies are needed. Several techniques for reduc-
ing the risk or extent of unwanted bulk tissue
heating are described above. In particular, the use
of skin cooling (e.g., forced-air cooling) and/or
allowing sufficient time between consecutive
nFP treatment passes can facilitate cooling of the
treatment region. A decrease in skin temperature
also tends to decrease the epidermal MTZ diam-
eter for a particular set of applied energy param-
eters [21]. Therefore, tissue cooling effects
should be considered when planning or compar-
ing nFP treatments.
• About 3–5 nFP treatment sessions are generally
recommended; the exact number depends on
the particular indication and desired end result.
• Other side effects associated with nFP treat-
ment include a moderate erythema and/or
edema developing immediately after the treat-
ment and lasting up to 5 days; the severity of
these side effects exhibit a positive correlation
with MTZ energies and densities.
FP is based upon the concept of restricting
thermal damage or alteration to well-defined
microscopic zones within of the skin, whereby
the surrounding healthy tissue can facilitate a
rapid wound healing of the small damaged tissue
volumes. Typically, about 10–30% of the skin
surface is thermally damaged or destroyed using
focused laser beams in an nFP procedure. About
3–5 nFP sessions are generally recommended for
treating a particular region of skin; the exact
number of sessions can depend on the indication
and desired end result. Although patient satisfac-
tion (an indicator of treatment efficacy) generally
improves with the number of treatment sessions,
the improvement in satisfaction between the third
and the fourth treatment appears to be only mar-
ginal [31]. The optimal number of nFP treatment
sessions needed for greater patient satisfaction
and clinical improvement is not generally known,
and depend at least in part on the particular nFP
parameters used and the condition being treated.
The optimal time interval(s) between successive
nFP treatment sessions for achieving optimal
efficacy and a minimum of side effects also
remains to be determined. In one particular
example, it has been proposed that longer inter-
vals between nFP treatment sessions, e.g., up to
2 months, are preferable when treating Fitzpatrick
skin type IV–VI to reduce the risk of post inflam-
matory hyperpigmentation (PIH) [32].
• Discomfort during nFP treatment increases
significantly with the energy applied per MTZ
and the MTZ density per pass.
• Different approaches such as prior and/or
simultaneous skin cooling, local application
of a topical anesthetic, etc. can be used to
reduce or eliminate perceived pain.
One of the side effects of nFP treatment is
patient discomfort during the treatment itself.
This discomfort increases mainly with the energy
applied per MTZ, but also with the MTZ density
per pass [32]. Several different approaches are
currently used to decrease discomfort during
treatment. Concomitant skin cooling during laser
treatments not only reduces undesirable side
effects such as bulk heating, but also reduces dis-
comfort associated with nFP laser treatments
[33]. Providers of various nFP systems often rec-
ommend either contact or air convection cooling.
Some nFP laser system providers recommend the
use of anesthetic cream prior to the nFP treat-
ment, while others do not recommend the use of
additional anesthetics. Because of a lack of com-
parative trials, it is currently not well investigated
whether there is a significant difference in patient
pain perception with different nFP systems.
• Bronzing due to the MENDs formation and
migration through the epidermis and stratum
corneum can be observed 3–7  days after an
nFP procedure.
Other side effects associated with nFP treat-
ment include a moderate erythema and edema
developing immediately after the treatment and
10  Fractional Photothermolysis

182
typically lasting for up to about 1  week. The
severity of these side effects show a positive cor-
relation with MTZ energies; MTZ areal densities
are not only associated with an increase in ery-
thema and edema, but also correlate with
observed post inflammatory hyperpigmentation
(PIH) [32]. Although a reduction in efficacy has
been observed for nFP skin rejuvenation proce-
dures with lower energy settings, lower applied
energies are also correlated with a reduction in
the duration and severity of side effects like ery-
thema and edema [32]. A patient’s downtime cor-
responds to the duration and the severity of the
post-treatment erythema and edema, and is typi-
cally on the order of a few days. The authors’
experience suggests that the consistent use of
cooling pads during the first 24 h after nFP treat-
ment further reduces the severity of erythema and
edema. During the third to seventh days after an
nFP procedure, the treated skin often shows a
slight bronzing due to the MEND formation and
migration through the epidermis and stratum cor-
neum as noted above. This bronzing effect tends
to be evenly distributed over the treated area, and
most patients describe this effect as cosmetically
not unpleasant and feeling slightly “suntanned.”
Such bronzing effect can contribute to the epider-
mal elimination of melanin. As this bronzing is
related to trans- epidermal melanin elimination, it
is generally more accentuated for darker skin
types and within treatment areas of enhanced
melanin density.
The 1927 nm Thulium laser has been recently
introduced in an nFP system and promoted
among other indications the removal of superfi-
cial pigment, including for non-facial areas.
Published details or studies of this system are not
available as of the publication date of this vol-
ume. This system can produce a larger MTZ
diameter of up to approximately 600  μm. Its
wavelength is more superficially absorbed
(OPD ≈ 100 μm) as compared, for example, to
nFP systems based on the 1540 nm or 1550 nm
lasers (OPD ≈ 1000 μm) but less absorbed than
aFP systems based on CO2 lasers (OPD ≈ 10 μm).
Thus it is designed to generate thermal injury in
relatively superficially tissue without significant
disruption of the epidermal barrier. A representa-
tive example of the clinical course after treatment
with the Thulium laser is shown in Fig. 10.8. For
post-nFP aftercare, a hydrating, non-greasy
moisturizer is generally recommended because
patients commonly report a sensation of rough
and dry skin, most likely due to the MEND shed-
ding that commonly occurs several days after the
procedure. Furthermore, there is an increased
risk of the formation of acne-like lesions, espe-
cially with the use of higher treatment energies.
Using a non-occlusive aftercare product may
reduce this risk. Patients with a positive history
of facial herpes simplex should take oral antiviral
medication prior to nFP treatment to prevent or
inhibit viral reactivation. The effectiveness of
systemic or topical corticosteroids in reducing
side effects such as edema and erythema without
compromising treatment efficacy is yet to be
determined.
• The risk of post-inflammatory hyperpigmen-
tation in patients having darker skin types can
be decreased significantly by reducing the
density of MTZs, and by simultaneous skin
cooling.
Non-ablative FP procedures can be associated
with minor petechial bleeding, especially if
patients continue to traumatize the skin during the
first few days after the treatment (e.g., by wearing
tight wristbands, necklaces, etc.). Chan et al. [34]
observed
that
a
mild-to-moderate
post-­
inflammatory hyper- pigmentation (PIH) occurs
in about 7.1–17.1% of Asians undergoing nFP
treatment; the likelihood of this side effect
depends on the laser settings and evaluation
method. The risk of PIH, especially for darker
skin type patients, can be reduced significantly by
decreasing the extent (including the overall area)
of dermo-epidermal junction destruction, e.g., by
reducing total MTZ densities and using simulta-
neous skin cooling [32, 34, 35]. Furthermore, pro-
tection from sunlight during the weeks after nFP
treatment should be emphasized to the patient to
further reduce the likelihood of unwanted PIH. It
remains to be determined whether lengthening the
time intervals between successive nFP treatments
can help to reduce the occurrence of PIH.
Currently available data suggests that nFP treat-
ments can be customized to the patients’ desires
D. Manstein et al.

183
a
b
c
d
Fig. 10.8  Clinical course of after single treatment with
Thulium laser. Treatment was performed with Fraxel Dual
(Solta), λ = 1927 nm, 10 mJ/MTZ, ≈800 MTZ/cm2, treat-
ment level 7, 50% density. Clinical appearance at baseline
(a), 2  days (b), 6  months (c) and 10  months (d). After
significant improvement of the dyschromia at 1 and 6 months,
there is partial recurrence of dyschromia at the 10 months fol-
low up. This is likely due to continued sun exposure as the
patient participated in frequent outdoor sports without
proper UV protection (Courtesy of Steven Struck, M.D.)
10  Fractional Photothermolysis

184
to balance the aggressiveness of treatments to
achieve a higher efficacy with the likelihood of
causing undesirable side effects.
• The main indications for nFP are treatment of
photoaging, various kinds of scars and treat-
ment of dyschromia.
• Improvement of deep rhytides and skin tight-
ening is limited.
• Melasma has a high risk of recurrence.
Non-ablative FP has been shown to be effec-
tive on a wide variety of conditions [36–40],
including but not limited to a variety of indica-
tions related to collagen remodeling, e.g., treat-
ment of photoaging including fine and moderate
rhytides (Fig.  10.9), treatment of traumatic
(Fig.  10.10), surgical, burn (Fig.  10.11) and
acne scarring, striae distensae, and treatment of
dyschromia e.g., superficial pigmented lesions
like solar lentigines. The authors would like to
­highlight the ability of nFP to improve various
kinds of scars including textural skin alterations
after involution of hemangiomas (Fig. 10.12),
as for these indications remarkable improve-
ment was reported that was previously difficult
to obtain. Although, nFP has the ability to
improve the appearance of rhytides, by increase
epidermal thickness, papillary dermal collagen
and increase the number of fibroblasts, [41]
a
b
Fig. 10.9  Clinical improvement of fine and moderate
(dynamic) rhytides. A series of 3 nFP treatments was per-
formed with Fraxel re:store (Solta), λ = 1550 nm, 70 mJ/
MTZ, approx. 200 MTZ/cm2. (a) Baseline. (b) 6 months
after last treatment. Note: Treatment was performed as
part of a clinical study, and the use of neurotoxins (not
applied to this patient) would likely have provided similar
results
a
b
Fig. 10.10  Clinical improvement of a traumatic scar. A
traumatic scar that was persistent for more than 10 years
received a series of 3 nFP treatments with Fraxel re:store
(Solta), λ = 1550 nm, MTZ energy 70 mJ, ≈200 MTZ/cm2.
The scar virtually disappeared after the completion of the
series of treatments. (a) Baseline. (b) 6 months after last
treatment
D. Manstein et al.

185
abltaive FP hold superior clinical outcomes due
to reaching deeper dermal ablation and coagu-
lation [42].
Treatment of melasma with nFP is an option
but it should be used with caution, because of the
relative high rate of repigmentation and some-
times even an increase in pigmentation after nFP
treatments [43].
• Many novel indications for nFP are emerging.
• Determination of optimal nFP parameters for
par- ticular indications is an area of ongoing
study
Other indications that have shown some prom-
ise for treatment using nFP in small case studies
are minocycline-induced hyperpigmentation [44],
a
b
Fig. 10.11  Clinical improvement of a burn scar. A burn
scar which occurred 30 years ago, obtained a series of 5
nFP treatments with Fraxel re:store (Solta), λ = 1550 nm,
MTZ energy 40 mJ, ≈450 MTZ/cm2, 23% density, treat-
ment level 8. Significant improvement of texture and pig-
mentation is observed. (a) Baseline. (b) 5 months after the
last treatment (Courtesy of Steven Struck, M.D.)
a
b
Fig. 10.12  Clinical improvement of scarring. Skin alter-
ations mimicking dermal scarring had developed after the
involution of an early childhood hemangioma and were
stable for approximately 13 years prior to FP treatment. A
series of 5 nFP treatments achieved a significant smooth-
ening of skin surface (Solta, re:store, λ  =  1550  nm,
≈40  mJ/MTZ, treatment level 8). (a): Baseline. (b):
1 month after last treatment
10  Fractional Photothermolysis

186
granuloma anulare [45], striae rubra [46], Nevus
of Ota [47], alopecia areata [48], and Poikiloderma
of Civatte [49]. While results of these case reports
suggest promising results, further clinical studies
are needed before nFP can be established as a
standard of care for such indications. Nevertheless,
it is encouraging to see that nFP may be an option
for treating such clinical problems. Although a
wide variety of nFP systems, treatment parame-
ters, and regimens have been shown to provide
measurable clinical improvement for various der-
matological indications, determination of optimal
parameters and conditions for particular indica-
tions remains an area of ongoing study.
Ablative Fractional
Photothermolysis (aFP)
• A variety of different aFP laser systems are
available, and most of them are based on CO2
and Er:YAG lasers.
Ablative FP systems utilize wavelengths that
are strongly absorbed within tissue as compared
to wavelengths used in nFP systems. The result-
ing high energy densities lead to vaporization of
tissue. An overview of selected aFP systems cur-
rently available commercially is provided in
Table 10.2.
• Ablative Fractional Photothermolysis (aFP) is
a procedure characterized by formation of
microscopically small zones of removed
(ablated) tissue surrounded by a small cuff of
thermally damaged tissue embedded in viable
tissue.
Vaporization of tissue within an MTZ gener-
ated in an aFP procedure forms a tapered cavity
lined by a thin layer of eschar [14]. The thin layer
of eschar is surrounded by an annular coagula-
tion zone containing denatured collagen and cell
necrosis. While the zones of denatured collagen
and cell necrosis substantially overlap, the extent
of the zone of cell necrosis is slightly larger due
to the lower thermal damage threshold for cell
necrosis as compared to that for collagen dena-
turation. A varying degree of thermal damage in
the residual tissue immediately adjacent to the
evaporated tissue of aFP procedures has been
observed, similar to that resulting from conven-
tional ablative resurfacing techniques. The ther-
mal coagulation zone around the laser cavity
typically varies with the type of laser and pulse
duration used. For example, the CO2 laser used in
conventional resurfacing procedures produces
typically more residual thermal damage as com-
pared to the Er:YAG laser [50], and thermal
effects generated by a laser tend to increase with
longer pulse duration [51].
• The pulse duration and temporal pulse shape
affect residual thermal damage.
• Mechanical factors applied during the post
treatment regime might affect clinical skin
tightening.
Analogous to traditional ablative procedures,
the amount of residual thermal injury in aFP pro-
cedures may also be affected by the temporal pro-
file of the laser pulse. Typical temporal profiles
for energy delivery include continuous wave
(CW), superpulsed [52], and ultrapulsed [53]
mode. Although such dependency of thermal in
jury on pulse profile appears reasonable, there is
currently no investigational data available that
specifically relates the extent of thermal damage
for aFP procedures to the temporal pulse profiles.
The amount of immediate skin shrinkage result-
ing from an aFP treatment (with CO2 laser) is
typically greater than that observed in nFP proce-
dures. However, histological analysis indicates
that nFP procedures may even exhibit a greater
total volume of denatured collagen, as compared
to an aFP process performed with similar energy
per MTZ (comparison of data from Hantash et al.
[14] and Thongsima et  al. [28]). This seems to
contradict the general observation that the extent
of skin shrinkage is related to the total amount of
denaturated collagen. The authors hypothesize
that as collagen denaturation and skin shrinkage
occur at virtually the same time while the laser
cavity is being formed, that part of the denatur-
ated collagen is removed during the cavity form-
ing process. Histology reveals a static image of
D. Manstein et al.

187
the amount of denaturated collagen after the com-
pletion of the MTZ formation. Further research is
indicated to investigate the dynamics of the vari-
ous processes occurring within the short time of
the formation of ablative MTZs. In general,
immediate tissue contraction during aFP due to
collagen shrinkage is an indicator of anticipated
skin tightening. However, the role of wound heal-
ing on the clinically relevant skin tightening
should also taken into consideration. Animal stud-
ies have demonstrated that the skin tightening,
including the direction of contraction can also be
significantly affected by factors that were applied
during the wound healing process after the com-
pletion of an aFP procedure. In particular, direc-
tion of mechanical forces (e.g., gravity or elastic
wound dressings) applied during the initial sev-
eral days have been shown to affect significantly
the outcome [54]. These observations should
stimulate further research before specific clinical
recommendations on a modified post treatment
regime can be made.
• Ablative FP impairs the epidermal barrier and
can facilitate enhanced drug delivery but also
bacterial infections.
• The use of antibiotic prophylaxis is typically
indicated for aFP procedures of a larger areas.
• Impairment of epidermal barrier results in tem-
porary serous oozing and punctuate bleeding.
The depth and diameter of MTZs formed
using a particular aFP system is primarily depen-
dent on the energy applied to the tissue to form
each MTZ. Figure 10.13 illustrates the increase
of depth and diameter of an ablated MTZ with
increasing energy. Furthermore, because the stra-
tum corneum is also evaporated in the core of
MTZs formed during aFP, there is an actual dis-
ruption of the physical epidermal barrier that is
proportional to the size and density of MTZs.
Accordingly, aFP leads to more significant
impairment of the protective and barrier function
of the epidermis as compared with non- ablative
techniques. This aspect presents opportunities for
the concurrent delivery of drugs to the tissue but
also imposes additional risks, such as an increased
risk of bacterial infection following aFP proce-
dures. Therefore, the use of antibiotic ­prophylaxis
is typically indicated for aFP procedures of larger
areas. The physical disruption of the epidermal
barrier is also evidenced by serous oozing and
punctuate bleeding following aFP procedures.
However, such side effects related to the disrup-
tion of the epidermal barrier resolve typically
within about 12–24 h after the disruption occurs
[55]. Although ablated MTZs can reach a depth
in excess of 1 mm, they heal relatively fast. A
representative time line of the histological wound
healing for an aFP procedure is illustrated in
Fig. 10.14. Analysis of in-vivo histology at dif-
ferent times after an aFP treatment revealed that
re-epithelialization has taken place within 48 h of
the treatment. The basement membrane was
restored within 7 days, and a coagulation zone
could be observed up to approximately 1 month
after the procedure. A representative time line of
the clinical course after an aFP procedure is pre-
a
b
c
d
e
f
g
Fig. 10.13  Skin histology resulting from aFP at different
energy levels. H&E staining. Lesions were produced
within excised skin with Fraxel re:pair (Solta),
λ = 10,600 nm. MTZ diameter and depth increases with
energy. (a) 10 mJ, (b) 20 mJ, (c) 30 mJ, (d) 40 mJ, (e)
50 mJ, (f) 60 mJ, (g) 70 mJ (Courtesy of Solta Medical,
Biomedical Research Team)
10  Fractional Photothermolysis

188
sented in Fig. 10.15. The duration of wound heal-
ing from aFP is shorter as compared to traditional
ablative CO2 resurfacing procedures, but is
­considered longer than that observed in nFP
procedures.
• Currently aFP is primarily used for dermato-
logical indications that require collagen
remodeling.
• The relative efficacy of aFP and nFP for vari-
ous indications remains to be determined.
Almost all dermatological indications that
have been treated by nFP procedures have also
been treated by aFP procedures [56–58]. The
authors are not aware of any extensive clinical
studies performed to date that the authors are
aware of comparing the outcomes of nFP and
aFP procedures for the same conditions. It is
important for the clinician to have more com-
parative data available to better assess whether
the typically enhanced profile of side effects
associated with aFP procedures is justified by
improved clinical outcomes. Generally, aFP
procedures are observed to provide enhanced
collagen ­remodeling, e.g., for indications such
as skin tightening [59], treatment of skin laxity,
and treatment of moderate to severe rhytides
[60], and overall produces satisfactory results
for these collagen-­sensitive responses with
acceptable post-treatment patient downtime.
Figures 10.16 and 10.17 illustrate cases of clin-
ical improvement of photoaging with concur-
rent respectively moderate and severe rhytides.
Although decreased patient downtime is desir-
able, traditional ablative resurfacing proce-
dures—with generally long downtime periods—
are still the gold standard of treatment for
marked photodamage.
• Options for anesthesia are similar to conven-
tional ablative resurfacing techniques.
Anesthesia for aFP treatments can be pro-
vided by topical agents, local infiltration, cool-
ing, and/or nerve blocks. The level of patient
pain tolerance, the laser parameters used (e.g.,
pulse energies and durations), and treatment
location are all factors to be considered for indi-
vidual pain management. The use of systemic
agents, including narcotics, sedation or intrave-
nous anesthesia, may be warranted for some
patients, particularly when treatment of larger
areas is performed on sensitive patients.
Postoperative management is aimed to alleviate
edema, exudates, and postoperative. Discomfort.
Elevation of the treatment area, cool compresses,
and application of petrolatum ointment are typi-
cally used in postoperative care. When marked
edema and/ or erythema occur following aFP
treatment, a short term course of oral corticoste-
roids may be prescribed.
a
b
c
d
e
Fig. 10.14  Wound healing resulting from aFP at differ-
ent time points. H&E staining. Skin lesions were pro-
duced with Fraxel re:pair (Solta), λ = 10,600 nm at 20 mJ/
MTZ. Analysis of in-vivo histology at different times after
an aFP treatment revealed that re-epithelialization has
taken place within 48 h of the treatment. The basement
membrane was restored within 7 days, and a dermal coag-
ulation zone could be observed up to approximately
1 month after the procedure. At 3 months the lesions were
resolved without evidence of fibrosis. (a) 0  day, (b)
2 days, (c) 7 days, (d) 30 days, (e) 90 days (Hantash et al.
[56])
D. Manstein et al.