DE RM A TO L O GI CA L SU RG ER Y AND LAS ER S
BJD
British Journal of Dermatology
Fractional carbon dioxide laser resurfacing of rhytides and photoageing: a prospective study using profilometric analysis €fer,1 M. Koller,2 F. Zeman,2 A. Klein,1 U. Hohenleutner,1 M. Landthaler1 and E. Kohl,1 J. Meierho 1 S. Hohenleutner 1
Department of Dermatology and 2Centre for Clinical Trials, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
Summary Correspondence Elisabeth Kohl. E-mail: [email protected]
Accepted for publication 19 December 2013
Funding sources The study was partially funded by Alma Lasers GmbH.
Conflicts of interest None declared. DOI 10.1111/bjd.12807
Background Results of profilometric skin analyses after fractional ablative skin resurfacing are not only important for evaluating the efficacy of this therapy but are also relevant for physicians practising laser and aesthetic skin therapy. Currently, objective measurements of wrinkle reduction after fractional CO2 laser resurfacing are scarce, and it remains unclear whether the various facial areas respond differently to this therapy. Objectives To measure wrinkle parameters, the homogeneity of melanin distribution and skin roughness in four facial areas (periorbital, perioral, forehead, cheeks) before and after three fractional CO2 laser treatments. Methods Twenty-five women were analysed with regard to wrinkle parameters and mottled pigmentation on the face. We measured wrinkle size, depth and width and the homogeneity of melanin distribution and skin roughness in four facial areas before and after three fractional CO2 laser treatments. Additionally, the investigators rated clinical improvement using five-point grading scales. Results Wrinkles were significantly reduced in all facial areas, and the best results for wrinkle size and depth were found for the cheeks ( 583%, P = 0018 and 513%, P = 0018) and the periorbital area ( 351%, P < 0001 and 311%, P = 0001, respectively). The percentage improvements of rhytides evaluated by the investigators were mostly similar to those found from in vivo measurements. The homogeneity of melanin distribution in the skin was improved by 214% on the cheeks (P = 0012) and by 240% in the periorbital area (P < 0001). Clinical investigators rated the improvement of mottled pigmentation considerably higher (51–75%). Conclusions After a serial treatment with the fractional CO2 laser, we measured considerably varying wrinkle reduction depending on the area of the face, and the best results were found for the cheeks.
What’s already known about this topic?
• • •
Fractional carbon dioxide laser resurfacing is widely used for skin rejuvenation. Several studies have demonstrated clinical improvement of wrinkles and photoaged skin. Objective data on wrinkle reduction are not available.
What does this study add?
•
858
We objectively measured wrinkle reduction and improvement of mottled skin after a series of three treatments with the fractional carbon dioxide laser in several areas of the face.
British Journal of Dermatology (2014) 170, pp858–865
© 2013 British Association of Dermatologists
Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al. 859
Several studies have evaluated the clinical and histological effects of fractional CO2 lasers and their efficacy with regard to improving photoaged skin.1–6 In 2007, Hantash et al.5 were the first to describe an ablative fractional CO2 laser that produces a pattern of so-called microscopic treatment zones. Each laser spot creates a column of ablated and coagulated tissue that is surrounded by healthy skin, thus enabling rapid wound healing. In a first clinical study published in 2009, Rahman et al.7 reported a marked improvement regarding rhytides, pigmentation, laxity and skin texture 3 months after one to two treatments. Longo et al.8 found intense collagen remodelling after fractional CO2 laser resurfacing, which was still detectable 3 months after the treatment. Despite these promising findings, no objective data on wrinkle parameters before and after full-face treatment are currently available.9 Therefore, we investigated the objective reduction in wrinkle depth and size, the differences in wrinkle reduction in distinct facial areas and the objective improvement in mottled pigmentation and skin roughness. Additionally, we assessed the correlation of subjective investigator assessments with in vivo measurements. This constitutes a profilometric and clinical analysis of photoaged skin and wrinkles in four defined facial areas after three treatments with a fractional CO2 laser.
Materials and methods Study design We present a prospective, monocentric and one-armed study including 28 patients, who were analysed before and after laser therapy with regard to treatment efficacy. The study was approved by the institutional review board and the ethics committee of the University of Regensburg. Written informed consent was obtained from each patient before enrolment. Inclusion and exclusion criteria The main inclusion criteria were oral and written informed patient consent, wish for treatment of wrinkles and photoaged skin with the fractional CO2 laser, white women, age ≥ 18 years and Glogau photodamage classification type II–IV. Exclusion criteria were unrealistic expectations, concomitant ultraviolet therapy, pregnancy, any cosmetic procedure or treatment of the face 6 months before study treatment (for example, botulinum toxin, dermabrasion, chemical peeling, laser therapy, facelift or filler), Fitzpatrick skin type IV–VI, any skin diseases in the face impairing the assessment of the efficacy of the study treatment, systemic treatment with photosensitizing drugs, systemic treatment with retinoids 3 months before study treatment and suspected lack of compliance. Study treatment Each patient received three full-face treatments in an interval of 1–6 months. Each visit was photodocumented in a standardized manner (frontal and at 675° for both sides) using a © 2013 British Association of Dermatologists
FotoFinder mediscope (FotoFinder Systems GmbH, Bad Birnbach, Germany). Before laser treatment and at the follow-up visit 3 months after the last treatment, we performed in vivo measurements of skin topography and the distribution of melanin using an Antera 3DTM skin imaging device (Miravex, Dublin, Ireland). To ensure comparability, patients cleaned their face with Menalindâ washing lotion (Paul Hartmann AG, Heidenheim, Germany) directly before photodocumentation and in vivo measurements. All patients had their measurement areas marked on several adhesive transparent foils (OpSite Flexigrid; Smith and Nephew, Hamburg, Germany) to ensure that the in vivo measurements were conducted in identical areas (forehead, cheeks and perioral and periorbital areas) at the followup visit. Aciclovir (2 9 400 mg) was given as a prophylactic herpes treatment from 2 days before to 5–7 days after treatment. Study participants received 1 g metamizol orally for pain management 30 min before, and 800 mg ibuprofen 2 h before the start of treatment, but no topical anaesthetic cream. The eyes were protected with a moist gauze and laser protection glasses. All fractional CO2 laser treatments included the entire face and were conducted by the same clinician. Only the upper part of the eyelids was treated, but the area in direct proximity to the lashes remained untreated. Immediately after the treatment, the patients cooled the face with cold, wet compresses. During the entire treatment, cool air was used as an anaesthetic. Patients used Cicalfate restorative cream (Pierre Fabre Dermo-Kosmetik GmbH, Freiburg, Germany) several times a day for 7 days. Technical data We used a fractional CO2 laser (EXELO2; Alma Lasers GmbH, N€ urnberg, Germany; 106 lm, microbeam spot size 250 lm) with adjustable parameters for density of microspots, pulse width and energy. We chose a round treatment area (diameter 1 cm) and used the Soft Random Mode, in which laser spots were randomly placed in the treatment areas and their borders were gently faded out. Therefore, no geometric patterns were visible on the skin after treatment. We used a spot density of 25 or 50 spots cm 2 and conducted several passes to achieve a homogeneous distribution of microspots. For instance, to achieve a spot density of 200 spots cm 2 we used four passes at a spot density of 50 spots cm 2. The mean treatment parameters are displayed in Table 1. Pulse duration and pulse energy were slightly altered for each treatment. In the first treatment, a mean 236 microspots cm 2 were applied; as the patients responded well to the treatment, the number of microspots was increased by 24% in the second treatment and by 44% in the third treatment (Table 1) to increase skin surface ablation. The treatments resulted in skin surface ablation of 116%, 143% and 167%, respectively. In every treatment session, we slightly reduced the pulse energy and the number of microspots cm 2 in the periocular area and on the nose. For epidermal protection during treatment, we used an air cooling device directly attached to the laser scanner (Zimmer British Journal of Dermatology (2014) 170, pp858–865
860 Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al.
Treatment 1 Pulse duration, ms Pulse energy, mJ Microspots per cm2 Microspots per face
25 384 236 64 488
04 50 62 22 516
Treatment 2 25 380 292 79 724
03 41 64 20 391
Cryo 6; Zimmer MedizinSysteme GmbH, Neu-Ulm, Germany). On average, we used airflow settings of 14 07 during the first treatment, 13 04 during the second treatment and 13 05 during the last treatment. Skin topography and distribution of melanin were measured in vivo with the Antera 3D imaging system (Miravex) consisting of a handheld imaging device and a connected laptop with preinstalled proprietary software.10 The imaging technique of the Antera 3D allows three-dimensional imaging of partially diffusive and diffusive surfaces. It is based on multidirectional illumination and computer-aided reconstruction of the surface, utilizing the differences between images acquired from the surface as a result of illuminations from different angles. The skin topography and the concentration of chromophores are derived from the spatial and spectral analysis of the acquired image data. Skin texture reconstruction is achieved using a technique based on shape from shading,11 substantially modified in order to eliminate skin glare and improve the accuracy of measured data (Patent Cooperation Treaty application PCT/EP2010/001168, Irish Patent No. S85695). The texture reconstructed in this way is then used for quantitative skin analysis of factors such as depth and width of wrinkles, skin lesions and overall skin roughness. Several lightemitting diodes at seven different wavelengths illuminate the skin from different directions. Three-dimensional images of the back-reflected light are generated and processed to map the distribution and concentration of melanin and haemoglobin. Unlike traditional imaging techniques, where only three colour channels (red, green and blue) are used, the Antera 3D uses reflectance mapping of seven different light wavelengths spanning the entire visible spectrum. This allows for a more precise analysis of the skin’s colorimetric properties, which are determined mostly by two dominant chromophores: melanin and haemoglobin. Acquired spectral images are transformed into skin spectral reflectance maps, and the skin surface shape is used to compensate for light intensity variation due to the varying direction of incident illumination. The reflectance data are transformed into skin absorption coefficients and used to quantify melanin and haemoglobin concentrations using mathematical correlation with known spectral absorption data of these chromophores.12 The acquired images can be visualized in both two and three dimensions in different modes to display the natural skin colour, skin texture, melanin and haemoglobin. To measure differences in skin topography, melanin and haemoglobin in specific areas, examiners had to produce identical images of British Journal of Dermatology (2014) 170, pp858–865
Treatment 3 25 386 340 93 040
03 51 48 13 296
Table 1 Mean SD values for treatment parameters (n = 25) of the first, second and third treatments
the respective facial areas, because the software could only partially compensate shifts and rotations of the images. In vivo skin measurements We measured the periorbital and perioral areas, the forehead and the cheeks of each patient in vivo before and after each treatment. The follow-up evaluation was 3 months after the third treatment session. Because of the lack of reference points, measurements and analysis were not possible in some cases for technical reasons. For analysis, we selected the deepest wrinkle in the pretreatment image and marked the wrinkle in both images. To measure melanin, we marked a representative area in the pretreatment image. Subsequently, the identical area was automatically marked in the follow-up image, and the concentration and distribution of melanin were calculated by the software. Wrinkle size was calculated as the average area of the wrinkle cross-sections multiplied by a constant, and the mean wrinkle depth as the average of the maximum depth within the cross-sections along the wrinkle. The mean wrinkle width was calculated as the average of the cross-section widths, and the average of melanin as the sum of the melanin values at each point within the selected area divided by the number of points. The absolute melanin variation was defined as the mean of the deviation of all melanin values from the melanin average. Clinical evaluation Clinical improvement was assessed by two experienced dermatologists, who were not involved in the study and who made their ratings independently of each other. Follow-up pictures taken 3 months after the third treatment session were compared with pretreatment pictures regarding the following aspects: mottled pigmentation, overall appearance, skin laxity, periocular and perioral wrinkles, and wrinkles on the cheeks and the forehead. Ratings were made on a five-point scale with the following response categories: 0, no improvement; 1, minor or mild improvement, 1–25%; 2, moderate improvement, 26–50%; 3, marked improvement, 51–75%; and 4, very significant improvement, 76–100%. Statistical analysis The sample size was calculated based on the primary outcome, reduction of wrinkle depth, as assessed using three-dimensional © 2013 British Association of Dermatologists
Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al. 861
in vivo optical skin imaging. We assumed that the treatment would result in a mean reduction of 30 lm with an SD of 50 lm. Furthermore, we assumed that the correlation between score 1 (before treatment) and score 2 (after treatment) was r = 050. Setting alpha error at 005 and beta error at 020 (power 80%), 24 patients were needed in order to detect the proposed mean reduction using the paired t-test. In order to compensate for four dropouts we decided to enrol 28 patients in this study. SAS 9.2 was used for sample size calculation (SAS Institute Inc., Cary, NC, U.S.A.). Statistical analyses commenced with descriptive statistics, using counts, ranges, percentages, and means and SDs or medians and interquartile ranges. Inter-rater agreement was assessed with Cohen’s weighted kappa (two raters, one ordinal scale, squared weights). Before and after differences were calculated with paired t-tests and Wilcoxon tests. P-values < 005 were considered significant. The software package SPSS for Windows, version 19.0, was used for all statistical analyses (IBM, Armonk, NY, U.S.A.).
Results Patient characteristics Patient recruitment took place between April and December 2011. In total 35 women were screened, and 28 met all inclusion criteria and none of the exclusion criteria. Two patients dropped out after the first treatment (one due to cardiac arrhythmia independent of laser therapy and the other because of professional reasons) and one patient did not appear for the follow-up visit. Thus, data analyses were based on 25 patients. The mean age was 574 89 years (range 41–75). The treating investigator assessed the Fitzpatrick wrinkle score before the first laser treatment (Table 2). Treatment results Profilometric analysis showed a significantly reduced wrinkle depth and size in all investigated areas (Table 3; Fig. 1). The best improvements regarding wrinkle depth, size and width were observed on the cheeks (Figs 2, 3). Periocular wrinkles Table 2 Patient characteristics: Fitzpatrick wrinkle score (n = 25) prior to first treatment in different facial areas Fitzpatrick wrinkle scorea Periorbital Forehead Cheeks Perioral a
62 58 53 63
14 16 20 17
Fitzpatrick wrinkle scores are based on grading of wrinkling into three classes: I, mild, 1–3; II, moderate, 4–6; III, severe, 7–9.
© 2013 British Association of Dermatologists
showed the second best results in terms of wrinkle size and depth. Wrinkles on the forehead showed slightly better results regarding size and depth than perioral wrinkles. All four facial areas showed significantly reduced average roughness (Table 3). Likewise, the best results were observed on the cheeks and the second best results in the periorbital area. Pigmentary irregularities were also seen to improve (Fig. 4). The distribution of melanin measured as melanin variation was significantly different after treatment (Table 4). The periocular and perioral areas and the cheeks had similar results. The melanin content (melanin average) was also slightly reduced, but the reduction on the cheeks was not statistically significant. Clinical evaluations were made by two investigators independently of each other. The inter-rater agreement was moderate (mottled pigmentation j = 070, overall appearance j = 064, skin laxity j = 051, periocular wrinkles j = 073, perioral wrinkles j = 063, wrinkles on the cheeks j = 074, wrinkles on the forehead j = 050). The average across the two assessments was used for further statistical analyses. Using a five-point scale, the clinical investigators considered the results for mottled pigmentation to be the best. The mean investigator ratings showed slightly improved (1–25%) periorbital, perioral and forehead rhytides (Table 5). Improvement of cheek rhytides, skin laxity and overall appearance was considered moderate (26–50%). Pain during treatment was assessed using a visual analogue scale (0 representing no pain, 10 worst possible pain). Patients reported a score of 57 for the first treatment, 61 for the second treatment and 62 for the third treatment, which may be labelled moderate pain. Patients were asked about side-effects at the second and third visits, as well as at the follow-up visit. All patients experienced crusting, swelling and erythema after each treatment, reporting the longest duration of crusting, swelling and erythema after the first treatment (Table 6). On average, crusting began 1 day and swelling 2 days after treatment. One patient experienced an episode of herpes labialis after aciclovir was discontinued 5 days after laser treatment. No further side-effects were observed.
Discussion The objective of this trial was the profilometric and clinical analysis of rhytides and photoaged facial skin after three treatments with a fractional CO2 laser. The profilometric skin analysis showed a significant reduction in wrinkle size and depth in all facial areas. The clinical investigators noted mildly improved perioral, periorbital and forehead rhytides and moderately improved rhytides on the cheeks. Karsai et al.9 reported a periorbital wrinkle reduction of 225% after one single treatment with the fractional CO2 laser, yet failed to mention the manner of selecting wrinkles for measurement. Depending on the treatment area, the homogeneity of melanin distribution in the skin was improved by 214–240%. In line with these results, the clinical investigators found a marked improvement British Journal of Dermatology (2014) 170, pp858–865
862 Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al. Table 3 Wrinkle parameters and skin roughness at baseline and 3 months after the last treatment, and mean percentage reduction at the 3-month follow-up visit
Parameter Periorbital (n = 21) Wrinkle size Wrinkle depth, mm Wrinkle width, mm Roughness, Sa Perioral (n = 24) Wrinkle size Wrinkle depth, mm Wrinkle width, mm Roughness, Sa Cheek (n = 7) Wrinkle size Wrinkle depth, mm Wrinkle width, mm Roughness, Sa Forehead (n = 23) Wrinkle size Wrinkle depth, mm Wrinkle width, mm
Before treatment
Three months after the last treatment
P-value
Mean reduction, %
344 010 149 190
161 004 012 83
223 007 144 147
90 003 003 46
< 0001 0001 0211 0001
351 313 34 223
407 012 153 225
160 004 012 91
313 010 144 203
121 003 016 173
< 0001 < 0001 0002 0004
232 198 59 96
339 010 16 200
163 004 02 61
141 005 13 148
102 003 06 26
0018 0018 0128 < 0001
583 513 188 166
224 127 007 004 145 023
< 0001 0001 0019
253 230 52
300 183 009 005 153 017
The sample sizes vary due to missing reference points and inconsistent matching of the images.
in mottled pigmentation. Skin laxity and overall appearance had improved moderately. Skin roughness was reduced by 96–258%. The average duration of crusting was 4–5 days, swelling 4 days and erythema 4–6 days. Our findings showed that improvement of wrinkle size and depth depends on the treatment area. Rhytides on the cheeks responded considerably better to therapy than those in other facial areas, which may be explained in several ways. Neocollagenesis could be more pronounced on the cheeks and therefore result in greater wrinkle reduction. Less mimic movement on the cheeks compared with the perioral and periocular areas may contribute to the particularly good improvement on the cheeks. Skin thickness should not play a major role, because the skin on the cheeks is not thinner than the skin in the periocular and perioral areas. The effects on neocollagenesis with rising penetration depth in the dermis
(a)
could be assumed to increase in thinner skin. Based on the histological analysis by Grunewald et al.,13 the energy settings used in our study created microscopic ablation zones that reached at least the papillary dermis. Contrary to our results, Tierney et al.1 reported the best clinical improvement on the lower eyelid and upper lip. Echographic analysis 3 months after ablative fractional resurfacing showed reduced solar elastosis and increased total skin thickness, particularly in these anatomic sites.1 In our study wrinkles on the cheeks were evaluated in only seven out of 25 patients. This is due primarily to the low number of wrinkles of our study participants in this area. Secondly, profilometric measurements on the cheeks were often not possible, as exact positioning of the camera for follow-up measurements was frequently not feasible due to absent reference points. For future studies, larger adhesive foils would be
(b)
Fig 1. Profilometry of the right periorbital area of a 47-year-old white woman, (a) before and (b) after ablative fractional resurfacing, showing improvement of periocular wrinkles. Decrease of 512% in wrinkle depth and 546% in wrinkle size 3 months after the treatment. Improvement in periorbital wrinkles was rated mild (1–25%) by both investigators. British Journal of Dermatology (2014) 170, pp858–865
© 2013 British Association of Dermatologists
Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al. 863
(a)
(b)
Fig 2. A 61-year-old white woman (a) before and (b) after three treatments with the fractional CO2 laser.
useful on the cheeks to mark the position of the ear or the eye in order to ensure exact positioning of the camera. However, the profilometric results of the cheeks are in accordance with the ratings of the clinical investigators. In all investigated areas, wrinkle size decreased more than wrinkle depth, and wrinkle width was considerably reduced on the cheeks only. The investigator evaluations concerning mottled pigmentation differed from the profilometric measurements. In contrast to the objective improvement in the homogeneity of melanin distribution of 214–240%, the subjective evaluation showed a marked improvement of 51–75%. Investigator ratings concerning wrinkles are mostly inferior to profilometric measurements. This finding is remarkable but not surprising, as Karsai et al.9 have reported a similar constellation. Notably, clinical investigators assessed the improvement of overall appearance superior to the average improvement of wrinkles. In addition, the investigators evaluated improvements in skin laxity as being better than those of periorbital, perioral and forehead rhytides. In comparison with the results of other clinical trials, the assessments of our investigators yielded altogether poorer results.1,7,14 The clinical results of Rahman et al.7 were considerably better, in particular for the improvement of rhytides. After one to two treatments with the fractional CO2 laser, the average investigator score for wrinkle improvement was 230. However, wrinkle depth was not measured and treatment parameters and number of treatments varied; therefore these results are unsuitable for comparison.
Many of our follow-up photographs showed an increase in the palpebral fissure height. However, evaluating the skin laxity of the eyelids was not an objective of this trial. In our opinion, this increased vertical height is due to reduced skin laxity of the eyelids. Such improvement of skin laxity and eyelid rhytides after ablative fractional resurfacing has been described before.15 The skin-tightening effects of ablative fractional resurfacing have recently been shown in an animal model. Although immediate post-treatment skin shrinkage was 115%, a 90% reduction was measured 4 months after the last treatment.16 Although the spot density increased by 24% in the second treatment and by 44% in the third treatment, the pain scores increased by only 7% and 8%, respectively. These results indicate that pain during treatment increases slightly with rising density and longer treatment duration and correlates with pulse energy. Duration of crusting decreased by 09 days, swelling by 04 days and erythema by 06 days from the first to the last treatment. This decrease is contradictory because we markedly increased density with every treatment. According to patient reports, erythema started 04 days later at the second treatment and 11 days later at the last treatment. Very few authors have described scarring after fractional CO2 laser treatment,17,18 and no complications except one episode of herpes occurred in our trial. The risk of hypo- and hyperpigmentation is low compared with conventional CO2 resurfacing.19–23 In this trial, we did not observe any post-treatment pigmentary changes.
© 2013 British Association of Dermatologists
Wrinkle size
Fig 3. Mean reduction of profilometrically measured wrinkle size on (a) the cheeks and (b) the periorbital area 3 months after the last treatment.
50
P = 0·018 n=7
40 30 20 10 0
–58·34%
Before treatment
3 months aer the last treatment
Wrinkle size
(b) 60
(a) 60
50
P < 0·001 n = 21
40 30 20 10 0
–35·0%
Before treatment
3 months aer the last treatment
British Journal of Dermatology (2014) 170, pp858–865
864 Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al.
(a)
(b)
Fig 4. A 75-year-old white woman (a) before and (b) after three treatments with the fractional CO2 laser. Table 4 Analysis of mottled pigmentation (melanin variation) and melanin average prior to the first treatment and 3 months after the last treatment, and percentage reduction
Parameter Periocular (n = 22) Melanin variation Melanin average Forehead (n = 25) Melanin variation Melanin average Cheek (n = 8) Melanin variation Melanin average
Before treatment
Three months after the last treatment
P-value
Percentage reduction
0046 0011 067 010
0035 0012 064 011
< 0001 0034
240 44
0042 0012 060 010
0032 0009 055 010
< 0001 0009
236 82
0038 0013 061 008
0030 0010 059 011
0012 0575
214 31
The sample sizes vary due to missing reference points and inconsistent matching of the images.
Table 5 Investigator evaluations 3 months after the last treatment as evaluated on a five-point scale (n = 25) Mean investigator ratinga Periorbital rhytides Perioral rhytides Forehead rhytides Cheek rhytides Mottled pigmentation Skin laxity Overall appearance
11 10 10 19 25 15 19
08 08 08 12 10 08 07
a
0, no improvement; 1, minor or mild improvement, 1–25%; 2, moderate improvement, 26–50%; 3, marked improvement, 51– 75%; 4, very significant improvement, 76–100%.
Considering the results of this study, fractional CO2 laser treatment may reduce wrinkles, particularly on the cheeks, and improve overall appearance and mottled pigmentation in ageing facial skin. This finding is relevant for adequately advising patients and for choosing the appropriate therapeutic and British Journal of Dermatology (2014) 170, pp858–865
Table 6 Side-effects of the treatment (n = 25)
Duration of post-treatment crusting Duration of post-treatment swelling Duration of post-treatment erythema Pain score during treatmenta
Treatment 1
Treatment 2
Treatment 3
50 days
38 days
41 days
42 days
36 days
38 days
60 days
44 days
54 days
57 22
61 20
62 21
a On a 10-point visual analogue scale, with 0 representing no pain and 10 the worst possible pain.
aesthetic procedures. However, our study has several limitations. Firstly, the study design was neither controlled nor randomized, and laser treatment was partly limited by the pain © 2013 British Association of Dermatologists
Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al. 865
that the patients experienced during treatment. Therefore, further increases in pulse energy were not invariably possible. As predefined in the study protocol, we did not use pain medication other than metamizol and ibuprofen before treatment. To avoid increased water absorption into the skin, we did not use any topical anaesthetic cream as used by other investigators.1,22,24 Intensified cold air cooling reduces pain but, in our experience, also reduces treatment efficacy; therefore we used low levels. However, the impact of topical anaesthetic creams and cold air cooling should be investigated in future trials. We used laser parameters as recommended by the manufacturer and increased energy and pulse durations according to the duration and severity of side-effects, degree of sun damage and elastosis, and individual pain tolerance. However, the most effective parameters are not yet clear. In conclusion, we investigated the efficacy of the fractional CO2 laser for reducing wrinkles and mottled pigmentation in facial skin. Profilometric analysis in 25 patients showed a significant reduction of wrinkle size and depth for all four investigated facial areas 3 months after the last treatment. This therapy also improved pigmentary irregularities that were evaluated clinically, as well as by means of measuring the homogeneity of melanin distribution. Based on these results we could show the efficacy of a series of three treatments with the fractional CO2 laser for treating pigmentary irregularities, lentigines and wrinkles. These objective results are relevant for practitioners of laser and aesthetic skin therapies for photoaged skin. Future work is needed to investigate optimal treatment parameters and intervals. For experienced practitioners, the fractional CO2 laser has an excellent benefit–risk profile, allows safe treatment and leads to reproducible results.
Acknowledgments We thank Ms Monika Schoell for the linguistic revision of our manuscript.
References 1 Tierney EP, Hanke CW, Petersen J et al. Clinical and echographic analysis of ablative fractionated carbon dioxide laser in the treatment of photodamaged facial skin. Dermatol Surg 2010; 36:2009– 21. 2 Ciocon DH, Engelman DE, Hussain M, Goldberg DJ. A split-face comparison of two ablative fractional carbon dioxide lasers for the treatment of photodamaged facial skin. Dermatol Surg 2011; 37:784–90. 3 Helbig D, Paasch U. Molecular changes during skin aging and wound healing after fractional ablative photothermolysis. Skin Res Technol 2011; 17:119–28. 4 Hunzeker CM, Weiss ET, Geronemus RG. Fractionated CO2 laser resurfacing: our experience with more than 2000 treatments. Aesthet Surg J 2009; 29:317–22.
© 2013 British Association of Dermatologists
5 Hantash BM, Bedi VP, Kapadia B et al. In vivo histological evaluation of a novel ablative fractional resurfacing device. Lasers Surg Med 2007; 39:96–107. 6 Tierney EP, Hanke CW. Ablative fractionated CO2, laser resurfacing for the neck: prospective study and review of the literature. J Drugs Dermatol 2009; 8:723–31. 7 Rahman Z, MacFalls H, Jiang K et al. Fractional deep dermal ablation induces tissue tightening. Lasers Surg Med 2009; 41:78–86. 8 Longo C, Galimberti M, De Pace B et al. Laser skin rejuvenation: epidermal changes and collagen remodeling evaluated by in vivo confocal microscopy. Lasers Med Sci 2013; 28:769–76. 9 Karsai S, Czarnecka A, J€ unger M, Raulin C. Ablative fractional lasers (CO2 and Er:YAG): a randomized controlled double-blind split-face trial of the treatment of peri-orbital rhytides. Lasers Surg Med 2010; 42:160–7. 10 Clementoni MT, Lavagno R, Catenacci M et al. 3D in vivo optical skin imaging for intense pulsed light and fractional ablative resurfacing of photodamaged skin. Facial Plast Surg Clin North Am 2011; 19:737–57. 11 Horn BK. Obtaining shape from shading information. In: The Psychology of Computer Vision (Winston PH, ed.). New York: McGrawHill, 1975; 115–55. 12 Anderson RR, Parrish JA. The optics of human skin. J Invest Dermatol 1981; 77:13–19. 13 Grunewald S, Bodendorf M, Illes M et al. In vivo wound healing and dermal matrix remodelling in response to fractional CO2 laser intervention: clinicopathological correlation in non-facial skin. Int J Hyperthermia 2011; 27:811–18. 14 Tierney EP, Hanke CW, Petersen J. Ablative fractionated CO2 laser treatment of photoaging: a clinical and histologic study. Dermatol Surg 2012; 38:1777–89. 15 Tierney EP, Hanke CW, Watkins L. Treatment of lower eyelid rhytids and laxity with ablative fractionated carbon-dioxide laser resurfacing: case series and review of the literature. J Am Acad Dermatol 2011; 64:730–40. 16 Park SH, Kim DW, Jeong T. Skin-tightening effect of fractional lasers: comparison of non-ablative and ablative fractional lasers in animal models. J Plast Reconstr Aesthet Surg 2012; 65:1305–11. 17 Fife DJ, Fitzpatrick RE, Zachary CB. Complications of fractional CO2 laser resurfacing: four cases. Lasers Surg Med 2009; 41:179–84. 18 Biesman BS. Fractional ablative skin resurfacing: complications. Lasers Surg Med 2009; 41:177–8. 19 Alster TS, West TB. Resurfacing of atrophic facial acne scars with a high-energy, pulsed carbon dioxide laser. Dermatol Surg 1996; 22:151–4, discussion 154–5. 20 Nanni CA, Alster TS. Complications of carbon dioxide laser resurfacing. An evaluation of 500 patients. Dermatol Surg 1998; 24:315– 20. 21 Hedelund L, Haak CS, Togsverd-Bo K et al. Fractional CO2 laser resurfacing for atrophic acne scars: a randomized controlled trial with blinded response evaluation. Lasers Surg Med 2012; 44:447–52. 22 Chapas AM, Brightman L, Sukal S et al. Successful treatment of acneiform scarring with CO2 ablative fractional resurfacing. Lasers Surg Med 2008; 40:381–6. 23 Alexiades-Armenakas MR, Dover JS, Arndt KA. Fractional laser skin resurfacing. J Drugs Dermatol 2012; 11:1274–87. 24 El-Domyati M, Abd-El-Raheem T, Abdel-Wahab H et al. Fractional versus ablative erbium:yttrium-aluminum-garnet laser resurfacing for facial rejuvenation: an objective evaluation. J Am Acad Dermatol 2013; 68:103–12.
British Journal of Dermatology (2014) 170, pp858–865
BJD
British Journal of Dermatology
Fractional carbon dioxide laser resurfacing of rhytides and photoageing: a prospective study using profilometric analysis €fer,1 M. Koller,2 F. Zeman,2 A. Klein,1 U. Hohenleutner,1 M. Landthaler1 and E. Kohl,1 J. Meierho 1 S. Hohenleutner 1
Department of Dermatology and 2Centre for Clinical Trials, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
Summary Correspondence Elisabeth Kohl. E-mail: [email protected]
Accepted for publication 19 December 2013
Funding sources The study was partially funded by Alma Lasers GmbH.
Conflicts of interest None declared. DOI 10.1111/bjd.12807
Background Results of profilometric skin analyses after fractional ablative skin resurfacing are not only important for evaluating the efficacy of this therapy but are also relevant for physicians practising laser and aesthetic skin therapy. Currently, objective measurements of wrinkle reduction after fractional CO2 laser resurfacing are scarce, and it remains unclear whether the various facial areas respond differently to this therapy. Objectives To measure wrinkle parameters, the homogeneity of melanin distribution and skin roughness in four facial areas (periorbital, perioral, forehead, cheeks) before and after three fractional CO2 laser treatments. Methods Twenty-five women were analysed with regard to wrinkle parameters and mottled pigmentation on the face. We measured wrinkle size, depth and width and the homogeneity of melanin distribution and skin roughness in four facial areas before and after three fractional CO2 laser treatments. Additionally, the investigators rated clinical improvement using five-point grading scales. Results Wrinkles were significantly reduced in all facial areas, and the best results for wrinkle size and depth were found for the cheeks ( 583%, P = 0018 and 513%, P = 0018) and the periorbital area ( 351%, P < 0001 and 311%, P = 0001, respectively). The percentage improvements of rhytides evaluated by the investigators were mostly similar to those found from in vivo measurements. The homogeneity of melanin distribution in the skin was improved by 214% on the cheeks (P = 0012) and by 240% in the periorbital area (P < 0001). Clinical investigators rated the improvement of mottled pigmentation considerably higher (51–75%). Conclusions After a serial treatment with the fractional CO2 laser, we measured considerably varying wrinkle reduction depending on the area of the face, and the best results were found for the cheeks.
What’s already known about this topic?
• • •
Fractional carbon dioxide laser resurfacing is widely used for skin rejuvenation. Several studies have demonstrated clinical improvement of wrinkles and photoaged skin. Objective data on wrinkle reduction are not available.
What does this study add?
•
858
We objectively measured wrinkle reduction and improvement of mottled skin after a series of three treatments with the fractional carbon dioxide laser in several areas of the face.
British Journal of Dermatology (2014) 170, pp858–865
© 2013 British Association of Dermatologists
Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al. 859
Several studies have evaluated the clinical and histological effects of fractional CO2 lasers and their efficacy with regard to improving photoaged skin.1–6 In 2007, Hantash et al.5 were the first to describe an ablative fractional CO2 laser that produces a pattern of so-called microscopic treatment zones. Each laser spot creates a column of ablated and coagulated tissue that is surrounded by healthy skin, thus enabling rapid wound healing. In a first clinical study published in 2009, Rahman et al.7 reported a marked improvement regarding rhytides, pigmentation, laxity and skin texture 3 months after one to two treatments. Longo et al.8 found intense collagen remodelling after fractional CO2 laser resurfacing, which was still detectable 3 months after the treatment. Despite these promising findings, no objective data on wrinkle parameters before and after full-face treatment are currently available.9 Therefore, we investigated the objective reduction in wrinkle depth and size, the differences in wrinkle reduction in distinct facial areas and the objective improvement in mottled pigmentation and skin roughness. Additionally, we assessed the correlation of subjective investigator assessments with in vivo measurements. This constitutes a profilometric and clinical analysis of photoaged skin and wrinkles in four defined facial areas after three treatments with a fractional CO2 laser.
Materials and methods Study design We present a prospective, monocentric and one-armed study including 28 patients, who were analysed before and after laser therapy with regard to treatment efficacy. The study was approved by the institutional review board and the ethics committee of the University of Regensburg. Written informed consent was obtained from each patient before enrolment. Inclusion and exclusion criteria The main inclusion criteria were oral and written informed patient consent, wish for treatment of wrinkles and photoaged skin with the fractional CO2 laser, white women, age ≥ 18 years and Glogau photodamage classification type II–IV. Exclusion criteria were unrealistic expectations, concomitant ultraviolet therapy, pregnancy, any cosmetic procedure or treatment of the face 6 months before study treatment (for example, botulinum toxin, dermabrasion, chemical peeling, laser therapy, facelift or filler), Fitzpatrick skin type IV–VI, any skin diseases in the face impairing the assessment of the efficacy of the study treatment, systemic treatment with photosensitizing drugs, systemic treatment with retinoids 3 months before study treatment and suspected lack of compliance. Study treatment Each patient received three full-face treatments in an interval of 1–6 months. Each visit was photodocumented in a standardized manner (frontal and at 675° for both sides) using a © 2013 British Association of Dermatologists
FotoFinder mediscope (FotoFinder Systems GmbH, Bad Birnbach, Germany). Before laser treatment and at the follow-up visit 3 months after the last treatment, we performed in vivo measurements of skin topography and the distribution of melanin using an Antera 3DTM skin imaging device (Miravex, Dublin, Ireland). To ensure comparability, patients cleaned their face with Menalindâ washing lotion (Paul Hartmann AG, Heidenheim, Germany) directly before photodocumentation and in vivo measurements. All patients had their measurement areas marked on several adhesive transparent foils (OpSite Flexigrid; Smith and Nephew, Hamburg, Germany) to ensure that the in vivo measurements were conducted in identical areas (forehead, cheeks and perioral and periorbital areas) at the followup visit. Aciclovir (2 9 400 mg) was given as a prophylactic herpes treatment from 2 days before to 5–7 days after treatment. Study participants received 1 g metamizol orally for pain management 30 min before, and 800 mg ibuprofen 2 h before the start of treatment, but no topical anaesthetic cream. The eyes were protected with a moist gauze and laser protection glasses. All fractional CO2 laser treatments included the entire face and were conducted by the same clinician. Only the upper part of the eyelids was treated, but the area in direct proximity to the lashes remained untreated. Immediately after the treatment, the patients cooled the face with cold, wet compresses. During the entire treatment, cool air was used as an anaesthetic. Patients used Cicalfate restorative cream (Pierre Fabre Dermo-Kosmetik GmbH, Freiburg, Germany) several times a day for 7 days. Technical data We used a fractional CO2 laser (EXELO2; Alma Lasers GmbH, N€ urnberg, Germany; 106 lm, microbeam spot size 250 lm) with adjustable parameters for density of microspots, pulse width and energy. We chose a round treatment area (diameter 1 cm) and used the Soft Random Mode, in which laser spots were randomly placed in the treatment areas and their borders were gently faded out. Therefore, no geometric patterns were visible on the skin after treatment. We used a spot density of 25 or 50 spots cm 2 and conducted several passes to achieve a homogeneous distribution of microspots. For instance, to achieve a spot density of 200 spots cm 2 we used four passes at a spot density of 50 spots cm 2. The mean treatment parameters are displayed in Table 1. Pulse duration and pulse energy were slightly altered for each treatment. In the first treatment, a mean 236 microspots cm 2 were applied; as the patients responded well to the treatment, the number of microspots was increased by 24% in the second treatment and by 44% in the third treatment (Table 1) to increase skin surface ablation. The treatments resulted in skin surface ablation of 116%, 143% and 167%, respectively. In every treatment session, we slightly reduced the pulse energy and the number of microspots cm 2 in the periocular area and on the nose. For epidermal protection during treatment, we used an air cooling device directly attached to the laser scanner (Zimmer British Journal of Dermatology (2014) 170, pp858–865
860 Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al.
Treatment 1 Pulse duration, ms Pulse energy, mJ Microspots per cm2 Microspots per face
25 384 236 64 488
04 50 62 22 516
Treatment 2 25 380 292 79 724
03 41 64 20 391
Cryo 6; Zimmer MedizinSysteme GmbH, Neu-Ulm, Germany). On average, we used airflow settings of 14 07 during the first treatment, 13 04 during the second treatment and 13 05 during the last treatment. Skin topography and distribution of melanin were measured in vivo with the Antera 3D imaging system (Miravex) consisting of a handheld imaging device and a connected laptop with preinstalled proprietary software.10 The imaging technique of the Antera 3D allows three-dimensional imaging of partially diffusive and diffusive surfaces. It is based on multidirectional illumination and computer-aided reconstruction of the surface, utilizing the differences between images acquired from the surface as a result of illuminations from different angles. The skin topography and the concentration of chromophores are derived from the spatial and spectral analysis of the acquired image data. Skin texture reconstruction is achieved using a technique based on shape from shading,11 substantially modified in order to eliminate skin glare and improve the accuracy of measured data (Patent Cooperation Treaty application PCT/EP2010/001168, Irish Patent No. S85695). The texture reconstructed in this way is then used for quantitative skin analysis of factors such as depth and width of wrinkles, skin lesions and overall skin roughness. Several lightemitting diodes at seven different wavelengths illuminate the skin from different directions. Three-dimensional images of the back-reflected light are generated and processed to map the distribution and concentration of melanin and haemoglobin. Unlike traditional imaging techniques, where only three colour channels (red, green and blue) are used, the Antera 3D uses reflectance mapping of seven different light wavelengths spanning the entire visible spectrum. This allows for a more precise analysis of the skin’s colorimetric properties, which are determined mostly by two dominant chromophores: melanin and haemoglobin. Acquired spectral images are transformed into skin spectral reflectance maps, and the skin surface shape is used to compensate for light intensity variation due to the varying direction of incident illumination. The reflectance data are transformed into skin absorption coefficients and used to quantify melanin and haemoglobin concentrations using mathematical correlation with known spectral absorption data of these chromophores.12 The acquired images can be visualized in both two and three dimensions in different modes to display the natural skin colour, skin texture, melanin and haemoglobin. To measure differences in skin topography, melanin and haemoglobin in specific areas, examiners had to produce identical images of British Journal of Dermatology (2014) 170, pp858–865
Treatment 3 25 386 340 93 040
03 51 48 13 296
Table 1 Mean SD values for treatment parameters (n = 25) of the first, second and third treatments
the respective facial areas, because the software could only partially compensate shifts and rotations of the images. In vivo skin measurements We measured the periorbital and perioral areas, the forehead and the cheeks of each patient in vivo before and after each treatment. The follow-up evaluation was 3 months after the third treatment session. Because of the lack of reference points, measurements and analysis were not possible in some cases for technical reasons. For analysis, we selected the deepest wrinkle in the pretreatment image and marked the wrinkle in both images. To measure melanin, we marked a representative area in the pretreatment image. Subsequently, the identical area was automatically marked in the follow-up image, and the concentration and distribution of melanin were calculated by the software. Wrinkle size was calculated as the average area of the wrinkle cross-sections multiplied by a constant, and the mean wrinkle depth as the average of the maximum depth within the cross-sections along the wrinkle. The mean wrinkle width was calculated as the average of the cross-section widths, and the average of melanin as the sum of the melanin values at each point within the selected area divided by the number of points. The absolute melanin variation was defined as the mean of the deviation of all melanin values from the melanin average. Clinical evaluation Clinical improvement was assessed by two experienced dermatologists, who were not involved in the study and who made their ratings independently of each other. Follow-up pictures taken 3 months after the third treatment session were compared with pretreatment pictures regarding the following aspects: mottled pigmentation, overall appearance, skin laxity, periocular and perioral wrinkles, and wrinkles on the cheeks and the forehead. Ratings were made on a five-point scale with the following response categories: 0, no improvement; 1, minor or mild improvement, 1–25%; 2, moderate improvement, 26–50%; 3, marked improvement, 51–75%; and 4, very significant improvement, 76–100%. Statistical analysis The sample size was calculated based on the primary outcome, reduction of wrinkle depth, as assessed using three-dimensional © 2013 British Association of Dermatologists
Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al. 861
in vivo optical skin imaging. We assumed that the treatment would result in a mean reduction of 30 lm with an SD of 50 lm. Furthermore, we assumed that the correlation between score 1 (before treatment) and score 2 (after treatment) was r = 050. Setting alpha error at 005 and beta error at 020 (power 80%), 24 patients were needed in order to detect the proposed mean reduction using the paired t-test. In order to compensate for four dropouts we decided to enrol 28 patients in this study. SAS 9.2 was used for sample size calculation (SAS Institute Inc., Cary, NC, U.S.A.). Statistical analyses commenced with descriptive statistics, using counts, ranges, percentages, and means and SDs or medians and interquartile ranges. Inter-rater agreement was assessed with Cohen’s weighted kappa (two raters, one ordinal scale, squared weights). Before and after differences were calculated with paired t-tests and Wilcoxon tests. P-values < 005 were considered significant. The software package SPSS for Windows, version 19.0, was used for all statistical analyses (IBM, Armonk, NY, U.S.A.).
Results Patient characteristics Patient recruitment took place between April and December 2011. In total 35 women were screened, and 28 met all inclusion criteria and none of the exclusion criteria. Two patients dropped out after the first treatment (one due to cardiac arrhythmia independent of laser therapy and the other because of professional reasons) and one patient did not appear for the follow-up visit. Thus, data analyses were based on 25 patients. The mean age was 574 89 years (range 41–75). The treating investigator assessed the Fitzpatrick wrinkle score before the first laser treatment (Table 2). Treatment results Profilometric analysis showed a significantly reduced wrinkle depth and size in all investigated areas (Table 3; Fig. 1). The best improvements regarding wrinkle depth, size and width were observed on the cheeks (Figs 2, 3). Periocular wrinkles Table 2 Patient characteristics: Fitzpatrick wrinkle score (n = 25) prior to first treatment in different facial areas Fitzpatrick wrinkle scorea Periorbital Forehead Cheeks Perioral a
62 58 53 63
14 16 20 17
Fitzpatrick wrinkle scores are based on grading of wrinkling into three classes: I, mild, 1–3; II, moderate, 4–6; III, severe, 7–9.
© 2013 British Association of Dermatologists
showed the second best results in terms of wrinkle size and depth. Wrinkles on the forehead showed slightly better results regarding size and depth than perioral wrinkles. All four facial areas showed significantly reduced average roughness (Table 3). Likewise, the best results were observed on the cheeks and the second best results in the periorbital area. Pigmentary irregularities were also seen to improve (Fig. 4). The distribution of melanin measured as melanin variation was significantly different after treatment (Table 4). The periocular and perioral areas and the cheeks had similar results. The melanin content (melanin average) was also slightly reduced, but the reduction on the cheeks was not statistically significant. Clinical evaluations were made by two investigators independently of each other. The inter-rater agreement was moderate (mottled pigmentation j = 070, overall appearance j = 064, skin laxity j = 051, periocular wrinkles j = 073, perioral wrinkles j = 063, wrinkles on the cheeks j = 074, wrinkles on the forehead j = 050). The average across the two assessments was used for further statistical analyses. Using a five-point scale, the clinical investigators considered the results for mottled pigmentation to be the best. The mean investigator ratings showed slightly improved (1–25%) periorbital, perioral and forehead rhytides (Table 5). Improvement of cheek rhytides, skin laxity and overall appearance was considered moderate (26–50%). Pain during treatment was assessed using a visual analogue scale (0 representing no pain, 10 worst possible pain). Patients reported a score of 57 for the first treatment, 61 for the second treatment and 62 for the third treatment, which may be labelled moderate pain. Patients were asked about side-effects at the second and third visits, as well as at the follow-up visit. All patients experienced crusting, swelling and erythema after each treatment, reporting the longest duration of crusting, swelling and erythema after the first treatment (Table 6). On average, crusting began 1 day and swelling 2 days after treatment. One patient experienced an episode of herpes labialis after aciclovir was discontinued 5 days after laser treatment. No further side-effects were observed.
Discussion The objective of this trial was the profilometric and clinical analysis of rhytides and photoaged facial skin after three treatments with a fractional CO2 laser. The profilometric skin analysis showed a significant reduction in wrinkle size and depth in all facial areas. The clinical investigators noted mildly improved perioral, periorbital and forehead rhytides and moderately improved rhytides on the cheeks. Karsai et al.9 reported a periorbital wrinkle reduction of 225% after one single treatment with the fractional CO2 laser, yet failed to mention the manner of selecting wrinkles for measurement. Depending on the treatment area, the homogeneity of melanin distribution in the skin was improved by 214–240%. In line with these results, the clinical investigators found a marked improvement British Journal of Dermatology (2014) 170, pp858–865
862 Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al. Table 3 Wrinkle parameters and skin roughness at baseline and 3 months after the last treatment, and mean percentage reduction at the 3-month follow-up visit
Parameter Periorbital (n = 21) Wrinkle size Wrinkle depth, mm Wrinkle width, mm Roughness, Sa Perioral (n = 24) Wrinkle size Wrinkle depth, mm Wrinkle width, mm Roughness, Sa Cheek (n = 7) Wrinkle size Wrinkle depth, mm Wrinkle width, mm Roughness, Sa Forehead (n = 23) Wrinkle size Wrinkle depth, mm Wrinkle width, mm
Before treatment
Three months after the last treatment
P-value
Mean reduction, %
344 010 149 190
161 004 012 83
223 007 144 147
90 003 003 46
< 0001 0001 0211 0001
351 313 34 223
407 012 153 225
160 004 012 91
313 010 144 203
121 003 016 173
< 0001 < 0001 0002 0004
232 198 59 96
339 010 16 200
163 004 02 61
141 005 13 148
102 003 06 26
0018 0018 0128 < 0001
583 513 188 166
224 127 007 004 145 023
< 0001 0001 0019
253 230 52
300 183 009 005 153 017
The sample sizes vary due to missing reference points and inconsistent matching of the images.
in mottled pigmentation. Skin laxity and overall appearance had improved moderately. Skin roughness was reduced by 96–258%. The average duration of crusting was 4–5 days, swelling 4 days and erythema 4–6 days. Our findings showed that improvement of wrinkle size and depth depends on the treatment area. Rhytides on the cheeks responded considerably better to therapy than those in other facial areas, which may be explained in several ways. Neocollagenesis could be more pronounced on the cheeks and therefore result in greater wrinkle reduction. Less mimic movement on the cheeks compared with the perioral and periocular areas may contribute to the particularly good improvement on the cheeks. Skin thickness should not play a major role, because the skin on the cheeks is not thinner than the skin in the periocular and perioral areas. The effects on neocollagenesis with rising penetration depth in the dermis
(a)
could be assumed to increase in thinner skin. Based on the histological analysis by Grunewald et al.,13 the energy settings used in our study created microscopic ablation zones that reached at least the papillary dermis. Contrary to our results, Tierney et al.1 reported the best clinical improvement on the lower eyelid and upper lip. Echographic analysis 3 months after ablative fractional resurfacing showed reduced solar elastosis and increased total skin thickness, particularly in these anatomic sites.1 In our study wrinkles on the cheeks were evaluated in only seven out of 25 patients. This is due primarily to the low number of wrinkles of our study participants in this area. Secondly, profilometric measurements on the cheeks were often not possible, as exact positioning of the camera for follow-up measurements was frequently not feasible due to absent reference points. For future studies, larger adhesive foils would be
(b)
Fig 1. Profilometry of the right periorbital area of a 47-year-old white woman, (a) before and (b) after ablative fractional resurfacing, showing improvement of periocular wrinkles. Decrease of 512% in wrinkle depth and 546% in wrinkle size 3 months after the treatment. Improvement in periorbital wrinkles was rated mild (1–25%) by both investigators. British Journal of Dermatology (2014) 170, pp858–865
© 2013 British Association of Dermatologists
Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al. 863
(a)
(b)
Fig 2. A 61-year-old white woman (a) before and (b) after three treatments with the fractional CO2 laser.
useful on the cheeks to mark the position of the ear or the eye in order to ensure exact positioning of the camera. However, the profilometric results of the cheeks are in accordance with the ratings of the clinical investigators. In all investigated areas, wrinkle size decreased more than wrinkle depth, and wrinkle width was considerably reduced on the cheeks only. The investigator evaluations concerning mottled pigmentation differed from the profilometric measurements. In contrast to the objective improvement in the homogeneity of melanin distribution of 214–240%, the subjective evaluation showed a marked improvement of 51–75%. Investigator ratings concerning wrinkles are mostly inferior to profilometric measurements. This finding is remarkable but not surprising, as Karsai et al.9 have reported a similar constellation. Notably, clinical investigators assessed the improvement of overall appearance superior to the average improvement of wrinkles. In addition, the investigators evaluated improvements in skin laxity as being better than those of periorbital, perioral and forehead rhytides. In comparison with the results of other clinical trials, the assessments of our investigators yielded altogether poorer results.1,7,14 The clinical results of Rahman et al.7 were considerably better, in particular for the improvement of rhytides. After one to two treatments with the fractional CO2 laser, the average investigator score for wrinkle improvement was 230. However, wrinkle depth was not measured and treatment parameters and number of treatments varied; therefore these results are unsuitable for comparison.
Many of our follow-up photographs showed an increase in the palpebral fissure height. However, evaluating the skin laxity of the eyelids was not an objective of this trial. In our opinion, this increased vertical height is due to reduced skin laxity of the eyelids. Such improvement of skin laxity and eyelid rhytides after ablative fractional resurfacing has been described before.15 The skin-tightening effects of ablative fractional resurfacing have recently been shown in an animal model. Although immediate post-treatment skin shrinkage was 115%, a 90% reduction was measured 4 months after the last treatment.16 Although the spot density increased by 24% in the second treatment and by 44% in the third treatment, the pain scores increased by only 7% and 8%, respectively. These results indicate that pain during treatment increases slightly with rising density and longer treatment duration and correlates with pulse energy. Duration of crusting decreased by 09 days, swelling by 04 days and erythema by 06 days from the first to the last treatment. This decrease is contradictory because we markedly increased density with every treatment. According to patient reports, erythema started 04 days later at the second treatment and 11 days later at the last treatment. Very few authors have described scarring after fractional CO2 laser treatment,17,18 and no complications except one episode of herpes occurred in our trial. The risk of hypo- and hyperpigmentation is low compared with conventional CO2 resurfacing.19–23 In this trial, we did not observe any post-treatment pigmentary changes.
© 2013 British Association of Dermatologists
Wrinkle size
Fig 3. Mean reduction of profilometrically measured wrinkle size on (a) the cheeks and (b) the periorbital area 3 months after the last treatment.
50
P = 0·018 n=7
40 30 20 10 0
–58·34%
Before treatment
3 months aer the last treatment
Wrinkle size
(b) 60
(a) 60
50
P < 0·001 n = 21
40 30 20 10 0
–35·0%
Before treatment
3 months aer the last treatment
British Journal of Dermatology (2014) 170, pp858–865
864 Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al.
(a)
(b)
Fig 4. A 75-year-old white woman (a) before and (b) after three treatments with the fractional CO2 laser. Table 4 Analysis of mottled pigmentation (melanin variation) and melanin average prior to the first treatment and 3 months after the last treatment, and percentage reduction
Parameter Periocular (n = 22) Melanin variation Melanin average Forehead (n = 25) Melanin variation Melanin average Cheek (n = 8) Melanin variation Melanin average
Before treatment
Three months after the last treatment
P-value
Percentage reduction
0046 0011 067 010
0035 0012 064 011
< 0001 0034
240 44
0042 0012 060 010
0032 0009 055 010
< 0001 0009
236 82
0038 0013 061 008
0030 0010 059 011
0012 0575
214 31
The sample sizes vary due to missing reference points and inconsistent matching of the images.
Table 5 Investigator evaluations 3 months after the last treatment as evaluated on a five-point scale (n = 25) Mean investigator ratinga Periorbital rhytides Perioral rhytides Forehead rhytides Cheek rhytides Mottled pigmentation Skin laxity Overall appearance
11 10 10 19 25 15 19
08 08 08 12 10 08 07
a
0, no improvement; 1, minor or mild improvement, 1–25%; 2, moderate improvement, 26–50%; 3, marked improvement, 51– 75%; 4, very significant improvement, 76–100%.
Considering the results of this study, fractional CO2 laser treatment may reduce wrinkles, particularly on the cheeks, and improve overall appearance and mottled pigmentation in ageing facial skin. This finding is relevant for adequately advising patients and for choosing the appropriate therapeutic and British Journal of Dermatology (2014) 170, pp858–865
Table 6 Side-effects of the treatment (n = 25)
Duration of post-treatment crusting Duration of post-treatment swelling Duration of post-treatment erythema Pain score during treatmenta
Treatment 1
Treatment 2
Treatment 3
50 days
38 days
41 days
42 days
36 days
38 days
60 days
44 days
54 days
57 22
61 20
62 21
a On a 10-point visual analogue scale, with 0 representing no pain and 10 the worst possible pain.
aesthetic procedures. However, our study has several limitations. Firstly, the study design was neither controlled nor randomized, and laser treatment was partly limited by the pain © 2013 British Association of Dermatologists
Profilometry of rhytides after fractional ablative resurfacing, E. Kohl et al. 865
that the patients experienced during treatment. Therefore, further increases in pulse energy were not invariably possible. As predefined in the study protocol, we did not use pain medication other than metamizol and ibuprofen before treatment. To avoid increased water absorption into the skin, we did not use any topical anaesthetic cream as used by other investigators.1,22,24 Intensified cold air cooling reduces pain but, in our experience, also reduces treatment efficacy; therefore we used low levels. However, the impact of topical anaesthetic creams and cold air cooling should be investigated in future trials. We used laser parameters as recommended by the manufacturer and increased energy and pulse durations according to the duration and severity of side-effects, degree of sun damage and elastosis, and individual pain tolerance. However, the most effective parameters are not yet clear. In conclusion, we investigated the efficacy of the fractional CO2 laser for reducing wrinkles and mottled pigmentation in facial skin. Profilometric analysis in 25 patients showed a significant reduction of wrinkle size and depth for all four investigated facial areas 3 months after the last treatment. This therapy also improved pigmentary irregularities that were evaluated clinically, as well as by means of measuring the homogeneity of melanin distribution. Based on these results we could show the efficacy of a series of three treatments with the fractional CO2 laser for treating pigmentary irregularities, lentigines and wrinkles. These objective results are relevant for practitioners of laser and aesthetic skin therapies for photoaged skin. Future work is needed to investigate optimal treatment parameters and intervals. For experienced practitioners, the fractional CO2 laser has an excellent benefit–risk profile, allows safe treatment and leads to reproducible results.
Acknowledgments We thank Ms Monika Schoell for the linguistic revision of our manuscript.
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British Journal of Dermatology (2014) 170, pp858–865
