In Vivo Investigation of the Safety and Efficacy of Pulsed Dye Laser with Two Spot Sizes in Port-Wine Stain Treatment: A Prospective Side-by-Side Comparison

Abstract

Objective: Pulsed dye laser (PDL) with 7 and 10 mm spot sizes is widely used on a regular basis for the treatment of port-wine stain (PWS). Background data: No studies have reported on the differences in efficacy outcomes resulting from the use of different laser spot sizes in the treatment of PWS by PDL. Thus, an in vivo investigation into the differences in safety and efficacy of treatment between two spot sizes (7 vs. 10 mm) of PWS by PDL was conducted. Materials and methods: A total of 35 PWS patients underwent three treatment sessions by using a 595 nm wavelength PDL (Vbeam^®, Candela Corp) with two laser settings: (1) 7 mm spot size, radiant exposure of 12 J/cm² and (2) 10 mm spot size, radiant exposure of 10 J/cm². Cryogen spray cooling and 1.5 msec pulse duration were applied. Therapeutic outcomes were evaluated by visual and chromametric evaluation 3 months after the final treatment. Results: Average blanching rates were 34.03% and 36.51% at sites treated by PDL with 7 and 10 mm laser spot sizes, respectively (p < 0.05). Conclusions: On the basis of the laser setting, the therapeutic outcomes of PDL with 7 and 10 mm spot sizes were similar. PDL with a 10 mm laser spot size is more efficacious with lower radiant exposure than PDL with a 7 mm spot size; it can also reduce the treatment time.

Introduction

Port-wine stain (PWS), a congenital vascular malformation characterized by ectatic capillaries and post-capillary venules in the dermis, occurs in 0.3–0.5% of newborns.¹ The initial stain usually appears as a pink–red flat patch, gradually changing into a darker purple color, even thickening and forming nodules with age.² About 70% of PWS lesions occur in the face and neck and may cause psychosocial and physical problems.³

Pulsed dye laser (PDL) currently represents the mainstream choice for PWS treatment in accordance with selective photothermolysis.^4,5 However, most PWS lesions cannot be removed.⁶ Recent advances in laser technology have led to the development of PDL equipment with various settings for a more refined regulation of the laser beam during PWS treatment: wavelength, pulse duration, spot size, and cooling system.^7,8 PDL with 7 and 10 mm spot sizes is widely used on a regular basis to treat PWS lesions. Regardless of this, no studies have compared the safety and efficacy of PDL with different spot sizes in the treatment of PWS.^9,10 Accordingly, we conducted the current study to investigate the safety, efficacy, and outcomes of PWS treatments by PDL with 7 and 10 mm spot sizes.

This study was approved by the Investigational Review Board at Shanghai Ninth People's Hospital. All patients—minors and adults—provided verbal and informed consent or assent to participate in the study.

Materials and Methods

Subjects

A total of 35 untreated patients with PWS were included in the study. Each of two contiguous test sites of the PWS lesion in the same anatomical region and the same stain color was treated by PDL with 7 and 10 mm laser spot sizes for each patient. Facial anatomic areas were subdivided into several regions in accordance with the method used by Renfro and Geronemus.¹¹ All sites treated by PDL with 7 and 10 mm spot sizes were compared and subdivided into the same anatomical region for each patient. The sites for treatment using Vbeam with a 7 mm spot size and Vbeam with a 10 mm spot size were selected by randomization (Fig. 1): A random sequence software program was used (www.dxy.cn/bbs/topic/21117904) to generate randomized sequences: 1 − xx. Random sequence numbers were then assigned to the patients. The patients assigned with an odd number were treated by using Vbeam with a 7 mm spot size on the left of/above two contiguous test sites; the areas on the right/below the test sites were treated by using Vbeam with a 10 mm spot size. Meanwhile, the patients assigned with an even number received the opposite treatment. (Clinical trial registration number: ChiCTR-OOC-16009700). Patient demographic information is listed in Table 1.

FIG. 1.

Participant enrollment, randomization, and analysis.

Table 1.

Patient Demographics

Patient	Sex	Age	Treatment site of PWS	Skin type
Case 1	M	18 years	Face (lateral aspect of the cheek)	III
Case 2	M	9 years	Face (forehead)	IV
Case 3	F	2 years	Face (temple)	III
Case 4	F	4 months	Neck	III
Case 5	F	2 years	Face (lateral aspect of the cheek)	IV
Case 6	F	4 months	Face (medial aspect of the cheek)	III
Case 7	M	4 months	Face (lateral aspect of the cheek)	III
Case 8	M	6 years	Face (temple)	IV
Case 9	F	3 months	Face (forehead)	III
Case 10	M	13 years	Face (temple)	IV
Case 11	F	2 months	Face (medial aspect of the cheek)	III
Case 12	M	2 months	Face (medial aspect of the cheek)	III
Case 13	M	4 years	Face (temple)	IV
Case 14	M	3 years	Face (lateral aspect of the cheek)	IV
Case 15	F	26 years	Face (lateral aspect of the cheek)	III
Case 16	F	10 months	Face (lateral aspect of the cheek)	III
Case 17	F	1 year	Face (lateral aspect of the cheek)	III
Case 18	F	4 years	Face (medial aspect of the cheek)	IV
Case 19	F	6 months	Face (lateral aspect of the cheek)	III
Case 20	F	8 months	Face (medial aspect of the cheek)	III
Case 21	M	20 years	Neck	IV
Case 22	M	2 years	Face (temple)	IV
Case 23	F	1 month	Face (lateral aspect of the cheek)	III
Case 24	F	2 years	Face (temple)	III
Case 25	M	3 months	Face (temple)	III
Case 26	F	18 years	Face (forehead)	IV
Case 27	M	6 months	Face (medial aspect of the cheek)	III
Case 28	M	2 years	Face (medial aspect of the cheek)	IV
Case 29	F	37 years	Face (forehead)	III
Case 30	M	18 years	Face (lateral aspect of the cheek)	IV
Case 31	F	27 years	Face (lateral aspect of the cheek)	III
Case 32	F	16 years	Face (lateral aspect of the cheek)	III
Case 33	F	23 years	Face (lateral aspect of the cheek)	III
Case 34	F	25 years	Face (chin)	IV
Case 35	M	2 months	Trunk (chest)	III

PWS, port-wine stain.

PDL treatment protocol: Vbeam with a 7 mm spot size

The Vbeam (Candela Corp., Irvine, CA) treatment protocol requires a 595 nm wavelength for PDL with 12 J/cm² radiant exposure, 1.5 msec pulse duration, 7 mm spot size, and cryogen spray cooling (40 msec of cooling with a 20 msec delay).

PDL protocol: Vbeam with a 10 mm spot size

The Vbeam (Candela Corp., Irvine, CA) treatment protocol requires a 595 nm wavelength for PDL with 10 J/cm² radiant exposure, 1.5 msec pulse duration, 10 mm spot size, and cryogen spray cooling (40 msec of cooling with a 20 msec delay).

Follow-up and assessment

All patients underwent three laser treatments of two test treatment sites by using Vbeam with 7 and 10 mm spot sizes at 6-week intervals. Follow-up was conducted 3 months after the final treatment to assess the efficacy of the treatment and color improvement, as well as to observe for side effects. Treatment efficacy was evaluated by chromametric and visual methods.

All test treatment areas were independently measured and assessed, despite their variation among patients. In addition, the test treatment sites for each patient were subdivided into similar anatomical locations to avoid bias attributed to site variation.¹¹

Chromametric assessment

A chromameter (CR-400; Minolta, Japan) was used to assess the change in color at the two test treatment sites independently, before treatment and 3 months after the final treatment. The L*, a*, and b* color system of the International Commission on Illumination or Commission Internationale de l'Eclairage was used for objective assessment of PWS skin.^12,13 The change in color or improvement (ΔE) and the efficacy of color improvement (blanching rate) quantitatively measure efficacy in PWS treatment.

Visual assessment

Standard digital photographs (60D camera; Canon) of each patient were taken before treatment and 3 months after the final treatment. Four plastic surgeons evaluated the color improvement of the lesions in a double-blind manner. The color improvement of the PWS skin was graded as follows: score of 5 (75–100%, excellent); score of 4 (50–75%, good); score of 3 (25–50%, fair); score of 2 (1–25%, poor); and score of 1 (0%, no improvement).¹⁴ The average score was used when the color improvement was scored differently.

Follow-ups on post-treatment responses and side effects were conducted.

Data analysis

SPSS ver. 19.0 (IBM Corporation) and GraphPad Prism 5 (GraphPad Software, Inc.) were used to analyze the therapeutic outcomes. For visual and chromametric assessment, the differences in efficacy outcomes of PDL with 7 and 10 mm spot sizes were compared and analyzed by using the Wilcoxon signed-rank test. Spearman's rank correlation coefficients were also used to compare the efficacy outcomes from the chromametric and visual evaluations for PDL with 7 and 10 mm spot sizes. p Value ≤0.05 was considered statistically significant.

Results

Patient information

A total of 35 patients with untreated PWS, consisting of 15 Asian men and 20 Asian women aged 1 month to 37 years (mean age = 8 years), participated in this study. The patient skin types according to the Fitzpatrick Skin Type were type III in 22 (63%) patients and type IV in 13 (37%) patients. No hypertrophic lesion was observed. PWS was observed in the facial region of 32 (91%) patients, neck region of 2 (5.7%) patients, and trunk of 1 (2.9%) patient. Patient information is summarized in Table 1.

Efficacy outcomes

Skin color assessment (ΔE, blanching rate) by chromametry

The ΔE and blanching rate were measured before treatment and 3 months after the third treatment and then compared. The average ΔEs for the sites treated by PDL with 7 and 10 mm spot sizes were 8.62 (SD = 4.43) and 8.73 (SD = 5.09), respectively (p = 0.635) (Fig. 2A). The average blanching rates for the sites treated by PDL with 7 and 10 mm spot sizes were 34.03% (SD = 32.65%) and 36.51% (SD = 30.05%), respectively (p = 0.719) (Fig. 2B). These results indicate no difference in efficacy outcome between PDL with a 7 mm spot size and PDL with a 10 mm spot size.

FIG. 2.

ΔE (color improvement) was measured pre-treatment and 3 months post-treatment. ΔE was calculated by: \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6} \begin{document}$$\Delta E = \sqrt {{{ ( \Delta L^* ) }^2} + {{ ( \Delta a^* ) }^2} + {{ ( \Delta b^* ) }^2}}$$ \end{document} The average ΔE was calculated as 8.62 (SD = 4.43) for sites treated by PDL with 7 mm spot size and 8.73 (SD = 5.09) for sites treated by PDL with 10 mm spot size (p = 0.635) (A). The blanching rate (efficacy of color improvement) was measured pre-treatment and post-treatment. The Blanching rates were calculated according to: Blanching rate = (1 − ΔE after treatment/ΔE before treatment) × 100 (%). The average blanching rate of the PWS was 34.03% (SD = 32.65%) for sites treated by PDL with 7 mm spot size and 36.51% (SD = 30.05%) for sites treated by PDL with 10 mm spot size (p = 0.719) (B). Scores of color improvement by visual evaluation for sites treated by PDL with 7 and 10 mm spot size. The mean score for color improvement of PWS lesions was 3.26 (SD = 0.97) for sites treated by PDL with 7 mm spot size and 3.17 (SD = 1.01) for sites treated with 10 mm laser spot size (p = 0.831) (C). Comparison of efficacy outcomes between chromameter and visual evaluation; the Spearman's rank correlation coefficient was 0.488 (p ≤ 0.001) (D). PDL, pulsed dye laser; PWS, port-wine stain.

Visual assessment

The mean scores for color improvement of PDL with 7 and 10 mm spot sizes were 3.26 (SD = 0.97) and 3.17 (SD = 1.01), respectively (p = 0.831). These results indicate that PWS treatment by PDL with both 7 and 10 mm spot sizes exhibits similar efficacy levels in improving the lesion color (Fig. 2C).

Relationship between visual and chromametric assessments

The Spearman's rank correlation coefficient was 0.488 (p ≤ 0.001) for the comparison of efficacy outcomes between the chromametric and visual evaluations for all treatment sites. This finding indicates no difference between the visual and chromametric assessments of the effectiveness of PDL with 7 and 10 mm spot sizes at the tested sites (Fig. 2D).

Photographs of representative patients with PWS from the group whose lesions were localized to the facial region and treated by PDL with 7 and 10 mm spot sizes are shown in Figs. 3 –5; the photographs were taken before treatment, immediately after treatment (to examine the immediate purpura responses), and 3 months after final treatments.

FIG. 3.

Patients with untreated facial PWS, before treatment (A). Three months after final treatment, there was similar efficacy of color improvement between the sites treated by PDL with the 7 mm spot size (120% radiant exposure than 10 mm) and the sites treated by PDL with the 10 mm spot size site (B).

FIG. 4.

FIG. 5.

Side effects

Edema and purpura developed in all (100%) and 33 (94%) patients, respectively, at the sites treated with 7 and 10 mm laser spot sizes. Crusting and blistering occurred in 10 (29%) and 2 (5.7%) patients at the sites treated with 7 and 10 mm laser spot sizes, respectively. No patient developed pigmentation change, infection, scarring, or atrophy at either test site.

Discussion

At present, PDL systems are regarded as the gold standard for the treatment of PWS lesions in accordance with selective photothermolysis. Recent technological advances have led to an increase in the availability of choices in spot size, pulse duration, and epidermal cooling system. PDL systems with either 7 or 10 mm laser spot size are widely used for PWS treatment, and numerous studies on PWS treatment by PDL have been previously reported.^15
–17 In the current study, each of the 35 patients was treated by PDL with both 7 and 10 mm laser spot sizes. The outcomes of these treatments were compared.

Visual and chromametric assessments provided subjective and objective evaluations, suggesting a similarity in color improvement between sites treated by PDL with 7 and 10 mm spot sizes (which had higher and lower radiant exposure, respectively). The blanching rate of PWS with PDL treatment ranged from 1.38% to 66.68%. This variation in blanching rates may be attributed to the heterogeneity of blood vessel size in PWS in various patients.^18

–21

Reinisch proposed the use of variously sized beams to limit penetration into the dermis. By using the spot size arguments, the properties of spots can be used to change the behavior of particular wavelengths in the skin. For instance, a 1064 nm laser can be used to heat progressively larger depths of skin by increasing the spot size (Fig. 6).²²

FIG. 6.

The size of laser spot size affected the depth of penetration. 0.5 mm laser spot size (A), 1.0 mm laser spot size (B), 2.0 mm laser spot size (C), with 1064 nm laser.

δ is the optical penetration depth for homogeneously absorbing layers (such as tissue water for IR applications), and δ represents the diameter of the particle. Generally, the spot size should be 3–4x > δ, as larger spots increase the probability of photons scattering back into the incident collimated beam.²³ Photons that are scattered out of the beam are essentially wasted. Traveling “alone,” they carry insufficient energy to cause macroscopic thermal responses in tissues. The consequences of spot size are explained as follows. For small beams (narrow), scattered photons are carried out of the beam path after only a few scattering events. A good analogy is a highway with exits. With a narrow highway, any movement obliges the car to “take” the exit, and the car does not return to the road. Meanwhile, on a superhighway with many lanes, cars can move about and stay within the original boundary of the thoroughfare. Only cars on the extreme left and right are likely to “get” off the road. Large spots increase the dermal/epidermal damage ratio as well as the relative penetration depth. Therefore, absolute epidermal damage will be greater with the larger spot with the same fluence as the smaller spot. For PWS treatment, the radiant exposure can be reduced by 20% when a larger spot size is used, because the large spot size generates larger amounts of heat. A clinical example of the effect of spot size is illustrated by Goldman,²⁴ who found that for 3 mm versus 6 mm spots with the Nd:YAG laser, roughly half the fluence is required with the larger spot for leg vein clearance.

Thus, in our study, PDL with the 10 mm spot size using low radiant exposure (10 J/cm², 1.5 msec) acquired efficacy and safety outcomes similar to those of PDL with the 7 mm spot size using high radiant exposure (12 J/cm², 1.5 msec). The larger spot size can provide uniform transmission of energy to treat lesions, increase therapeutic efficacy, and shorten treatment time for PWS.

The limitations of this study include the following: (1) The study included a limited number of subjects; (2) follow-up was conducted 3 months after the third treatment (longer follow-ups were lacking in this study); and (3) three sessions of laser treatment using two spot sizes were conducted (this number of treatments is too low to effectively compare the two spot sizes).

Conclusions and Summary

In summary, this study provides preliminary data of PWS treatment by PDL with 7 and 10 mm laser spot sizes that exhibited high and low radiant exposures, respectively. The outcomes of these treatment were compared. In addition, their safety and efficacy were evaluated. Thus, in our study, PDL with a 10 mm spot size, which has low radiant exposure (10 J/cm², 1.5 msec), obtained blanching efficacy and safety similar to that of PDL with a 7 mm spot size, which has high radiant exposure (12 J/cm², 1.5 msec: 120% of the radiant exposure of the 10 mm spot size). PDL using optimal laser parameters with the 10 mm spot size may provide efficacy and safety during treatment and shorten the process.

Footnotes

Acknowledgments

This study was supported by the Shanghai Health System Important Disease Joint Research Project (Grant No. 2013ZYJB0014).

Author Disclosure Statement

No competing financial interests exist.

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