Efficacy and Safety of Low-Fluence 730-nm Picosecond Laser in the Treatment of Melasma in Chinese Patients

Supplemental Digital Content is Available in the Text.

Abstract

BACKGROUND

The 730-nm picosecond laser has shown promise in treating various benign pigmentary conditions, and it is yet to be determined whether it is effective and safe for melasma.

OBJECTIVE

The aim of this study was to investigate the potential benefits and risks of using the 730-nm picosecond laser to remove melasma.

MATERIALS AND METHODS

This is a retrospective review of all patients who presented to the clinic between April 2021 and April 2022 for the treatment of melasma with 730-nm picosecond laser alone. The efficacy of the laser was assessed based on the Melasma Area and Severity Index (MASI) score using high-resolution photographs evaluated by blinded dermatologists.

RESULTS

A total of 25 Chinese with Fitzpatrick skin Type II to IV were included. Patients were treated for an average of 3.56 ± 0.77 treatment sessions. The mean MASI scores decreased by 33.7% from 11.38 ± 6.60 to 7.55 ± 6.08 at an average of 8.48 ± 2.16 weeks of follow-up (p < .001). Among the patients, 1 experienced a 79% decrease, 6 had a decrease ranging from 51% to 75%, 10 had a decrease ranging from 26% to 50%, 5 had a decrease of less than 25%, and 3 experienced no changes in MASI scores. No hyper/hypopigmentation was observed.

CONCLUSION

Low-fluence 730-nm picosecond laser is an effective and safe modality for the treatment of melasma in Chinese patients.

Melasma is an acquired, chronic, and recurrent pigmentary disorder characterized by brown macules of variable darkness on sun-exposed areas of the body. Hyperpigmentation, caused by an excessive deposit of melanin in the epidermis or dermis, typically occurs on the forehead, cheeks, nose, and upper lip. Melasma is more commonly found in women, especially those with Fitzpatrick skin phototypes III to V.¹ The etiology of melasma is complicated and unclear. Multiple factors, such as genetics, UV rays, pregnancy, exogenous hormones, and the use of hormonal contraceptives, may be involved.² Various treatments have been used for melasma, such as topical hypopigmentation agents, oral tranexamic acid, chemical peels, Q-switched (QS) nanosecond lasers, and intense pulsed light (IPL). However, these treatments often have limited effectiveness and can even cause hyperpigmentation.³

Recently, picosecond lasers with pulse durations operating at subnanosecond domain were introduced. Picosecond lasers could destroy the target chromophore more effectively by greater photomechanical or photoacoustic effect with less undesirable heat diffusion into surrounding normal tissues such as the epidermis. This is because of the short pulse width, which is much less than the thermal relaxation time of melanosomes. Ho and colleagues demonstrated that a shorter pulse is more efficient for the same amount of laser energy, implying that lower fluence can be used for pigmented lesions treatment by using picosecond pulse lasers. Lower fluence can also reduce collateral damage to the epidermis.^4–8 Less epidermal thermal injury suggests fewer side effects, especially postinflammatory hyperpigmentation (PIH), which is considered to be the main adverse effect after laser-based or light-based treatments of benign pigmented disorders. In the past few years, some researchers have reported treating melasma with low-fluence 1,064-nm (with pulse durations of 750/450 ps) or 755-nm (with pulse durations of 750/700/650/600/550 ps) picosecond laser, showing improvements without PIH.^9–12 These findings suggest that picosecond lasers can be used in the treatment of melasma.

A novel 730-nm picosecond titanium sapphire laser with a pulse duration of 246 ps has recently become commercially available.¹³ This laser modality shows promise in treating melasma due to its superior melanin absorption compared with the 1,064-nm and 755-nm lasers, as well as its appropriate penetration depth and shorter pulse duration. In this study, the authors report the first use of low-fluence 730-nm picosecond laser for melasma treatment.

Materials and Methods

Study Design

This study was a retrospective analysis conducted on patients who received 730-nm laser treatment for melasma at the clinic between April 2021 and April 2022. Informed consent was obtained from all patients before treatment. The study adhered to the principles of the 1975 Declaration of Helsinki. The exclusion criteria for this study included a recent history (within the past 3 months) of using topical or oral medications such as hydroquinone (HQ), azelaic acid, tranexamic acid, tretinoin, triple combined cream, vitamin C, or undergoing laser/IPL treatment. In addition, patients who received combination treatment with other energy devices (such as other lasers, IPL, or radio frequency devices) or topical/oral medications for melasma were excluded from the study. High-fluence 730-nm picosecond laser treatment for freckles or lentigines that overlapped with melasma lesions, which could increase the risk of rebound hyperpigmentation, was also considered an exclusion criterion. Patients who were pregnant or lactating during the study period and those who did not have baseline or follow-up digital photography for evaluation were excluded from the analysis.

Laser Treatment

The 730-nm picosecond laser, which was used in this study, is a separate handpiece attached to a Nd:YAG laser device (Picoway; Candela Medical, Marlborough, MA). It has a pulse duration of 246 picoseconds with spot sizes of 2, 3, and 4 mm. The energy of the laser ranges from 0.6 to 1.0 J/cm² when using the 4-mm spot size. The therapeutic end points were defined as mild erythema without petechiae or whitening. Single-pass treatment without pulse overlap was administered initially. If the desired end points were not achieved, a second pass with higher fluence could be given. It is important to note that the use of high-fluence 730-nm picosecond laser for the treatment of freckles and lentigines can result in immediate whitening, which is a notable difference from using low fluence.

Before each treatment session, a topical anesthetic agent consisting of 5% lidocaine was applied to the treatment area and left on for 30 minutes. Standardized digital photography (Thinkview; BOSE Electronic, Co., Wuhan, China) was taken at baseline, before each treatment session, and at each subsequent visit. A cold air cooling device (COOL8; ADSS Development, Co. Ltd., Beijing, China) was used to relieve patients' burning sensation and pain during laser treatment. After the procedure, medical cooling masks were used to aid in recovery. Finally, patients were advised to protect themselves from ultraviolet radiation and to use sunscreens with a sun protection factor of more than 30 and a PA rating of more than +++ after each treatment.

Assessment of Responses and Complications

The patient’s medical records were reviewed to extract relevant data. The information collected in this study included the treatment age, skin type based on the Fitzpatrick scale, use of topical/oral medications and other energy devices, spot size, fluence, repetition, number of treatment sessions, interval of treatment sessions, follow-ups, and digital photographs at baseline and follow-ups. The high-resolution digital photographs of the subjects at baseline and follow-ups were collected and deidentified by the treating dermatologist. Two blinded dermatologists independently assessed the randomized deidentified photographs according to the Melasma Area and Severity Index (MASI; see Supplemental Digital Content, Table S1, http://links.lww.com/DSS/B507), an outcome measure developed by Kimbrough–Green and colleagues.¹⁴ Adverse events such as erythema, edema, pain, blistering, crusting, purpura, petechia, or itching were extracted from patients' records. Scarring, hyperpigmentation, or hypopigmentation were evaluated by observing the photographs.

Statistical Analysis

Statistical analysis for this study was conducted using IBM SPSS Statistics for Windows (version 22.0; IBM, Corp., Armonk, NY). Descriptive statistics were used to present continuous variables as mean ± SD, while categorical variables were presented as percentages. The minimum and maximum values for continuous variables were also included. To evaluate the significance of differences before and after the treatments, a paired Student t-test was performed. The statistical testing was 2-sided and conducted with a confidence level of 95% (α = 0.05).

Results

Demographics

A total of 106 patients were treated with low-fluence 730-nm picosecond laser. Of those, 2 patients were excluded because they received 1,064-nm picosecond laser treatment for melasma less than 3 months before the study. Sixty-five patients were excluded due to other laser/IPL devices or medicine treatment for melasma during the study. Four patients were excluded because they received high-fluence 730-nm picosecond laser treatment for freckles or solar lentigines located on melasma lesions that may lead to rebound hyperpigmentation and mislead the efficacy and safety evaluation. In addition, 10 patients were excluded because of lack of follow-up photography (see Supplemental Digital Content, Figure S1, http://links.lww.com/DSS/B503, Selection of study population). These 10 patients did not return to the clinic after only 1 treatment session. Subsequent telephone follow-up revealed that these patients considered the treatment results acceptable and did not report any worsening of pigmentation. However, it was discovered that the patients were residing in provinces far away from the clinic and were reluctant to incur the high expenses associated with transportation and travel to the clinic for taking photographs.

Table 1 summarizes the demographics of the 25 included patients. All the patients were female, with 22 of them having Fitzpatrick skin Type III (88%). The treatment parameters for melasma lesions included a spot size of 4 mm, a frequency of 6 Hz, and a fluence of 0.6 to 0.7 J/cm². A maximum of 2 passes were conducted per treatment session. The mean number of treatment sessions was 3.56 ± 0.77 (range 3–5), with a mean interval of 7.72 ± 2.70 (range 4–13) weeks and a mean follow-up time of 8.48 ± 2.16 (range 4–13) weeks.

TABLE 1.

Demographics

Variable (n = 25)	Value
Sex (F/M)	25/0
Age (yr), mean ± SD (min–max)	40.56 ± 6.02 (31–53)
Fitzpatrick skin type, n (%)
II	1 (4)
III	22 (88)
IV	2 (8)

Efficacy Analysis

A statistically significant improvement in melasma was observed after 3.56 ± 0.77 treatment sessions, as evidenced by a decrease in the average MASI scores from 11.38 ± 6.60 to 7.55 ± 6.08 (p < .001; Figure 1). The degree of improvement varied among the patients, with 1 (4%) patient achieving excellent improvement, showing a 79% reduction in the MASI score. Furthermore, 6 (24%) patients experienced a 51% to 75% decrease in MASI scores, while 10 (40%) patients had a decrease of 26% to 50%. Only 5 (20%) patients had a reduction of less than 25%, and 3 (12%) patients showed no change in MASI scores before and after treatment (see Supplemental Digital Content, Figure S2, http://links.lww.com/DSS/B504, The patient numbers displaying any level of MASI scores decrease post-treatment). Please refer to Figure 2 (see Supplemental Digital Content, Figure S3, http://links.lww.com/DSS/B505, Melasma in a 35-year-old woman, baseline and post-treatment figures) for representative photographs of lesions before and after treatment.

Figure 1.

The mean Melasma Area and Severity Index (MASI) scores before and after low-fluence 730-nm picosecond laser treatment. The mean MASI scores decreased by 33.7% from 11.38 ± 6.60 to 7.55 ± 6.08 after an average of 3.56 ± 0.77 treatment sessions (*p < .001).

Figure 2.

Melasma in a 33-year-old woman. (A–C) Baseline; (A′–C′) 9 weeks post-treatment after 5 treatment sessions (730 nm, 0.6 J/cm², 4 mm, 1 pass); the Melasma Area and Severity Index (MASI) score decreased by 79% from 8.4 to 1.8.

Safety Analysis

All patients experienced mild pain with the use of topical numbing and cold air cooling device. Immediately after the treatment, there was mild erythema (see Supplemental Digital Content, Figure S4, http://links.lww.com/DSS/B506, Immediate mild erythema following laser treatment), which resolved within 24 hours. No pigment darkening, superficial crusting, purpura, scarring, blistering, hyperpigmentation, or hypopigmentation were observed.

Discussion

Prior studies^6,9–12,15 (see Supplemental Digital Content, Table S2, http://links.lww.com/DSS/B508, Summary of Different Picosecond Lasers Studies in Melasma Treatment) have shown that treating melasma with different picosecond lasers, such as 755, 1,064 and 595 nm, was both effective and safe.

A prospective randomized split-face controlled trial conducted by Choi and colleagues¹⁵ recruited 39 Asian patients to compare the efficacy and safety of 1,064-nm and 595-nm picosecond lasers combined with HQ and HQ only. The results showed that after 6 laser treatment sessions, the reduction of mMASI scores on the side treated with laser was found to be superior to the side treated with HQ only. Moreover, no cases of mottled hypopigmentation or rebound hyperpigmentation were reported during the 7-week follow-up visit.

In another split-face study conducted by Lee and colleagues,¹⁰ the efficacy of the 755-nm picosecond laser and QS nanosecond Nd:YAG laser in treating melasma in Asian individuals was compared. After 4 treatment sessions, it was observed that the side of the face treated with the 755-nm picosecond laser showed greater clearance at the 3-month follow-up compared with the side treated with the QS nanosecond laser. Importantly, no instances of dyspigmentation or PIH were observed during the study.

It is important to note that in all the studies mentioned above,^6,9–12,15 the clinical end point used was mild erythema rather than whitening. This indicates that the lasers' fluence was relatively low when compared with those used for the treatment of freckles or solar lentigines.

The recently developed 730-nm picosecond laser with a pulse duration of 246 ps has been shown to be effective and safe in the treatment of benign pigmentary lesions, including freckles, solar lentigines, and nevus of Ota.^16–19 Kauvar and colleagues¹⁹ conducted a histologic analysis to compare the differences between 730-nm picosecond laser and 755-nm nanosecond laser in clearing lentigines. Treatment of lentigines with the 730-nm picosecond laser resulted in vacuolar degeneration of the lower layer of epidermal keratinocytes and papillary dermal vacuoles, along with congested vessels, mild red blood cell extravasation in the upper dermis, and a moderate superficial perivascular lymphocytic infiltrate. However, the treatment with the 755-nm nanosecond laser led to extensive vacuolar degeneration of the lower layer of epidermal keratinocytes coalescing to form intraepidermal vesicles, dermal–epidermal clefting, a sparse superficial perivascular lymphocytic infiltrate, and mild extravasation of erythrocytes in the upper dermis. These histopathologic findings suggested that the 730-nm picosecond laser produces excellent selectivity for pigment with minimal disruption of the dermal–epidermal junction, which may reduce healing times and the risk of adverse events. With the specificity of better melanin absorption compared with the 1,064-nm and 755-nm lasers, as well as proper penetration depth and shorter pulse duration, the 730-nm picosecond laser holds promise in melasma treatment. The 730-nm picosecond laser shows potential for treating melasma due to its superior melanin absorption, appropriate penetration depth, and shorter pulse duration compared with the 1,064-nm and 755-nm lasers.^6,9–12,15

The aim of this study was to analyze the efficacy and safety of the 730-nm picosecond laser in treating melasma. The study results demonstrate that low-fluence 730-nm laser may deliver significant cosmetic benefits in the treatment of melasma with a very low risk of PIH. In this study, the authors found that melasma improved significantly after 3 to 5 treatment sessions (3.56 ± 0.77), aligning with the results reported by Lee and colleagues,¹⁰ Hong and colleagues,¹² and Choi and colleagues.¹⁵ The number of treatment sessions was significantly lower than that reported by Kung and colleagues⁶ and Lee and colleagues,⁹ who reported 8 to 9 and 6 to 14 treatment sessions, respectively. In this study, the average interval was 7.72 ± 2.70 weeks, lasting between 4 and 13 weeks. This interval was significantly longer compared with the 1-week to 2-week intervals seen in the studies by Lee and colleagues,⁹ Hong and colleagues,¹² and Choi and colleagues.¹⁵ Longer treatment intervals improve patient compliance and affordability.

During the follow-up period of this study, which lasted 8.48 ± 2.16 weeks and ranged from 4 to 13 weeks, no instances of PIH were observed, and any initial erythema subsided within 24 hours after the treatment. The treatment was well-tolerated without any downtime, with mild pain and mild erythema. These findings strongly support the safety of this treatment modality.

On the follow-up day, all 25 patients underwent additional treatments that could potentially affect the assessment of efficacy and safety. These treatments included IPL for skin rejuvenation and QS nanosecond Nd:YAG laser for skin tone improvement. Because of the impact of these alternative treatments, it was not feasible to extend the follow-up period for these patients.

Despite the overall significant decrease in the average MASI scores post-treatment, it is noteworthy that 5 patients exhibited less than a 25% decrease in MASI scores, and 3 patients did not experience any decrease at all. This highlights the necessity for a more effective therapy to address these specific cases.

When interpreting the results of this study, it is important to consider several weaknesses. First, the retrospective nature of the study led to heterogeneity in treatment sessions, intervals, and follow-up times. Second, the sample size was small. Third, there was no control group included in the study. Finally, the follow-up periods were not long enough to adequately assess the recurrence rate of melasma, which is prone to relapse. To provide more credible evidence on the efficacy and safety of the 730-nm picosecond laser in the treatment of melasma, further prospective randomized controlled clinical trials with larger sample sizes are required. However, despite these limitations, the study still provides inspiration for laser therapy as it is the first study to use the 730-nm picosecond laser in treating melasma.

Conclusion

The study results suggest that the low-fluence 730-nm picosecond laser is an effective and safe modality for the treatment of melasma in Chinese patients. No instances of hypopigmentation or hyperpigmentation were observed. However, to establish a conclusive understanding of the role of this laser in melasma treatment, further prospective, randomized controlled clinical studies with larger scale are warranted.

Supplementary Material

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