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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 39  |  Issue : 3  |  Page : 118-124

Facilitated delivery of topical steroids after fractional ablative carbon dioxide laser failed to prevent the postthyroidectomy hypertrophic scar


1 Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
2 Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
3 Department of General Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
4 Department of Trauma Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan

Date of Submission25-May-2021
Date of Decision06-Jun-2021
Date of Acceptance14-Jun-2021
Date of Web Publication20-Sep-2021

Correspondence Address:
Prof. Ching-Hua Hsieh
No. 123, Ta-Pei Road, Niaosong District, Kaohsiung City 83301
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ds.ds_29_21

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  Abstract 


Background: The ablative fractional laser can destroy the epidermal barrier and enhance the infiltration and distribution of drugs into the dermis. Objectives: This study was designed to investigate whether steroid delivery followed by the fractional ablative laser can prevent the formation of postthyroidectomy scar. Methods: This prospective split-scar design study recruited 12 adult female patients who underwent thyroidectomy between March 2018 and December 2018. The whole scar was treated with a fractional ablative carbon dioxide laser with topical 0.05% clobetasol propionate ointment only applied on the treatment side. The Patient and Observer Scar Assessment Scale (POSAS) questionnaire was used for outcome assessment at 1 year following the first treatment. The follow-up assessment by scar esthetic scale using digital photographs at 6 months and 1 year after first treatment was also done by three blinded plastic surgeons. Results: The POSAS revealed the improvement was not significant on vascularity, pigmentation, thickness, relief, pliability, surface area, and overall opinion on the improvement (all P > 0.05). The digital photographs evaluation also did not reveal a significant difference between the treatment side and control side. The overall esthetic score in the assessment of digital photographs was 4.4 ± 1.5, 4.2 ± 1.9, and 3.4 ± 1.9 at 6 months, and 2.8 ± 1.9, 3.1 ± 1.9, and 2.4 ± 2.1 at 1 year, with 0–10 indicating totally identical to significantly different comparing the whole scar with surrounding normal skin. Conclusion: This prospective scar-split study revealed that the application of topical steroid after fractional ablative carbon dioxide laser has no significant effect to prevent the formation of postthyroidectomy scar.

Keywords: Clobetasol propionate ointment, fractional ablative carbon dioxide laser, hypertrophic scar, laser assisted drug delivery, steroid ointment, thyroidectomy


How to cite this article:
Lin KC, Wu SC, Chi SY, Lin HP, Lin CH, Tsai YJ, Hsieh MH, Hsu SY, Hsieh CH. Facilitated delivery of topical steroids after fractional ablative carbon dioxide laser failed to prevent the postthyroidectomy hypertrophic scar. Dermatol Sin 2021;39:118-24

How to cite this URL:
Lin KC, Wu SC, Chi SY, Lin HP, Lin CH, Tsai YJ, Hsieh MH, Hsu SY, Hsieh CH. Facilitated delivery of topical steroids after fractional ablative carbon dioxide laser failed to prevent the postthyroidectomy hypertrophic scar. Dermatol Sin [serial online] 2021 [cited 2021 Oct 19];39:118-24. Available from: https://www.dermsinica.org/text.asp?2021/39/3/118/326268

Authors Ko-Chien Lin and Shao-Chun Wu contributed equally to this article





  Introduction Top


Thyroidectomy results in an undesired scar at the anterior neck of the patient. A postthyroidectomy scar without optimal esthetic appearance may cause negative scar perception and furtherly lead to negative body image and decreased quality of life.[1],[2] Although intralesional injection of steroids has been widely used to treat postthyroidectomy hypertrophic or keloid scars, the use of steroid injection may lead to some side effects, including telangiectasia, dermal and fat atrophy, and hypopigmentation of the surrounding skin.[3],[4],[5] In addition, pain during treatment is generally not tolerable during the intralesional injection.[6]

Laser treatment of postthyroidectomy scars has validated its effectiveness in scar treatment.[7],[8] In the comparison of nonablative and ablative fractional laser systems for the revision of thyroidectomy scars, the clinical improvement for nonablative and ablative fractional laser was highly similar; however, the ablative fractional laser was better at reducing scar hardness, whereas the nonablative fractional laser was superior for lightening scar color.[8] Subsequently, the concept of laser-assisted drug delivery (LADD) emerged as the ablative fractional laser procedure can destroy the epidermal barrier by tissue vaporization, thus enhancing the infiltration and distribution of drugs deeply into the dermis.[9] For example, the ablative fractional carbon dioxide laser can break the epidermis and create exposed spots into the dermis at a depth of 0.5–1 mm, thereby facilitating drug delivery deeply into the dermis.[9] In 2013, Waibel et al. first published a paper on the laser-assisted delivery of topical steroids using a fractional ablative carbon dioxide laser for hypertrophic scarring and found promising results in treating scars while decreasing the adverse effects caused by intralesional steroid injection.[10] Many animal and clinical studies have also revealed that LADD is useful for the delivery of many kinds of drugs, including steroids, 5-fluorouracil, and verapamil hydrochloride, and presents with favorable outcomes.[3],[4],[11],[12],[13] For example, in the treatment of androgenetic alopecia, using ablative fractional carbon dioxide laser combined with minoxidil shows significant result.[14] A fractional 2940 nm erbium-doped yttrium aluminum garnet (Er: YAG) LADD of 0.5% timolol maleate is effective for deep infantile hemangioma[15] and of topical 4% hydroquinone cream for melasma is an efficaciously.[16] Further, using ablative fractional Er: YAG laser combined with topical cidofovir 75 mg/mL ointment for treating plantar warts also reveals a significant reduction in lesion size and symptoms release.[17]

Our institute has routinely applied LADD to treat postthyroidectomy scars using the fractional ablative carbon dioxide laser with topical steroid delivery in the clinical setting, with favorable outcomes. The procedure reduces the occurrence of scars in the anterior neck following thyroidectomy, minimizing their undesired effects. After cutting injuries, the wound healing process continues in the first 2 weeks with fibroblast infiltration and collagen synthesis during the proliferative phase of healing. Afterward, wound contracture and collagen remodeling occur in the remodeling phase, then the scar becomes softened and flattened with lighter color 1 year postinjury.[18] Therefore, this study was designed to investigate whether early utilization of the LADD procedure with steroid delivery followed by thyroidectomy can prevent the formation of postthyroidectomy scar better than the only utilization of the fractional ablative carbon dioxide laser. To reduce the variability among study participants, the study was performed in a split-scar manner.


  Patients and Methods Top


Enrollment of the patients

This was a prospective study that recruited patients who underwent thyroidectomy between March 2018 and December 2018 in the cosmetic center. This study was preapproved by the institutional review board (reference number: 201800240A3). Informed consent was obtained from all participants included in the study. A total of 12 adult female patients who had undergone thyroidectomy through a transcervical incision by the same surgeon were enrolled. Only patients with linear and symmetric scars with complete healing at the time of suture removal were included. The following groups of patients were excluded: Patients who have no willing to participate in the study, patients who could not be followed up for over 1 year, patients who had immunocompromised diseases or autoimmune diseases, and those who had a history of keloids elsewhere on the body.

Study design

Patients received a treatment protocol for split-scar design 2–4 weeks following the thyroidectomy. The thyroidectomy scar was divided into right or left equal halves, with one side being the treatment side and the other side being the control area. The selection of side for treatment or as control was random. Before each laser treatment, local anesthetic Lidopin 5% cream (Panion and BF Biotech Inc., USA) was administered for each patient over the scar for 30 min for pain relief. The Lidopin 5% cream was gently removed using a normal saline-rinsed gauze. The whole scar was treated with a fractional ablative carbon dioxide laser (eCO2 Plus™, manufactured by Lutronic, South Korea) with two passes under a 10,600 nm wavelength, 120 mm spot size, pulse energy of 50 mJ, 30 W of power, and a density of 200. Topical steroid ointment (clobetasol propionate, 0.05%) was applied once and rubbed over the treatment side for 3 min to enhance drug absorption. In contrast, no treatment over the control area was performed, which encompassed the other half of the scar. After treatment, both sides of the scar were covered with hydrocolloid dressing (DuoDERM® Extra Thin). The patients underwent five treatment courses performed by the same doctor according to the same protocol, with each course given 4 weeks after the previous treatment. The treatment and control areas remained the same throughout the study course. Digital photographs were recorded before every session, 1 month after the fifth treatment (i.e., 6 months after the first treatment), and 7 months after the fifth treatment (i.e., 1 year after the first treatment). The patients and the performing surgeon answered the Patient and Observer Scar Assessment Scale (POSAS) questionnaire[19],[20],[21],[22] at the last follow-up (i.e., 1 year after the first treatment).

Evaluation of the outcome

Patient and Observer Scar Assessment Scale

The POSAS questionnaire included two parts. The first part included patient self-evaluation with regards to the following six aspects: Pain (has the scar been painful for the past few weeks?), itching (has the scar been itching the past few weeks?), color (is the scar color different from the color of your normal skin at present?), stiffness (is the stiffness of the scar different from your normal skin at present?), thickness (is the thickness of the scar different from your normal skin at present?), and irregularity (is the scar more irregular than your normal skin at present?) as well as one overall opinion of the scar (what is your overall opinion of the scar compared to normal skin?). The second part of the POSAS was answered by the treating surgeon to compare scars on the treatment and control sides with regards to the following scar characteristics: vascularity, pigmentation, thickness, relief, pliability, surface area, and overall opinion of the scar.

Assessment of digital photographs by three blinded plastic surgeons

Standardized digital photographs of the last follow-up (i.e., 1 year after first treatment) were evaluated by three blinded plastic surgeons who did not know which side was the treatment or control side. These plastic surgeons had been certified with the board of plastic surgery and were not involved in the laser or any other treatment of these patients. In the blinded fashion of not knowing which side was the treatment side, these three plastic surgeons rated the differences of the scar condition on both sides with a score ranging from 0 (totally identical) to 10 (significantly different) and guessed which side was the treatment side. However, if the opposite side was actually the treatment side (i.e., the plastic surgeon suggested the control side as the treatment side), the score would be converted to be negative, ranging from 0 (totally identical) to −10 (significantly different). Further, giving the overall esthetic opinion of the scar, these three plastic surgeons scored the digital photographs, which were taken 6 months and 1 year after the first treatment course, comparing the whole scar with surrounding normal skin with a number ranging from 0 (totally identical) to 10 (significantly different).

Statistical analysis

The scores of the study were plotted and presented as a mean with standard deviation. The Kruskal–Wallis one-way ANOVA test (Windows version 23.0; SPSS, Inc., Chicago, IL, USA) was used to compare the observer scar assessment scale of the POSAS evaluated by the treating doctor between the treatment and control sides and to compare the overall esthetic opinion of the scar at 6 months and 1 year after the first treatment course. A P < 0.05 was considered statistically significant.


  Results Top


Patient characteristics

The average age of the enrolled 12 female patients was 37.2 years (range, 23–59 years). There were no skin allergic changes, wound infections, or adverse effects in all patients after the treatment course during the study period. All patients had completed the follow-up. The photographs of four patients are shown in [Figure 1], [Figure 2], [Figure 3], [Figure 4], which showed 6 months (left picture) and 1 year (right picture) after the first treatment course.
Figure 1: The photograph of the patient 6 months (left picture) and 1 year (right picture) after the first treatment course of facilitated delivery of topical 0.05% clobetasol propionate ointment following fractional ablative carbon dioxide laser treatment. The right side of the neck scar was the treatment side.

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Figure 2: The photograph of the patient 6 months (left picture) and 1 year (right picture) after the first treatment course. The right side of the neck scar was the treatment side.

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Figure 3: The photograph of the patient 6 months (left picture) and 1 year (right picture) after the first treatment course. The right side of the neck scar was the treatment side.

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Figure 4: The photograph of the patient 6 months (left picture) and 1 year (right picture) after the first treatment course. The left side of the neck scar was the treatment side

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Assessment of the scar by Patient and Observer Scar Assessment Scale

In the assessment of the scar using POSAS at 1 year after the first treatment, the self-evaluation by patients [Figure 5] revealed that the score in the aspect of pain and itching was 2.8 ± 1.5 and 4.0 ± 2.3, respectively. The score of the color difference was 4.6 ± 2.7. The scores of stiffness, thickness, and irregularity of the scar were 2.8 ± 1.7, 3.7 ± 2.8, and 3.4 ± 2.4, respectively. The average score of overall opinion was 3.8 ± 2.5. In the assessment of the scar by the treating doctor using POSAS [Table 1] and [Figure 6], the improvement of POSAS score was not significant for each scar parameter, including vascularity, pigmentation, thickness, relief, pliability, and surface area (all P > 0.05). Regarding the overall opinion on the improvement, there was no significant improvement of the score on the treatment side compared with the score on the control side (5.2 ± 1.7 vs. 4.9 ± 2.4, respectively, P = 0.662).
Figure 5: The patient scar assessment of the postthyroidectomy scar by the patients themselves using Patient and Observer Scar Assessment Scale

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Figure 6: The observer scar assessment of the postthyroidectomy scar by the treating doctor using Patient and Observer Scar Assessment Scale

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Table 1: Assessment of the scar by Patient and Observer Scar Assessment Scale

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Assessment of digital photographs by three blinded plastic surgeons

The evaluation of the digital photographs of the 1-year follow-up by three blinded plastic surgeons [Figure 7] demonstrated that, with a negative value, there were 6, 6, and 5 patients per each doctor who had a better esthetic outcome of the control side compared with the treatment side. This resulted in the average esthetic improvement of the treatment side compared to the control side of 0.1 ± 1.6, 0.1 ± 3.7, and 0.9 ± 2.8. The results indicated that it is difficult for the blinded doctors to clarify the actual treatment site in many patients, implying that even though there were some differences in scar condition, the treatment site may not always result in a significant improvement of the scar. The addition of clobetasol propionate following the fractional ablative carbon dioxide laser did not decrease scar formation following thyroidectomy. In addition, the overall esthetic score about the scar by three blinded plastic surgeons in the assessment of digital photographs was 4.4 ± 1.5, 4.2 ± 1.9, and 3.4 ± 1.9 at 6 months, and 2.8 ± 1.9, 3.1 ± 1.9, and 2.4 ± 2.1 at 1 year (0–10 indicate totally identical to significantly different) in rating the difference between the scar and the surrounding normal skin [Figure 8]. Although there was a trend of decreased score of the scars at 1 year compared to those at 6 months, a significant difference was only found in the assessment of doctor number 1 (P = 0.027) but not in the assessments of other two doctors (P = 0.174 and P = 0.233).
Figure 7: Evaluation of the esthetic improvement of the postthyroidectomy scar between the treatment and control sides by three blinded plastic surgeons according to the digital photographs that were taken at 1-year after the first treatment course. The scale of 0–10 indicates totally identical to significantly different between both sides of the scar. In the blinded manner, if the plastic surgeon indicated the control side to be the treatment side, then score was converted to be negative, ranged from 0 (totally identical) to −10 (significantly different)

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Figure 8: The overall esthetic opinion of the scar by three blinded plastic surgeons in the assessment of digital photographs 6 months and 1 year in rating the difference of the scar compared with the surrounding normal skin. The scale of 0–10 indicate totally identical to significantly different from the normal skin

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  Discussion Top


This prospective split-scar study revealed that the application of topical 0.05% clobetasol propionate ointment after fractional ablative carbon dioxide laser failed to improve the esthetic outcome of the scar formation following thyroidectomy. The improvements in various scar parameters, including vascularity, pigmentation, thickness, relief, pliability, and surface area were not significant. In addition, the assessment of digital photographs at 1-year after the first treatment course by three blinded plastic surgeons also failed to identify a significant improvement in the treatment side compared to the control side.

Many studies have reported beneficial effects of the use of topical steroids following fractional ablative carbon dioxide laser in the treatment of hypertrophic scars[10] and keloids.[23] In addition, two other studies using triamcinolone with varying dosages of 10–40 mg/ml following the fractional ablative carbon dioxide laser, reported significant improvements in postburn hypertrophic scars based on the Vancouver scar scale.[3],[11] We believe that the failure in the improvement of the scar with topical clobetasol propionate use was not due to the dosage of drug or the protocol of laser used in the treatment, because such a protocol is routinely used in our institute to treat the postthyroidectomy scar and is associated with favorable outcomes with significant improvements in terms of itchiness, indicative characteristics, and general appearance of hypertrophic scarring without any adverse effects (unpublished data). We suggest that the failure to improve the scar using topical clobetasol propionate following a fractional ablative laser treatment may be due to different efficacy timing of steroids in reducing scar formation. In a study of intralesional injection of triamcinolone acetonide in 108 patients with pathological scars, who were divided into the early stage group (≤6 months after injury) and the static stage group (>6 months after injury), the overall efficacy of the early-stage group was significantly inferior to that of the static stage group.[24] One possible explanation is that the low dosage of glucocorticoids could not effectively inhibit the proliferation of fibroblasts at the early stage of scar formation, during which a massive infiltration of macrophages occurs, with secretion of relevant cytokines. At the static stage, glucocorticoids can more significantly reduce the proliferation of fibroblasts and induce their apoptosis when the infiltration of macrophages and secretion of cytokines is markedly reduced.[24] Therefore, the fundamental mechanisms and effective strategies to inhibit aberrant scar formation and to effectively treat a hypertrophic scar may be different.[25]

It had been reported that the early postoperative treatment with fractional ablation carbon dioxide laser is safe and effective in improving thyroidectomy scars.[26] The mechanism of scar prevention in laser therapy has not been clarified, but fractional lasers may influence the secretion of various cytokines and growth factors by stimulating angiogenesis and cellular responses.[27],[28] In this study, although a significant difference in the scars at 1 year was only found in the assessment of one of three doctors, there was a trend of scar improvement during the follow-up period. With only 12 patients in this study, the vast variation in scar formation after thyroidectomy among different patients would interfere with the accuracy in the measurement of the outcomes, thus presenting with one limitation of this study concerning the interpretation of the results. Notably, a similar evaluator-blinded, split-scar study with early postoperative fractional ablative carbon dioxide laser treatment begun 1 month after surgery and total five sessions at 1-month intervals is proved to be effective in improving thyroidectomy scars in 24 patients.[26] Although the selection of site for treatment in that study is not randomly assigned as our study, the results implied the use of early postoperative fractional ablation carbon dioxide laser alone may be a promising option for scar prevention following thyroidectomy and worthy of further investigation. In addition, to treat thyroidectomy scars, a meta-analysis study disclosed that the effectiveness of ablative fractional laser on scar thickness is superior to other laser sources[7] and it had been reported that ablative fractional laser was better at reducing scar hardness whereas nonablative fractional laser was superior for lightening color.[8] Increase the frequency of laser treatment or in combined with other laser, such as pulsed dye laser or potassium-titanyl-phosphate laser,[7] or with botulinum toxin type A[29],[30] may be considered to improve the therapeutic effects.

This study has some limitations. First, the patients enrolled in the study all live in Southern Taiwan and might not represent patients in other regions, as they may have similar types of skin. Second, in this study, only the evaluators of the photographs were blinded with regards to the treatment site, and the treating physician was not blinded while performing the scar assessment. The sentence is revised to “Since the evaluator knew which side was the treatment site, he might had been more prone to give a higher score for the treatment site.” However, because the differences between the treatment and control sites are very small, we believe that the possible bias was minimized. Further, whether the lack of efficacy might be due to insufficient treatment frequency and/or duration warrant further investigation. Finally, the study is limited to a relatively small group of patients; thus, the elimination of the variation among the study population would be difficult, albeit a split-scar design was used. Therefore, there might have been a possible bias in the outcome comparison.


  Conclusion Top


This prospective scar-split study revealed that the application of topical 0.05% clobetasol propionate ointment after fractional ablative carbon dioxide laser has no significant effect to improve the final esthetic outcome of the scar formation following thyroidectomy.

Acknowledgments

We would like to thank for the statistical analyses assisted by the Biostatistics Center, Kaohsiung Chang Gung Memorial Hospital.

Financial support and sponsorship

This research was supported by the grant of Chang Gung Memorial Hospital (CDRPG8K0011) to Ko-Chien Lin.

Conflicts of interest

There are no conflicts of interest.



 
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Sethukumar P, Ly D, Awad Z, Tolley NS. Scar satisfaction and body image in thyroidectomy patients: Prospective study in a tertiary referral centre. J Laryngol Otol 2018;132:60-7.  Back to cited text no. 2
    
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Majid I, Imran S. Fractional carbon dioxide laser resurfacing in combination with potent topical corticosteroids for hypertrophic burn scars in the pediatric age group: An open label study. Dermatol Surg 2018;44:1102-8.  Back to cited text no. 3
    
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Waibel JS, Wulkan AJ, Rudnick A, Daoud A. Treatment of hypertrophic scars using laser-assisted corticosteroid versus laser-assisted 5-fluorouracil delivery. Dermatol Surg 2019;45:423-30.  Back to cited text no. 4
    
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On HR, Lee SH, Lee YS, Chang HS, Park C, Roh MR. Evaluating hypertrophic thyroidectomy scar outcomes after treatment with triamcinolone injections and copper bromide laser therapy. Lasers Surg Med 2015;47:479-84.  Back to cited text no. 5
    
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Park KY, Lee Y, Hong JY, Chung WS, Kim MN, Kim BJ. Vibration anesthesia for pain reduction during intralesional steroid injection for keloid treatment. Dermatol Surg 2017;43:724-7.  Back to cited text no. 6
    
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Borgia F, Vaccaro M, Gasco L, Lotti J, Lotti T, Guarneri C. Laser treatment of post-thyroidectomy scar. J Biol Regul Homeost Agents 2017;31:121-9.  Back to cited text no. 7
    
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Khandelwal A, Yelvington M, Tang X, Brown S. Ablative fractional photothermolysis for the treatment of hypertrophic burn scars in adult and pediatric patients: A single surgeon's experience. J Burn Care Res 2014;35:455-63.  Back to cited text no. 11
    
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Sabry HH, Abdel Rahman SH, Hussein MS, Sanad RR, Abd El Azez TA. The efficacy of combining fractional carbon dioxide laser with verapamil hydrochloride or 5-fluorouracil in the treatment of hypertrophic scars and keloids: A clinical and immunohistochemical study. Dermatol Surg 2019;45:536-46.  Back to cited text no. 12
    
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Cavalié M, Sillard L, Montaudié H, Bahadoran P, Lacour JP, Passeron T. Treatment of keloids with laser-assisted topical steroid delivery: A retrospective study of 23 cases. Dermatol Ther 2015;28:74-8.  Back to cited text no. 13
    
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Salah M, Samy N, Fawzy MM, Farrag AR, Shehata H, Hany A. The effect of the fractional carbon dioxide laser on improving minoxidil delivery for the treatment of androgenetic alopecia. J Lasers Med Sci 2020;11:29-36.  Back to cited text no. 14
    
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Sun L, Wang C, Cao Y, Lv X, Tian L, Liu D, et al. Fractional 2940-nm Er: YAG laser-assisted drug delivery of timolol maleate for the treatment of deep infantile hemangioma. J Dermatolog Treat 2020;24;1-7.  Back to cited text no. 15
    
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Badawi AM, Osman MA. Fractional erbium-doped yttrium aluminum garnet laser-assisted drug delivery of hydroquinone in the treatment of melasma. Clin Cosmet Investig Dermatol 2018;11:13-20.  Back to cited text no. 16
    
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