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<p>Phototherapies play an&#xa0;important role in the treatment of hyperpigmentation. However, the effects of different phototherapies on skin pigmentation have not been comprehensively evaluated to date. We analyzed the efficacy and patient satisfaction of 14 distinct phototherapies for melasma using a&#xa0;network meta-analysis of 22 randomized controlled trials. Cluster analysis revealed that fractional CO<sub>2</sub> laser combines&#xa0;the advantages of high efficacy and patient satisfaction. We therefore evaluated the effect of fractional CO<sub>2</sub> laser on forearm skin pigmentation in volunteers. Reflectance confocal microscopy showed that&#xa0;fractional CO<sub>2</sub> laser effectively inhibited pigmentation, and the inhibitory effect was more pronounced as the scanning spacing decreased. Gene Set Enrichment Analysis revealed that&#xa0;fractional CO<sub>2</sub> laser inhibited melanogenesis in photoaging skin. Transcriptome sequencing of skin samples from guinea pigs treated with fractional CO<sub>2</sub> laser showed that&#xa0;the key regulators of melanogenesis (microphthalmia-associated transcription factor, tyrosinase and dopachrome tautomerase) were&#xa0;significantly downregulated on the seventh day after&#xa0;treatment with fractional CO<sub>2</sub> laser. Gene Set Enrichment Analysis further revealed that the cyclic adenosine monophosphate signaling pathway was inhibited on the third day after treatment, whereas the phosphatidylinositol 3-kinase-protein kinase B pathway was activated on the fifth and seventh days. Fractional CO<sub>2</sub> laser effectively reversed hyperpigmentation and may even inhibit skin pigmentation by exfoliating the superficial stratum corneum, destroying melanin granules, and regulating signaling pathways related to melanogenesis.</p>

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The Therapeutic Potential of Fractional CO2 Laser for Hyperpigmentation: Evidence From Network Meta-analysis, Clinical and Animal Studies

  • 期刊论文

  • 发表日期：

    2026年6月29日

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  • Haoran Guo,
  • Hui Li,
  • Ling Jiang,
  • Chuhan Fu,
  • Jianyun Lu,
  • Zhen Tang,
  • Jing Chen,
  • Qinghai Zeng

摘要

Phototherapies play an important role in the treatment of hyperpigmentation. However, the effects of different phototherapies on skin pigmentation have not been comprehensively evaluated to date. We analyzed the efficacy and patient satisfaction of 14 distinct phototherapies for melasma using a network meta-analysis of 22 randomized controlled trials. Cluster analysis revealed that fractional CO2 laser combines the advantages of high efficacy and patient satisfaction. We therefore evaluated the effect of fractional CO2 laser on forearm skin pigmentation in volunteers. Reflectance confocal microscopy showed that fractional CO2 laser effectively inhibited pigmentation, and the inhibitory effect was more pronounced as the scanning spacing decreased. Gene Set Enrichment Analysis revealed that fractional CO2 laser inhibited melanogenesis in photoaging skin. Transcriptome sequencing of skin samples from guinea pigs treated with fractional CO2 laser showed that the key regulators of melanogenesis (microphthalmia-associated transcription factor, tyrosinase and dopachrome tautomerase) were significantly downregulated on the seventh day after treatment with fractional CO2 laser. Gene Set Enrichment Analysis further revealed that the cyclic adenosine monophosphate signaling pathway was inhibited on the third day after treatment, whereas the phosphatidylinositol 3-kinase-protein kinase B pathway was activated on the fifth and seventh days. Fractional CO2 laser effectively reversed hyperpigmentation and may even inhibit skin pigmentation by exfoliating the superficial stratum corneum, destroying melanin granules, and regulating signaling pathways related to melanogenesis.