Objective assessment of intensive targeted treatment for solar lentigines using intense pulsed light with wavelengths between 500 and 635 nm

Abstract

Background and objectives:
Solar lentigines are commonly found in sun-exposed areas of the body including hands, neck, or face. This study evaluates the efficacy of an intense pulsed light (IPL) device, with wavelengths between 500 and 635 nm and delivered with a targeted tip, for the treatment of solar lentigines on Japanese skin.

Study design/materials and methods:
Forty Japanese patients with solar lentigines received one IPL treatment with a targeted treatment tip that emits wavelengths between 500 and 635 nm and contact cooling. Pulses were delivered through a targeted tip to each lentigo until mild swelling and a gray color were observed. Digital photographs and gray level histogram values were taken pre- and post-treatment, and patient assessments were recorded post-treatment.

Results:
Significant improvement was observed for all patients in digital photographs and mean values of gray level histograms (P < 0.0001). Ninety percent of patients reported satisfaction with the improvement of the treatment area and convenience of the procedure. Complications were minor and transitory, consisting of a slight burning sensation and mild erythema which resolved within 5 hours of treatment. No serious adverse events were observed.

Conclusions:
A short-wavelength IPL, delivered with a targeted tip and contact cooling, offers a highly efficacious treatment for solar lentigines in Japanese skin with minimal downtime and complications. Lasers Surg. Med. © 2015 Wiley Periodicals, Inc.

Full text

Lasers in Surgery and Medicine 48:30–35 (2016)
Objective Assessment of Intensive Targeted Treatment
for Solar Lentigines Using Intense Pulsed Light With
Wavelengths Between 500 and 635 nm
Yohei Tanaka, MD, PhD,
1,2
Yuichiro Tsunemi, MD, PhD,
2
and Makoto Kawashima, MD, PhD
2
1
Clinica Tanaka Plastic, Reconstructive Surgery and Anti-aging Center, Matsumoto, Nagano 390-0874, Japan
2
Department of Dermatology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan
Background and Objectives: Solar lentigines are
commonly found in sun-exposed areas of the body
including hands, neck, or face. This study evaluates the
efficacy of an intense pulsed light (IPL) device, with
wavelengths between 500 and 635 nm and delivered with a
targeted tip, for the treatment of solar lentigines on
Japanese skin.
Study Design/Materials and Methods: Forty Japanese
patients with solar lentigines received one IPL treatment
with a targeted treatment tip that emits wavelengths
between 500 and 635 nm and contact cooling. Pulses were
delivered through a targeted tip to each lentigo until mild
swelling and a gray color were observed. Digital photo-
graphs and gray level histogram values were taken pre-
and post-treatment, and patient assessments were
recorded post-treatment.
Results: Significant improvement was observed for all
patients in digital photographs and mean values of gray
level histograms (P<0.0001). Ninety percent of patients
reported satisfaction with the improvement of the treat-
ment area and convenience of the procedure. Complica-
tions were minor and transitory, consisting of a slight
burning sensation and mild erythema which resolved
within 5 hours of treatment. No serious adverse events
were observed.
Conclusions: A short-wavelength IPL, delivered with a
targeted tip and contact cooling, offers a highly efficacious
treatment for solar lentigines in Japanese skin with
minimal downtime and complications. Lasers Surg. Med.
48:30–35, 2016. ß2015 Wiley Periodicals, Inc.
Key words: Asian patients; gray level histogram values;
minimally invasive treatment; photorejuvenation; short-
wavelength intense pulsed light
INTRODUCTION
Non-ablative photorejuvenation has become an integral
procedure in the emerging discipline of laser dermatologic
surgery [1]. Asianpatients with Fitzpatrick skin typesIII–V
are rarely highlighted in publications on cutaneous
disorders or cutaneous laser surgery [2]. However, Asian
patients seek to treat superficial pigmented lesions without
complications and post-treatment downtime. Although the
high melanin content confers better photo protection, photo
damage in the form of pigmentary disorders is common in
Asian skin [3]. Furthermore, post-inflammatory hyperpig-
mentation (PIH) occurring after cutaneous injury remains a
hallmark of skin of color [2,4].
With increasing use of lasers and light sources to treated
pigmentary disorders, prevention, and management of
PIH is of great interest in Asian skin, which has a tendency
for PIH due to the melanin-rich epidermis.
Intense pulsed light (IPL) therapy using incoherent
broad spectrum light has been reported to be effective for
treating superficial pigmented lesions [5–15]. A multi-
pass, low fluence regimen is required when using large IPL
handpieces in order to minimize patient discomfort and
risk of side effects, as well as avoid unintended thermal
effects in surrounding normal tissue [5].
The IPL device used in this study possesses a small
treatment tip to minimize irradiation to surrounding
tissue.
In this study, Japanese patients received one treatment
using a targeted IPL device with contact cooling and
wavelengths ranging from 500 to 635 nm. Treatment
efficacy was evaluated using a novel method to objectively
quantify color change of treated lentigines.
MATERIALS AND METHODS
Patient Selection
Forty Japanese patients (32 females and 8 males) aged
30–71 years (mean age, 47.3 12.4 years) with Fitzpatrick
skin type III–V were enrolled in this study. All patients had
visited the Clinica Tanaka Anti-Aging Center to remove
Conflict of Interest Disclosures: All authors have completed
and submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest and none were reported.
Financial Disclosure Statement: This study was conducted
without financial support from a third party. We have no
relevant financial activities outside the submitted work.
Correspondence to: Yohei Tanaka, MD, PhD, Clinica Tanaka
Plastic, Reconstructive Surgery and Anti-aging Center, M-1 Bld
1F, 3-4-3, Ote, Matsumoto, Nagano 390-0874, Japan.
E-mail: info@clinicatanaka.jp
Accepted 4 October 2015
Published online 14 October 2015 in Wiley Online Library
(wileyonlinelibrary.com).
DOI 10.1002/lsm.22433
ß2015 Wiley Periodicals, Inc.

solar lentigines on their cheeks. Patients who had received
prior treatment for pigmentary lesions or had skin disease,
ephelides, and/or melasma on the cheeks were excluded
from this study. Use of skin care products containing skin
lightening agents such as tretinoin, hydroquinone, or
arubutin was excluded throughout the study. All patients
were advised of the potential treatment risks and provided
written informed consent for participation in the study
prior to initiation of procedures. Subjects received one
treatment and were followed for 2–6 months.
Device Description
The IPL device used in this study emits a light spectrum
between 500 and 635 nm from a flashlamp to selectively
target melanin (AcuTip500; Cutera, Inc., Brisbane, CA)
(Fig. 1). Light was delivered to the targeted area with a
6.35 mm targeted tip, with minimum irradiation of the
surrounding normal tissue. To avoid any burning sensa-
tion and side effects, the sapphire contact cooling tip was
set to a fixed temperature of 208C. The sapphire block was
cooled with fluids using thermoelectric coolers circulated
by a pump and a cooling system. Pre- and parallel cooling of
the epidermis was accomplished using the temperature-
controlled sapphire window.
Treatment and Assessments
Before the IPL treatment, the pigmented area of the
patient’s face was wiped with an alcohol pad to remove any
makeup. No topical anesthetics or medications were
administered before, during, or after the treatment.
Traditionally, clear ultrasound gel is used during IPL
treatment to improve light transmission into the skin and
aid in epidermal cooling. However, in this study ultra-
sound gel was not used during treatment. The authors
have determined after years of experience that safety and
efficacy are not compromised when ultrasound gel is not
used with this targeted small tip IPL device.
A single treatment was performed on the pigmented
lesion with three to four passes of adjacent pulsesranging in
fluence from 10 to 14 J/cm
2
and pulse durationof 6.7–9.3 ms.
The average interval between passes was 1–2 minutes, and
in total, 60–150 pulses were administered to each lentigo.
Fluence varied depending on patient skin type and
immediate skin reaction observed during treatment.
Conventional IPL treatments usually regard a mild
darkening of the pigmentation as the clinical end point,
whereas in this study, pulses were delivered until a mild
swelling and gray color were observed in the lesion (Fig. 2).
Fig. 1. The absorption coefficients of melanin (brown) and
relative irradiance of the IPL device (green). Courtesy of Cutera,
Inc.
Fig. 2. A schematic of IPL treatment for pigmentation with a
large handpiece (top) and the IPL treatment with a small
handpiece used in this study (bottom).
Fig. 3. The improvement measured by the values of the gray level
histograms at the first pre-treatment visit and the last post-
treatment visit. A statistically significant difference was observed
(P¼0.0001). Data represent the means SD. Significant differ-
ence is indicated by ().
Fig. 4. Subjective volunteer assessments were performed using
questionnaires. Subjective patient assessments are shown as
follows: very satisfied (blue), satisfied (light blue), fairly satisfied
(green), and not satisfied (red).
OBJECTIVE ASSESSMENT OF INTENSIVE TARGETED TREATMENT 31

If the patient reported a severe burning sensation, the time
between pulses was extended to adequately cool the skin.
Immediately after the procedure, patients were allowed to
apply make-up and instructed to apply sunblock daily.
Digital photographs and gray level histograms, at
baseline and 2–6 months post-treatment, were evaluated
as objective assessments. Digital photographs were con-
ducted with a Power Shot G7 camera (Canon Inc., Tokyo,
Japan). Best practices were followed to ensure the
conditions in both pre- and post-treatment photographs
were as identical as possible. The gray level histograms
were created using enlargedgrayscale images of the treated
areas processed with Adobe Photoshop (Adobe, San Jose,
CA). The number of pixels at each gray level value from
0 (darkest) to 255 (brightest) were plotted on a histogram.
The pre- and post-treatment mean values of the gray level
histograms were compared and the difference was tested for
statistical significance using Wilcoxon’s signed-rank test
(P<0.05 was set as a cutoff for statistical significance).Data
are presented as mean and standard deviation.
Subjective assessments were performed using question-
naire data collected 2–6 months post-treatment. Patients
rated their degree of satisfaction with improvement of the
treated lesion, and convenience of the procedure. Scores
were based on a 5-point scale ranging from 0 to 4
(0 ¼worse; 1 ¼little satisfaction or not satisfied; 2 ¼fairly
satisfied; 3 ¼satisfied; and 4 ¼very satisfied).
RESULTS
Objective assessments evaluated by digital photo-
graphs and gray level histograms showed significant
improvement in all patients at 2–6 months following one
treatment. The mean values of the pre- and post-
treatment gray level histograms were 143.7 8.6 and
162.9 9.8, respectively. The mean difference of 19.2
gray level points indicated a clinically and statistically
significant improvement of treated solar lentigines at
follow-up (P<0.0001) (Fig. 3). Forty percent of subjects
had greater than 20 points increase in mean gray level
Fig. 5. A 30-year-old Japanese woman. (A) Pre-treatment. (B) Just after the treatment. (C) 10 days
post-treatment. (D) 90 days post-treatment. Four passes at 14 J/cm
2
(100 pulses) were applied.
Enlarged color image (E,H), grayscale image (F,I), and gray level histogram (G,J) of the treated
area pre- and post-treatment, respectively. Significant improvements were observed in digital
photographs and gray level histograms.
32 TANAKA ET AL.

value following treatment and demonstrated significant
clearing of the treated lesion. Five percent of subjects
experienced very significant lesion clearing, defined as
greater than 30 points increase in mean gray level
value. moderate clearing, or an increase between 10 and
20 gray level points post-treatment, was observed in
40% of subjects and 15% of subjects showed mild or
minimal improvement.
Ninety percent of patients reported satisfaction with
both improvement of treated lentigines and convenience
of the procedure (Fig. 4). The mean satisfaction ratings
for improvement of treated lentigines and convenience
of the procedure were 3.1 1.0 and 3.4 1.0, respectively.
Patients were satisfied with the high efficacy of the
treatment as well as the minimal discomfort and
side effects. Patients also expressed satisfaction with
the short procedure time, and minimal to no post-
treatment downtime. Representative cases are shown in
Figures5,6,and7.
Treated areas slightly darkened immediately after the
first pass. after additional passes, the treated areas swelled
and turned gray in color. Microcrusts from the treatment
lesion desquamated from the skin within 3–14 days.
Complications were minor and transitory, with a slight
burning sensation reported in four patients and mild
erythema in two patients. All side effects resolved within
5 hours of the treatment. No patients reported severe
burning sensation during the treatment and no anesthesia
was used. Additionally, there were no reports of PIH,
hypopigmentation, epidermal burn, scar formation, or
lesion recurrence during the study.
DISCUSSION
We previously reported that we can achieve various
effects in the targeted tissue with a limited wavelength and
contact cooling [16–20]. Many IPL devices emit broad-
spectrum light between 560 and 1,200 nm. Wavelengths
between 600–1,300 nm affect a large volume and depth of
Fig. 6. A 47-year-old Japanese man. (A) Pre-treatment. (B) 14 days after the treatment. (C) 60 days
post-treatment. (D) 180 days post-treatment. Three passes at 10 J/cm
2
(60 pulses) were applied.
Enlarged color image (E,H), grayscale image (F,I), and gray level histogram (G,J) of the treated
area pre- and post-treatment, respectively. Significant improvements were observed in digital
photographs and gray level histograms.
OBJECTIVE ASSESSMENT OF INTENSIVE TARGETED TREATMENT 33

tissue [21], and wavelengths near 800 nm are used for
photodynamic cancer therapy and induction of thermal
effects [22–24]. Wavelengths above 1,000 nm are not
strongly absorbed by melanin and not ideal for pigmenta-
tion treatment. The IPL device used in this study is
designed to select for wavelengths between 500 and
635 nm. Shorter wavelengths, such as those within this
range, are strongly absorbed by melanin and are highly
effective for treating excess pigment.
The mechanism of action for IPL treatment is based on
the theory of selective photothermolysis. The controlled
absorption of thermal energy by target melanin chromo-
phores within pigmentary lesions leads to their destruc-
tion without significant thermal damage to surrounding
normal tissue [25]. We also theorize IPL treatment may
stimulate a rapid differentiation of keratinocytes, accom-
panied by an upward transfer of melanocytes and
subsequent elimination of melanocytes during desquama-
tion of the microcrusts [16].
Microcrusts were observed after the IPL treatment in
this study. This microcrust formation seemed to depend on
the density and amount of pigment contained in the lesion.
A tendency towards a reduction of pigmentation was
observed in all subjects after the treatments; however, the
amount of pigment removed differed in each subject which
seemed to depend on the melanin density and distribution.
Although active melanocytes are left behind and pigmen-
tation may recur after the pigmented lesions are tempo-
rarily removed as extruded microcrusts [16], recurrence
was not observed throughout this study.
Ten percent of study patients were not satisfied with
their individual results. The efficacy of IPL therapy for
superficial pigment removal is dependent upon the
melanin density and distribution. Ephelides and lentigo
simplex that are severely pigmented are known to be more
effectively treated by IPL, however additional treatment
sessions, or a higher energy output, may be required for
these patients. Further studies are necessary to determine
Fig. 7. A 59-year-old Japanese woman. (A) Pre-treatment. (B) 4 days after the treatment. (C)
30 days post-treatment. (D) 60 days post-treatment. Three passes at 12 J/cm
2
(135 pulses) were
applied. Enlarged color image (E,H), grayscale image (F,I), and gray level histogram (G,J) of the
treated area pre- and post-treatment, respectively. Significant improvements were observed in
digital photographs and gray level histograms.
34 TANAKA ET AL.

if higher output or a second treatment may enhance the
effects.
In this study we introduced the gray level histogram, a
novel method for objective evaluation of post-treatment
color change in solar lentigines. Additional studies are
suggested to validate this method for pigmentation
measurement. While not yet validated, the gray level
histogram could serve as an effective patient communica-
tion tool to easily demonstrate measureable lightening of
pigmented lesions.
It should be noted that this was a preliminary study based
on a fairly small number of patients. We cannot exclude the
possibility that intrinsic and extrinsic factors in everyday
life may affect the changes demonstrated in this study.
Therefore, furtherstudies which include a larger number of
patients followed for a longer period of time are recom-
mended to evaluate the treatment effects more exactly.
CONCLUSION
This study demonstrated significant improvement of
lentigines and high patient satisfaction in a Japanese
population, without severe complications and side effects,
after a single intensive targeted IPL treatment using
wavelengths between 500 and 635 nm and contact cooling.
Furthermore, this non-ablative approach is convenient for
patients and requires almost no downtime.
REFERENCES
1. Nelson JS, Majaron B, Kelly KM. What is nonablative
photorejuvenation of human skin? Semin Cutan Med Surg
2002;21:238–250.
2. Ho SG, Chan HH. The Asian dermatologic patient: Review of
common pigmentary disorders and cutaneous diseases. Am J
Clin Dermatol 2009;10:153–168.
3. Chan HH. Effective and safe use of lasers, light sources, and
radiofrequency devices in the clinical management of Asian
patients with selected dermatoses. Lasers Surg Med
2005;37:179–185.
4. Kono T, Manstein D, Chan HH, Nozaki M, Anderson RR.
Q-switched ruby versus long-pulsed dye laser delivered with
compression for treatment of facial lentigines in Asians.
Lasers Surg Med 2006;38:94–97.
5. Willey A, Anderson RR, Azpiazu JL, Bakus AD, Barlow RJ,
Dover JS, Garden JM, Kilmer SL, Landa N, Manstein D, Ross
EV, Jr, Sadick N, Tanghetti EA, Yaghmai D, Zelickson BD.
Complications of laser dermatologic surgery. Lasers Surg
Med 2006;38:1–15.
6. Bitter PH. Noninvasive rejuvenation of photodamaged skin
using serial, full-face intense pulsed light treatments.
Dermatol Surg 2000;26:835–842.
7. Goldberg DJ, Cutler KB. Nonablative treatment of rhytids
with intense pulsed light. Lasers Surg Med 2000;26:196–200.
8. 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 patients. Lasers Surg Med 2002;30:
298–305.
9. Kawada A, Shiraishi H, Asai M, Kameyama H, Sangen Y,
Aragane Y, Tezuka T. Clinical improvement of solar
lentigines and ephelides with an intense pulsed light source.
Dermatol Surg 2002;28:504–508.
10. Alam M, Hsu TS, Dover JS, Wrone DA, Arndt KA. Non-
ablative laser and light treatments: Histology and tissue
effects-a review. Lasers Surg Med 2003;33:30–39.
11. Kligman DE, Zhen Y. Intense pulsed light treatment of
photoaged facial skin. Dermatol Surg 2004;30:1085–1090.
12. Wang CC, Hui CY, Sue YM, Wong WR, Hong HS. Intense
pulsed light for the treatment of refractory melasma in Asian
persons. Dermatol Surg 2004;30:1196–1200.
13. Weiss RA, Weiss MA, Beasley KL, Munavalli G. Our approach
to non-ablative treatment of photoaging. Lasers Surg Med
2005;37:2–8.
14. Dover JS, Bhatia AC, Stewart B, Arndt KA. Topical 5-amino-
levulinic acid combined with intense pulsed light in the
treatment of photoaging. Arch Dermatol 2005;141:1247–1252.
15. Tanaka Y, Tsunemi Y, Kawashima M. Intensive targeted
treatment for senile lentigines using intense pulsed light with
relatively short wavelengths (500-635nm) in asian patients.
34th American society for laser medicine and surgery,
Phoenix convention center/sheraton Phoenix downtown
hotel, Phoenix, Arizona, USA. Lasers Surg Med 2014;46(4):
368.
16. Yamashita T, Kuwahara T, Gonzalez S, Takahashi M. Non-
invasive visualization of melanin and melanocytes by reflec-
tance-mode confocal microscopy. J Invest Dermatol 2005;
124:235–240.
17. Tanaka Y, Gale L. Beneficial applications and deleterious
effects of near-infrared from biological and medical points of
view. Opt Photonics J 2013;3(4A):31–39.
18. Tanaka Y, Tsunemi Y, Kawashima M, Nishida H. The impact
of near-infrared in Plastic Surgery. Plast Surg Int J 2013;
Article ID 973073:1–13.
19. Tanaka Y, Tsunemi Y, Kawashima M, Nishida H, Tatewaki
N. Objective assessment of skin tightening using water-
filtered near-infrared (1000-1800nm) device with a contact
cooling and freezer stored gel in Asians. Clin Cosmet Investig
Dermatol 2013;6:167–176.
20. Tanaka Y. The impact of near-infrared radiation in derma-
tology. Review. World J Dermatol 2012;1:30–37.
21. Tanaka Y, Tatewaki N, Nishida H, Eitsuka T, Ikekawa N,
Nakayama J. Non-thermal DNA damage of cancer cells
using near-infrared irradiation. Cancer Sci 2012;103(8):
1467–1473.
22. Anderson RR, Parrish JA. The optics of human skin. J Invest
Dermatol 1981;77:13–19.
23. B€
aumler W, Abels C, Karrer S, Weiss T, Messmann H,
Landthaler M, Szeimies RM. Photo-oxidative killing of
human colonic cancer cells using indocyanine green and
infrared light. Br J Cancer 1999;80:360–363.
24. Orenstein A, Kostenich G, Kopolovic Y, Babushkina T, Malik
Z. Enhancement of ALA-PDT damage by IR-induced hyper-
thermia on a colon carcinoma model. Photochem Photobiol
1999;69:703–707.
25. Anderson RR, Parrish JA. Selective photothermolysis: Precise
microsurgery by selective absorption of pulsed radiation.
Science 1983;220:524–527.
OBJECTIVE ASSESSMENT OF INTENSIVE TARGETED TREATMENT 35