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

Discussion

This is the first study to investigate the clinical outcome of three NAFL treatments all influencing early wound healing phases, starting as early as immediately before surgery. We found a beneficial effect of NAFL treatment compared with untreated controls. A randomized, controlled, blinded, split-wound design was used and scars were evaluated on POSAS, VSS, photo evaluation and patient-reported outcomes. Under these standardized conditions, VSS showed that the NAFL-treated halves appeared statistically significantly improved compared with the control scar halves. The standardized assessment comparing the appearance of the scar halves on site, during photo evaluation, and by the patients demonstrated a low degree of correspondence.

The clinical effect of NAFL treatments was subtle but consistent, as reflected in the primary outcome and the VSS. In specific cases no clinical differences were detected, and in three cases the NAFL-treated halves appeared worse than the untreated controls. On the other hand, we found that patients responded to the NAFL treatment by gaining up to 11 points on POSAS total (range 6–60). This variation may be explained by inter- and intraindividual factors such as scar location, type of scar, individual reaction to NAFL-induced cytokine response and patients' age.

The anatomical region with the best response to NAFL was the thorax (POSAS total, median difference 3, P ≤ 0·001). On the thorax a higher median POSAS total score of 14 was detected for the untreated control halves. Thus, the enhanced effect of NAFL may be explained by either a higher effect on the thorax location or NAFL inducing a better effect on severe scarring. Scars in this study scored low on both the treated (median 11, IQR 9–12) and control halves (median 12, IQR 10–16) on POSAS total, indicating that our study population did not have severe scarring in general. Improvement on a mild scar might be difficult to detect, even on POSAS, and the clinical relevance must be questioned even though the changes were statistically significant. With regard to age, patients aged ≤ 50 years and those aged > 50 years both responded, with improved NAFL-treated scars compared with untreated scars, and thus the NAFL scar improvement did not relate to age.

Various scales have been used in scar evaluation, and VSS is more frequently used than POSAS.[11,12,21–23] However, only a few scar characteristics are examined by VSS and therefore POSAS was added. Not all patients were able to evaluate the stiffness and thickness of their scars on POSAS, as their scars were located on the dorsum of the thorax. Despite the fact that POSAS patient and VAS in many cases are suboptimal evaluation tools, we found them to be the best available methods to capture patients' perceptions of their acquired scars.

Cutaneous infection developed in three of 32 patients (9%) after excision. In the literature reporting on infection in relation to excisions the rate is typically < 5%.[24,25] The higher infection rate in our study may be explained by the fact that the lengths of all three infected scars were longer than the mean scar length (4·9 cm) in this study. Liu et al. found correspondingly that excisions with larger defect size were significantly more at risk of secondary infection.[25] Another factor is age, as the patients with infection in our study were all aged > 75 years. No infections were seen after the second or third NAFL treatment, thus the NAFL treatment in itself was not considered to be the reason for infection. A larger patient group is necessary to gain more reliable safety data.

While most patients rated the treated side as being superior to the control side, 25% favoured the control side. This may be due to the short follow-up time of 3 months, as the full potential of the NAFL-induced remodelling process may not have been reached at this stage. Capon et al. applied diode laser immediately after skin closure and found no significant difference at 3 months of follow-up; in contrast, at the 12-month follow-up the treated scars appeared significantly improved compared with the controls.[10] Thus a 12-month follow-up may reveal greater benefit of the NAFL treatment. All patients recommended the treatment, possibly due to the longer time spent on each patient in a study situation compared with regular consultations.

Particular strengths of this study are the randomized, allocation-concealed, controlled and blinded split-wound study setup with internal controls, an aspect that is unprecedented in the field of early laser intervention to reduce scar formation.[26] Furthermore, the detailed and validated POSAS as the primary outcome measure enabled detection of differences in scar characteristics such as relief, thickness, pliability and overall scar appearance that would have been overlooked by VSS. To explore the effect of early NAFL treatment further, a standardized assessment was done, as presented in Table 5. The low level of agreement in the standardized assessment results may indicate that on-site, photo and patient evaluations focus on different aspects of the scar appearance. Similarly, Zhang et al. concluded, in a recently published review, that subjective and objective scar grading reveal disagreement between patients and clinicians.[27]

The present study further adds that even experienced clinicians disagree when using on-site scar evaluation and photo evaluation, which may be explained by the lack of a three-dimensional effect in two-dimensional photographs, and that pliability is not captured on photographs. Furthermore, the algorithm to provide the final result of the photo evaluation was conservative as the dermatologists had to agree intra- and interpersonally to conclude a difference between the treated and control scar halves. This was mirrored by only eight NAFL-treated scar halves being rated by dermatologists as superior to the corresponding control halves. Additionally, disagreement between objective evaluations and patient evaluation may be explained by the fact that on-site evaluation and photo evaluation were blinded, whereas the patients were not. The results may thus be biased, as reflected by the 21 NAFL-treated scar halves rated superior to the corresponding control scar halves (Table 5). Hence, several confounding factors may account for the low level of agreement between scar assessment on photo, on-site and patient evaluation.

Although this study demonstrated a high standard of methodological quality, it does possess some limitations. We conducted data analysis only on the patients completing the study, which underestimates variability in data. However, using the spilt-wound design, randomization was not affected but simply resulted in a smaller sample size. We deemed it acceptable that data were missing for 6% of patients (two of 32), as this had been accounted for when estimating the sample size. The dropouts were not likely to have influenced the results of the efficacy analysis. Only one blinded evaluator performed the on-site evaluation, and additional evaluators would have strengthened our findings. On the other hand, two independent evaluators were used in the photo evaluation. Furthermore, the patients were not blinded, as a sham laser treatment was not provided on the untreated control wound half. Thus, the patient-reported outcomes may be biased. Lastly, the follow-up time of 3 months is rather short for scar evaluation, as scar tissue undergoes constant remodelling for at least a year after wounding.

We conclude that three NAFL treatments provided in early wound healing may improve scar formation. Although the NAFL-treated wounds did not heal without scarring, the NAFL procedure examined in this study offers a viable contribution to the enigma of scarless healing.

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