Treatment Of Melasma Research Articles

Efficacy of Subdermal Poly-d,l-Lactic Acid Injections for the Treatment of Melasma.

Melasma is a chronic, recurrent skin disorder with limited long-term treatment success using conventional therapies like hydroquinone and laser treatments, which primarily target epidermal components while leaving dermal aspects untreated. To evaluate the efficacy and safety of poly-d,l lactic acid (PDLLA) subdermal injections for treating moderate melasma. Three female patients (age range: 45-59 years) with Fitzpatrick skin types III and IV received three PDLLA injection sessions at 3-week intervals. Treatment outcomes were assessed using the Melasma Area and Severity Index (MASI) and patient satisfaction scores at 12-week follow-up. All patients showed significant MASI score improvements (reduction range: 3.60-6.30 points). Patient satisfaction ratings ranged from 3 to 4 out of 4. Temporary side effects included mild edema and bruising, resolving within 72 h. PDLLA subdermal injections showed promising results in melasma treatment, potentially due to its biostimulatory effects on collagen production and dermal remodeling. Further research, including histopathological analysis, is needed to confirm long-term efficacy and safety, and understand underlying mechanisms.

Glutathione as a skin-lightening agent and in melasma: asystematic review.

Hyperpigmentary disorders, including melasma, are challenging to treat. Glutathione has anti-melanogenic and antioxidant properties, which led to its use as a skin-lightening agent. Our objective was to review the published evidence and literature on the efficacy and safety of glutathione as a skin-lightening agent and in the treatment of melasma. A literature search was done in the PubMed, Embase, and Cochrane library databases using the search terms "glutathione as a skin-lightening agent" and "glutathione in melasma" for the past 10 years. The level of evidence, strength of recommendation, and risk of bias assessment were evaluated. Among various forms of topical glutathione, glutathione 0.5% was significantly more effective compared to glutathione 0.1% and placebo. For glutathione alone versus glutathione plus microneedling, more improvement was seen. Five randomized controlled trials and a single open-arm clinical study on oral glutathione at doses of 250 mg once a day, 250 mg twice a day, and 500 mg once a day showed a significant reduction in the melanin index compared to placebo. The combination of topical 2% glutathione plus oral glutathione was superior to monotherapy alone. There was only one placebo-controlled study on intravenous (IV) glutathione [6/16 (37.5%) vs. 3 (18.7%), (p0.054)]. The risk of bias assessment showed that almost an equal number of studies have low and high risk of bias. Topical versus oral glutathione both provide moderately efficacious skin-lightening outcomes that are localized versus generalized and have minimal versus substantial adverse effects, but they are unsustainable, with variable costs. IV glutathione is contraindicated due to lack of efficacy and side effects. It may work more as an antioxidant in melasma.

Latin American consensus on the treatment of melasma.

Melasma is a chronic, relapsing hyperpigmentation disorder that primarily affects photoexposed areas, occurring most frequently in adult women with darker skin phototypes. The primary factors contributing to its development include sun exposure, sex hormones (e.g., pregnancy), and genetic predisposition. Melasma is highly prevalent in Latin America, where many countries lie in intertropical zones and exhibit significant ethnic diversity because of centuries of intermixing among Native Americans, Europeans, and Sub-Saharan Africans. Nine Latin American experts formulated a DELPHI-based consensus to develop a valuable approach for treating melasma in this diverse population. After establishing an accurate diagnosis, assessing the impact on quality of life, and determining disease severity, the consensus recommends mitigating known triggers and promoting rigorous photoprotection. Active therapy should be tailored based on individual characteristics (e.g., pregnancy status, previous treatments, skin sensitivity). Treatment options include topical depigmenting agents, systemic therapies, and procedural interventions such as laser therapy, microneedling, and chemical peels. Periodic reassessment of the treatment is essential, with strategies adjusted if targeted outcomes are not achieved. Once clinical remission is attained, patients should continue using topical depigmenting agents and maintain strict photoprotection measures to prevent recurrence.

Efficacy of Microneedle as an Assisted Therapy for Melasma: A Meta-analysis and Systematic Review of Randomized Controlled Trials.

Melasma is a common hyperpigmentary disorder, it has variety of treatment options, but it usually has a poor curative effect and high recurrence rate. Microneedles have shown certain prospects in the treatment of melasma as an assisted therapy, but there is no consensus on its efficacy and safety. To evaluate the efficacy and safety of microneedles as an adjuvant treatment for melasma. Statistical tools were used to adjust the improvement of MASI scores in all studies to obtain standardized mean differences (SMD), and then, meta-analysis were performed. Risk ratio (RR) was utilized to assess adverse reactions, clinical effectiveness, and patient satisfaction. The effects of microneedle-assisted treatment for melasma begin to manifest at the 4th week, with optimal results observed at the 24th week, and with a high patient satisfaction. Compared with oral medication alone, microneedle-assisted therapy began to be more effective at week 12 and continued by 24weeks. Compared with laser therapy alone, microneedle-assisted therapy also showed stronger efficacy, at the 8th week, microneedle-assisted treatment was significantly more effective, reaching its peak at the 12th week. Finally, in the comparison of microneedle and microinjection therapy, microneedle has always been more significant than micro-injection. Microneedle is a valuable adjunctive therapy for melasma treatment. It enhances long-term clinical outcomes compared to monotherapy and is associated with high patient satisfaction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Melasma Revisited: National Survey Reveals How Dermatologists Diagnose and Treat This Complex Skin Condition.

Melasma is a chronic condition characterized by dark patches on the facial skin. It has a known female gender dominancy, and women usually think of melasma as being a serious cosmetic problem. Treatment of melasma can be seriously challenging, thus, dermatologists may employ different approaches for melasma. This study aimed to investigate how dermatologists diagnose and treat patients with melasma and to present the general characteristics of patients with melasma. A survey was conducted using Google Forms targeting dermatologists in Turkiye. A total of 199 dermatologists (142 females/57 males) participated in the study. Most of the participants (52.3%) were residents. Majority gender of the patients was female and most common age range of patients with melasma was 30-40 years. Mixed melasma was the most common type (57.4%). Malar region was the most frequent location (58.6%). Wood's lamp examination was used by 25.6% of the participants. Topical treatment was the first-line choice for melasma therapy (95%), with Kligman's formula being the most used topical agent (69.8%). Oral therapy was not used by 70.8% of the participants. Tranexamic acid was the first choice for oral treatment (23.4%). Only 24.9% of the dermatologists used laser/light therapy, and Q-switched Nd-YAG laser was the most preferred device (58%). The most common recurrence rate was 41%-60% (45.9%). The findings of the current study investigating the melasma management in Turkiye revealed a female predominance and peak prevalence in the 30-40 years age group. Kligman's formula is the preferred topical treatment, whereas oral tranexamic acid remains underutilized. Recurrence rates are high, highlighting the need for preventative strategies. This study emphasizes the importance of personalized approaches and ongoing research for effective melasma management.

Combined Efficacy of Q-Switched 785 nm Laser and Tranexamic Acid Cream in the Treatment of Melasma: A Prospective Clinical Study

Background and Objectives: Melasma, a hypermelanotic dermatologic condition that mainly affects women, poses challenges due to its complex etiology involving environmental and genetic factors. Its pathophysiology, marked by intricate histological changes, is not fully understood. This study explored the efficacy and safety of a new 785 nm picosecond laser in treating facial melasma. Materials and Methods: An 11-participant cohort, comprising women with Fitzpatrick phototypes II-III, underwent a treatment protocol with a new 785 nm picosecond laser. The clinical evaluation used the Global Aesthetic International Score (GAIS) and the Five-Point Likert Scale Questionnaire. The aim of the study was to understand the capacity of the 785 nm wavelength laser to interact with both the pigmentary and vascular components of melasma. Results: The GAIS outcomes revealed excellent (18.2%), good (54.5%), poor (18.2%), and no results (9.1%). The Likert Scale responses varied from very satisfied (18.2%) to slightly satisfied (9.1%). Clinical images at three months demonstrated resolution of melasma with no adverse events. Conclusions: This non-invasive procedure showed positive outcomes and high patient tolerance, emphasizing its potential in melasma management. However, in order to fully understand the interactions of pigmentary and vascular components with the 785 nm wavelength laser, further research is required. The small cohort represents a limitation for this study, therefore studies that include a larger number of patients are needed to assess the effectiveness of this laser treatment for facial melasma.

Evaluation the efficacy of microneedling with topical metformin solution compared with microneedling with topical vitamin C solution in treatment of melasma.

Several treatment modalities have been used for the treatment of melasma. Topical metformin is an anti-diabetic drug, which has melanopenic action. Vitamin C acts on melanin by inhibiting the tyrosinase enzyme, thus inhibiting melanogenesis. To compare the efficacy and safety of microneedling combined with topical metformin solution versus microneedling combined with topical vitamin C in the treatment of melasma. A spitted-face interventional comparative on 30 female patients suffering from melasma. The right side of the face was treated with microneedling and topical metformin, while the left side was treated with microneedling and topical vitamin C solution. Hemi-MASI score decreased significantly after treatment from before treatment in both groups P-value < 0.001. The percentage of improvement of Hemi-MASI score metformin group was 48.29%, While with vitamin C group was 37.19%. There was a significant improvement in dermoscopic findings in microneedling with topical metformin than with topical vitamin C group. Microneedling with topical metformin or topical vitamin C solution can be an effective and safe therapeutic option for treating melasma with no significant side effects.

Potential Molecular Mechanisms of Danggui-Shaoyao-San in the Treatment of Melasma Based on Network Pharmacology with Molecular Docking

Although Danggui-Shaoyao-San (DSS) is frequently used in China to treat melasma, its underlying mechanism still needs to be better understood. Our aim is to determine the mechanism behind DSS in treating melasma through network pharmacology (NP). The DSS active compounds alongside corresponding target genes are identified by accessing the TCMSP database and SwissTargetPrediction. Melasma-associated targets are retrieved from the GeneCards, DisGeNet, Durgbanks, OMIM, and TTD databases. Next, we build a component-target association network via Cytoscape software while generating a protein-protein interaction network utilizing the STRING database. Subsequently, both core target genes and active compounds are determined. Through the DAVID database and Bioinformatics tools, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses are conducted. Lastly, the CB-Dock2 server is deployed to conduct molecular docking (MOD). The results manifest that alisol B, cerevisterol, and Wallichilide, among others, are active compounds in DSS, while PTGS2, ESR1, and ESR2 are core target genes. Both GO and KEGG analyses showcase that the potential core drug components modulate pathways in cancer, chemical carcinogenesis-receptor activation, calcium, relaxin, and estrogen signaling by exerting their effects on biological processes. These processes include negative gene expression regulation as well as positive regulation of both cytosolic calcium ion concentration and transcription from the RNA polymerase II promoter, thereby playing an anti-melasma pharmacological role. The MOD displays that core target genes have good binding activity with the active compounds. To conclude, NP demonstrates that DSS can serve as an innovative medication for treating melasma.

Melasma removal using Q-Switched Neodymium-doped Yttrium Aluminium Garnet laser toning and high-intensity focussed ultrasound.

To evaluate the effectiveness of combining high-intensity focussed ultrasound and a Q-switched neodymium-doped yttrium aluminium garnet 1064nm low-fluence toning laser in the treatment of melasma. The experimental study was conducted from November 2020 to August 2021 at the medical physics laboratory, College of Medicine, Mustansiriyah University, Baghdad, Iraq, and comprised individuals of either gender aged >25 years having mixed form melasma in malar and forehead areas. Each participant received high-intensity focussed ultrasound treatment on the right side. After 2 weeks, Q-switched neodymium-doped yttrium aluminium garnet 1064nm low-fluence toning laser was applied to the melasma patches 4 times at one-week intervals. Melasma area and severity index scores were noted at baseline and at each visit for each patient. Visual analogue scale was used for objective evaluation. After the 4 laser sessions, all the patients completed a 3-month follow-up. Data was analysed using SPSS 24. Of the 25 subjects, 15(60%) were females and 10(40%) were males. The overall mean age was 41.6±8.46 years (range: 22-60 years). There was a significant improvement with high-intensity focussed ultrasound (p<0.05). In the 3rd laser session, there was a significant difference in melasma area and severity index score of 2.48 for the right side and 3.12 for the left side (p<0.05). In the 4th session, there was a significant difference in melasma area and severity index score of 1.68 for the right side and 2 for the left side (p<0.05). No post-inflammatory hyperpigmentation or rebound was noted. High-intensity focussed ultrasound combined with toning laser was more effective than Q-switched neodymium-doped yttrium aluminium garnet 1064nm low-fluence laser alone in removing difficult melasma from the malar area in the 2nd, 3rd and 4th sessions, and from the forehead in the 3d and 4th sessions.

Optical Coherence Tomography as a Diagnosis-Assisted Tool for Guiding the Treatment of Melasma: A Case Series Study.

Background/Objectives: Multiple underlying pathomechanisms may lead to melasma, but there has been no report on the use of optical coherence tomography (OCT) to reveal specific pathomechanisms in individual patients and provide individualized treatments accordingly. Using real-time OCT images, we studied the pathomechanisms of melasma in 12 female patients and the effects of individualized treatments. Methods: Patients were divided into good and bad improved groups according to the improvement in hyperpigmentation at month 4. Results: In the bad improved group, all melanin or confetti melanin had significantly decreased at month 2 or month 4 while granular melanin ratio at month or month 4 significantly increased, the most parameters of dendritic-sharped cells (DCs) before and after treatment were not significantly different, the collagen area or collagen density at month 4 significantly decreased. In the good improved group, there was slightly low all melanin/confetti melanin at month 4 and high granular melanin at month 4 in comparison to the bad improved group. Moreover, most of the parameters in the DCs at month 4 significantly increased while most parameters in collagen at month 4 significantly decreased. Conclusions: OCT is useful in revealing the involved pathomechanisms of melasma in individualized patients. Positive treatment results can be achieved through individualized therapy regimen targeting the pathomechanisms.

Nano-vesicular systems for melanocytes targeting and melasma treatment: In-vitro characterization, ex-vivo skin retention, and preliminary clinical appraisal

Melasma represents an acquired melanogenesis disorder resulting in skin’s hyperpigmentation effect. Although several approaches are adopted for melasma treatment, nanotechnology presents the most convenient one. Therefore, the present work aimed to formulate and characterize three nano-vesicular systems namely, liposomes, penetration enhancer containing vesicles (PEVs) and invasomes to enhance the topical delivery of the skin whitening agent; alpha arbutin (α-arbutin) for the treatment of melasma. Liposomes were prepared according to a 23 full factorial design and the selected formula was further employed for the preparation of PEVs and invasomes. Results showed that the three vesicular systems exhibited nano-sizes ranging from 151.95 to 672.5 nm, negative charges ranging from −12.50 to −28.20 mV, high entrapment efficiencies ranging from 80.59 to 99.53 %, good stability and prolonged-release of α-arbutin for 24 h after dispersion in hydrogel form. The deposition study from the vesicular hydrogel confirmed their effectiveness for the drug’s accumulation in the skin reaching an average of 1.6-fold higher in the stratum corneum, 1.6–1.8-fold higher in the epidermis, and 1.6–1.8-fold higher in the dermis compared to the free drug dispersion in hydrogel. A preliminary clinical split-face study on patients suffering from melasma revealed that α-arbutin-loaded liposomes and PEVs in hydrogel forms showed better clinical outcomes compared to the free α-arbutin hydrogel as well as to the previously published α-arbutin encapsulated in chitosan nanoparticles and dispersed in hydrogel form. This delineates the aforementioned nano-vesicular systems as effective and clinically superior delivery means for melasma management.

Energy-based methods and nanocarrier-based approaches for melasma treatment

Melasma is a chronic disease caused by excessive melanin production in the skin, affecting the quality of life, especially in women. As a kind of skin hyperpigmentation, it can be caused by sun exposure, genetics, hormones, drugs, or inflammation. Melasma treatment can be effective when the product penetrates well into the skin. As an essential skin barrier, the stratum corneum displays a significant role in topical and transdermal drug delivery. In this regard, numerous strategies have been developed to increase the skin permeability and efficiency of drugs. This review explores energy-based methods and nanocarrier-based approaches for melasma treatment, focusing on enhancing drug delivery to the viable epidermis and overcoming SC. Physical methods have some advantages like increasing the skin penetration and also some drawbacks, including frequent visits, high costs, and the need for advanced equipment and trained operators. Further, these methods are often combined with high energy and special technics. As an emerging physical-based method that could be used to treat patients with multiple medications, microneedle patch is drawing interest due to its ease of use, ability to pinpoint drug delivery, and fewer side effects. In addition, they can penetrate drug molecules into deeper layers of skin and provide more sustainable results compared to conventional methods. Nanocarrier-based systems like transferosome and ethosome (deformable liposomes) are also effective options for skin penetration and treating melasma and skin hyperpigmentation. Despite several benefits, such as high entrapment efficiency, good permeation, and increased bioavailability of drugs through the skin, their stability problems and limitations toward nanoparticle production on an industrial scale are the most significant drawbacks of this method. In the current review, we looked at the articles published between 2010 and August 2023 on energy-based methods and nanocarriers-based approaches have been used to treat melasma.

Topical Ascorbic Acid Mesotherapy with Microneedling versus Topical Tranexamic Acid Mesotherapy with Microneedling for Melasma: A Therapeutic Comparative Study

Background &amp; objectives: Melasma is a common skin hyperpigmentation syndrome that frequently includes reproductive-aged females, and numerous therapies with various consequences have been suggested. Thus, the objective was to compare the microneedling and mesotherapeutic effects of ascorbic acid versus tranexamic acid for melasma treatments. Methods: This interventional therapeutic prospective study was conducted on 40 patients with melasma at Khabat Consultation Center for Skin Diseases, Sulaimaniyah, Iraq, from March 2022 to August 2022. Sociodemographic data of patients were collected together with a family history of melasma using a well-designed questionnaire. Half of the patients were treated with ascorbic acid, while the rest were treated with tranexamic acid using a derma pen. Results: Highly significant reduction of MASI score were seen before and after treatment (p&lt;0.001) were seen in mean scores before and after treatments for both types of treatments (ascorbic acid and tranexamic acid). Moreover, ascorbic acid results in the highest mean score reduction in skin type III (p=0.746), while tranexamic acid results in the highest mean score in skin type IV (p&lt;0.05). Furthermore, the dermal melasma recorded the highest mean score, and the lowest level was observed in the epidermal melasma for both ascorbic acid and tranexamic acid groups. No significant difference was found between both studied groups in sociodemographic data and other studied variables (family history, skin type, previous treatment, and duration of melasma). Conclusions: Both types of therapy mesotherapy was effective in treating melasma; however, their potencies varied on different skin types and according to melasma types.

Patterns and Motivations of Topical Steroid Use for Skin Whitening in Jazan, Saudi Arabia: A Cross-Sectional Survey.

Background The use of topical steroids for skin whitening is prevalent in many regions, including Saudi Arabia. This study aims to analyze the patterns, motivations, and demographic factors associated with the use of topical steroids for cosmetic purposes in Jazan, Saudi Arabia. Methods This cross-sectional survey was conducted online over three weeks. A structured questionnaire was distributed to adults residing in Jazan, collecting data on demographics, topical steroid use, motivations, and product sources. Descriptive statistics were used to analyze the data. Results Among the 340 participants, 173 (50.9%) reported using topical steroids for skin whitening. The majority of users were female (149, 43.8%) and aged between 20 and 30 years (78, 22.9%). Most participants had used topical steroids for less than a year (127, 73.4%), with usage predominantly in the evening (86, 49.7%). Topical steroids were primarily purchased from pharmacies (70, 40.5%), with significant monthly expenditure variability: 55 participants (31.8%) spent between 50 and 110 SAR, and 62 (35.7%) spent more than 150 SAR. Motivations for use included a preference for lighter skin (49, 28.4%) and treatment of melasma (42, 24.3%). Recommendations from friends (71, 41.0%) and TV advertisements (34, 19.8%) influenced product choice. Conclusion Topical steroid use for skin whitening is widespread among adults in Jazan, with a notable emphasis on cosmetic outcomes and substantial financial investment. There is a critical need for increased public education on the risks associated with topical steroids and enhanced professional guidance to promote safer usage practices.

52891 Preliminary Evaluation of the Efficacy and Safety of Leukocyte-Poor Platelet-Rich Plasma in the Treatment of Melasma in Asian Patients

52891 Preliminary Evaluation of the Efficacy and Safety of Leukocyte-Poor Platelet-Rich Plasma in the Treatment of Melasma in Asian Patients

53756 An effective multimodal dermocosmetic approach in the treatment of melasma

53756 An effective multimodal dermocosmetic approach in the treatment of melasma

51821 Isobionic-amide/cysteamine complex : A novel skin depigmenting combination for the treatment of melasma

51821 Isobionic-amide/cysteamine complex : A novel skin depigmenting combination for the treatment of melasma

53726 Melasma treatment by intradermal injection with botulinum toxin A: A split-face randomized, double-blind, placebo-controlled trial and in vitro study of its anti-melanogenic effect

53726 Melasma treatment by intradermal injection with botulinum toxin A: A split-face randomized, double-blind, placebo-controlled trial and in vitro study of its anti-melanogenic effect

Comparison of platelet-rich plasma efficacy with and without photoactivation in melasma: A randomized double-blind study.

Photoactivation has been suggested to enhance the efficacy of platelet-rich plasma (PRP) in conditions other than dermatological diseases. To evaluate the efficacy of photoactivated PRP (P-PRP) treatment for melasma by comparing it with non-photoactivated, classical PRP (C-PRP). The study consisted of 38 female patients diagnosed with melasma between April 2022 and May 2023. The patients were randomized into the P-PRP and C-PRP groups. Three sessions of P-PRP or C-PRP were applied to the patients at 2-week intervals. The Melasma Area and Severity Index (MASI) and Melasma Quality of Life Index (MELASQoL) scores were compared before and 2 weeks after treatment. The median age was 38 years, and the median disease duration was 60 months. Clinically, 94.7% of the cases were centrofacial and 5.3% were malar. According to Wood's lamp examination, 55.3% of the cases were epidermal, 13.2% were dermal, and 31.6% were mixed-type. The median pre- and post-treatment scores were 14.5 and 9, respectively, for MASI and 36.5 and 17, respectively, for MELASQoL. The post-treatment MASI and MELASQoL scores of both groups significantly decreased (p < 0.001 for both). However, the intergroup difference was not significant. When all patients were evaluated together a moderate, positive, and significant relationship was detected between PRP and the pre- and post-treatment MASI and MELASQoL scores (r = 0.494 and p = 0.002). No side effects associated with PRP were observed. PRP is an effective and safe treatment method for melasma. Further studies are needed to evaluate the contribution of photoactivation to PRP treatment in melasma.

Mechanisms of Selected Cassipourea Metabolites for Melasma Treatment: Network Pharmacology and Molecular Dynamics Study

Background Melasma is a common dyschromia, mainly found in women with darker skin types. Although asymptomatic, melasma significantly impacts patients’ quality of life. Due to this complex pathogenesis, melasma is difficult to treat. Plant and plant-derived products have been explored as alternatives for the treatment of melasma. Methods This study utilized network pharmacology coupled with molecular docking and molecular dynamics simulations to investigate the molecular mechanisms of three selected Cassipourea metabolites in the treatment of melasma. Results Of the 202 genes obtained from the 14 profiled metabolites, only PTGS2, TYR, ESR2, and ESR1 were common among metabolites and targets implicated in melasma. From this, The gene ontology highlighted the intracellular steroid hormone receptor, signalling pathway, macromolecular complex, and estrogen receptor activity as the top enriched functional annotations, while the KEGG pathway analysis identified five signalling pathways, from which the prolactin signalling pathway, endocrine resistance, and estrogen signalling pathway were implicated in the pathogenesis of melasma. These pathways were further connected by their linkage to ESR2 and ESR1., Of all Cassipourea metabolites and standards, with afzelechin having the highest docking score for both gens. Further binding interaction analysis showed that ESR2-bound tamoxifen had the highest binding free energy of -47.68 kcal/mol, however, among the interacting Cassipourea metabolites, sitosterol-glycoside exhibited the highest negative binding affinity for both ESR2 (-40.50 kcal/mol) and ESR1 (-78.97 kcal/mol) over 150 ns simulation, suggesting its potential as a dual modulator. Altogether, the metabolites presented remarkable binding stability and thermodynamic compactness with the apo-genes. Conclusion The finding that the selected Cassipourea metabolites are associated with the genes and enzymes implicated in melasma pathogenesis, together with their significant binding effects on the enriched genes, suggests their regulatory potential on the profiled targets and, consequently, in the treatment of melasma.