Basal cell carcinoma (BCC) is the most prevalent cutaneous malignancy. It correlates strongly with ultraviolet exposure. The incidence of BCC continues to climb annually. Consequently, the demand for safe, cosmetically favorable, and highly effective therapies is pressing. Photodynamic therapy (PDT) has captured significant research interest due to its therapeutic efficacy against BCC. This study aims to investigate current research hotspots, knowledge gaps, and future trends concerning PDT in BCC management. We mapped the research landscape and developmental trends of dermatological PDT for BCC. This analysis utilized visual knowledge graphs derived from the Web of Science Core Collection (WoSCC) and Scopus. A comprehensive literature search covered publications on BCC and PDT from 2001 to 2025. Search queries were conducted in English. Subsequent evaluations included scientific performance analysis, collaboration networks (authors, institutions, and countries), reference co-citation networks, and keyword burst analysis. We utilized VOSviewer, CiteSpace, and Bibliometrix to process the resulting data. The initial search retrieved 2458 records. Following deduplication and data conversion, 1551 articles were included in the final analysis. Publication volume surged notably between 2004 and 2009. The United States and the United Kingdom emerged as the primary contributing nations. Maastricht University was identified as the leading research institution. References exhibiting the highest centrality predominantly centered on key consensus guidelines established by the International Society for Photodynamic Therapy. They also focused on the therapeutic efficacy and cosmetic advantages in treating nodular BCC. High-frequency keywords were dominated by "Photodynamic therapy" and "Basal cell carcinoma." Furthermore, cluster analysis mapped all keywords into three fundamental domains: disease classification, core pharmacology and mechanisms, and combined or controlled treatment modalities. Within the analyzed corpus of 1551 papers, R. Szeimies and C. Morton emerged as the most prolific authors. They made the most substantial contributions to the field. Keyword analysis also illuminated other high-frequency terms. These included Actinic keratosis, Squamous cell carcinoma, Aminolevulinic acid, Methyl aminolevulinate, Imiquimod, and Pain. Finally, the keyword timeline visualization revealed several emerging research hotspots. Notably, these are optical coherence tomography, immunotherapy, drug delivery, and the hedgehog pathway. PDT offers a dual advantage over conventional therapies for BCC. It successfully balances clinical efficacy with superior cosmetic outcomes. This study represents the first global, quantitative literature analysis on the intersection of BCC and PDT. It identifies several established research hotspots. These encompass the metabolic mechanisms of photosensitizer precursors, the expansion of targeted clinical indications, and the management of pain-related adverse events. Furthermore, we identified a shift toward novel research frontiers. Emerging trends heavily focus on precise localization through non-invasive optical imaging and the development of innovative carriers to breach the skin barrier. They also highlight advanced diagnostic and therapeutic protocols that integrate immunomodulators with molecular targeted pathways. Ultimately, these findings provide valuable navigational guidance for future research endeavors.
Bladder cancer (BC) is the sixth most common cancer in men and one of the top 10 cancers in terms of the global cancer burden. Despite the rapid development and widespread application of photodynamic therapy (PDT) in BC research, a comprehensive analysis and bibliometric evaluation of the development trends in this field have yet to be conducted. This study aims to quantify and visualize the research output, major contributors, intellectual structure, and emerging frontiers in photodynamic therapy for bladder cancer research from 2000 to 2025. Articles on PDT in BC published from 2000 to 2025 were retrieved from the Web of Science Core Collection (WoSCC) database. A bibliometric analysis was performed using VOSviewer, CiteSpace, Python, and the R package "bibliometrix". A total of 595 articles from 42 countries were included in the analysis, of which the majority originated from China and the United States. The number of publications related to PDT in BC continues to increase annually. The National University of Singapore, the University of Leuven, the German National Cancer Center, and the University of Coimbra in Portugal were the main research institutions with the highest publication volumes. Photodiagnosis and Photodynamic Therapy was the leading journal in this research area, while The Journal of Urology was the most frequently co-cited publication. A total of 106 authors contributed to these articles, of whom, Fernandes and Olivo contributed the highest number of publications, and Dougherty was the most commonly co-cited author. The main research topics in this field included the development and optimization of novel photosensitizers, combination therapy strategies, and the integration of photodynamic diagnosis and therapy. Further, the core keywords representing emerging research hotspots included "hypericin", "5-aminolevulinic acid", "protoporphyrin IX", "photosensitizer", "nanoparticles", and "immunotherapy". A bibliometric analysis was conducted to examine research on PDT in BC from 2000 to 2025. The investigation identified key trends, collaborative networks, and central research themes, including the application of hypericin and the integration of immunotherapy. While China and the United States were the leading contributors in terms of publication output, international collaborative efforts remained relatively limited. The findings underscore a notable evolution in the field, characterized by a focus on photosensitizer optimization and the development of novel therapeutic strategies. Emerging research directions notably include advancements in nanotechnology, immunotherapeutic approaches, and combination treatment regimens. In summary, this analysis provides a comprehensive mapping of the current knowledge landscape, offering valuable insights to guide future research initiatives in this domain.
Repeated low-level red-light therapy (RLRL) has emerged as a promising ocular photobiomodulation strategy for childhood myopia control. Published randomized trials have reported substantial reductions in axial elongation and refractive progression, and some studies have described apparent axial shortening during active treatment. However, the rapid clinical adoption of RLRL has raised important questions regarding mechanism, rebound after discontinuation, device-specific safety, and standardized clinical implementation. This structured narrative review summarizes current evidence on RLRL for childhood myopia, with emphasis on efficacy, biological plausibility, choroidal responses, rebound effects, retinal safety, device dosimetry, and regulatory considerations. The strongest mechanistic evidence in children supports rapid choroidal thickening and increased choroidal perfusion after RLRL, whereas mitochondrial photobiomodulation, dopamine signaling, and scleral remodeling remain biologically plausible but incompletely verified pathways. Follow-up studies have documented rebound axial elongation after treatment cessation, although cumulative benefits may partly persist. Clinical trial safety findings are generally reassuring, but case reports of retinal injury, transient optical coherence tomography (OCT) abnormalities, cone-level changes, and independent radiometric evaluations indicate that safety cannot be generalized across all red-light devices. RLRL should therefore be interpreted as a device-dependent intervention rather than a uniform treatment category. Future studies should prioritize independent multicenter trials, standardized radiometric reporting, masked retinal imaging review, long-term safety surveillance, and clinically practical protocols for treatment initiation, monitoring, and discontinuation. Repeated low-level red-light therapy (RLRL) has become a prominent nonpharmacological approach for controlling childhood myopia progression, particularly in East Asia. The current clinical evidence includes randomized trials in children with established myopia, premyopia, and high myopia, as well as studies evaluating its adjunctive use with orthokeratology, accompanied by an expanding body of mechanistic and safety-related research. This structured narrative review synthesized evidence on repeated low-level red-light therapy (RLRL) for childhood myopia from PubMed/MEDLINE, Embase, Web of Science, the Cochrane Library, and Scopus from database inception to May 22, 2026. Suggested search terms included combinations of "myopia," "child*," "premyopia," "red light," "low-level red light," "repeated low-level red-light," "photobiomodulation," "axial length," "spherical equivalent," "choroid," "safety," "retinal damage," "dosimetry," "radiometry," and "rebound." Reference lists of relevant reviews and key primary studies were manually screened to identify additional records. Priority was given to randomized clinical trials, prespecified follow-up studies, imaging-based mechanistic studies, laboratory safety evaluations, systematic reviews, and official regulatory or journal guidance. Because device parameters were incompletely reported in parts of the literature and the original working draft did not specify a reproducible search strategy, the present article is presented as a structured narrative review rather than a formal systematic review or meta-analysis. Short-term efficacy has been consistently favorable in published randomized controlled trials (RCTs), with several studies reporting substantially less axial elongation than spectacles or sham controls, and some even demonstrating measurable axial shortening. The strongest human mechanistic evidence points to rapid choroidal thickening and increased choroidal perfusion. Broader photobiomodulation biology supports mitochondrial and vascular hypotheses, whereas dopamine-mediated and scleral-remodeling pathways remain largely inferential. Rebound after treatment cessation has now been documented, particularly for axial length. Safety findings remain mixed: clinical trial data are generally reassuring, but isolated reports of retinal injury, transient OCT lesions, cone-density changes, and independent device-radiometry studies all suggest that caution remains necessary. RLRL may be among the most effective myopia-control strategies currently under investigation in the short term, but the field has not yet reached full clinical maturity. The existing evidence is geographically concentrated, device-specific safety validation remains incomplete, and the long-term boundaries of ocular safety are still uncertain. Therefore, clinical application should be standardized, guided by retinal imaging, and evaluated according to specific device parameters rather than generalized to all "red-light" products.
Endometrial hyperplasia (EH) is a common precancerous condition in gynecology. Conventional treatments are limited by recurrence, side effects, and fertility concerns. Photodynamic therapy (PDT), a minimally invasive and lesion-selective treatment, has emerged as a promising alternative. This review will summarize the clinical applications of PDT in EH and evaluate its diagnostic and therapeutic potential. Literature was systematically retrieved from PubMed, Embase, and ClinicalTrials.gov using the search terms 'endometrial hyperplasia', 'endometrial hyperplasia disease', 'endometrial disease', 'photodynamic therapy', and 'photodynamic diagnosis'. Articles related to PDT or photodynamic diagnosis (PDD) published between 1978 and 2025 were collected. Additionally, the bibliographies of relevant papers were manually screened to identify further eligible studies. Of the 11 included articles on endometrial hyperplasia diseases, 7 were therapeutic studies and 4 were diagnostic studies. PDT using various photosensitizers (Photogem, 5-ALA, and Photoditazin) demonstrated complete remission rates ranging from 68 % to 94 %, with recurrence rates between 6 % and 33 %. Among 17 patients who attempted pregnancy after PDT, 4 achieved 7 pregnancies resulting in 6 live births. In addition, hysteroscopic PDD demonstrated high diagnostic value in distinguishing endometrial lesions and guiding targeted intervention. Photodynamic therapy offers a minimally invasive, fertility-preserving alternative for the management of endometrial hyperplastic diseases. Its ability to integrate diagnosis and treatment, adapt to personalized regimens, and be combined with other modalities positions PDT as a promising strategy in gynecologic precision medicine. Continued innovation, standardization of treatment parameters, and expansion of clinical evidence are essential for routine adoption.
Photodynamic therapy (PDT) and proton therapy (PT) are established cancer treatment modalities, each characterized by distinct therapeutic advantages. PDT operates through the light-induced activation of photosensitizers (PSs), resulting in the generation of oxygen-dependent reactive oxygen species (ROS) that mediate cytotoxic effects, whereas PT provides highly conformal dose delivery in the centre of tumor with reduced irradiation of surrounding normal tissues. We hypothesize that proton irradiation may synergistically enhance PDT efficacy and fluorescence-guided imaging through proton-induced secondary electron production, increased PS excitation and ROS production, particularly within high Linear Energy Transfer (LET) regions near the Bragg peak. Following PDT, residual PS accumulated within the tumor may still be exposed to proton irradiation. At the Bragg peak, proton irradiation may therefore induce PDT-related effects through two complementary mechanisms. First, protons traveling through tissue generate Cherenkov radiation, which can excite PS molecules and promote the formation of ROS. Second, proton interactions produce abundant secondary electrons that can directly excite PSs, resulting in enhanced fluorescence emission. Emerging experimental evidence suggests that accelerated protons can directly activate PSs, increase Singlet oxygen (1O₂) production, and amplify fluorescence signals, while the spatial confinement of proton dose minimizes background autofluorescence from surrounding tissues. Collectively, these mechanisms support a potential theranostic paradigm in which proton irradiation not only directly causes cytotoxic radiation damage but also potentiates photodynamic activity and imaging contrast. If validated, this concept could motivate further translational and clinical research toward the development of proton-activated PDT as an integrated strategy for improving tumor control while limiting collateral tissue damage. It should also be mentioned that proton irradiation is not biologically inert, and the known accumulation of PSs in normal tissues highlights the importance of improved tumor-to-normal tissue PS uptake ratios, optimization of treatment timing, and careful evaluation of off-target effects.
Actinic keratosis (AK) is a common premalignant condition arising from chronic ultraviolet exposure and frequently occurs within fields of sun-damaged skin that harbour subclinical dysplasia. To summarize the mechanistic rationale, clinical evidence, safety profile, and practical considerations for a sequential regimen of short-course topical 5-fluorouracil (5-FU) pretreatment followed by daylight-mediated photodynamic therapy (dPDT) for field-directed management of AK. We performed a narrative synthesis of randomized controlled trials, split-site studies, mechanistic investigations and cohort reports identified through comprehensive searches of major biomedical databases. An intra-individual randomized trial demonstrated that pretreatment with 4% 5-FU cream prior to daylight-PDT achieved superior overall clearance 87% versus 74% especially in thicker (grade II) lesions. Across the reviewed studies, the sequential use of 5-fluorouracil followed by daylight photodynamic therapy achieved higher rates of complete lesion clearance, particularly in grade II cases. These benefits were sustained in 12 months, with lower recurrence rates and strong patient satisfaction. While the combination approach was linked to temporary redness and scaling, these side effects were mild and did not result in treatment discontinuation in the reported trials. Short-course topical 5-FU pretreatment before dPDT is a biologically plausible and clinically promising strategy to improve lesion and field clearance in AK, particularly for moderately thick lesions. Larger multicentre randomized trials with standardized protocols and longer follow-up are required to define optimal dosing, timing, and applicability to hyperkeratotic high-grade lesions.
Management of basal cell carcinoma (BCC) in cosmetically critical facial areas remains challenging when surgery is contraindicated or declined. Although Hedgehog pathway inhibitors (HHIs) and photodynamic therapy (PDT) are established non-surgical options, monotherapies have limitations. Combining systemic targeted therapy with local treatment may improve outcomes. To evaluate the efficacy and safety of short-course oral Sonidegib combined with fractional CO₂ laser-assisted 5-aminolevulinic acid photodynamic therapy (ALA-PDT) for treating facial BCC unsuitable for surgery. This retrospective case series involved 7 consecutive patients with histologically confirmed facial BCC unsuitable for or declined surgery. Patients received oral Sonidegib (200 mg daily for 6 weeks) combined with six sessions of ALA-PDT preceded by ablative fractional CO₂ laser pretreatment. Clinical responses were assessed at 1, 3, and 6 months using modified WHO criteria. All patients completed treatment. Complete response (CR) rates were 71.4% (5/7) at 1 month and 100% (7/7) at 3 and 6 months, with no recurrences. No typical systemic adverse events associated with long-term Sonidegib (e.g., muscle spasms, dysgeusia) occurred. PDT-related reactions were mild and transient, with no scarring or pigmentary changes. Short-course Sonidegib combined with fractional CO₂ laser-assisted ALA-PDT demonstrates high efficacy and favorable tolerability for facial BCC unsuitable for surgery, offering a durable non-surgical alternative warranting prospective validation.
Herpes simplex virus (HSV) infections are a common clinical concern, often requiring effective antiviral treatments. Anti-microbial photodynamic therapy (aPDT) has gained attention as a potential adjunct to conventional therapies for managing HSV outbreaks. This systematic review aimed to evaluate the efficacy of aPDT in treating HSV infections. Following PRISMA guidelines, PubMed/MEDLINE, Scopus, Embase, and Web of Science online databases were systematically searched for relevant studies on July 2025. Healing time was considered as the primary outcome, and secondary outcomes included lesion size, viral load, and patient-reported outcomes. Clinical studies evaluating efficacy of aPDT against other therapeutic approaches with at least 10 patients were considered eligible. Quality appraisal of the included studies was conducted using the revised Cochrane risk-of-bias tool for randomized trials (RoB2) and the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I). In addition, the certainty of evidence was assessed with a modified version of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework adapted for reviews without quantitative synthesis. aPDT monotherapy demonstrated clinical outcomes comparable to conventional antiviral therapy, with reductions in viral load and edema but limited superiority in clinical healing parameters. In contrast, adjunctive use of aPDT with antiviral therapy consistently improved pain, inflammatory markers, viral load, healing outcomes, and recurrence rates compared with either treatment alone. aPDT appears to be an effective adjunctive therapy for HSV infections, but further high-quality studies are necessary to refine treatment protocols and confirm its clinical benefits.
Basal cell carcinoma (BCC) is a common skin malignancy, often occurring in cosmetically sensitive facial areas. We report a case of a 46-year-old woman with BCC of the right nasal ala. The lesion had persisted for nine years, gradually enlarging, with recent ulceration and crusting. Skin biopsy confirmed BCC. The patient underwent Mohs micrographic surgery (MMS), with the wound left to heal by secondary intention for 48 h, followed by sequential 5-aminolevulinic acid photodynamic therapy (ALA-PDT) once weekly for five consecutive weeks. A freshly prepared 20 % 5-aminolevulinic acid (ALA) solution (118 mg, Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd) was topically applied to the entire open defect of the right nasal ala and its 0.5 cm peripheral marginal area, occluded with aluminum foil to block light, and incubated for 3 h. After removal of the covering, the area was irradiated with 635-nm red light at 80 mW/cm²and 120 J/cm² for 20 min (Wuhan Yage Optic and Electronic Technique Co., Ltd). Approximately 5 months and 12 days after the final PDT session, repeat histopathology showed no residual tumor, and hypertrophic scar formation was observed. No recurrence or further BCC was noted during the 5-year follow-up. This case demonstrates that MMS combined with ALA-PDT can achieve effective local tumor control while preserving function and optimizing cosmetic outcome for BCCs larger than 1 cm in aesthetically sensitive facial areas.
Traditional photodynamic therapy (PDT) is limited by low penetration of light in the tissue. Cherenkov radiation-induced PDT (CR-PDT) uses Cherenkov luminescence from charged particles passing through the tissue as an internal light source to excite photosensitizers (PS) used to treat deep tumors. This systematic review was carried out according to PRISMA 2020 protocols and was registered in the PROSPERO database (CRD420261309392). PubMed, Web of Science, and Scopus databases were searched (January 2015-February 2026). Sixteen preclinical studies (14 in vitro/in vivo, 2 early translational) were included after screening 894 records. Beta-emitters (primarily 89Zr, 18F-FDG, 90Y) activated diverse PS, frequently nanoparticle-encapsulated (e.g., mesoporous silica nanoparticles, extracellular vesicles, or graphene oxide hybrids), producing reactive oxygen species (ROS) via Type I/II mechanisms. In vitro, dose-dependent reductions in metabolic activity (assessed by MTT/MTS assays and flow cytometry), which reflect acute biological response but not clonogenic survival in two studies) reached >70-80% reduction in cell viability with optimized nanoplatforms. In vivo, significant tumor growth regression and survival benefits were observed in animal models (murine breast, ovarian, liver, and pancreatic xenografts). Cherenkov luminescence imaging (CLI) provided inherent theranostic monitoring of distribution and response. The risk of bias (ROB) was low in general. CR-PDT represents an experimental preclinical strategy for internally activated theranostic PDT in deep-seated tumor models. Nanotechnology enhances efficacy, but clinical translation requires standardized dosimetry and larger studies.
Moderate and high hyperopia is a common clinical refractive error that severely affects distant and near visual functions. Traditional correction relies on high-power positive spherical lenses, which are prone to problems such as thick lens thickness, heavy weight, poor wearing comfort, and limited visual correction effect, resulting in low wearing compliance and reduced life quality of patients. Existing telescopic correction devices have the defects of large volume and narrow imaging field of view, which cannot meet the needs of daily clinical correction. This study aims to construct an improved optical correction system based on the Galilean telescope principle, and explore a low-burden, high-efficiency novel correction scheme for moderate and high hyperopia. Based on the afocal imaging theory of Galilean telescopes, a novel diopter-splitting optical structure was constructed with a zero-diopter air lens as the core component. The total diopter of hyperopic refractive error was decomposed and redistributed optically. A low-power positive lens was adopted to undertake the major correction of hyperopia, while the residual refractive diopter was matched with a negative eyepiece corresponding to the hyperopic degree. Combined with a positive spherical objective lens, the optical interval between lens groups was precisely optimized to form a compact Galilean telescopic correction system with the magnification limited within 2.0 × . Optical simulation was conducted to explore the quantitative relationships among optical magnification, system structural size, imaging distortion and field of view, so as to determine the optimal wearable structural parameters for clinical application. The proposed novel optical system can effectively correct moderate and high hyperopia merely by using low-power positive lenses, which completely eliminates the clinical drawbacks of traditional high-power lenses such as excessive thickness and heavy weight. When the magnification is controlled within the range of 1.2 × -1.5 ×, the system features an ultra-compact structure, excellent wearability, wide imaging field of view and negligible optical distortion. Excessively high magnification (over 2.0 ×) will greatly narrow the peripheral visual field, reduce the effective imaging area, and significantly weaken the practical wearable value of the device. Reasonable low magnification can effectively magnify retinal images, relieve blurred vision caused by refractive defocus, and alleviate long-term visual fatigue in hyperopic patients. The improved Galilean telescopic correction system realizes innovative diopter-splitting correction for moderate and high hyperopia, breaking the limitations of traditional hyperopia correction lenses and conventional telescopic optical devices. The optimized low-magnification optical structure has the advantages of compact volume, wide field of view, low distortion and good wearing adaptability. It can effectively improve visual acuity and daily visual quality of patients with moderate and high hyperopia, and greatly enhance life satisfaction. This system has broad application prospects in clinical optometric correction and low-vision rehabilitation.
Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA-PDT) is a an established treatment for condylomata acuminata; however, its application to the vulvar region is frequently associated with significant pain and localized tissue damage, which adversely affects patient tolerance and treatment adherence. This study evaluated whether a refined nursing intervention could improve clinical outcomes compared with conventional nursing. This retrospective cohort study included 55 female patients with vulvar condylomata acuminata treated with ALA-PDT. Patients were divided into refined nursing (n=30) and conventional nursing (n=25) groups. Primary outcomes were treatment interval, completion rate, lesion clearance, and HPV clearance. Secondary outcomes included pain scores (VAS), patient satisfaction, and adverse events. Multivariable logistic regression identified predictors of lesion clearance. Compared to conventional nursing, the refined nursing group showed that treatment intervals significantly shortened (8.2±1.1 vs. 12.5±2.2 days), completion rate increased (96.7% vs. 76.0%), HPV clearance became higher at 6 months (86.7% vs. 64.0%), and patients were more satisfactory (96.7% vs. 64.0%). Peak pain during treatment was significantly lower in the refined group (4.3±1.5 vs. 5.9±2.1). Receiving ≥3 treatment sessions was independently associated with lesion clearance. Refined nursing significantly shortens treatment intervals, reduces intra-procedural pain, improves treatment adherence, HPV clearance, and patient satisfaction. Completing three or more sessions is a key predictor of better efficacy.
Repeated low-level red-light (RLRL) therapy, a photobiomodulation approach for myopia control, has shown potential in modulating choroidal and axial structures. Recent studies have combined RLRL with optical interventions such as orthokeratology (OK) and defocus incorporated multiple segment (DIMS) spectacles. However, the efficacy and safety of these combinations remain unclear. This study synthesized current evidence on RLRL combined with optical interventions for pediatric myopia control. A systematic search of PubMed, EMBASE, Cochrane Library, Web of Science, CNKI and Wanfang Data was conducted up to July 14, 2025. Randomized and cohort studies comparing RLRL combined with OK or DIMS versus monotherapy were included. Primary outcomes were axial length (AL), spherical equivalent refraction (SER), and subfoveal choroidal thickness (SFChT). Fixed- or random-effects models were used based on heterogeneity. Risk of bias was assessed with ROB2 and ROBINS-I. Eight studies were included. Compared with optical monotherapy, combination therapy was associated with reduced axial elongation, slower SER progression, and greater increases in SFChT. Structural changes were observed as early as 1 month and persisted through 12 months. No significant differences were detected in short-term ocular surface adverse events. However, heterogeneity and regional concentration of data were noted. Adjunctive RLRL therapy may enhance optical myopia control effects, particularly in reducing axial elongation and increasing choroidal thickness, possibly through choroidal modulation. These findings should be viewed as early biological signals, not definitive evidence of long-term superiority. Larger multicenter randomized trials with extended follow-up are needed to confirm durability, safety, and dose-response characteristics.
Intraductal photodynamic therapy (PDT) is a promising minimally invasive treatment for bile duct tumors, but clinical efficacy is limited by uneven intraductal light distribution and light dose attenuation induced by intraluminal blood and bile. To develop an optical transmission device for intraductal PDT of bile duct tumors and optimize the light irradiation strategy. The power density distribution was analyzed by COMSOL simulation, and laser attenuation by blood and bile was quantified using an integrating sphere power meter. A fiber-balloon catheter was constructed and evaluated in two pigs that received hematoporphyrin derivative (2 mg/kg) 48 h preoperatively. Under cholangiographic guidance, the device was inserted via enterotomy, and laser irradiation was delivered at 100 mW/cm² for 1200 s. Histopathology was assessed at 3 days post-PDT. Blood and bile caused 32.5 % to 45.8 % laser power attenuation. In a 1-cm-diameter duct, eccentric fiber positioning produced 2- to 3-fold wall power density variations. The balloon catheter maintained stable central fiber positioning, expelled intraluminal fluids, and caused no adverse events. Histopathology revealed circumferential, uniform bile duct epithelial necrosis at 3 days post-PDT. The cylindrical fiber balloon catheter is safe and feasible, and it can effectively improve the uniformity of light irradiation during intraductal PDT for bile duct tumors.
Chemotherapy resistance from temozolomide (TMZ) continues to be a major cause of glioblastoma (GBM) recurrence. Emerging evidence indicates that cytoprotective autophagy constitutes a key resistance mechanism​ to TMZ. Photodynamic therapy (PDT) has been shown to modulate the sensitivity of glioblastoma cells (GCs) to TMZ through multiple pathways. This study aims to explore how PDT regulates the sensitivity of GCs to TMZ chemotherapy by inhibiting autophagy formation. The vitality and proliferation ability of U251 cells were evaluated under different treatments using cell counting kit-8 (CCK-8), colony formation, and fluorescence assays, respectively. The reactive oxygen species (ROS) levels were measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence probes. The features of autophagy were assessed via lysosomal fluorescent probes, monodansylcadaverine (MDC) staining, and transmission electron microscopy (TEM). Compared to TMZ group, samples treated with the combination of TMZ and PDT showed a marked reduction in both cell viability and proliferative ability. Despite this anti-tumor effect, cell death, as assessed by propidium iodide (PI) staining, was not significantly increased during the first 4 h of the combination treatment. But the fluorescence intensity of ROS was significantly higher in Combination group, compared with the other group. The fluorescent analyses and TEM observations confirmed an increase in cytoprotective autophagy in the late phase of TMZ therapy. However, the PI staining assay revealed that the TMZ with synergistic PDT enhanced the percentage of GCs death. The combination of TMZ and PDT suppresses autophagy by increasing ROS levels, thereby improving the sensitivity of GCs to TMZ chemotherapy. This finding represents a novel biomedical engineering strategy to overcome TMZ resistance.
To compare the efficacy of laser ablation combined with photodynamic therapy (LA-PDT) versus PDT alone in the treatment of cervical intraepithelial neoplasia grade 2/3 (CIN2/3). Patients diagnosed with CIN2/3 were enrolled and allocated to either the LA-PDT or the PDT group based on patients' choice. Pathological regression and human papillomavirus (HPV) clearance were compared at 12-month follow-up between the two groups. A total of 77 patients in the LA-PDT group and 68 patients in the PDT group completed follow-up. Baseline characteristics showed no significant differences between the two groups. At the 12-month follow-up, both the pathological complete remission rate and HPV clearance rate were significantly higher in the LA-PDT group compared to the PDT group (98.7% vs. 86.4%, P < 0.05; 92.3% vs. 86.4%, P < 0.05). Univariate and multivariate analyses indicated that the pre-treatment pathology of CIN3 was an independent risk factor for both lesion persistence and HPV persistence. Among the 111 patients with CIN2, the pathological complete remission rate was 98.2% and the HPV clearance rate was 95.5%. Among the 33 patients with CIN3, both the pathological complete remission rate and HPV clearance rate were significantly higher in the LA-PDT group than in the PDT group (94.1% vs. 56.3%, P < 0.05; 76.5% vs. 37.5%, P < 0.05). LA-PDT for CIN2/3 demonstrates high efficacy and saves time and economic costs. The combined therapy shows significant advantages over PDT alone, particularly for patients with CIN3.
This study aimed to assess the effect of antimicrobial photodynamic therapy (PDT) on accumulation of Streptococcus mutans (S. mutans) on the surface of orthodontic composite used in fixed retainers. In this in vitro study, 60 Ortho Connect Flow composite discs were evaluated in two groups (n = 30) of fresh and aged (by thermocycling and toothbrushing). Composite discs in each group were inoculated with S. mutans, and evaluated in 5 subgroups (n = 6) of control, diode laser alone (660 nm, 200 mW, 400 mW/cm2, 24 J/cm2, continuous-wave mode, for 60 s), methylene blue (MB = 100 µg/mL), PDT with diode laser (with the aforementioned parameters) and MB, and 0.2 % chlorhexidine (CHX). After the treatments, S. mutans colonies were counted, and data were analyzed by three-way and two-way ANOVA (alpha = 0.05). The CHX group showed the lowest colony count. The effects of 660 nm diode laser, MB, and their interaction (PDT) on colony count were all significant (P < 0.05). The PDT group also showed a significantly lower colony count than other groups (P < 0.05). The difference in colony count between the fresh and aged discs was not significant (P > 0.05). The results of this in vitro study showed that PDT with 660 nm diode laser (with the aforementioned parameters) and MB significantly prevented the accumulation of S. mutans on the surface of orthodontic composite, and may be suitable as an adjunct for biofilm control.
Interstitial photodynamic therapy (iPDT) is an emerging loco-regional treatment for glioblastoma based on intracerebral illumination delivered through stereotactically implanted optical fibers. Despite encouraging oncological results, treatment-related morbidity remains significant, and the contribution of unintended light-induced thermal effects has never been experimentally investigated. This study aimed to preclinically characterize temperature changes during illumination using MRI-based thermometry. Fifty-seven minutes of illumination were performed in ex vivo calf brain model at room temperature baseline. The temperature was monitored using the proton resonance frequency shift (PRFS) method on a 1.5 T MRI system. Thermometric measurements were first validated against fiber-optic temperature probes during single diffusing fiber illumination. Spatio-temporal thermal distributions were then evaluated for three diffusing fiber configurations with inter-fiber spacings of 2.0, 1.0, and 0.6 cm. Macroscopic assessment of thermal tissue damage was performed after illumination. MRI thermometry showed excellent agreement with fiber optic temperature probes. Cumulative heating strongly depended on inter-fiber spacing. At the barycenter of the diffusing part of the three fibers, the mean ± SD final temperature estimated was 43.7 ± 0.7 °C at 2.0 cm spacing, 46.6 ± 5.9 °C at 1.0 cm spacing, and 53.5 ± 10.2 °C at 0.6 cm spacing. No macroscopic thermal tissue damage was observed. MRI thermometry provides a robust and translatable tool to quantify thermal effects during iPDT. Diffusing fiber spacing critically influences temperature distribution, supporting the use of thermometric monitoring to enhance procedural safety. Future clinical thermometric data could be implemented into treatments planning systems to refine fiber placement and enable patient-specific strategies aimed at maximizing therapeutic efficacy while minimizing the risk of thermal injury.
To determine the diagnostic accuracy and optimal threshold values of anterior and posterior corneal parameters obtained with the Sirius+ Scheimpflug-Placido tomography system in detecting clinical keratoconus (KCN) and subclinical keratoconus (sKCN). In this cross-sectional study, 112 eyes (40 KCN, 32 sKCN, and 40 healthy controls) were classified based on clinical and tomographic findings. Corneal tomography was performed using the Sirius+ system under standardized conditions. The evaluated parameters included anterior and posterior symmetry indices (SIf, SIb), anterior and posterior keratoconus vertex values (KVf, KVb), and minimum corneal thickness (THKmin). Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis, including area under the curve (AUC), sensitivity, specificity, and optimal cut-off values. THKmin progressively decreased from controls to sKCN and KCN (528.08 ± 36.26, 479.30 ± 32.55, and 455.75 ± 37.76 µm, respectively; p ≤ 0.001). Conversely, SIf and SIb values increased significantly across groups (SIf: 0.21±0.36, 1.19±0.82, 3.86±3.09 D; SIb: 0.05±0.07, 0.37±0.39, 1.01±0.65 D; all p ≤ 0.001). Similarly, KVf and KVb values showed a progressive increase, with KVb demonstrating marked elevation in KCN (p < 0.001). For differentiating sKCN from controls, SIb showed the highest diagnostic performance (AUC = 0.934), with 90.0% sensitivity and 85.0% specificity at a cutoff value of >0.11 D Conclusion: Posterior corneal parameters derived from Sirius+ tomography, particularly SIb and KVb, demonstrated superior diagnostic performance in detecting both clinical and subclinical keratoconus. Posterior surface-based multiparametric analysis may improve early detection and should be incorporated into routine tomographic evaluation.
Evaluating retinal fundus image for diabetic retinopathy (DR) assessment is used to reduce the risk of blindness among diabetic patients. To do this, DR staging is one of the challenging tasks in screening DR that includes the assessment of disease severity or progression. We introduce a novel Radiomics and machine learning algorithm (MLA) framework that analyzes localized vascular leakage sources in Optical coherence tomography angiography (OCT-A) images, using fundus fluorescein angiography (FFA) as reference, to noninvasively stage DR. By extracting 23 optimized features from leakage-prone regions and employing X-Gradient (XGboost), Adaptive Boost, and Multilayer Perceptron (MLP) classifiers, our approach achieves unprecedented accuracy in differentiating moderate NPDR to early proliferative diabetic retinopathy. We developed a novel radiomic and MLA framework to extract features (vascular, image-based, and clinical) from leakage source regions in OCT-A images identified by corresponding FFA images. XGboost, Adaptive Boost, MLP classifier were created to evaluate their diagnostic accuracy for different DR stages. MLA performance was comprehensively evaluated via multiple metrics (accuracy, precision, recall, AUC, sensitivity, specificity) and visualized through confusion matrices (CMs) and receiver operating characteristic (ROC) curves to ensure robust clinical applicability. A dataset of 99 patients and 179 images was included. For staging in DR, the highest accuracy (96.6 ± 1.4% [95% CI: 93.9 - 99.3%]) and AUC (98.9 ± 0.5%) were observed for the XGBoost classifier with all image-based features alone. The MLP performed better with vascular and clinical features. (Accuracy: 92.5 ± 3.2%92.5[95% CI: 86.2 - 98.8%], AUC: 95.2%) Entropy, Haralick, GLCM, eccentricity, vessel branch, vessel density, tortuosity (combining geometric analysis and wavelet transform), fractal dimension analysis (combining box counting and wavelet-based), and fast blood sugar emerged as particularly significant discriminative features across DR stages. Our approach identifies distinctive vascular and textural biomarkers-including hybrid fractal dimension, vessel tortuosity, and Haralick features-that effectively differentiate DR stages while providing new pathophysiological insights into microvascular remodeling in leakage-prone areas. By bridging non-invasive OCT-A with leakage-specific assessment, this method offers a clinically viable tool for early detection, progression prediction, and personalized DR management. Although limited by macular-centric scans and exclusion of very early/advanced stages, our findings establish a foundation for future multi-center studies with wider fields of view. This work represents a significant advance toward AI-enhanced ophthalmology, paving the way for actionable diagnostic paradigms in diabetic eye disease.