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

13/10/2026 • by Bs CKI Phẫu thuật tạo hình, tái tạo và thẩm mỹ Trương Hoài Anh •

Nền tảng khoa học về cơ chế vật lý của Laser và các ứng dụng đột phá trong y học da liễu. Hướng dẫn bác sĩ cách lựa chọn bước sóng, cài đặt thông số điều trị rối loạn sắc tố, sang thương mạch máu và tái tạo bề mặt da an toàn.


📂 Chuyên mục: Tài liệu thẩm mỹ, Da liễu thẩm mỹ, Trẻ hóa da

🏷️ Từ khóa: laser thẩm mỹ, laser da liễu, điều trị sắc tố, xóa xăm, trẻ hóa da bằng laser

Trang: / 558
Trang 1 Trang 2 Trang 3
📖 Xem bản dịch / Nội dung văn bản

189
Adverse Events and Clinical Pitfalls
of FP
• Excessive bulk heating (confluent thermal
damage) must be avoided.
• Treatment of small areas can be particularly
prone to bulk heating.
• In order to minimize the risk of bulk heating,
the following strategies should be considered:
skin cooling, lowering MTZ areal densities,
and providing sufficient time between passes
to allow cooling of the treated tissue.
Although fractional photothermolysis is gen-
erally considered to be safer than traditional abla-
tive techniques that damage a confluent tissue
layer, there are some clinical pitfalls that should
be avoided. Following are several important
a
b
c
d
e
f
Fig. 10.15  Clinical course after aFP treatment. A single
aFP treatment was performed with device Fraxel re:pair
(Solta), 135 μm handpiece, λ = 10,600 nm, 70 mJ/MTZ,
≈300 MTZ/cm2, treatment level 8, 30% nominal cover-
age. Photographs represent baseline (a), immediately
after treatment (b), 3 days (c), 1 week (d), 1 month (e) and
6 months (f) (Courtesy of Steven Struck, M.D.)
10  Fractional Photothermolysis

190
considerations and cautions that should be recog-
nized and addressed when performing FP proce-
dures. One major concern for FP treatments is
generation of bulk heating in the treated tissue.
Bulk heating can facilitate undesirable effects
such as post-inflammatory hyperpigmentation
(which is more commonly observed in Asian
patients) or even result in scarring (Fig. 10.18). To
reduce the risk or extent of such side effects,
proper evaluation of the condition being treated
should be performed (e.g., acne scars, melasma,
rhytides, etc.). An appropriate density of MTZ
formation should also be selected based on the
patient’s skin type to produce effective results
while minimizing the risk of side effects due to
bulk heating. Furthermore, it is important to cool
the tissue in the treatment region during FP proce-
dures. For example, a dynamic air cooling device
(such as the one produced by Zimmer, Inc.) has
been used simultaneously with many FP treat-
ments. It is also recommended to allow sometime
between successive treatment passes over a
Fig. 10.16  Clinical
improvement of
moderate rhytides. A
single aFP treatment was
performed with Active
FX (80 mJ/MTZ,
density 4) and Deep FX
(15 mJ, 15% density)
(Lumenis,
λ = 10,600 nm). The
images exhibit baseline
(left) and 3 months after
a single treatment (right)
(Courtesy of Kevin
Duplechain, M.D.)
Fig. 10.17  Clinical
improvement of severe
rhytides. A single aFP
treatment was performed
with Active FX (80 mJ/
MTZ, density 4) and
Deep FX (15 mJ, 15%
density) (Lumenis,
λ = 10,600 nm). The
images exhibit baseline
(left) and 3 months after
a single treatment (right)
(Courtesy of Kevin
Duplechain, M.D.)
D. Manstein et al.

191
specific body area. However, treatment of small
face or body areas may not allow sufficient time
for skin cooling between passes, which can lead
to bulk heating and scarring. Some observations
of neck and periorbital area scarring, likely
caused by local bulk heating, have been reported
[61].
• For highly-focused laser beams, a precise
positioning of the handpiece is needed.
• Minor positional deviations from the focal
plane could cause significant alteration of spot
size and fill factor.
Operator technique is particularly important
when using ablative FP (aFP) systems. The
highly-focused laser beams generated by these
ablative systems are configured to deliver a
small spot size. Therefore, precise positioning
of the handpiece is relative to the tissue being
treated is extremely important. Any minor devi-
ation of the laser beam focal point from the
desired focal plane can cause significant altera-
tion of the spot size and fill factor because of the
convergent geometry of the focused beam. This
can lead to bulk heating in specific areas, fol-
lowed by potential scarring and pigmentation
changes.
• Particular caution should be exercised at areas
of thin skin and low density of skin appendages.
For patients seeking FP treatment of non-­
facial (e.g., poikiloderma of the neck, periorbital
rhytides), the physician should also be aware of
the lower density of appendageal units in such
areas. This lower density may slow tissue healing
and leave the treated area more susceptible to
infection and scarring. Adequate selection of
MTZ density becomes very important when
treating such areas of the body to avoid unwanted
side effects.
• The use of antiviral prophylaxis is not clearly
established for FP; a history of herpes simplex
virus (HSV), ablative treatments (aFP), and/or
treatment of large areas are factors favoring
anti-viral prophylaxis.
Complications of FP treatment can be caused
by local infections, particularly when performing
aFP procedures that disrupt the stratum corneum.
A universal prophylactic regimen has not yet
been established for such procedures. Patients
with a history of herpes simplex virus affecting
the lips or any facial area are generally advised to
undergo a 1- or 2-day course of oral antivirals
concurrent with the FP procedure. A consensus
for appropriate antibacterial antibiotic prophy-
laxis in conjunction with FP procedures is not
clearly established, either. Antibiotic prophylaxis
is typically indicated when treating large areas
using ablative modalities.
• Pre-operative sun avoidance and discontinua-
tion of retinoids are important factors for min-
imizing side effects.
Pre-operative and post-operative consider-
ations must be discussed and addressed with the
patient prior to initiating a course of FP treat-
ments. During the pre-operative interview and
physical examination, it is important to confirm
the absence of sun burns and sun tanning, which
should be strictly observed for at least 2–4 weeks
prior to the procedure and, ideally, for the
same length of time after the treatment. This
Fig. 10.18  Scar on the upper lip several months after
nFP treatment delivered without adequate skin cooling.
Bulk tissue heating has occurred due to delivery of multi-
ple passes within small areas in relatively short time.
Note: The lesion resolved over 6 months after intralesional
steroid injections and the patient requested additional FP
treatments because of otherwise excellent cosmetic
improvement
10  Fractional Photothermolysis

192
is important in order to reduce the risk of post-­
inflammatory hyperpigmentation, and may be
most relevant to patients living in the tropics and
with a history of sun tanning. Similarly, patients
with solar lentigos and melasma may be given a
choice to first attempt chemical bleaching, fol-
lowed by FP in order to remove remaining pig-
mentation and address textural and rhytides
concerns. On the other hand, late-onset hypopig-
mentation is virtually never observed as result-
ing from FP treatments, in contrast to traditional
resurfacing modalities. During the pre-operative
period for FP, it is also important to address any
prior use of retinoids, either alone or in combi-
nation with other topicals. The patient must be
instructed to stop the use of topical retinoids for
at least 1 week prior to each FP procedure. Use
of oral retinoid therapy (isotretinoin) should
preferably be discontinued for a period of a few
months prior to performing an FP procedure.
• Post-operatively, sun avoidance, compliance
with medication and proper recognition and
management of complications are key.
Post-operatively, patients must be instructed
on proper skin care and strict sun avoidance in
order to prevent side effects and complications,
including pigment alteration. Appropriate antivi-
ral or antibiotic prophylaxis, if recommended,
must be followed by the patient in order to avoid
skin infection and/ or potential scarring.
Complications should be recognized early and
without any delay appropriately managed.
Future Directions
• New indications treatable by FP will continue
to be identified.
Fractional photothermolysis (FP) has been
established as a treatment modality for various indi-
cations. To date, these indications are mostly aes-
thetic in nature. The beneficial effects of FP are not
limited to collagen remodeling, pigment removal
and closure of small vessels. Because FP can induce
a strong wound healing reaction and induces HSP
production, FP procedures may be developed to
affect tissue regeneration, immune regulation,
nerve fiber density, etc. Further investigation of
these effects and others are warranted. FP appears
to be an important tool that is capable of affecting
many different biological pathways, and therefore
it can be expected that more indications treatable
using FP techniques, including a wide spectrum of
dermatological diseases, will continue to emerge.
• Ablative FP can serve to facilitate drug and
cell delivery into the skin.
Another important area of further develop-
ment is the use of aFP for enhanced delivery of
drugs and (stem) cells into different layers of the
skin. It has been demonstrated that transcutane-
ous delivery of a photosensitizer can be enhanced
using a low-density aFP procedure [62, 63]. The
delivery of drugs or other substances that typi-
cally do not pass through the epidermis can thus
be facilitated in a controlled manner over large
areas using aFP treatment. aFP may make it pos-
sible to achieve topical delivery of a plethora of
effective agents into the skin. For example, entire
cell populations could be delivered through gate-
ways formed by ablated MTZs and open up new
strategies for controlled distribution of targeted
(stem) cells into different layers of the skin. FP
may potentially be used, not only for the delivery
of (stem) cells, but also to simultaneously induce
an appropriate and controlled wound healing
response within the recipient tissue. Such wound
healing response may create a microenvironment
that facilitates growth and differentiation of
delivered and/or resident stem cells.
• The channels created by aFP could be used for
delivery of focused optical radiation of virtu-
ally any wavelength to deeper skin layers.
The microscopic ablated MTZ channels cre-
ated by aFP could also be used as a gateway for
delivery of focused optical radiation to deeper
layers of the skin. The delivered optical energy
could be virtually of any wavelength as the opti-
D. Manstein et al.

193
cal barriers of tissue absorption and scattering
may be avoided when the radiation is directed
through these small channels. Spatial and tempo-
ral alignment of ablative and delivered radiation
sources is critical for forming such microscopic
gateways and directing further radiation through
the newly-formed gateways.
• FP is also performed with a home-use product.
Home-use dermatology devices represent an
area of growing interest and recent developments.
The ability for the patient/consumer to perform a
treatment conveniently at home and the huge
commercial market potential are just two of the
many factors driving the market for such devices.
A primary concern when using a home-use
device is guaranteed safety. This presents a chal-
lenge as the consumer, typically possesses only
very limited skill with respect to medical device
procedures. In particular, the ability to set the
treatment parameters sufficiently high, to treat a
wide range of skin types without completely
jeopardizing efficacy, is a prime challenge for
home-use laser applications. FP offers three key
characteristics that could facilitate the develop-
ment of FP-based home use products. First, the
tissue effects of FP are not skin type dependent,
as not melanin but water is the main chromo-
phore. Second, although each individual MTZ
induces a guaranteed wound healing response on
a microscopic scale, the density needed to achieve
a clinical improvement can be distributed over
many treatments, e.g., using a daily application
of low densities over a period of weeks. Such a
treatment regime, which could be easily per-
formed in an at home environment, could result
in safe, minimal incremental effects but signifi-
cant overall improvement after completion of a
treatment course. And third, as relatively low
energy is required to generate individual MTZs,
the energy source (laser) could be produced rela-
tively inexpensively and be battery operated. The
first FDA-approved home-use FP laser device
was commercially released, (the PaloVia device
from Palomar Medical, MA.) This device is a
rechargeable, handheld, non-ablative fractional
photothermolysis laser that can be used for self-­
treatment of wrinkles. The parameters of the
laser were altered to increase the safety profile
for daily or multiple uses per week; operating at
a low wavelength to eliminate the potential of eye
damage, reducing skin coverage percent and
implements a contact sensor that ensure laser
emittance only when full contact around the opti-
cal window is achieved. Side effects of mild ery-
thema and trace edema are observed, while no
severe side effects were reported. This device
demonstrated effectiveness at self-treating wrin-
kles at home with 87% of patients reporting an
improvement in wrinkle appearance after 1 and
3 months of treatment [64].
• FP can potentially be applied to other organs
besides skin.
Although the focus of FP procedures to date
has been on treating skin tissue (skin is the most
accessible organ of the body), the concepts and
effects associated with FP treatment of skin tis-
sue will likely be applicable to other biological
organs and structures. For example, as we learn
how to improve scars within the skin by FP, this
could become a successful modality to improve
fibrosis or degeneration in other organs. Virtually
any organ system is plagued by diseases or con-
ditions caused by such processes. FP procedures
may become a novel treatment option to improve
or restore the functionality of an affected organ.
Potential examples of future non-dermatologi-
cal indications treated with FP are scars (fibro-
sis) of the vocal cord or the heart. Obviously, the
delivery systems for such FP procedures would
have to be modified to be compatible with the
specific anatomy, and further research has to be
performed to investigate the effects of FP on dif-
ferent organ systems. Overall, it appears likely
that in the future FP will also be utilized by spe-
cialties other than dermatology.
• FP treatments show great future promise, but
alternative concepts, such as conventional
laser resurfacing and peeling techniques
should still be considered.
10  Fractional Photothermolysis

194
Despite the efficacy and current popularity of
FP procedures, the conventional resurfacing tech-
niques including chemical peeling procedures
should not be forgotten and will maintain a clini-
cal role, in particularly when cost effectiveness is
a consideration. Fractional treatments are not a
universal solution to all types of dermatological
conditions, but they certainly provide the clinician
and patient additional options to achieve a desired
clinical outcome. Further research is still needed
to provide data that facilitates the selection of
optimal parameters for FP treatment of various
conditions.
Conclusion
Fractional Photothermolysis (FP) exploits the
concept that ‘size matters’ with respect to
laser-­induced damage of biological tissue.
Three-­dimensional patterns of microscopic
treatment zones (MTZs) promote tissue regen-
eration with fast wound healing in the absence
of fibrosis. FP can be applied as a non-ablative
(thermal damage) or ablative (tissue removal)
modality. FP is currently used primarily to
treat fine and moderate rhytides, scars of vari-
ous types, pigmentary disorders, and to repair
photodamaged skin. Novel indications treat-
able using FP continue to emerge. Due to the
recognized efficacy of FP procedures, a prolif-
eration of FP systems employing different
wavelengths and exposure parameters have
been introduced into the marketplace and FP
procedures are offered by a large number of
clinicians. Despite the significant progress in
developing effective FP procedures to date,
the search for ideal treatment parameters and
conditions for the many indications is still
ongoing. There is ample space for future
developments of FP, including identification
of additional treatable indications, adjuvant
treatment modalities to modify the wound
healing response, and improved delivery of
drugs and/or (stem)cells in combination with
aFP treatments. In the future, FP might not be
limited to treatment of skin, but may become
an effective technique for treating and regen-
erating different organ systems.
References
1. Hruza GJ, Dover JS.  Laser skin resurfacing. Arch
Dermatol. 1996;132(4):451–5.
2. Waldorf HA, Kauvar AN, Geronemus RG.  Skin
resurfacing of fine to deep rhytides using a char-free
carbon dioxide laser in 47 patients. Dermatol Surg.
1995;21(11):940–6.
3. Williams EF III, Dahiya R.  Review of nonablative
laser resurfacing modalities. Facial Plast Surg Clin
North Am. 2004;12(3):305–10. v.
4. Bernstein LJ, Kauvar AN, Grossman MC, Geronemus
RG.  The short- and long-term side effects of car-
bon dioxide laser resurfacing. Dermatol Surg.
1997;23(7):519–25.
5. Helm TN, Shatkin S Jr. Alabaster skin after CO laser
resurfacing: evidence for suppressed melanogen-
esis rather than just melanocyte destruction. Cutis.
2006;77(1):15–7.
6. Laws RA, Finley EM, McCollough ML, Grabski
WJ. Alabaster skin after carbon dioxide laser resur-
facing with histologic correlation. Dermatol Surg.
1998;24(6):633–6.
7. Hohenleutner S, Koellner K, Lorenz S, Landthaler
M, Hohenleutner U. Results of nonablative wrinkle
reduction with a 1,450-nm diode laser: difficulties in
the assessment of “subtle changes”. Lasers Surg Med.
2005;37(1):14–8.
8. Manstein D, Herron GS, Sink RK, Tanner H, Anderson
RR. Fractional photothermolysis: a new concept for
cutaneous remodeling using microscopic patterns of
thermal injury. Lasers Surg Med. 2004;34(5):426–38.
9. Laubach HJ, Manstein D. Fractional photothermoly-
sis. Hautarzt. 2007;58(3):216–8. 220–223.
10. Anderson RR, Parrish JA. Selective photothermoly-
sis: precise microsurgery by selective absorption of
pulsed radiation. Science. 1983;220(4596):524–7.
11. Xia Jiang HG, Zhou C, Chai X, Deng H.  The role
of transforming growth factor β1 in fractional laser
resurfacing with a carbon dioxide laser. Lasers Med
Sci. 2014;29:681–7.
12. Wind BS, Meesters AA, Kroon MW, Beek JF, van
der Veen JP, van der Wal AC, Bos JD, Wolkerstorfer
A.  Formation of fibrosis after nonablative and
ablative fractional laser therapy. Dermatol Surg.
2012;38(3):437–42.
13. Grossman AR, Majidian AM, Grossman PH. Thermal
injuries as aresult of CO2 laser resurfacing. Plast
Reconstr Surg. 1998;102(4):1247–52.
14. Hantash BM, Bedi VP, Chan KF, Zachary CB.  Ex
vivo histological characterization of a novel abla-
tive fractional resurfacing device. Lasers Surg Med.
2007;39(2):87–95.
15. Alexiades-Armenakas
MR,
Dover
JS,
Arndt
KA.  Fractional laser skin resurfacing. J Drugs
Dermatol. 2012;11(11):1274–87.
16. Walsh JT Jr, Deutsch TF. Pulsed CO2 laser tissue abla-
tion: measurement of the ablation rate. Lasers Surg
Med. 1988;8(3):264–75.
D. Manstein et al.

195
17. Hale GM, Querry MR. Optical constants of water in
the 200-nm to 200-microm wavelength region. Appl
Opt. 1973;12(3):555–63.
18. Warner DW, Morgan NE, Eby TA, Myers MC,
Taylor DA. Water measurement in biological tissue.
In: Romig AD, Chambers WF, editors. Microbeam
analysis. 21st ed. San Francisco: San Francisco Press;
1987. p. 238–40.
19. Walsh JT Jr, Cummings JP.  Effect of the dynamic
optical properties of water on midinfrared laser abla-
tion. Lasers Surg Med. 1994;15(3):295–305.
20. Manstein D, Zurakowski D, Thongsima S, Laubach H,
Chan HH. The effects of multiple passes on the epider-
mal thermal damage pattern in nonablative fractional
resurfacing. Lasers Surg Med. 2009;41(2):149–53.
21. Laubach H, Chan HH, Rius F, Anderson RR,
Manstein D.  Effects of skin temperature on lesion
size in fractional photothermolysis. Lasers Surg Med.
2007;39(1):14–8.
22. Kositratna G, Manstein D. Skin freezing during abla-
tive fractional resurfacing: in-vitro effects on thermal
lesion size. Lasers Surg Med. 2009;(Suppl 21).
23. Brightman L, Goldman MP, Taub AF. Sublative reju-
venation: experience with a new fractional radiofre-
quency system for skin rejuvenation and repair. J
Drugs Dermatol. 2009;8(11 Suppl):s9–s13.
24. Hantash BM, Ubeid AA, Chang H, Kafi R, Renton
B.  Bipolar fractional radiofrequency treatment
induces neoelastogenesis and neocollagenesis. Lasers
Surg Med. 2009;41(1):1–9.
25. Laubach HJ, Makin IR, Barthe PG, Slayton MH,
Manstein D. Intense focused ultrasound: evaluation of
a new treatment modality for precise microcoagulation
within the skin. Dermatol Surg. 2008;34(5):727–34.
26. Gliklich RE, White WM, Slayton MH, Barthe PG,
Makin IR. Clinical pilot study of intense ultrasound
therapy to deep dermal facial skin and subcutaneous
tissues. Arch Facial Plast Surg. 2007;9(2):88–95.
27. Bedi VP, Chan KF, Sink RK, et al. The effects of pulse
energy variations on the dimensions of microscopic
thermal treatment zones in nonablative fractional
resurfacing. Lasers Surg Med. 2007;39(2):145–55.
28. Thongsima S, Zurakowski D, Manstein D. Histological
comparison of two different fractional photothermol-
ysis devices operating at 1,550 nm. Lasers Surg Med.
2010;42(1):32–7.
29. Laubach HJ, Tannous Z, Anderson RR, Manstein
D.  Skin responses to fractional photothermolysis.
Lasers Surg Med. 2006;38(2):142–9.
30. Hantash BM, Bedi VP, Sudireddy V, Struck SK,
Herron GS, Chan KF. Laser-induced transepidermal
elimination of dermal content by fractional photother-
molysis. J Biomed Opt. 2006;11(4):041115.
31. Alster TS, Tanzi EL, Lazarus M. The use of fractional
laser photo-thermolysis for the treatment of atrophic
scars. Dermatol Surg. 2007;33(3):295–9.
32. Kono T, Chan HH, Groff WF, et al. Prospective direct
comparison study of fractional resurfacing using dif-
ferent fluences and densities for skin rejuvenation in
Asians. Lasers Surg Med. 2007;39(4):311–4.
33. Fisher GH, Kim KH, Bernstein LJ, Geronemus
RG.  Concurrent use of a handheld forced cold air
device minimizes patient discomfort during frac-
tional photothermolysis. Dermatol Surg. 2005;31(9 Pt
2):1242–3. discussion 1244
34. Chan HH, Manstein D, Yu CS, Shek S, Kono
T, Wei WI.  The prevalence and risk factors of
post-­inflammatory hyperpigmentation after frac-
tional resurfacing in Asians. Lasers Surg Med.
2007;39(5):381–5.
35. Lin JY, Chan HH. Pigmentary disorders in Asian skin:
treatment with laser and intense pulsed light sources.
Skin Therapy Lett. 2006;11(8):8–11.
36. Bak H, Kim BJ, Lee WJ, et al. Treatment of striae
distensae with fractional photothermolysis. Dermatol
Surg. 2009;35(8):1215–20.
37. Tierney EP, Kouba DJ, Hanke CW. Review of frac-
tional photothermolysis: treatment indications and
efficacy. Dermatol Surg. 2009;35(10):1445–61.
38. Cohen SR, Henssler C, Johnston J.  Fractional pho-
tothermolysis for skin rejuvenation. Plast Reconstr
Surg. 2009;124(1):281–90.
39. Haedersdal M, Moreau KE, Beyer DM, Nymann P,
Alsbjorn B.  Fractional nonablative 1540  nm laser
resurfacing for thermal burn scars: a randomized con-
trolled trial. Lasers Surg Med. 2009;41(3):189–95.
40. Laubach HJ, Anderson RR, Luger T, Manstein
D. Fractional photo-thermolysis for involuted infantile
hemangioma. Arch Dermatol. 2009;145(7):748–50.
41. Friedmann DP, Tzu JE, Kauvar AN, Goldman
MP.  Treatment of facial photodamage and rhytides
using a novel 1,565 nm non-ablative fractional erbium-­
doped fiber laser. Lasers Surg Med. 2016;48:174–80.
42. Hwang YJ, Lee YN, Lee YW, Choe YB, Ahn
KJ.  Treatment of acne scars and wrinkles in asian
patients using carbon-dioxide fractionl laser resur-
facing: its effects on skin biophysical profiles. Ann
Dermatol. 2013;25(4):445–53.
43. Karsai S, Raulin C.  Fractional photothermoly-
sis: a new option for treating melasma? Hautarzt.
2008;59(2):92–100.
44. Izikson L, Anderson RR. Resolution of blue minocy-
cline pigmentation of the face after fractional photo-
thermolysis. Lasers Surg Med. 2008;40(6):399–401.
45. Karsai S, Hammes S, Rutten A, Raulin C. Fractional
photothermolysis for the treatment of granu-
loma annulare: a case report. Lasers Surg Med.
2008;40(5):319–22.
46. Katz TM, Goldberg LH, Friedman PM. Nonablative
fractional photothermolysis for the treatment of striae
rubra. Dermatol Surg. 2009;35(9):1430–3.
47. Kouba DJ, Fincher EF, Moy RL. Nevus of Ota suc-
cessfully treated by fractional photothermolysis
using a fractionated 1440-nm Nd:YAG laser. Arch
Dermatol. 2008;144(2):156–8.
48. Yoo KH, Kim MN, Kim BJ, Kim CW. Treatment of
alopecia areata with fractional photothermolysis laser.
Int J Dermatol. 2010;49(7):845–7.
49. Behroozan DS, Goldberg LH, Glaich AS, Dai T,
Friedman PM. Fractional photothermolysis for treat-
10  Fractional Photothermolysis

196
ment of poikiloderma of civatte. Dermatol Surg.
2006;32(2):298–301.
50. Khatri KA, Ross V, Grevelink JM, Magro CM,
Anderson RR. Comparison of erbium:YAG and car-
bon dioxide lasers in resurfacing of facial rhytides.
Arch Dermatol. 1999;135(4):391–7.
51. Walsh JT Jr, Flotte TJ, Anderson RR, Deutsch
TF. Pulsed CO laser tissue ablation: effect of tissue
type and pulse duration on thermal damage. Lasers
Surg Med. 1988;8(2):108–18.
52. Fitzpatrick RE, Ruiz-Esparza J, Goldman MP.  The
depth of thermal necrosis using the CO laser: a com-
parison of the superpulsed mode and conventional
mode. J Dermatol Surg Oncol. 1991;17(4):340–4.
53. Fitzpatrick RE, Goldman MP, Satur NM, Tope
WD. Pulsed carbon dioxide laser ­resurfacing of photo-
aged facial skin. Arch Dermatol. 1996;132(4):395–402.
54. Wanner M, Farinelli W, Manstein D. Ablative fractional
resurfacing evaluation of different exposure parameters
in a pig model. Lasers Surg Med. 2008;20(Suppl):28.
55. Hantash BM, Bedi VP, Kapadia B, et al. In vivo histo-
logical evaluation of a novel ablative fractional resur-
facing device. Lasers Surg Med. 2007;39(2):96–107.
56. Hunzeker CM, Weiss ET, Geronemus RG. Fractionated
CO2 laser resurfacing: our experience with more than
2000 treatments. Aesthet Surg J. 2009;29(4):317–22.
57. Chapas AM, Brightman L, Sukal S, et al. Successful
treatment of acneiform scarring with CO2 abla-
tive fractional resurfacing. Lasers Surg Med.
2008;40(6):381–6.
58. Waibel J, Beer K. Ablative fractional laser resurfac-
ing for the treatment of a third-degree burn. J Drugs
Dermatol. 2009;8(3):294–7.
59. Rahman Z, MacFalls H, Jiang K, et al. Fractional deep
dermal ablation induces tissue tightening. Lasers Surg
Med. 2009;41(2):78–86.
60. Dierickx CC, Khatri KA, Tannous ZS, et  al.
Micro-fractional ablative skin resurfacing with
two novel erbium laser systems. Lasers Surg Med.
2008;40(2):113–23.
61. Avram MM, Tope WD, Yu T, Szachowicz E, Nelson
JS. Hypertrophic scarring of the neck following abla-
tive fractional carbon dioxide laser resurfacing. Lasers
Surg Med. 2009;41(3):185–8.
62. Haedersdal M, Sakamoto FH, Farinelli WA, Doukas
AG, Tam J, Anderson RR.  Fractional CO(2)
laser-assisted drug delivery. Lasers Surg Med.
2010;42(2):113–22.
63. Erlendsson AM, Anderson RR, Manstein D, Waibel
JS.  Developing technology: ablative fractional
lasers enhance topical drug delivery. Dermatol Surg.
2014;(Suppl 12):S142–6.
64. James Leyden TJS, Herndon JH Jr. Multicenter clini-
cal trial of a home-use nonablative fractional laser
device for wrinkle reduction. J Am Acad Dermatol.
2012;67(5):975–84.
D. Manstein et al.

197
© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Sub-surfacing Lasers
Michael Howard Gold
Abstract
Sub-surfacing lasers consist of a variety of
medical devices.
KTP lasers.
Pulsed dye lasers.
Keywords
Sub-surfacing lasers · Non-ablative lasers ·
Photorejuvenation · Laser toning · Fine lines
and wrinkles · Skin dyschromias
Outline and Introduction
1. Sub-surfacing lasers consist of a variety of
medical devices
(a) KTP lasers
(b) Pulsed dye lasers
(c) 1064 nm Q-Switched Nd: YAG lasers
(d) 1064 nm Long Pulsed Nd: YAG lasers
(e) 1319/1320 nm Nd: YAG lasers
(f) 1450 nm Diode lasers
(g) 1540 Erbium Glass lasers
(h) Intense Pulsed Light Sources
2. Developed to meet need of efficacy in
rejuvenation without associated downtime
(a) Erbium
and
CO
laser
resurfacing
standards
(b) Adverse events, too much downtime
(c) New devices to effect collagen in dermis,
minimal downtime
(d) Epidermal cooling required for treatment
to be safe and effective
(e) All
have
clinical
studies
showing
effectiveness
(f) All have a rejuvenation effect
(g) All have potential for adverse events
including blistering, burns, pigmentary
concerns, scars
Indications
and
Contraindications—
Clinical information regarding these devices with
published evidence of safety and efficacy.
M. H. Gold
Gold Skin Care Center and Tennessee Clinical
Research Center, Nashville, TN, USA
e-mail: goldskin@goldskincare.com
11
• Ablative laser resurfacing has been the
gold standard throughout the 1980s and
1990s for improving skin texture by ren-
ovating photo damaged and aging skin.
• Although excellent results have been
obtained with the use of ablative laser
devices, the use of non-ablative laser sys-
tems have been increasingly popular as an
alternative to obtaining the same results.

198
Introduction
The field of sub-surfacing lasers is also known
commonly by the terms non-ablative laser resur-
facing, photorejuvenation, and laser toning. A
variety of lasers and light sources have been
developed and utilized for sub-surfacing and will
be the subject of this review.
Included in the overall category of sub-
surfacing lasers are a diverse range of technologies
which include the KTP lasers at 532  nm; the
pulsed dye lasers at 585–595 nm; the Nd:YAG
lasers which encompass the 1064 nm long pulsed
systems, the 1064 nm Q-switched laser systems,
and the 1319/1320 nm laser systems; the 1450 nm
diode laser systems; the erbium glass laser sys-
tems at 1540  nm; as well as the spectrum of
intense pulsed light (IPL) systems at wavelength
range of 500–1200  nm. All of these medical
devices have proven successful for non-ablative
laser/light source resurfacing, photorejuvenation,
and the improvement of acne scars [1, 2].
These devices were developed, from a
historical point of view, to rival the ablative laser
resurfacing systems which enjoyed much
popularity in the 1980s and 1990s. The ablative
laser systems, predominantly identified by the
erbium laser systems at 2940 nm and the carbon
dioxide resurfacing lasers with a wavelength of
10,600  nm, were and are the mainstays of the
ablative laser resurfacing systems. The ablative
laser resurfacing systems are the gold standard
for skin resurfacing and still to this day are the
standards to which all other laser or light sources
for rejuvenation of the skin are judged as to their
safety and efficacy. The ablative laser resurfacing
systems work by removing the entire epidermis
and portions of the dermis which results in a
wound that, upon healing, gives a desired rejuve-
nation effect. These devices have been used for
many years and have proven effective in improv-
ing skin roughness, fine lines and wrinkles, and
skin dyschromias which are common manifesta-
tions associated with skin aging and photodam-
age. These ablative laser resurfacing devices can
produce very nice and long-lasting results, as evi-
denced in Figs.  11.1 and 11.2. However, when
performing these types of laser procedures,
patients must understand that there will be sig-
nificant downtime with these treatments, lasting
upwards of 1 week or more before full reepitheli-
zation will occur, and then several more weeks
where the skin is still pink until complete healing
has occurred. As well, some patients have pro-
longed erythema, as seen in Fig.  11.3, which
requires appropriate and thoughtful intervention
from qualified clinicians to help minimize. And,
as a long term sequelae to many of these
a
b
c
Fig. 11.1  (a–c) Clinical examples of ablative laser resurfacing with long-lasting results
• The mechanism of ablative laser
resurfacing involves the removal of the
epidermis and the dermis, causing a
wound to develop which may take up to
several months to heal.
• The use of non-ablative laser systems
have minimal side-effects by causing
direct thermal damage to the dermis,
while sparing the epidermis, and
re-during the risk of post-treatment
adverse effects and downtime.
M. H. Gold

199
a
b
Fig. 11.2  (a, b) Clinical examples of ablative laser resurfacing with long-lasting results
a
b
Fig. 11.3  (a, b) Clinical example of prolonged erythema after ablative laser resurfacing
11  Sub-surfacing Lasers

200
procedures, a significant number (reported any-
where from 10 to 20%) may develop a post-treat-
ment hypopigmentation, which may not be
evident for several months to years following the
initial procedure, as depicted in Fig.  11.4.
However, these ablative laser resurfacing devices
still remain the gold standard for skin resurfacing
but other devices were developed in an attempt to
reproduce these kinds of results, with minimal
downtime, predictable results, and less chances
for adverse or long term results [3–5].
The purpose of the development of the non-
ablative laser resurfacing is to affect changes in
the skin similar to what the ablative laser resur-
facing devices achieve. These devices were
developed to improve the skin’s texture, to
improve facial lines and wrinkles and surface
irregularities including facial scars. In addition,
some of these devices also address pigmentary
dyschromias and vascular changes in the skin
associated with photodamage and actinically
damaged skin. The non-ablative lasers and light
sources work via thermal injury to the dermis,
with epidermal sparing, thereby reducing the
potential for any associated with these proce-
dures. These medical devices have been demon-
strated to work over a period of time and through
a series of treatments, usually in the realm of five
to six treatments given at 3–4 week intervals [3].
Maintenance therapy, although not addressed
in many accounts of sub-surfacing lasers, is usu-
ally required at certain time intervals, as well as
proper skin care to maintain the rejuvenation
effect one is attempting to achieve. In contrast to
the amount of literature which the ablative laser
resurfacing devices have enjoyed in the medical
literature, these sub-surfacing lasers have not had
an overwhelming scientific base in the literature
but have had descriptive coverage of the various
devices and their effects.
Various classifications of these sub-surfacing
lasers have been used over the past several
years—we will classify them as shown in
Table 11.1. Table 11.1 shows that these medical
devices can be classified into (1) vascular
lasers, (2) mid-infrared lasers and (3) intense
pulsed light sources. The remainder of this
chapter will review the literature of the vascular
lasers, the mid-infrared lasers, and the IPLs.
This chapter will not review the realm of frac-
tional lasers, which include non-ablative lasers,
ablative fractional lasers, radiofrequency based
Fig. 11.4  Clinical example of long-term sequelae after ablative laser resurfacing
M. H. Gold

201
fractional lasers, or the microneedling frac-
tional lasers. They will be reviewed elsewhere
in this textbook.
Vascular Lasers
KTP Lasers
The KTP lasers have traditionally been utilized to
treat small caliber facial telangiectasias on the
face and there is little in the medical literature
which can be attributed to the use of the KTP
lasers in rejuvenation of the skin. In a study by
Lee [6], 150 patients were treated with the KTP
laser and the 1064  nm laser separately and
together for non-ablative facial rejuvenation.
Patients in this series received three to six treat-
ments of both the KTP laser alone, the 1064 nm
laser alone, and the combination of both devices.
Skin biopsies looking at histologic effects in the
skin were performed at 1, 2, 3, and 6 months fol-
lowing the last treatment. The results showed that
the KTP laser was superior to the 1064 nm laser
in improving the parameters of photorejuvena-
tion of the skin but that the combination of
devices was superior to either one of the devices
used alone. Post-therapy skin biopsies confirmed
the presence of new collagen formation as well as
Table 11.1  Sub-surfacing lasers
Device type
Device name
Manufacturer
1.  Vascular lasers
KTP laser
Excel V™
Cutera
The RevLite SI
Cynosure
Pulsed dye lasers
Veam perfecta
Syneron
Cynergy
Cynosure
NLite
ICN Pharmaceuticals
NLite.htm
2.  Mid-infrared lasers
Q-switched 1064 nm
Medlite C6
Cynosure
RevLite
Long-pulsed 1064 nm
YAG 5
Cynosure
Gentle YAG
Syneron
Apogee Elite
Cynosure
1319/1320 nm
Profile 1064 nm
Sciton
CoolTouch® C3
Syneron
1450 nm
Profile 1319
Sciton
1510 nm
SmoothBeam
Syneron
Aramis
Quantel
3.  Intense pulsed light sources
Lumenis one™/M 22
Lumenis
BBL
Sciton
Harnony
Alma lasers
PPX/isolaz
Solta
Ellipse flex
DDD
• Studies have shown that KTP lasers
have better collagen formation results
when compared to 1064 nm lasers in the
treatment of skin photo-rejuvenation.
• Pulsed dye lasers (PDL) function best in
the treatment of vascular lesions (i.e.,
port wine stains and hemangiomas) with
significant production of procollagen
type I and type III.
• Increased activity of dermal fibroblasts
and mucin, as well as the thickening of
the stratum spinosum in the dermis, has
been noticed in the restoration of degen-
erated skin.
• The use of modern PDL systems for
skin rejuvenation provides non-ablative
results by minimizing side-effects and
reducing purpura.
11  Sub-surfacing Lasers

202
a result of these lasers systems. Others, including
Goldberg [7] found similar results in ten
patients—again treated with a millisecond Nd:
YAG laser and a millisecond KTP laser showed
greater effects on tissue rejuvenation. Tan et al.
[8] also demonstrated this synergistic effect of
these two laser systems—25% more improve-
ment with the combined systems at 1 month for
more than one third of the patients which
increased to 40% at the end of 4 months.
Pulsed Dye Lasers
Pulsed dye laser, also known commonly as
flashlamp-pumped pulsed dye lasers, are the
­prototype medical devices that were developed
which adhere to the principle of selective
­photothermolysis [9]. Selective photothermolysis
is a principle which states that a specific wave-
length of light can specifically destroy a chromo-
phore within the skin, which in the case of the
pulsed dye lasers is hemoglobin. The pulsed dye
laser systems have improved in many facets over
the years, especially in their methods of epider-
mal cooling and in that they have longer pulse
durations than their predecessor devices, which
reduces the incidences for purpura as a result of
the therapy, considered one of the necessities of
the early pulsed dye lasers but also one of the
drawbacks from the treatment. These devices
have been routinely used to treat vascular lesions
(facial telangectasia, diffuse erythema, and other
superficial vascular lesions) and their successes
in the treatment of port wine stains and heman-
giomas have been well reviewed in the medical
literature [10–12]. Pulsed dye lasers have shown
to be useful in reducing the erythema and improv-
ing stretch marks [13] and these devices have and
these devices have also been used successfully to
treat hypertrophic scars and keloidal lesions,
especially being able to reduce the associated
erythema sometimes associated with these
lesions [14, 15]. In the process, many of these
scars have shown dermal remodeling and an
associated shrinkage of the scar itself. The exact
mechanism of pulsed dye induced collagen for-
mation is not clear but it has been proposed that
thermal induced damage to vascular endothelium
may produce cytokines leading to dermal remod-
eling and thus the improvement of fine lines and
wrinkles [3].
Several
clinical
evaluations
have
been
performed which support the use of the pulsed
dye lasers for a non-ablative rejuvenation effect.
Rostan et al. [16] utilized a long pulsed 595 nm
laser in evaluating wrinkles of the cheeks. Fifteen
patients received a series of four treatments at
monthly intervals, either with the laser on or with
cryogen only in the control group. The group per-
formed skin biopsies prior to the pulsed dye laser
treatments and at 4–6 weeks following the last
laser treatment, as well as 3 months following the
last laser treatment. They specifically looked at
routine histology, procollagen I production and
the activity of dermal fibroblasts. They found that
the Grenz zone was moderately thicker in 50% of
patients in both groups treated, but the degree of
thickening was greater in the treatment groups
than the controls. Similar findings were also seen
at 3 months following the laser treatments, when
an increase in dermal collagen was also observed
in the treatment sites. A statistically significant
improvement in the clinical grading scale for
photodamage was also noted in the study.
Zelickson et  al. [12] evaluated ten patients
with mild to moderate facial lines and wrinkles
and ten patients with moderate to severe facial
lines and wrinkles that were treated with a single
laser treatment with a 585 nm pulsed dye laser
with a 450 μm pulse duration. Clinically nine out
of ten patients in the mild to moderate wrinkle
group showed 50% or more improvement with
3/10 showing 75% or more improvement. All of
the patients maintained their improvements for
6 months following their last laser treatment. In
contrast, only 3/10 patients in the moderate to
severe wrinkle group improved during the study.
Skin biopsies from those patients in the mild to
moderate group were performed at 6 and
12  weeks following the laser treatment. The
biopsy specimens showed a thickened stratum
spinosum and a thickened collagen layer in the
superficial dermis as well as increased mucin in
the superficial dermis. They also performed ultra-
structural evaluations which demonstrated an
M. H. Gold

203
increase in collagen fibers and an increase in the
number of fibroblasts in the treated skin. They
also noted that there was an increase in normal
appearing elastic fibers and a decrease in the
clumping of degenerated elastic fibers in the skin.
Zelickson and Kist [17, 18] have also reported
results from skin biopsies performed after two
periorbital 585 nm pulsed dye treatments or IPL
treatments (6 week apart) in which in-situ hybrid-
ization mRNA probe studies were performed
6 weeks after the second treatment.
These studies showed an 18% increase in type
I collagen production after the IPL treatments
compared to a 23% increase in type I collagen
production after the pulsed dye therapy.
Collagenase transcriptase activity was 32% for
the IPL and 40% for the pulsed dye laser. The
authors concluded that the observed increases in
mRNA in fibroblasts indicated that through this
non-ablative light, extracellular matrix protein
production by dermal fibroblasts is increased,
thus resulting in the effects seen.
Others have also looked at the pulsed dye
lasers for its potential in rejuvenation of the skin.
Bjerring et al. [19] utilized a 585 nm pulsed dye
laser with a 350 um pulse duration and studied
suction blisters which had been treated with the
pulse dye laser. Using special markers for the
production of type III procollagen they were able
to demonstrate significant increases in type III
procollagen levels after a single treatment with
the pulsed dye laser, but also demonstrated a drop
in type III procollagen levels after a retreatment.
Goldberg et al. [20] also performed skin biopsies
with a similar pulsed dye laser looking at facial
lines and wrinkles. In this study, patients received
two pulsed dye laser treatments. Pre-treatment
and 6 month post-treatment clinical evaluations
and skin biopsies were analyzed. Forty percent of
the individuals noted mild improvement in their
wrinkle appearance. Ultrastructural analyses
showed increases in type I and III collagen in
those treated with the pulsed dye lasers. A second
study by these authors [21] evaluated clinical,
histologic, and ultrastructural changes after non-
ablative treatments utilizing varying settings in
the same subject. Ten patients were included in
this clinical trial. The patients were randomly
divided into two groups of five. All of the patients
received 595 nm pulsed dye laser treatments to
the periorbital areas. The first group was treated
once, while the second group was treated twice at
a 1  month interval. Each side of the face was
treated with distinctly different laser settings.
Seventy percent of the patients noted mild to
moderate improvement clinically after treatment
at 6 months following the last treatment. There
was no difference between receiving one or two
treatments in this study. Histologic and electron
microscopy improvement was noted in all of the
patients.
The major side effect of pulsed dye lasers in
the past was purpura, which has virtually been
eliminated with today’s more sophisticated
machines, with longer pulse durations and
improved epidermal cooling. However, purpura
is a side effect still sometimes seen, and blister
formation, pigmentary dyschromias, as well as
scarring have been noted with the pulsed dye
lasers.
• Q-switched 1064  nm laser systems
stimulate
deep
dermal
collagen
stimulation have shown to cause
re-epithelization faster than carbon
dioxide systems. Further studies have
shown that Q-switched
• 1064  nm laser devices significantly
decrease solar elastosis and thicken
upper
papillary
dermal
zones
of
collagen.
• 1064  nm Nd: YAG laser devices have
useful skin tightening mechanisms for
skin rejuvenation.
• With the use of epidermal cooling
devices, such as cryogen, 1319/1320 nm
laser devices have provided optimal
results in the formation of new collagen,
reduction of lines and wrinkles. These
non-ablative laser systems leave the epi-
dermis intact and provide great results
in all skin rejuvenating procedures.
• 1450  nm mid infrared diode laser
systems have functioned successfully in
11  Sub-surfacing Lasers

204
Mid-Infrared Lasers
Q-Switched, 1064 nm Nd: YAG Lasers
Several investigations have evaluated the effects
of the Q-switched 1064 nm laser system for the
treatment of facial lines and wrinkles. These
Q-switched laser systems were originally
designed for the treatment of densely pigmented
blue-black tattoos but have also been found to be
potentially useful in the rejuvenation of the skin,
due to its deep penetration into the skin and
thereby stimulating dermal collagen. Goldberg
and Whitworth [22] evaluated the Q-switched
1064 nm laser in a comparative study to carbon
dioxide laser systems. Eleven subjects were
included in this evaluation. All of the patients
treated with the carbon dioxide laser systems
improved in this clinical study. Nine of the eleven
patients improved with the Q-switched 1064 nm
laser. Complete reepithelization occurred faster
(3–6 days earlier) in the patients treated with the
Q-switched laser as compared to the carbon diox-
ide systems. The authors concluded that the
Q-switched 1064 nm laser may play a role in the
treatment of rhytids. Goldberg and Metzler [23]
utilized a 1064 nm Q-switched laser and a topical
carbon solution in an attempt to potentiate the
laser effects. Two hundred forty two solar dam-
aged sites were treated with three treatments on
61 patients. The investigators found that as a
result of this adjuvant care, patients had improve-
ments in skin texture and skin elasticity. Goldberg
and Silapunt [24] evaluated skin biopsies from
infraauricular skin treated with two passes of the
Q-switched laser before and after 3 months fol-
lowing the last treatment in eight patients.
Clinically, six of the eight patients in the trial
showed improvement by an independent observer.
Four of the six biopsy specimens evaluated
showed decreases in solar elastosis and a mildly
thickened upper papillary dermal zone of collagen.
More organization of the collagen bundles was also
seen in this clinical study. Cisneros et al. [25] eval-
uated 22 patients who were treated twice with the
Q-switched laser system—all with improvement.
1064 nm Nd:YAG Lasers
Very little literature exists as far as the efficacy of
utilizing the 1064 nm long pulsed Nd: YAG laser
in the treatment of fine lines and wrinkles. In a
recent study by Taylor [26], a comparison was
made to the skin tightening ability of the long
pulsed 1064 nm laser in comparison to the mono-
polar radiofrequency device. In this particular
clinical trial the results showed that the 1064 nm
was as useful in skin tightening as the radiofre-
quency device. Clinical examples are shown in
Figs. 11.5 and 11.6.
1319/1320 nm Laser Systems
These mid-infrared laser systems have had a lot
of play in the non-ablative, sub-surfacing laser
field of rejuvenation. The 1320 nm laser system,
known as CoolTouch®, from the CoolTouch®
Corporation (Roseville, CA), now owned by
Syneron Candela was the original sub-surfacing
device developed specifically for the treatment of
facial lines and wrinkles utilizing the non-ablative
technique.
Subsequently, a 1319  nm laser system from
Sciton (Palo Alto, CA) has also been introduced
to this realm of sub-surfacing lasers.
The goal of these laser systems has always
been to create a dermal wound resulting in the
the treatment of active inflammatory
acne vulgaris, acne scars on the face,
fine lines and wrinkles. This laser
system targets dermal water, creates a
wound in the dermis and triggers the
regeneration process of collagen.
• 1540  nm Erbium Glass laser devices
have clinically proven dermal remodel-
ing by treating fine lines and wrinkles,
acne vulgaris and acne scars, and atro-
phic scars on the face. These lasers use a
sapphire lens cooling device throughout
the treatment process.
M. H. Gold

205
formation of new collagen, a reduction in lines
and wrinkles, and to leave the epidermis intact.
This has been achieved very well through the
use of these devices and appropriate epidermal
cooling. Clinical examples are shown in
Figs. 11.7 and 11.8.
Utilizing unique delivery systems for cryogen
spray delivery to the skin and with thermal sen-
sors, the CoolTouch device was and is the proto-
type of the 1319/1320 nm laser systems on the
market. It has had extensive clinical investiga-
tions performed using it over the years. Clinical
Fig. 11.5  Clinical example of skin tightening using 1064 nm
Fig. 11.6  Clinical example of skin tightening using 1064 nm
11  Sub-surfacing Lasers

206
assessment and skin biopsy clinical studies have
been carried out by Goldberg [27], Trelles et al.
[28] and Levy et al. [29]. In all of these clinical
evaluations, skin biopsies performed at the end of
the treatments showed evidence of new collagen
formation. All of the patients had solar elastosis
prior to treatment and demonstrated improve-
ment clinically and histologically following the
treatments. Goldberg [30] also evaluated ten
patients with facial lines and wrinkles who
received treatment five times with the CoolTouch
device over 3–4 week intervals. At 6 months fol-
lowing the last treatment, all of the patients
reported a subjective improvement in the quality
of their skin; only six of the ten were felt to be
clinically improved by the investigator. All of the
subjects showed evidence of new collagen for-
mation at 6 months in skin biopsies.
Fatemi et  al. [31] showed that with the
1320 nm laser system that three passes from the
device are better than a single pass in causing the
early laser-induced histologic changes seen
which noted included vascular damage, apopto-
sis,
and
edema—the
beginning
of
the
­inflammatory mediator cascade required for col-
lagen formation to occur.
Fig. 11.7  Clinical example of 1319/1320 nm treatment
Fig. 11.8  Clinical example of 1319/1320 nm treatment
M. H. Gold

207
1450 nm Diode Lasers
The 1450  nm mid infrared diode laser system,
known as the SmoothBeam from Syneron
Candela Corporation (Wayland, MA), has been
used as a treatment for active inflammatory acne
vulgaris and for the treatment of acne scars on the
face. It can also be used in a non-ablative fashion
for the treatment of fine lines and wrinkles as
well. This laser system works similarly to the
1320 nm laser systems in that its wavelength tar-
gets dermal water, creates a wound in the dermis,
and in the regeneration process forms new der-
mal collagen resulting in the desired effect.
In a study by Tanzi and Alster [32], they
compared the 1450 nm diode laser to the 1320 nm
Nd:YAG laser in the treatment of atrophic facial
scars. Twenty patients with mild to moderate
atrophic facial acne scars received three monthly
treatments with the 1450 nm laser to one half of
the face and the 1320 nm laser to the other half of
the face. Clinical evaluations and skin biopsy
specimens were performed at various time inter-
vals, including up to 1 year post the last treat-
ment. Mild to moderate clinical improvement
was observed clinically in the majority of patients
studied. The 1450 nm diode laser showed greater
clinical scar response at the parameters studied
(fluences from 9 to 14 J/cm2). The same group
also have investigated the 1450 nm laser for the
treatment
of
rhytids—periorbital
rhytids
improved more so than transverse neck lines
[33].
Acne vulgaris treatment with the 1450  nm
diode laser has received much attention.
Paithankar et al. [34] treated patients with acne to
their entire back area affected with acne and
found that when treating four times at 3  week
intervals, a statistical and clinical decrease in
acne lesions was noted. Friedman et al. [35] also
studied the effects of the 1450 nm diode laser on
sebaceous glands on the back and noted damage
to the glands following therapy.
The SmoothBeam laser has shown quite a bit
of efficacy over the years. Even with its sophisti-
cated cryogen cooling, significant pain has been
noted to occur in many patients, which has lim-
ited this machines ultimate further widespread
use. A clinical example is shown in Fig. 11.9.
1540 nm Erbium Glass Laser
The 1540 nm erbium glass laser has seen extensive
study in Europe for the treatment of fine lines and
wrinkles, acne scars, and for the treatment of
Fig. 11.9  Clinical example of 1450 nm treatment
11  Sub-surfacing Lasers

208
atrophic scars on the face. It has also been used
successfully to treat active inflammatory acne
vulgaris. Less clinical work appears to have been
done on this device in the United States. This
device utilizes a sapphire lens cooling device
which delivers its contact cooling. Clinical evalu-
ations with the device include Fournier et al. [36]
in which patients treated with this device had a
40% reduction in wrinkles and a 17% increase in
epidermal thickness at 6  weeks following the
fourth treatment. The study evaluated 42 patients
over a 14 month period of time. Lupton and Alster,
looking at histologic effects from the erbium glass
laser, demonstrated significant dermal remodeling
and clinical satisfaction in 24 individuals 6 months
after their final treatment (four treatments at
1 month intervals). In another study, Lupton et al.
[37] evaluated the use of the 1540 nm Er: Glass
laser in 24 patients’ facial wrinkles. Mild to mod-
erate improvement in facial lines and wrinkles
were seen in all of the study subjects; dermal
fibroplasia was noted in the skin biopsy
specimens.
All of the mid infrared devices have shown
safety and efficacy. As noted with the 1450 nm
diode laser, pain is its most common adverse
event. All of the mid infrared laser systems can
cause significant discomfort without proper
epidermal cooling. As well, most of these
devices will result in some erythema and edema
which, in the majority of cases, will resolve
within 24–48 h. As with all laser systems, other
adverse events can be seen with these devices,
including pigmentary alterations and scarring
of the skin. A clinical example is shown in
Fig. 11.10.
Intense Pulsed Light (IPL) Sources
IPLs have been around since the early 1990s and
have withstood the test of time and criticism to
become the most widely used medical devices in
the world for photo-rejuvenation. The first of
Fig. 11.10  Clinical example of 1540 nm treatment
• Intense Pulsed Light (IPL) devices emit
polychromatic light in broad ranges of
wavelengths, selectively filtered to tar-
get specific chromophores, between 500
and 1200 nm.
• IPLs treat vascular lesions, pigmentation,
and have shown to have an effect in the
production of collagen and elastic fibers
in the dermis. Studies have shown that
IPL
photo-rejuvenation
treatments
using cooling apparatuses considerably
increase
epidermal
thickness,
and
improve skin texture.
• The necessary cooling devices are
required in all non-ablative devices to
avoid the adverse effects relating to skin
damaged. Blisters and pigmentary
lesions can occur without the proper
handling of cooling devices.
M. H. Gold

209
these light sources was a high-intensity flashlamp
medical devices were initially developed for the
treatment of vascular anomalies of the skin, spe-
cifically leg veins and telangectasias [38]. IPLs
are pulsed light sources which emit polychro-
matic light in a broad wavelength of the light
spectrum, usually between 500 and 1200  nm.
Many different variations on the IPL theme are
now available, some with smaller absorption
ranges, others with radiofrequency included to
potentiate the effect of the broadband light, and
still others with a vacuum apparatus included to
bring the light in a colder relationship to the light
itself. IPL devices of today are much more
sophisticated than their predecessors but always
are cautioned that not all IPLs are the same. In a
recent well performed study by Town et al. [39]
various IPLs were evaluated to determine their
true pulse width (in an independent means) and
to evaluate their true output in joules per centime-
ter squared over the time of the pulse. Differences
were observed between devices and even based
on some of the manufacturers’ claims. These
devices are very popular in today’s culture; one
must be aware of the company developing it and
what clinical work rests behind it.
Although not true lasers, these devices also
follows the principles of selective photothermol-
ysis [9] in that with varying filters, or cut-off fil-
ters, one can use the IPL to selectively target a
specific chromophore in the skin to cause a select
affect upon that structure. It has been clearly
demonstrated that the IPLs can treat vascular
lesions, pigmentary concerns, and does have an
effect on the collagen and elastic fibers in the der-
mal tissues [40]. These photorejuvenation effects
of the IPL will now be reviewed.
The first major study in the field of
photorejuvenation associated with a series of IPL
treatments was published by Biter in 2000 [41].
In this trial, 49 individuals received a series of
treatments with an IPL device, with a minimum
of four treatments given at 3 week intervals. In
his study, he found that all of the parameters of
photodamaged skin were improved in over 90%
of those entered into this clinical trial. These
included skin wrinkling, skin coarseness, irregu-
lar pigmentation, large pore size, and skin telan-
gectasias. Skin biopsies taken from the forehead
and 4 weeks after the last IPL treatment showed
new collagen in both the papillary and reticular
dermis as well as a resolution of any superficial
dermal infiltrates.
Other studies utilizing an IPL demonstrating
non-invasive resurfacing have also been per-
formed. In his study, Hernandez-Perez et al. [42]
evaluated five patients with five treatment ses-
sions with an IPL.  Moderate to very good
improvement in the signs of photodamage were
observed. Skin biopsy specimens were obtained
at baseline and at 1 week following the final (5th)
treatment. These biopsy specimens showed an
increase in epidermal thickness, and an improve-
ment in dermal concerns—specifically dermal
elastosis, edema of the dermis, telangectasias
present, as well as any dermal infiltrate. In
another investigation, Negishi et al. [43] evalu-
ated 73 individuals with an IPL. The patients in
this clinical evaluation received at least five treat-
ment sessions with the IPL. Clinical results noted
a greater than 60% improvement in skin texture,
in reduction of telangectasias, and in reducing
pigmentary concerns in more than 80% of the
patients who participated in the trial. Skin biop-
sies obtained at baseline and at 3 weeks follow-
ing the final therapy showed an increase in types
I and III collagen, as demonstrated by immunos-
taining. Goldberg, in several clinical trials,
looked at rhytids following IPL therapy and
clearly demonstrated an improvement in skin
wrinkles which were also demonstrated histo-
logically [44, 45]. Prieto et al. [46] in their evalu-
ation of IPL induced rejuvenation effects found
similar collagen changes as compared to other
authors but also found, through routine histology
and electron microscope analyses, that after
1 week following therapy, there was no perifol-
licular infiltrate evident. Furthermore, at 3 and
12 months, demodex and an associated lymphoid
infiltrate were observed. The authors postulated
that because of the transient therapeutic effect of
the coagulative necrosis of demodex organisms, a
nonablative effect can occur. A long term evalua-
tion by Weiss et al. [47] demonstrates that once
the rejuvenation has had its effect, it can last for
up to 5 years—83% of patients followed contin-
11  Sub-surfacing Lasers

210
ued improvement in skin texture; telangectasias
improvement of 82%; and pigmentation remained
improved in 79%.
Examples of photorejuvenation as a result of
IPLs are shown in Figs. 11.11 and 11.12.
As noted, IPLs have much play in today’s
laser world. Because they are more sophisticated
than ever before, most with exceptional cooling
apparatus’ to increase the safety of the devices,
more and more physicians and others are utiliz-
ing them on a daily basis all over the world.
Remember, these are medical devices that can
damage the skin and cause horrific effects, as can
all of the devices described in this report.
Before
After 4 Treatments
a
b
Fig. 11.11  (a, b) Clinical example of photorejuvenation with IPL
a
b
Fig. 11.12  (a, b) Clinical example of photorejuvenation with IPL
M. H. Gold

211
Techniques/Devices
Table 11.1 lists the names and manufacturers of
the most commonly used lasers/light sources in
each category along with the web address of
those companies where further information to
specifics may be obtained.
Adverse Events
All of the sub-surfacing devices have the potential
to do harm. Because their mechanism of actions
requires dermal injury with sparing of the
epidermis, skin cooling becomes of paramount
importance. Without proper epidermal cooling,
which these machines do have, skin burning and
blisters can occur. As a result, all of these devices
have the potential to cause pigmentary changes
and/or scars. These can be minimized by proper
understanding and usage of the devices.
Future Directions
Personal opinion: The sub-surfacing devices have
given us a good head start into the non-ablative
laser world. I do believe other technology, more
sophisticated and yielding even better results
(safely) have been developed, namely the fractional
lasers and RF fractional devices. I think that the
IPLs have been an incredible addition to our reju-
venation efforts and I think they, in particular, will
continue to be utilized, either alone or in combina-
tion, for the treatment of photo-damage. I think that
the newer fractional resurfacing devices offer
increased efficacy over the sub-surfacing devices,
and even in the fractionated realm it appears that
the newer devices being developed are more abla-
tive in nature than non-ablative. There will always
be a role for the non-ablative resurfacing concept—
positive results with none to minimal downtime.
Hopefully, more devices of these kinds will be
developed, benefiting physicians and patients alike.
Conclusions
Sub-surfacing, or non-invasive resurfacing, or
photorejuvenation, have been a very popular
part of the laser culture these past 15 years or
so. Many of the devices described have shown
a great deal of clinical efficacy, although at
times, it has been difficult to document due to
these changes being, at times, subtle. But our
patients have been the ones who have bene-
fited from these devices as they have always
known the changes to be real, all with minimal
to no downtime, one of the most important
concepts of modern day lasers. Many of these
procedures are now being replaced with the
fractionated laser systems, which is covered
elsewhere in this text. Sub-surfacing devices
can provide you and your patients with much
satisfaction.
References
1. Nelson JS, Majaron B, Kelly KM. What is nonablative
photorejuvenation of human skin? Semin Cutan Med
Surg. 2002;21:238–50.
2. Kelly KM, Kristen M, Majaron B, Nelson
JS.  Nonablative laser and light rejuvenation. The
newest approach to photodamaged skin. Arch Facial
Plast Surg. 2001;3:230–5.
3. Alam M, Hsu T-S, Dover JS, Wrone DA, Arndt
KA. Nonablative laser and light treatments: histology
and tissue effects—a review. Lasers Surg Med.
2003;33:30–9.
4. Papadavaid E, Katsambas A. Laser resurfacing review.
Int J Dermatol. 2003;42:480–7.
5. Fitzpatrick RE. Laser resurfacing of rhytids. Dermatol
Clin. 1997;15:431–47.
6. Lee MC. Combination aura 532 nm and lyra 1064 nm
lasers for non-invasive skin rejuvenation and toning.
Lasers Surg Med. 2002;30:32.
7. Goldberg DJ.  Non-ablative dermal remodeling:
comparing 3 different wavelengths: does it make a
difference? Lasers Surg Med. 2002;30:31.
8. Tan MH, Dover JS, Hsu TS, Arndt KA, Stewart
B. Clinical evaluation of enhanced nonablative skin
rejuvenation using a combination of 532- and 1064-
nm laser. Lasers Surg Med. 2004;34:439–45.
9. Anderson RR, Parrish RR. Selective photothermolysis:
precise microsurgery by selective absorption of pulsed
radiation. Science. 1983;220:524–7.
10. Alster TS, Kurban AK, Grove GL, Grove MJ, Tan
OT.  Alteration of argon laser induced scars by the
pulsed dye laser. Lasers Surg Med. 1993;13:368–73.
11. Ashinoff R, Geronemus RG.  Flashlamp-pumped
pulsed dye laser for port wine stains in infancy:
earlier versus later treatment. J Am Acad Dermatol.
1991;24:467–72.
12. Zelickson BD, Kilmer SK, Bernstein E, et al. Pulsed
dye laser therapy for sun damaged skin. Lasers Surg
Med. 1999;25:229–36.
11  Sub-surfacing Lasers

212
13. McDaniel DH, Ash K, Zukowski M.  Treatment of
stretch marks with the 585  nm flashlamp-pumped
pulsed dye laser. Dermatol Surg. 1996;22:332–7.
14. Alster TS.  Improvement of erythematous and
hypertrophic scars by the 585 nm flashlamp-pumped
pulsed dye laser. Ann Plast Surg. 1994;32:186–90.
15. Alster TS, Williams CM.  Treatment of keloid
sternotomy scars with 585 nm flashlamp-pulsed dye
laser. Lancet. 1995;345:1198–2000.
16. Rostan E, Bowes LE, Iyer S, Fitzpatrick RE. A double-
blind, side by side comparison study of low fluence
long pulse dye laser to coolant treatment for wrinkling
of the cheeks. J Cosmet Laser Ther. 2001;3:129–36.
17. Zelickson BD, Kist DA.  Pulsed dye laser and
photoderm treatment stimulated production of type
I collagen and collagenase transcriptase in papillary
dermis fibroblasts. Lasers Surg Med. 2001;13:31.
18. Zelickson BD, Kist DA. Effect of pulsed dye laser and
intense pulsed light source on the dermal extracellular
matrix remodeling. Lasers Surg Med. 2000;12:17.
19. Bjerring P, Clement M, Heikendorff L. Selective non-
ablative wrinkle reduction by laser. J Cutan Laser
Ther. 2000;2:9–15.
20. Goldberg D, Tan M, Sarradet MD.  Non-ablative
dermal remodeling with a 585 nm, 350 um flashlamp
pulsed dye laser: clinical and ultrastructural analysis.
Dermatol Surg. 2003;29:162–4.
21. Goldberg DJ, Sarradet MD, Hussain M, Krishtul A,
Phelps R.  Clinical, histologic, and ultrastructural
changes after nonablative treatment with a 595-nm
flashlamp-pumped pulsed dye laser: comparison of
varying settings. Dermatol Surg. 2004;30:979–82.
22. Goldberg DJ, Whitworth J.  Laser skin resurfacing
with the Q-switched Nd:YAG lasers. Dermatol Surg.
1997;23:903–6.
23. Goldberg DJ, Meltzer C.  Skin resurfacing utilizing
a low-fluence Nd:YAG laser. J Cutan Laser Ther.
1999;1:23–7.
24. Goldberg DJ, Silapunt S.  Q-switched Nd: YAG
laser: rhytid improvement by nonablative dermal
remodeling. J Cutan Laser Ther. 2000;2:157–60.
25. Cisneros JL, Del Rio R, Palau M.  The Q-switched
neodymium (Nd) laser with quadruple frequency.
Dermatol Surg. 1998;23:345–50.
26. Taylor MB, Prokopenko I. Split-face comparison of
radiofrequency versus long-pulse Nd-YAG treatment
of facial laxity. J Cosmet Laser Ther. 2006;8(1):17–22.
27. Goldberg DJ.  Non-ablative subsurface remodeling:
clinical and histologic evaluation of a 1,320  nm
Nd:YAG laser. J Cutan Laser Ther. 1999;1:153–7.
28. Trelles MA, Allones I, Luna R. Facial rejuvenation
with a nonablative 1,320  nm Nd: YAG laser: a
preliminary clinical and histologic evaluation.
Dermatol Surg. 2001;27:111–6.
29. Levy JL, Trelles MA, Lagarde JM, Borrel MT,
Mordon S.  Treatment of wrinkles with the non-
ablative 1,320  nm Nd: YAG laser. Ann Plast Surg.
2001;47:482–8.
30. Goldberg
DJ. 
Full-face
nonablative
dermal
remodeling with a 1320 nm Nd: YAG laser. Dermatol
Surg. 2000;26:915–8.
31. Fatemi A, Weiss MA, Weiss RA.  Short-term
histological effects of nonablative resurfacing: results
with a dynamically cooled millisecond-domain
1320  nm Nd:YAG laser. Dermatol Surg. 2002;28:
172–6.
32. Tanzi EL, Alster TS. Comparison of a 1450-nm diode
laser and a 1320-nm Nd: YAG laser in the treatment
of atrophic facial scars: a prospective clinical and
histologic study. Dermatol Surg. 2004;30:152–7.
33. Alster TS, Tanzi EL.  Treatment of transverse neck
lines with a 1,450 nm diode laser. Lasers Surg Med.
2002;14:33.
34. Paithankar DY, Ross EV, Saleh BA, Blair MA, Graham
BS.  Acne treatment with a 1,450  nm wavelength
laser and cryogen spray cooling. Lasers Surg Med.
2002;31:106–14.
35. Friedman PM, Jih MH, Kimyai-Asadi A, Goldberg
LH. Treatment of inflammatory facial acne vulgaris
with the 1450 nm diode laser: a pilot study. Dermatol
Surg. 2004;30:147–51.
36. Fournier N, Dahan S, Barneon G, et al. Nonablative
remodeling: a 14 month clinical ultrastructural
imaging and profilometric evaluation of a 1540 nm
ER: Glass laser. Dermatol Surg. 2002;28:926–31.
37. Lupton JR, Williams CM, Alster TS.  Nonablative
laser skin resurfacing using a 1540 nm erbium glass
laser: a clinical and histologic analysis. Dermatol
Surg. 2002;28:833–5.
38. Goldman MP, Eckhouse S. Photothermal sclerosis of
leg veins. Dermatol Surg. 1996;22:323–30.
39. Town G, Ash C, Eadie E, Moseley H. Measuring key
parameters of intense pulsed light (IPL) devices. J
Cosmet Laser Ther. 2007;9(3):148–60.
40. Raulin C, Greve B, Grema H.  IPL technology: a
review. Lasers Surg Med. 2003;32:78–87.
41. Bitter PH. Noninvasive rejuvenation of photodamaged
skin using serial, full-face intense pulsed light
treatments. Dermatol Surg. 2000;26:835–43.
42. Hernandez-Perez E, Ibiett EV. Gross and microscopic
findings in patients submitted to nonablative full face
resurfacing using intense pulsed light: a preliminary
study. Dermatol Surg. 2002;28:651–5.
43. Negishi K, Wakamatsu S, Kushikata N, Tezuka Y,
Kotani Y, Shiba K.  Full face photorejuvenation of
photodamaged skin by intense pulsed light with
integrated contact cooling: initial experiences in
Asian skin. Lasers Surg Med. 2002;30:298–305.
44. Goldberg DJ, Cutler KB.  Nonablative treatment of
rhytids with intense pulsed light. Lasers Surg Med.
2000;26:196–200.
45. Goldberg DJ, Samady JA.  Intense pulsed light and
Nd: YAG laser. Nonablative treatment of facial
rhytids. Lasers Surg Med. 2001;28:141–4.
46. Prieto VG, Sadick NS, Lloreta J, Nicholson J, Shea
CR. Effects of intense pulsed light on sun-damaged
human skin. Routine and ultrastructural analysis.
Lasers Surg Med. 2002;30:82–5.
47. Weiss RA, Weiss MA, Beasley KI. Rejuvenation of
photoaged skin: 5 year results with intense pulsed
light of the face, neck, and chest. Dermatol Surg.
2002;28:1115–9.
M. H. Gold

213
© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Non-invasive Rejuvenation/Skin
Tightening: Light-Based Devices
Marina Perper, John Tsatalis, Ariel E. Eber,
and Keyvan Nouri
Abstract
The popularity of non-invasive cosmetic
improvement of the skin has continued to
grow amongst patients and practitioners alike.
Cost and pain remain the principal limiting
factors for patients.
The safety of epidermal treatment in dark
skin types has remained a challenge.
Today, non-invasive treatment of photoag-
ing can be achieved with light devices. A com-
bination treatment which in my experience
has proven to be safe and painless is described
here.
Keywords
Non-invasive · Epidermal treatment · Skin
rejuvenation · Skin tightening · Photoaging ·
Light-based devices
Introduction
• The popularity of non-invasive cosmetic
improvement of the skin has continued to
grow amongst patients and practitioners alike.
• Cost and pain remain the principal limiting
factors for patients.
• The safety of epidermal treatment in dark skin
types remains a challenge.
• Today, non-invasive treatment of photoaging
can be achieved with light devices. A combina-
tion treatment which in my experience has
proven to be safe and painless is described here.
A place in modern aesthetic procedures for
non-invasive modalities is now well earned.
The appeal of such procedures in the eyes of
prospective patients is understandable. As for
doctors, the possibility of improving someone’s
appearance without having to resort to drastic,
painful and potentially risky procedures rapidly
M. Perper · J. Tsatalis · A. E. Eber · K. Nouri (*)
Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine,
Miami, FL, USA
e-mail: m.perper@umiami.edu; jxt252@miami.edu;
a.eber@med.miami.edu; knouri@med.miami.edu
12

214
became the choice of many. It is to be under-
stood that the changes induced are not as dra-
matic
as
those
obtained
by
aggressive
modalities, but they are not as drastic or irre-
versible either, thereby becoming a plus not a
minus. Good candidates for these procedures
are the ones who can live with the idea of grad-
ual, subtle changes that, on the other hand, will
not draw unnecessary stares, such as after an
invasive Plastic Surgery correction. In addition,
non-invasive procedures can now be directed at
specific elements of photoaging, to specifically
correct them. In such manner, the skin may be
divided in three basic strata: Deep, being the
reticular dermis; mid, being the papillary der-
mis and superficial being the epidermis. Each
of these strata exhibit distinct changes attribut-
able to premature aging, namely: flaccidity,
thinning or loss of substance, and brown (pig-
mentary) and red (vascular) dyschromias on the
surface of the skin.
However, two are the limiting factors that
need to be considered:
1. Cost: Being that multiple repeated procedures
are needed to effect a change and
2. Pain: The interest of patients in these proce-
dures is, in general, inversely proportional to
the pain inflicted by them and therefore it is in
the interest of the practitioner to be able to
provide his patients with procedures that can
be performed with as little pain as possible.
The procedures described here can be carried out
without pain and without anesthesia whatsoever.
They are safe for all skin types and promote easy
patient’s acceptance because of lack of discom-
fort during and after treatment as well as carefree
post operative time. As mentioned before, patients
should understand that a series of treatments may be
necessary to achieve the desired change. They are to
understand as well, that the changes obtained after
these procedures are subtle and may not be noticed
after each individual session, but through comple-
tion of a series and or, upon photographic com-
parison of before and after pictures. Improvement
however, can be noticed after only one treatment
session (Figs. 12.1, 12.2, 12.3, 12.4 and 12.5) and
improves after multiple or combined multiple ses-
sions (Figs. 12.6, 12.7, 12.8 and 12.9). If the patient
desires dramatic changes he or she is probably not a
good candidate for these procedures.
Pre
6 months
Fig. 12.1  Six months post one Titan treatment
M. Perper et al.

215
Fig. 12.2  Six months post one Titan treatment
Fig. 12.3  Eight months post one Titan treatment
12  Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices

216
Pre
2 months
Fig. 12.4  82 year old woman before and 1 month post a single Titan treatment
Before
After
Fig. 12.5  One month post one Titan treatment
M. Perper et al.

217
a
b
Fig. 12.6  (a) Three months post one Titan 3 Nd:YAG showing better skin quality and (b) in lateral view
12  Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices

218
Fig. 12.7  Pre and 6 month post combination treatment Titan plus Nd:YAG
Fig. 12.8  Pre and post one Titan and 5 Nd:YAG
M. Perper et al.

219
On the other hand, we have gradually improved
our understanding of how skin tightening takes
place and how it can be induced painlessly and
immediately using light. A long way has passed
since we were trying to elicit a change using flash
intense heating with radiofrequency. In a simi-
lar manner, when we use the Nd:YAG laser as
later described, a change in skin quality is first
noticeable after only a few days when treating the
mid layer with laser, and there is even a change
that is noticed immediately: pore size reduction.
Dyschromias will also improve within a matter of
days, again using light, intense pulsed light. So,
all in all, these change account for an excellent
acceptance level for the vast majority of patients
who undergo these treatments, provided we have
outlaid a plan of treatment and of expected level
of improvement in all detail prior to starting the
series and never a posteriori.
Photoaging in the Deep Stratum
of the Skin Causing Skin Laxity
Can Be Treated with Light
• Skin tightening can best be induced using long,
gradual, sustained multi second pulses of heat
• If the tissue is heated in this manner, it can be
done painlessly
• Immediate skin tightening is observed in nearly
all patients regardless of age or skin type
For the purpose of this writing we will limit
ourselves to the mid and lower thirds of the face
and neck. Unwanted skin flaccidity starts at vari-
able degrees for individual patients during the
third decade of life. Jowls, loss of sharpness in
the mandibular lines, laxity of cheeks and deepen-
ing of the nasallabial fold individually or collec-
tively may appear. The traditional approach years
ago, was that of a rhytidectomy or face lift. The
problem was that this procedure, alone, corrects
by pulling the lax skin following one vector of
movement, causing in some cases, distortion of
landmarks of the face such as the corners of the
mouth. Inducing skin contraction by delivering
deep, sustained heat to the deep dermis, aims to
cause a minute global shrinking, that will revert
the skin to its original position to some degree.
Achieving that with light, requires a source of heat
that can be on for extended periods of time and
that does not cause pain on contact with the skin.
In other words, a long pulse of light, and cooling
of the treatment surface of the device, the one that
Fig. 12.9  Seven days after combination treatment of one Titan, 3 Nd:YAG and 5 IPL
12  Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices

220
gets in contact with the surface of the skin while
the light is on. The light must have a wavelength
which allows for penetration to the level of the
target, i.e.,: the deep reticular dermis. The closest
to such a device is Titan by Cutera, Inc.
Titan is an infrared light device emitting light at
1100–1800  nm in multi second cycles. At these
wavelengths, there is a moderate level of water
absorption and therefore it can thoroughly heat the
dermis over a period of seconds. It differs from other
infrared devices in that they usually have much
smaller spot sizes and also have very short pulse
durations (milliseconds) as well as a very high water
absorption which results in shallow heating only. It
has a spot area of 1 cm × 1.5 cm. Although it is an
infrared lamp, it is not a flashlamp. “Flashlamps”
produce light at lower wavelengths (more visible
light) and are usually pulsed at short (millisecond)
durations. This is a broadband infrared lamp that
emits longer wavelengths and is better suited for
­multi-­second pulse durations. Heat penetration
depth from this device is estimated to be about
1–2 mm, but some heating does occur down to about
5 mm. These calculations were done using dermal
scattering coefficients and water penetration depths
for near infrared wavelengths to estimate an “effec-
tive penetration depth” for a particular wavelength.
The total intensity was then calculated by adding up
the contribution from individual wavelengths. These
models were then confirmed by actual thermal mea-
surements of ex-­vivo tissue samples and an appro-
priate filter design was selected based on the desired
thermal profile obtained by the manufacturer.
Technique: Both, physician and patient should
wear appropriate protection goggles. This author
uses now a technique that differs from the tradi-
tional one for this device. It is a gliding tech-
nique, in which the treatment window is glided in
vertical lines on the cheeks and neck. The
machine is then set to emit the highest possible
pulse which also has the longest possible pulse,
lasting several seconds. The fluence is set at 65 J/
cm2. But since the device is engineered to emit a
pre-cooling pulse of cold, as well as a trans-­
cooling and post cooling pulse, care is taken to
avoid the pre and post-cooling because they are
unnecessary in this particular technique. So, the
device is made to begin contact with the skin sur-
face immediately after the blue light indicator of
cold emission is followed by the yellow light of
infrared light emission. Then the handpiece is
glided in a vertical fashion until the yellow light
stops. When the blue light alone continues, at the
end of each pulse, care should be taken to with-
draw the handpiece from skin contact. This
avoids unpleasant cold sensation for the patient.
As mentioned above, I use the “S” handpiece at a
setting of 65 J/cm, with pulses of 9.2 s duration. I
find the “V” and “XL” handpieces less adequate
for the glide technique due to their sharp edges.
At the beginning heat is almost impercep-
tible for the patient. The strokes are then
repeated, over and over with some overlapping
to produce the desired goal: incremental, sus-
tained heating that because it is not sudden
and intense, it is painless. Many strokes are
necessary to elicit visible contraction, in my
experience from 40 to 60 in each area, consid-
ering each cheek one area, and each side of the
neck one area as well. Gliding is facilitated by
the use of a hydrophilic gel such as K-Y Jelly.
(Johnson and Johnson). Contraction can be
seen with the patient lying down but it becomes
more apparent when the patient sits up. The
contrast with the untreated side demonstrates
the contraction to the patient (Figs.  12.10,
12.11, and 12.12) with the simple use of a
Fig. 12.10  Immediate skin contraction after Titan on left
cheek
M. Perper et al.

221
a
b
Treated side
Untreated side
Fig. 12.11  (a)
Immediate skin
contraction on treated
cheek and (b) in close up
mirror. As mentioned, this technique, properly
performed is painless even in the beard area in
men, in which the traditional “stamping” tech-
nique usually hurts. The following principle
must be understood: The skin will contract by
applying heat slowly, steadily, progressively
and sustainably. Overlapping strokes is per-
mitted and desirable always guided by pain
sensation. No pain is necessary to elicit con-
traction, with gentle heat applied for enough
time, thus 40–60 gliding strokes of the hand-
piece are needed. Intense heat applied by the
conventional “stamping technique” hurts and
may not be the best for the patient. An animal
hide will contract if put in a dryer with enough
heat for enough time (Figs. 12.12 and 12.13).
12  Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices

222
A Most Impressive Case of Tissue
Contraction: Animal hide subjected to
sustained slow heat for enough time
a
b
A Most Impressive Case of Tissue
Contraction: Animal hide subjected to
sustained slow heat for enough time
Pre
Immediate Post
Pre
Immediate Post
Fig. 12.12  (a, b) Animal hide contraction with slow sustained heat
Appropriate heating was applied to
elicit contraction
A Flame (intense brief heat) would have
burned the hide, not contracted it
Fig. 12.13  Slow and low heating can bring about appro-
priate contraction
Sudden intense heat in brief pulses (such as
that produced by a flame) will fail to contract
the hide. Similar intense pulses in patients,
whether originated by radiofrequency or light,
will not offer the best contraction possible in
clinical practice.
No post-operative care is required. Post-­
operative pain, swelling or bruising do not
occur.
These treatment sessions can be repeated to
improve results. Usually at monthly intervals
until the desired level of improvement is
achieved. I also recommend maintenance treat-
ments every year for patients under 50 and
every 6  months for patients over 50  years of
age. Genetics, skin type, degree of sun protec-
tion and outdoor lifestyles will necessitate dif-
ferent maintenance schedules.
M. Perper et al.

223
A 1064 nm Nd:YAG Laser Is Used
to Treat the Mid Stratum of the Skin
• The Nd:YAG laser can be used to improve
skin quality.
• We use a repetition rate of 10 Hz at 15 J/cm, in
300 ms pulses.
• An airbrush technique about 1–2 cm from the
skin surface is used.
• We use five sessions of 5000 pulses each.
• Improvement can be observed within a month
from each procedure.
• When adequately performed, the procedure is
painless for most patients.
With this modality, an improvement in the
quality of the skin is sought for. Improvement
will start to be perceived by the patient usu-
ally after 1 week and will be at a peak after
1 month. An improvement in skin texture, soft-
ening of very fine static rhytids, a reduction of
pore size, a diminution of actinic bronzing and
an improvement in skin clarity and glow may
result. Again, this technique is safe in all skin
types.
Because of its wavelength, this laser can be
used to reach the level of the papillary dermis.
When engineered to deliver 15  J, in 300  ms
pulses with a spot size of 5 mm, it can be deliv-
ered painlessly even at a repetition rate of 10 Hz.
Technique: Again, both, physician and patient
should wear appropriate protection goggles.
First, we must understand the following
principles:
1. The degree and speed of heating will be pro-
portional to the speed of the hand of the
­operator as well as the distance between the
handpiece and the skin.
2. Small areas heat up faster than larger ones. A
repeated air brush movement is needed.
3. The face must be divided in relatively small
areas rather than attempting to treat the entire
face at the same time. In this manner, the fore-
head is considered one area, each cheek with
the corresponding side of the nose will be
another, and the perioral area and chin another
area.
4. The operator will move to the next area in
circles. Each will be treated generally with
five consecutive passes.
5. Pain or immediate redness are NOT treatment
goals or endpoints.
6. The machine counts pulses automatically. The
number of pulses will vary. Typically, 5000
pulses for 5 monthly sessions. Lately, I have
found that more pulses in a single session are
more rewarding and safe. We now deliver
15,000–25,000 in a single treatment session.
Improvement of the Superficial
Stratum of the Skin Using Light
• Intense pulsed light (IPL) can be used to
improve some epidermal signs of photoaging.
• Pigmented or vascular dyschromias are
exceedingly common and are ideal targets for
this procedure.
• The procedure can be safely applied in dark
skin types in the following manner: The pro-
cedure is done at daily intervals for 5 days.
• We use the “Limelight” device by Cutera, Inc.
• We start at 8 J/cm, “C” mode for skin types
III–V and “B” for skin types I–II.
• We use increments of 2 J/cm daily.
• Mild burning sensation during each pulse is
expected. No pain afterwards.
• The cooled tip is kept in situ after each pulse
long enough for the burning sensation to
disappear.
Intense pulsed light (IPL) has been used for a
number of years and an abundant body of litera-
ture has been published on the subject. We will
deal in this chapter with the means to make this
procedure safe for all skin types and to minimize
discomfort and post-operative the undesirable
treatment effects that we usually see when a con-
ventional technique is used.
The device that we use (“Limelight” by
Cutera, Inc.) emits light between 520 and
1100  nm. It has a cooled sapphire handpiece.
Three distinct factory-set programs are available
labeled A, B and C. A delivers the shortest wave-
length and pulse duration and is aimed to treat
12  Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices

224
skin types I–II mainly with vascular dyschro-
mias. B has a longer wavelength emission and
correspondingly shorter cooling times. It is used
in pigmented and vascular dyschromias in skin
type I–III. The C program is the safest for darker
skin types and emits in the longest wavelength
range available for the machine. It also has the
longest pulse duration. A so-called “Pigment
mode” is available. This has a shorter cooling
time and appears to be more effective in pigmen-
tary targets. We use this mode carefully in darker
types.
The initial fluence used for treatments will
vary from 8 J/cm2 for skin types II–IV to 12 J/
cm2 for skin type I–II. We do daily treatments for
1 week with increments in fluence of 2 J/cm2 per
day if tolerated. Two passes are the routine, per
session. We take the time to cool the skin leaving
the cool handpiece in situ for a few seconds or
after the burning sensation from the light pulse
disappears, after the emission of the light pulse.
This aids significantly to decrease the level of the
discomfort produced by these treatments, espe-
cially in dark skin types. We do not apply pre-or
post-treatment cooling pads. Daily sessions will
turn the chromophore in the skin darker by the
day, augmenting the ultimate effect on pigmented
lesions. On the other hand, gradual increments in
fluence permit to reach higher levels safely. This
is crucial in dark skin tones or suntanned skin.
Patients can expect darkening of the pig-
mented target lesions after 48 h and spontaneous
sloughing of the lesions within 1 week. By doing
daily treatments we curtail erythema post treat-
ment and are able to deliver ultimately higher flu-
ences, which, we feel aids in the final result. In
this manner for example we are able to deliver up
to 16 J/cm2 in skin type IV by the fifth day.
Low-Level Light Therapy (LLLT)
for Skin Rejuvenation
Low level laser therapy, phototherapy or photo-
biomedulation, is an upcoming, non-invasive
treatment modality for improve the appearance of
wrinkles, dyspigmentation, telangiectasia, and
loss of elasticity occurring hand in hand with
aging. The therapy exposes tissue to low-levels of
red and near infrared (NIR light) and stimulates
or inhibits a variety of cellular processes using a
lesser degree of energy or power than more tradi-
tional treatments such as ablation, cutting, and
thermally coagulating tissue. Unlike traumatic
ablative (e.g., laser resurfacing) and non-ablative
(e.g., intense pulsed light [IPL]), treatments that
produce secondary tissue repair through con-
trolled damage to either the epidermis or the der-
mis, Significant variation in dosimetry parameters
between different LLLTs, including wavelength,
irradiance or power density, pulse structure,
coherence, polarization, energy fluence, irradia-
tion time, contact vs. non-contact application,
and repetition regimen, warrants additional
assessment of the devices. For our purposes, we
will describe the use of LED (light-emitting
diode) therapy, a type of LLLT which facilitates
non-thermal, non-ablative skin rejuvenation, in
improving wrinkles and skin laxity. Because
LED light sources have dot-shaped (punctiform)
emission characteristics and narrow spectral
bandwidths, it is recommended to apply a poly-
chromatic spectrum covering a broader spectral
region for skin rejuvenation and skin repair.
Although
varying
parameters
may
be
employed during LED treatment, treatments
applied on the face most typically involve 633,
and 830 nm at fluences of 126 and 66 J/cm2. We
focus on successful treatment procedures
described by Bhat et  al. using the Omnilux
Revive LED lamp for facial skin rejuvenation.
While using the Omnilux Revive LED lamp
for rejuvenation, patients are first seated comfort-
ably in a chair and are pre-cleansed with a cleans-
ing lotion. The patient then receives non-coherent
red light at a wavelength of 630(±3) nm and an
intensity of 80 mW/cm2 at a dose of 96 J/cm2.
Patients are treated three times weekly for 3
weeks for a total of nine treatments. Each session
lasts 20 min.
Results using this method have proved prom-
ising, with substantial patient satisfaction indi-
cated just 5 weeks after treatment. Reduction in
fine lines and wrinkles, smoother and firmer skin,
and perception of softer skin have been noted as
beneficial effects of the treatment. Further, unlike
M. Perper et al.

225
more invasive methods including ablative and
non-ablative laser treatments, no pain or adverse
effects have been noted from the LED treatment.
Limitations of this treatment modality include
little improvement in skin elasticity and
hydration.
Photodynamic Therapy (PDT)
for Skin Rejuvenation
Photodynamic therapy (PDT) is a treatment that
can be performed using both laser and nonlaser
light. Mechanistically, PDT uses oxygen and
light in combination with a photosensitizing
agent to selectively target cells. Photosensitizing
agents are drugs that only activate when struck
with a specific wavelength of light. PDT can be
used to treat a variety of skin issues such as acne
and unwanted ageing, although it has been tradi-
tionally used for the treatment of superficial basal
cell carcinoma and actinic keratosis. Other uses
for PDT are still being investigated.
The most common complication of this treat-
ment is the “PDT effect”. The “PDT effect” is
expressed as redness, peeling, and crusting of the
skin. Exposure to sunlight during a 48-h period
after treatment can make the reaction worse.
Oftentimes, though, those with the most dramatic
reactions have superior results.
While PDT is not commonly used for facial
rejuvenation, it is a less-invasive alternative that
has gained traction with clinicians. When used in
combination with intense pulsed light (standing
in as the photosensitizing agent), PDT is an effec-
tive treatment. This combination is used to treat
vascular erythema, fine rhytides, epidermal dys-
chromia, and photodamage. In treatment of pho-
toaging, PDT-IPL therapy has the added benefit
of treating premalignant lesions. Additionally,
healing times are brief. Unfortunately, PDT-IPL
therapy is unable to resurface the skin and cannot
penetrate deep enough to treat other unwanted
skin lesions. Other techniques involve using a
pulse-dye laser in conjunction with PDT.
There are three stages in photodynamic ther-
apy. The first, involves the practitioner thor-
oughly cleaning the skin and gently scraping the
skin to increase absorption of the photosensitiz-
ing agent. Three to six hours are allowed for the
drug to be fully absorbed. The second stage lasts
from 5 to 45 min and consists of the light being
directed at the treatment area. The third stage
involves skin sensitivity following the treatment
for up to 2 weeks. In one study, PDT was per-
formed twice at 1-month intervals, and results
were evaluated 1 month after the final treatment.
Lesions were treated with noncoherent red light
of emission wavelength 580–740  nm, dose of
100  J/cm2, and fluence rate of 100  mW/cm2.
Parameters vary per clinician and should be
based on prior success, however. Recomm­
endations for PDT for different lesions have been
published.
Bibliography
1. Alexiades-Armenakas M. Assessment of the mobile
delivery of infrared light (1100-1800 nm) for the treat-
ment of facial and neck skin laxity. J Drugs Dermatol.
2009;8(3):221–6.
2. Avci P, et al. Low-level laser (light) therapy (LLLT)
in skin: stimulating, healing, restoring. Semin Cutan
Med Surg. 2013;32(1):41–52.
3. Dang Y, Ren Q, Hoecker S, Liu H, Ma J, Zhang J. 
Biophysical, histological and biochemical changes
after non-ablative treatments with the 595 and
1320 nm lasers: a comparative study. Photodermatol
Photoimmunol Photomed. 2005;21(4):204–9.
4. Dang YY, Ren QS, Liu HX, Ma JB, Zhang JS. 
Comparison of histologic, biochemical, and mechani-
cal properties of murine skin treated with the 1064-
nm and 1320-nm Nd:YAG lasers. Exp Dermatol.
2005;14(12):876–82. Institute for Laser Medicine
and Biophotonics, Shanghai Jiaotong University of
Shanghai, China.
5. Goldberg DJ.  Non-ablative subsurface remodel-
ing: clinical and histologic evaluation of a 1320-nm
Nd:YAG laser. J Cutan Laser Ther. 1999;1(3):153–7.
6. Goldberg DJ, Samady JA.  Intense pulsed light and
Nd:YAG laser nonablative treatment of facial rhytids.
Lasers Surg Med. 2001;28(2):141–4.
7. Goldberg DJ, Silapunt S. Q-switched Nd:YAG laser:
rhytid improvement by non-ablative dermal remodel-
ing. J Cutan Laser Ther. 2000;2(3):157–60.
8. Hassan KM, Benedetto AV. Facial skin rejuvenation:
Ablative laser resurfacing, chemical peels, or pho-
todynamic therapy? Facts and controversies. Clin
Dermatol. 2013;31(6):737–40.
9. Min-Wei CL. Novel 3-in 1 wavelength light source
for photorejuvenation. J Drugs Dermatol. 2009;7(4):
335–9.
12  Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices

226
10. Morton CA, McKenna KE, Rhodes LE. Guidelines for
topical photodynamic therapy: update. Br J Dermatol.
2008;159(6):1245–66.
11. Negishi K, et al. An objective evaluation on the effects
of non-ablative skin tightening with a broadband
infrared light device. Presented at the 26th annual
meeting of the American Society of Laser Medicine
and Surgery; Apr 2006; Boston, MA.
12. Prieto VG, Diwan AH, Shea CR, Zhang P, Sadick
NS. Effects of intense pulsed light and the 1,064 nm
Nd:YAG laser on sun-damaged human skin: histo-
logic and immunohistochemical analysis. Dermatol
Surg. 2005;31(5):522–5.
13. Ruiz-Esparza J. Immediate skin contraction induced
by near painless, low fluence irradiation by a new
infrared device. A report of 25 patients treated
with this novel non-invasive, non-ablative method.
Dermatol Surg. 2006;32(5):601–10.
14. Ruiz-Rodriguez R, Lopez-Rodriguez L. Nonablative
skin resurfacing: the role of PDT. J Drugs Dermatol.
2006;5(8):756–62.
15. Schmults CD, et  al. Nonablative facial remodeling
erythema reduction and histologic evidence of new
collagen formation using a 300-microsecond 1064-­
nm Nd:YAG laser. Arch Dermatol. 2004;140:1373–6.
16. Sze-Hon C, et al. Nonablative infrared skin tighten-
ing in type IV to V Asian skin: a prospective clinical
study. Dermatol Surg. 2007;33:146–51.
17. Tan MH, Dover JS, Hsu TS, Arndt KA, Stewart
B. Clinical evaluation of enhanced nonablative skin
rejuvenation using a combination of a 532 and a
1,064 nm laser. Lasers Surg Med. 2004;34(5):439–45.
18. Taub AF, et al. Multicenter clinical perspectives on a
broadband infrared light device for skin tightening. J
Drugs Dermatol. 2006;5(8):771–8.
19. Trelles M, Allones I, Velez M, Mordon SJ. Nd:YAG
laser combined with IPL treatment improves clinical
results in non-ablative photorejuvenation. J Cosmet
Laser Ther. 2004;6(2):69–78.
20. Wunsch A, Matuschka K. A controlled trial to deter-
mine the efficacy of red and near-infrared light
treatment in patient satisfaction, reduction of fine
lines, wrinkles, skin roughness, and intradermal
collagen density increase. Photomed Laser Surg.
2014;32(2):93–100.
21. Zelickson B, et  al. Ultrastructural effects of titan
infrared handpiece on forehead and abdominal skin.
Presented and published in the meeting abstracts of
the 25th annual meeting of the American Society for
Laser Medicine and Surgery; Apr 2005; Orlando, FL.
M. Perper et al.

227
© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Laser and Light Therapies for Acne
Ali Rajabi-Estarabadi, Ariel E. Eber,
and Keyvan Nouri
Abstract
• Acne vulgaris is a very common cutaneous
disorder which can cause permanent scar-
ring and disfigurement.
• Acne is a multifactorial disorder of pilose-
baceous units and affects the areas of skin
with the greatest concentration of seba-
ceous follicles such as the face, neck, chest,
and back.
• Common therapies for acne treatment
include retinoids, keratolytic agents, anti-
microbials, and anti-inflammatory agents.
• The need for an alternative treatment has
led to the investigation of lasers and light
sources as a new treatment.
• The 1450 nm diode laser, 585- and 595-nm
pulsed dye lasers (PDLs), near infrared
diode lasers, 1320  nm Nd:YAG laser,
532 nm potassium titanyl phosphate laser,
1064  nm long-pulsed Nd:YAG laser,
1540 nm Erbium (Er):Glass Laser, and the
1550  nm Er:Glass fractional laser are
among the most common lasers used to
treat acne and acne scarring.
• 1540  nm Erbium (Er):Glass Laser, and the
1550 nm Er:Glass fractional laser are among
the most common lasers used to treat acne and
acne scarring.
• These lasers target the underlying causes of acne
including the colonization of Priopionibacterium
acnes, high levels of sebum production, altered
keratinization, inflammation, and bacterial col-
onization of hair follicles on the face, neck, and
back.
Keywords
Acne vulgaris · Acne scarring · 1450 nm
diode laser · 585- and 595-nm pulsed dye
lasers (PDLs) · Near infrared diode lasers ·
1320 nm Nd:YAG laser · 532 nm potassium
titanyl phosphate laser · 1064 nm long-pulsed
Nd:YAG laser · 1540 nm Erbium (Er):Glass
Laser · 1550 nm Er:Glass fractional laser
A. Rajabi-Estarabadi (*) · A. E. Eber · K. Nouri
Department of Dermatology and Cutaneous Surgery,
University of Miami, Miller School of Medicine,
Miami, FL, USA
e-mail: arajabi@med.miami.edu;
a.eber@med.miami.edu; knouri@med.miami.edu
13

228
Introduction
Acne vulgaris is the most common skin disorder. It
affects approximately 35–90% of adolescents and
continues to be a common problem in those over the
age of 20 [1–3]. In fact, in the U.S., it is estimated
that approximately 9.6 million individuals visited a
doctor for acne treatment in 2010, and over 60% of
these patients were over the age of 18 [4].
This common cutaneous disorder can cause
permanent scarring and disfigurement, which may
lead to severe consequences in psychological and
personality development. In fact, it is associated
with a high prevalence of depression and skin dis-
ease related suicide [5, 6]. For these reasons,
effective management of acne can improve self-
esteem, body image and other life quality issues
[7, 8].
Acne is a multifactorial disorder of the piloseba-
ceous unit and affects areas of the body with the
greatest concentration of sebaceous follicles includ-
ing the face, chest, neck and back. There are key
components that are thought to contribute to the
development of acne and include: Hypercornification
combined with excess sebum production provoking
clogging of the pores, Propionobacterium acnes (P.
acnes) proliferation in this environment causing an
increase in inflammatory cytokine production and
free fatty acids, and finally, further irritation from
inflammatory factors and free fatty acids. Studies
also suggest genetic, neuroendocrine, and dietary
factors may contribute to the multifactorial process
of acne vulgaris pathogenesis [9–11].
Currently, no acne grading or classifying sys-
tem can be recommended. However, clinicians
may find it useful to determine the severity of
acne according to certain specifications. Such
systems can assist in more specific classification
of disease, determining appropriate treatment
options, and monitoring improvement during
a treatment course. There are several accepted
tools that take into account type of acne, sever-
ity of acne, number of acne lesions (comedomes,
papules, pustules etc.), anatomical location/
extent of acne, quality of life and other psy-
chosocial metrics, and scarring among others.
Although most patients will improve with time,
some do not and have serious long term effects
from acne. These include redness, hyperpigmen-
tation, and permanent scars (atrophic, hypertro-
phic and keloids) [12].
Common therapies used for the treatment of
acne vulgaris include keratolytic agents, antimi-
crobials, anti-inflammatories, retinoids, hor-
monal
treatments,
microdermabrasion,
and
chemical peels [12, 13]. The need for an alterna-
tive treatment has led to the investigation of lasers
and light sources as a potential treatment. The
mechanism of action relies upon the fact that
lasers can emit wavelengths that cause direct
destruction of P. acnes or photo-thermal damage
to the sebaceous glands.
Laser-Based Therapies
Lasers release coherent light that can provide
very high radiance by focusing on a small tar-
geted area of tissue. The mechanisms of action
are that lasers can emit wavelengths which are
selectively absorbed by oxyhemoglobin of the
dilated vasculature within inflamed acne, activate
bacterial porphyrins resulting in self destruction
of P. acnes, or decrease sebum production by
photothermal damage to the sebaceous glands.
Lasers offer alternative options for acne treat-
ment which may have the benefit of rapid action,
low systemic adverse effects, and do not require
everyday treatment. Laser treatments of acne
include the 1450-nm diode, 585-nm pulsed dye
laser, 1320 Neodymium: Yttrium and 1540
Erbium (ER): Glass Laser.
585-nm Pulsed Dye Lasers
The 585-nm and 595-nm pulsed-dye lasers (PDL)
directly target P. acnes. The mode of action of the
PDL is based on the principle of selective photo-
thermolysis, a targeted damaging of specific
structures in the skin without damaging the sur-
rounding area [14].
A. Rajabi-Estarabadi et al.

229
It is traditionally useful for the treatment of vas-
cular lesions as well as hemangiomas, port-wine
stains, and facial telangiectasia [15]. However, the
pulsed dye laser can also activate bacterial porphy-
rins and thereby produce selective photothermoly-
sis of the dilated vasculature within inflamed acne
[16–18].
Seaton et al. did a randomized double-blind
study in 41 patients with mild to moderate facial
acne. They randomly assigned patients to PDL or
sham treatment. Twelve weeks after a single PDL
treatment, with two different fluences given at
each side of the midline, they reported reduced
inflammatory acne lesions by 49% on both sides
of the face [19].
Orringer et al. conducted a randomized con-
trolled study in split-face of 26 patients. After
12  weeks lesion count did not significantly
change in comparison with non-treated sites;
however, a trend of improvement in inflamma-
tory acne was described [20].
Leheta compared treatment outcomes of PDL
treatment with two regular acne treatments. One
group of 15 patients was treated with PDL, and
compared with two other groups which received
regular topical treatments (topical vitamin A
acid, benzoyl peroxide) or chemical peels (tri-
chloroacetic acid 25%). Significant decrease in
all three groups was seen; although, in the fol-
low-up period remission was significantly higher
in the PDL group [21].
Jasim et  al. did a split-face study in ten
patients, in which half of the face was treated
with PDL and the untreated site served as a con-
trol side. They showed visible improvement of
acne lesions on the treated site in 50% of the
patients. PDL seems to be an effective treatment
for acne vulgaris [22].
Potassium Titanyl Phosphate
(KTP) Laser
The potassium titanyl phosphate (KTP) laser has
generally been used for the treatment of telangi-
ectasia and rosacea but has also recently been
shown to be effective for the treatment of acne
[23]. It uses a broad spectrum green light which
is thought to photoactivate bacterial porphyrins
and produce limited non-specific thermal injury
to sebaceous glands [24].
In a split face study of 26 patients after four
treatments with a KTP laser, a 34.9% and 20.7%
reduction in acne severity was shown at 1 week
and 4 weeks, respectively [25]. In another study,
25 patients who were treated with the KTP laser
at fluences ranging from 6 to 12 J/cm2achieved
60–70% clearing after six treatments [26]. Bowes
et al. conducted a split-face study whereby they
treated one-half of the face of 11 patients with
mild to moderate acne with the KTP laser. They
reported a 35.9% decrease in acne after 1 month,
while the control half had a 1.8% increase. They
noted that there was decreased sebum produc-
tion, but there was a minimal effect on P. acnes
[24].
Yilmaz et al. also evaluated efficacy and safety
of 532-nm KTP laser and compared the effect of
once and twice weekly application in the treat-
ment of mild to moderate acne vulgaris in two
groups of 38 patients, group 1 applying once
weekly and group two, twice weekly. They
reported statistically significant improvement at
second control session (p = 0.005) in group I, and
at first (p = 0.004), and second (p < 0.001) control
sessions in group II for treated sides [27].
1450-nm Diode Laser
The 1450-nm laser with a dynamic cooling
device has received Food and Drug Administration
approval for the treatment of acne. The 1450-nm
diode laser is a longer wavelength laser that pen-
etrates to the level of the sebaceous gland within
the mid-dermis. This wavelength is primarily
absorbed by water, so it does not greatly affect
the epidermis but does thermally ablate sebo-
cytes, along with P. acnes [28, 29].
In a multicenter, blinded study, 61 patients
were treated every month for 4 consecutive
months using the 1450-nm diode. There was a
13  Laser and Light Therapies for Acne

230
26% drop out rate, but the remaining 45 patients
had 65% improvement 1 month following treat-
ment, and at 6 months five patients required no
additional acne therapy [30].
Friedman et  al. used three irradiation ses-
sions of the 1450-nm diode laser to treat 19
patients with inflammatory facial acne at 4- to
6-week intervals. After one treatment, the aver-
age lesion count decreased by 37% (P < 0.01).
Mean lesion counts improved by 58% (P < 0.01)
after the second irradiation and by 83%
(P  <  0.01) after the third session. They also
experienced erythema and edema for up to 24 h
after laser treatment [29].
In another study, Alam et al. performed a trial
in a split-face of 25 patients and compared the
1450-nm diode laser with the 595 nm PDL. They
reported that the 1450-nm diode laser produced
similar acne reduction with longer remissions (up
to 3 months) when compared to the 595 nm PDL
after 4 monthly treatments [31].
Astner et  al. applied 1450-nm diode laser
twice in in the management of refractory acne
vulgaris in 13 patients. This study demonstrated
that mean total lesion and inflammatory lesion
counts decreased from 66  ±  14 and 23  ±  5 at
baseline to 34 ± 12.9 and 14 ± 7 at 3-month fol-
low-up (p < 0.05). Side effects were mild, includ-
ing transient erythema [32].
In another study, 11 patients were treated with
a 1450-nm diode laser in a split-face bilateral
paired trial, every 3  weeks for a total of three
treatments. One-half of the faces received a sin-
gle-pass consisting of stacked double pulses. The
other side received a double-pass treatment of
single pulses. The mean acne severity scores
decreased from 3.3 at baseline to 2.1 and 2.2 for
the stacked-pulse and double-pass sides, respec-
tively. One subject’s acne severity increased dur-
ing the study from Grade 3 to Grade 5 [33].
Perez-Maldonado et  al. conducted study on
eight patients with a history of acne and used
1450-nm diode laser on the right side of the nose
over a 6-week period, for a total of three treat-
ments and left the other side of the nose untreated.
They observed a maximum of 18% reduction in
sebum output after three treatments [34].
A study recruited patients with moderate to
severe acne vulgaris. A split-face format was
used: the side of the face to be treated was ran-
domized with the other side serving as a within-
patient control. They performed three treatments
monthly using 1450 diode laser with a double-
pass technique. On average, the lesion count and
acne grade reduced by the same amount on both
sides of the face. Twelve months after the last
treatment the change in lesion count and grade
between the treated and control sides remained
similar. They reported improvement of both side
of the face and they suggested a possible sys-
temic effect of laser [35].
1320 Neodymium: Yttrium Aluminum
Garnet Laser (Nd:YAG)
The 1320 neodymium: yttrium aluminum garnet
laser (Nd:YAG) is a deep-penetrating, long wave-
length, mid-infrared laser that has been shown to
have thermolytic effect upon sebaceous glands.
In one study the 1320 Nd: YAG laser was used to
treat 50 patients with moderate to severe acne (6
weekly treatments). The patients were followed
for 1 year thereafter. Eighty percent of patients
felt they had 75–100% improvement after the
fourth of these six treatments. However, 72% of
the patients felt that the benefit seemed to fade
beyond 3 months. 82% of the patients that had
acne scarring had ‘noticeable’ improvement. The
one major complication reported was one patient
developing a pitted scar from the treatment [36].
Orringer et al. conducted a randomized, con-
trolled, single-blind, split-face clinical trial in 46
patients with facial acne. Patients received a
series of three nonablative laser treatments using
1320-nm Nd:YAG laser to half of the face. The
authors reported no significant differences
between treated and control sides of the face in
terms of changes in mean papule or pustule
counts [37].
A. Rajabi-Estarabadi et al.

231
1540 Erbium (ER): Glass Laser
Similar to the 1320-nm Nd:YAG laser system,
the 1540-nm erbium glass laser is a novel, mid-
infrared range laser that targets intracellular
water to a depth of 0.4–2 mm. Minimal absorp-
tion by melanin makes the laser essentially safe
for the treatment of dark-skinned or tanned indi-
viduals [38]. Also, this laser was shown to pro-
vide deep dermal penetration and subsequent
alteration of sebaceous activity through thermal
coagulation.
A study found that there was a 78% lesion
reduction in 25 patients with facial and truncal
acne after 4 monthly treatments with the 1540-
nm laser [39]. Also, another study used this laser
in 20 patients with facial inflammatory acne in
combination with an active contact-cooling
device over the patient’s entire face. Patients
underwent four sessions at 2-week intervals.
Investigators reported a lesion count reduction of
70% after 3  months. No side effects were
observed after any treatment with the Er:glass
laser [40].
Bogle et al. evaluated the use of the 1540-nm
erbium:glass laser to treat patients with moderate
to severe acne four times at 2-week intervals.
Patients rated improvement as 68%, and the mean
investigator improvement assessment was 78%
after 6-month follow-up [41].
1550-nm Fractionated Erbium Glass
The wavelength of 1550 nm fractionated Er:glass
is absorbed primarily by water, targeting the
sebaceous glands and surrounding dermal matrix.
In a randomized controlled split-face study, 24
patients with active acne lesions were treated
using 1550-nm fractionated erbium:glass laser on
one side of the face for four sessions with a
2-week interval. This study showed a significant
reduction (p  <  0.0001) in the mean count of
lesions and the size of sebaceous glands after
treatment. Also, the authors reported complete
clearance of all lesions after treatment and during
the follow-up in 17 (70.8%) patients [42].
Liu et al. evaluated the short-term and long-
term effects of the 1550-nm erbium:glass frac-
tionated laser in the treatment of 45 patients with
facial acne vulgaris. Nine male and 36 female
acne patients were treated four times at 4-week
intervals. After four treatments, all patients had
an obvious reduction of lesion counts and IGA
score, with the peak lesion counts decreasing to
67.7%. Eight patients had follow-up for 2 years,
27 patients for 1  year, and all patients for
6  months. The mean percentage reduction was
72% at the half-year follow-up, 79% at the 1-year
follow-up, and 75% at the 2-year follow-up.
Three patients observed a significant improve-
ment in preexisting hyper-pigmentation after
treatments. All patients reported that their skin
was less prone to oiliness [43].
Light Based Therapies
• The most commonly used light based devices
are the blue light, red light, and intense pulsed
light system.
• Propionibacterium acnes produces endoge-
nous porphyrins, which absorb light to form a
highly reactive singlet oxygen which can
cause self-destruction of P. acnes.
Blue Light
P. acnes containing fluorescent porphyrins can be
killed by a blue light-induced photodynamic
effect. Activation of protoporphyrin IX, found in
P. acnes, in the presence of oxygen produces a
metastable intermediate that destroys the bacte-
rium. Protoporphyrin IX absorption peaks occurs
at wavelengths found in the visible light spec-
trum [43–48].
Thirty patients with mild to moderate acne
lesions on the face and/or the back and/or the
chest participated in this study by Kawada et al.
The patients were irradiated with high-intensity,
narrow-band, blue light twice a week up to
13  Laser and Light Therapies for Acne

232
5  weeks. This study showed 64% reduction of
acne lesions [49].
Elman et  al., treated 46 acne patients with
420 nm UV-free blue light for eight treatments of
8–15 min. 80% of patients showed a significant
reduction of 59–67% of inflammatory acne
lesions after eight treatments. The reduction in
lesions was steady in the follow-up, at 8 weeks
after the end of therapy [50].
In a split face study, 28 patients with symmet-
rical facial acne received blue light on one side of
the face twice weekly for 4 consecutive weeks.
The authors reported that the mean percentage
improvement was 52% after eight sessions and
first significant improvement happened after four
sessions of irradiation (P  ≤  0.009). After eight
sessions of blue light irradiation acne exacerba-
tion was found in four patients [51].
Tremblay et al. treated 45 patients with pure
blue light (415  nm) for two treatments of
20 min per week for a period of 4–8 weeks. The
mean improvement score of the acne lesions was
3.14 at 4 weeks and 2.90 at 8 weeks, after which
lesions of nine patients were cleared completely.
They reported that 50% of patients were highly
satisfied with the treatment and no adverse event
occurred [52].
In a study, Omi et al. investigated the use of
high-intensity, narrow-band, blue light on 28
patients with facial acne. The study showed
64.7% improvement in acne lesions after eight
serial biweekly 15-min treatment sessions [53].
Morton et al. evaluated the effect of narrow-
band blue light in the reduction of inflammatory
and non-inflammatory lesions in 30 patients with
mild to moderate acne. The patients received
eight treatment sessions (each session 10 or
20-minute) over 4 weeks. This study concluded
that the aforementioned modality was effective in
reducing the number of inflamed lesions in sub-
jects with mild to moderate acne. They reported a
statistically significant decrease in inflamed
counts at 8  weeks assessments and no adverse
events [54].
In a study by De Arruda et al. the efficacy of
blue light treatment was evaluated in comparison
with topical benzoyl peroxide 5% formulation in
60 patients with facial acne grades II and III. 30
patients were irradiated by using blue light for 8
times twice a week, and 30 patients were treated
with topical Benzoyl Peroxide 5% formulation,
auto-applied twice a day, every day. The authors
reported the same improvement result by the blue
light and benzoyl peroxide (p > 0.05) and the side
effects were less frequent in the group treated
with blue light [55].
Blue/Red Light Combinations
Although by theory porphyrins should respond
well to blue light, it is a shorter wavelength, and
therefore does not penetrate well into the skin
[56].
Longer wavelengths with Q-bands, such as
red light, has been combined with blue light in
acne therapy. Red light (wavelength 600–650 nm)
penetrates deeper into the skin than blue light. In
fact, 635 nm light may penetrate through the skin
up to 6 mm compared with 1–2 mm for light at
400–500 nm. Red light has also been shown to be
effective in acne treatment by activating porphy-
rins in the Q band and decreases inflammation by
controlling cytokine release from macrophages
[57–61].
In a randomized, controlled, single-blind
study, Papageorgiou et al. compared mixed blue
and red light (415 nm and 660 nm, respectively)
phototherapy with blue (415 nm) or 5% benzoyl
peroxide in 140 patients with mild-to-moderate
acne. With the use of the combined blue-red light
radiation, a final improvement of 76% in inflam-
matory lesions was noted with follow-up of
12  weeks, which was significantly superior to
those achieved by blue light or benzoyl peroxide.
Also, the final mean improvement in comedones
by using blue–red light was 58%, which was bet-
ter than the result of other active treatments; how-
ever, the differences was not statistically
significant [57].
Goldberg and Russel evaluated 22 patients
with mild to severe symmetric facial acne vul-
garis with a combination of blue and red light.
They were treated over eight sessions, two per
week 3 days apart, alternating between blue light
(20 min/session) and red light (20 min/session).
A. Rajabi-Estarabadi et al.

233
Patients received a mild microdermabrasion
before each session. Acne was assessed at base-
line and at weeks 2, 4, 8 and 12. At the 4-week
follow-up, the mean lesion count reduction was
significant at 46% (p = 0.001). At the 12-week
follow-up, the mean lesion count reduction was
also significant at 81% (p = 0.001). Severe acne
showed a marginally better response than mild
acne. Comedones did not respond as well as
inflammatory lesions [61].
In a study performed by Lee et al., 24 patients
with mild to moderately severe facial acne were
treated with quasimonochromatic LED devices,
alternating blue and red light twice a week for
4  weeks. 8  weeks after the final treatment the
mean percentage improvements in non-inflam-
matory and inflammatory lesions were 34.28%
and 77.93%, respectively. None of the patients
reported any adverse reaction related to the treat-
ment [60].
Intense Pulsed Light (IPL)
Intense pulsed light (IPL) uses a flash lamp to
deliver wide spectrum, non-coherent visible light
(green, yellow, and red) to near-infrared wave-
lengths. Treatment of acne with IPL has shown
some very promising results. In a study by
Gregory and co-workers, 50 patients with mild to
severe acne were treated with IPL for 1 month.
These patients showed a 60% lesion reduction at
the 1-month follow-up, versus 32% increase in
controls [62]. In a study done by Elman and co-
workers of 19 patients with acne, they showed
that the IPL produced an 85% clearance of
inflammatory lesions and 87% clearance of non-
inflammatory lesions in 2 months [63].
They also conducted a study to test the role of
pulsed light and heat energy in acne clearance. A
system with light pulses and heat was used in bi-
weekly treatments for 4 weeks with wavelengths
between 430 and 1100 nm. This study showed
approximately a 75% clearance of the inflamma-
tory lesions 1 month after the last treatment [64].
Wat et al. evaluated efficacy of IPL in treat-
ment of acne vulgaris in a systematic review.
They identified twenty-one studies (2 random-
ized controlled trials, 7 prospective right–left
comparison trials, 11 uncontrolled open-label tri-
als, and 1 retrospective observational study) for a
total of 544 patients. They categorized the studies
into two groups of IPL alone and IPL in combi-
nation with PDT. The authors reported that effi-
cacy of IPL in treatment of acne ranged from
34% to 88.3% (depending on the type of acne
lesion: inflammatory or noninflammatory), with
most of the studies showing an improvement
between 40% and 60%. Also, this review stated
that although IPL monotherapy showed benefit in
the treatment of acne vulgaris, but the evidence
supports greater efficacy for treatment with IPL
in combination with PDT [65].
Ianosi et al. compared the effectiveness of IPL
and vacuum versus IPL with placebo in 180
patients with mild to moderate comedonal and
inflammatory acne (group A—60 patients treated
with vacuum and IPL, group V—60 patients
treated with IPL, and control group—60 patients
treated with Sebium H2O Micellaire Solution).
They reported a significant reduction in the num-
ber of papules, pustules, and comedones in
groups A and V compared with those in the con-
trol group (p < 0.001) with decrease of the pap-
ules in group A being rapider than group V. Also,
patients belonging to group A were more satis-
fied compared with those in group V (p = 0.004)
and significantly more satisfied compared with
those of the control group (p < 0.001) [66].
In a study, the investigators compared the clin-
ical efficacy of IPL with benzoyl peroxide 5% in
the treatment of inflammatory acne in 50 patients
with mild-to-severe acne. The study showed
treatment with both benzoyl peroxide and IPL
resulted in improvement of the acne after 5 weeks
of treatment. Benzoyl peroxide showed better
results than IPL which was statistically signifi-
cant at the midpoint of the study (after the 3rd
week of treatment). However, this difference was
insignificant at the end of study [67].
Mohamad et  al. performed controlled, sin-
gle-blind, split-face clinical trial to compare the
clinical efficacy of IPL with 1064-nm long-
pulsed Nd:YAG in treatment of 74 patients with
facial acne vulgaris. All participants received
three sessions of IPL on the right side of the face
and 1064-nm Nd:YAG on the left side of the
face at 4-week intervals. The inflammatory acne
13  Laser and Light Therapies for Acne

234
lesions were reduced on the IPL and 1064-nm
Nd:YAG treated sides by 67.1% and 70.2%,
respectively (p < 0.05), while non inflammatory
acne lesions were reduced by 18.3% and 19.3%,
respectively (p > 0.05). Also, the authors stated
no significant difference in the efficacy of the
two modalities in reducing both types of acne
lesions (p > 0.05) [68].
A study by Barakat et al., accursed 24 patients
with acne vulgaris to evaluate efficacy of IPL in
six treatment sessions. They showed a significant
reduction of all acne lesions especially inflamma-
tory type at 2 weeks and 3 months after end of the
treatment (p < 0.05) [69].
Conclusion
The treatment of acne is a difficult process due
to its multifarious pathogenesis. Using laser
and light sources alone or combination ther-
apy have been shown to be an effective treat-
ment for mild to severe inflammatory and
cystic acne, in various skin types. However,
further investigation is necessary to determine
safety and long-term efficacy, and to establish
the optimal parameters to maximize the effec-
tiveness of this evolving treatment modality.
References
1. Perper M, Tsatalis J, Eber AE, Cervantes J, Nouri K. 
Lasers in the treatment of acne. G Ital Dermatol
Venereol. 2017;152(4):360–72.
2. Collier CN, Harper JC, Cafardi JA, et al. The preva-
lence of acne in adults 20 years and older. J Am Acad
Dermatol. 2008;58(1):56–9.
3. Stathakis V, Kilkenny M, Marks R. Descriptive epide-
miology of acne vulgaris in the community. Australas
J Dermatol. 1997;38(3):115–23.
4. Yentzer BA, Hick J, Reese EL, Uhas A, Feldman
SR, Balkrishnan R.  Acne vulgaris in the United
States: a descriptive epidemiology. Cutis. 2010;86(2):
94–9.
5. Dalgard F, Gieler U, Holm JO, Bjertness E, Hauser S. 
Self-esteem and body satisfaction among late adoles-
cents with acne: results from a population survey. J
Am Acad Dermatol. 2008;59(5):746–51.
6. Cotterill JA, Cunliffe WJ. Suicide in dermatological
patients. Br J Dermatol. 1997;137(2):246–50.
7. Cunliffe WJ. Acne and unemployment. Br J Dermatol.
1986;115(3):386.
8. St. Sauver JL, Warner DO, Yawn BP, et al. Why patients
visit their doctors: assessing the most prevalent con-
ditions in a defined American population. Mayo Clin
Proc. 2013;88(1):56–67.
9. Muizzuddin N, Giacomoni P, Maes D. Acne—a mul-
tifaceted problem. Drug Discov Today Dis Mech.
2008;5(2):e183–8.
10. Toyoda M, Morohashi M. Pathogenesis of acne. Med
Electron Microsc. 2001;34(1):29–40.
11. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guide­
lines of care for the management of acne vulgaris. J
Am Acad Dermatol. 2016;74(5):945–73. e933
12. Leyden JJ. Therapy for acne vulgaris. N Engl J Med.
1997;336(16):1156–62.
13. Keri J, Shiman M.  An update on the management
of acne vulgaris. Clin Cosmet Investig Dermatol.
2009;2:105–10.
14. Erceg A, de Jong EM, van de Kerkhof PC, Seyger MM. 
The efficacy of pulsed dye laser treatment for inflam-
matory skin diseases: a systematic review. J Am Acad
Dermatol. 2013;69(4):609–15.
15. Nouri K, Ballard CJ.  Laser therapy for acne. Clin
Dermatol. 2006 Jan-Feb;24(1):26–32.
16. Bjerring P, Clement M, Heickendorff L, Lybecker H,
Kiernan M.  Dermal collagen production following
irradiation by dye laser and broadband light source. J
Cosmet Laser Ther. 2002;4:39–43.
17. Patel N, Clement M. Selective nonablative treatment
of acne scarring with 585 nm flashlamp pulsed dye
laser. Dermatol Surg. 2002;28:942–5.
18. Tan OT, Sherwood K, Gilchrest BA. Treatment of chil-
dren with port-wine stains using the flashlamp pulsed
tunable dye laser. N Engl J Med. 1989;320:416–21.
19. Seaton ED, Charakida A, Mouser PE, Grace I,
Clement RM, Chu AC. Pulsed-dye laser treatment for
inflammatory acne vulgaris: randomized controlled
trial. Lancet. 2003;362:1347–52.
20. Orringer JS, Kang S, Hamilton T, Schumacher W,
Cho S, Hammerberg C, et al. Treatment of acne vul-
garis with a pulsed dye laser: a randomized controlled
trial. JAMA. 2004;291:2834–9.
21. Leheta TM.  Role of the 585-nm pulsed dye laser
in the treatment of acne in comparison with other
topical therapeutic modalities. J Cosmet Laser Ther.
2009;11:118–24.
22. Jasim ZF, Al-Qarqaz F, Handley JM. Effect of single
pulsed dye laser treatment on acne vulgaris [letter].
Dermatol Surg. 2005;31:1483.
23. Jih MH, Kimyai-Asadi A.  Laser treatment of acne
vulgaris. Semin Plast Surg. 2007;21(3):167–74.
24. Bowes LE, Manstein D, Anderson RR.  Effects of
532 nm KTP laser exposure on acne and sebaceous
glands. Lasers Surg Med. 2003;18:S6–7.
25. Baugh W, Kucaba W. Nonablative phototherapy for
acne vulgaris using the KTP 532 nm laser. Dermatol
Surg. 2005;31:1290–6.
26. Lee MC. Aura 532 nm laser for acne vulgaris—3-year
experience. New Orleans, LA: Presented at: 2003
ASDS-ACMMSCO Combined Annual Meeting;
October 9–12, 2003.
27. Yilmaz O, Senturk N, Yuksel EP, Aydin F, Ozden MG,
Canturk T, Turanli A.  Evaluation of 532-nm KTP
laser treatment efficacy on acne vulgaris with once
A. Rajabi-Estarabadi et al.

235
and twice weekly applications. J Cosmet Laser Ther.
2011;13(6):303–7.
28. Paithankar DY, Ross EV, Saleh BA, Blair MA,
Graham BS. Acne treatment with a 1450 nm wave-
length laser and cryogen spray cooling. Lasers Surg
Med. 2002;31:106–14.
29. Friedman PM, Jih MH, Kimyai-Asadi A, Goldberg LH. 
Treatment of inflammatory facial acne vulgaris with
the 1450-nm diode laser: a pilot study. Dermatol Surg.
2004;30:147–51.
30. Mazer JM. Treatment of facial acne with a 1450 nm
diode laser: a comparative study. Lasers Surg Med.
2004;34:S67.
31. Alam M, Peterson SR, Silapunt S, Chopra K,
Friedman PM, Goldberg LH.  Comparison of the
1450 nm diode laser for the treatment of facial acne: a
left–right randomized trial of the efficacy and adverse
effects. Lasers Surg Med. 2003;32:S30.
32. Astner S, Tsao SS. Clinical evaluation of a 1,450-nm
diode laser as adjunctive treatment for refractory facial
acne vulgaris. Dermatol Surg. 2008;34(8):1054–61.
33. Uebelhoer NS, Bogle MA, Dover JS, Arndt KA,
Rohrer TE.  Comparison of stacked pulses versus
double-pass treatments of facial acne with a 1,450-nm
laser. Dermatol Surg. 2007;33(5):552–9.
34. Perez-Maldonado A, Rünger TM, Krejci-Papa N. 
The 1,450-nm diode laser reduces sebum production
in facial skin: a possible mode of action of its effec-
tiveness for the treatment of acne vulgaris. Lasers
Surg Med. 2007;39(2):189–92.
35. Darne S, Hiscutt EL, Seukeran DC. Evaluation of the
clinical efficacy of the 1,450 nm laser in acne vul-
garis: a randomized split-face, investigator-blinded
clinical trial. Br J Dermatol. 2011;165(6):1256–62.
36. Chernoff G. The utilization of 1320 nm Nd:YAG energy
for the treatment of active acne vulgaris. Cooltouch
Inc: White Paper; 2004.
37. Orringer JS, Kang S, Maier L, Johnson TM, Sachs DL,
Karimipour DJ, Helfrich YR, Hamilton T, Voorhees JJ. 
A randomized, controlled, split-face clinical trial of
1320-nm Nd:YAG laser therapy in the treatment of
acne vulgaris. J Am Acad Dermatol. 2007;56(3):432–8.
38. Lupton JR, Williams CM, Alster TS. Nonablative laser
skin resurfacing using a 1540 nm erbium glass laser:
a clinical and histologic analysis. Dermatol Surg.
2002;28(9):833–5.
39. Boineau D, Angel S, Nicole A, Dahan S, Mordon S. 
Treatment of active acne with an Er:glass (1.54 um)
laser. Lasers Surg Med. 2004;34:S55.
40. Kassir M, Newton D, Maris M, Euwer R, Servell P. 
Er:glass (1.54 mm) laser for the treatment of facial
acne vulgaris. Lasers Surg Med. 2004;34:S65.
41. Bogle MA, Dover JS, Arndt KA, Mordon S. Evaluation
of the 1,540-nm Erbium:Glass laser in the treatment
of inflammatory facial acne. Dermatol Surg. 2007;
33(7):810–7.
42. Moneib H, Tawfik AA, Youssef SS, Fawzy MM. 
Randomized split-face controlled study to evaluate
1550-nm fractionated erbium glass laser for treat-
ment of acne vulgaris—an image analysis evaluation.
Dermatol Surg. 2014;40(11):1191–200.
43. Liu Y, Zeng W, Hu D, Jha S, Ge Q, Geng S, Xiao S,
Hu G, Wang X.  The long-term effect of 1550  nm
erbium:glass fractional laser in acne vulgaris. Lasers
Med Sci. 2016;31(3):453–7.
44. Lee W, Shalita A, Poh-Fitzpatrick M.  Comparative
studies of porphyrin production in Propionibacterium
acnes and Propionibacterium granulosum. J Bacteriol.
1978;133:811–5.
45. Weishaupt K, Gomer C, Dougherty T. Identification
of singlet oxygen as the cytotoxic agent in photoin-
activation of a murine tumor. Cancer Res. 1976;36:
2326–9.
46. Niedre M, Yu C, Patterson M, et al. Singlet oxygen
luminescence as an in  vivo photodynamic therapy
dose metric: validation in normal mouse skin with
topical amino-levulinic acid. Br J Cancer. 2005;92:
298–304.
47. Taub AF.  Photodynamic therapy in dermatology:
history and horizons. J Drugs Dermatol. 2004;3(1
Suppl):S8–S25.
48. Arakane K, Ryu A, Hayashi C, Masunaga T,
Shinmoto K, Mashiko S, et al. Singlet oxygen (1Dg)
generation from coproporphyrin in Propionibacterium
acnes on irradiation. Biochem Biophys Res Com.
1996;223:578–82.
49. Kawada A, Aragane Y, Kameyama H, Sangen Y,
Tezuka T.  Acne phototherapy with a high-intensity,
enhanced, narrow-band, blue light source: an open
study and in  vitro investigation. J Dermatol Sci.
2002;30(2):129–35.
50. Elman M, et al. The effective treatment of acne vul-
garis by a highintensity, narrow band 405–420  nm
light source. J Cosmet Laser Ther. 2003;5(2):111–7.
51. Tzung TY, et  al. Blue light phototherapy in the
treatment of acne. Photodermatol Photoimmunol
Photomed. 2004;20(5):266–9.
52. Tremblay JF, Sire DJ, Lowe NJ, Moy RL.  Light-
emitting diode 415  nm in the treatment of inflam-
matory acne: an open-label, multicentric, pilot
investigation. J Cosmet Laser Ther. 2006;8(1):31–3.
53. Omi T, Bjerring P, Sato S, et al. 420 nm intense con-
tinuous light therapy for acne. J Cosmet Laser Ther.
2004;6(3):156–62.
54. Morton CA, Scholefield RD, Whitehurst C, Birch
J.  An open study to determine the efficacy of blue
light in the treatment of mild to moderate acne. J
Dermatol Treat. 2005;16(4):219–23.
55. de Arruda LH, Kodani V, Bastos Filho A, Mazzaro
C.  A prospective, randomized, open and compara-
tive study to evaluate the safety and efficacy of blue
light treatment versus a topical benzoyl peroxide 5%
formulation in patients with acne grade II and III. An
Bras Dermatol. 2009;84(5):463–8.
56. Kjelstad B, Johnson A. An action spectrum for blue
and near ultraviolet inactivation of Propionibacterium
acnes; with emphasis on a possible porphyrins photo-
sensitization. Photochem Photobiol. 1986;43:67–70.
57. Papageorgiou P, Katsambas A, Chu A. Phototherapy
with blue (415 nm) and red (660 nm) light in the
treatment of acne vulgaris. Br J Dermatol. 2000;
973-978(22):142.
13  Laser and Light Therapies for Acne

236
58. Cunliffe WJ, Goulden V. Phototherapy and acne vul-
garis. Br J Dermatol. 2000;142:853–6.
59. Young S, et al. Macrophage responsiveness to light
therapy. Lasers Surg Med. 1989;9:497–505.
60. Lee SY, et al. Blue and red light combination LED
phototherapy for acne vulgaris in patients with skin
phototype IV. Lasers Surg Med. 2007;39(2):180–8.
61. Goldberg DJ, Russell BA.  Combination blue (415
nm) and red (633 nm) LED phototherapy in the treat-
ment of mild to severe acne vulgaris. J Cosmet Laser
Ther. 2006;8(2):71–5.
62. Gregory AN, Thornfeld CR, Leibowitz KR, Lane M. 
A study on the use of a novel light and heat energy
system to treat acne vulgaris. Cosmet Dermatol. 2004;
17:287–91.
63. Elman M, Lebzelter J.  Evaluating pulsed light and
heat energy in acne clearance radiancy. White Paper;
2002.
64. Elman M, Lask G. The role of pulsed light and heat
energy (LHE (TM)) in acne clearance. J Cosmet Laser
Ther. 2004;6:91–5.
65. Wat H, Wu DC, Rao J, Goldman MP.  Application
of intense pulsed light in the treatment of dermato-
logic disease: a systematic review. Dermatol Surg.
2014;40(4):359–77.
66. Ianosi S, Neagoe D, Calbureanu M, Ianosi G. Investi­
gator-blind, placebo-controlled, randomized compar-
ative study on combined vacuum and intense pulsed
light versus intense pulsed light devices in both com-
edonal and papulopustular acne. J Cosmet Laser Ther.
2013;15(5):248–54.
67. El-Latif AA, Hassan FA, Elshahed AR, Mohamed
AG, Elsaie ML. Intense pulsed light versus benzoyl
peroxide 5% gel in treatment of acne vulgaris. Lasers
Med Sci. 2014;29(3):1009–15.
68. Mohamed EE, Tawfik K, Elsaie M.  Intense pulsed
light versus 1,064 long-pulsed neodymium: yttrium-
aluminum- garnet laser in the treatment of facial acne
vulgaris. J Clin Diagn Res. 2016;10(7):WC01–3.
69. Barakat MT, Moftah NH, El Khayyat MA,
Abdelhakim ZA.  Significant reduction of inflam-
mation and sebaceous glands size in acne vul-
garis lesions after intense pulsed light treatment.
Dermatol Ther. 2017;30(1).
A. Rajabi-Estarabadi et al.

237
© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Lasers for Psoriasis
and Hypopigmentation
Laura Jordan, Summer Moon,
and James M. Spencer
Abstract
Psoriasis and pigmentary disorders have a pro-
found impact on the quality of life of affected
patients. Despite multiple medical therapies for
psoriasis, certain clinical scenarios present ther-
apeutic dilemmas. The excimer laser has been
found to be efficacious not only for patients
suffering from psoriasis but also for several dis-
orders of hypopigmentation including vitiligo,
linear scleroderma, pityriasis alba, and chemi-
cal, punctate, and post-resurfacing leucoderma.
Additionally, due to the excimer laser’s reduced
cumulative dose and number of treatment ses-
sions, it offers several potential advantages
over whole-body phototherapy, including low-
ered carcinogenicity, phototoxicity, and cost of
treatment. This paper considers the variety of
applications for the excimer laser on psoriasis
and hypopigmentation and reviews its associ-
ated indications, contraindications, techniques,
adverse events, and future directions.
Keywords
Excimer laser · Psoriasis · Vitiligo · Pigmentary
disorders · Hypopigmentation · Leucoderma ·
Scleroderma · Pityriasis alba · Psoralen and
ultraviolet A (PUVA) · Minimal erythema
dose (MED) · Light therapy · Tacrolimus
Introduction
• Psoriasis and vitiligo have been found to ben-
efit from light therapy in the UVB range
(290–320 nm).
• The 308 nm xenon-chloride excimer laser is
now utilized for select patients with psoriasis
and vitiligo.
• The efficacy and safety of the excimer laser is
well documented.
• Striae, linear scleroderma, pityriasis alba, and
chemical, punctate, and post-resurfacing leu-
coderma have been found to respond to the
308 nm excimer laser.
One of the most recent advancements in pho-
totherapy is the development of localized deliv-
ery systems. One such device is the excimer laser.
The use of the excimer laser was first reported in
dermatology by Bónis et al. in 1997 for psoria-
sis treatment [1]. Psoriasis has been reported to
respond best to light at a wavelength of 313 nm
[2]. Since the excimer laser emits light at a
wavelength of 308 nm, it was a logical choice for
L. Jordan (*)
Kansas City University Consortium,
Tri-County Dermatology Residency Program,
Cuyahoga Falls, OH, USA
S. Moon
Dermatology Specialists of West Florida, FL, USA
J. M. Spencer
Spencer Dermatology and Skin Surgery Center,
Spencer Dermatology, Carillon Outpatient Center,
St. Petersburg, FL, USA
e-mail: james.spencer@spencerdermatology.com
14

238
investigation. Further, these lasers, as with UV
light in general, offer a selective immunosup-
pressant action which provides a safe treatment
for chronic skin manifestations [3]. The excimer
laser has been found to be efficacious not only
for patients suffering from psoriasis but also for
several disorders of hypopigmentation including
vitiligo. Additionally, due to the excimer laser’s
reduced cumulative dose and number of treat-
ment sessions, it offers several potential advan-
tages over whole-body phototherapy, including
lowered carcinogenicity, phototoxicity, and cost
of treatment [4]. This chapter serves to discuss
the use of the excimer laser for psoriasis and dis-
eases of hypopigmentation.
Excimer lasers are a group of lasers utilized
in a variety of medical specialties, most notably
ophthalmology. There are several types of excimer
lasers, all of which operate in the ultraviolet spec-
trum. Excimer refers to the formation of “excited
dimers” via an inducible mixture of a halogen
and noble gas. Electric current is delivered to the
gas producing unstable, high-energy dimers that
quickly dissociate giving off laser light [5]. The
laser light is delivered to its target via a fiber optic
cable. The mechanism of physiologic response
is poorly understood but does not appear to be a
thermal mechanism. Thus, the excimer lasers do
not operate under the theory of selective photo-
thermolysis. Excimer lasers are capable of “cold
ablation,” which is precise tissue ablation with
minimal surrounding thermal effects. This unique
property enables the laser to be used in precision
surgeries such as corneal reshaping. It is theorized
that the energy of the photons from excimer lasers
exceeds the energy of many chemical bonds which
keep organic material together. This principle
forms the theory termed “ablative decomposition,”
under which excimer lasers are thought to operate.
Excimer Lasers
Psoriasis
• Total cumulative dose is lower than traditional
light therapy.
• Uninvolved skin is spared.
• Psoriatic plaques can tolerate several times the
minimal erythema dose (MED).
The benefits of using the 308  nm excimer
laser for psoriasis were fully elucidated in the late
1990s. Bónis et al. showed that psoriatic lesions
treated with the excimer laser cleared with fewer
treatments than narrow band UVB therapy [1].
Utilization of the laser also spared the unin-
volved skin from UV exposure, reducing the risk
of carcinogenicity and photoaging. Kemény et al.
also found that remissions for up to 2 years were
seen in some patients [6]. Laser therapy demon-
strated efficacy at lower cumulative doses when
compared to conventional light therapy. It was
also noted that psoriatic plaques can tolerate sev-
eral times the minimal erythema dose (MED) of
normal skin without burning. Exposure of three
to four times the MED has demonstrated early
clearance and long remissions. Doses greater
than six times the MED, however, have shown to
be complicated by blistering, pain, and reduced
compliance. In 2002, Feldman et  al. reported
that 80 patients treated with lower multipli-
ers of the MED given twice weekly achieved
75% or greater clearance in 72% of subjects in
an average of 6.2 treatments [7]. The pulse dye
laser (PDL) has also been studied for the treat-
ment of psoriasis. The basis for using the PDL
is selective photothermolysis of the exagger-
ated vascular network within psoriatic plaques.
Small studies have revealed its possible benefit
[8–10]. Additionally, Al-Mutairi et al. studied 42
patients, finding PDL to be more beneficial than
the excimer laser in treating nail psoriasis [11].
Nonetheless, stronger data exists to support the
use of the 308 nm excimer laser for the treatment
of psoriasis [7].
The use of excimer lasers is a source of research
in the field of psoriasis treatment. Kagen et  al.
determined that a single 10 MED ­administration
of lesion-limited high-dose (TURBO) ultraviolet
B light using the excimer laser was sufficient in
clearing a psoriatic plaque. The study hypoth-
esizes that this success is likely due to the laser’s
focus on the pathogenic T cell mechanisms which
are active in psoriasis [12]. Additionally, com-
bination therapy using excimer lasers has been
investigated. Tang et al. studied the combination
of the excimer laser with topical Calcipotriene
and Dong et al. with topical flumetasone on the
treatment of psoriasis vulgaris. Both studies found
that combination therapy potentially improved
L. Jordan et al.

hacklink satın al mumu模拟器 雷电模拟器 向日葵 giftcardmall/mygift giftcardmall balance mygift giftcardmall matbet matbet giriş Casibom Casibom Resmi Adres Casibom Casibom Casibom Giriş Adresi Casibom Casibom Casibom Güncel Giriş Casibom Deneme Bonusu Veren Siteler Deneme Bonusu Veren Siteler Deneme Bonusu Veren Siteler Deneme Bonusu Veren Siteler Deneme Bonusu Veren Siteler Deneme Bonusu Veren Siteler Deneme Bonusu Deneme Bonusu Veren Siteler Deneme Bonusu Fixbet Fixbet Güncel Giriş Fixbet Betgaranti Betgaranti Güncel Adres Betgaranti Fixbet Fixbet Güncel Giriş Fixbet Fim İzle Fim İzle Giriş Fim İzle Deneme Bonusu Deneme Bonusu Veren Siteler Deneme Bonusu Grandpashabet Grandpashabet Güncel Giriş Grandpashabet Fim İzle Fim İzle Güncel Adres Fim İzle jojobet jojobet giriş jojobet jojobet giriş jojobet jojobet giriş Casibom Casibom Giriş Adresi Casibom Casibom Casibom Güncel Adres Casibom Casibom Casibom Giriş Adresi Casibom Casibom Casibom Giriş Casibom Turk İfsa Turk İfsa Güncel Giriş Turk İfsa Canlı Maç Canlı Maç İzle Canlı Maç Porno İzle Porno İzle Güncel Adres Porno İzle Turk İfsa Turk İfsa Güncel Giriş Turk İfsa Porno İzle Porno İzle Güncel Adres Porno İzle Jojobet Jojobet Giriş Jojobet Canlı Maç Canlı Maç İzle Canlı Maç Deneme Bonusu Film İzle Deneme Bonusu Veren Siteler Deneme Bonusu Türkçe Dublaj Film İzle Film İzle Deneme Bonusu Deneme Bonusu Giriş Deneme Bonusu Deneme Bonusu Deneme Bonusu Veren Siteler Deneme Bonusu Casibom Casibom Resmi Adres Casibom Casibom Güncel Adres Casibom Casibom Güncel Adres Casibom Casibom Resmi Adres Casibom Casibom Giriş Adresi perabet perabet giriş holiganbet holiganbet giriş Casibom Lesfillmercom Casibom Lesfillmercom Giriş Casibom Casibom Güncel Giriş Casibom Casibom Güncel Giriş Casibom Tevfikmuratyildirimcom Casibom Gerbergirlcom Casibom Gerbergirlcom Güncel Giriş Casibom Tevfikmuratyildirimcom Casibom Tevfikmuratyildirimcom Casibom Spcelectriccontrolcom Casibom Casibom Resmi Adres Casibom Casibom Giriş Adresi jojobet jojobet giriş jojobet jojobet giriş marsbahis marsbahis giriş jojobet jojobet giriş jojobet jojobet giriş jojobet jojobet giriş Casibom Casibom Giriş Casibom Casibom Giriş Adresi Casibom Casibom Giriş Adresi Casibom Casibom Giriş Casibom Casibom Güncel Giriş vaycasino vaycasino giriş vaycasino güncel giriş vaycasino vaycasino giriş vaycasino güncel giriş matbet matbet giriş matbet güncel giriş vaycasino vaycasino güncel giriş vaycasino giriş matbet matbet giriş pusulabet pusulabet giriş pusulabet pusulabet güncel giriş pusulabet giriş matbet matbet güncel giriş matbet giriş Casibom Casibom Resmi Adres Casibom Casibom Güncel Giriş Casibom Casibom Giriş Adresi Casibom Casibom Resmi Adres pusulabet pusulabet giriş pusulabet güncel giriş Fixbet Fixbet Güncel Giriş Salvobet Salvobet Giriş Salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet casibom casibom casibom casibom casibom casibom casibom casibom casibom casibom Turk Porno Turk Porno Giriş Turk Porno casibom casibom casibom casibom casibom casibom casibom casibom casibom casibom casibom casibom casibom casibom casibom casibom casibom casibom casibom casibom Casibom Casibom Giriş Adresi Casibom salvobet salvobet salvobet salvobet salvobet casibom casibom casibom casibom Casibom Casibom Resmi Adres Casibom Casibom Giriş Adresi casibom casibom jojobet izmir escort izmir buca escort buca escort jojobet casibom holiganbet holiganbet giriş jojobet holiganbet holiganbet giriş jojobet jojobet jojobet jojobet giriş jojobet güncel giriş izmir escort izmir buca escort buca escort izmir escort bayan salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet salvobet marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis marsbahis Deneme Bonusu Veren Siteler Deneme Bonusu Veren Siteler Giriş Deneme Bonusu Veren Siteler Deneme Bonusu Deneme Bonusu Veren Siteler Deneme Bonusu Deneme Bonusu Veren Deneme Bonusu Veren Giriş Deneme Bonusu Veren salvobet salvobet salvobet salvobet Casibom betgaranti betgaranti betgaranti matbet matbet giriş matbet matbet giriş Casibom Casibom Salvobet jojobet Salvobet Salvobet Salvobet Casibom Casibom Casibom Güncel Adres Casibom Güncel Giriş Marsbahis Marsbahis Marsbahis bahsegel Fixbet Fixbet Güncel Adres Grandpashabet Grandpashabet Giriş Grandpashabet Grandpashabet Güncel Giriş 1xbet 1xbet Resmi Adres Casibom Casibom Giriş Marsbahis Marsbahis Marsbahis Deneme Bonusu Deneme Bonusu Veren Siteler Deneme Bonusu Deneme Bonusu Veren Siteler Casibom Casibom Resmi Adres Casibom Casibom Resmi Adres Casibom Casibom Resmi Adres Grandpashabet Grandpashabet Güncel Adres Grandpashabet Grandpashabet Giriş Adresi jojobet jojobet giriş jojobet güncel giriş vaycasino vaycasino giriş vaycasino güncel giriş jojobet jojobet giriş jojobet güncel giriş Deneme Bonusu Deneme Bonusu Veren Siteler Listesi Grandpashabet Grandpashabet Giriş Grandpashabet Grandpashabet Grandpashabet Resmi Adres Grandpashabet Grandpashabet Güncel Giriş Grandpashabet Grandpashabet Güncel Adres Grandpashabet Grandpashabet Güncel Giriş Grandpashabet Grandpashabet Güncel Giriş Grandpashabet Grandpashabet Giriş Adresi Deneme Bonusu Deneme Bonusu Veren Siteler Deneme Bonusu Deneme Bonusu Veren Siteler grandpashabet grandpashabet grandpashabet Grandpashabet Grandpashabet Resmi Adres Grandpashabet Grandpashabet Resmi Adres Deneme Bonusu Deneme Bonusu Veren Siteler Grandpashabet Grandpashabet Giriş Adresi Deneme Bonusu Deneme Bonusu Veren Siteler Deneme Bonusu Deneme Bonusu Veren Siteler vaycasino vaycasino giriş jojobet grandpashabet casibom Casibom Casibom Giriş casibom www.giftcards.com Marsbahis grandpashabet jojobet jojobet grandpashabet casibom jojobet Casibom Casibom Casibom Casibom Casibom Grandpashabet Grandpashabet Giriş Marsbahis Marsbahis Marsbahis Marsbahis Grandpashabet Grandpashabet Resmi Adres grandpashabet grandpashabet giriş Casibom Fixbet Fixbet Giriş Casibom Deneme Bonusu Deneme Bonusu Veren Siteler Holiganbet Holiganbet Güncel Adres Nevşehir escort Kapadokya escort Nevşehir escort bayan nevşehir eskort escort nevşehir Casibom Casibom Giriş Adresi Kapadokya esc Casibom Casibom Resmi Adres Matbet Matbet Matbet Güncel Adres Pusulabet Pusulabet Giriş Adresi imajbet giriş Deneme Bonusu Deneme Bonusu Veren Siteler Deneme Bonusu Deneme Bonusu Veren Siteler Trabzon escort escort trabzon Trabzon escort bayan Deneme Bonusu Deneme Bonusu Veren Siteler