Methyl Aminolevulinate Research Articles

Is a single day patient friendly methyl aminolevulinate photodynamic therapy illumination scheme for superficial basal cell carcinoma feasible? A randomized multicenter pilot trial

Background: Topical methyl aminolevulinate photodynamic therapy (MAL-PDT) is highly effective for the treatment of superficial basal cell carcinoma (sBCC). Current European treatment protocol requires two hospital visits, which is costly and unpractical. The aim of this study was to evaluate the efficacy of fractionated MAL-PDT, using two light fractions at 3 and 4 h compared to illumination at 3 and 5 h after MAL-application.Methods: Thirty patients were randomized into two groups. The first group received illumination at 3 and 4 h (20 + 55 J/cm2) after MAL-application (3/4 group). In the other group, two light fractions were performed at 3 and 5 h (20 + 55 J/cm2) after MAL-application (3/5 group). The lesion response was evaluated at 3 and 12 months posttreatment.Results: In the 3/5 group, 70.0% showed a complete response (CR) at 3 months compared to 63.6% in the other group. At 12 months, 100% showed a CR in the 3/5 group compared to 80.0% in the other group. However, most failures/recurrences were eventually due to the presence of a more aggressive BCC subtype, mostly caused by sampling error of the primary punch biopsy.Conclusion: Single day protocol for MAL-PDT for sBCC is feasible and this study shows promising results.

Daylight-Mediated Photodynamic Therapy for Actinic Keratosis

ABSTRACT Actinic (solar) keratoses are premalignant lesions caused by prolonged exposure to ultraviolet radiation, with the potential to progress into squamous cell carcinoma. Hence, use of appropriate therapies is critical for effective treatment. Daylight-mediated photodynamic therapy with methyl aminolevulinate cream is a convenient new option for the safe and effective treatment of actinic (solar) keratosis lesions, offering similar efficacy to conventional photodynamic therapy, nearly painless treatment, and reduced in-clinic times. Use of appropriate therapies and optimization of clinical practice are critical for safe and effective treatment. Nurses play a key role in ensuring best clinical practice and effective treatment. This article explains the practicalities and principles of daylight-mediated photodynamic therapy to ensure best practice by treating nurses.

Ablative fractional laser–assisted photodynamic therapy provides superior long-term efficacy compared with standard methyl aminolevulinate photodynamic therapy for lower extremity Bowen disease

Ablative fractional laser (AFL)-assisted methyl aminolevulinate (MAL) photodynamic therapy (PDT) (AFL-MAL-PDT) has shown significantly higher efficacy and lower recurrence rates at 12months than conventional methyl aminolevulinate photodynamic therapy (MAL-PDT) for the treatment of Bowen disease (BD). However, long-term follow-up data are not available. To compare the 5-year efficacy and recurrence rates of AFL-MAL-PDT with those of conventional MAL-PDT for the treatment of lower extremity BD. A total of 60 patients with 84 BD lesions were randomly assigned to a single session of AFL-MAL-PDT or 2 sessions of MAL-PDT with a 1-week interval between sessions. Patients were followed up at 3, 12, 24, 36, 48, and 60months after treatment. Efficacy, recurrence rates, and risk factors for unsuccessful treatments were assessed. After 5years, the overall clearance rate of AFL-MAL-PDT (84.78%) was significantly better than that of MAL-PDT (44.74%) for BD lesions. The recurrence rate was significantly lower for AFL-MAL-PDT (9.3%) than for MAL-PDT (41.38%). Diameters larger than 20mm and lesions with a history of previous treatment were independent factors for treatment failure. The small sample size and single-center study design were limitations. For patients with lower extremity BD lesions, AFL-MAL-PDT showed significantly higherlong-term efficacy and lower recurrence rates than standard MAL-PDT.

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.

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.

Photodynamic Therapy Interventions in Facial Photodamage: A Systematic Review

IntroductionPhotodynamic therapy (PDT) involves the combination of a light source and a photosensitizing agent to induce tissue damage via the generation of singlet oxygen. Although topical PDT has been approved for other indications, its use in facial photodamage is uncertain. AimsTo assess the efficacy and safety of PDT in facial skin photoaging. MethodsAll randomized clinical trials (RCTs) evaluating the efficacy and safety of any form of topical PDT for the treatment of facial photodamage (dermatoheliosis) or photoaging in patients older than 18 years, were included. Photodynamic-therapy using any topical photosensitizing agent at any dose, and with any light-source, were considered. Comparators were chemical exfoliation, intense pulsed light (IPL), light emitting diodes (LED), dermabrasion or microdermabrasion, ablative or non-ablative lasers, injectables, surgery, placebo and/or no treatment.A systematic search in PubMed, Embase, Lilacs, Google Scholar and RCT's registry databases, was performed. ResultsSearch was conducted up to May 4th 2016. Four authors independently selected and assessed methodological quality of each RCT. According to inclusion criteria, twelve studies were included (6 aminolevulinate (ALA) trials and 6 methyl aminolevulinate (MAL) trials), but the majority of them had methodological constraints particularly in randomization description and patients/outcome assessors blindness. Discussion and conclusionsOverall results indicated that PDT either with ALA or with MAL was effective and safe for facial photodamage treatment, but high quality of evidence was found mainly for MAL studies.

Photodynamic therapy for aesthetic-cosmetic indications.

Photodynamic therapy (PDT) is a well-established, non-invasive treatment for a variety of dermatologic disorders, including actinic keratosis. Furthermore, PDT results in marked improvements in the signs of skin aging, although currently there are no standardized guidelines for PDT in skin rejuvenation. Two types of PDT are available: conventional-PDT (c-PDT) and the newly introduced daylight-PDT (DL-PDT). Both require a topical photosensitizer, a light source and oxygen, and both are comparable regarding safety and efficacy for treatment of photo-induced skin aging. Treatment is particularly effective for improvement of fine wrinkles, skin roughness, actinic elastosis and mottled hyperpigmentation. The most widely studied topical sensitizers used in PDT are 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL). A range of pre-treatment procedures help improve skin absorption of the photosensitizer and lead to significantly improved efficacy. A variety of activating light sources can be used for c-PDT, while DL-PDT uses natural daylight, making it easier to treat larger areas of photodamaged skin. A major limitation of c-PDT is significant treatment-related pain, but DL-PDT has proved to be an almost pain-free procedure. Treatment duration is based on individual patient need but most patients receive 2 to 3 treatment cycles, with results fully evident 3-6 months post-treatment. PDT for aesthetic-cosmetic treatments has established its value in modern procedural dermatology as mono- or combination therapy. A major, unique advantage of PDT is that it is a non-invasive treatment that effectively rejuvenates photodamaged skin, while successfully treating a range of dermatologic conditions, including prevention and therapy of pre-cancerous actinic keratosis.

Randomized clinical trial testing the efficacy and safety of 0.5% colchicine cream versus photodynamic therapy with methyl aminolevulinate in the treatment of skin field cancerization: study protocol

BackgroundThe primary clinical manifestation of skin field cancerization is the presence of actinic keratoses (AKs). Current treatments for AKs related to skin field cancerization include photodynamic therapy (PDT) and colchicine. The objective of this study is to evaluate the efficacy and safety of 0.5% colchicine cream versus PDT with methyl aminolevulinate (MAL-PDT) in the treatment of skin field cancerization.MethodsIn a randomized controlled and open clinical trial with a blind histopathological and immunohistochemical analysis, 36 patients with up to 10 AKs on their forearms will be included from the outpatient clinic. The forearms will be randomized into two groups, clinically evaluated and biopsied for histopathology and immunohistochemistry (p53 and Ki67). One forearm will be treated with 0.5% colchicine cream for 10 days, and the other forearm will receive one session of MAL-PDT; the forearms will subsequently be reassessed clinically and histologically after 60 days (T60) of treatment. The primary endpoint will be the point of complete clearance of AKs in T60. The sample size will enable a detection in the reduction of over 10% in AK counts between the groups with power of 0.9 and an alpha of 0.05, accounting for an estimated dropout rate of 10%, resulting in 36 patients (72 forearms). All participants included in the randomized study will be part of the analysis, and the final outcomes of any dropouts will be the value of their last visit (LOCF). The statistical analysis will be performed using SPSS 22.0, and a p value < 5% will be considered to be significant.DiscussionIt is expected that colchicine will be superior to MAL-PDT in reducing AKs and in the skin field cancerization, and there will be good tolerability in both groups. Colchicine intervention is novel in that it provides a new alternative to MAL-PDT. Moreover, this drug is inexpensive that may be a potential treatment of skin field cancerization that can be prescribed in public health systems with good results.Trial registrationThe trial is registered in Brazilian Registry for Clinical Trials (Registration number: RBR-8y3sj9, date assigned May 4, 2016, retrospectively registered).

Protoporphyrin IX formation after application of methyl aminolevulinate on the face and scalp with and without prior curettage.

Pulse photodynamic therapy (PDT) is carried out as classical PDT except that methyl aminolaevulinate (MAL) is removed after 30 min. Protoporphyrin IX (PpIX) accumulation becomes lower after 3 h in pulse-PDT than in classical PDT, but pulse-PDT still has full treatment effect on actinic keratosis (AK). The present study aimed to investigate when PpIX formation in classical PDT without curettage reaches the PpIX level in pulse-PDT with curettage in the skin of the face and scalp. Fourteen patients with AKs in the face and scalp were included in this pilot study. Each patient had two fields randomly allocated to two different regimes: (i) continuing MAL incubation without prior curettage (-Cur) and (ii) 30 min MAL incubation after curettage (+Cur). The PpIX level in each field was measured with a hand-held fluorescence photometer every 30 min for 6 h after MAL application. No illumination was performed. The median PpIX level in the +Cur field after 3 h was 22 arbitrary units (AU), which represents the amount of PpIX that could have been photobleached after pulse-PDT with maximal treatment effect. After 3 h the median PpIX level in the -Cur field was 20 AU, which was not significantly different from the level in the +Cur field (p = 0.9). We propose PDT without curettage as follows: 3 h of MAL incubation and subsequently sufficient illumination. The treatment effect of this regime should be tested to verify if curettage of the face and scalp area may be omitted in PDT.

Field Cancerization Therapies for Management of Actinic Keratosis: A Narrative Review.

Actinic keratoses (AKs) are atypical, precancerous proliferations of keratinocytes that develop because of chronic exposure to ultraviolet (UV) radiation. Treatment of AK can be lesion-directed or field-directed. Field cancerization theory postulates that the skin surrounding AK is also at increased risk for possible malignant transformation since it has been exposed to the same chronic UV light. Field-directed therapies thus have the potential to address subclinical damage, reduce AK recurrence rates, and potentially reduce the risk of squamous cell carcinoma (SCC) development. Published clinical studies have found lesion clearance rates ranging from 81 to 91% for photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL). Clinical studies have also been published on various topical treatments. Complete clinical clearance (CCC) was significantly higher in patients treated with a combination of 5-fluorouracil and salicylic acid (5-FU-SA) than in the vehicle group across multiple studies, and CCC ranged between 46 and 48% following treatment with imiquimod. Additionally, treatment with diclofenac sodium (DFS) found reduction in lesion sizes to range from 67 to 75%. Reported results have been similar for another non-steroidal anti-inflammatory drug (NSAID), piroxicam, which has more cyclooxygenase (COX)-1 activity than DFS. Active treatments with ingenol mebutate were also significantly more effective than vehicle at clearing AK lesions. All treatments resulted in mild, localized skin reactions. PDT using conventional light sources was associated with increased severity of pain and/or discomfort, while PDT using daylight as the light source was associated with less pain and occasionally no pain at all. Though no widely accepted algorithm for the treatment of AKs exists, field-directed therapy can be particularly useful for treating photo-exposed areas containing multiple AKs. Additional research with more direct comparisons between these field-directed therapies will help clinicians determine the best therapeutic approach. Here, we provide a balanced and comprehensive narrative review of the literature, considering both light-based and topical therapies with a focus on their field-therapy aspects, and propose a therapeutic algorithm for selecting an appropriate treatment in the clinical setting.

How to choose among the multiple options to enhance the penetration of topically applied methyl aminolevulinate prior to photodynamic therapy

How to choose among the multiple options to enhance the penetration of topically applied methyl aminolevulinate prior to photodynamic therapy

Photodynamic Therapy Activated by Intense Pulsed Light in the Treatment of Nonmelanoma Skin Cancer.

Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) has proven to be a highly effective conservative method for the treatment of actinic keratosis (AK), Bowen’s disease (BD), and superficial basal cell carcinoma (sBCC). PDT is traditionally performed in association with broad-spectrum continuous-wave light sources, such as red or blue light. Recently, intense pulsed light (IPL) devices have been investigated as an alternative light source for PDT in the treatment of nonmelanoma skin cancers (NMSC). We herein report our observational findings in a cohort of patients with a diagnosis of AK, sBCC, and BD that is treated with MAL-PDT using IPL, as well as we review published data on the use of IPL-PDT in NMSC.

Comparing Topical Treatments for Basal Cell Carcinoma

Superficial basal cell carcinoma is a type of keratinocyte carcinoma that has increasing incidence and substantial morbidity. Jansen etal. report on a randomized trial with 5 years of follow-up that found imiquimod to be more effective than 5-fluorouracil or methyl aminolevulinate photodynamic therapy in preventing superficial basal cell carcinoma recurrence. However, the toxicity and cost of topical treatments, as well as patient preferences, need to be evaluated when making treatment decisions in clinical practice.

Daylight-Mediated Photodynamic Therapy With Methyl Aminolevulinate in Actinic Keratosis Treatment.

Research has shown daylight-mediated photodynamic therapy (PDT) for the treatment of actinic keratosis (AK) to be effective, tolerable, and convenient, with excellent patient satisfaction and cosmesis. Although success has been demonstrated in areas with similar latitudes to Switzerland and Scandinavia, this treatment has not been studied in a Canadian population. The purpose of this study is to investigate the effectiveness, safety, and patient satisfaction of daylight-mediated methyl 5-aminolevulinate (MAL)-PDT to make recommendations for its use in Canadian practice. A retrospective chart review of patients who received treatment of daylight-mediated MAL-PDT for the indication of AK at the Institute of Cosmetic and Laser Surgery in Oakville, Ontario, between 2009 and 2016. A total of 112 patients were included, consisting of 94 males and 18 females with a mean age of 63.79 years. A total of 177 sites were treated among all patients, mostly consisting of the face (n = 92) and scalp (n = 55). A total of 13.4% of patients experienced side effects, the most common being redness (n = 4) and scabbing (n = 4). Of the 42 patients who expressed their level of satisfaction, 83.3% reported being happy with the treatment, χ2(1) = 18.67, P ≤ .05; 6.3% of patients were noted to be completely clear, 86.6% had a good response, 0.9% had a mild response, and 0% had no response, χ2(1) = 101.04, P ≤ .05. Daylight-mediated MAL-PDT is a suitable treatment option for AK lesions in a Canadian population due to the demonstrated efficacy, patient satisfaction, tolerability, and convenience.

Daylight Photodynamic Therapy Versus 5-Fluorouracil for the Treatment of Actinic Keratosis: A Case Series.

IntroductionThe incidence of actinic keratosis (AK) continues to increase worldwide. Currently available options for the treatment of AK include topical 5-fluorouracil (5-FU) and daylight-mediated photodynamic therapy (DL-PDT). This split-face pilot study compared DL-PDT using 16% methyl aminolevulinate (MAL) cream versus 5-FU cream in patients with AK on the face/scalp.MethodsFive male subjects (mean age 70 years) with grade I–III AK on the face/scalp were enrolled. Subjects received a single session of DL-PDT with 16% MAL on one side and topical 5% 5-FU for 21 days on the other side. Evaluations of efficacy, safety, and subject satisfaction were conducted 48 h, 7 days, 14 days, 1 month, and 3 months after treatment.ResultsAt 3 months, the lesion complete response rate was 80% and 93% for DL-PDT and 5-FU, respectively. Lesion partial response was 20% and 7%, respectively. Fewer treatment-related adverse events (AEs) were reported with DL-PDT than with 5-FU, and they resolved spontaneously in 5–7 and 27–30 days, respectively. Subjects preferred DL-PDT because of the lower incidence of AEs and rapid recovery compared with 5-FU.ConclusionDL-PDT is a convenient alternative to 5-FU with good efficacy and a favorable safety profile, allowing patients to effectively treat their AK without compromising their social life.FundingGalderma.

Photodynamic Therapy Interventions in Facial Photodamage: A Systematic Review

IntroductionPhotodynamic therapy (PDT) involves the combination of a light source and a photosensitizing agent to induce tissue damage via the generation of singlet oxygen. Although topical PDT has been approved for other indications, its use in facial photodamage is uncertain. AimsTo assess the efficacy and safety of PDT in facial skin photoaging. MethodsAll randomized clinical trials (RCTs) evaluating the efficacy and safety of any form of topical PDT for the treatment of facial photodamage (dermatoheliosis) or photoaging in patients older than 18 years, were included. Photodynamic-therapy using any topical photosensitizing agent at any dose, and with any light-source, were considered. Comparators were chemical exfoliation, intense pulsed light (IPL), light emitting diodes (LED), dermabrasion or microdermabrasion, ablative or non-ablative lasers, injectables, surgery, placebo and/or no treatment.A systematic search in PubMed, Embase, Lilacs, Google Scholar and RCT's registry databases, was performed. ResultsSearch was conducted up to May 4th 2016. Four authors independently selected and assessed methodological quality of each RCT. According to inclusion criteria, twelve studies were included (6 aminolevulinate (ALA) trials and 6 methyl aminolevulinate (MAL) trials), but the majority of them had methodological constraints particularly in randomization description and patients/outcome assessors blindness. Discussion and conclusionsOverall results indicated that PDT either with ALA or with MAL was effective and safe for facial photodamage treatment, but high quality of evidence was found mainly for MAL studies.

Patient and physician satisfaction in an observational study with methyl aminolevulinate daylight photodynamic therapy in the treatment of multiple actinic keratoses of the face and scalp in six European countries.

BackgroundGuidelines recommend treating actinic keratoses (AKs) as they are recognized as precursors of invasive squamous cell carcinoma.ObjectiveThe objective of this study was to collect real‐world clinical data on the use of methyl aminolevulinate daylight photodynamic therapy (MAL DL‐PDT) for the treatment of face and scalp AK in Europe.MethodsA prospective, multicenter, non‐interventional study was conducted in six European countries in patients receiving a single treatment of MAL DL‐PDT for face and/or scalp AK. Patient‐reported outcomes were assessed by patient questionnaires at baseline and at 3 months after treatment, efficacy was assessed at 3 months using a 6‐point global improvement scale, and adverse events (AE) were recorded at each visit.ResultsOverall, 325 patients were enrolled from 52 investigational centres, 314 of whom attended the 3‐month visit. Most patients had multiple lesions (58.4% had >10 lesions) with lesions mainly located on the scalp (60.0%) and/or forehead (54.2%). AKs were predominantly grade I (39.4%) or grade II (33.2%), and 10.5% of patients had grade III lesions. The proportions of patients and physicians that were overall satisfied to very satisfied with the MAL DL‐PDT treatment were 80.4% and 90.3%, respectively. The vast majority of patients (90.0%) would consider using MAL DL‐PDT again if needed. Physician‐assessed efficacy at 3 months was at least much improved in 83.5% of patients, with 45.9% of patients requiring no retreatment. Related AEs were reported in 15% of patients.ConclusionUse of MAL DL‐PDT for multiple face and/or scalp AKs resulted in high levels of patient and physician satisfaction in clinical practice in Europe, reflecting the good efficacy and high tolerability of this convenient procedure.

Topical calcipotriol before ablative fractional laser-assisted photodynamic therapy enhances treatment outcomes for actinic keratosis in Fitzpatrick grades III-V skin: A prospective randomized clinical trial

Topical calcipotriol before ablative fractional laser-assisted photodynamic therapy enhances treatment outcomes for actinic keratosis in Fitzpatrick grades III-V skin: A prospective randomized clinical trial

Daylight photodynamic therapy versus cryosurgery for the treatment and prophylaxis of actinic keratoses of the face\xa0\u2212\xa0protocol of a multicenter, prospective, randomized, controlled, two-armed study

BackgroundPhotodynamic therapy with daylight (DL-PDT) is efficacious in treating actinic keratosis (AK), but the efficacy of field-directed, repetitive DL-PDT for the treatment and prophylaxis of AK in photodamaged facial skin has not yet been investigated.Methods/designIn this multicenter, prospective, randomized, controlled, two-armed, observer-blinded trial, patients with a minimum of 5 mild-to-moderate AK lesions on photodamaged facial skin are randomly allocated to two treatment groups: DL-PDT with methyl aminolevulinate (MAL) and cryosurgery. In the DL-PDT group (experimental group), 5 treatments of the entire face are conducted over the course of 18 months. After preparation of the lesion and within 30 min after MAL application, patients expose themselves to daylight for 2 h. In the control group, lesion-directed cryosurgery is conducted at the first visit and, in the case of uncleared or new AK lesions, also at visits 2 to 5. The efficacy of the treatment is evaluated at visits 2 to 6 by documenting all existing and new AK lesions in the face. Cosmetic results and improvement of photoaging parameters are evaluated by means of a modified Dover scale.Primary outcome parameter is the cumulative number of AK lesions observed between visits 2 and 6.Secondary outcome parameters are complete clearance of AK, new AK lesions since the previous visit, cosmetic results independently evaluated by both patient and physician, patient-reported pain (visual analogue scale), patient and physician satisfaction scores with cosmetic results, and patient-reported quality of life (Dermatology Life Quality Index). Safety parameters are also documented (adverse events and serious adverse events).DiscussionThis clinical trial will assess the efficacy of repetitive DL-PDT in preventing AK and investigate possible rejuvenating effects of this treatment. (Trial registration: ClinicalTrials.gov Identifier: NCT02736760).Trial registrationClinicalTrials.gov Identifier: NCT02736760. Study Code Daylight_01. EudraCT 2014–005121-13.