Skin Rejuvenation Using Intense Pulsed Light a Randomized Controlled Split-Face Trial with Blinded Response Evaluation

STUDY Skin Rejuvenation Using Intense Pulsed Light A Randomized Controlled Split-Face Trial With Blinded Response Evaluation

Lene Hedelund, MD; Eva Due, MD; Peter Bjerring, MD, DMSc; Hans Christian Wulf, MD, DMSc; Merete Haedersdal, MD, PhD, DMSc

Objective: To evaluate efficacy and adverse effects of Results: Skin texture was significantly improved at all intense pulsed light rejuvenation in a homogeneous group clinical assessments except at the 6-month examination of patients. (PϽ.006). The improvements peaked at 1 month after treatment, at which time 23 (82%) of 28 patients had bet- Design: Randomized controlled split-face trial. ter appearances of treated vs untreated sides. Most patients obtained mild or moderate improvements, and 16 Setting: University dermatology department. patients (58%) self-reported mild or moderate efficacy on skin texture. Rhytids were not significantly different Patients: Thirty-two female volunteers with Fitzpa- on treated vs untreated sides, and 19 patients (68%) re- trick skin type I through III and class I or II rhytids. ported uncertain or no efficacy on rhytids. Significant improvements of telangiectasia (PϽ.001) and irregular pig- Interventions: Subjects were randomized to 3 intense Ͻ pulsed light treatments at 1-month intervals or to no treat- mentation (P .03) were found at all assessments. Three ment of right or left sides of the face. patients withdrew from the study because of pain related to treatment. Main Outcome Measures: Primary end points were skin texture and rhytids. Secondary end points were tel- Conclusions: Three intense pulsed light treatments im- angiectasia, irregular pigmentation, and adverse effects. proved skin texture, telangiectasia, and irregular pig- Efficacy was evaluated by patient self-assessments and mentation but had no efficacy on rhytids. Adverse events by blinded clinical and photographic evaluations up to were minimal, but included scar in 1 patient. 9 months after final treatment. Adverse effects were assessed clinically and by noninvasive skin reflectance measurements. Arch Dermatol. 2006;142:985-990

ONABLATIVE SKIN REJUVE- glass laser (1540 nm). The IPL systems nation is used for the emit polychromatic light in a wavelength treatment of photodam- spectrum of 500 to 1200 nm.5 With the aged skin, including skin aid of different cutoff filters, the spectral texture, rhytids, telangi- range can be narrowed to selectively tar- ectasia,N and irregular pigmentation.1 Treat- get variable structures of the skin.5,6 ments of telangiectasia and irregular pig- Controlled split-face trials, which com- mentation are well established; possible pare treated vs untreated control sites, improvement of skin texture and rhytids have demonstrated the efficacy of visible by nonablative remodeling is widely dis- (532- to 595-nm) and midinfrared (1064- cussed. The mechanism of action is to 1540-nm) lasers for the treatment of 7-11 thought to be based on selective absorp- skin texture and rhytids. tion of light in hemoglobin or tissue wa- ter, leading to the formation of a dermal CME course available at repair zone and subsequent collagen syn- www.archdermatol.com thesis.2-4 Devices in the visible and midin- Author Affiliations: frared parts of the electromagnetic spec- The objective of this randomized con- Departments of Dermatology, trum are used for nonablative remodeling, trolled split-face trial was to evaluate the University of Copenhagen and including intense pulsed light (IPL), po- Bispebjerg Hospital, efficacy and adverse effects of IPL rejuve- Copenhagen (Drs Hedelund, tassium-titanyl-phosphate laser (532 nm), nation, with the primary end points being Due, Wulf, and Haedersdal), pulsed dye lasers (585 and 595 nm), Nd: skin texture and rhytids. The efficacy on and Aarhus University Hospital, YAG lasers (1064 and 1320 nm), diode la- telangiectasia and irregular pigmentation Aarhus (Dr Bjerring), Denmark. sers (532 and 1450 nm), and erbium: was secondarily assessed. To our knowl-

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 01/27/2020 edge, this study is the first randomized controlled split- level of satisfaction concerning rhytids, skin texture, telangi- face trial comparing a treated vs an untreated control ectasia, and irregular pigmentation (using a visual analog scale, site after IPL rejuvenation in a homogeneous group of ranging from 0 [unsatisfied] to 10 [maximum satisfaction]).13 patients. Potential adverse effects such as wounds, erythema, hypopig- mentation, hyperpigmentation, and scars were evaluated clinically using a 4-point scale (indicating none, mild, moderate, METHODS or severe). Photographs were taken using a Canon digital camera (EOS D30) equipped with a lens-mounted ring flash (Canon Macro Lens EF 100 mm 1:2.8; Canon Inc, Tokyo, Japan). All Thirty-two healthy female volunteers (mean age, 47 years) with photographs were taken in raw format under identical condi- Fitzpatrick skin type I through III and class I or II rhytids were tions and camera settings. Standardized views (en face and 45° treated. Inclusion criteria were nonsmokers with symmetrical oblique) were used, and a single laboratory processed all pho- skin texture, facial rhytids, irregular pigmentation, and telan- tographs. giectasia on the right and left sides of the face. Exclusion cri- Objective measurements of skin pigmentation were per- teria were pregnancy, any visible asymmetry of skin texture and formed by skin reflectance spectroscopy (UV-Optimize, Model facial rhytids, irregular pigmentation, and telangiectasia, any 550/660 nm; Matic, Nærum, Denmark). The instrument mea- sign of infection or inflammatory skin disease, previous for- sures pigmentation (melanin) and redness (hemoglobin) in- mation of hypertrophic scars or keloids, use of oral isotreti- dependent of each other, based on skin reflection of 555- and noin in the past 12 months, current use of aspirin or nonste- 660-nm wavelengths and gives the objective results on wide roidal anti-inflammatory drugs, exposure to UV irradiation biological scales. Zero percent pigmentation corresponds to ab- within the past 4 weeks, and previous skin rejuvenation pro- solutely white skin with no melanin pigmentation at all, and cedures in the facial area. The patients were recruited from the 100% pigmentation corresponds to theoretically absolutely black community by advertisements in local newspapers, and all gave skin without any reflection. The instrument performs 3 inde- informed consent. The study was approved by the human study pendent measurements and gives the mean value at the dis- committee and was conducted from January 12, 2004, to Janu- play.14-17 Three measurements were performed on each side of ary 20, 2005. the face (ie, cheek, periorbital, and perioral regions). Specific The patients were randomized to 3 IPL treatments at 1-month landmarks ensured that measurements were continually taken intervals or to no treatment of the right or left sides of the face. at the same skin area. The randomization was carried out before treatment by pa- Preoperative sample size calculations revealed a required tients’ drawing lots between 2 opaque sealed envelopes con- sample size of 27 patients (based on a .05 significance level, taining “right” or “left” marked cards representing the site for 90% power, 15% uncertainty, and an expected 55% to im- intervention with IPL. Twenty-nine of 32 patients received the prove on treated sides). Nonparametric statistical methods were allocated treatment, and 28 patients completed the study (2 pa- used. The Friedman test and Wilcoxon matched pairs test were tients allocated to treatment on the right side and 1 patient al- used for paired comparisons. Differences between treated vs located to treatment on the left side withdrew from the study untreated control sides were compared using a sign test (bi- before finishing the treatment because of pain related to the nomial test). Descriptive data are presented as median (inter- treatment, and 1 patient allocated to treatment on the right side quartile range [IQR]). withdrew from the study after the final treatment because of lack of time). The IPL treatments were performed with a second- generation IPL system (Ellipse Flex; Danish Dermatologic De- RESULTS velopment A/S, Hørsholm, Denmark), which in contrast to the first-generation system uses dual mode filters that restrict the emitted light to a wavelength band from 530 to 750 nm, in- Blinded clinical evaluations found significant improve- hibiting shorter and longer wavelengths from reaching the skin ments of skin texture at 1, 3, and 9 months after treat- surface. In addition, the pulse is more stable in the second- ment (PϽ.006) on treated vs untreated facial sides, generation IPL system, with only minor pulse decay that re- whereas no significant differences were found at 6 months sults in a more stable spectral light distribution throughout the after treatment (Table 1 and Table 2). The greatest im- pulse duration. Energies varied between 7.5 and 8.5 J/cm2 de- provement was found at 1 month after treatment, when livered at two 2.5-millisecond pulses with a 10-millisecond in- 23 patients (82%) scored better appearances of treated terpulse delay. Because longer wavelengths from 750 through vs untreated sides, with 10 patients (36%), 9 patients 1200 nm are removed, the emitted fluence levels are signifi- (32%), and 4 patients (14%) having marked, moderate, cantly lower than in comparable IPL systems. Before IPL treatment, the skin was covered with a transpar- and mild differences, respectively. At 3 and 9 months af- ent gel to optimize optical coupling between the light guide and ter treatment, the improvements declined, when 11 pa- skin. Postoperative evaluations were performed at 1, 3, 6, and tients (42%) and 15 patients (56%), respectively, scored 9 months after the final treatment. Evaluations were per- better appearances of treated vs untreated sides, with most formed by a blinded independent physician (E.D.) and by pa- patients having small differences. By photographic evalu- tient self-reports. The physician graded differences of skin tex- ations, no significant differences were found between ture, rhytids (periorbicular rhytids, perioral rhytids, and facial treated vs untreated sides at any time point (Figure 1). rhytids overall), telangiectasia, and irregular pigmentation on By patient self-assessment at the end of the study, 16 pa- the left side vs the right side of the face by clinical on-site and tients (58%) reported mild or moderate improvements photographic evaluations (using a 4-point scale, indicating no of skin texture and a corresponding median satisfaction difference, mild difference, moderate difference, or marked difference). Moreover, photographs were assessed using the 9-point level of 5.1 (IQR, 4.0-7.0) (Figure 2). rhytid assessment scale by Fitzpatrick et al.12 At the end of the By clinical and photographic evaluations, no signifi- study, the patient self-reported treatment efficacy (using a 6-point cant differences were found of rhytids on treated vs un- scale, indicating worse appearance, no efficacy, uncertain ef- treated sides (Table 1, Table 2, and Figure 1), and the ficacy, mild efficacy, moderate efficacy, or marked efficacy) and rhytid severity scores were not significantly different

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 01/27/2020 Table 1. Blinded Clinical Evaluations of Treated vs Untreated Sides of the Face at 1, 3, 6, and 9 Months After Treatment*

Treated Side Best Untreated Side Best

Time After No Mild/Moderate/ Mild/Moderate/ P Treatment, mo Difference Total Marked Total Marked Value Skin Texture 1 4 (1) 82 (23) 14/32/36 (4/9/10) 14 (4) 7/4/4 (2/1/1) Ͻ.001 3 54 (14) 42 (11) 31/12/0 (8/3/0) 4 (1) 4/0/0 (1/0/0) .006 6 56 (15) 33 (9) 26/7/0 (7/2/0) 11 (3) 7/4/0 (2/1/0) .15 9 41 (11) 56 (15) 37/19/0 (10/5/0) 4 (1) 4/0/0 (1/0/0) Ͻ.001 Periorbital Rhytids 1 0 (0) 57 (16) 7/21/29 (2/6/8) 43 (12) 7/11/25 (2/3/7) .57 3 8 (2) 46 (12) 27/15/4 (7/4/1) 46 (12) 19/23/4 (5/6/1) Ͼ.99 6 33 (9) 37 (10) 30/7/0 (8/2/0) 30 (8) 22/7/0 (6/2/0) .82 9 7 (2) 58 (15) 19/31/8 (5/8/2) 35 (9) 23/12/0 (6/3/0) .31 Perioral Rhytids 1 4 (1) 57 (16) 14/11/32 (4/3/9) 39 (11) 4/21/14 (1/6/4) .44 3 23 (6) 46 (12) 12/35/0 (3/9/0) 31 (8) 19/4/8 (5/1/2) .50 6 48 (13) 37 (10) 26/11/0 (7/3/0) 15 (4) 7/7/0 (2/2/0) .18 9 52 (13) 36 (9) 16/16/4 (4/4/1) 12 (3) 4/8/0 (1/2/0) .15 Overall Rhytids 1 7 (2) 54 (15) 14/11/29 (4/3/8) 40 (11) 11/18/11 (3/5/3) .56 3 42 (11) 27 (7) 8/19/0 (2/5/0) 31 (8) 19/8/4 (5/2/1) Ͼ.99 6 52 (14) 15 (4) 15/0/0 (4/0/0) 33 (9) 15/15/4 (4/4/1) .27 9 38 (10) 19 (5) 12/0/8 (3/0/2) 42 (11) 19/19/4 (5/5/1) .21 Telangiectasia 1 10 (3) 79 (22) 0/29/50 (0/8/14) 11 (3) 7/4/0 (2/1/0) Ͻ.001 3 4 (1) 89 (23) 12/42/35 (3/11/9) 8 (2) 0/8/0 (0/2/0) Ͻ.001 6 11 (3) 81 (22) 15/48/19 (4/13/5) 7 (2) 7/0/0 (2/0/0) Ͻ.001 9 15 (4) 85 (23) 19/48/19 (5/13/5) 0 (0) 0/0/0 (0/0/0) Ͻ.001 Irregular Pigmentation 1 11 (3) 71 (20) 14/32/25 (4/9/17) 18 (5) 7/0/11 (2/0/3) .004 3 12 (3) 77 (20) 35/31/12 (9/8/3) 12 (3) 0/8/4 (0/2/1) Ͻ.001 6 22 (6) 67 (18) 19/48/0 (5/13/0) 11 (3) 4/7/0 (1/2/0) .002 9 22 (6) 59 (16) 30/30/0 (8/8/0) 19 (5) 15/4/0 (4/1/0) .03

*Data are given as percentages, with the exact number of patients in parentheses. Because of rounding, percentages may not all total 100. The treatment was considered ineffective if no difference was seen between the treated and untreated sides. The treatment was considered to have a positive effect when the treated side obtained a better appearance than the untreated side and, conversely, a negative effect when the untreated side obtained a better appearance than the treated side. P values less than .05 show significant differences between the percentages of patients with best appearance of treated vs untreated sides.

(Table 3). By patient self-assessment, 19 patients (67%) nes and freckles during the first week after treatment. One reported uncertain or no efficacy on rhytids and a cor- patient had a crust on the chin after the first treatment, responding median satisfaction level of 2.5 (IQR, 1.3- which developed into an atrophic scar. There were no 5.0) (Figure 2). reported incidences of purpura or pigmentary changes. Significant improvements of telangiectasia were found No adverse effects were observed on untreated sides. The at 1 to 9 months after surgery by clinical evaluations (79%- percentages of skin pigmentation remained constant, and 89% [22-23 patients], PϽ.001) and by photographic no significant differences were seen between treated vs evaluations (53%-71% [15-20 patients], PϽ.001). By pa- untreated sides at any time. At 1 month after treatment, tient self-assessment, 13 patients (46%) reported mod- the percentages were 23.5% (IQR, 20.0%-25.4%) vs erate or marked improvements of telangiectasia and a 23.1% (IQR, 18.8%-25.9%) (P=.10). At 9 months after corresponding median satisfaction level of 5.2 (IQR, 4.9- treatment, the percentages were 23.1% (IQR, 22.3%- 8.3). Significant improvements of irregular pigmenta- 26.8%) vs 23.6% (IQR, 20.1%-26.8%) (P=.18). Three tion were found at 1 to 9 months after treatment by clini- patients withdrew from the study because of pain re- cal evaluations (59%-77% [16-20 patients], PϽ.03) and lated to treatment. by photographic evaluations (61%-86% [17-24 patients], PϽ.007). By patient self-assessment, 13 patients (46%) reported moderate or marked improvements of ir- COMMENT regular pigmentation and a corresponding median satisfaction level of 5.4 (IQR, 5.0-7.7). Although IPL rejuvenation had no efficacy on rhytids, Adverse effects, including slight erythema and edema, there was long-term improvement of skin texture, tel- were observed in all patients immediately after treat- angiectasia, and irregular pigmentation. To our knowl- ment. All patients showed photo darkening of lentigi- edge, the present study is the first randomized con-

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 01/27/2020 Table 2. Blinded Photographic Evaluations of Treated vs Untreated Sides of the Face at 1, 3, 6, and 9 Months After Treatment*

Treated Side Best Untreated Side Best

Time After No Mild/Moderate/ Mild/Moderate/ P Treatment, mo Difference Total Marked Total Marked Value Skin Texture 1 57 (16) 32 (9) 29/4/0 (8/1/0) 11 (3) 7/4/0 (2/1/0) .15 3 69 (18) 23 (6) 23/0/0 (6/0/0) 8 (2) 8/0/0 (2/0/0) .29 6 64 (18) 29 (8) 21/4/4 (6/1/1) 7 (2) 4/4/0 (1/1/0) .11 9 63 (17) 30 (8) 26/4/0 (7/1/0) 7 (2) 7/0/0 (2/0/0) .11 Periorbital Rhytids 1 18 (5) 46 (13) 18/29/0 (5/8/0) 35 (10) 14/21/0 (4/6/0) .68 3 27 (7) 50 (13) 35/12/4 (9/3/1) 23 (6) 12/12/0 (3/3/0) .17 6 18 (5) 39 (11) 18/21/0 (5/6/0) 43 (12) 25/18/0 (7/5/0) Ͼ.99 9 11 (3) 52 (14) 15/37/0 (4/10/0) 37 (10) 30/4/4 (8/1/1) .54 Perioral Rhytids 1 36 (10) 39 (11) 18/14/7 (5/4/2) 25 (7) 21/4/0 (6/1/0) .48 3 31 (8) 42 (11) 19/19/4 (5/5/1) 27 (7) 23/4/0 (6/1/0) .48 6 32 (9) 43 (12) 18/14/11 (5/4/3) 25 (7) 21/4/0 (6/1/0) .36 9 41 (11) 37 (10) 11/26/0 (3/7/0) 22 (6) 19/0/4 (5/0/1) .46 Overall Rhytids 1 70 (19) 15 (4) 7/7/0 (2/2/0) 15 (4) 15/0/0 (4/0/0) Ͼ.99 3 73 (19) 15 (4) 8/8/0 (2/2/0) 12 (3) 4/8/0 (1/2/0) Ͼ.99 6 64 (18) 21 (6) 14/7/0 (4/2/0) 14 (4) 7/4/4 (2/1/1) .75 9 68 (17) 16 (4) 12/4/0 (3/1/0) 16 (4) 8/4/4 (2/1/1) Ͼ.99 Telangiectasia 1 21 (6) 71 (20) 43/21/7 (12/6/2) 7 (2) 4/4/0 (1/1/0) Ͻ.001 3 27 (7) 65 (17) 46/19/0 (12/5/0) 8 (2) 4/4/0 (1/1/0) Ͻ.001 6 39 (11) 53 (15) 25/21/7 (7/6/2) 7 (2) 7/0/0 (2/0/0) .001 9 40 (10) 60 (15) 40/12/8 (10/3/2) 0 0/0/0 (0/0/0) Ͻ.001 Irregular Pigmentation 1 7 (2) 81 (22) 22/44/15 (6/12/4) 11 (3) 0/7/4 (0/2/1) Ͻ.001 3 8 (2) 85 (22) 23/42/19 (6/11/5) 8 (2) 4/4/0 (1/1/0) Ͻ.001 6 21 (6) 61 (17) 29/18/14 (8/5/4) 18 (5) 11/4/4 (3/1/1) .007 9 4 (1) 86 (24) 36/36/14 (10/10/4) 11 (3) 4/4/4 (1/1/1) Ͻ.001

*Data are given as percentages with the exact number of patients in parentheses. Because of rounding, percentages may not all total 100.

trolled split-face trial evaluating efficacy and adverse effects bers of treatments, treatment intervals, and treatment areas of IPL rejuvenation by comparing a treated vs an un- make it difficult to compare and draw conclusions about treated control site. Three randomized controlled stud- the efficacy of the different nonablative devices avail- ies that included split-face trials previously evaluated the able for treatment of skin texture and rhytids. In the pres- efficacy of IPL rejuvenation alone vs IPL treatment in com- ent study, 3 IPL treatments at 1-month intervals im- bination with botulinum toxin A18 or with topical 20% proved the skin texture but had no efficacy on rhytids. 5-aminolevulinic acid.19,20 In all 3 studies, better results Treatment outcomes might have changed with the use were achieved after combined treatment, although marked of different treatment variables and an increased num- improvements of skin texture were demonstrated in up ber of treatments. However, the clinical improvements to 90% of patients after IPL treatments alone. In con- of vascular and pigmented lesions are similar to previ- trast to the results of our study, one study19 reported rhy- ous findings in controlled trials after IPL rejuvena- tid improvement in 80% of patients treated only with IPL. tion.18,23 Bjerring et al23 reported improvements of telan- Uncontrolled before-after trials support these find- giectasia and irregular pigmentation in 81.8% and 54.5% ings.1,21,22 Bitter1 reported a 10% to 90% improvement of of patients, respectively, at 3 months after 2 IPL treat- fine rhytids in 91% of patients after 4 full-face treatments using a wavelength band (530-750 nm) similar to ments with IPL, and in a study by Goldberg and Cutler21 that used in our study. In another study,18 telangiectasia some improvement of rhytids was found in all patients and lentigines improved markedly in 86% and 71% of at 6 months after 1 to 4 treatments with IPL. However, patients, respectively, at 26 weeks after 5 treatments with none of the previous studies evaluated an untreated con- IPL. trol area, which stresses the importance of our study. In our study, the patients were more satisfied with the Nonablative skin rejuvenation with lasers and IPL results on skin texture, telangiectasia, and irregular pig- sources is being investigated with great interest, but no mentation than with the results on rhytids. Moreover, clear reproducible treatment strategies have been de- patient satisfaction with the results on skin texture was fined. Differences in wavelengths, treatment settings, num- of the same magnitude as the satisfaction level with the

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Figure 1. A patient at 3 months after 3 intense pulsed light treatments on the left side of the face demonstrates improvement in telangiectasia and irregular pigmentation, without efficacy on skin texture and rhytids. A, Untreated right side. B, En face. C, Treated left side.

Table 3. Scores on 9-Point Rhytid Assessment Scale* Marked Effect Mild Effect No Effect Moderate Effect Uncertain Effect Worse Median (25%-75% Interquartile A Range) Rhytid Score 100 Time After Treated Side of Untreated Side P Treatment, mo Face of Face Value Periorbital Rhytids 0 3.0 (2.0-4.5) 3.0 (2.0-4.5) .82 50 1 3.0 (2.0-4.5) 3 (2-5) .85 3 3 (2-5) 3 (2-5) .62

% of Patients 6 3.0 (2.0-4.5) 3 (2-4) .67 9 3.0 (2.0-4.5) 3 (2-5) Ͼ.99 Perioral Rhytids 0 0 3 (1-4) 2.5 (1.0-4.0) .83 1 2.5 (1.5-4.0) 2.5 (1.5-4.0) .33 B 3 3.0 (1.5-4.0) 3 (1-5) Ͼ.99 10 6 3 (1-4) 2.5 (1-4) .52 9 2 (1-4) 2 (1-4) .30

*Scale by Fitzpatrick et al.12

photographic evaluations, which indicates that the im- Patients’ Satisfaction on VAS provements were too small to be visible on photo- 0 Skin Rhytides Irregular Telangiectasia graphs. It is possible that information loss of small changes Texture Pigmentation in depth perception caused by conversion of 3-dimensional (clinical) into 2-dimensional (photographic) meth- Figure 2. Patient self-assessment of skin texture, rhytids, irregular ods contributes to the conflicting assessment of skin tex- pigmentation, and telangiectasia at the end of the study. A, Efficacy rated on ture by clinical and photographic evaluations. Therefore, a 6-point scale. B, Satisfaction rated using a visual analog scale (VAS). clinical evaluations are preferred to judge skin texture in clinical trials, and the use of more than 1 blinded on- results on telangiectasia and irregular pigmentation. Clini- site evaluator may increase the validity of the results.24 cal evaluations, which supported these patient assess- If photographs are used, the use of parallel-polarized light ments, showed no improvement on rhytids but signifi- might be considered for better images of skin texture. cant improvement of skin texture at all assessments except In summary, 3 IPL treatments improved skin tex- at the 6-month examination, at which time a suntan in ture, telangiectasia, and irregular pigmentation, but they most patients may have masked the improvement. How- had no efficacy on rhytids. Adverse events were mini- ever, no skin texture improvement was demonstrated by mal, but included scar in 1 patient.

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 01/27/2020 Accepted for Publication: December 19, 2005. 8. Bernstein EF, Ferreira M, Anderson D. A pilot investigation to subjectively mea- Correspondence: Lene Hedelund, MD, Department of sure treatment effect and side-effect profile of non-ablative skin remodeling using a 532 nm, 2 ms pulse-duration laser. J Cosmet Laser Ther. 2001;3:137- Dermatology, University of Copenhagen and Bispebjerg 141. Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen, 9. Rostan E, Bowes LE, Iyer S, Fitzpatrick RE. A double-blind, side-by-side com- Denmark ([email protected]). parison study of low fluence long pulse dye laser to coolant treatment for wrin- Author Contributions: Study concept and design: Hede- kling of the cheeks. J Cosmet Laser Ther. 2001;3:129-136. lund, Bjerring, Wulf, and Haedersdal. Acquisition of data: 10. Carniol PJ, Farley S, Friedman A. Long-pulse 532-nm diode laser for nonablative facial skin rejuvenation. Arch Facial Plast Surg. 2003;5:511-513. Hedelund and Due. Analysis and interpretation of data: 11. Goldberg DJ, Rogachefsky AS, Silapunt S. Non-ablative laser treatment of facial Hedelund, Wulf, and Haedersdal. Drafting of the manu- rhytides: a comparison of 1450-nm diode laser treatment with dynamic cooling script: Hedelund. Critical revision of the manuscript for im- as opposed to treatment with dynamic cooling alone. Lasers Surg Med. 2002; portant intellectual content: Due, Bjerring, Wulf, and Hae- 30:79-81. dersdal. Statistical analysis: Hedelund. Administrative, 12. Fitzpatrick RE, Goldman MP, Satur NM, Tope WD. Pulsed carbon dioxide laser technical, and material support: Bjerring, Wulf, and Hae- resurfacing of photo-aged facial skin. Arch Dermatol. 1996;132:395-402. 13. Larnier C, Ortonne JP, Venot A, et al. Evaluation of cutaneous photodamage us- dersdal. Study supervision: Wulf and Haedersdal. ing a photographic scale. Br J Dermatol. 1994;130:167-173. Financial Disclosure: None reported. 14. Wulf HC. Method and an apparatus for determining an individual’s ability to stand Funding/Support: This study was supported by the Aage exposure to ultraviolet radiation. inventor. US patent 4 882 598. November 21, Bang Foundation, the Gerda and Aage Haensch Foun- 1989. dation, the Hans and Nora Buchard Foundation, and the 15. Sandby-Moller J, Poulsen T, Wulf HC. Influence of epidermal thickness, pigmentation and redness on skin autofluorescence. Photochem Photobiol. 2003; Danish Hospital Foundation for Medical Research (re- 77:616-620. gion of Copenhagen, the Faroe Islands, and Green- 16. Na R, Stender IM, Henriksen M, Wulf HC. Autofluorescence of human skin is land). age-related after correction for skin pigmentation and redness. J Invest Dermatol. Role of the Sponsors: The study sponsors had no role 2001;116:536-540. in study design, data collection, data analysis, data in- 17. Lock-Andersen J, Knudstorp ND, Wulf HC. Facultative skin pigmentation in cau- terpretation, or writing of the article. casians: an objective biological indicator of lifetime exposure to ultraviolet radiation? Br J Dermatol. 1998;138:826-832. 18. Carruthers J, Carruthers A. The effect of full-face broadband light treatments alone REFERENCES and in combination with bilateral crow’s feet botulinum toxin type A chemodenervation. Dermatol Surg. 2004;30:355-366. 1. Bitter PH. Noninvasive rejuvenation of photodamaged skin using serial, full-face 19. Dover JS, Bhatia AC, Stewart B, Arndt KA. Topical 5-aminolevulinic acid com- intense pulsed light treatments. Dermatol Surg. 2000;26:835-842. bined with intense pulsed light in the treatment of photoaging. Arch Dermatol. 2. Goldberg DJ, Samady JA. 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