Enhanced reduction of polymicrobial biofilms on the orthodontic brackets and enamel surface remineralization using zeolite-zinc oxide nanoparticles-based antimicrobial photodynamic therapy.

The aim of this study was to evaluate the anti-biofilm and anti-metabolic activities of zeolite-zinc oxide nanoparticles (Zeo/ZnONPs)-based antimicrobial photodynamic therapy (aPDT) against pre-formed polymicrobial biofilms on the orthodontic brackets, as well as, assess the remineralization efficacy on polymicrobial biofilms induced enamel lesions. Following synthesis and characterization of Zeo/ZnONPs, cell cytotoxicity, hemolytic effect, and intracellular reactive oxygen species (ROS) production were determined. The anti-biofilm and anti-metabolic activities of aPDT using different concentrations of Zeo/ZnONPs were investigated. Microhardness tester and DIAGNOdent Pen were used to evaluate the changes of remineralization degree on the treated enamel slabs duration 1 and 3 months. No significant cytotoxicity and erythrocyte hemolysis were observed in treated cells with Zeo/ZnONPs. When irradiated, suggesting that the Zeo/ZnONPs were photoactivated, generating ROS and leading to reduce dose-dependently the cell viability and metabolic activity of polymicrobial biofilms. Also, the enamel surface microhardness value of exposed enamel showed a steady increase with the concentration of Zeo/ZnONPs. No statistically significant differences were shown between aPDT and sodium fluoride varnish as the control group. Overall, Zeo/ZnONPs-based aPDT with the greatest remineralization efficacy of enamel surface can be used as an anti-biofilm therapeutic method, which is involved with their potent ability to produce ROS.

Iridium(III) Complex-Derived Polymeric Micelles with Low Dark Toxicity and Strong NIR Excitation for Phototherapy and Chemotherapy.

Iridium(III) complexes are potent candidates for photodynamic therapy. However, their clinical usage is impeded by their poor water solubility, high dark toxicity, and negligible absorption in near-infrared region (NIR region). Here, it is proposed to solve these challenges by developing an iridium(III) complexe-based polymeric micelle system. This system is self-assembled using an iridium(III) complex-containing amphiphilic block polymer. The upconversion nanoparticles are included in the polymeric micelles to permit NIR excitation. Compared with the nonformulated iridium(III) complexes, under NIR stimulation, this polymeric micelle system exhibits higher 1 O2 generation efficiency, negligible dark toxicity, excellent tumor-targeting ability, and synergistic phototherapy-chemotherapy effect both in vitro and in vivo.

TREatment of ATopic eczema (TREAT) Registry Taskforce: an international Delphi exercise to identify a core set of domains and domain items for national atopic eczema photo- and systemic therapy registries.

BACKGROUND: Evidence of immunomodulatory therapies to guide clinical management of atopic eczema (AE) is scarce, despite frequent and often off-label use. Patient registries provide valuable evidence for the effects of treatments under real-world conditions that can inform treatment guidelines, give the opportunity for health economic evaluation and the evaluation of quality of care, as well as pharmacogenetic and dynamic research, which cannot be adequately addressed in clinical trials. OBJECTIVES: The TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek international consensus on a core set of domains and items ('what to measure') for AE research registries, using a Delphi approach. METHODS: Participants from six stakeholder groups were included: doctors, nurses, nonclinical researchers, patients, industry and regulatory body representatives. The eDelphi comprised three sequential online rounds, requesting participants to rate the importance of each proposed domain item. Participants could add domain items to the proposed list in round 1. A final consensus meeting was held to ratify the core set. RESULTS: Participants (n = 479) from 36 countries accessed the eDelphi platform, of whom 86%, 79% and 74% completed rounds 1, 2 and 3, respectively. At the face-to-face consensus meeting attended by 42 participants the final core set was established containing 19 domains with 69 domain items (49 baseline and 20 follow-up items). CONCLUSIONS: This core set of domains and items to be captured by national AE systemic therapy registries will standardize data collection and thereby allow direct comparability across registries and facilitate data pooling between countries. Ultimately, it will provide greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immunomodulatory therapies.

Photodynamic therapy in the treatment of symptomatic oral lichen planus: A systematic review.

BACKGROUND: The aim of this systematic review was to assess the efficacy of photodynamic therapy (PDT) in the treatment of symptomatic oral lichen planus (OLP). METHODS: This systematic review aimed to address the following focused question: "Is PDT effective in the treatment of symptomatic OLP?" Indexed databases such as MEDLINE, EMBASE, and CENTRAL were searched up to and including August 2017. RESULTS: Six clinical studies were included. The risk of bias was considered high in 5 studies and moderate in one study. Parameters of PDT such as wavelengths, energy fluence, power density and exposure time ranged between 320-660 nm, 120 J/cm2 , 130 mW/cm2 , and 70-150 seconds, respectively. The follow-up period ranged from 4 to 48 weeks. All included studies reporting clinical scores showed that PDT was effective in the treatment of OLP in adult patients at follow-up. However, PDT did not show significant improvement when compared with steroid therapy. CONCLUSION: Photodynamic therapy appears to have some effect in the symptomatic treatment of OLP in adult patients. However, further randomized controlled trials with long follow-up period, standardized PDT parameters, and comparing the efficacy of PDT with steroid therapy are warranted to obtain strong conclusions in this regard.

Safety evaluation of repeated intravenous infusion of sinoporphyrin with and without PDT in rats.

Photodynamic therapy (PDT) is a promising antineoplastic modality in the oncology field. We assessed the safety of repeated intravenous administrations of sinoporphyrin, a porphyrin derivative, with and without illumination in rats. Toxicokinetic studies of single and multiple administrations of sinoporphyrin were also carried out. Sprague-Dawley rats were randomly assigned to the dark-toxicity and PDT groups. Animals in the dark toxicity group received an i.v. infusion of sinoporphyrin at 3 doses: 2 mg kg-1, 6 mg kg-1, and 18 mg kg-1. The PDT group included 2 doses of sinoporphyrin (2 mg kg-1 and 18 mg kg-1), and the rats received 60 J of 630 nm laser illumination 24 h after photosensitizer infusion. The treatments were repeated every 7 days for 5 cycles and were followed by a 14-day recovery period. Systematic analyses were conducted at the end of treatment and recovery periods. Blood samples were obtained 5 min, 30 min, 2 h, 8 h, 24 h, 48 h, 72 h, and 96 h after the first and fifth treatments for toxicokinetic studies. Sinoporphyrin-PDT led to the death of one out of 270 rats; the dead animal had been treated with 18 mg kg-1 sinoporphyrin and died at the end of the fifth PDT treatment. Liver injury, the primary toxicity observed in the study, was identified using biochemical tests, necropsy, and histopathology. Elevated white blood cell and neutrophil counts were found in the rats in both the dark toxicity and PDT groups. Skin lesions at the illumination site were obvious in the PDT group. Pigment deposits were detected in multiple organs such as the liver, spleen, lymph nodes, and ovaries in the 6 mg kg-1 and 18 mg kg-1 groups. No other abnormalities were observed. The toxicokinetic parameters of single and multiple sinoporphyrin administrations were calculated and compared. Repeated sinoporphyrin administrations both alone and in combination with laser illumination were tolerable, and all toxicities were transient. The no observed adverse effect level (NOAEL) for repeated sinoporphyrin administration and sinoporphyrin-PDT was 6 mg kg-1 and 2 mg kg-1, respectively. Further studies are warranted.

Photodynamic Therapy: A Clinical Consensus Guide.

BACKGROUND: The American Society of Dermatologic Surgery (ASDS) periodically develops consensus documents for its members concerning various aspects of dermatologic surgery. Advances in photodynamic therapy (PDT) have been many and PDT use has been established in a variety of skin conditions. OBJECTIVE: The ASDS board of directors proposed a committee of experts in the field to develop consensus documents on different treatments. An expert panel reviewed the literature on PDT and discussed the findings. The consensus was reached with evidence-based recommendations on different clinical applications for PDT. PATIENTS AND METHODS: This consensus document includes discussions regarding PDT, including different photosensitizers and various light source activators, historical perspective, mechanism of action, various therapeutic indications and expected outcomes, pre- and post-care, and management of adverse outcomes. RESULTS: Photodynamic therapy is highly effective for pre-cancerous lesions, superficial nonmelanoma skin cancers, inflammatory acne vulgaris and other conditions. New protocols including laser mediated PDT significantly improve results for several indications. CONCLUSION: The ASDS consensus document on PDT will be helpful for educating members on safe and effective PDT for a variety of indications.

[Approaches to phototherapy in children with chronic dermatosis (review of literature)].

The article covers main aspects of phototherapy and photochemotherapy in treatment of skin diseases in children, risks of such methods usage, prophylactic and therapeutic measures, and precaution means for such treatment in pediatrics.

Vascular-targeted photodynamic therapy with TOOKAD® Soluble in localized prostate cancer: standardization of the procedure.

INTRODUCTION: Vascular-targeted photodynamic therapy with TOOKAD(®) Soluble is an innovative focal therapy procedure assessed in localized prostate cancer treatment. MATERIALS AND METHODS: This mini-invasive technique destroys targeted tissues using a photosensitizer [TOOKAD(®) Soluble (WST11), STEBA Biotech] activated by laser light in the presence of oxygen. Its application for prostate cancer requires intravenous infusion of TOOKAD(®) Soluble and the illumination of the targeted area by transperineal optical fibers inserted under trans-rectal ultrasound guidance under general anesthesia. CONCLUSION: Based on the experience gained through hundreds of procedures, we describe here the standardized technique of vascular-targeted photodynamic therapy with TOOKAD(®) Soluble defined during the phase II and III trials.

Practical approach to the use of daylight photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: a European consensus.

INTRODUCTION: Daylight-mediated photodynamic therapy has been shown to be an effective therapy for actinic keratoses (AKs) and a simple and tolerable treatment procedure in three randomized Scandinavian studies and two recent Phase III randomized controlled studies in Australia and Europe. OBJECTIVES: To establish consensus recommendations for the use of daylight photodynamic therapy (DL-PDT) using topical methyl aminolaevulinate (MAL) in European patients with AKs. METHODS: The DL-PDT consensus recommendations were developed on behalf of the European Society for Photodynamic Therapy in Dermatology and comprised of 10 dermatologists from different European countries with experience in how to treat AK patients with PDT. Consensus was developed based on literature review and experience of the experts in the treatment of AK using DL-PDT. RESULTS: The recommendations arising from this panel of experts provide general guidance on the use of DL-PDT as a dermatological procedure with specific guidance regarding patient selection, therapeutic indications, when to treat, pre-treatment skin preparation, MAL application and daylight exposure for patients with AK in different countries of Europe. CONCLUSIONS: This consensus recommendation provides a framework for physicians to perform DL-PDT with MAL cream while ensuring efficiency and safety in the treatment of patients with AK in different European countries.

Daylight PDT with MAL - current data and practical recommendations of an expert panel.

Photodynamic Therapy (PDT) is one of the standard treatment modalities for actinic keratoses (AKs). Daylight PDT (DL-PDT) with MAL cream is a rather recent development, which, instead of an artificial light source, uses daylight for the activation of the photosensitizer. The present review summarizes available data based on a selective literature search, highlights practical aspects, and reflects the authors' expert knowledge in using DL-PDT. With respect to efficacy, study data shows that DL-PDT is noninferior to conventional PDT (cPDT). However, given that DL-PDT is markedly less painful, it is significantly better tolerated than cPDT. In Europe, DL-PDT can be performed from March to October, on sunny as well as on cloudy days. UV protection of untreated areas of the body should be observed. Outside temperature should not fall below 10°C. On hot days, patients should be advised to stay in the shade if necessary. Representing a useful addition to current therapeutic options, DL-PDT with MAL cream is, among others, suitable for patients with field cancerization and/or those who have experienced severe pain associated with cPDT.

A survey of photodynamic therapy services in dermatology departments across Scotland.

There is good evidence to support the use of topical PDT for superficial nonmelanoma skin cancer and dysplasia; however, there is little information available on the structure, process and outcomes of PDT in clinical practice. We undertook a national survey to determine how PDT was being undertaken in dermatology centres in Scotland. We highlight important information on the practicalities of PDT service delivery and the types of patients and diagnoses treated, and provide preliminary information on the outcomes achieved. These data will be invaluable as a starting point to agree on minimum standards for PDT and criteria to audit against these standards.

Photodynamic therapy for skin rejuvenation: treatment options - results of a consensus conference of an expert group for aesthetic photodynamic therapy.

In addition to providing effective treatment for non-melanoma skin cancers or their precursors, photodynamic therapy (PDT) has also attracted considerable attention for its use on aesthetic dermatology. In a first consensus publication the mechanisms of action of its photorejuvenation effects and recent studies were presented; in this paper treatment protocols for the different anatomical regions exposed to chronic sun damage like face, neck, décolleté and the back of the hands are given and suitable procedures for pre- and after-care are discussed.

Photodynamic therapy of lung cancer with photosensitizers based on polycationic derivatives of synthetic bacteriochlorin (experimental study).

BACKGROUND: One of the tasks of anticancer photodynamic therapy is increasing the efficacy of treatment of cancer nodes with large (clinically relevant) sizes using near-infrared photosensitizers (PS). METHODS: The anticancer efficacy and mechanisms of the photodynamic action of PS based on polycationic derivatives of synthetic bacteriochlorin against Lewis lung carcinoma were studied in vitro and in vivo. RESULTS: It was found that studied PS have high phototoxicity against Lewis lung carcinoma cells: the IC50 values were about 0.8 µM for tetracationic PS and 0.5 µM for octacationic PS. In vivo studies have shown that these PS provide effective inhibition of the tumor growth with an increase in the lifespan of mice in the group by more than 130%, and more than 50% survival of mice in the group. CONCLUSIONS: Photosensitizers based on polycationic derivatives of synthetic bacteriochlorin have high photodynamic efficacy caused by the induction of necrosis and apoptosis of cancer cells, including cancer stem cells, and a sharp decrease of mitotic and proliferative activity. Studied polycationic photosensitizers are much more effective at destroying cancer stem cells and newly formed cancer vessels in comparison with anionic photosensitizers, and ensure the cessation of tumor blood flow without hemorrhages and thrombosis.

New guidelines in the treatment of persistent central serous chorioretinopathy: PDT with half-dose verteporfin.

BACKGROUND: In persistent central serous chorioretinopathy (CSC) resolution of detachment can be achieved by photodynamic therapy. Our objective was to evaluate the efficacy of half-dose verteporfin compared to full-dose verteporfin. PATIENTS AND METHODS: In 2009 the standard PDT regimen for CSC in our clinic was changed from full-dose to half-dose verteporfin. After a retrospective analysis 11 cases of half-dose PDT with documented course in 11 patients are presented. A comparison was performed with a control group of 11 consecutive patients with documented course who had received full-dose PDT before 2009. RESULTS: Prior to PDT there were no statistically significant differences between the groups concerning age, central foveal thickness, thickness of detachment, BCVA (EDTRS) and size of spot. 6 weeks after PDT a significant reduction of foveal thickness and detachment was detected in both groups, as well as a significant increase in BCVA. No statistically significant differences in outcome could be found between the two groups (Mann-Whitney U-test, p < 0.05). CONCLUSIONS: PDT with half-dose verteporfin seems to be an effective and safe treatment for persistent CSC. Our data showed comparable results after half-dose and after full-dose PDT.

Photodynamic therapy for American cutaneous leishmaniasis: the efficacy of methylene blue in hamsters experimentally infected with Leishmania (Leishmania) amazonensis.

The aim of this study was to investigate the effectiveness of Photodynamic Therapy (PDT) using Methylene Blue (MB) as the photosensitizing compound and a Light-Emitting Diode (LED) in American cutaneous leishmaniasis (ACL). Hamsters were experimentally infected with Leishmania (Leishmania) amazonensis. After the development of the lesions in the footpad, the animals were treated with MB three times a week for 3 months. Ten minutes after each application of MB, the lesions were irradiated with LED for 1 h. The lesions were evaluated weekly by the measurement of the hamster footpad thickness. At the end of the treatment the parasitic load was quantified in the regional lymph node of the hamsters. The treatment promoted a decrease in the thickness of infected footpad (P=0.0001) and reduction in the parasitic load in the regional lymph node (P=0.0007) of the animals from group treated with MB+LED. PDT using MB+LED in ACL caused by L. amazonensis shows a strong photodynamic effect. This therapy is very promising, once it is an inexpensive system and the own patient can apply it in their wound and in their house without the need of technical assistance.

Photodynamic therapy procedures in coronavirus (COVID-19) outbreak: perception of health risks among clinical dental faculty and dental students.

OBJECTIVE: The aim of the study was to investigate clinical faculty members and final year dentistry students' perceptions regarding their health concerns and risks of performing photodynamic therapy (PDT) procedure in dental clinics amidst the COVID-19 pandemic. SUBJECTS AND METHODS: A 21-item questionnaire comprising open and closed questions was sent to dental faculty members (n=43) and final year dentistry students (n=99) of Riyadh Elm University during mid-January 2021 that ended only after two weeks. The survey included health risks perception of performing PDT procedures, the impact of the COVID-19 outbreak on PDT performance and stress levels, perceived efficacy of the preventive steps, perception of the effect of the probable suspension of PDT procedure in dental clinics, and influence of alternative teaching methods of PDT procedure on clinical competence were reported. RESULTS: A response rate of 82% for faculty members (n=35) and 75% for students (n=74) was recorded. 91% of faculty members and 95% of students felt that their health was not at risk during performing PDT procedure in dental clinics amidst the COVID-19. 82% of faculty and 83% of students expressed that the PPE and universal preventive steps to perform PDT procedure were enough for preventing the cross-infection with the virus. 89% of faculty members and 91% of students thought that a provisional suspension of PDT procedures in dental clinics would assist in containment of the virus and reduce the infection risk from the contact and not the PDT procedure. CONCLUSIONS: Students and faculty members reported that their health is not at risk while performing PDT procedure in dental clinics amidst the COVID-19 outbreak.

Contemporary approaches and future perspectives of antibacterial photodynamic therapy (aPDT) against methicillin-resistant Staphylococcus aureus (MRSA): A systematic review.

The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) causing skin and soft tissue infections in both the community and healthcare settings challenges the limited options of effective antibiotics and motivates the search for alternative therapeutic solutions, such as antibacterial photodynamic therapy (aPDT). While many publications have described the promising anti-bacterial activities of PDT in vitro, its applications in vivo and in the clinic have been very limited. This limited availability may in part be due to variabilities in the selected photosensitizing agents (PS), the variable testing conditions used to examine anti-bacterial activities and their effectiveness in treating MRSA infections. We thus sought to systematically review and examine the evidence from existing studies on aPDT associated with MRSA and to critically appraise its current state of development and areas to be addressed in future studies. In 2018, we developed and registered a review protocol in the International Prospective Register of Systematic Reviews (PROSPERO) with registration No: CRD42018086736. Three bibliographical databases were consulted (PUBMED, MEDLINE, and EMBASE), and a total of 113 studies were included in this systematic review based on our eligibility criteria. Many variables, such as the use of a wide range of solvents, pre-irradiation times, irradiation times, light sources and light doses, have been used in the methods reported by researchers, which significantly affect the inter-study comparability and results. On another note, new approaches of linking immunoglobulin G (IgG), antibodies, efflux pump inhibitors, and bacteriophages with photosensitizers (PSs) and the incorporation of PSs into nano-scale delivery systems exert a direct effect on improving aPDT. Enhanced activities have also been achieved by optimizing the physicochemical properties of the PSs, such as the introduction of highly lipophilic, poly-cationic and site-specific modifications of the compounds. However, few in vivo studies (n = 17) have been conducted to translate aPDT into preclinical studies. We anticipate that further standardization of the experimental conditions and assessing the efficacy in vivo would allow this technology to be further applied in preclinical trials, so that aPDT would develop to become a sustainable, alternative therapeutic option against MRSA infection in the future.

Techniques to Improve Photodynamic Therapy.

Photodynamic therapy [dye-light therapy] is an excellent technique for use in detection and treatment of cancerous tissues. While this therapy is effective, it is limited by the phototoxic reactions that can occur in the surrounding normal tissues. These damaging side effects are of particular importance when treating neurosensory organs, such as the human eye. We report here new treatment strategies to enhance photodynamic effectiveness while limiting side effects to normal tissues.

Baseline factors predicting the need for corneal crosslinking in patients with keratoconus.

INTRODUCTION: The primary purpose of crosslinking is to halt the progression of ectasia. We retrospectively assessed the condition of keratoconus patients who were followed-up at least twice after the initial examination to evaluate keratoconus progression, to identify definitive factors to predict a later need for corneal crosslinking (CXL). METHODS: The medical charts of 158 eyes of 158 keratoconus patients (112 males and 46 females; mean age, 27.8 ± 11.7 years), who were followed up at the Department of Ophthalmology, Keio University School of Medicine at least twice after the initial examination to evaluate keratoconus progression were retrospectively reviewed. Best-spectacle corrected visual acuity, intraocular pressure, steepest corneal axis on the anterior float (Ks), thinnest corneal thickness according to Pentacam® HR, and corneal endothelial cell density were assessed. Gender, age, onset age of keratoconus, history of atopic dermatitis, and Pentacam® indices were also recorded. CXL was performed when the eye showed significant keratoconus progression, an increase in the steepest keratometric value, or an increase in the spherical equivalent or cylinder power of the manifest refraction by more than 1.0 D versus the respective values 2 years prior. Predictor variables and the requirement for CXL were analyzed using logistic regression. RESULTS: Fifty-eight eyes required CXL treatment. The best predictor of the requirement for CXL was patient age, followed by the Pentacam® Rmin (the minimum sagittal curvature evaluated by Pentacam®) value. The incidence of CXL was 86.4% in the < 20 years age group, with an Rmin of ≤ 5.73 mm, whereas 10.8% in the ≥ 27 years age group with an Rmin > 5.73 mm underwent treatment. CONCLUSIONS: An age of < 20 years and an Rmin value of ≤ 5.73 mm predicted keratoconus progression and the requirement for CXL treatment in the near future.