Abstract: 【Abstract】 Objective To investigate the efficacy and safety of low-fluence fractional CO2 laser for the treatment of refractory persistent erythema in rosacea. Methods This single-center retrospective cohort study included rosacea patients predominantly presenting with refractory persistent erythema who underwent low-fluence fractional CO2 laser treatment at the Department of Dermatology, Xiangya Hospital, Central South University between January 2020 and December 2021. All patients completed 3 sessions of laser treatment at 2-month intervals, with a fluence of 120 - 150 mJ/pixel. Primary efficacy endpoints were the clinical erythema assessment （CEA） score and patient self-assessment （PSA） score. Secondary efficacy endpoints included scores for other rosacea symptoms （flushing, edema, and telangiectasia）, visual analog scale （VAS） scores, and dermatology life quality index （DLQI） scores. Facial images and epidermal barrier function parameters were collected before and after treatment, and treatment-related adverse reactions were recorded. Normally or approximately normally distributed measurement data across multiple time points were analyzed using repeated-measures analysis of variance, non-normally distributed measurement data from multiple related samples were compared using the Friedman test, and paired t-tests were used for comparisons between two related samples. Results A total of 117 patients with rosacea were included, comprising 56 males （47.9%） and 61 females （52.1%）, with ages of 24.25 ± 3.30 years. All patients presented with persistent erythema as the main clinical manifestation, among whom 41 （35.0%） had a CEA score of 1 point and 76 （65.0%） had a CEA score of 2 points. After the low-fluence fractional CO2 laser therapy, significant changes over time were observed in both CEA and PSA scores （F = 29.17, 38.91, respectively, both P < 0.001）; at 2 months after the first treatment, CEA scores decreased from 1.65 ± 0.48 points at baseline to 1.48 ± 0.52 points （P = 0.042）, and PSA scores decreased from 1.82 ± 0.55 points at baseline to 1.62 ± 0.60 points （P = 0.037）; at 2 months after the third treatment, both CEA and PSA scores showed further significant reduction （both P < 0.001）, and the edema scores significantly decreased compared with the baseline scores （P = 0.017）. However, no significant differences were observed in flushing or telangiectasia scores across time points （F = 1.87, 1.08, respectively, both P > 0.05）. Compared with the baseline scores, the DLQI and VAS scores significantly decreased at 2 months after the third treatment （both P < 0.001）. Epidermal barrier function assessment revealed significant improvements in erythema, sebum, pores, and texture at 1 month after the first treatment compared with baseline values （all P < 0.001）. All patients experienced transient post-treatment erythema in the treated area, which resolved within 3 - 7 days. Sand-like punctate crusting occurred in 9 patients （7.7%）, and completely resolved within 3 - 5 days. No adverse reactions （such as persistent erythema, hyperpigmentation, and infection） were reported. Conclusion Low-fluence fractional CO2 laser could be an effective and safe treatment option for refractory persistent erythema in rosacea patients.

Key words: Rosacea, Lasers, gas, Fractional CO2 laser, Refractory erythema perstans, Treatment outcome