Photodiagnosis and photodynamic therapy最新文献

Purpose: To develop and validate algorithms that automatically measure horizontal ocular alignment in children's primary gaze photographs using deep learning and computer vision.

Materials and methods: We proposed two-stage artificial intelligence (AI) system, including deep learning (DL) algorithms for automatic segmentation of eye structure and computer vision (CV) algorithms to measure horizontal ocular alignment. DL algorithms were trained using a public ocular images dataset. The measurements of CV algorithms were tested in primary gaze photographs recruited from a tertiary hospital.

Results: The DL training dataset involved 11,018 ocular and corresponding ground truth images. We then used 147 primary gaze photographs to validate the CV algorithms. The strabismus angles measured by the AI system closely followed the Hirschberg test (HT) using linear regression analysis (slope = 0.919, p < 0.001). There was excellent agreement between the two methods, as measured by the intra-class correlation coefficient (ICC = 0.98). Compared to the angle measured by HT, the proposed algorithms achieved a limits of agreement (LoA) of -7.1 to 6.3 prism diopters (PD) and coefficients of variation (CoV) of 13.5%.

Conclusion: In conclusion, we proposed an automated DL and CV system to measure horizontal ocular alignment using gaze photographs. Our system produced predictions similar to the measurement by Hirschberg test. In addition, the two-stage AI system provided an explanation of the rationale for clinical decisions.

Background: Mycobacteroides abscessus is a common rapidly- growing non-tuberculosis mycobacteria (NTM) that exhibits resistance to most antibiotics and is associated with low cure rates, highlighting an urgent need for new therapeutic strategies. Our previous clinical study has found that ALA-PDT may represent a novel and promising approach for treating M.abscessus infection, although its precise mechanism of action remains to be elucidated.

Methods: To investigate the mechanism by which ALA-PDT kills intracellular M. abscessus, we established an intracellular infection model using THP-1 to evaluate its bactericidal effect. Subsequently, RNA-sequencing analysis and targeted in vitro experiments were performed to explore the underlying mechanisms.

Results: ALA-PDT significantly reduced the intracellular survival of M. abscessus in THP-1. RNA sequencing revealed that ALA-PDT modulates multiple cellular pathways, notably inducing the upregulation of autophagy-related genes. Consistently, ALA-PDT increased autophagosome formation and LC3 expression in both infected and uninfected macrophages. The bactericidal effect of ALA-PDT against intracellular M. abscessus was markedly attenuated by an autophagy inhibitor, confirming the functional role of autophagy. In addition, ALA-PDT promoted the generation of reactive oxygen species (ROS), while a ROS inhibitor suppressed the ALA-PDT induced increase in LC3 expression and the decrease in intracellular bacterial survival. Transcriptomic analysis suggested that EP300 may play a key regulatory role in this process. In vitro experiments confirmed that ALA-PDT downregulated EP300 expression, and an EP300 activator significantly reversed the ALA-PDT-mediated increase in LC3 expression and reduction in intracellular bacteria. Finally, ALA-PDT was found to alter the acetylation levels in THP-1, pointing to a potential epigenetic mechanism.

Conclusions: These findings demonstrate that ALA-PDT activates antibacterial autophagy via the ROS-EP300 pathway to eliminate intracellular M. abscessus, uncovering a potential epigenetic immune mechanism. This work provides a theoretical foundation for the clinical application of ALA-PDT in treating M. abscessus infections.

Objective: For diagnosis and monitoring of ocular neoplastic lesions, ultrasonography (US) measurements are pivotal. Using color fundus photographs rather than US may allow follow-up with an ophthalmologist close to patients' home and may reduce the need of patients to travel to specialized ocular-oncological centers. This study aims to compare measurements of choroidal melanoma (CM) diameters in ultra-widefield color fundus images (UWF-CF) to measurements based on US.

Patients and methods: In this comparative retrospective study patients with CM and available US and UWF-CF were included. Standardized US measurements and UWF-CF were compared using Bland-Altman plots and paired t-tests to evaluate agreement of methods.

Results: 53 eyes of 53 patients with CM (31 male (58.5%), mean age 63±13 years) were included in this study. Mean transversal diameter (TD) was not statistically significantly different between US (9.06±2.65mm) and UWF-CF (9.04±3.07mm; p=0.920). Mean longitudinal diameter (LD) was statistically significantly greater in UWF-CF (10.01±2.86mm) as compared to US (9.31±2.55mm; p=0.009).

Conclusions: Tumor diameters can be assessed accurately in UWF-CF. TD on UWF-CF is comparable to US measurements via a standardized procedure. Differences may be explained by the presence of e.g. fibrosis or hard exudates obscuring basal tumor diameters.

Introduction: Apical periodontitis (AP) results from microbial infection within the root canal system. Although mechanical and chemical debridement techniques have advanced, real-time intraoperative visualization of bacterial persistence remains limited. This study evaluated whether fluorescence-aided root canal treatment (FARCT) using protoporphyrin IX fluorescence (PpIX-FL) could assist clinicians in visualizing bacterial persistence in real time during routine endodontic procedures.

Methods: Fifty patients (23 initial treatments, 27 retreatments) underwent root canal treatment. PpIX-FL was visualized in real time under 405-nm excitation using a dental operating microscope. Fluorescent areas were documented, and multivariate logistic regression analysis was performed to assess associations with clinical factors. Histological examination and confocal microscopy were conducted to verify bacterial presence corresponding to PpIX-FL.

Results: PpIX-FL was detected in 56.0% of cases, particularly in isthmuses, fins, and contaminated gutta-percha. Fluorescence was significantly more prevalent in retreatment cases (OR=8.32; p=0.05) and teeth with periapical lesions ≥2 mm (OR=61.06; p=0.005). Confocal imaging and Gram staining confirmed that red autofluorescence areas corresponded with Gram-positive bacterial infiltration into dentinal tubules.

Conclusions: PpIX-FL enables reagent-free, real-time visualization of bacterial contamination within the root canal system. FARCT should be regarded as an adjunctive visualization approach rather than a stand-alone diagnostic or therapeutic modality. The present findings demonstrate the clinical feasibility of PpIX-based autofluorescence for fluorescence-guided visualization in endodontic retreatment and anatomically complex cases.

Background: Cutaneous Mycobacterium marinum (M. marinum) infection poses substantial diagnostic and therapeutic challenges and often necessitates prolonged multidrug antibiotic regimens, which are frequently associated with poor adherence and potential toxicity. This study aimed to evaluate the feasibility, efficacy, and safety of a treatment strategy combining oral clarithromycin with red-light photobiomodulation (PBM) and microwave therapy.

Methods: A single-center retrospective study was conducted on patients with M. marinum infection confirmed by culture and/or nested polymerase chain reaction (nested PCR) between 2021 and 2024. Clinical data were collected, and treatment outcomes were analyzed for patients who received combination therapy with oral clarithromycin, PBM and microwave treatment.

Results: All 14 patients were microbiologically confirmed to have M. marinum infection by culture and/or nested polymerase chain reaction (PCR)-based species identification. The median treatment duration was 4.5 weeks. Clinical cure was achieved in 10 patients, while 2 patients showed marked improvement and 2 exhibited partial improvement. No clinical recurrence was observed during a follow-up period of up to 36 months.

Conclusions: A clarithromycin-based regimen supplemented with PBM and microwave therapy appears to be safe and potentially effective for cutaneous M. marinum infection and may facilitate early clinical improvement with favorable tolerability. During follow-up, no clinical relapse was documented.

Background: Urinary cytology and white-light (WL) cystoscopy are standard tools for diagnosing bladder cancer; however, their sensitivity is limited for flat, visually inconspicuous lesions such as carcinoma in situ (CIS). Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (ALA) enhances tumor visualization; however, few studies have specifically evaluated CIS detection sensitivity stratified by cytology grade.

Objective: To evaluate the diagnostic accuracy of ALA-based PDD during transurethral resection of bladder tumors (TURBT) for detecting CIS, with cytology-stratified analyses and by anatomical site.

Methods: We retrospectively analyzed 89 patients with histologically confirmed CIS who underwent PDD-assisted TURBT at Kochi Medical School between 2018 and 2025. Detection rates at both lesion and patient levels using WL and PDD were compared using McNemar's test. Preoperative urinary cytology was classified according to the Papanicolaou system (classes I-V).

Results: In total, 217 CIS lesions were analyzed. Detection rates increased from 53.5% with WL to 87.1% with PDD (p < 0.001), with no WL-positive/PDD-negative lesions observed. PDD markedly improved detection across all subsites, particularly at the bladder neck (+56%) and dome (+37%). Overall, 31.5% of patients had at least one WL-negative/PDD-positive lesion and no WL-negative/PDD-negative lesions (true PDD-benefit), with corresponding proportions of 31.3%, 42.9%, and 24.4% for cytology classes I-II, III, and IV-V, respectively. The incremental benefit of PDD was evident across cytology strata, including cytology-negative (classes I-II) and equivocal (class III) patients.

Conclusions: ALA-based PDD-assisted TURBT significantly improves CIS detection compared with WL cystoscopy, providing consistent benefits across anatomical sites and cytologic strata.

Background: Periodontitis, a prevalent infectious disease driven by polymicrobial dental plaque biofilms, is associated with systemic health risks. Porphyromonas gingivalis acts as a keystone pathogen within these biofilms, with the fimA gene encoding the major fimbrial subunit FimA serving as a key virulence factor facilitating bacterial adhesion and biofilm formation, critical for persistence and periodontal destruction. Berberine, a benzylisoquinoline alkaloid with antimicrobial properties, is limited by poor solubility and bioavailability. This study explores antimicrobial photodynamic therapy (aPDT) using berberine-loaded human dental pulp stem cell-derived exosomes (Ber@hDPSCs-Exos) to enhance anti-biofilm efficacy against P. gingivalis.

Materials and methods: Exosomes were isolated from hDPSCs and characterized by transmission electron microscopy, flow cytometry (CD81 expression), and Bradford assay. Berberine was loaded into exosomes via ultrasonication, with encapsulation efficiency assessed by UV spectrophotometry. The minimum biofilm inhibitory concentration (MBIC) of Ber@hDPSCs-Exos, minimum biofilm inhibitory dose (MBID) of a 405 nm diode laser, and MBIC of aPDT were determined against P. gingivalis biofilms using colorimetric assays. The expression of the fimA virulence gene was evaluated via quantitative real-time PCR. Statistical analysis was performed using one-way ANOVA (P < 0.05).

Results: hDPSCs-Exos exhibited spherical morphology, high CD81 expression (80.3%), and a protein concentration of 460.75 µg/mL. Berberine encapsulation efficiency was 74.9%. Ber@hDPSCs-Exos inhibited P. gingivalis biofilm formation with an MBIC of 125 µg/mL, while the diode laser MBID was 240 s (103.9 J/cm²). aPDT with 31.2 µg/mL Ber@hDPSCs-Exos and 60 s irradiation significantly reduced biofilm biomass (OD570 nm ∼2.44). Sub-MBIC aPDT (15.6 µg/mL, 120 s) downregulated fimA expression by 3.1-fold (P < 0.05).

Conclusion: Ber@hDPSCs-Exos-based aPDT effectively inhibits P. gingivalis biofilm formation and reduces fimA expression, offering a promising adjunctive treatment for periodontitis management. Further in vivo studies are required to confirm the clinical potential of this approach.

Purpose: To evaluate choroidal vascular alterations in the contralateral eyes of patients with neovascular age-related macular degeneration (N-AMD) and subretinal fibrosis (SRFi) using optical coherence tomography angiography (OCTA).

Methods: This retrospective study included 57 patients (57 eyes) with unilateral N-AMD and a normal fellow eye. Patients were classified by multimodal imaging into SRFi (24 eyes) and non-SRFi (32 eyes) groups. Best-corrected visual acuity (BCVA, logMAR), subfoveal choroidal thickness (SFCT), and OCTA-derived choriocapillaris and choroidal vessel density (VD, %) were measured. Group differences were assessed using binarized OCTA scans, and correlation and logistic regression analyses were performed.

Results: SFCT was significantly reduced in the SRFi group compared with controls (P<0.05) and was positively correlated with choroidal VD (r=0.414, P=0.045). Multivariate logistic regression identified SFCT (OR=0.98, 95% CI: 0.96-0.99, P=0.006) and choroidal VD (OR=0.85, 95% CI: 0.72-1.00, P=0.047) as independent risk factors for SRFi.

Conclusion: Decreased SFCT and choroidal VD in the contralateral eyes of N-AMD patients with SRFi suggest a potential role in disease pathogenesis and progression. These parameters may serve as early biomarkers for the onset of SRFi in N-AMD.

Purpose: To characterize subclinical macular microvascular alterations in eyes with high myopia (HM) using optical coherence tomography angiography (OCTA) and to investigate the relationship between retinal microvasculature, retinal thickness (RT), and axial length (AL).

Methods: In this prospective, cross-sectional study, 108 eyes with HM (spherical equivalent ≤ -6.00 D, axial length ≥ 26 mm) and 96 age- and sex-matched healthy control eyes were examined. Macular vascular density (VD) in the superficial and deep capillary plexuses (SCP and DCP), foveal avascular zone (FAZ) metrics, and RT were quantified after ocular magnification correction. Correlations between OCTA parameters, RT, and AL were evaluated using Pearson's correlation analysis.

Results: In both SCP and DCP, foveal VD was significantly higher in HM eyes compared with controls (P < 0.001), whereas parafoveal VD was markedly reduced (P < 0.001). FAZ area and perimeter were significantly enlarged in HM eyes (P = 0.01 and P = 0.02, respectively). The foveal RT was significantly higher in the HM group compared with controls (P < 0.001). In contrast, the parafoveal RT was significantly lower in the HM group compared with controls (P < 0.001). Correlation analysis revealed that VD was positively associated with regional RT in the HM group (all P < 0.01). Notably, while AL showed a negative association with parafoveal VD and a positive correlation with FAZ metrics, no significant correlation was observed between AL and foveal VD in the HM group.

Conclusions: Eyes with HM without pathological changes exhibit a distinct pattern of macular microvascular remodeling, characterized by reduced parafoveal VD alongside increased foveal VD. These findings suggest that microvascular attenuation is more pronounced in the parafoveal region than in the foveal center and highlight OCTA-derived vascular metrics as candidate imaging features for characterizing non-pathological HM, which warrant validation in longitudinal studies.