Clinical safety and tolerability of repeated high-fluence 405 nm blue light exposure in chronic wounds

Antimicrobial blue light requires substantially higher fluences than conventional photobiomodulation to achieve antibacterial effects, but concerns regarding tissue toxicity have limited its clinical translation for chronic wounds. The objective of this phase I clinical trial was to evaluate whether repeated high-fluences antimicrobial blue light could be delivered safely to chronic wounds. In this four-week dose-escalation design, twenty-two patients with chronic wounds received 405-nm blue light at 20, 60, or 100 J/cm² three times weekly for two weeks. Safety was assessed using the CTCAE Skin Domain (CTCAE^SD), adverse event monitoring, pain assessment (NRS-11 and Wong-Baker FACES) and clinical wound evaluation. All but one patient demonstrated Grade 1 (mild/asymptomatic) CTCAE^SD reactions throughout till follow-up. This patient developed a Grade 2 blister near the wound bed that could not be excluded as treatment related. Adverse events (n = 28) were considered unrelated to treatment, and no serious adverse events occurred. Pain was predominantly rated as absent or mild, with no significant differences between dose groups (p > 0.05). Clinical wound assessments showed no dose-dependent aggravation or negative impact on wound healing (p > 0.05). Wound surface temperatures remained below 42 degrees except during one interrupted treatment session. High fluences of 405 nm blue light photobiomodulation was generally well tolerated in this small cohort and was considered safe for use in patients with chronic wounds. This clinical safety study supports further evaluation of whether antimicrobial fluences can reduce bacterial burden and if it translates into improved healing of chronic wounds.