Daylight Photodynamic Therapy Research Articles

Methyl aminolevulinate daylight photodynamic therapy applied at home for non-hyperkeratotic actinic keratosis of the face or scalp: an open, interventional study conducted in Germany.

The efficacy and safety of methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) for actinic keratosis (AK) treatment has previously been demonstrated in several studies. To evaluate patient-reported outcomes, effectiveness and tolerability of patient self-applied MAL DL-PDT. An open study was conducted in Germany in patients with thin or non-hyperkeratotic and non-pigmented AK. At baseline, the investigator delimited the target anatomical area and skin preparation was discretionary. On day 1, the patient performed MAL DL-PDT at home, in accordance with instructions (after applying sunscreen and skin preparation by abrasive pad). Patient questionnaires were completed on day 1 and 3 months post-treatment. Effectiveness was assessed by investigator at 3 months. Pain and adverse events (AE) were recorded. Patients (n = 50) were mostly elderly (mean age: 73.4 years) men (86%). After treatment on day 1, 94% of patients were overall satisfied or very satisfied with the treatment and 98% found the instructions convenient. At 3 months, most patients were satisfied or very satisfied with treatment effectiveness (88%) and aspect of their skin (80%). At 3 months, 62% of overall lesions were completely clear. The main related AEs were mild and expected (erythema, procedural pain and skin burning sensation). Patient self-application of MAL DL-PDT resulted in high levels of patient satisfaction, effectiveness and tolerability.

Daylight photodynamic therapy in 25 patients with actinic keratosis and evaluation of efficacy by confocal microscopy.

Daylight photodynamic therapy (PDT) has been reported as having similar efficacy to conventional photodynamic therapy in actinic keratosis treatment. 25 patients with actinic keratosis of the scalp and/or face were submitted to a daylight photodynamic therapy session. Adverse reactions were evaluated after one week and efficacy after 3 months. Confocal Microscopy was performed in 6 patients, before and one week after the treatment. Our aim was to compare our results with others studies and analyse the changes occurring in the epidermis and upper dermis with confocal microscopy. 76% of the patients were male. The mean age was 74.2 years. In 51.7% of patients the treatment site was the scalp. Mean cure rate at 3 months was 74%. Aesthetic results were excellent in all patients and only one patient reported mild pain during the 2 h exposure. Confocal Microscopy showed a normalization of the honeycomb pattern in all of the patients. This therapy has similar results to conventional photodynamic therapy and stands out for less discomfort, fewer adverse effects and better cost-effectiveness. Using confocal microscopy it's possible to in vivo demonstrate the efficacy of this method, with normalization of the honeycomb pattern in the epidermis following succcessful PDT.

Efficacy of Single Day-Light Photodynamic Therapy Session with Aminolevulinic Acid 5% Thermosetting Gel with a Penetration-Empowering Facial Mask in the Treatment of Severe Actinic Damage of the Face and Scalp

Introduction: Photodynamic therapy (PDT) is an effective treatment of actinic keratosis (AK) and severe photo aging. Day-light PDT (DL-PDT) is considered an alternative of C-PDT with similar efficacy but with significantly lower procedure-associated pain. A new formulation of ALA at “low” concentration (5%) in a thermosetting gel is available for C-PDT or DL-PDT. When used for PDT the incubation time of this gel is in general 2-2.5 hours. This formulation with high content of water could be feasible for application with penetration-empowering dual mask which could optimize and speed-up the penetration of the active compound through the skin. This mask device comes in two layers. The first layer is wet and in contact with the applied gel. The second layer, which is dry and overlaid on the first, allows the key ingredients to penetrate the stratum-corneum utilizing a micro-current circuit using two anodes placed on each side of the mask acting as natural batteries. This mask could reduce the incubation time of the photosensitizer needed to allow adequate skin penetration before the PDT procedure. Study aim: To evaluate in a pilot-study the efficacy and tolerability of DL-PDT with a thermosetting 5% ALA gel applied using a specific mask penetration-enhancer device. Subjects and methods: A total of 15 men aged >50 years with severe actinic damage of the face or scalp were enrolled in this pilot study. ALA 5% gel was applied (2.5 ml) on the face and scalp. The empowering mask was then put on the treatment area with an incubation time of 1.5 hour. A single day-light session of 20-30 minute (according to the UV fluence of the day) was performed. The primary outcome was the evolution of a 7-item actinic damage score (ADS) evaluating: elastosis, hyperpigmentation, telangiectasia, fine wrinkles, deep wrinkles, stellate pseudo-scar, and presence of actinic keratosis lesions. For each parameter, a 4-grade scale score (0=sign absent; 3: sign severe) was calculated. Therefore, the maximum level of ADS was 21. The baseline visit was performed just before the DL-PDT session; the final evaluation visit was performed two months after the DL-PDT session. A patient-assessed procedurerelated pain score using a 4-point scale (0: no pain; 3: severe pain) was performed at the end of the DL-session. Results: Before DL-PDT, the ADS, mean (SD), score was 16 (5). A total of 74 AK clinically relevant lesions were also present at baseline. At the final visit, the ADS score was significantly reduced to 5(5), corresponding to a -69% reduction. AK lesions at the final visit were reduced by 70% (from 74 to 22). DL-PDT was in general very well tolerated. The procedure-related pain score mean (SD) value was 0.5 (0.5). Conclusion: In subjects with severe actinic damage, a single DL-PDT session with ALA 5% thermosetting gel, with penetration-empowering mask application, was very effective and well tolerated in reducing clinical signs of skin photo damage and reducing AK lesion number.

Daylight photodynamic therapy for severe facial and scalp actinic keratosis: a prospective non-sponsored single-centre study employing the actinic keratosis area and severity index (AKASI)

Daylight photodynamic therapy (DL-PDT) is an effective and convenient treatment for multiple actinic keratosis (AKs). There are limited tools to evaluate the outcome of AK treatment. Recently, the actinic keratosis area and severity index (AKASI) has been proposed as a quantitative tool for assessing AK severity. To investigate patient satisfaction and efficacy of DL-PDT for severe AKs and to validate AKASI scoring as a quantitative tool for assessing the outcome of DL-PDT treatment. In this prospective single-centre study, we analysed the results of patients treated with one or two cycles of DL-PDT for severe AKs in the facial or scalp area. Forty patients (37 male and three female) with a mean age of 74 years (range: 56-87 years) were included and received either one (n = 20) or two (n = 20) cycles of DL-PDT. At baseline, most patients (95%) had 20 or more lesions. Patients treated with one cycle of DL-PDT showed a mean AKASI reduction of 45.5% (p < 0.001). Patients eligible for two cycles of DL-PDT demonstrated a mean AKASI reduction of 23.7% (p < 0.05) after one and 48.2% (p < 0.001) after two cycles. Patients participating in this study were either very satisfied (67.5%) or satisfied (32.5%). Almost all patients (97.5%) would recommend DL-PDT to other patients. DL-PDT is a well-tolerated, safe and efficient treatment option for field cancerisation in the facial and scalp area with high patient satisfaction. AKASI scoring has proven useful as a quantitative tool for assessing the outcome of DL-PDT treatment.

Treatment of actinic cheilitis with daylight photodynamic therapy - clinical and histopathological evaluation

Treatment of actinic cheilitis with daylight photodynamic therapy - clinical and histopathological evaluation

Ablative Fractional Laser-assisted Daylight Photodynamic Therapy for Actinic Keratoses of the Scalp and Forehead in Organ Transplant Recipients: A Pilot Study.

Ablative Fractional Laser-assisted Daylight Photodynamic Therapy for Actinic Keratoses of the Scalp and Forehead in Organ Transplant Recipients: A Pilot Study.

Low-level light-assisted photodynamic therapy using a wearable cap-like device for the treatment of actinic keratosis of the scalp.

Daylight photodynamic therapy (dlPDT) is a painless and increasingly cost-effective treatment for actinic keratosis (AK). New protocols avoid incubation, minimizing pain and adverse events. However, it is time-consuming and dependent on specific weather conditions. In patients with AK of the scalp, we evaluated the efficacy of indoor photodynamic therapy (PDT) using a wearable low-level light therapy (LLLT) device, without pre-incubation with a photosensitizing agent. In this pilot study, 27 patients with thin and moderately thick AK (Olsen Grades I-II) underwent a single 15-minute session of LLLT using a wearable cap-like device immediately after application of methyl-aminolevulinate (MAL) cream, with no prior preparation of the affected area. Treatment efficacy was quantified by measuring the reduction in AK lesion number and the AK quality of life (AKQoL) score. All AK lesions were mapped at baseline for follow-up 2 months later. Paired pre/post scalp biopsies from 5 patients were analysed using histological and immunohistochemical techniques (p53, p27, cyclin D1, p63, and Ki67 expression). Data were analysed using the Wilcoxon signed-rank test. In all patients we observed a global reduction in the number of AK lesions (71%; p < 0.0001) and AKQoL score (from 5.6 to 4.4; p = 0.034) 2 months after treatment. Histology and immunohistochemistry of skin biopsies from 5 patients also revealed marked improvements after LLLT. No patients reported any pain during treatment. PDT using LLLT is a rapid, painless, and efficacious modality for the treatment of AK.

Efficacy of different photoprotection strategies in preventing actinic keratosis new lesions after photodynamic therapy. The ATHENA study: a two-center, randomized, prospective, assessor-blinded pragmatic trial

Background: Treatment of actinic keratosis (AK) and field cancerization with photodynamic therapy (PDT) is an effective therapeutic approach with a significant reduction in the number of AK lesions (–75% or more) associated with a significant cosmetic improvement of the photodamaged skin. Recently, also, the daylight PDT (DL-PDT) has proven to be as effective as the conventional PDT (C-PDT), but with a better tolerability. After C-PDT and DL-PDT it is advised to use photoprotection strategies to improve the clinical evolution and prevent the appearance of new AK lesions that usually appear 3–6 months after the last phototherapy session. However, there are no robust clinical data regarding the type of photoprotection to be used (SPF level, duration of treatment, etc.) after successful PDT.Study aim: The present study (ATHENA trial) evaluated the efficacy and tolerability of a topical product based on 0.8% piroxicam and 50+ solar filters (ACTX), applied twice a day as sequential therapy after C-PDT or DL-PDT on the evolution of AK lesions number compared to the use of very high photoprotection products commonly used in this clinical setting (SPF50+ or SPF100+ associated with photolyase) (Standard Sunscreens: SS group). Subjects and methods: This was a multicenter, randomized, two-arm, prospective controlled, assessor-masked outcome evaluation, parallel group (1:1), pragmatic study of 6 months duration in patients with multiple AK lesions suitable for photodynamic therapy. The objectives of the study were the evaluation of the evolution of the number of AK lesions during the period of treatment/application of the study products, and the Investigator global clinical assessment score (IGA score; 4: marked improvement, 3: good, 2: moderate; 1 no improvement; 0: worsening) 2, 3, and 6 months after the last PDT session. A total of 68 subjects (50 men, 18 women; mean age 70 years), 34 assigned to treatment with ACTX and 34 to treatment with SS (17 treated with a SPF50+ and 17 with a photolyase-containing SPF100+ products), were enrolled in the study.Results: The number of AK lesions present before C-PDT/DL-PDT was 11.8 ± 5.8 in the ACTX group and 12.4 ± 6.9 in the SS group. In both groups, there was a progressive reduction of AK lesions observed at baseline (–86% and –87% after 2 months and –88% and –83% at month 3 in ACTX and in the SS group, respectively). At month 6, AK mean lesion number was 1.8 ± 1.6 in the ACTX and 3.2 ± 2.3 in the SS group; this difference was statistically significant (p = 0.03). The IGA score at the end of the study was 3.2 in the ACTX and 2.7 in the SS group (p = 0.05). The percentage of subjects with an IGA score of 4/3 (very good or good) was 81% in the ACTX and 55% in the SS group (p = 0.06).Conclusion: In subjects with AK treated with C-PDT or DL-PDT, a “medicalized” photoprotection treatment is associated with a favorable clinical outcome with progressive reduction of lesions. In contrast to a very high photoprotection (SPF50+ or SPF100+/photolyase), the use of piroxicam 0.8%/SPF 50+ is associated with a significantly greater improvement in clinical evolution of AK lesions.

Daylight versus conventional photodynamic therapy for the treatment of actinic keratosis: A meta-analysis of randomized controlled trials.

Daylight photodynamic therapy (dPDT) is suggested to be effective for actinic keratosis (AK). We performed a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of dPDT versus conventional photodynamic therapy (cPDT) in patients with AK. Relevant studies were identified through a systematic search of PubMed, Embase, and the Cochrane Library. A fixed or random effect model was applied, depending on the heterogeneity. Six RCTs with 369 patients with 5,556 AK lesions that were undergoing dPDT or cPDT with red light and methyl aminolevulinate (MAL) were included. Overall, the incidence of complete response (CR) was not significantly different between the two groups (risk ratio [RR]: 0.93, p = 0.07). Subgroup analyses indicated that dPDT was non-inferior to cPDT for CR in studies only included grade III AK lesions (RR: 0.97, p = 0.41), but less effective for CR in studies which also included grade III lesions (RR = 0.87, p < 0.001). Subsequent meta-analyses showed that dPDT was associated with a significantly reduced maximal pain score (mean difference = -4.51, p < 0.001) and a lower risk of adverse events (RR = 0.70, p < 0.001) as compared with cPDT. These results suggested although dPDT was better tolerated, the treatment efficacy of dPDT is non-inferior to cPDT with red light and MAL only in grade III AK lesions. The relative therapeutic efficacy of dPDT in AK of grade III lesions in comparison with cPDT should be further evaluated.

Conventional versus daylight photodynamic therapy for actinic keratosis: A randomized and prospective study in China.

Conventional photodynamic therapy (C-PDT) is an effective treatment for actinic keratoses (AKs) in Asia, with some unmet needs. Severe PDT-associated pain results in low treatment willingness. Daylight photodynamic therapy (DL-PDT) is a more simple and tolerable treatment that has the same efficacy as C-PDT in Europe. However, few studies have been conducted with Asian patients. To evaluate the efficacy and safety of DL-PDT vs. C-PDT for treating AK patients in China. This randomized and prospective study was conducted in Shanghai, China. Sixty patients with AKs (grades I-III) were randomized into two groups (DL-PDT and C-PDT). PDT was performed once every two weeks for a total of three times. Patients were evaluated before each treatment (baseline and two weeks after the first and second treatment) and at one month after the third treatment. Endpoints included efficacy (lesion response) and safety (pain scale and adverse events). A total of 55 patients completed the study. At the first month after 3 sessions of PDT, the overall lesion clearance rate of DL-PDT (95.5%) was similar to that of C-PDT (96.8%). However, in some particular parts (eyebrow and sideburns), C-PDT resulted in higher rates of cured lesions than DL-PDT. Additionally, patients undergoing DL-PDT had nearly no pain, showing significantly lower pain scores than those undergoing C-PDT (1.7 ± 0.9 for DL-PDT vs. 5.2 ± 1.7 for C-PDT). Moreover, fewer subjects undergoing DL-PDT had related adverse events than those undergoing C-PDT (36.7% vs. 63.3%). DL-PDT was effective, better tolerated and nearly painless compared with C-PDT in AK patients in China.

Efficacy and safety of daylight photodynamic therapy after tailored pretreatment with ablative fractional laser or microdermabrasion: a randomized, side-by-side, single-blind trial in patients with actinic keratosis and large-area field cancerization.

Physical pretreatments can potentiate the efficacy of daylight photodynamic therapy (dPDT), but clinical comparative studies remain limited. Performed in large skin areas with actinic keratoses (AKs) and photodamage, this blinded, randomized clinical trial compared the efficacy and safety of dPDT after tailored skin pretreatment using ablative fractional laser (AFL) or microdermabrasion (MD). Two ≥ 50-cm2 side-by-side skin areas were randomized to receive a single treatment with AFL-dPDT or MD-dPDT. Pretreatment parameters were tailored according to AK grade and skin constitution to ensure standardized immediate end points. Subsequently, methyl aminolaevulinate was applied, followed by 2-h daylight exposure. The primary outcome comprised blinded assessment of AK clearance at the 3-month follow-up. In 18 patients with 832 AKs, AFL-dPDT provided significantly higher AK clearance (81% vs. 60%, P < 0·001), led to fewer new AKs (P < 0·001) and showed superior improvement in dyspigmentation (P = 0·003) and skin texture (P = 0·001) vs. MD-dPDT. Peaking at days 3-6, AFL-PDT induced more intensified local skin responses (P = 0·004), including instances of Staphylococcus aureus infection (n = 3). Patients nonetheless preferred AFL-dPDT (P = 0·077), due to lower pretreatment-related pain (P = 0·002) and superior cosmesis (P = 0·035) and efficacy compared with MD-dPDT. AFL-dPDT is an effective treatment for patients with AK with extensive field cancerization, although AFL pretreatment is associated with intensified local skin reactions.

Sequential methyl-aminolevulinate daylight photodynamic therapy and diclofenac plus hyaluronic acid gel treatment for multiple actinic keratosis evaluation

No conflict of interest.

A noninterventional study on methyl aminolevulinate daylight-photodynamic therapy in the treatment of multiple actinic keratoses of the face and scalp in six European countries

A noninterventional study on methyl aminolevulinate daylight-photodynamic therapy in the treatment of multiple actinic keratoses of the face and scalp in six European countries

Improved effect on 2 cases of disseminated superficial actinic porokeratosis with daylight photodynamic therapy

Improved effect on 2 cases of disseminated superficial actinic porokeratosis with daylight photodynamic therapy

A novel light source with tuneable uniformity of light distribution for artificial daylight photodynamic therapy.

Implementation of daylight photodynamic therapy (dPDT) is somewhat limited by variable weather conditions. Light sources have been employed to provide artificial dPDT indoors, with low irradiances and comparable treatment times to dPDT. Uniform light distribution across the target area is desirable in effective treatment planning, particularly for large areas. A novel light source is developed with tuneable direction of light emission in order to meet this challenge. Wavelength composition of the novel light source is controlled such that the protoporphyrin-IX (PpIX) weighted spectra of both the light source and daylight match. The uniformity of the light distribution is characterised on a flat surface, a model head and a model leg. For context, a typical conventional PDT light source is also characterised. Additionally, the wavelength uniformity across the treatment site is characterised. The PpIX-weighted spectrum of the novel light source matches the PpIX-weighted daylight spectrum, with irradiance values within the bounds for effective dPDT. By tuning the direction of light emission, improvements are seen in the uniformity across large anatomical surfaces. Wavelength uniformity is discussed. We have developed a light source that addresses the challenges in uniform, multiwavelength light distribution for large area artificial dPDT across curved anatomical surfaces.

Photodynamic therapy of necrobiosis lipoidica using methyl aminolevulinate: A retrospective follow-up study.

Necrobiosis lipoidica (NL) is a rare, treatment-resistant, granulomatous skin disease of unknown origin, frequently seen in patients with diabetes. In this retrospective study we evaluated the long-term efficacy of methyl aminolaevulinate-based photodynamic therapy (MAL-PDT), including 80 treatments (70 conventional and 10 daylight PDT), on 65 unselected NL patients treated routinely in our clinic. Superficial curettage, avoiding skin oozing or bleeding, was performed prior to MAL application. Conventional MAL-PDT had a 100% cure rate (CR) in 64% (45/70) of the treatment series. With daylight PDT we observed a 100% CR in 80% of the treatment series (8/10), an insignificant difference compared to conventional PDT (p = 0.48). The overall cure rate was 66% (53/80). We observed no correlation between CR and gender, age at first PDT treatment, duration of NL prior to PDT treatment, number of NL elements, or diabetes. New lesions faded, whereas old lesions were clearly visible after inactivation of NL. MAL-PDT proved to have full efficacy in 66% of the treatments, with conventional PDT and daylight PDT producing an almost identical result. We observed no correlation between CR and time of follow-up. However, we recommend at least six months to pass before final evaluation of treatment effect.

Long-term efficacy data for daylight-PDT

Conventional photodynamic therapy (c-PDT) is an established successful treatment for non-melanoma skin cancers (NMSC). Daylight PDT (DL-PDT) was introduced to overcome the main inconveniencies associated with c-PDT such as pain during illumination and long clinic visits. DL-PDT was shown to have similar short-term efficacy to c-PDT for the treatment of mild/moderate actinic keratosis (AKs) but it is associated with better tolerability. Since AKs tend to regress and reoccur over time, data on long-term efficacy of DL-PDT become crucial. We performed a systematic review search up to February 2018 of available studies on DL-PDT long-term efficacy using the MEDLINE database and made a manual search of selected references. Most current studies on DL-PDT have limited follow-up periods of 3 to 6 months. Only 2 randomized, intra-individual studies provided efficacy data on AK treatment at 12 month-follow-up and supported the long-term efficacy of this novel treatment modality showing a low recurrence rate, varying from 8.7% to 13%. Current evidences for other NMSCs are limited and efficacy seems to be not as good as for AK. DL-PDT is a very promising treatment for mild to moderate AKs of the face and scalp. Efficacy outcomes of DL-PDT are similar to those of c-PDT in the short-term. Additional studies are required to increase our knowledge on DL-PDT long-term efficacy, as limited data are currently available.

The background and philosophy behind daylight photodynamic therapy.

Conventional photodynamic therapy (PDT) is associated with side effects, primarily related to the waiting time between pretreatment with application of photosensitizer and illumination. Pain during illumination is a major issue for the patients and options for effective pain relief are limited. Post-treatment inflammation can often be severe and cause inconvenient down-time for the patients and their employers. To avoid the problems of pain and patients crowding in the clinic we eliminated red light treatment of high PpIX concentration and introduced illumination in daylight which may be performed at home. We also investigated if protoporphyrin IX (PpIX) could be activated continuously during its formation which might reduce pain and inflammation. Continuous activation of PpIX during its formation turned out to minimize pain as single PpIX molecules are activated continuously without accumulation of PpIX in the skin. PpIX molecules are formed in the mitochondria and the photodynamic effect only takes place in the mitochondria when continuously activated. This results primarily in apoptosis with little inflammation. Continuous activation of PpIX can be obtained by performing photodynamic therapy in daylight, as well as with daylight-emitting light sources of appropriate wavelengths. Use of daylight prevents the patients from crowding in the clinic. Daylight-PDT completely fulfils the purpose of minimizing pain and inflammation, as well as limiting the strain on the clinic treating the patients.

Pain perception during photodynamic therapy: why is daylight PDT with methyl aminolevulinate almost pain-free? A review on the underlying mechanisms, clinical reflections and resulting opportunities

Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is an established and efficacious method for the treatment of non-melanoma skin cancer. However, treatment of especially larger areas often leads to pain, stinging and burning sensation during illumination. The use of daylight (DL) during MAL incubation was investigated in clinical trials and compared to conventional illumination with red LEDs. All clinical trials on MAL DL-PDT show it to be considerably and statistically significantly less associated with pain than conventional PDT while being as efficacious. Fluence rate and light dose seem to be the strongest indicators for pain during PDT. The article summarizes the current knowledge base and shows that the model is able to explain why activation by DL produces less to no pain. Recent clinical trials performed in other latitudes than Northern Europe or Australia confirm that MAL DL PDT is applicable also in regions closer to the equator. MAL DL-PDT carries the potential of MAL self-application by the patient. In several clinical trials, MAL DL-PDT has been compared to topical preparations being administered by the patients themselves. The results show that MAL DL-PDT is superior or at least non-inferior to the tested topical preparations and that its tolerability is better.

Daylight photodynamic therapy for field cancerization: lessons from molecular biology.

Actinic keratoses (AKs) represent in-situ squamous cell carcinomas that potentially invade subepidermal structures and may metastasize. Until now, it is unpredictable to determine which AK lesions show this aggressive behavior. As AKs usually occur in large sun exposed areas, field-directed treatments have become the standard treatment regimen. Among these, conventional photodynamic therapy (cPDT) with 5-aminolaevulinic acid (ALA) or methyl-aminolevulinate (MAL) using red light is particularly effective in the treatment of AKs, but acceptance of the therapy is impaired by severe pain during treatment. Daylight PDT (dPDT) has demonstrated to be an equally effective alternative treatment option which is less painful. Recent attempts to determine the risk of AKs that demonstrate particular aggressive biological behavior by implementation of clinical and histological characteristics of AKs have not lead to conclusive results. Therefore, a look at the molecular biology of AKs could serve as a useful tool to develop a risk profiling for separation of those patients that are of particular risk to develop invasive tumor and, by this, to facilitate a more effective and adapted treatment option.