Melasma, a complex and clinically challenging facial pigmentary disorder, lacks in vivo pathologic tools for definitive diagnosis and accurate efficacy assessment. To use 2-photon microscopy (TPM) for noninvasive pathologic detection of melasma and therapeutic response monitoring to hydroquinone cream, 2%. This single-center, evaluator-blinded, observational study consisting of 2 sequential phases was conducted at the Dermatology Outpatient Clinic of China-Japan Friendship Hospital from January to September 2024. The study population included patients aged 18 to 60 years with clinically diagnosed melasma who were not treated for the condition in the past 3 months, without other facial dermatoses, free of malignant disease history, and not pregnant and nonlactating. In the first phase, participants underwent noninvasive TPM 3-dimensional imaging of lesional and perilesional areas. In the second phase, all participants were treated with hydroquinone cream, 2% twice daily for 12 weeks. In phase 1, the main outcome was TPM pathologic features. In phase 2, the main measures were modified Melasma Area and Severity Index (mMASI) scores, dermoscopic scores, and TPM indexes at baseline and weeks 4, 8, and 12. The TPM images of 120 lesional and perilesional areas from 60 patients (57 female individuals, 3 male individuals; median IQR age, 39.5 37.0-45.8 years) were analyzed. Compared with the perilesions, melasma lesions showed increased melanin across all epidermal layers (stratum corneum: median IQR, 1 0-2 vs 0 0-0; stratum granulosum: median IQR, 1 1-2 vs 0 0-0; superficial stratum spinosum: median IQR, 2 1-3 vs 1 1-1; deep stratum spinosum: median IQR, 3 2-3 vs 2 1-2; stratum basale: median IQR, 3 3-4 vs 2 2-3) in a mottled distribution, reduced viable epidermal thickness (median IQR, 43.5 39.0-48.0 µm vs 48.0 43.9-54.0 µm; median difference, -4.50; 95% CI, -6.58 to -3.70), flattened rete ridges (94.17%; 95% CI, 88.45%-97.15% vs 69.17%; 95% CI, 60.42%-76.73%), increased activated (median IQR, 2 1-2 vs 1 1-1; median difference, 1; 95% CI, 0.70-1.00) and pendulous (median IQR, 0 0-1 vs 0 0-0) melanocytes at the dermal-epidermal junction (DEJ), and more severe solar elastosis (median IQR, 2 2-3 vs 2 1-2) (all P<.001). Among them, 53 patients (88.3%) completed 12 weeks of hydroquinone treatment, the mean mMASI scores and dermoscopic pigmentary scores decreased by 29.81% (95% CI, 22.75%-36.72%; P < .001) and 36.16% (95% CI, 30.07%-42.25%; P < .001), respectively, after treatment. TPM showed significant decreases in melanin content of each epidermal layer (stratum corneum: median IQR, 1 1-2 vs 1 0-1; stratum granulosum: median IQR, 2 1-2 vs 1 0-1; superficial stratum spinosum: median IQR, 2 2-3 vs 1 1-2; deep stratum spinosum: median IQR, 3 3-3 vs 2 2-3; and stratum basale: median IQR, 3 3-4 vs 2 2-3; all P < .001) and activated melanocytes at the DEJ (median IQR, 2 2-2 vs 1 1-2; P < .001) after treatment, but no statistical changes in pendulous melanocytes or solar elastosis during treatment. This observational study found that TPM may offer a new paradigm in pigmentary disorder management by enabling in vivo detection of pathologic features and assessment of cellular-level treatment responses.
Ning et al. (Wed,) studied this question.