Archives of Dermatological Research · 2 authors, 2 centres
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This randomized controlled trial compared 40% urea pretreatment versus fractional Er:YAG laser pretreatment before methylene blue photodynamic therapy (MB/PDT) for moderate toenail onychomycosis. At 40-week follow-up, the urea pretreatment group achieved a 60% complete cure rate versus 30% in the laser group, though the laser group reported higher patient satisfaction. Both pretreatments were safe and effective, but urea provided superior medium-term outcomes.
**Background:** Onychomycosis is a common fungal nail infection with limited treatment options due to poor drug penetration and adverse effects of oral antifungals. Photodynamic therapy (PDT) is a promising alternative, but requires effective pretreatment to enhance photosensitizer delivery across the nail plate. Both urea (a keratolytic agent) and fractional Er:YAG laser (which creates microchannels) have been proposed as pretreatments, but no direct comparison existed prior to this study.
**Methods:** This was a 40-week randomized controlled trial conducted at a private dermatology clinic in Madrid, Spain. Twenty patients with moderate first-toe toenail onychomycosis (OSI 6.0–15.9) confirmed by PAS staining and fungal culture were randomly assigned to two groups (1:1 ratio using Research Randomizer software). Group I (n=10) received pretreatment with 40% urea ointment under occlusion for 12 hours nightly over 4–7 days (depending on hyperkeratosis thickness). Group II (n=10) received fractional Er:YAG laser pretreatment (Pixel 2940 nm module, Harmony platform; 9×9 pixel matrix, 17 mJ/pixel, 1400 mJ maximum pulse energy, 150 µm ablation zone diameter, 9 pulses per area). Both groups then received 9 sessions of MB/PDT (2% methylene blue solution, 3 min incubation, photoactivation with 635 nm LED lamp at 37 J/cm², 70 mW/cm², 10 min exposure) at 2-week intervals over 16 weeks. Outcomes were assessed at baseline, 28-week, and 40-week follow-up using OSI scores, degree of improvement (categorized as no 0–25%, mild 26–50%, moderate 51–75%, outstanding 76–100%), nail involvement percentage, PAS staining, and patient satisfaction (1–5 scale). Statistical analysis used repeated measures ANOVA with Bonferroni correction; p<0.05 was considered significant.
**Key Results:** Both groups showed significant clinical and mycological improvement. In the urea+MB/PDT group, mean OSI decreased from 12.2±5.3 at baseline to 2.7±1.8 at 28 weeks and 3.7±3.6 at 40 weeks. In the Fr Er:YAG+MB/PDT group, mean OSI decreased from 15.9±6.1 to 7.1±6.2 at 28 weeks and 8.5±5.6 at 40 weeks. The mean degree of improvement at 28 weeks was 76.5±17.1% (urea) vs 57.2±37.1% (laser); at 40 weeks it was 75.3±33.4% vs 44.4±36.2%. Nail involvement decreased from 38.0±20.8% to 4.5±4.0% (urea) and from 31.5±21.5% to 13.5±8.8% (laser) at 40 weeks. Mycological cure (PAS negative) at 40 weeks was 70% (7/10) in the urea group vs 40% (4/10) in the laser group. Complete cure (mycological cure + ≥80% clinical improvement) at 40 weeks was 60% (urea) vs 30% (laser). The laser group showed earlier improvement (peak at 28 weeks) but a rebound by 40 weeks, while the urea group showed sustained or improving results. Patient satisfaction was higher in the laser group (mean 3.9 vs 3.2 on 1–5 scale). No statistically significant intergroup differences were found for any outcome (p>0.05). No side reactions were reported; two urea patients had mild periungual irritation.
**Clinical Implications:** Both 40% urea and fractional Er:YAG laser are safe and effective pretreatments for MB/PDT in moderate toenail onychomycosis. Urea pretreatment appears more effective in the medium term (40 weeks), achieving a 60% complete cure rate compared to 30% with laser pretreatment. The laser group showed earlier improvement but a tendency toward relapse, possibly due to heterogeneous photosensitizer diffusion through microchannels versus the homogeneous pretreatment achieved with urea. However, laser pretreatment offered greater patient convenience and satisfaction, avoiding nightly occlusive applications. The lack of statistical significance between groups is likely due to the small sample size (n=10 per group). These findings support urea+MB/PDT as a promising alternative for patients who cannot tolerate or have failed conventional antifungal therapy, while Fr Er:YAG+MB/PDT may be preferred for patients seeking convenience. Further studies with larger samples and longer follow-up are needed to establish optimal laser parameters and assess recurrence rates.