Just Accepted by Journal of Cosmetic and Laser Therapy
A prospective, split-face, randomized study of the efficacy and safety of a novel fractionated intense pulsed light treatment for melasma in Asians
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
Woo Jin Yun, Sang Min Lee, Ji Su Han, Sang Hyung Lee, Seo Youn Chang, Sik Haw, Jung Bok Lee, Chong Hyun Won, Mi Woo Lee, Jee Ho Choi, Sung Eun Chang 10.3109/14764172.2015.1027227 Abstract Background: Intense pulse light (IPL) has been reported to effectively treat melasma in previous studies, but an aggravation of pigmentation was noted. Fractionated IPL is a novel technique in which microsecond-domain fractionated pulses are delivered to the target area. Objective: To compare the safety and efficacy of low-fluency, frequently scheduled fractionated IPL and conventional IPL for melasma treatment. Materials and Methods: This was a 14-week, split-face study in which 30 Asian women were treated with weekly fractionated IPL on one side of the face and biweekly conventional IPL on the other side. Results: The non-inferiority of a weekly fractionated IPL regimen to a biweekly conventional IPL regimen was verified by a lower margin of the 95% confidence interval for the difference in the Melasma Area and Severity Index (MASI) change from baseline of 2.61 for each side. This value was greater than the previously determined non-inferiority margin of –2.68 (P < 0.025). On the fractionated IPL side, the modified MASI score decreased continuously, but in the conventional IPL group, the MASI score rebounded during the treatment course. Conclusion: Fractionated IPL shows moderate efficacy as a melasma treatment and is therefore a good alternative to conventional IPL as there is no indication of melasma exacerbation. Fractionated IPL can also be used as a maintenance treatment for melasma.
© 2015 Informa UK, Ltd. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication.
A prospective, split-face, randomized study of the efficacy and safety of a novel fractionated intense pulsed light treatment for melasma in Asians
Woo Jin Yun1, Sang Min Lee1, Ji Su Han1, Sang Hyung Lee1, Seo Youn Chang1, Sik Haw2, Jung Bok Lee3, Chong Hyun Won1, Mi Woo Lee1, Jee Ho Choi1, Sung Eun Chang1 1
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
Department of Dermatology, Asan Medical Center, University of Ulsan College of
Medicine, Seoul, Korea, 2Department of Dermatology, Ilsan Paik Hospital, College of Medicine, Inje University, Goyang, Korea, 3Department of Clinical Epidemiology and Biostatics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
"This study was supported by 2011 health technology transfer and industry development support of Ministry of Health and Welfare of Korea and partially by Asan Medical Center SRC 2011." correspondence: Sung Eun Chang, MD, PhD, Department of Dermatology and Research Institute of Dermatology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, KOREA. Tel: +82-2-3010-3460. Fax: +82-2-486-7831. Email:
[email protected]
Short title: Abstract Background: Intense pulse light (IPL) has been reported to effectively treat melasma in previous studies, but an aggravation of pigmentation was noted. Fractionated IPL is a novel technique in which microsecond-domain fractionated pulses are delivered to the target area. Objective: To compare the safety and efficacy of low-fluency, frequently scheduled fractionated IPL and conventional IPL for melasma treatment. Materials and Methods: This was a 14-week, split-face study in which 30 Asian women were treated with weekly fractionated IPL on one side of the face and biweekly conventional IPL on the other side. Results: The non-inferiority of a weekly fractionated IPL regimen to a biweekly conventional IPL regimen was verified by a lower margin of the 95% confidence interval for the difference in the Melasma Area and Severity Index (MASI) change from baseline of 2.61 for each side. This value was greater than the previously determined non-inferiority margin of –2.68 (P < 0.025). On the fractionated IPL side, the modified MASI score decreased continuously, but in the conventional IPL group, the MASI score rebounded during the treatment course.
1
Conclusion: Fractionated IPL shows moderate efficacy as a melasma treatment and is therefore a good alternative to conventional IPL as there is no indication of melasma exacerbation. Fractionated IPL can also be used as a maintenance treatment for melasma.
Keywords: Lasers and light sources, Cosmeceuticals Introduction Melasma is a pigmentary disorder common in middle-aged women of higher skin phototypes.(1) In Asian countries, melasma is the cause of more than
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
50% of consultations in outpatient esthetic clinics.(2) Melasma can be treated with intense pulsed light (IPL), which emits a noncoherent broad-spectrum light of wavelengths ranging from 500 nm to 1200 nm.(3, 4) This wavelength flexibility allows versatility in the choice of proper parameters for different target lesions involving a wide range of chromophores.(4) For pigment lesions, IPL is expected to cause less injury to melanocytes than conventional Q-switched lasers, resulting in less postinflammatory hyperpigmentation (PIH).(4) Although several studies have reported some favorable clinical outcomes in the treatment of melasma with IPL, a drawback of this therapy approach is the possibility of pigment accentuation due to nonspecific heat diffusion. For example, the appearance of formerly invisible melasma after IPL treatment and the aggravation of melasma during repeated treatment sessions have been reported.(5) It is plausible that a longer pulse duration and higher peak energy, which result in nonselective heat diffusion, could be implicated in pigment accentuation. Due to successful clinical outcomes without melasma exacerbation with the use of low-fluence Q-switched Nd: YAG lasers, we decided to apply a lower fluence and a more frequent schedule in the IPL treatment of melasma.(6)
2
The recently developed IPL methodology with a fractionated pulse was used in our present study. This fractionated IPL system delivers more than 40 subpulses of a 40-μs duration within milliseconds. In contrast to conventional IPL, fractionated IPL attenuates peak fluence and reduces nonselective heat diffusion, and is assumed to be safer than its conventional counterpart. With increased safety due to the fractionation of the total fluence, fractionated IPL would be more suitable as a frequent low-peak fluence treatment strategy for
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
melasma, provided that a clinical efficacy equivalent to conventional IPL could be demonstrated. To evaluate the efficacy and safety of fractionated IPL in a double-frequency schedule, we carried out a split-face study comparing weekly irradiation of fractionated IPL with biweekly irradiation of conventional IPL. This investigation was a prospective, randomized, controlled, single-blind, noninferiority clinical trial and our hypothesis was that weekly irradiation with fractionated IPL would be as effective as an alternate weekly irradiation regimen with conventional IPL.
Patients and methods
Ethical considerations The present study was approved by the institutional review board of the Asan Medical Center. All patients were informed of the benefits and risks of the treatments and informed consent was obtained from each patient before enrollment. Investigators complied with national and international Good Clinical Practice guidelines and the Declaration of Helsinki.
3
Inclusion and exclusion criteria Exclusion criteria included underlying chronic or inflammatory systemic disease, malignancy, photosensitivity, pregnancy, and breastfeeding. Subjects who used hydroquinone-, α-hydroxy acid-, and/or retinoic acid-containing topical agents or who were exposed to any other lasers or chemical peels on the face during the previous 3 months were also excluded.
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
IPL systems The IPL systems used in the current study were the Ellipse Flex (Danish Dermatologic Development, Hoersholm, Denmark) with a 530-nm to 750-nm filter for the conventional IPL group, and the EclatST (Union Medical, Seoul, South Korea) with a 550-nm to 850-nm filter for the fractionated IPL group. EclatST emits 40–200 fractionated subpulses within a microsecond time frame.
Treatment Each patient was treated with either novel fractionated IPL or conventional IPL on each cheek. Treatment was randomly allocated to either facial cheek with a computer program so that one cheek was treated with fractionated IPL and the other with conventional IPL. The fractionated IPL group received weekly fractionated pulse IPL treatment each week for six weeks starting from the baseline or the first visit. The IPL group received conventional IPL treatment every second week. Thus, a total of six treatment sessions were carried out with the novel IPL protocol with fractionated pulse on one side of
4
the participant’s face, whilst three sessions with conventional IPL treatment were performed on the other side (Figure 1). No preoperative local anesthesia was applied. The parameters of the fractionated pulse IPL were set at a fluence of 13 J/cm2 with two passes; conventional IPL treatment was performed with 7 J/cm2, 2.5-ms double pulses with a delay time of 10 ms, and a single pass. The appearance of
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
barely perceptible erythema immediately after treatment was used to determine parameter selection. During the study, the treatment protocol was fixed and was not adjusted according to treatment response. All patients were followed up at 1 and 2 months after the final treatment. They were instructed to avoid sun exposure and wear a broad-spectrum sunscreen during and after treatment.
Evaluation The primary outcome measure of the current study was the change in the MASI half face score from the baseline at two months after treatment. The modified MASI half face scores validated by Pandya et al.(7) were used as follows: modified MASI score = area (treated cheek) × darkness (treated cheek) The range of the total score was 0 to 24. The area of involvement was scored as follows: 0, absent; 1, 10%; 2, 10%–29%; 3, 30%–49%; 4, 50%–69%; 5, 70%–89%; and 6, 90%–100%. Darkness was scored as follows: 0, absent; 1, slight; 2, mild; 3, marked; and 4, severe. Before each treatment and at one
5
and two months after the final treatment, the modified MASI scores were independently evaluated by two investigators, and standardized digital photographs were taken. Normal MASI scores for full face therapies range from 0 to 48, and –5.36 is the expected decrease in this score for conventional IPL treatment.(3) As our investigation was a split-face study involving half cheek treatment, the non-
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
inferiority margin was calculated to be –2.68 (half –5.36). The secondary outcome measures were serial changes in the MASI score during the treatment course, the investigator's global assessment, and patient satisfaction (based on a questionnaire). At each session, investigators rated the level of improvement according to the following scale: –1, worsening of melasma (
A prospective, split-face, randomized study of the efficacy and safety of a novel fractionated intense pulsed light treatment for melasma in Asians
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
Woo Jin Yun, Sang Min Lee, Ji Su Han, Sang Hyung Lee, Seo Youn Chang, Sik Haw, Jung Bok Lee, Chong Hyun Won, Mi Woo Lee, Jee Ho Choi, Sung Eun Chang 10.3109/14764172.2015.1027227 Abstract Background: Intense pulse light (IPL) has been reported to effectively treat melasma in previous studies, but an aggravation of pigmentation was noted. Fractionated IPL is a novel technique in which microsecond-domain fractionated pulses are delivered to the target area. Objective: To compare the safety and efficacy of low-fluency, frequently scheduled fractionated IPL and conventional IPL for melasma treatment. Materials and Methods: This was a 14-week, split-face study in which 30 Asian women were treated with weekly fractionated IPL on one side of the face and biweekly conventional IPL on the other side. Results: The non-inferiority of a weekly fractionated IPL regimen to a biweekly conventional IPL regimen was verified by a lower margin of the 95% confidence interval for the difference in the Melasma Area and Severity Index (MASI) change from baseline of 2.61 for each side. This value was greater than the previously determined non-inferiority margin of –2.68 (P < 0.025). On the fractionated IPL side, the modified MASI score decreased continuously, but in the conventional IPL group, the MASI score rebounded during the treatment course. Conclusion: Fractionated IPL shows moderate efficacy as a melasma treatment and is therefore a good alternative to conventional IPL as there is no indication of melasma exacerbation. Fractionated IPL can also be used as a maintenance treatment for melasma.
© 2015 Informa UK, Ltd. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication.
A prospective, split-face, randomized study of the efficacy and safety of a novel fractionated intense pulsed light treatment for melasma in Asians
Woo Jin Yun1, Sang Min Lee1, Ji Su Han1, Sang Hyung Lee1, Seo Youn Chang1, Sik Haw2, Jung Bok Lee3, Chong Hyun Won1, Mi Woo Lee1, Jee Ho Choi1, Sung Eun Chang1 1
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
Department of Dermatology, Asan Medical Center, University of Ulsan College of
Medicine, Seoul, Korea, 2Department of Dermatology, Ilsan Paik Hospital, College of Medicine, Inje University, Goyang, Korea, 3Department of Clinical Epidemiology and Biostatics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
"This study was supported by 2011 health technology transfer and industry development support of Ministry of Health and Welfare of Korea and partially by Asan Medical Center SRC 2011." correspondence: Sung Eun Chang, MD, PhD, Department of Dermatology and Research Institute of Dermatology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, KOREA. Tel: +82-2-3010-3460. Fax: +82-2-486-7831. Email:
[email protected]
Short title: Abstract Background: Intense pulse light (IPL) has been reported to effectively treat melasma in previous studies, but an aggravation of pigmentation was noted. Fractionated IPL is a novel technique in which microsecond-domain fractionated pulses are delivered to the target area. Objective: To compare the safety and efficacy of low-fluency, frequently scheduled fractionated IPL and conventional IPL for melasma treatment. Materials and Methods: This was a 14-week, split-face study in which 30 Asian women were treated with weekly fractionated IPL on one side of the face and biweekly conventional IPL on the other side. Results: The non-inferiority of a weekly fractionated IPL regimen to a biweekly conventional IPL regimen was verified by a lower margin of the 95% confidence interval for the difference in the Melasma Area and Severity Index (MASI) change from baseline of 2.61 for each side. This value was greater than the previously determined non-inferiority margin of –2.68 (P < 0.025). On the fractionated IPL side, the modified MASI score decreased continuously, but in the conventional IPL group, the MASI score rebounded during the treatment course.
1
Conclusion: Fractionated IPL shows moderate efficacy as a melasma treatment and is therefore a good alternative to conventional IPL as there is no indication of melasma exacerbation. Fractionated IPL can also be used as a maintenance treatment for melasma.
Keywords: Lasers and light sources, Cosmeceuticals Introduction Melasma is a pigmentary disorder common in middle-aged women of higher skin phototypes.(1) In Asian countries, melasma is the cause of more than
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
50% of consultations in outpatient esthetic clinics.(2) Melasma can be treated with intense pulsed light (IPL), which emits a noncoherent broad-spectrum light of wavelengths ranging from 500 nm to 1200 nm.(3, 4) This wavelength flexibility allows versatility in the choice of proper parameters for different target lesions involving a wide range of chromophores.(4) For pigment lesions, IPL is expected to cause less injury to melanocytes than conventional Q-switched lasers, resulting in less postinflammatory hyperpigmentation (PIH).(4) Although several studies have reported some favorable clinical outcomes in the treatment of melasma with IPL, a drawback of this therapy approach is the possibility of pigment accentuation due to nonspecific heat diffusion. For example, the appearance of formerly invisible melasma after IPL treatment and the aggravation of melasma during repeated treatment sessions have been reported.(5) It is plausible that a longer pulse duration and higher peak energy, which result in nonselective heat diffusion, could be implicated in pigment accentuation. Due to successful clinical outcomes without melasma exacerbation with the use of low-fluence Q-switched Nd: YAG lasers, we decided to apply a lower fluence and a more frequent schedule in the IPL treatment of melasma.(6)
2
The recently developed IPL methodology with a fractionated pulse was used in our present study. This fractionated IPL system delivers more than 40 subpulses of a 40-μs duration within milliseconds. In contrast to conventional IPL, fractionated IPL attenuates peak fluence and reduces nonselective heat diffusion, and is assumed to be safer than its conventional counterpart. With increased safety due to the fractionation of the total fluence, fractionated IPL would be more suitable as a frequent low-peak fluence treatment strategy for
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
melasma, provided that a clinical efficacy equivalent to conventional IPL could be demonstrated. To evaluate the efficacy and safety of fractionated IPL in a double-frequency schedule, we carried out a split-face study comparing weekly irradiation of fractionated IPL with biweekly irradiation of conventional IPL. This investigation was a prospective, randomized, controlled, single-blind, noninferiority clinical trial and our hypothesis was that weekly irradiation with fractionated IPL would be as effective as an alternate weekly irradiation regimen with conventional IPL.
Patients and methods
Ethical considerations The present study was approved by the institutional review board of the Asan Medical Center. All patients were informed of the benefits and risks of the treatments and informed consent was obtained from each patient before enrollment. Investigators complied with national and international Good Clinical Practice guidelines and the Declaration of Helsinki.
3
Inclusion and exclusion criteria Exclusion criteria included underlying chronic or inflammatory systemic disease, malignancy, photosensitivity, pregnancy, and breastfeeding. Subjects who used hydroquinone-, α-hydroxy acid-, and/or retinoic acid-containing topical agents or who were exposed to any other lasers or chemical peels on the face during the previous 3 months were also excluded.
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
IPL systems The IPL systems used in the current study were the Ellipse Flex (Danish Dermatologic Development, Hoersholm, Denmark) with a 530-nm to 750-nm filter for the conventional IPL group, and the EclatST (Union Medical, Seoul, South Korea) with a 550-nm to 850-nm filter for the fractionated IPL group. EclatST emits 40–200 fractionated subpulses within a microsecond time frame.
Treatment Each patient was treated with either novel fractionated IPL or conventional IPL on each cheek. Treatment was randomly allocated to either facial cheek with a computer program so that one cheek was treated with fractionated IPL and the other with conventional IPL. The fractionated IPL group received weekly fractionated pulse IPL treatment each week for six weeks starting from the baseline or the first visit. The IPL group received conventional IPL treatment every second week. Thus, a total of six treatment sessions were carried out with the novel IPL protocol with fractionated pulse on one side of
4
the participant’s face, whilst three sessions with conventional IPL treatment were performed on the other side (Figure 1). No preoperative local anesthesia was applied. The parameters of the fractionated pulse IPL were set at a fluence of 13 J/cm2 with two passes; conventional IPL treatment was performed with 7 J/cm2, 2.5-ms double pulses with a delay time of 10 ms, and a single pass. The appearance of
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
barely perceptible erythema immediately after treatment was used to determine parameter selection. During the study, the treatment protocol was fixed and was not adjusted according to treatment response. All patients were followed up at 1 and 2 months after the final treatment. They were instructed to avoid sun exposure and wear a broad-spectrum sunscreen during and after treatment.
Evaluation The primary outcome measure of the current study was the change in the MASI half face score from the baseline at two months after treatment. The modified MASI half face scores validated by Pandya et al.(7) were used as follows: modified MASI score = area (treated cheek) × darkness (treated cheek) The range of the total score was 0 to 24. The area of involvement was scored as follows: 0, absent; 1, 10%; 2, 10%–29%; 3, 30%–49%; 4, 50%–69%; 5, 70%–89%; and 6, 90%–100%. Darkness was scored as follows: 0, absent; 1, slight; 2, mild; 3, marked; and 4, severe. Before each treatment and at one
5
and two months after the final treatment, the modified MASI scores were independently evaluated by two investigators, and standardized digital photographs were taken. Normal MASI scores for full face therapies range from 0 to 48, and –5.36 is the expected decrease in this score for conventional IPL treatment.(3) As our investigation was a split-face study involving half cheek treatment, the non-
J Cosmet Laser Ther Downloaded from informahealthcare.com by Kainan University on 04/04/15 For personal use only.
inferiority margin was calculated to be –2.68 (half –5.36). The secondary outcome measures were serial changes in the MASI score during the treatment course, the investigator's global assessment, and patient satisfaction (based on a questionnaire). At each session, investigators rated the level of improvement according to the following scale: –1, worsening of melasma (
