Therapeutic approaches for refractory melasma: Fractional CO2 Laser and Q-Switched Nd:YAG Laser with tranexamic acid injections
DOI:
https://doi.org/10.66344/jpad.v36i1.3233Keywords:
Refractory melasma, Fractional CO2 laser, QSNY laser, tranexamic acidAbstract
Background Melasma is characterized by dyspigmentation that is difficult to treat. This is due to the complex underlying factors and high risk to recurrence. Objective Investigating the clinical outcomes from utilizing fractional CO2 laser and Q-Switched Nd:YAG laser (QSNY) in combination with tranexamic acid (TA) in treating refractory melasma. Methods The cross sectional study included sixty women with refractory melasma. Patients were randomly assigned into two groups (30 patients per group) to receive either the fractional CO2 laser or the QSNY laser treatment. Patients from both groups were supplemented with intradermal microinjections of TA (4 mg/ml), and laser sessions were conducted every month for a total of four successive sessions per patient. Treatment outcomes were assessed via calculating modified melasma area and severity index (mMASI) at baseline and after 30, 60, 90, and 120 days of post-treatment. Results There was a significant reduction in mMASI score (p<.001) after each therapy session. The fractional CO2 laser with TA demonstrated higher efficacy in reducing mean mMASI score (1.98±1.0) relative to the Nd-YAG laser with TA (3.1±1.5), (p<.001). Although the clinical effectiveness of fractional CO2 laser with TA was higher, patient satisfaction among study groups were found with no significant difference (p>.05). Conclusion Fractional CO2 laser and QSNY laser treatments in combination with intradermal TA injections are effective approaches in decreasing the overall mMASI scores in women with refractory melasma. Further studies are necessary to enhance our understanding and to guide optimal clinical practice regarding refractory melasma.References
Ghasemiyeh P, Fazlinejad R, Kiafar MR, Rasekh S, Mokhtarzadegan M, Mohammadi-Samani S. Different therapeutic approaches in melasma: advances and limitations. Front Pharmacol. 2024;15:1337282.
Espósito ACC, Cassiano DP, da Silva CN, Lima PB, Dias JAF, Hassun K, et al. Update on Melasma-Part I: Pathogenesis. Dermatol Ther (Heidelb). 2022;12(9):1967-88.
Bostan E, Cakir A. The dermoscopic characteristics of melasma in relation to different skin phototypes, distribution patterns and wood lamp findings: a cross-sectional study of 236 melasma lesions. Arch Dermatol Res. 2023;315(7):1927-38.
Filoni A, Mariano M, Cameli N. Melasma: How hormones can modulate skin pigmentation. J Cosmet Dermatol. 2019;18(2):458-63.
Beyzaee AM, Patil A, Goldust M, Moslemi M, Kazeminejad A, Rokni GR. Comparative Efficacy of Fractional CO2 Laser and Q-Switched Nd:YAG Laser in Combination Therapy with Tranexamic Acid in Refractory Melasma: Results of a Prospective Clinical Trial. Cosmetics. 2021;8(2):37.
Piccolo D, Fusco I, Crisman G, Zingoni T, Conforti C. Efficacy and Safety of Q-Switched 1064/532 nm Nd:YAG Lasers on Benign Hypermelanosis in Dark-Skinned Individuals-A Preliminary Study. J Clin Med. 2024;13(6):1615.
R DK, Sood R, Tiwari P. Melasma management: Unveiling recent breakthroughs through literature analysis. Health Sci Rev 2025;14:100213.
Maeda K. Mechanism of Action of Topical Tranexamic Acid in the Treatment of Melasma and Sun-Induced Skin Hyperpigmentation. Cosmetics 2022;9(5):108.
Aurangabadkar SJ. Optimizing Q-switched lasers for melasma and acquired dermal melanoses. Indian J Dermatol Venereol Leprol. 2019;85(1):10-7.
Tawfic SO, Abdel Hay RM, Abouelazm DI, Said ER. Tranexamic Acid Microinjection Alone Versus Its Combination With Fractional Carbon Dioxide Laser in Melasma Treatment: A Dermoscopic Evaluation. Dermatol Surg. 2022;48(5):556-61.
Elmasry MF, Khalil MMF, Badawi A, Zaki NS, Fahim A. Efficacy of Fractional Carbon Dioxide (CO2) Laser versus Q-Switched Neodymium-Doped Yttrium Aluminum Garnet (Nd:YAG) and Potassium-Titanyl-Phosphate (KTP) Lasers in the Treatment of Acanthosis Nigricans. Clin Cosmet Investig Dermatol. 2023;16:705-15.
Guo H, Zhang X, Li H, Fu C, Jiang L, Hu Y, et al. Dynamic panoramic presentation of skin function after fractional CO(2) laser treatment. iScience 2023;26(9):107559.
Aryal E, Khadka A, Bhattarai S. Correlation of quality of life and severity in patients with melasma. J Kathmandu Med College. 2022;11(4):210-4.
El-Sinbawy ZG, Abdelnabi N, Sarhan N, Elgarhy LH. Clinical & ultrastructural evaluation of the effect of fractional CO2 laser on facial melasma. Ultrastruct Pathol. 2019;43:135-44.
Devi AK, Utomo B, Indramaya DM, Listiawan MY, Sawitri, Murtiastutik D, et al. Profile of melasma patients in dermatology and venerology outpatient clinic Dr. Soetomo General Academic Hospital, Surabaya, Indonesia. Bali Med J. 2022;11(1):166-73.
Liu W, Chen Q, Xia Y. New Mechanistic Insights of Melasma. Clin Cosmet Investig Dermatol. 2023;16:429-42.
Zhang J, Wang T, Li Z, Qin C, Dai J, Zhao Y, et al. Hormonal Crosstalk in Melasma: Unraveling the Dual Roles of Estrogen and Progesterone in Melanogenesis. Int J Mol Sci. 2025;26(22):10856.
Daroach M, Vinay K, Bishnoi A, Parsad D, Kumaran MS. Extrafacial Melasma: A Scenario Less Explored. Indian Dermatol Online J. 2022;13:484-6.
Chen W, Wan Y, Sun Y, Gao C, Li J. Prevalence of depression in melasma: a systematic review and meta-analysis. Front Psychiatry. 2024;14:1276906.
Platsidaki E, Efstathiou V, Markantoni V, Kouris A, Kontochristopoulos G, Nikolaidou E, et al. Self-Esteem, Depression, Anxiety and Quality of Life in Patients with Melasma Living in a Sunny Mediterranean Area: Results from a Prospective Cross-Sectional Study. Dermatol Ther (Heidelb). 2023;13(5):1127-36.
Tawfic SO, Abdel Halim DM, Albarbary A, Abdelhady M. Assessment of combined fractional CO(2) and tranexamic acid in melasma treatment. Lasers Surg Med. 2019;51(1):27-33.
Eassa BI, Ammar AM, Shoaib OA, Elsaie ML. Fractional carbon dioxide laser assisted delivery of tranexamic acid versus ascorbic acid in the treatment of melasma: a split face comparative study with digital skin analysis. Lasers Med Sci. 2025;40(1):282.
Liu B, Sood R, Wang F, Zhang F, Sun L, Qiu X, et al. Principles and clinical applications of transcutaneous laser-assisted drug delivery: A narrative review. Scars Burn Heal. 2024;10:20595131241234715.
Mamdouh Kamal S, Hegab DS, Mohamed El Maghraby G, Ahmad El- Ashmawy A. Efficacy and Safety of Topical Tranexamic Acid Alone or in Combination with Either Fractional Carbon Dioxide Laser or Microneedling for the Treatment of Melasma. Dermatol Pract Concept. 2023;13(3):e2023195.
Qu Y, Wang F, Liu J, Xia X. Clinical observation and dermoscopy evaluation of fractional CO(2) laser combined with topical tranexamic acid in melasma treatments. J Cosmet Dermatol. 2021;20(4):1110-6.
Kwon S-H, Na JI, Choi JY, Park KC. Melasma: Updates and perspectives. Experiment Dermatol 2019;28(6):704-8.
Hawwam SA, Ismail M, El-Attar YA. Split-face comparative study between intradermal tranexamic acid injection alone versus intradermal tranexamic acid injection combined with Q-switched Nd:YAG laser in melasma treatment: dermoscopic and clinical evaluation. Lasers Med Sci. 2022;37(4):2193-201.
Agarwal M, Velaskar S. Laser Skin Rejuvenation With Fractional 1064 Q-switched Nd:YAG In 252 Patients: An Indian Experience. J Cosmet Dermatol. 2020;19(2):382-7.
Ehsan I, Aman S, Nadeem MA, Kazmi AH. Efficacy of Q-switched Nd:YAG Laser 1,064nm for the treatment of melasma. J Pak Assoc Dermatol. 2020;30:106-10.
Lee YS, Lee YJ, Lee JM, Han TY, Lee JH, Choi JE. The Low-Fluence Q-Switched Nd:YAG Laser Treatment for Melasma: A Systematic Review. Medicina (Kaunas) 2022;58(7):936.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Journal of Pakistan Association of Dermatologists
This work is licensed under a Creative Commons Attribution 4.0 International License.
Submission declaration
Authors retain the copyright to their work and grant the 'Journal of Pakistan Association of Dermatologists (JPAD)' the right of first publication under a Creative Commons Attribution 4.0 International (CC BY 4.0) license. This license allows others to share, adapt, and reuse the work for any purpose, including commercial use, as long as appropriate credit is given to the original authors and the journal.
By submitting a manuscript, authors confirm that the work has not been published previously (except as an abstract, lecture, or academic thesis), is not under review elsewhere, and has been approved by all authors and relevant authorities. Once accepted, the article will be openly accessible under the CC BY 4.0 license, ensuring wide dissemination and reuse with proper attribution.
