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Photodynamic Therapy (PDT) is a rapidly evolving, non-invasive treatment modality with considerable promise in dental pharmacotherapeutics. This review article comprehensively examines PDT, beginning with its principles and then delving into its diverse applications in dentistry, including periodontal disease, endodontics, oral cancer, dental implants, and dental caries. Each area presents the latest research and discusses the potential benefits and challenges. The unique advantages of PDT are highlighted, such as selective targeting, broad-spectrum antimicrobial effect, lack of resistance development, and its synergistic effect with other treatments. However, challenges such as photosensitizer delivery, light penetration, oxygen availability, and the need to standardize protocols are also acknowledged. The review further explores future perspectives of PDT in dentistry, including advancements in photosensitizer design, overcoming hypoxic limitations, personalized protocols, integration with other therapies, and standardization and regulation. The potential of advanced technologies, such as nanotechnology and synthetic biology, to improve PDT outcomes is also discussed. The review concludes that while PDT has shown immense potential to revolutionize dental pharmacotherapeutics, further high-quality research is needed to translate this potential into everyday dental practice. The promising future of PDT in dentistry suggests a more effective and less invasive treatment option for a range of dental conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To quantify corneal cross-linking (CXL)-induced stiffening via mechanical testing to estimate the impact of changes in hydration levels (H) and evaluate depth-dependent tissue hydration after CXL., Methods: Eighty-three porcine corneal buttons were divided into three groups: Standard protocol CXL (S-CXL), accelerated CXL (A-CXL), and untreated (nonirradiated riboflavin-only) controls. Samples were hydrated or dehydrated to modulate H and dynamic mechanical analyzer compression tests were performed to measure Young's modulus (E). To extract the solid tissue network modulus, the cornea was modeled as a biphasic material after measuring E at different H. Corneal hydration was correlated with depth-dependent tissue thickness characterized by confocal reflection microscopy (CRM)., Results: Young's modulus increased fourfold after S-CXL (0.72 ± 0.1 MPa) and threefold after A-CXL E (0.53 ± 0.12 MPa) versus controls (0.17 ± 0.045 MPa). However, H decreased from 4.07 ± 0.35 in controls to 2.06 ± 0.2 after S-CXL and 2.79 ± 0.12 after A-CXL. After H modulation and biphasic mechanical modeling, Young's modulus for corneal solid tissue network showed only a 1.8-fold increase after S-CXL (2.25 MPa) and 1.5-fold increase after A-CXL (1.85 MPa) versus controls (1.22 MPa). With CRM, the overall thickness of the corneal tissue was found to linearly correlate to hydration H as expected. No appreciable depth dependence of hydration-induced thickness changes throughout the corneal buttons were observed., Conclusions: Corneal tissue hydration changes significantly impact measured corneal stiffness after CXL using mechanical testing. Not considering H leads to major overestimation of the stiffening effect of the CXL procedure. Depth-dependence of corneal thickness because of changing hydration is strongly dependent on the integrity of the tissue.

Photodynamic therapy (PDT) is an alternative to cancer treatment, demonstrating selectivity and significant cytotoxicity on malignant tissues. Such therapy involves two nontoxic components: photosensitizer (PS) and non-ionizing radiation. In optimal dosage combinations, PDT causes cellular and tissue effects by oxygen-dependent processes, leading tumor cells to regulated cell death pathways. Regulated necrosis, called necroptosis, can be triggered by PDT and is characterized by caspase-8 inhibition and RIPK1, RIPK3, and MLKL activities, leading to plasma membrane pores formation with subsequent cellular content release into the extracellular space. For this review, studies accessed by PubMed describing the relation between necroptosis and PDT were summarized. The results showed that PDT can trigger necroptosis mechanisms in different tumor cells. Moreover, a mix of different cell death types can co-occur. It is also important to highlight that necroptosis triggered by PDT is related to damage-associated molecular patterns (DAMPs) release, involving immunogenic cell death and vaccination. The cell death response is directly related to the photosensitizer chemical characteristics, concentration, incubation time, cellular location, and irradiation parameters. The synergism among all cell death types is an excellent advantage for avowing tumor resistance mechanisms and developing new solutions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

High Epidermal growth factor receptor (EGFR) in Cutaneous Squamous Cell Carcinoma (cSCC) is associated with poor prognosis and advanced metastatic stages, severely impeding the efficacy of EGFR-targeting immunotherapy. This is commonly attributed to the combinatory outcomes of hypoxic tumor microenvironment (TME) and immunosuppressive effector cells together. Herein, a novel paradigm of EGFR-targeting oxygen-saturated nanophotosensitizers, designated as CHPFN-O 2 , has been specifically tailored to mitigate tumor hypoxia in EGFR-positive cSCC and achieve Cetuximab (CTX)-mediated immunotherapy (CIT). The conjugated CTX in CHPFN-O 2 serves to initiate immune responses by recruiting Fc receptor (FcR)-expressing immune effector cells towards tumor cells, thereby eliciting antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular trogocytosis (ADCT) and antibody-dependent cellular cytotoxicity (ADCC). Besides, CHPFN-O 2 can engender a shift from a tumor-friendly to a tumor-hostile one through improved tumor oxygenation, contributing to oxygen-elevated photodynamic therapy (oxPDT). Notably, the combination of oxPDT and CIT eventually promotes T-cell-mediated antitumor activity and successfully inhibits the growth of EGFR-expressing cSCC with good safety profiles. This comprehensive oxPDT/CIT integration aims not only to enhance therapeutic efficacy against EGFR high cSCC but also to extend its applicability to other EGFR high malignancies, thus delineating a new avenue for the highly efficient synergistic treatment of EGFR-expressing malignancies., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: We evaluated the timing at and extent to which midterm to long-term keratometric changes can occur in year 1 to 7 after corneal collagen cross-linking (CXL) in patients with keratoconus., Methods: We conducted a subgroup analysis of a retrospective cohort study of all consecutive patients who underwent CXL at our cornea center between 2007 and 2011. The inclusion criteria comprised CXL according to the Dresden protocol and a full set of keratometry parameters collected by Scheimpflug tomography preoperatively and at year 1, 3, 5, and 7 after CXL. In addition, best-corrected visual acuity was evaluated., Results: Sixty-three eyes of 47 patients were enrolled. Mean age was 25.46 years ±7.39 years (80.9% male patients). All relevant keratometric parameters showed significant improvement at year 1 after CXL (except for posterior astigmatism). According to mixed-effects model analysis, they all showed further significant change at different points in time between year 1, 3, 5, and 7 (except for K1). In addition, best-corrected visual acuity improved statistically significant between year 1, 3, 5, and 7. Suspected disease progression was noted in 22.2% of patients, mostly between year 1 and 3 after CXL., Conclusions: After initial improvement 1 year after CXL, keratometric and functional parameters were stable until year 5 after CXL in most cases; further improvement can take place even after up to 7 years post-CXL. By contrast, in case of disease progression, changes seem to occur already between year 1 and 3 after CXL., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Corneal collagen cross-linking (CXL) can halt corneal ectasia. Leaving corneal epithelium intact during treatment may reduce the incidence of complications. However, it is under debate whether this reduces efficacy and if oxygen supplementation may be necessary to optimize the cross-linking effect. This study aimed to investigate the impact of hyperbaric oxygenation (HBO) on intracorneal oxygen concentrations during epi-off and epi-on CXL., Methods: CXL was performed using riboflavin and ultraviolet-A (UV-A) irradiance (3 mW/cm 2 for 30 min) on porcine corneas under normobaric and hyperbaric conditions, with and without supplemented oxygen, with and without epithelium. Intracorneal oxygen concentrations were continuously monitored before and during irradiation. Biomechanical properties were assessed through tensile strength testing., Results: HBO alone did not cause perceivable changes in stromal oxygen concentrations. Oxygen supplementation resulted in higher oxygen concentration in corneal stroma during CXL. HBO may cause a further increase in oxygen levels, although this was not statistically significant in this study. Notably, a tendency of oxygen levels to rise continuously during UV-irradiation was observed using HBO. Biomechanical properties showend no statistically significant differences between any groups., Conclusions: In this ex-vivo model, HBO increased stromal oxygen levels during CXL, regardless of the presence of corneal epithelium. The dynamics in oxygen concentrations in corneal stromal tissue during CXL suggest that time is an important factor to consider in modifications of established protocols. Also, we hypothesize that stromal levels of riboflavin and UV-A irradiance may be more critical to the CXL effect when oxygen is supplemented and epithelium is not removed.

Purpose: To compare safety and efficacy of isolated and combined UV-light corneal crosslinking (CXL) and fine-needle diathermy (FND) to regress pathological corneal vessels in vivo., Methods: Mice with inflamed and pathologically vascularized corneas received CXL or FND as monotherapy or a combination of both treatments. Corneal pathological blood and lymphatic vessels, immune cells and the morphology of anterior segment structures were evaluated., Results: All three approaches were able to regress blood and lymphatic vessels in mice. A comparative analysis of the three methods revealed that the FND monotherapy and the CXL + FND combination were significantly more effective than the CXL monotherapy, one and 2 weeks after therapy and especially in regressing lymphatic vessels. Furthermore, the combination therapy induced significantly less immune cell recruitment compared to the monotherapies. All three methods were safe to use in regards of corneal integrity., Conclusions: A combination of FND and CXL led to regression of pathological corneal lymphatic and blood vessels and reduced the infiltration of immune cells into inflamed murine corneas. This approach offers a new effective, safe and clinically usable strategy to treat eyes with mature pathological blood vessels and even more so for lymphatic vessels, for example prior to high-risk corneal transplantation., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Cancer stem cells, characterized by high tumorigenicity and drug-resistance, are often responsible for tumor progression and metastasis. Aldehyde dehydrogenases, often overexpressed in cancer stem cells enriched tumors, present a potential target for specific anti-cancer stem cells treatment. In this study, we report a self-assembled nano-prodrug composed of aldehyde dehydrogenases activatable photosensitizer and disulfide-linked all-trans retinoic acid for diagnosis and targeted treatment of cancer stem cells enriched tumors. The disulfide-linked all-trans retinoic acid can load with photosensitizer and self-assemble into a stable nano-prodrug, which can be disassembled into all-trans retinoic acid and photosensitizer in cancer stem cells by high level of glutathione. As for the released photosensitizer, overexpressed aldehyde dehydrogenase catalyzes the oxidation of aldehydes to carboxyl under cancer stem cells enriched microenvironment, activating the generation of reactive oxygen species and fluorescence emission. This generation of reactive oxygen species leads to direct killing of cancer stem cells and is accompanied by a noticeable fluorescence enhancement for real-time monitoring of the cancer stem cells enriched microenvironment. Moreover, the released all-trans retinoic acid, as a differentiation agent, reduce the cancer stem cells stemness and improve the cancer stem cells enriched microenvironment, offering a synergistic effect for enhanced anti-cancer stem cells treatment of photosensitizer in inhibition of in vivo tumor growth and metastasis., (© 2024. The Author(s).)

Purpose: To evaluate the safety and efficacy of different time-point combinations of intrastromal corneal ring segment (ICRS) implantation using femtosecond technology) and corneal collagen crosslinking (CXL) for the treatment of moderate-to-severe keratoconus (KCC)., Methods: This study included 69 eyes of 69 patients with keratoconus who underwent ICRS and CXL treatment at an Eye Hospital between March 2020 and March 2023. The patients were divided into two groups: Group 1 (n = 33 eyes of 33 patients), which received ICRS and CXL treatment in one session, and Group 2 (n = 36 eyes of 36 patients), which included treatment with ICRS for at least 6 months following CXL application. Preoperative and postoperative evaluations included visual acuity, autorefractometer refraction, corneal tomographic measurements using the Sirius (CSO) Scheimpflug camera and the TONOREF™ III device, and documentation of observed complications. Uncorrected visual acuity (UCVA) and best-corrected spectacle visual acuity (BCVA) were measured in each eye individually, and visual acuity was assessed using the logarithm of the minimum angle of resolution (logMAR)., Results: In Group 1, mean UCVA improved from 0.81 ± 0.34 to 0.45 ± 0.25 (p < 0.01), and mean BCVA improved from 0.76 ± 0.35 to 0.38 ± 0.20 (p < 0.01). In Group 2, mean UCVA improved from 0.71 ± 0.32 to 0.43 ± 0.30 (p < 0.01), and mean BCVA improved from 0.65 ± 0.25 to 0.31 ± 0.23 (p < 0.01). Both groups showed significant reductions in manifest spherical and cylindrical refraction (p < 0.01). Group 1 exhibited greater reductions in maximum keratometry (Kmax), flat keratometry (K1), steep keratometry (K2) (p < 0.05), and astigmatic aberration compared with group 2 (p < 0.01). The use of simultaneous or separate CXL and ICRS does not significantly increase the incidence of complications., Conclusions: Both combined and separate CXL and ICRS treatments resulted in significant improvement in UCVA and BCVA and reduced manifest refraction. Although improvements were observed in groups 1 and 2 in terms of K1, K2, and Kmax at 6 months, the improvements were more pronounced in Group 1. These results highlight the potential benefits of simultaneous ICRS + CXL treatment and underscore the importance of optimising the timing of CXL treatment to achieve the best visual outcomes., (© 2024. The Author(s).)

Activation of the innate immune Stimulator of Interferon Genes (STING) pathway potentiates antitumor immunity. However, delivering STING agonists systemically to tumors presents a formidable challenge, and resistance to STING monotherapy has emerged in clinical trials with diminishing natural killer (NK) cell proliferation. Here, we encapsulated the STING agonist diABZI within polymersomes containing a Type I photosensitizer (NBS), creating a nanoagonist (PNBS/diABZI) for highly responsive tumor immunotherapy. This structure promoted H-aggregation and intersystem crossing of NBS, resulting in a ∼ 3-fold amplification in superoxide anion and singlet oxygen generation. The photodynamic therapy directly damaged hypoxia tumor cells and stimulated the proliferation of NK cells and cytotoxic T lymphocytes, thereby sensitizing STING immunotherapy. A single systemic intravenous administration of PNBS/diABZI eradicated orthotopic mammary tumors in murine models, achieving long-term antitumor immune memory to inhibit tumor recurrence and metastasis and significantly improving long-term tumor-free survival. This work provides a design rule for boosting reactive oxygen species production by promoting the intersystem crossing process, highlighting the potential of Type I photosensitizer-polymer vehicles for augmenting STING immunotherapy.

Oral squamous cell carcinoma (OSCC) is the most prevalent and deadly malignancy of the head and neck. The standard treatments for OSCC are surgery, radiotherapy, and chemoradiotherapy, which can cause severe cosmetic and functional damage to the oral cavity and impair the patients' quality of life. Photodynamic therapy (PDT) is a promising alternative that uses light-activated photosensitizers to induce selective phototoxicity and necrosis in the target tissues. PDT has several advantages over conventional treatments, such as minimal invasion, low side effects, high selectivity and preservation of the oral function and appearance. This review explores the principles, mechanisms, and current applications of PDT for OSCC. We address the challenges, such as the depth of light penetration and tissue hypoxia, and underscore the progressive innovations in photosensitizer enhancement, nanotechnological integration, and precision therapy. The exploration of biomarkers for refining patient selection and tailoring individualized treatment regimens is also undertaken. PDT holds promise as a secure and efficacious modality for OSCC management. Nonetheless, additional investigation is imperative to refine treatment protocols and validate sustained therapeutic success., Competing Interests: The authors declare that they have no competing interests., (© 2024 Zhang et al.)

The Greek roots of the word "photodynamic" are as follows: "phos" (φω~ς) means "light" and "dynamis" (δύναμις) means "force" or "power". Photodynamic therapy (PDT) is an innovative treatment method based on the ability of photosensitizers to produce reactive oxygen species after the exposure to light that corresponds to an absorbance wavelength of the photosensitizer, either in the visible or near-infrared range. This process results in damage to pathological cancer cells, while minimizing the impact on healthy tissues. PDT is a promising direction in the treatment of many diseases, with particular emphasis on the fight against cancer and other diseases associated with excessive cell growth. The power of light contributed to the creation of phototherapy, whose history dates back to ancient times. It was then noticed that some substances exposed to the sun have a negative effect on the body, while others have a therapeutic effect. This work provides a detailed review of photodynamic therapy, from its origins to the present day. It is surprising how a seemingly simple beam of light can have such a powerful healing effect, which is used not only in dermatology, but also in oncology, surgery, microbiology, virology, and even dentistry. However, despite promising results, photodynamic therapy still faces many challenges. Moreover, photodynamic therapy requires further research and improvement.

Photodynamic therapy (PDT) represents a targeted approach for cancer treatment that employs light and photosensitizers (PSs) to induce the generation of reactive oxygen species (ROS). However, PDT faces obstacles including insufficient PS localization, limited light penetration, and treatment resistance. A potential solution lies in nanogenerators (NGs), which function as self-powered systems capable of generating electrical energy. Recent progress in piezoelectric and triboelectric NGs showcases promising applications in cancer research and drug delivery. Integration of NGs with PDT holds the promise of enhancing treatment efficacy by ensuring sustained PS illumination, enabling direct electrical control of cancer cells, and facilitating improved drug administration. This comprehensive review aims to augment our comprehension of PDT principles, explore associated challenges, and underscore the transformative capacity of NGs in conjunction with PDT. By harnessing NG technology alongside PDT, significant advancement in cancer treatment can be realized. Herein, we present the principal findings and conclusions of this study, offering valuable insights into the integration of NGs to overcome barriers in PDT., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Cancer treatment continues to be a substantial problem due to tumor complexities and persistence, demanding novel therapeutic techniques. This review investigates the synergistic potential of combining photodynamic therapy (PDT) and tailored medication delivery technologies to increase mitochondrial toxicity and improve cancer outcomes. PDT induces selective cellular damage and death by activating photosensitizers (PS) with certain wavelengths of light. However, PDT's efficacy can be hampered by issues such as poor light penetration and a lack of selectivity. To overcome these challenges, targeted drug delivery systems have emerged as a promising technique for precisely delivering therapeutic medicines to tumor cells while avoiding off-target effects. We investigate how these technologies can improve mitochondrial targeting and damage, which is critical for causing cancer cell death. The combination method seeks to capitalize on the advantages of both modalities: selective PDT activation and specific targeted drug delivery. We review current preclinical and clinical evidence supporting the efficacy of this combination therapy, focusing on case studies and experimental models. This review also addresses issues such as safety, distribution efficiency, resistance mechanisms, and costs. The prospects of further research include advances in photodynamic agents and medication delivery technology, with a focus on personalized treatment. In conclusion, combining PDT with targeted drug delivery systems provides a promising frontier in cancer therapy, with the ability to overcome current treatment limits and open the way for more effective, personalized cancer treatments.

Purpose: The purpose of this study was to investigate corneal stiffening after epithelium-off accelerated corneal cross-linking (CXL; 9 mW/cm²) in progressive keratoconus (KC) with different methods of epithelial debridement., Methods: This was a retrospective, interventional, and non-randomized study. In group 1, the epithelium was removed using a hockey knife (N = 45). In group 2 (N = 39) and group 3 (N = 22), the epithelial thickness was measured by optical coherence tomography (OCT) and the epithelium was ablated by excimer laser, but, in group 3, stromal ablation was performed additionally to correct high order aberrations (HOAs). Corneal biomechanics (integrated invers radius [IIR], stress-strain index [SSI]) and corneal tomography (thinnest corneal thickness [TCT]) were assessed with Corvis ST and Pentacam prior to and 1 month after CXL., Results: Corneal tomography did not differ among the groups preoperatively (P > 0.05). TCT decreased significantly in all groups after surgery (all P < 0.05). Nonetheless, corneal biomechanical stiffening was found in all three groups indicated by a decreased IIR and an increased SSI (all P < 0.05). For group 3, the HOA improved significantly (P < 0.001). Among the groups, there were no significant differences in changes of biomechanical parameters, but TCT was significantly reduced after laser ablation., Conclusions: Corneal stiffening after CXL is independent from epithelial removal. In particular, despite the removal of stromal tissue to correct HOA, a stiffening effect was achieved in keratoconic corneas, even it was less pronounced compared to mechanical epithelial removal. The reduction in HOA indicates a possible improvement in visual acuity., Translation Relevance: Cross-linking stiffens the keratoconus independent of epithelial debridement technique and may compensate minor stromal laser ablation.

Objective: Keloids are characterized by abnormal activation of fibroblasts and excessive collagen deposition. Keloids are notoriously difficult to treat effectively due to their high recurrence rate after therapy. Our study explored the use of the punch technique in conjunction with photodynamic therapy, a novel approach that may swiftly reduce keloid volume, promote collagen remodeling, mitigate inflammation and enhance the wound healing process., Methods: In our study, we conducted a retrospective analysis of 47 keloid patients who were treated with cross-punch technique combined with photodynamic therapy (punch+PDT group), compared them with a control group of 42 patients who received cross-punch therapy alone (punch group). The visual Analog Scale (VAS) scoring system, the Dermatology Life Quality Index (DLQI) questionnaire and the subjective scoring of patients were implemented to assess the improvement rate at baseline (month 0) and 12-month follow-up (month 12)., Results: The results demonstrated significant enhancements in both VAS scores and DLQI scores on month 12 when compared with those on month 0. Notably, the subjective scoring indicated a marked difference, with 93.62 % of patients in the punch+PDT group and 59.52 % in the punch group reporting good or excellent improvement., Conclusion: Patients in the punch+PDT group had a significant improvement rate than those in the punch group., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Photodynamic therapy (PDT) has shown good short-term efficacy in the treatment of oral leukoplakia (OLK). However, the malignant transformation of OLK was seldom evaluated in most PDT studies. Therefore, this study evaluated the effect of PDT on the risk of malignant transformation of OLK., Methods: Kaplan-Meier survival analysis, COX regression, and sensitivity analysis were used to evaluate the effects of PDT on the risk of malignant transformation of OLK. Subgroup analyses were performed to explore the role of PDT in OLK patients with different clinical characteristics., Results: OLK patients with older age (HR=1.032, P = 0.018) and non-homogeneous lesion (HR=2.104, P = 0.044) had higher risk of malignant transformation. Patients who had finished a complete course of PDT (HR=0.305, P = 0.006) had a significant lower risk of malignant transformation, while those who hadn't finished a complete course of PDT (HR=0.692, P = 0.352) cannot be considered to have such a protective effect. In the subgroup analyses, complete PDT course showed a significant protective effect on malignant transformation of OLK in patients with female sex, no smoking or drinking habits, non-homogeneous lesions, lesions on oral mucosa outside the dangerous region, and any grade of epithelial dysplasia., Conclusions: A complete course of PDT could significantly reduce the risk of malignant transformation of OLK, especially in those patients with risk factors of malignant transformation., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: As a rare subcutaneous infection, protothecosis is easily misdiagnosed. Similar to other subcutaneous infection, there is no unified standard for treatment, for cases not suitable for surgery, clinicians often use antifungal drugs based on their experience, and the course of treatment varies from several months to several years. Based on the fact that there are few relevant materials and researches on photodynamic therapy (PDT), we conducted a study based on a clinical case that used oral itraconazole combined with 5-aminolevylinic acid photodynamic therapy (ALA-PDT) to treat a patient with cutaneous protothecosis caused by Prototheca wicherhamii., Methods: Different concentrations of ALA and different light doses were used to investigate the effects of ALA-PDT on the growth inhibition of P. wickerhamii in vitro with Colony-counting Methods. And we used transmission electron microscopy (TEM) to visualize the structural changes and the effects of ALA-PDT treating on cellular structures of the P. wickerhamii. Futher, we performed the susceptibility test of P. wickerhamii to itraconazole before and after ALA-PDT in vitro., Results: We have successfully treated a patient with cutaneous protothecosis caused by P. wickerhamii by using combination therapy in a total of 9-week course of treatment. In vitro, ALA-PDT can inhibit the growth of P. wickerhamii when the ALA concentration was 5 mg/mL (P < 0.01), and this effect became stronger as the concentration of ALA or light dose is increased. Using TEM, we confirmed that ALA-PDT can disrupt the cell wall structure and partition structure of P. wickerhamii, which may contribute to its inhibitory effect. Further studies showed that the MIC of itraconazole for P. wickerhamii was decreased after ALA-PDT., Conclusions: ALA-PDT combined with oral itraconazole can be used to treat cutaneous protothecosis. Accordingly, ALA-PDT can destroy the cell wall and partition structure of P. wickerhamii leading to an inhibitory effect on it in vitro, and the effect is enhanced with the increase of ALA concentration and light dose. Also, the sensitivity of P. wickerhamii to itraconazole is observed increased after ALA-PDT. So our study provides a theoretical basis for the promising treatment against cutaneus protothecosis., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Female vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease of the vulva and its etiology is unknown. The main clinical symptoms are itching, burning and dyspareunia, and there is a lack of effective treatment., Methods: Clinical and follow-up data of women with VLS who underwent 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) from January 2023 to December 2023 in the department of obstetrics and gynecology, Qilu Hospital of Shandong University, were retrospectively analyzed. According to the inclusion and exclusion criteria, 36 patients with VLS who received ineffective conventional treatment (intractable VLS) were enrolled. Objective signs and subjective symptoms of vulvar lesions were recorded before treatment and 6 months after the end of treatment according to corresponding scoring criteria. Quality of life was evaluated using the Dermatology Life Quality Index (DLQI)., Results: All patients received six sessions of ALA-PDT treatment and follow-up visits. After ALA-PDT treatment, 24 of 36 (66.67 %) patients' itching symptoms completely disappeared, 10 of 36 (27.78 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients' symptoms were not significantly relieved. 16 of 36 (44.4 %) patients' itching symptoms completely disappeared, 9 of 36 (25 %) patients' itching symptoms were relieved from severe to mild, and only 2 of 36 (5.56 %) patients still had severe pain. Compared to 22 patients with dyspareunia before treatment, only 9 patients still had dyspareunia with varying degrees of dyspareunia relief after treatment. Clinical signs improved significantly in the patients after ALA-PDT treatment. The total scores of clinical signs were (5.31 ± 1.67 vs 3.67 ± 1.71) before and after treatment. All patients showed improvement in DLQI after treatment. The main side effects of ALA-PDT were pain, erythema and swelling which were transient and tolerable. All patients were "satisfied" or "very satisfied" with the results of the treatment., Conclusions: ALA-PDT is a safe and effective treatment for women with intractable vulva lichen sclerosus., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Acne is a chronic inflammatory skin disease. Photodynamic therapy (PDT) is a highly effective and safe drug-device combination treatment, typically using red and blue light. However, direct comparisons of aminolevulinic acid (ALA)-based PDT using these two light sources are lacking. Therefore, we compared the efficacy and adverse effects of ALA-based 450 nm blue laser-mediated PDT (BL-PDT) and 630 ± 10 nm red light-emitting diode-mediated PDT (RL-PDT) in the treatment of moderate-to-severe acne vulgaris, including analyses of different lesion types., Methods: Sixteen patients with moderate-to-severe acne vulgaris were recruited. All patients underwent BL-PDT on the left side of the face and RL-PDT on the right side. Treatments were administered thrice at 2-week intervals, and follow-up continued for 2 weeks after the final treatment. The average rates of improvement in inflammatory and non-inflammatory acne lesions, IGA (Investigator's Global Assessment) scales, and IGA success rates were calculated. In addition, adverse effects during and after each treatment were recorded., Results: At the 2-week follow-up after the final treatment, the average rates of improvement in total acne, inflammatory, and non-inflammatory lesions were 48.0 %, 63.0 %, and 30.0 % in the BL-PDT group and 42.2 %, 58.1 %, and 27.5 % in the RL-PDT group, respectively. The IGA scores for the two groups decreased by 1.8 and 1.7 points, respectively, and the IGA success rate was 53.3 % in both groups. There were no significant differences between the BL-PDT and RL-PDT groups in any measure of effectiveness. However, the BL-PDT group exhibited more severe adverse effects, especially pain and hyperpigmentation., Conclusions: BL-PDT and RL-PDT have similar efficacies in moderate-to-severe acne vulgaris and are particularly effective for inflammatory acne lesions. RL-PDT benefits from milder adverse effects than those of BL-PDT., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The combination of photodynamic therapy (PDT) and LL-37 has never been tested in an animal study and our research team background suggests this strategy might be a promising alternative to intensify periodontitis resolution. This study aimed to assess the effects of multiple sessions of PDT with chlorin-e6 conjugated to the antimicrobial peptide LL-37 loaded nanoemulsion, as adjunctive therapy in experimental periodontitis in rats., Methods: Experimental periodontitis was induced in 81 rats. After disease establishment, animals were assigned to three groups: SRP (scaling and root planning); SRP + 1PDT, SRP followed by a single PDT session; SRP + 4PDT (n = 27), SRP followed by four PDT sessions at 0, 24, 48 and 72 h after SRP. Animals were subjected to euthanasia at 7, 14 and 28 days, and samples were submitted to osteoclast quantification, immunological and microtomography analysis., Results: All treatments resulted in significant periodontal improvements and there was no significant difference between the groups in both local inflammatory response and healing process. Minimal adjunctive effects could be found for the combined therapy in terms of cytokine levels (IL-1β and IL-10), with no statistical significance. However, the number of TRAP-positive osteoclasts per mm of alveolar bone linear surface for the group treated with PDT sessions was significantly lower than those treated with SRP only., Conclusions: Multiple PDT sessions with chlorin-e6 and LL-37 nanoemulsion as an adjunct to scaling and root planning reduced the presence of osteoclast in the local site but did not contribute towards bone regeneration and IL-1β and IL-10 levels., Competing Interests: Declaration of competing interest This manuscript has been read and approved in final form by all authors and the authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Our previous clinical trial demonstrated that antimicrobial photodynamic therapy (aPDT) with methylene blue (MB) and potassium iodide (KI) effectively killed Candida albicans (C. albicans) in adult AIDS patients with oral candidiasis, regardless of biofilm formation or 25S rDNA genotype. This study evaluated changes in antifungal susceptibility and virulence gene expression in C. albicans before and after aPDT, and explored factors related to clinical aPDT efficacy., Methods: Twenty-one adult AIDS patients with C. albicans oral candidiasis were divided into Group a (400 μM MB, N = 11) and Group b (600 μM MB, N = 10). Both groups received two aPDT treatments, where MB was applied for 5 min, followed by 300 mM KI, and illuminated for 30 min (37.29 J/cm²). C. albicans isolates were collected before and after treatment to assess antifungal susceptibility (fluconazole, itraconazole, flucytosine, amphotericin B) and gene expression (CAT1, HWP1). Peripheral blood tests were analyzed for correlations with aPDT efficacy., Results: aPDT reduced minimum inhibitory concentration (MIC) values for amphotericin B, fluconazole, and flucytosine, with significant reductions primarily after the first treatment. MIC reductions differed between groups, with Group a showing greater decreases in flucytosine and fluconazole MICs, and Group b in amphotericin B MICs. No significant changes in CAT1 or HWP1 expression were observed. Clinical efficacy of aPDT negatively correlated with leukocyte and neutrophil levels., Conclusions: aPDT effectively reduces MICs of antifungal drugs against C. albicans isolated from treated patients, particularly after the first treatment. The concentration of MB required to reduce MICs varies among different antifungal drugs. aPDT does not alter CAT1 or HWP1 expression, and its clinical efficacy in eradicating C. albicans is negatively associated with leukocyte and neutrophil levels., Competing Interests: Declaration of competing interest MRH declares the following potential conflicts of interest. Scientific Advisory Boards: Transdermal Cap Inc, Cleveland, OH; Hologenix Inc. Santa Monica, CA; Vielight, Toronto, Canada; JOOVV Inc, Minneapolis-St. Paul MN; Consulting; USHIO Corp, Japan; Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany. The other authors declare there is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Acne vulgaris is a chronic inflammatory skin disease involving the pilosebaceous unit., Objective: To assess the efficacy and safety of a chlorin e6 derivative-mediated photodynamic therapy (STBF-PDT) in the treatment of mild to moderate acne patients., Methods: In this prospective patient single-blind randomized split-face controlled study, patients diagnosed with mild to moderate acne were treated with four sessions of STBF-PDT on one-half of the face, while the other half were treated with the same dose of red-light treatment without photosensitizer. Follow-up assessment including the skin lesion clearance rate, facial fluorescence scattering spots on VISIA Porphyrins mode, and skin physiological parameters was conducted before and after treatment as well as 2 and 4 weeks after the final treatment., Results: A total of 26 patients were recruited, of which 22 patients completed this study. STBF-PDT is significantly effective in improving lesions in patients with acne. The clearance rate of total lesions was 67.42±8.51 % in the STBF-PDT group and 41.05±11.97 % in the control group 4 weeks after the treatment (P < 0.001). The average clearance rate of inflammatory lesions was 84.41±7.13 % in the STBF-PDT group and 50.10±13.91 % in the control group, with a statistically significance (P < 0.0001). The skin sebum of the STBF-PDT side was significantly lower than that on the control side. There was no obvious adverse reaction especially no pain or reactive acne., Conclusion: STBF-PDT may be a safe and effective treatment for mild to moderate acne and can significantly inhibit sebum secretion., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier B.V.)

Oral verrucous carcinoma (OVC) and proliferative verrucous leukoplakia (PVL) share similar histological characteristics and may have a common origin. When they appear simultaneously, the risk of malignant transformation in PVL increases. In elderly patients with both conditions, a safe, effective, simple, and minimally invasive treatment is preferable. Photodynamic therapy (PDT), a non-invasive treatment, utilizes specific wavelengths of light to activate photosensitizers, generating reactive oxygen species that selectively target malignant tissues with cytotoxic effects. This case report describes an elderly patient with coexisting extensive leukoplakia, PVL, and OVC, who achieved complete remission with no recurrence at 10 months following PDT. The treatment resulted in a satisfactory clinical outcome, preserving both the appearance and function of the oral cavity., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Pathological scars result from abnormal wound healing and represent a fibrotic process in the repair of skin injuries. Post-burn scars are prone to malignant transformation, especially when ulceration occurs, raising concerns for precancerous lesions. We report a case of a 56-year-old female with a 50-year history of a large burn scar on her left forearm. The scar developed non-healing ulceration with local pain and itching over the past three years. Treatment with hematoporphyrin photodynamic therapy (HpD-PDT) led to resolution of the ulceration, thinning of the scar tissue, and significant alleviation of pain and itching. After a five-year follow-up, there has been no recurrence of ulceration, suggesting that photodynamic therapy effectively promotes wound healing in scarred tissue with ulcerations., (Copyright © 2024. Published by Elsevier B.V.)

Background: To evaluate the anatomical and functional outcomes of high-density subthreshold micropulse laser (HSML) treatment in a cohort of patients diagnosed with chronic central serous chorioretinopathy (CSCR) whose treatment with photodynamic therapy (PDT) was delayed due to the worldwide shortage of verteporfin., Methods: Prospective interventional study which included 42 eyes of 40 patients diagnosed with chronic CSCR and on the waiting list for PDT who received rescue therapy with HSML using the Navilas® System device (OD-OS GmBH, Teltwo, Germany). Best corrected visual acuity (BCVA), subretinal fluid (SRF), and subfoveal choroidal thickness (SFCT) were measured at inclusion and during the follow-up visits at 2, 4, and 6 months., Results: The mean waiting time from the indication of PDT until treatment with HSML was 14.6 ± 9.7 months (range 5-21). There were no differences in the pre-treatment BCVA compared with the 6-month follow-up visit (67 ± 16.7 letters and 67.5 ± 8.2 letters respectively, p = 0.136). However, there was a significant decrease in the mean SFCT of -39.6 ± 37.1 μm (p = 0.030). Additionally, there was a decrease in SRF height between the pre-treatment measure (123.0 ± 49.8 μm) and the 2, 4, and 6-month follow-up visits after HSML of -58.5 ± 68.2 μm, -53.2 ± 76.3 μm, and -65.4 ± 53.6 μm respectively (p < 0.001). A complete resolution of the SRF was observed in 16/42 eyes (38.1 %) and a reduction of the SRF height in 85.7 % of the overall cohort was observed after HSML treatment., Conclusion: A significant anatomical improvement in SRF and a decrease in SFCT were observed in patients with CSCR who were previously waiting for PDT and were rescued by HSML. However, the rate of complete SRF resolution was low., Competing Interests: Declaration of competing interest None to declare, (Copyright © 2024. Published by Elsevier B.V.)

Background: Pain associated with aminolevulinic acid photodynamic therapy (ALA-PDT) for the treatment of facial dermatoses results in low patient compliance. Two-step photodynamic therapy (two-step PDT) may improve comfort by optimizing light amplitude and exposure time., Objective: To investigate the efficacy of two-step PDT in reducing the pain generated during the treatment of facial skin disorders., Methods: Twenty-six patients with AK were randomly divided into two groups; the experimental group was treated with two-step photodynamic therapy and the control group was treated with conventional photodynamic therapy. The pain intensity of the patients at different times was assessed using the pain numerical rating scale (NRS)., Results: A total of 26 patients completed three ALA-PDT treatments, 13 and 13 patients in each group, respectively. The mean NRS scores of patients in the experimental group (3.28±1.41, 3.33±1.43, 3.42±1.78) were lower than those of the control group (5.00±1.94, 5.09±1.86, 4.86±1.64) on each occasion. The incidence of certain adverse reactions was lower in the experimental group than in the control group. There was no difference between the two groups in terms of clinical outcome, recurrence rate and patient satisfaction., Conclusion: Two-step photodynamic therapy can reduce pain and the incidence of some adverse reactions, but does not affect clinical efficacy, recurrence rate and patient satisfaction., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: Oral 5-aminolevulinic acid for transurethral resection of bladder tumor reduces bladder cancer recurrence compared with standard white-light transurethral resection of bladder tumor. However, data regarding risks of adverse events with this drug are unclear. The aim of the present study was to identify risk factors associated with oral 5-aminolevulinic acid induced adverse events in photodynamic diagnosis-transurethral resection of bladder tumor., Methods: We studied 104 cases of 5-aminolevulinic acid-photodynamic diagnosis-transurethral resection of bladder tumor from October 2021 to April 2023, administering 20 mg/kg 5-aminolevulinic acid orally at least 2 h pre-surgery. Four major adverse events associated with 5-aminolevulinic acid were selected to identify risk factors for their occurrence, including perioperative hypotension, nausea and/or vomiting, photosensitivity, and liver dysfunction. Univariate and multivariate analyses were conducted to identify the risk factors of those adverse events., Results: Perioperative hypotension (11.5 %), nausea and/or vomiting (37.5 %) photosensitivity (31.7 %), and liver dysfunction (51.9 %) were observed. Multivariate analyses revealed that spinal anesthesia was associated with hypotension (p = 0.02), whereas advanced age (p < 0.01) and higher body mass index (p < 0.01) were associated with nausea and/or vomiting. Also, male sex (p < 0.01) and longer operative time (p = 0.01) were associated with photosensitivity, and renin-angiotensin system inhibitors use was associated with postoperative liver dysfunction (p < 0.01)., Conclusions: For elderly male obese patients taking renin-angiotensin system inhibitors, particular attention is needed during the perioperative period of photodynamic diagnosis-transurethral resection of bladder tumor under spinal anesthesia due to the higher risk of onset of the adverse events involved in oral administration of 5-aminolevulinic acid., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The combination of therapy-induced immunogenic cell death (ICD) and immune checkpoint blockade can provide a mutually reinforced strategy to reverse the poor immunogenicity and immune escape behavior of tumors. In this work, a chimeric peptide-engineered immunostimulant (ER-PPB) is fabricated for endoplasmic reticulum (ER)-targeted photodynamic immunotherapy against metastatic tumors. Among which, the amphiphilic chimeric peptide (ER-PP) is composed of ER-targeting peptide FFKDEL, hydrophilic PEG 8 linker and photosensitizer protoporphyrin IX (PpIX), which could be assembled with a PD-1/PD-L1 blocker (BMS-1) to prepare ER-PPB. After passively targeting at tumor tissues, ER-PPB will selectively accumulate in the ER. Next, the localized PDT of ER-PPB will produce a lot of ROS to destroy the primary tumor cells, while increasing the ER stress to initiate a robust ICD cascade. Moreover, the concomitant delivery of BMS-1 can impede the immune escape of tumor cells through PD-1/PD-L1 blockade, thus synergistically activating the immune system to combat metastatic tumors. In vitro and in vivo results demonstrate the robust immune activation and metastatic tumor inhibition characteristics of ER-PPB, which may offer a promising strategy for spatiotemporally controlled metastatic tumor therapy., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This study aims to assess whether photodynamic therapy (PDT) offers a clinically effective alternative for treating oral aphthous ulcers, contributing to the ongoing quest for methods to expedite their treatment process amidst the limited understanding of their etiology., Materials and Method: The study involved thirty volunteers with aphthous ulcers, split equally between a control group and a PDT group. Patients in the PDT group received laser treatment using Indocyanine green upon admission, while the control group received no intervention. Lesion diameter was measured at presentation and on the 3rd, 5th, and 7th days for all patients, with wound healing assessed on the 7th day. Additionally, pain levels were evaluated using the Visual Analog Scale (VAS) preoperatively and on the 1st, 3rd, 5th, and 7th days for the PDT group, and on the corresponding days for the control group., Results: Lesion diameters in the PDT group showed a significant reduction over time (p = 0.001), particularly from preoperative to final measurements. The control group also exhibited a decrease, albeit slower (p = 0.001). The 7th-day healing scores favored the PDT group significantly (p = 0.012). VAS scores in the PDT group decreased significantly over time (p = 0.001), indicating pain reduction. A similar trend was observed in the control group, albeit slower. Between-group differences in healing data and pain data were statistically significant., Conclusion: PDT proves effective in reducing aphthous ulcer diameters and pain intensity, facilitating faster healing than the control group. These results advocate for PDT as a viable treatment option for aphthous lesions., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Pharyngotonsillitis (PT) is an inflammatory and infectious condition affecting the tonsils in the oropharynx, predominantly caused by a variety of viral, fungal, and bacterial pathogens, including Streptococcus pyogenes. With the increasing challenge of antibiotic resistance, alternative therapeutic approaches are needed., Methods: This study explores the effectiveness and safety of Photodynamic Therapy (PDT) as a therapeutic approach for managing acute PT. PDT involves the use of a photosensitizer, light, and molecular oxygen. We utilized a curcumin-based photosensitizer incorporated into a gum formulation, followed by exposure to blue LED irradiation (455 ± 30 nm, intensity of 200 mW for 6 min) with 1 to 2 PDT sessions depending on the clinical case., Results: The treatment's impact was assessed through systematic monitoring of clinical progression post-treatment, encompassing clinical history, examination, and follow-up. In all three cases examined, PDT was observed to effectively eradicate the infection and prevent its recurrence during the period evaluated., Conclusion: Photodynamic Therapy, using a curcumin-based photosensitizer and blue LED light, appears to be a promising alternative to traditional antibiotics for the treatment of PT, demonstrating both efficacy in infection eradication and safety in application. Further studies are recommended to substantiate these findings and explore long-term outcomes., (Copyright © 2024. Published by Elsevier B.V.)

Background: Long-term results of photodynamic therapy (PDT) combined with vascular endothelial growth factor (VEGF) inhibitors for pachychoroid neovasculopathy (PNV) are not yet clear., Methods: This study is a retrospective, observational case series. We retrospectively examined untreated PNV cases (22 cases, 22 eyes, mean age of 71.0 years) who underwent PDT therapy in combination with VEGF inhibitors followed by additional treatments with pro re nata protocol. Visual acuity, number of treatments, and time to recurrence were examined. In addition, foveal choroidal thickness and choroidal vascularity index (CVI) were evaluated in 13 of 22 patients who were followed up with SpectralisOCT R from baseline., Results: Fifteen (68%) cases had polyps at baseline. LogMAR visual acuity averaged 0.24 ± 0.20 (range, - 0.079 to 0.82) at baseline and significantly improved after 1, 2, and 3 years (p = 0. 004, 0.0003, 0.002, respectively). Fourteen patients (64%) recurred, with an average time to recurrence of 1.8 ± 0.9 years. Foveal choroidal thickness decreased significantly after 1 year (average from 326 μm to 263 μm) and remained unchanged up to 3 years (255 μm). CVI also decreased after 1 year (average from 0.62 to 0.61) and remained unchanged until 3 years later (0.60)., Conclusions: We examined the 3-year course of PDT in combination with the VEGF inhibitor for untreated PNV. Visual acuity was improved, foveal choroidal thickness and CVI were decreased after 3 years., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Postoperative recurrence of tongue squamous cell carcinoma (TSCC) has always been a clinical problem for patients and doctors. Surgery and radiotherapy are the main treatment methods for TSCC, but reoperation often leads to functional impairment. Side effects of radiotherapy include mucosal gland damage, dry mouth, weakened or lost taste. Improved treatment is needed., Objective: To evaluate the clinical outcome of a patient with TSCC treated with Microdrop aminolevulinic acid (ALA) photodynamic treatment (PDT) twice., Methods: ALA was dissolved in 5 % lidocaine and the concentration of ALA was 20 % by Microdrop method. Then, the tumor tissue was expanded 1 cm outward, and the injection points were evenly distributed with an upper and lower left and right interval of 2-3 mm. The 1 ml syringe was used to perform the injection in the skin of the tumor area, and there was a small cuticle at each injection point. A pathologically confirmed patient with TSCC received twice Microdrop ALA-PDT treatments, which were evaluated at 1 month and 4 months later., Results: After 3 h of Microdrop ALA injection, the wavelength of semiconductor laser was set to 630 nm, and the energy of 300 mW /cm 2 was irradiated for 30 min. After two treatments, the lesions were not visible, and no recurrence occurred after 4 months of follow-up. The patient's tongue function was well preserved and the cosmetic effect was good., Conclusion: Microdrop ALA-PDT may be effective in the salvage treatment of select tongue squamous cell carcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hidroacanthoma simplex (HS) is a rare skin appendage tumor that typically appears on the trunk and lower limbs in the elderly. Although HS is a predominantly benign condition, the presence of cellular atypia and dermal infiltration on histological examination indicates malignant HS (MHS). 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) uses a photosensitizer and corresponding light source to cause irreversible damage or death of target cells through a photochemical reaction. Here, we reported the successful treatment of a MHS patient with ALA-PDT using plum-blossom needle pretreatment combined with CO 2 laser. After five courses of ALA-PDT, the lesions were completely resolved, and the autonomic activity and smooth surface of the left ring finger were restored. This suggests that ALA-PDT is an effective, minimally invasive and safe treatment modality for MHS., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: To review the evidence on the safety and effectiveness of epithelium-off corneal collagen cross-linking (CXL) for the treatment of progressive corneal ectasia., Methods: A literature search of the PubMed database was most recently conducted in March 2024 with no date restrictions and limited to studies published in English. The search identified 359 citations that were reviewed in abstract form, and 43 of these were reviewed in full text. High-quality randomized clinical trials comparing epithelium-off CXL with conservative treatment in patients who have keratoconus (KCN) and post-refractive surgery ectasia were included. The panel deemed 6 articles to be of sufficient relevance for inclusion, and these were assessed for quality by the panel methodologist; 5 were rated level I, and 1 was rated level II. There were no level III studies., Results: This analysis includes 6 prospective, randomized controlled trials that evaluated the use of epithelium-off CXL to treat progressive KCN (5 studies) and post-laser refractive surgery ectasia (1 study), with a mean postoperative follow-up of 2.4 years (range, 1-5 years). All studies showed a decreased progression rate in treated patients compared with controls. Improvement in the maximum keratometry (Kmax) value, corrected distance visual acuity (CDVA), and uncorrected distance visual acuity (UDVA) was observed in the treatment groups compared with control groups. A decrease in corneal thickness was observed in both groups but was greater in the CXL group. Complications were rare., Conclusions: Epithelium-off CXL is effective in reducing the progression of KCN and post-laser refractive surgery ectasia in most treated patients with an acceptable safety profile., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Vulvar lichen sclerosus (VLS) is often associated with irritable symptoms of itching, burning pain and can lead to scarring, architectural changes and sexual dysfunction as well as a decline in quality of life. The etiology of the disease is unknown. This study sought to assess the therapeutic effects of Photodynamic Therapy (PDT) in VLS, and improvment of patient quality of life and sexual funtion., Methods: From January 2022 to April 2023, a total of 65 patients with vulvar sclerosus (VLS) were treated with PDT in our hospital. All 65 patients were divided into two groups: early-stage group and late-stage group. The Cattaneo scoring method, the Dermatology Life Quality Index (DLQI) and the Female Sexual Function Index (FSFI) scores were used to evaluate the clinical effectiveness of the treatment on patients' symptoms and clincal signs, quality of life as well as sexual function before and at 6-month after treatment., Results: The total effective rate of early-stage patients was significantly greater than that of late-stage patients at 6-month after PDT treatment (90.91 % [40/44] vs 76.19 % [16/21], p < 0.05). At 6-month follow-up, the symptoms and clinical signs of patients in early-stage group were significantly improved compared with baseline, the average scores of itching, skin elasticity, whitening and lesion range were significantly lower than the scores before treatment (p < 0.05). In late-stage group, The decrease in scores of itching, whitening and lesion range at the 6-months follow-up is significant(p < 0.05), but skin elasticity (p = 0.0625). On post-treatment follow-up examination, FSFI score was seen to have significantly improved in early-stage patients(from a median score of 17.45 to 21.1, p < 0.05); DLQI also significantly improved after treatment (from a median score of 7 to 4, p < 0.05). In late stage patients, The DLQI score improved significantly after treatment (from a median score of 18 to 15, p < 0.05). However, the improvement in sexual function is not statistically significant (pre-treatment: median=10.55, post-treatment: median=10, p = 0.1865)., Conclusion: Photodynamic therapy can effectively improve most symptoms and clinical signs, as well as quality of life of patients with VLS, especially for earlly stage patients. Moreover, improvement in sexual function is observed in early stage patients after PDT treatment. This study suggests that early and timely PDT treatment are recommended to achieve better results., Competing Interests: Declaration of competing interest none., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: The aim of this study was to investigate the corneal microstructure and Langerhans cells using in vivo confocal microscopy in keratoconus patients before and after cross-linking, and to correlate the morphologic findings with clinical and patient-reported outcomes, including eye rubbing (ER) behavior., Methods: Patients with progressive keratoconus undergoing iontophoresis-assisted epithelium-on cross-linking (I-CXL) were consecutively enrolled. In vivo confocal microscopy was performed before and 6 months after treatment. Patients were asked to quantify their ER behavior on a Visual Analogue Scale (VAS) and completed the Keratoconus Outcomes Research Questionnaire and the Ocular Surface Disease Index questionnaires at the same time points. Visual acuity, tear osmolarity, topography, aberrometry, and pachymetry of both eyes were assessed., Results: Thirteen patients were included in this pilot study. Preoperatively, the mean Langerhans cells density was 35,615 cells per mm 2 , and the median morphology was 3. The mean ER VAS before treatment was 7,077 out of 10. The ER VAS showed significant positive correlations with both Langerhans cells density and morphology of the study eye. After treatment, a statistically significant reduction in ER VAS and in Langerhans cells variables was observed. The mean sub-basal plexus nerve density was comparable to pre-operative values 6 months after I-CXL., Conclusions: Based on this preliminary evidence, the presence of high density of mature Langerhans cells in the central cornea of keratoconus patients and its correlation with eye rubbing support the role of inflammation in keratoconus. The reduction in these markers after treatment may suggest a potential of CXL in moderating immune-related inflammation and eye rubbing in the medium term., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Candidiasis is a common fungal infection, with Candida tropicalis infections being relatively rare. These infections develop into skin fungal infections under conditions such as broad-spectrum antibiotic use, diabetes, and immunosuppression. Traditionally, antifungal drugs have been the primary treatment; however, issues like hepatotoxicity and the need for long-term use persist. Consequently, new treatment approaches are essential. Most previous reports have focused on Candida albicans, with fewer addressing Candida tropicalis. This study reports a case where a patient with a skin Candida tropicalis infection was treated with a combination of surgery and ALA photodynamic therapy(635 nm, 120 J/cm 2 , 177 mW/cm 2 ). After just one session of this combined treatment, the patient achieved significant clinical remission. Therefore, the combination of surgery and ALA-PDT may offer a safe and effective treatment option., (Copyright © 2024. Published by Elsevier B.V.)

Objective: 5-aminolevulinic acid (5-ALA) is a precursor of the photosensitizer Protoporphyrin IX (PpIX) and photodynamic therapy (PDT) with 5-ALA has been used in clinical practice. However, tumor cellular hypoxia severely affects the efficiency of photodynamic therapy. In this study, photodynamic therapy was combined with tirapazamine to investigate the effects of the combined intervention and the related mechanisms it may involve., Methods: Colony formation assays were used to demonstrate cell proliferation. Transwell assays were performed to observe the effect on cell invasion and metastasis after the corresponding intervention. DCFH-DA probe was used to detect the reactive oxygen species content. Flow cytometry was used to detect the effects of the interventions on apoptosis and cell cycle. The relevant pathways that may be involved are explored by examining the expression levels of the relevant proteins and genes., Results: Colony formation assays indicated that the combined intervention inhibited cell proliferation. Transwell assays demonstrated that PDT combined with TPZ effectively inhibited tumor cell invasion and metastasis. In addition, fluorescence intensity generated by DCFH-DA oxidation was detected indicating that the combined intervention increased the formation of reactive oxygen species. Flow cytometry clearly showed that the combination of PDT and TPZ further increased apoptosis and cell cycle arrest. The results of western blotting and qRT-PCR experiments confirmed that the combination therapy inhibited HIF-1α/VEGF axis and the PI3K/Akt/mTOR pathway activation., Conclusion: 5-ALA-PDT combined with TPZ can inhibit cell proliferation, increase apoptosis, and inhibit the PI3K/Akt/mTOR pathway, thus inhibiting tumor growth and metastasis and improving anti-cancer effects., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Intraoperative photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is a widely adopted technique to enhance the extent of resection during high-grade glioma (HGG) surgery. Recent updates to the package insert for 5-ALA in Japan now allow its use in combination with drugs that may induce photosensitivity, such as talaporfin sodium (TS). TS is employed in intraoperative photodynamic therapy (PDT) and has been shown to improve overall survival. The combination of 5-ALA with TS is expected to offer further benefits. However, the safety of this combination had not been established. This study reports on the safety of 5-ALA-PDD with TS-PDT in the treatment of recurrent HGG., Methods: 7 patients with recurrent HGG underwent tumor resection using a combination of 5-ALA-PDD and TS-PDT. The incidence of photosensitivity as an adverse effect associated with 5-ALA and TS was evaluated as described in the package insert. Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0., Results: Tumor-specific fluorescence intensity was strong in 4 cases and weak in 3. Photosensitivity occurred in only 1 patient (14.3%). Three patients exhibited CTCAE grade 1 or 2 abnormal liver function, and 1 patient experienced CTCAE grade 1 γ-GTP elevation. All abnormalities improved during follow-up., Conclusions: The combined use of 5-ALA-PDD and TS-PDT for HGG surgery did not increase the risk of serious adverse events in our study. Further investigations with a larger number of cases are needed for a more accurate assessment of its safety and efficacy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Trichosporon species are part of the normal microbiota of humans which can cause both superficial and invasive infections, primarily affecting immunocompetent and immunocompromised hosts, respectively. Giant ulcer caused by Trichosporon asahii is relatively uncommon in immunocompetent hosts. Increased drug resistance and biofilm-associated virulence makes the treatment of infectious ulcers challenging. Herein, we present a case of a massive ulcer caused by T. asahii which resulted in completed healing when treated with photodynamic therapy (PDT) and voriconazole. It provided the feasibility for PDT combined with antifungal drugs to treat similar refractory cases., Competing Interests: Declaration of competing interest All authors declare no potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy of CO2 fractional laser and microneedling pretreatment combined with ALA-PDT for moderate-to-severe acne, aiming to optimize clinical treatment., Methods: Patients were randomly divided into three groups: Group A (CO2 fractional laser + ALA-PDT), Group B (microneedling + ALA-PDT), and Group C (ALA-PDT). Each group underwent photodynamic therapy once a week for 3 weeks. Efficacy was assessed at the end of the 4th week, and recurrence was assessed at the end of the 12th week., Results: A total of 150 patients with moderate to severe acne were included in this study, with 50 patients in each group. Four weeks after the end of treatment, the effective rates were 88 % for Group A, 62 % for Group B, and 36 % for Group C. Statistically significant differences were found between the groups (P < 0.05), with Group A showing superior efficacy compared to Group B (P < 0.05). No serious systemic or local adverse reactions were observed in any group. No recurrence was seen in any group 12 weeks after the end of treatment, and some patients continued to show improvement in skin lesions over time., Conclusion: Both the CO2 fractional laser group and the microneedling group improved the efficacy of photodynamic therapy for moderate to severe acne compared to the control group, with the CO2 fractional laser group demonstrating better efficacy and fewer adverse effects., (Copyright © 2024. Published by Elsevier B.V.)

Background: Acral actinic keratosis (AK) lesions are considered difficult to treat, and published data for photodynamic therapy (PDT) on these lesions is limited. Thus, we evaluated sustained efficacy, safety, and satisfaction after PDT for AK on the hands., Methods: We analysed subgroup data for treatment on the hands from a randomised, double-blind, intra-individual phase III study. All participants previously underwent up to two field-directed red light PDTs with 10 % 5-aminolevulinic acid nanoemulsion gel (BF-200 ALA). Assessments included pain during PDT, clearance and recurrence rates, and satisfaction., Results: 24 participants treated on the hands were included; 21 participants were analysed. Complete clearance rates with BF-200 ALA were 90.9 % (lesion-based) and 76.2 % (per participant's side), both markedly higher than with vehicle. The lesion recurrence rate with BF-200 ALA was 29.0 %. Adverse events reflected the mode of action. Mean pain intensities were 4.8 ± 3.8 (BF-200 ALA) and 0.8 ± 2.1 (vehicle) on an 11-point numeric rating scale. Most participants (81.0 %) rated their satisfaction with BF-200 ALA as very good or good., Conclusion: This subgroup analysis indicates that PDT with BF-200 ALA provides a suitable treatment for AK lesions on the hands., Competing Interests: Declaration of competing interest R.A. received honoraria as scientific advisor, trial investigator and lecturer for AbbVie, Boehringer-Ingelheim, Bristol-Myers Squibb, Incyt, Janssen, Leo, Lilly, Novartis, Sanofi-Aventis, and UCB. R.-M.S. has received grants from Almirall, Biofrontera, Dr. Wolff-Group, Galderma, Leo Pharma, Novartis, and photonamic for clinical studies; has received consulting fees and speakers’ honoraria from Abbvie, Almirall, Eli Lilly, Galderma, Janssen, and Leo Pharma, and is Vice-President of the EURO-PDT Society. T.D. has received funding from Almirall, Biofrontera, Galderma, Meda, Schulze & Böhm GmbH for research support; has received consulting fees from Almirall, Biofrontera, GSK, Dr. Pfleger, Galderma, Janssen-Cilag, Leo, Meda, Neracare, Novartis, Scibase, smartinmedia AG, UCB, Vichy; and has received speakers honoraria from Almirall, Biofrontera, Galderma, GSK, infectopharm, Leo, Meda, Neracare, Novartis, Janssen-Cilag, Riemser. R.S. and M.-T.Z. were employees of Biofrontera Bioscience GmbH at the time the manuscript was written. N.P. is an employee of Biofrontera Bioscience GmbH. U.R. and R.D. have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Photodynamic therapy (PDT) has been emerging as a promising treatment for unresectable cholangiocarcinoma (CCA). A number of experiments have demonstrated that PDT could enhance antitumor immunity significantly. However, the impact of PDT on peripheral immune system for unresectable CCA remains unclear., Methods: In a clinical trial comparing the perioperative and long-term outcomes of PDT+stent treatment and stent alone treatment for unresectable CCA, we tested the levels of lymphocytes (CD4+ T cells, CD8+ T cells, NK cells, B cells and Treg cells) and immune-related cytokines (IL-4, IL-6, IL-10, TNF-α, TGF-β, perforin, GM-CSF and IFN-γ) in peripheral blood before and after PDT+stent treatment or stent alone treatment and analyzed the influence of PDT on peripheral immune system for unresectable CCA., Results: Before treatment, the levels of all the immune cells and immune-related cytokines did not show significant differences between the PDT+stent group and stent alone group. The ratio of CD8+ T cells increased significantly after PDT treatment, but other kinds of lymphocytes did not show significant difference. Increased level of IL-6 and decreased level of perforin and TGF-β after PDT treatment were demonstrated, whereas no significant changes were found for other immune-related cytokines., Conclusion: PDT altered the levels of immune cells and immune-related cytokines in the peripheral blood of unresectable CCA patients, potentially correlating with the therapeutic efficacy of PDT in unresectable CCA treatment. Future studies could delve deeper into this aspect to explore how PDT can be more effectively utilized in the management of unresectable CCA., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Gliomas of the brain are characterised by high aggressiveness, high postoperative recurrence rate, high morbidity and mortality, posing a great challenge to clinical treatment. Traditional treatments include surgery, radiotherapy and chemotherapy; they also have significant associated side effects, leading to difficulties in tumour resection and recurrence. Photodynamic therapy has been shown to be a promising new strategy to help treat malignant tumours of the brain. It irradiates the tumour site at a specific wavelength to activate a photosensitiser, which selectively accumulates at the tumour site, triggering a photochemical reaction that destroys the tumour cells. It has the advantages of being minimally invasive, highly targeted and with few adverse reactions, and is expected to be well used in anti-tumour therapy. However, the therapeutic effect of traditional PDT is limited by the weak tissue penetration ability of photosensitiser, hypoxia and immunosuppression in the tumour microenvironment. This paper reviews the current research status on the therapeutic principle of photodynamic therapy in glioma and the mechanism of tumour cell injury, and also analyses the advantages and disadvantages of the current application in glioma treatment, and clarifies the analysis of ideas to improve the tissue penetration ability of photosensitizers. It aims to provide a feasible direction for the improvement of photodynamic therapy for glioma and a reference for the clinical treatment of deep brain tumours., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Lung cancer, a highly prevalent and lethal form of cancer, is often associated with oxidative stress. Photodynamic therapy (PDT) has emerged as a promising alternative therapeutic tool in cancer treatments, but its efficacy is closely correlated to the photosensitizers generating reactive oxygen species (ROS) and the antioxidant capacity of tumor cells. In particular, glutathione (GSH) can reduce the ROS and thus compromise PDT efficacy. In this study, a GSH-responsive near-infrared photosensitizer (TBPPN) based on aggregation-induced emission for real-time monitoring of GSH levels and enhanced PDT for lung cancer treatment is developed. The strategic design of TBPPN, consisting of a donor-acceptor structure and incorporation of dinitrobenzene, enables dual functionality by not only the fluorescence being activated by GSH but also depleting GSH to enhance the cytotoxic effect of PDT. TBPPN demonstrates synergistic PDT efficacy in vitro against A549 lung cancer cells by specifically targeting different cellular compartments and depleting intracellular GSH. In vivo studies further confirm that TBPPN can effectively inhibit tumor growth in a mouse model with lung cancer, highlighting its potential as an integrated agent for the diagnosis and treatment of lung cancer. This approach enhances the effectiveness of PDT for lung cancer and deserves further exploration of its potential for clinical application., (© 2024 Wiley‐VCH GmbH.)

Damaged skin is susceptible to invasion by harmful microorganisms, especially Staphylococcus aureus and Escherichia coli , which can delay healing. Epigallocatechin-3-gallate (EGCG) is a natural compound known for effectively promoting wound healing and its potent anti-inflammatory effects. However, its application is limited due to its susceptibility to oxidation and isomerization, which alter its structure. The use of zeolitic imidazolate framework-8 (ZIF-8) can effectively tackle these issues. This study introduces an oxygen (O 2 ) and hydrogen peroxide (H 2 O 2 ) self-supplying ZIF-8 nanoplatform designed to enhance the bioavailability of EGCG, combining photodynamic therapy (PDT) and chemodynamic therapy (CDT) to improve antibacterial properties and ultimately accelerate wound healing. For this purpose, EGCG and indocyanine green (ICG), a photosensitizer, were successively integrated into a ZIF-8, and coated with bovine serum albumin (BSA) to enhance biocompatibility. The outer layer of this construct was further modified with manganese dioxide (MnO 2 ) to promote CDT and calcium peroxide (CaO 2 ) to supply H 2 O 2 and O 2 , resulting in the final nanoplatform EGCG-ICG@ZIF-8/BSA-MnO 2 /CaO 2 (EIZBMC). In in vitro experiments under 808 nm laser, EIZBMC exhibited synergistic antibacterial effects through PDT and CDT. This combination effectively released reactive oxygen species (ROS), which mediated oxidative stress to inhibit the bacteria. Subsequently, in a murine model of wound infection, EIZBMC not only exerted antibacterial effects through PDT and CDT but also alleviated the inflammatory condition and promoted the regeneration of collagen fibers, which led to accelerated wound healing. Overall, this research presents a promising approach to enhancing the therapeutic efficacy of EGCG by leveraging the synergistic antibacterial effects of PDT and CDT. This multifunctional nanoplatform maximizes EGCG's anti-inflammatory properties, offering a potent solution for promoting infected wound healing.

Purpose: This study aimed to identify preoperative factors that predict visual acuity and Kmax 3 years after corneal cross-linking (CXL) in patients with keratoconus (KC), and to develop a prediction model., Methods: We enrolled 68 patients with KC and followed up on 100 eyes that received CXL for at least 3 years. Preoperative data, including age, UDVA, CDVA, cylinder, SE, and the parameters of tomography including Kmax were collected as predictors. The primary outcomes were changes in CDVA (Delta CDVA) and Kmax (Delta Kmax) postoperatively. Univariate and multivariate linear regression were used to identify the correlation between the primary outcomes and predictors and establish prediction models., Results: Both CDVA and Kmax remained stable from baseline to 3 years after CXL: from 0.25 ± 0.18 to 0.22 ± 0.20 (P = 0.308) and from 58.70 ± 9.52 D to 57.02 ± 8.83 D (P = 0.187), respectively. Multivariate analysis showed that worse preoperative CDVA (ß coefficient - 0.668, P < 0.001) and lower preoperative Kmean (ß coefficient 0.018,P < 0.001) were associated with greater improvement in CDVA after CXL. A smaller preoperative eccentricity (ß coefficient 8.896, P = 0.01) and a higher preoperative Kmean (ß coefficient - 1.264, P < 0.001) predicted a more flattening of postoperative Kmax. The prediction model for CDVA (R 2  = 0.43) and Kmax (R 2  = 0.37) could accurately estimate treatment outcomes., Conclusions: CXL is highly effective in halting or preventing further progression of KC. The preoperative factors CDVA and Kmean were able to predict visual acuity changes 3 years after CXL. And preoperative eccentricity and Kmean could predict Kmax changes 3 years after CXL., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The poor 5-year survival rate for bladder cancers is associated with the lack of efficient diagnostic and treatment techniques. Despite cystoscopy-assisted photomedicine and external radiation being promising modalities to supplement or replace surgery, they remain invasive or fail to provide real-time navigation. Here, we report non-invasive fractionated photodynamic therapy of bladder cancer with full-course real-time near-infrared-II imaging based on engineered X-ray-activated nanotransducers that contain lanthanide-doped nanoscintillators with concurrent emissions in visible and the second near-infrared regions and conjugated photosensitizers. Following intravesical instillation in mice with carcinogen-induced autochthonous bladder tumours, tumour-homing peptide-labelled nanotransducers realize enhanced tumour regression, robust recurrence inhibition, improved survival rates, and restored immune homeostasis under X-ray irradiation with accompanied near-infrared-II imaging. On-demand fractionated photodynamic therapy with customized doses is further achieved based on quantifiable near-infrared-II imaging signal-to-background ratios. Our study presents a promising non-invasive strategy to confront the current bladder cancer dilemma from diagnosis to treatment and prognosis., (© 2024. The Author(s).)