Comparison Study of Fractional Carbon Dioxide Laser
Resurfacing Using Different Fluences and Densities for Acne
Scars in Asians: A Randomized Split-Face Trial XING-HUA YUAN, MD,*
SHU-XIA ZHONG, MD,* AND SHAN-SHAN LI, MD, PHD*
BACKGROUND Ablative 10,600-nm carbon dioxide (CO 2 ) fractional laser treatments have shown favorable outcomes for atrophic acne scars. OBJECTIVE To compare the efcacy and complications of fractional CO 2 laser treatments with different uences and densities for acne scars. METHODS Twenty patients were treated using a single session of fractional CO 2 laser in Deep FX mode. In Group A (n = 10), half of the face was treated with 20 mJ, density 10% and the other half with 20 mJ, density 20%. In Group B (n = 10), half of the face was treated with 10 mJ, density 10% and the other half with 20 mJ, density 10%. Patients were evaluated at baseline and 3 days, 1 week, 1 month, and 3 months after the procedure. RESULTS There was no signicant difference in efcacy between different laser settings within the groups, although adverse effects were more evident in patients treated with higher densities or uences. CONCLUSION Factional CO 2 laser treatment using the Deep FX mode may provide a signicant efcacy with lower uence and density with fewer complications than with higher energies for acne scars. The authors have indicated no signicant interest with commercial supporters. A trophic scars are dermal depressions com- monly caused by the destruction of collagen after inammatory acne. Conventional ablative laser therapy with carbon dioxide (CO 2 ) or erbium-doped yttrium aluminum garnet laser is the criterion standard for treatment of atrophic scars, 1,2 although its usage is frequently limited in Asian patients because of the lengthy recovery time and high risk of adverse effects, including infection, edema, and postinammatory hyperpigmentation (PIH). 2,3 To address these limitations, newer modalities employ- ing the principle of fractional photothermolysis (FP) have been developed. 4,5 These laser treatments create microscopic treatment zones (MTZs) sur- rounded by undamaged tissues and hence result in shorter recovery time and fewer adverse effects than traditional ablative laser resurfacing. Recent studies have shown favorable outcomes for atrophic acne scars with an ablative 10,600-nm CO 2 fractional laser system (CO 2 FS). 6,7 A CO 2 FS with two treatment modes (Active FX and Deep FX) is one of the more popular fractional CO 2 lasers available today, combining supercial and deep fractional CO 2 laser treatments. Cho and colleagues 8 used this laser to treat atrophic acne scars in 20 Korean patients. The treatment combined the Deep FX mode, which focused on the scars only, whereas the Active FX mode was used over the entire face. After one session, 50% of patients achieved marked improvement (>50%). The Deep FX mode with a smaller (120 lm) spot size has the potential to extend treatment from the epidermis to as deep as 3 *Department of Dermatology and Venereology, First Hospital of Jilin University, Changchun, China;
Department of Dermatology and Venereology, Yanbian University Hospital, Yanji, China 2014 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: 1076-0512 Dermatol Surg 2014;40:545552 DOI: 10.1111/dsu.12467 545 4 mm into the reticular dermis, but data on the efcacy and adverse effects of this novel resurfacing technique in dark-skinned patients are limited. In this study, we compared the efcacy and com- plications of fractional CO 2 laser treatment with the Deep FX mode using different uences and densities for acne scars in Asian patients in a randomized, split-face, evaluator-blinded study. Methods Patients This study followed the principles of the 1975 Declaration of Helsinki. Twenty Chinese subjects, 10 female and 10 male, aged 2231, with Fitzpatrick skin types IIIIV and moderate to severe atrophic acne scars were enrolled. Informed consent was obtained from each patient. Patients with a history of keloid scarring, isotretinoin use, pregnancy, lactation, immunosuppression, history of ller injection within the past year, or ablative or nonablative laser resurfacing within 1 year of study initiation were excluded from the study. Laser Treatment Patients were treated with a single session of the Deep FX microscanner handpiece of the fractional ultrapulse CO 2 laser (Ultrapulse Encore; Lumenis Inc., Santa Clara, CA). The treatment areas were cleansed with a mild cleanser and 70% alcohol. Local anesthesia, comprising a topical eutectic mixture of 2.5% lidocaine hydrochloric acid and 2.5% prilocaine cream (Compound Lidocaine Cream; Ziguang, Beijing, China), was applied to the entire face under occlusion before laser therapy. After an hour of application, the anesthetic cream was gently removed, and then, to obtain a com- pletely dry skin surface, alcohol was used to degrease the skin. Twenty patients were randomly divided into two groups. In Group A (n = 10), half of the face was treated with 20 mJ, density 10% and the other half with 20 mJ, density 20%. In Group B (n = 10), half of the face was treated with 10 mJ, density 10% and the other half with 20 mJ, density 10%. Facial treatment halves were also randomized. A single operator then administered a full-face, single-pass treatment without overlapping pulse. Immediately after each procedure, a thin layer of uticasone propionate cream (Ketinv; Glaxo Oper- ations UK Limited, Durham, UK) and a recombinant human epidermal growth factor hydrogel (Yifu; Huanuowei, Guilin, China) was applied to prevent an inammatory reaction and reduce facial dryness. Ice packing (4C) was applied to the treated surface for 30 minutes or more until the pain or burning sensation decreased. Subjects were instructed to clean the treated sites gently with a mild cleanser 24 hours after the treatment. The uticasone pro- pionate cream was applied twice daily for the rst 3 days and the recombinant human epidermal growth factor hydrogel 4 times daily for 1 week. After complete decrustation, all patients were instructed to wear a broad-spectrum sunscreen with a sun protection factor of 30 and to avoid sun exposure. Objective and Subjective Evaluations Photographs were taken using identical camera settings, lighting, and patient positioning at baseline and 3 days, 1 week, 1 month, and 3 months after treatment. Two blinded dermatologists compared before and after photographs in nonchronological order and provided objective clinical assessments of the acne scars. Acne scars were graded using the echelle devaluation clinique des cicatrices dacne grading scale at baseline and 1 and 3 months after the treatment. 9 The degree of improvement was further assessed on a 4-point scale (0, no improve- ment; 1, 025% [minimal improvement]; 2, 2650% [moderate] improvement; 3, 5175% [marked] improvement; 4, >75% [near total] improvement). Subjects also performed a self-assessment of their results (range 010) 1 and 3 months after the treatment. COMPARI SON STUDY OF CO 2 AFR DERMATOLOGI C SURGERY 546 Immediately after each procedure, subjects were asked to rate the pain associated with the treatment using a 10-point pain scale (0 = no pain to 10 = severe pain). The investigators evaluated the presence of bleeding, oozing, and edema during the treatment was on a 3-point scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Erythema was also assessed on a 3-point scale at the 3-day follow- up. Recovery times and other potential adverse effects, including hyper- and hypopigmentation, crusting, scarring, infection, and acneiform eruption, were recorded at each follow-up visit. Statistical Analysis We compared clinical assessment scores of acne scars using the nonparametric Wilcoxon signed rank test with SPSS version 17.0 (SPSS, Inc., Chicago, IL). Overall patient satisfaction levels and the grading scores of adverse effects associated with the treat- ments were analyzed using the Student t-test (paired samples), while the data which did not follow a normal distribution was analyzed using a nonparametric test. Differences were considered statistically signicant at p < .05. Results Follow-up results 3 months after a single laser treatment with the same uence and different densities (Group A) indicated that three of 10 patients treated using the lower density showed marked improvement (5175%), ve showed mod- erate improvement (2650%), and two showed minimal improvement (<25%). Five of 10 patients treated using the higher density showed marked improvement (5175%), three showed moderate improvement of (2650%), and two showed min- imal improvement (<25%) (Table 1). Three months after the laser procedure with the same density and different uences (Group B), two of 10 patients treated using the lower uence showed marked improvement (5175%) (Figure 1AB), six showed moderate improvement (2650%), and two showed minimal improvement (<25%). Four patients trea- ted using the higher uence showed marked improvement (5175%) (Figure 1CD), four showed moderate improvement of (2650%), and two showed minimal improvement (<25%) (Table 1). Overall patient satisfaction levels at the 3-month follow-up are shown in Tables 2 and 3. There was no statistically signicant difference between different densities (Group A) or uences (Group B) in clinical efcacy or patient satisfaction (p > .05). It was also observed that scar improvements and patient satisfaction were signicantly higher at the 3-month follow-up than at 1 month (p < .05). The results of adverse effects are shown in Tables 2 and 3. Pain, bleeding, oozing, edema, crusting, erythema, and PIH were found to be more evident or persisted for longer periods of time in patients treated with higher densities (Group A, p < .05) or higher uences (Group B, p < .05). Both sides of the faces in all 20 subjects showed PIH that resolved within 3 months except for a patient treated with the higher- density setting in Group A. There was no intervention for the PIHother than daily sunscreen use. Acneiform eruption (10%, n = 1), cutaneous pruritus (30%, n = 3), and skin dryness (60%, n = 6) were observed in patients in Group A. Four patients in Group B experienced cutaneous pruritus, and ve experienced skin dryness. All subjects with skin dryness were successfully treated within 2 weeks using a moistur- TABLE 1. Clinical Comparison of Different Energies in Group A and Group B Cases Improvement Grade Group A Improvement Grade Group B Density 10% Density 20% 10 mJ 20 mJ 1 1 1 2 2 2 2 3 2 3 3 2 2 1 1 4 2 2 2 3 5 3 3 3 3 6 3 3 2 2 7 2 3 2 2 8 1 1 1 1 9 2 2 2 2 10 3 3 3 3 YUAN ET AL 40: 5: MAY 2014 547 izing cream (Lauzome; Canada Highview & Ever- bright Medical Technology Co., Ltd., Changchun, China) three times daily. Acneiform eruptions in one subject were successfullytreatedwithin2 weeks using clindamycin phosphate gel and adapalene gel applied day and night, respectively. Some subjects also expe- riencedcutaneous pruritus inirradiationareas 25 days after treatment. The sensation was sustainable and automatically resolved within 1 week. Severe complications such as hypopigmentation, scarring, and infection were not observed in any of the 20 subjects. Discussion Ablative fractional resurfacing (AFR) with 10,600- nm CO 2 lasers uses fractionated laser beams to produce an array of microscopic columns of con- trolled deep dermal tissue volumetric ablation and vaporization surrounded by thermally induced TABLE 2. Overall Comparative Data Between Different Densities in Group A Density 10% Density 20% p-Value Pain, mean SD (range 010) 4.36 1.10 6.12 1.24 <.001 Edema, days, mean SD 3.10 0.57 4.50 0.53 .004 Crusting, days, mean SD 4.80 0.79 6.60 0.52 .003 Postinammatory hyperpigmentation duration, days, mean SD 50.50 8.64 62.50 11.06 .005 Infection, n 0/10 0/10 Scarring, n 0/10 0/10 Acneiform eruption, n 1/10 1/10 Cutaneous pruritus, n 3/10 3/10 Skin dryness, n 6/10 6/10 Hypopigmentation, n 0/10 0/10 Patient satisfaction, mean SD (range 010) 5.90 1.37 5.95 1.40 .85 SD, standard deviation. (A) (B) (C) (D) Figure 1. Twenty-seven-year-old male patient before (A) and 3 months after (B) treatment with 10 mJ, density 10% and before (C) and 3 months after (D) treatment with 20 mJ, density 10%. COMPARI SON STUDY OF CO 2 AFR DERMATOLOGI C SURGERY 548 annular coagulation zones of denatured collagen with interspersed regions of untreated tissue. 7,10 An ex vivo histologic study demonstrated that the depth of ablation in AFR depends on the pulse energy used, with higher energies resulting in greater penetration depth. 10 In turn, the depth of ablation and coagulation correlated directly with treatment efcacy in laser resurfacing. 1012 Various types of fractional ablative CO 2 lasers have been used for acne scar treatments with different penetration depths at variable energy levels. Manuskiatti and colleagues 12 treated 13 patients using a fractional CO 2 laser for three sessions. Patients with mild to moderate scars were irradiated with lower energy levels (7590 mJ/MTZ), whereas deeper scars were treated using a high-pulse energy level (105 mJ/ MTZ). A fractionated CO 2 laser system used in their study creates 150- to 200-lm-deep MTZs. At the 3-month follow-up, 69% of subjects had at least 25 50% improvement. Likewise, in a controlled split-- face trial, Jung and colleagues 13 treated mild to severe acne scars with a fractional CO 2 laser. Lower-uence, higher-density settings (30 mJ/pulse, 250 MTZs/cm 2 ) were compared with higher-uence, lower-density settings (70 mJ/pulse, 150 MTZs/ cm 2 ). More-pronounced effects were demonstrated on the sides treated with higher uence and lower density. Energy levels of 30 and 70 mJ corresponded to a depth of the necrotic columns approximately up to 282 and 486 lm, respectively, with the CO 2 FS used in their study, as assessed through histologic evaluation. Chapas and colleagues 6 treated 13 patients with moderate to severe acne scars using the novel ablative 30W CO 2 Fraxel re:pair device at pulse energies of 20100 mJ for two to three full-face treatments. Patients treated with higher energy levels (70100 mJ) on deeper scars on the cheeks for the second and third treatments received the highest improvement scores, with average over- all improvement of 5175% 3 months after the nal treatment. A previous study with this device showed tissue ablation and thermal effects as deep as 1 1.6 mm into the skin at the higher energies of 70 100 mJ. 14 Thus, based on previous studies, it was estimated that higher energy producing deeper tissue injury into the dermis correlated with more-pro- nounced clinical efcacy in laser resurfacing, 15,16 although it is unknown how deep the tissue injury depth would tend to balance the biologic effects of modulating and suppressing in wound healing responses, which presents in similar clinical efcacy with different energies. In our comparison study, we treated patients with moderate to severe acne scars using the Deep FX mode at energy levels of 10 and 20 mJ (Group B). Farkas and colleagues 17 reported that, with a single pulse, the Deep FX mode demonstrated tissue injury up to 1 mm from the tissue surface at 10 mJ and up to 2 mm at 20 mJ as assessed through histopathologic evaluation. At the 3-month follow-up, 80% of subjects had at least 2550% improvement, and 30% had 5175% improvement in their scar conditions. There was no TABLE 3. Overall Comparative Data Between Different Fluences in Group B 10 mJ 20 mJ p-Value Pain, mean SD (range 010) 4.39 1.19 4.98 1.13 .02 Edema, days, mean SD 2.50 0.52 3.50 0.53 .001 Crusting, days, mean SD 4.00 0.67 4.80 0.79 .003 Postinammatory hyperpigmentation duration, days, mean SD 46.80 11.51 56.80 11.46 .004 Infection, n 0/10 0/10 Scarring, n 0/10 0/10 Acneiform eruption, n 0/10 0/10 Cutaneous pruritus, n 4/10 4/10 Skin dryness, n 5/10 5/10 Hypopigmentation, n 0/10 0/10 Patient satisfaction, mean SD (range 010) 5.30 1.25 5.42 1.30 .83 SD, standard deviation. YUAN ET AL 40: 5: MAY 2014 549 signicant difference in clinical efcacy between 10 and 20 mJ laser irradiation. Tissue injury after treatment with the Deep FX mode was similar to the super-short-pulse Fraxel re:pair system, with the ablation microcolumns penetrating from the epi- dermis into the underlying papillary and reticular dermis. The penetration depth with the lower-energy level of this specic device may be in accordance with the depth using higher energy with other fractional ablative CO 2 lasers. In this study, with the lower-uence 10 mJ of the Deep FX mode corre- sponding to a depth of 1 mm, it was possible to achieve signicant clinical efcacy, as previously reported. It was hypothesized that penetration as deep as 2 mm into the deep reticular dermis with CO 2 FS treatment at higher energy may not result in greater efcacy for treating acne scars. We also compared the efcacy of CO 2 FS treatment with different densities and found that there was no statistically signicant difference between the lower- density 10% and higher-density 20%. The results of our study were compatible withthe previous report by Kono and colleagues 18 indicating therapeutic effects of 1,550-nm nonablative FP laser treatment in skin rejuvenation. It was considered fromtheir study that, when the fractional laser beamcreates a dense pattern of epidermal and dermal MTZs, the untreated tissues that surround the MTZs serve as a reservoir for thermal healing. Using higher density, the quantity of the undamaged tissues decreased, which was likely to result in no greater efcacy in scar improvement. Adverse effects such as pain, edema, crusting, and PIH were found to be more evident or persisted for longer periods in patients treated with higher den- sities or higher uences, as found in a previous study. 18 PIH is one of the most troubling adverse effects of laser irradiation when treating Asian patients. We observed that both sides of the faces in all 20 subjects had PIH that had almost resolved within 3 months. The majority of patients received laser irradiation in the summer and early autumn, when the sun is most intense, which may be responsible for the high rate of PIH observed. The pathogenesis of PIH is unknown. Some studies have found high density to be a causative factor of PIH. 6,18 In fractional resurfacing, too high a density can cause overlapping thermal injury zones and, if dense enough, act like traditional ablative laser resurfacing, which has a high risk of PIH. 18 It is estimated that the risk of PIH may be correlated with the extent of overlapping thermal injury zones. The extent of the overlapping thermal injury zones seems to be related to the density and uence setting of a fractional laser. Hantash and colleagues 10 found that higher uence achieved greater thermal lesion depth and width and resulted in greater lesion dimensions, which is likely to enhance the degree of overlapping thermal injury zones. When we applied the higher density or uence, the severity and duration of the PIH was more signicant. However, we could not compare the effect of higher density and uence on the characteristics of PIH. Because in our study, there was lack of a same control group. To avoid PIH, the use of lower densities and uences is of particular importance. Delayed hypopigmen- tation, which has been reported with traditional ablative CO 2 resurfacing, was not observed in our patients after CO 2 AFR treatments, but an extended follow-up period is essential, because the delayed pigment abnormality usually develops as late as 6 months to 1 year postoperatively. 19 Improvement in acne scars was signicantly greater at the 3-month follow-up than at 1 month, which was in accordance with previous reports. 6,12 Several studies have indicated that FP-induced heat shock protein (HSP) expression and new formation of collagen and elastic bers lasted for 36 months or even longer, which was in accordance with clinical observation of long-term biologic effects. 20,21 Expression of HSPs such as HSP70 and HSP47 plays an important role in wound healing responses, which lead to collagen remodeling and formation. It was estimated that 3 months or longer may be an appropriate treatment interval. If the interval is short, such as 12 months, the wound healing responses of the last treatment session may not produce the extreme effect, and several postoperative COMPARI SON STUDY OF CO 2 AFR DERMATOLOGI C SURGERY 550 safety indexes such as sebum excretion rate, trans- epidermal water loss, and the melaninerythema index may not completely recover. 22 Acne scars were graded using the ECCAgrading scale at baseline and at follow-up visits. 9 The ECCA grading scale is a tool designed to help dermatologists assess the severity of acne scars and in standardizing discussions about the treatment of scars. 9 The advantage of the ECCAgrading systemis that it could reect the overall facial atrophic acne scar conditions with both qualitative and quantitative grading scale, but it cannot reect the efcacy of each independent scar improvement without the true pre-/post-scar depth measured, which is a limitation of our study. Other limitations of this study were the small sample size and that there was only one treatment session using a single laser modality. To maximize the efcacy of scar treatment, various modalities should be combined due to a diverse range of scar condi- tions. Moreover, no treatment option available can offer near-total improvement of moderate to severe acne scars with only one treatment session. In conclusion, we demonstrated the efcacy and safety of a single-session treatment of acne scars with fractional CO 2 laser depending on different energy settings in Asian patients in a randomized, split-face, evaluator-blinded study design. Frac- tional CO 2 laser treatment using the Deep FX mode may provide a signicant efcacy for acne scars with lower uence and density and fewer compli- cations. Future work would be benecial, including longer follow-up for the assessment of scar improvement and possible late-emerging pigmentary changes. References 1. Alster TS, West TB. 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Ann Dermatol 2011;23:448 54. Address correspondence and reprint requests to: Shan- Shan Li, MD, PhD, Department of Dermatology and Venereology, First Hospital of Jilin University, 130000 Changchun, Jilin, China, or e-mail: shansalee@gmail.com COMPARI SON STUDY OF CO 2 AFR DERMATOLOGI C SURGERY 552