A COMPREHENSIVE SYSTEMATIC REVIEW OF THE EFFECTIVENESS OF MICRONEEDLING COMBINED WITH TOPICAL TRANEXAMIC ACID VERSUS INTRADERMAL TRANEXAMIC ACID INJECTION IN MELASMA

Abstract

Introduction: Melasma is a chronic facial hyperpigmentation disorder with substantial psychosocial burden, predominantly affecting reproductive-aged women with Fitzpatrick skin phototypes III-V. Tranexamic acid (TXA) has emerged as a depigmenting agent through competitive inhibition of the plasminogen-plasmin system. Two dominant minimally invasive locoregional delivery strategies are microneedling-assisted topical TXA (MN+TXA) and intradermal TXA microinjection (ID-TXA). No systematic review has restricted primary analysis to head-to-head comparisons of these routes.

Methods: The study strictly adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines to ensure methodological rigor and accuracy. Eligible studies included randomized controlled trials, split-face trials, and prospective comparative studies enrolling adults with clinically diagnosed melasma receiving locoregional TXA. Primary outcome was post-treatment melasma severity (MASI/mMASI/hemi-MASI). Effect measures were Hedges' g standardized mean differences, mean differences, and risk ratios pooled using DerSimonian-Laird random-effects models. Heterogeneity was quantified with τ², Cochran's Q, and I². Risk of bias was appraised with RoB 2 and ROBINS-I, and certainty of evidence with GRADE.

Results: Twenty-four primary studies comprising 1,160 participants were included; six head-to-head trials (353 participants) contributed to the primary meta-analysis. MN+TXA demonstrated significantly lower post-treatment severity compared to ID-TXA (SMD -0.42, 95% CI -0.77 to -0.06; P=0.023; I²=66.5%). Absolute advantage was 6.47 percentage points (95% CI 2.11-10.83; P=0.004). Probability of achieving ≥50% clearance was 35% higher with MN+TXA (RR 1.35, 95% CI 1.07-1.70; P=0.013). Patient satisfaction favored MN+TXA (SMD +0.72, 95% CI 0.50-0.95; P<0.001), with substantially lower procedural pain (MD -1.86, 95% CI -2.26 to -1.45; P<0.001). Post-inflammatory hyperpigmentation was numerically more frequent after MN+TXA (RR 1.71, 95% CI 0.61-4.78; P=0.310). No serious adverse events were reported. Certainty of evidence was moderate for patient satisfaction and pain, and low for efficacy outcomes.

Conclusion: Microneedling-assisted TXA delivery is at least as effective and modestly superior to intradermal injection on several endpoints, with markedly better tolerability and patient satisfaction. It should be preferred in routine practice for phototypes III-IV, with at least four sessions and rigorous photoprotection. Intradermal injection remains a reasonable alternative where microneedling devices are unavailable or post-inflammatory hyperpigmentation risk is judged high.