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Fractional ablative lasers enhance the delivery of topically applied photosensitizers improving photodynamic therapy (PDT) efficacy. The aim of this study was to compare the short- and medium-term efficacy of a pretreatment with urea 40% and fractional Er:YAG (Fr Er:YAG) laser radiation before PDT mediated by methylene blue (MB) for moderate toenail onychomycosis. Twenty-first-toe toenails were randomized to receive either urea 40% (Group I) or Fr Er:YAG laser (Group II) pretreatment and 9 sessions of MB\/PDT over the course of 16\u00a0weeks. At baseline, 28- and 40-week follow-ups, clinical efficacy was assessed by digital photographs [allowing determination of the onychomycosis severity index (OSI)], whereas mycological efficacy was assessed by histological examination and fungal culture. Details of the side effects and patients\u2019 satisfaction were also recorded. In both groups, a significant decrease in OSI values was observed at the 28-week follow-up and a slight rebound at the 40-week follow-up. The percentage of nail involvement decreased significantly in both groups at the 28-week follow-up, to continue declining gently in Group I at 40\u00a0weeks, in contrast to the rebound observed during this period in Group II. The mycological cure rate was 20% and 30% at 28-week follow-up and 70% and 40% at 40-week follow-up, in Group I and II, respectively. Patients reported being fairly satisfied, and no side effects were detected in any groups. Although both pretreatments favor the action of PDT for the treatment of onychomycosis, the use of urea at 40% is more effective in the medium term.<\/jats:p>","DOI":"10.1007\/s00403-022-02448-7","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T16:03:00Z","timestamp":1667232180000},"page":"787-794","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Urea versus fractional Er:YAG laser pretreatment of methylene blue photodynamic therapy in the treatment of moderate toenail onychomycosis: short- and medium-term effects"],"prefix":"10.1007","volume":"315","author":[{"given":"Enrique","family":"Alberdi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"issue":"5","key":"2448_CR1","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1002\/lsm.20048","volume":"34","author":"D Manstein","year":"2004","unstructured":"Manstein D, Herron GS, Sink RK, Tanner H, Anderson RR (2004) Fractional photothermolysis a new concept for cutaneous remodeling using microscopic patterns of thermal injury. 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