Efficacy of nano-sized ultrafine water clusters in reducing erythema following fractionated picosecond alexandrite laser treatment: a split-face, randomized, evaluator-blinded pilot study.

Post-procedural erythema following energy-based dermatological treatments is a common concern affecting patient satisfaction and downtime. Nano-sized ultrafine water clusters (UFW), generated by conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT/PSS) technology, represent a nanometer-scale water cluster species (average aerosol-phase particle diameter ≈ 1.4 nm). This split-face, randomized, evaluator-blinded pilot study evaluated the efficacy of UFW in reducing erythema following fractionated picosecond alexandrite laser (Fr-PSAL) treatment with a diffractive lens array. Twenty-five female subjects were assigned to a pre-treatment (n = 13) or post-treatment (n = 12) group. UFW was applied for 30 min to one randomly selected facial side; the contralateral side served as control. Two independent board-certified dermatologists, blinded to allocation, correctly identified the UFW-treated side with high concordance in both groups. In the post-treatment group, each evaluator achieved 11/12 correct identifications (91.7%, binomial p = 0.003); Cohen's kappa between evaluators was 0.625 (substantial agreement). In the pre-treatment group, Evaluator 1 identified 11/13 correct (84.6%, p = 0.011) and Evaluator 2 identified 12/13 correct (92.3%, p = 0.002); Cohen's kappa was 0.831 (almost perfect agreement). An exploratory semi-quantitative hemoglobin-enhanced image analysis provided objective support, although the strength of that support differed between the two groups. In the post-treatment group, the pre-specified primary metric (erythema density) was robustly significant (Cohen's d = - 0.93, p = 0.004). In the pre-treatment group, the pre-specified primary metric (erythema area) was also significant (d = - 0.57, p = 0.031), but this prophylactic-arm result depended on per-subject selection of the comparison timepoint and was not significant when a fixed 6 h timepoint was used (7/13 correct, 53.8%; p = 0.448); it should therefore be regarded as hypothesis-generating. No adverse events were observed. These results provide the first clinical evidence that UFW effectively reduces post-laser erythema, with findings consistent with both therapeutic and prophylactic mechanisms of action.