Laser Treatments in Early Wound Healing Improve Scar Appearance

A Randomized Split-wound Trial With Nonablative Fractional Laser Exposures vs. Untreated Controls

K.E. Karmisholt; C.A. Banzhaf; M. Glud; K. Yeung; U. Paasch; A. Nast; M. Haedersdal

Disclosures

The British Journal of Dermatology. 2018;179(6):1307-1314. 

In This Article

Patients and Methods

Study Design

A randomized, controlled intraindividual split-wound trial was carried out comparing the clinical appearance of surgical scars vs. untreated control scars after three consecutive NAFL exposures: immediately before excision, at suture removal and 6 weeks after excision. Blinded on-site clinical evaluation of scars was performed 3 months after the last NAFL exposure, supported by photo evaluation and patient evaluation. The study was approved by the Danish Research Ethics Committee (H-17012492) and registered at ClinicalTrials.gov (NCT03253484). All study participants provided written informed consent.

Patients

Thirty-two patients undergoing surgical excision were recruited from the Department of Dermatology, Bispebjerg Hospital, Denmark. NAFL treatments and follow-up evaluations were carried out between June 2017 and January 2018. Included patients were ≥ 18 years of age, had Fitzpatrick skin type I–III, were nonsmokers and were referred for excision with suspicion of either benign, premalignant or nonmelanoma skin cancer lesions. Postoperative wounds were estimated to be a minimum of 2·5 cm in size at any anatomical region. Exclusion criteria were a history of keloid scarring, patients with unstable systemic disease, pregnancy, recent sun exposure or infection in the test area.

Surgical Procedure

Elliptical demarcation was performed with a surgical marker around the lesions before excision. A central 0·5-cm section of each ≥ 2·5-cm-long wound was excluded from evaluation to prevent the NAFL bystander effect on the untreated control side. During the sterile procedure, after local infiltrative anaesthesia, the elliptically demarcated area including the lesion was removed by excision. Subcutaneous sutures were provided with polyglactin 910 (Vicryl, needle 3/8c – FS-2, 70 cm, V422H 4-0 or PS-2, 45 cm, V497H 3-0 – according to anatomical region) and superficial sutures with polyamide 6 (Ethilon, needle 3/8c – FS-2, 45 cm, EH7790H 5-0 or EH7144H 4-0 – according to anatomical region; all Ethicon, Somerville, NJ, U.S.A.). Sutures and sterile strips were distributed equally on each wound half to standardize the impact on the interventional and noninterventional halves. This ensured that the scars were as comparable as possible for evaluation (Figure 1). A drawing on a transparent sheet was used as a template to find the treated side, excluded buffer zone and untreated control side of the scars at each study visit. The surgical wounds were dressed with a dry bandage but no topical agents were applied.

Figure 1.

Study procedure shown for study patient #24. (a) First treatment with nonablative fractional laser (NAFL) immediately prior to surgery. Biological responses were erythema and oedema. The length of the elliptical demarcation was ≥ 2·5 cm. A double-lined 'exclusion zone' prevented the bystander effect of NAFL treatment in the control scar halves. (b) After suturing and bandaging. (c) Two weeks after surgery and immediately after suture removal. (d) Second NAFL treatment immediately after suture removal. Biological responses were erythema, oedema and laser grid. (e) Six weeks after surgery. (f) Six weeks after surgery immediately after the third NAF treatment. Biological responses were erythema, oedema and laser grid. (g) At the 3-month follow-up. t, NAFL-treated scar side; c, untreated control scar side.

Randomization, Concealment and Blinding

At baseline, the two lesion halves were randomized to NAFL treatments or untreated control. The sequence was concealed using consecutively numbered, closed, nontransparent envelopes prepared by a third party to ensure allocation concealment. The treating dermatologist (K.E.K.) was not blinded and was not involved in the evaluation. Outcome evaluation was performed on site by the same blinded trained physician (C.A.B.), on photographs by two blinded, experienced dermatologists (A.N. and U.P.) and by the patients themselves. The full randomization procedure is described in Appendix S1 (see Supporting Information).

Laser Interventions

All laser treatments were performed by the same dermatologist (K.E.K.) using a 1540-nm erbium–glass NAFL (Icon; Cynosure Palomar, Westford, MA, U.S.A.). A combined approach of targeting deep and more superficial skin compartments was achieved using a 15-ms pulse duration with an extra-deep handpiece (XD Microlens) with a spot size of 12 × 12 mm, microbeam density 25 microbeams cm−2, three stacks in two passes of 50 mJ per microbeam; and a superficial extra-fast handpiece (XF Microlens), with a spot size 15 mm in diameter, microbeam density 115 microbeams cm−2 and fluence of 40 mJ per microbeam. Treatment dosages were chosen according to a previous screening study testing the optimal dosages of 1540-nm NAFL for prevention of scar formation.[19] The first NAFL treatment was performed on top of the elliptical demarcation line, avoiding exposing the lesion itself. The second and third treatments were performed with the cicatrix located centrally on the NAFL probe area. A cooling bag was provided after each NAFL treatment.

Outcome Measures

All evaluations were performed at the 3-month follow-up. The primary outcome measure was on-site blinded clinical evaluation using the observer portion of the Patient Observer Scar Assessment Scale (POSAS) to derive a total score for each scar half. The POSAS observer evaluates separate scar components by the following items: vascularity, pigmentation, thickness, surface area, relief, pliability and overall opinion. Each component is assessed on a scale ranging from 1 to 10, where 1 indicates 'normal skin' and 10 represents the 'worst imaginable scar' compared with normal skin at a comparable anatomical site. The calculated sum of the six first items comprises the POSAS total score, ranging from 6 to 60 points (Table 1).[20]

Secondary outcomes comprised the following. Firstly, on-site clinical assessments based on the total Vancouver Scar Scale (VSS). VSS total scores vascularity, pigmentation and height from 0 to 3, and pliability from 0 to 5. A 0 score represents normal skin, while maximum scores indicate the worst possible outcome (scoring 14 on VSS total).

Secondly, a standardized assessment, carried out during on-site and photo evaluation, and evaluation by the patients themselves. The standardized assessment consisted of the following questions: is there a difference between the two scar halves (yes/no)? If 'yes', which side is superior? (Scar half 1 or scar half 2). Clinical photos were obtained under standardized lighting conditions and with the body positioned 40 cm from the camera. A digital camera was used (Canon EOS 60D) with a 60-mm macro objective and flash (Canon Macro Ring Lite MR-14EX; Canon, Lake Success, NY, U.S.A.). Two dermatologists (A.N. and U.P.) evaluated the clinical photos according to the standardized assessment. To avoid intraobserver discrepancy the evaluation procedure was performed twice by each of the two dermatologists and a final result was determined by the following algorithm: if any of the four ratings stated 'no difference' or if there was a mismatch as to which scar half was rated as superior, the final result was determined as 'no difference'.

Thirdly, patient-reported outcomes included POSAS patient (Table 2) (range 1–10; from 1, not at all/normal skin to 10, yes very much/yes very different from normal skin); a visual analogue scale (VAS) (range 0–10 cm; 0 indicating normal skin, 10 maximal scarring) and a questionnaire asking patients if they would recommend the treatment procedure to friends and family. Fourthly, reflectance measurements were recorded (Appendix S1; see Supporting Information).

Statistical Analysis

A sample size of 29 patients provided 90% power to detect a clinical minimal relevant difference of 6 (11% improvement) on POSAS total (range 6–60) with an estimated SD of 7 and a two-tailed significance level of 5%. As a pre-emptive measure against dropout, 32 patients were included. Each scar half was analysed in the group to which it was randomized. Two of the 32 patients dropped out of the study, but as each patient was his or her own control this did not break the randomization. Hence, we performed an intention-to-treat analysis on the primary outcome and no data imputation was needed for POSAS or VSS. A nonparametric test of paired data (Wilcoxon signed-rank test) was used because the data were not normally distributed. Spearman (nonparametric) correlation tests were used. The remaining outcomes were reported with descriptive statistics. SPSS for Windows version 22 (IBM, Armonk, NY, U.S.A.) was used.

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