Painless Photodynamic Therapy: Emerging Protocols and Light Delivery Systems for the Treatment of Actinic Keratoses

Abstract

Background/purpose: Photodynamic therapy (PDT) is a field-directed treatment for actinic keratoses (AK) with additional off-label uses in acne and photoaging. Although effective, conventional PDT is often limited by illumination-related pain. Building on the well-tolerated nature of daylight PDT, short- or no-incubation protocols have been developed to provide similarly painless treatment experiences within a controlled clinical setting. This review highlights the rationale, clinical outcomes, and practical implementation of these emerging approaches.

Methods: We conducted a narrative review using searches on PubMed, Embase, and Google Scholar with keywords such as 'photodynamic therapy,' 'painless PDT,' 'actinic keratosis,' and 'incubation time.' The review evaluated the literature on the treatment of AK, focusing on pain, efficacy, and workflow considerations, across evolving PDT protocols, including daylight PDT (dPDT), red and blue light painless PDT (pPDT), simulated daylight PDT (SD-PDT), and other novel delivery systems.

Results: Evidence suggests these modified protocols achieve clearance rates comparable to conventional PDT while significantly improving patient tolerability. Short-incubation protocols have demonstrated promising clinical results, offering a predictable, low-pain alternative that maintains efficacy and streamlines clinic workflow.

Conclusion: The emergence of painless PDT protocols-developed based on the tolerability and success of daylight PDT-has expanded the therapeutic potential of PDT in dermatology. These protocols enable clinicians to deliver effective, field-directed treatment for AK with reduced patient discomfort, facilitating broader adoption in both academic and community practice.

Keywords: Photodynamic therapy; actinic keratosis; aminolevulinic acid; painless photodynamic therapy.