Characteristics of dermal vascularity in melasma and solar lentigo.

BACKGROUND /PURPOSE: Melasma and solar lentigo (SL) are major benign hyperpigmented lesions, and both have been shown to involve the dermal vasculature. This review discusses current knowledge regarding the clinical characteristics of dermal vascularity in melasma and SL, as well as the results of relevant molecular biological investigations. METHODS: PubMed and Google Scholar were searched in December 2023 to identify articles related to melasma, SL, and the dermal vasculature in these lesions. RESULTS: Vascular morphologies in melasma and SL have been detected by histological and non-invasive methods, including modalities such as optical coherence tomography. Biological studies have indicated that factors secreted from vascular endothelial cells, such as stem cell factor and endothelin-1, can promote melanogenesis. With respect to phototherapy, blood vessel-targeting laser treatments are expected to provide long-term suppression of pigmentation, but this regimen is only effective when dilated capillaries are visible. CONCLUSION: In both melasma and SL, clinical and experimental investigations are revealing the contributions of dermal vascularity to hyperpigmentation. More effective treatment may require identification of hyperpigmentation subtypes. In the future, knowledge of treatment (including phototherapy) is expected to accumulate through reliable and validated non-invasive measurements.

Does Systemic Metformin Have a Role in Treating Melasma?

BACKGROUND: Melasma is a common pigmentary condition that affects the patients' quality of life and all the prescribed treatment options till now are not satisfactory, especially in dark-skinned patients. OBJECTIVE: To evaluate the efficacy and safety of systemic metformin (1,000 mg and 500 mg) combined with trichloroacetic acid (TCA) peeling versus TCA alone in the treatment of melasma. PATIENTS AND METHODS: The study included 60 melasma patients divided into 3 groups: Group A received systemic metformin (1000 mg/d), Group B received systemic metformin (500 mg/d) and Group C received placebo. The 3 treatment groups were treated by TCA 25% over the whole face bimonthly for a total of 6 sessions. Melasma area and severity index (MASI), and Melasma impact Quality of life Scale (MELASQOL) were used to assess the outcome. RESULTS: There was a statistically significant decrease in the MASI, and the MELASQOL in the 3 studied groups after treatment with significantly better improvement in Group (A) than Group (C) ( p = .045). CONCLUSION: Systemic metformin is a safe and promising therapeutic option for treating melasma.

Chemical Peels for Melasma: A Systematic Review.

BACKGROUND: Melasma is a common chronic, relapsing pigmentary disorder that causes psychological impact. Chemical peels are a well-known therapeutic modality used for accelerating the treatment of melasma. OBJECTIVE: To review the published evidence on the efficacy and safety of chemical peels in the treatment of melasma. METHODS: A systematic review was done. A meta-analysis could not be done due to the heterogeneity of data. RESULT: The authors conducted a PubMed search and included prospective case series of more than 10 cases and randomized controlled trials (RCTs) that have studied the safety and/or efficacy of chemical peel in melasma. Out of 24 studies, 9 were clinical/comparative trials and 15 were RCTs. The total sample size was 1,075. The duration of the study varied from 8 to 36 weeks. Only 8 studies were split face. All studies used self-assessment, physician global assessment, and Melasma Area and Severity Index (MASI) for quantifying the results. Glycolic acid was found to be the most safe and effective in melasma. CONCLUSION: Chemical peels were found to be safe and effective in the management of melasma.

Review of Fractional Nonablative Lasers for the Treatment of Dermatologic Conditions in Darker Skin Phototypes.

BACKGROUND: Fractional nonablative lasers (NAFLs) have demonstrated efficacy and safety for treating dermatologic conditions in patients with darker skin phototypes. Nonablative lasers are preferred in darker skin tones due to lower risk of postinflammatory hyperpigmentation. OBJECTIVE: This review aims to identify the ideal laser options and parameters for treating common dermatologic conditions in patients with skin types IV-VI. MATERIALS AND METHODS: A comprehensive literature search was conducted on PubMed in May 2023. Of 1,065 articles were identified, and 40 articles met the inclusion criteria. The studies were classified based on design, dermatologic condition, and skin phototype of patients, and assigned levels of evidence according to the Modified Criteria of the Oxford Center of Evidence Based Medicine. RESULTS: Strong level 1 evidence supports the treatment of melasma and atrophic scars using NAFL. Moderate level 2 evidence was found for using NAFL in acne vulgaris, striae, and skin rejuvenation; 45% of the studies examined skin types III-IV, 20% III-V, 7.5% II-IV, 5% II-V, 5% IV alone, and 2.5% I-IV. CONCLUSION: Further research is needed to determine the optimal treatment modalities and parameters for skin types V and VI. Appropriate device selection and conservative treatment settings are crucial for optimizing outcomes and minimizing adverse events.

Definition of refractory melasma and its treatment: a review.

Although patients with refractory melasma have been treated using various methods, there is still no precise definition or summary of the therapies. To define refractory melasma and conduct a review of the treatments, we searched for relevant publications in PubMed, Web of Science, and the Cochrane Library, and a total of 35 references were obtained. Refractory melasma can be roughly defined as an ineffective treatment for melasma, including topical bleaching agents, chemical peels, laser therapy, microdermabrasion for more than six months, or chemical peels treated more than six times. Meanwhile, physicians should be careful when treating patients with darker skin and dermal or mixed types of melasma since these individuals do not respond well to treatment. Lasers combined with other methods, especially different types of lasers or topical agents, are considered more effective than monotherapy. Oral tranexamic acid (TXA) is a prospective cure for refractory melasma. Other methods include a combination of chemical peels, microneedling, or injections with additional therapies. In conclusion, we were able to provide a rough definition of refractory melasma and list the available therapies. According to the literature, the most prevalent treatment is laser combination therapy. However, laser treatment should be considered only after topical agents and chemical peeling have failed. Considering its side effects, efficacy, and safety, oral TXA may be a better option, but more research is needed to make a firm conclusion. Moreover, maintenance therapy is required after treatment.

755-nm picosecond laser plus topical 20% azelaic acid compared to topical 20% azelaic acid alone for the treatment of melasma: a randomized, split-face and controlled trial.

PURPOSE: Melasma remains a refractory skin condition that needs to be actively explored. Azelaic acid has been used for decades as a topical agent to improve melasma through multiple mechanisms, however, there is a lack of research on its combination with laser therapy. This study evaluated the effectiveness of isolated treatment with topical 20% azelaic acid and its combination with 755-nm picosecond laser in facial melasma patients. METHODS: A randomized, evaluator-blinded, controlled study was conducted on 30 subjects with facial melasma in a single center from October 2021 to April 2022. All subjects received topical 20% azelaic acid cream (AA) for 24 weeks, and after 4 weeks, a hemiface was randomly assigned to receive 755-nm picosecond (PS) laser therapy once every 4 weeks for 3 treatments. Treatment efficacy was determined by mMASI score evaluations, dermoscopic assessment, reflectance confocal microscopy (RCM) assessments and patient's satisfaction assessments (PSA). RESULTS: Treatment with 20% azelaic acid, with or without picosecond laser therapy, significantly reduced the hemi-mMASI score (P < 0.0001) and resulted in higher patient satisfaction. Improvements in dermoscopic and RCM assessments were observed in both sides of the face over time, with no difference between the two sides. RCM exhibited better dentritic cell improvement in the combined treatment side. No patients had serious adverse effects at the end of treatment or during the follow-up period. CONCLUSION: The additional use of picosecond laser therapy showed no clinical difference except for subtle differences detected by RCM assessments.The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100051294; 18 September 2021).

Disorders of hyperpigmentation. Part II. Review of management and treatment options for hyperpigmentation.

Key challenges in the management of pigmentary disorders such as melasma and postinflammatory hyperpigmentation are their resistance to treatment, tendency to recur after treatment, and the risk of exacerbating hyperpigmentation with many treatment modalities. The second article in this 2-part continuing medical education series on pigmentary disorders focuses on the evidence behind medical and procedural treatments of dyschromias, including photoprotection, topical lightening agents, oral agents, chemical peels, and laser therapy.

A novel treatment for Riehl's melanosis targeting both dermal melanin and vessels.

BACKGROUND/PURPOSE: Riehl's melanosis is a difficult-to-treat condition characterized by persisting dermal hyperpigmentation. This study aimed to evaluate the efficacy of a histology-specific targeted therapy for Riehl's melanosis. METHODS: Skin biopsy samples of Riehl's melanosis were assessed to identify histology-specific targets for treatment. Subsequently, the efficacy of a combination involving a fractional picosecond laser and a pulsed dye laser (PDL) targeting the dermal melanin and vessels, respectively, was evaluated. Clinical improvement was assessed using the dermal pigmentation area and severity index (DPASI). The treatment outcomes were compared to those of a control, in this case a single laser treatment solely targeting pigmentation. RESULTS: Histological and immunohistochemical analyses identified dermal melanin pigment and dilated vessels as treatment targets for Riehl's melanosis. The combined treatment of the fractional picosecond laser and PDL showed a significant reduction of the DPASI scores, which was significantly better than the control group. Patients who underwent the combined laser treatment indicated high levels of satisfaction with no adverse events except of transient erythema and oedema. CONCLUSION: The combined treatment of a fractional picosecond laser and a PDL was more effective for Riehl's melanosis compared to single laser treatment. The treatment targets both dermal pigmentation and dilated vessels, offering promising results for those working to manage Riehl's melanosis.

The 675-nm wavelength for treating facial melasma.

BACKGROUND: Melasma is an acquired skin problem. It characterises sun-exposed areas, particularly on the face, with irregular borders and bilateral distribution. With this study, we want to strengthen the scientific literature regarding the use of a 675-nm laser device for the treatment of women and men with facial melasma pigmentary and vascular symptoms. MATERIALS AND METHODS: Eighteen patients were treated for facial melasma. A total of three sessions at 30-day intervals were performed with a 675-nm laser device. A five-point Global Aesthetic Improvement Scale was used to separately assess the improvement of the patient's skin 3 months after the last treatment (T1) compared to baseline (T0). The pain during treatment was measured using a Visual Analog Scale of 10 points. The non-ablative laser system used emits red light with a wavelength of 675 nm through a 13 × 13 mm scanning system. RESULTS: At T1 , a consistent improvement in the pigmentary and vascular components was visible. This is always combined with a considerable reduction in vascular expression. CONCLUSION: Our research shows that individuals with Fitzpatrick phototypes II to III can treat facial melasma with the 675-nm laser source system without risk. Due to its interaction with melanin, collagen and haemoglobin chromophores, as well as its excellent capacity to penetrate tissues with less heating, this system is promising in the treatment of pigmentary and vascular illnesses such as melasma. The great success of the technology we used came from the reduced levels of inflammation produced after the treatments and the low energy level implied.

Stem cell-derived exosomes in the treatment of melasma and its percutaneous penetration.

BACKGROUND AND OBJECTIVES: Melasma is a refractory skin disease due to its complex pathogenesis and difficult treatment. Studies have found that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) could serve as a novel cell-free therapeutic strategy in regenerative and esthetic medicine. It could potentially treat melasma, but the skin barrier is a challenge. In this study, we aim to explore the safety and efficacy of hUCMSC-Exos in the treatment of melasma and the means to promote its percutaneous penetration. MATERIALS AND METHODS: In the animal study about the effect of penetration, percutaneous penetration of PKH67-labeled hUCMSC-Exos was studied under microneedles, 1565 nm nonablative fractional laser (NAFL), and a plasma named Peninsula Blue Aurora Shumin Master (PBASM) treatments, observed by confocal laser scanning microscopy. In the clinical application study, 60 patients with melasma treated in our department were divided into four groups. NAFL combined with normal saline treatment was used for Group A. Microneedles, NAFL, and PBASM combined with hUCMSC-Exos treatments were used for Groups B, C, and D, respectively. Each patient received four treatments at 1-month intervals. Assessments were done using the degree of pain posttreatment, melasma area and severity score, improvement rate, physician global assessment score, satisfaction, and complications. RESULTS: In the animal study about the effect of penetration, hUCMSC-Exos can penetrate the deep dermis under microneedles, NAFL, and PBASM treatments. In the clinical application study, compared with Group A, Groups B, C, and D showed significantly improved therapeutic effect and patient satisfaction (p < 0.05), and there was no significant difference among Groups B, C, and D.(p > 0.05). Patients in Group B reported higher pain levels than those in the other three groups (p < 0.05); the treatment experience of patients in Group D was better. CONCLUSION: hUCMSC-Exos can improve the symptoms of melasma safely and effectively. Compared with microneedles, NAFL and PBASM can also achieve a good effect toward promoting penetration. These findings are worthy of exploration and clinical application.

Efficacy and Safety of Low Fluence Nd:YAG Laser Treatment in Melasma: A Meta-Analysis and Systematic Review.

BACKGROUND: Low-fluence, multisession therapy of Nd:YAG laser has been widely used for treating melasma. OBJECTIVE: To evaluate the efficacy and safety of low-fluence Nd:YAG laser toning for melasma using a systematic review and meta-analysis. METHODS: The PubMed, Web of Science, Embase, and Cochrane Library databases were searched till December 2020. A total of 50 studies (1,772 patients) and 66 studies were selected for the evaluation of the efficacy and complications, retrospectively. RESULTS: The mean Melasma Area and Severity Index/modified Melasma Area and Severity Index scores for laser toning as monotherapy at <4, 4 to <8, 8 to <12, 12 to <24, and ≥24 weeks after treatment compared with that at pretreatment were -0.51, -0.91, -0.97, -0.92, 0.01 SD, whereas those as combination therapy were -1.64, -1.26, -0.94, not available, -1.45 SD, respectively. An increase in light value and a decrease in relative lightness index have remained up to 8 weeks after laser toning. Complications including hypopigmentation/leukoderma, postinflammatory hyperpigmentation, and recurrence were noted. The incidence of hypopigmentation/leukoderma correlated with the number of laser sessions (p = .036). CONCLUSION: Low-fluence Nd:YAG laser toning as combination therapy has shown better efficacy than monotherapy and the efficacy seems to diminish with time. This study suggests the positive correlation of hypopigmentation/leukoderma with the number of laser sessions.

Trichloroacetic Acid With Microneedling Versus Trichloroacetic Acid Alone for Treating Melasma.

BACKGROUND: Melasma is a common acquired disorder of hyperpigmentation which is difficult to treat. OBJECTIVE: We aim to evaluate the efficacy and safety of combined microneedling with trichloroacetic acid in the treatment of melasma. PATIENTS AND METHODS: Forty women with facial melasma were included and randomly classified into 2 groups. Group A included 20 patients treated with bimonthly session of trichloroacetic acid 25% peeling (8 sessions) combined with a monthly session of microneedling (4 sessions). Group B included the other 20 patients that were treated by bimonthly trichloroacetic acid 25% peeling session (8 sessions) alone. RESULTS: After 1 and 3 months of treatment, the mean melasma area and severity index, modified melasma area and severity index, and melasma severity index scores showed significant improvement in each group (p < .05 for each). At 1 and 3 months, the mean percentages of change of all scores were significantly higher in group A than group B (p < .05). CONCLUSION: Combined trichloroacetic acid peel with microneedling is effective and a safe option for treating melasma.

Efficacy and Safety of Picosecond Laser in the Treatment of Melasma: A Network Meta-analysis.

BACKGROUND: The role of lasers in the treatment of melasma and acquired hyperpigmentation disease of the skin has been suggested by clinicians. However, there is no consensus on the most efficient and safe treatment method. OBJECTIVE: To systematically evaluate the efficacy and safety of picosecond laser in the treatment of melasma. METHODS AND MATERIALS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese scientific journal database, and Wanfang database were searched. The data for therapeutic efficacy, melasma area and severity score, and incidence rate of adverse reactions were extracted from the included studies. RESULTS: A total of 20 studies involving 1,182 patients were included in this network meta-analysis. Combined therapy with carbamic acid and 1064-nm picosecond laser was the best measure. Melasma area and severity index score of patients after low-power fractional CO2 laser treatment was higher than that of patients after the treatment with 1064-nm picosecond laser. CONCLUSION: Aminomethyl cyclic acid combined with 1064-nm picosecond laser may have the highest effective rate after treatment. Low-power fractional CO2 laser provided the lowest melasma area and severity index score after treatment, and the incidence rate of adverse reactions after treatment, was highest when intense pulsed light was used.

Efficacy and safety of picosecond laser for the treatment of melasma: a systematic review and meta-analysis.

Multiple laser modalities have been used for melasma treatment. However, the effectiveness of picosecond laser in treating melasma remains unclear. This meta-analysis investigated the effectiveness and safety of picosecond laser for melasma treatment. Randomized controlled trials (RCTs) comparing picosecond laser with conventional treatment for melasma were searched through five databases. The melasma area severity index (MASI)/modified MASI (mMASI) was used to quantify the degree of melasma improvement. Standardized mean differences and 95% confidence intervals were calculated using Review Manager for result standardization. Six RCTs, which used picosecond laser at 1064, 755, 595, and 532 nm wavelengths, were included herein. Picosecond laser significantly reduced the MASI/mMASI, but the results were highly heterogeneous (P = 0.008, I2 = 70%). In the subgroup analysis of 1064 and 755 nm picosecond lasers, 1064 nm picosecond laser significantly reduced the MASI/mMASI with no significant side effects (P = 0.04). Meanwhile, 755 nm picosecond laser did not significantly improve the MASI/mMASI compared with topical hypopigmentation agents (P = 0.08) and caused post-inflammatory hyperpigmentation. Other laser wavelengths could not be used in the subgroup analysis owing to an insufficient sample size. Picosecond laser at 1064 nm is safe and effective for melasma treatment. Picosecond laser at 755 nm is not superior to topical hypopigmentation agents in treating melasma. The exact efficacy of other wavelengths of picosecond laser for melasma treatment remains to be verified in large-scale RCTs.

Comparison of clinical results of oral tranexamic acid and platelet rich plasma therapies in melasma treatment.

The pathogenesis of melasma is not fully understood yet and this often causes difficulties in treatment. In our study, we aimed to compare the clinical results of oral tranexamic acid (TA) and platelet-rich plasma (PRP) therapies in patients with melasma. The clinical results of 30 melasma patients treated with oral TA and 30 melasma patients treated with PRP over the age of 18 who applied to the Inönü University Turgut Özal Medical Center Dermatology and Venereal Diseases Outpatient Clinic between September 2017 and June 2019 were retrospectively evaluated. Both oral TA and PRP therapies provided statistically significant improvement in melasma patients. 75% improvement in the MASI score was statistically significantly higher in the oral TA group compared to the PRP group. Although oral TA and PRP are both successful in the treatment of melasma, it has been found in our study that oral TA gives better results. More studies are needed to support our study, which is the first study comparing oral TA and PRP therapies in the literature.

Clinical, dermoscopic, and histopathologic evaluation of vitamin C versus PRP, with microneedling in the treatment of mixed melasma: A split-face, comparative study.

Melasma is a common esthetic problem affecting the face with a lot of risk factors being incriminated. Although several treatment options are available, none of them is satisfactory. This split face prospective study aimed to compare the efficacy of microneedling with vitamin C versus with platelet-rich plasma (PRP) in the management of mixed melasma. Ten females with bilateral mixed facial melasma were treated with six sessions of microneedling. After the needling vitamin C was applied on the right side of the face and PRP was applied on the left side. Clinical, dermoscopic, and histological assessment of the used treatments was done 1 month after the last session. The clinical and dermoscopic clearance of melasma was proved significantly on both sides of the face but was more significant with vitamin C (P = 0.005). Reduction of epidermal melanin and dermal melanophages was more observed with vitamin C. Moreover, MART-1 stain revealed a more significant reduction in the epidermal, dermal, and the total MART-1 positive cells with vitamin C (P = 0.044, 0.039, and 0.035, respectively). Microneedling with vitamin C was more efficient in treating mixed melasma than with PRP.

Combination of a 755-nm picosecond laser and hydroquinone 2% cream versus hydroquinone 2% cream alone for the treatment of melasma: A randomized, split-face, and controlled trial.

BACKGROUND: While combined laser and topical treatments are currently a common approach to melasma treatment, data on the efficacy and safety of this combined therapy remain scarce, with studies showing varied results. OBJECTIVE: To compare the efficacy and safety of hydroquinone (HQ) cream alone versus HQ cream combined with 755-nm picosecond (PS) laser in the treatment of melasma. METHOD: Twenty subjects presenting with mixed-type melasma were enrolled in the study. All patients were instructed to apply 2% HQ cream to both sides of the face for 4 weeks. Randomly assigned hemifaces of all patients thereafter received 5 biweekly PS laser treatments. Objective (measurement of average melanin content and melanin index) and subjective (grading of modified melasma area and severity index [mMASI] score and global percentage of pigment clearance) assessments of melasma clearance, and occurrence of adverse effects were evaluated at 1-, 3-, and 6-months after the final laser treatment. RESULTS: mMASI scores were significantly improved from baseline for both sides (p = 0.006 HQ alone, p < 0.001 HQ + PS laser), with no statistically significant difference when comparing HQ alone versus HQ + PS laser. Objective assessments (measurements of average melanin content and melanin index) of melasma clearance corresponded to the clinical evaluation using mMASI score. Mild postinflammatory hyperpigmentation was observed in 15% of the patients on the laser-treated side, while no adverse effects were reported on the HQ monotherapy side. CONCLUSIONS: Adjunctive treatment with a 755-nm PS laser does not provide additional benefit to topical HQ in the treatment of melasma. ClinicalTrail.gov PRS. number: NCT04597203.

Role of Platelet-Rich Plasma Therapy as an Adjuvant in Treatment of Melasma.

BACKGROUND: The management of melasma is an ongoing challenge. Platelet-rich plasma (PRP) therapy has been reported to be beneficial, but there is paucity of studies on PRP therapy in melasma. OBJECTIVE: To compare the efficacy of PRP therapy and hydroquinone versus hydroquinone alone in melasma. MATERIALS AND METHODS: Thirty patients were randomized to receive PRP microinjections on one side and normal saline on the other in a total of 3 sittings. Patients were concurrently advised 4% hydroquinone (HQ) cream application on both sides of the face. Efficacy was evaluated with hemi-modified Melasma Area Severity Index (MASI) scoring and a 4-scale patient satisfaction grading. RESULTS: Majority of the subjects (53.3%) in PRP + HQ group and 76.7% in HQ group had 25% to 50% improvement in their MASI scores. However, 40% in the PRP + HQ group and only 3.3% in the HQ group had 51% to 75% improvement. The difference in the percentage improvement was statistically significant. There was a greater percentage of subjects reporting a good response among the HQ + PRP group (53.3%) as compared with the HQ group (27%). CONCLUSION: Microinjections of PRP combined with topical HQ has better efficacy than topical HQ alone.

Therapeutic Effects of New Pulsed-Type Microneedling Radiofrequency for Refractory Facial Pigmentary Disorders.

BACKGROUND: Numerous treatments for pigmentary disorders have been used with variable outcomes. Recently, a new radiofrequency (RF) device with minimal pulse duration has been introduced. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of a pulsed-type microneedling RF device for treatment of facial pigmentary disorders. METHODS: Forty-four patients diagnosed with facial melasma or Riehl melanosis received 5 treatments with RF at 2-week intervals, and evaluation was performed at each visits, including 4 and 8 weeks after the last treatment. Treatment outcomes were evaluated by investigator global assessment, patient global assessment score, and skin biophysical parameters of erythema index, melanin index (MI), and transepidermal water loss. Gene array and immunohistochemical staining including melan-A, Fontana silver, CD44, basic fibroblast growth factor (bFGF), and periodic acid-Schiff were performed. RESULTS: Most of the patients showed clinical improvement. Erythema index, MI, and transepidermal water loss decreased after the first treatment. Histopathologic examination showed decrease of melanin pigment, melanophages, and blood vessel proliferation but thickened basement membrane after treatment. Expression of CD44 and b-FGF was decreased after treatment. There were no serious adverse events reported during the study. CONCLUSION: Pulsed-type microneedling RF could be a treatment option for facial pigmentary disorders.

Tranexamic Acid Microinjection Alone Versus Its Combination With Fractional Carbon Dioxide Laser in Melasma Treatment: A Dermoscopic Evaluation.

BACKGROUND: Melasma is a challenging pigmentation disorder. OBJECTIVE: To assess and compare the efficacy of tranexamic acid (TXA) intradermal microinjection alone versus its combination with low-power, low-density fractional CO2 laser in a sequential pattern in melasma. PATIENTS AND METHODS: This study included 29 patients with melasma. Half of the face was randomly assigned to fractional CO2 laser; the other half to TXA. This split-face session was repeated every 6 weeks for 3 sessions. In between, TXA was applied to the full face every 2 weeks. Treatment duration was 4 months. Dermoscopy, melanin index (M.I), and erythema index (E.I) were evaluated at baseline and 4 weeks after the last session. RESULTS: Melanin index, E.I, total dermoscopic score and different dermoscopic patterns of pigmentation, and vascular features showed significant reduction posttreatment on both sides of the face. No statistically significant difference was found regarding the degree and percentage of improvement in M.I, E.I, and total dermoscopic score between both sides. CONCLUSION: Tranexamic acid microinjection alone or combined with low-power, low-density fractional CO2 laser in a sequential pattern are comparatively effective and safe for melasma treatment; however, combined treatment is recommended. Dermoscopy is an essential noninvasive tool in the assessment of melasma and monitoring patients' response to treatment.