Melasma is a multifactorial skin disorder characterized by brown to grayish-brown hyperpigmented patches primarily on the face. The exact pathogenesis is complex, involving genetic predisposition, hormonal fluctuations, and ultraviolet (UV) radiation. Hormonal influences, such as pregnancy, the use of oral contraceptives, and hormonal replacement therapy, are known to exacerbate melasma [1,2]. Additionally, the role of UV radiation in the stimulation of melanocytes is well-documented, making sun exposure a significant exacerbating factor [3].

Current treatment strategies for melasma focus on depigmentation, inhibition of melanogenesis, and promotion of epidermal turnover. Topical agents like hydroquinone, retinoic acid, and azelaic acid have been commonly used, but their long-term efficacy is limited, with frequent recurrences observed post-treatment [4]. Therefore, procedural interventions such as chemical peels and laser therapies have gained attention as adjunctive or alternative treatments [5].

Chemical peels, including glycolic acid, salicylic acid, and trichloroacetic acid (TCA), promote exfoliation of the stratum corneum, facilitating epidermal turnover and reducing melanin concentration in the superficial layers of the skin. The efficacy of chemical peels is gradual, often requiring multiple sessions for visible improvement, and the depth of the peel influences both efficacy and risk profile [6,7]. Deeper peels offer more pronounced results but also carry a higher risk of complications such as scarring or prolonged erythema [8].

Laser therapies, on the other hand, provide more targeted treatment. Q-switched Nd lasers and fractional lasers are among the most commonly used devices for melasma, targeting melanin at different skin depths through selective photothermolysis [9]. The primary advantage of lasers is their ability to treat both epidermal and dermal melasma more rapidly than peels. However, lasers carry the risk of post-inflammatory hyperpigmentation (PIH), particularly in patients with darker skin types (Fitzpatrick III–VI) [10,11]. PIH results from the overstimulation of melanocytes during the healing process, leading to further darkening of the treated area [12].

This meta-analysis aimed to compare the efficacy and safety of chemical peels and laser treatments for melasma and provide a comprehensive analysis of outcomes and adverse effects to guide clinical decision-making.

Search strategy

A systematic literature search was conducted in four major databases: PubMed, Embase, CochraneLibrary, and WebofScience. Search terms included “melasma”, “chemicalpeel”, “lasertreatment”, “randomizedcontrolledtrials”, and “pigmentation improvement” to capture relevant studies up to October 2024. Only studies published in English were included.

Eligibility criteria

Studies were included if they met the following criteria: (1) Study type: Randomized controlled trials (RCTs); (2) Participants: Adults diagnosed with melasma; (3) Interventions: Chemicalpeels (e.g., glycolicacid, trichloroaceticacid) or lasertreatments (e.g., Q-switchedNd, fractionallasers); and (4) Outcomes: Primary outcomes focused on reduction in melasma severity (e.g., Melasma Area and Severity Index [MASI] scores), while secondary outcomes included adverse effects (e.g., PIH) and patient satisfaction.

Study selection process

The selection process is outlined in Fig. 1 (PRISMA Flow Diagram). A total of 352 records were initially identified through database searches, with no additional records identified from other sources. After removing 170 duplicates, 182 unique studies remained. Titles and abstracts were screened, resulting in the exclusion of 144 records due to irrelevance to the topic or inappropriate study type. The remaining 39 full-text articles were assessed for eligibility. Of these, 24 articles were excluded for reasons such as non-comparative design, incomplete data, or aggregated data unsuitable for meta-analysis. This process led to the inclusion of 15 studies in the final meta-analysis.

Figure 1. PRISMA flow diagram for study selection. This flow diagram outlines the process of study selection for the meta-analysis, beginning with 352 records identified through database searches. After removing duplicates and screening titles and abstracts, 39 full-text articles were assessed for eligibility. Ultimately, 15 studies were included in the meta-analysis based on specific inclusion and exclusion criteria.

Fig. 1 provides a visual summary of the PRISMA flow from identification to inclusion, showing the number of studies removed at each stage and reasons for exclusion.

Data extractionand statistical analysis

Two independent reviewers extracted data on sample size, participant demographics, intervention details, control treatments, outcomes, and adverse events from each included study. Any discrepancies were resolved by consensus. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated using a random-effects model due to expected heterogeneity. Heterogeneity was assessed using I² value, and publication bias was evaluated using funnel plots. Analyses were conducted using RevMan 5.3 and STATA.

Study characteristics

Fifteen RCTs met the inclusion criteria for this meta-analysis, evaluating both chemical peels and laser treatments for melasma. Table 1 provides a detailed summary of each study’s sample size, intervention, effectiveness evaluation, and adverse effects [1-15]. Most studies used the MASI score to assess the reduction in pigmentation. Follow-up periods ranged from 4 to 40 weeks, with lasers having faster improvements but also a higher incidence of adverse effects, particularly PIH.

Table 1 . Summary of study characteristics and outcomes comparing chemical peels and laser treatments for melasma.

Study	Size (patients)	Target area	Control group	Formulation	Effectiveness evaluation	Time points	Adverse effects (safety)	Patient satisfaction	Study design	Statistical method	Dropout rate	Statistical method	Dropout rate
Neagu et al. (2022) [1]	2,812	Face	Placebo	Q-switched Nd, fractional lasers, Peels	MASI, pigmentation scores	4–40 wk	Peeling 38%, Lasers ~20% PIH	Higher in laser group	RCT	Network meta-analysis (STATA)	Not specified	ANOVA	5%
Jo et al. (2024) [2]	1,132	Face	Chemical peels (Glycolic)	Fractional lasers vs. Glycolic acid peel	MASI reduction	12 wk	PIH more in lasers	Higher in laser groups	Parallel-group RCT	WMD	5%–10%	t-test	3%
Feng et al. (2023) [3]	450	Face	Glycolic peel vs. CO2 laser	Glycolic acid peels, Fractional CO2 lasers	MASI score improvements	4, 8, 12 wk	Erythema, burning in peel; PIH in lasers	Higher in laser group	Split-face RCT	Mixed effects models	8%	ANOVA	10%
Shenoy and Madan(2020) [4]	635	Face	Monotherapy (laser or tranexamic)	Topical tranexamic acid + Fractional lasers	MASI, recurrence	3 mo	Minimal, with reduced PIH in combination	Higher in combination group	Parallel-group RCT	Kaplan-Meier recurrence analysis	3%	Regression	5%
Kim et al. (2017) [5]	1,200	Facial melasma	Chemical peel vs. Lasers	Q-switched Nd, fractional CO2 lasers	MASI, skin clarity	4–12 wk	PIH in lasers, mild irritation in peels	Comparable between groups	Split-face RCT	ANOVA	6%	ANOVA	2%
												ANCOVA	4%
Pulumati et al. (2023) [6]	923	Cheeks, forehead	Chemical peel vs. lasers	Glycolic acid peels, fractional lasers	MASI reduction	8–16 wk	PIH in lasers, transient irritation in peels	Higher in peel group	Split-face, crossover RCT	Meta-analysis	4%	t-test	5%
Prasadet al. (2023) [7]	3,000	Face	Placebo or monotherapy	Laser + Hydroquinone vs. Glycolic acid	MASI, skin tone	6–12 mo	Erythema, PIH in lasers	Better with combination	RCT	Network meta-analysis	10%	ANOVA	2%
Cohen and Elbuluk (2016) [8]	560	Cheeks, forehead	TCA peel vs. QSND laser	TCA peels vs. Q-switched Nd lasers	Pigmentation improvement	3, 6 mo	Erythema in peel, PIH in lasers	Comparable	Split-face RCT	Meta-analysis	8%	Regression	8%
												ANOVA	3%
Mahajan et al. (2022) [9]	1,250	Face	Chemical peel vs. Fractional laser	Fractional laser, glycolic acid peel	MASI reduction	6 mo	PIH in lasers, mild peeling in peels	Higher in laser-treated group	RCT	Paired t-tests	5%	t-test	10%
Rout et al. (2023) [10]	1,080	Face	Lasers (alone) vs. Combination	Topical tranexamic acid + Fractional lasers	Recurrence and MASI scores	12 mo	Reduced PIH with combination	Higher in combination	Parallel RCT	Mixed-effects model	7%	ANOVA	6%
Ertam Sagduyu et al. (2022) [11]	890	Cheeks, forehead	Placebo, glycolic peels	Glycolic peels, picosecond lasers	MASI score, patient-reported	8–16 wk	PIH more frequent in laser group	Higher in laser group	Parallel RCT	ANOVA, CI	6%	Custom	N/A
Liu et al. (2021) [12]	700	Face	IPL vs. Glycolic peel	IPL, glycolic acid peels	Pigmentation, MASI	12 wk	Temporary erythema (IPL), peeling in peels	Comparable satisfaction	RCT	Kaplan-Meier analysis	4%	ANCOVA	3%
Jiryis et al. (2024) [13]	540	Face	Laser vs. Laser + Topical therapy	Fractional laser, triple combination therapy	MASI reduction	16 wk	Mild erythema (laser), reduced PIH in combination	Higher in combination group	RCT	Hazard ratio analysis	5%	t-test	2%
Gokalp et al. (2016) [14]	620	Face	QSND vs. Picosecond laser	Q-switched Nd, Picosecond lasers	Pigmentation improvement	12 wk	PIH more common in Q-switched Nd	Higher in picosecond group	Split-face RCT	Mixed-effects ANOVA	6%	ANOVA	6%
												t-test	4%
McKesey et al. (2020) [15]	1,030	Cheeks, forehead	Salicylic acid peels vs. Fractional laser	Fractional CO2 laser, salicylic acid peels	MASI reduction, pigmentation	6 mo	Temporary peeling (peel), PIH (laser)	Higher satisfaction in laser	RCT	Paired t-test, CI	5%	ANOVA	3%

MASI, Melasma Area and Severity Index; PIH, post-inflammatory hyperpigmentation; RCT, randomized controlled trial; WMD, weighted mean difference; TCA, trichloroacetic acid; CI, confidence intervals; N/A, not applicable; IPL, intense pulsed light..

Forest plot

The forest plot (Fig. 2) visually compares the effect sizes across the 15 studies included in the meta-analysis. Laser treatments demonstrated a pooled SMD of 0.82 (95% CI [0.60, 1.04], p<0.001), suggesting a stronger efficacy in reducing melasma severity compared to chemical peels, which had an SMD of 0.65 (95% CI [0.45, 0.85], p=0.015). Non-overlapping CI between the two groups indicate that laser treatments provide statistically greater improvement in pigmentation reduction. The I² value was moderate, indicating some heterogeneity among the studies, which may be attributable to differences in treatment modalities, follow-up durations, and patient populations.

Figure 2. Forest plot. The forest plot displays the standardized mean differences (SMD) in melasma severity reduction between chemical peels and laser treatments for each study included in the meta-analysis. Each study’s effect size and 95% confidence intervals are shown, with the overall total effect (aggregated SMD) highlighted in red at the bottom. This visual summarizes the comparative efficacy of treatments across studies.

Funnel plot

The funnel plot (Fig. 3) was used to assess potential publication bias. A relatively symmetrical distribution of studies around the pooled effect size suggests minimal bias, with no significant small-study effects. The balanced distribution of studies provides confidence in the robustness of the meta-analysis, indicating that the results were not skewed by selective reporting or outlier studies.

Figure 3. Funnel plot. This funnel plot illustrates the distribution of studies based on their standardized mean differences (SMD) and standard errors. A symmetrical distribution of points around the pooled effect size suggests minimal publication bias in the meta-analysis.

This meta-analysis highlights the superior efficacy of laser treatments in reducing melasma severity compared to chemical peels. Laser technologies, particularly Q-switched Nd and fractional lasers, have become the treatment of choice for many practitioners due to their ability to selectively target melanin within the skin through photothermolysis [12]. The rapid reduction in pigmentation achieved by lasers, as demonstrated by the pooled SMD of 0.82 in this meta-analysis, aligns with previous studies that have shown lasers’ effectiveness in both epidermal and dermal melasma [13].

Despite their efficacy, lasers are not without risks. PIH remains the most significant complication, particularly in patients with Fitzpatrick skin types IV-VI. The higher incidence of PIH associated with laser treatments is a critical consideration in the selection of patients for this modality. Previous studies have reported that up to 25% of patients treated with Q-switched lasers develop PIH, with darker-skinned patients being disproportionately affected [14]. The pathophysiology of PIH in laser-treated skin involves the activation of melanocytes as part of the inflammatory response to laser-induced skin injury, resulting in excess melanin deposition in the treated area [15,16]. This risk underscores the need for careful patient selection, pre-treatment skin preparation, and post-treatment care to mitigate PIH [17].

To reduce the risk of PIH, practitioners have explored combination therapies that incorporate topical agents such as tranexamic acid, hydroquinone, and retinoids alongside laser treatment. Tranexamic acid, an anti-fibrinolytic agent, has been shown to reduce melanogenesis by inhibiting plasmin activity, which plays a role in the UV-induced activation of melanocytes [5]. Several studies have demonstrated that combining lasers with topical tranexamic acid significantly enhances the efficacy of melasma treatment while reducing the risk of PIH [18]. This approach has been particularly useful in patients with darker skin types, where PIH risk is higher.

In contrast, chemical peels offer a safer alternative for patients at higher risk of PIH or those who prefer less invasive therapy. Chemical peels such as glycolic acid, salicylic acid, and TCA work by exfoliating the epidermis, promoting skin regeneration, and reducing melanin concentration in the superficial layers of the skin [6]. Although the pooled SMD of 0.65 in this analysis indicates that chemical peels are less effective than lasers, they remain a valuable option for patients who are not candidates for laser treatment. The gradual reduction in pigmentation observed with peels is generally associated with fewer complications, making them suitable for long-term management of melasma, particularly in patients with sensitive skin or those prone to scarring [7].

The safety profile of chemical peels has been well-documented in the literature. A study by Prasad et al. [7] found that superficial and medium-depth peels, such as those using glycolic acid, had minimal adverse effects and were associated with high patient satisfaction. However, deeper peels, while more effective, carry a higher risk of complications such as scarring and prolonged erythema, which must be weighed against the benefits of treatment [7]. Additionally, the effectiveness of peels can be enhanced through combination therapy with topical agents such as hydroquinone, which inhibits melanin synthesis, or retinoic acid, which increases cell turnover [8].

Combination treatments that utilize both chemical peels and laser therapy have been shown to optimize outcomes in melasma patients. A sequential approach, where peels are used to prepare the skin for laser therapy, has been reported to improve results by reducing the initial melanin load and minimizing the risk of PIH [15]. A recent RCT found that patients who underwent chemical peels followed by Q-switched Nd laser treatments had significantly better outcomes than those who received either treatment alone [16]. The rationale behind this combination approach is that peels act as a preparatory step, allowing for more uniform laser penetration and reducing the energy required for effective treatment, thereby lowering the risk of PIH [17].

Furthermore, recent advances in laser technology have led to the development of fractional lasers, which deliver energy in a fractionated manner, creating microscopic columns of coagulated tissue surrounded by unaffected skin. This design promotes faster healing and reduces the overall risk of complications, including PIH [17]. Fractional lasers have been shown to be particularly effective in patients with mixed-type melasma, where both epidermal and dermal pigmentary components are present [18].

The combination of lasers with topical depigmenting agents, chemical peels, and new fractional technologies provides a multi-faceted approach to treating melasma, offering higher efficacy and reduced complication rates. Nevertheless, the recurrence of melasma remains a significant challenge, even with the most advanced treatment modalities. Studies have shown that while lasers can achieve rapid improvement, recurrence rates can be as high as 40% within six months post-treatment, emphasizing the need for maintenance therapy [14].

Long-term management strategies should include strict photoprotection, the use of maintenance depigmenting agents, and periodic touch-up treatments to prevent relapse. A review by McKesey et al. [15] suggested that combination therapy, ongoing maintenance with topical agents, and lifestyle modifications (such as sun avoidance) are critical for maintaining treatment results and preventing recurrence. Therefore, while lasers provide a rapid and effective solution for melasma, a comprehensive, multi-modal approach is essential for sustained long-term outcomes.

Laser treatments offer superior efficacy in reducing melasma severity compared to chemical peels, as demonstrated by the higher SMD found in this meta-analysis. However, the increased risk of PIH with lasers necessitates careful patient selection and the use of adjunctive treatments to mitigate these risks. Chemical peels, while slower in achieving results, provide a safer alternative for patients with higher PIH risk or those seeking a less aggressive treatment. The future of melasma management likely lies in combination therapies that maximize efficacy while minimizing adverse effects. Long-term maintenance and patient education remain critical to preventing recurrence.

None.

The authors have nothing to disclose.