Activated melanocytes and senescent collagen fibers predict laser-treated melasma outcomes: An optical biopsy-based prospective cohort study

Photodiagnosis Photodyn Ther. 2025 May 24:54:104648. doi: 10.1016/j.pdpdt.2025.104648. Online ahead of print.

Abstract

Background: Melasma Area and Severity Index (MASI) score only assesses the pigmentation rather than photoaging. Picosecond alexandrite laser (PAL) with diffractive lens array (DLA) can improve photoaging and has been approved for melasma treatment. Prediction for post-laser outcome is limited.

Objective: To in vivo compare the photoaging milieu altered by a PAL with DLA in melasma lesions and adjacent perilesions, and to delineate the predictive factors for outcomes.

Methods: An optical biopsy with cellular resolution full-field optical coherence tomography (CRFF-OCT) was set up to evaluate the dynamic changes. Quantification was performed with the computer-aided detection (CADe) system.

Results: The mean MASI score decreased significantly (p < 0.001) in 12 of 15 patients but increased in the other three. An optical biopsy of 74,340 images showed the numbers of activated melanocytes and melanophages were significantly reduced post laser, and the basement membrane (BM) was repaired in melasma lesions, while basal lightening was noted in perilesions. The pre-treatment presence of activated melanocytes was associated with a high regional MASI score (p = 0.013), while the senescent collagen fibers and activated melanocyte patterns were associated with less MASI score improvement (p = 0.005). Senescent collagen fibers (p = 0.002) and baseline BM damage(p = 0.001) were strongly correlated to post-treatment melanophages. The baseline MASI score was not associated with activated melanocyte status or treatment outcomes.

Conclusion: Optical biopsy using CRFF-OCT revealed that patterns of activated melanocytes and senescent collagen fibers can serve as predictive markers for post-laser treatment outcomes. The photoaging characteristics of melasma were improved through the reduction of activated melanocytes and the repair of the BM.

Keywords: Basement membrane; Collagen; Melanocytes; Melasma; Optical coherence tomography.