Bringing the gentle properties of daylight photodynamic therapy indoors: A systematic review of efficacy and safety

Classic photodynamic therapy (PDT) is an effective, but painful, treatment of actinic keratosis (AK). Daylight PDT with simultaneous activation of protoporphyrin IX during its formation is almost painless and as effective. Recent studies suggest that this gentle simultaneous activation can be performed indoors by replacing daylight with a suitable light source. We aimed to systematically review efficacy and tolerability of indoor gentle PDT of AKs using various light sources. We systematically searched MEDLINE, Embase, and the Cochrane Library for clinical studies of treatment efficacy or adverse events. Indoor gentle PDT consists of application of methyl aminolevulinate or 5-aminolevulinic acid on the skin prior to long time illumination, starting no later than one hour after application. Fifteen studies met the selection criteria, enrolling 518 patients with more than 5,000 AKs undergoing indoor gentle PDT. The studies mainly included thin AKs comprised of 8 uncontrolled studies and 7 randomized controlled trials (RCT) of which 3 were designed as non-inferiority RCTs. Results from both controlled and uncontrolled trials indicated good treatment tolerability with very low pain scores like those of daylight PDT. Reduction of AK lesions 3 months after indoor gentle PDT in RCTs ranged from 52% to 79%, which is comparable to classic and daylight PDT. All 3 non-inferiority RCTs reported that indoor gentle PDT was non-inferior in terms of efficacy to classic PDT. The included studies used varying treatment protocols with different pretreatments, incubation time, light sources, and irradiation time. No standard protocol for indoor gentle PDT exists yet.