Zuguo Liu

Dry eye disease (DED) is a multifactorial disorder characterized by intricate pathogenesis, necessitating a multi‐target synergistic intervention strategy. Current anti‐inflammatory drugs for DED are limited by low bioavailability, ocular irritation, and inadequate relief. Herein, we propose a multifunctional hydrogel encapsulating Mizoribine, a small‐molecule water‐soluble immunosuppressant. The formulation undergoes in situ gelation on the ocular surface, forms a mucin‐adhered coating, and responds to pathological oxidative stress to enable controlled drug release. In vitro studies demonstrate the formulation effectively mitigates cellular oxidative stress by scavenging ROS and upregulating antioxidant factors. It also protects mitochondrial function, reduces apoptosis, and modulates macrophage polarization. In vivo, topical application of the hydrogel markedly alleviates clinical signs of disease. It also suppresses ocular surface inflammation and reverses conjunctival goblet cell loss. Molecular and cellular analyses indicate the hydrogel exerts its therapeutic effects primarily through antioxidative, anti‐inflammatory, and macrophage‐modulating mechanisms. Importantly, the formulation exhibits an excellent biosafety profile. Our findings highlight that this multifunctional hydrogel serves as a potent, convenient, and safe nanotherapeutic platform. By integrating ROS‐responsive, thermosensitive, and sustained drug‐release properties with antioxidant, anti‐inflammatory, and immunomodulatory functions, this formulation simultaneously targets multiple pathological pathways, offering a promising avenue for clinical translation in treating chronic ocular surface diseases.

AIM: To explore the feasibility of optical coherence tomography angiography (OCTA) in the early detection of syphilis and syphilitic chorioretinopathy. METHODS: Patients with newly diagnosed syphilis were enrolled from September 2022 to November 2023. All the participants underwent serological examinations including rapid plasma reagin (RPR) test and treponema pallidum particle agglutination (TPPA) test, as well as macular OCTA scanning. Quantitative indicators including macular vessel flow density (VFD), vessel length density (VLD), and foveal avascular zone (FAZ) were measured and analyzed. RESULTS: A total of 44 participants were recruited in this study, including 24 patients in the syphilis group (14 males, mean age: 30.83±9.59y) and 20 healthy individuals in the control group (6 males, mean age: 29.6±11.86y). Compared with the control group, the syphilis group presented significantly higher macular VLD and VFD (P<0.05), as well as an increased FAZ perimeter. Subgroup analysis was performed based on RPR titers, with patients divided into the low-titer subgroup (1:2–1:4) and high-titer subgroup (1:8–1:128). Both subgroups showed elevated VLD and VFD (excluding inner VFD) relative to controls (all P<0.05). Moreover, significant elevation of VFD was only observed in the high-titer subgroup. Receiver operating characteristic analysis identified outer VLD as the optimal indicator for distinguishing syphilis patients from controls, with an area under the curve of 0.802 (95%CI: 0.667–0.937). CONCLUSION: Syphilis patients with either low or high RPR titers show increased macular VLD and VFD in the absence of obvious visual impairment, indicating the potential of OCTA microvascular parameters for early auxiliary diagnosis of syphilitic ocular lesions.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway represents a cornerstone of innate immunity, functioning as the primary cytosolic DNA sensor in mammalian cells. Upon detecting pathogenic DNA or mislocalized self-DNA (such as leaked mitochondrial or micronuclear DNA), cGAS synthesizes the second messenger cGAMP, which subsequently activates endoplasmic reticulum-resident STING. This activation triggers an intricate signaling cascade involving liquid–liquid phase separation, dynamic organelle trafficking, and robust interferon and pro-inflammatory cytokine production, thereby bridging microbial defense, antitumor immunity, and cellular homeostasis. Despite these structural and functional insights, the pathway's context-dependent duality, dictating whether it activates protective acute immunity or drives pathological chronic inflammation, immunosuppression, and metabolic dysregulation, remains a critical, unresolved clinical challenge. This review systematically integrates recent breakthroughs across structural biology, nanotechnology, and clinical research to dissect the spatiotemporal dynamic regulation and non-canonical functions of the cGAS-STING axis. We comprehensively examine its cell-type-specific mechanisms and metabolic-immune crosstalk within the microenvironments of neurodegenerative diseases, oncology, and autoimmune disorders. Furthermore, we highlight emerging translational innovations, emphasizing the rational design of small molecule inhibitors, advanced nanocarrier delivery systems, and combination immunotherapies. By redefining the conventional understanding of cytosolic DNA sensing, this synthesis establishes a comprehensive roadmap for precision immunomodulation. Ultimately, it provides a crucial framework for developing next-generation, microenvironment-adaptive therapeutics that leverage spatiotemporal dynamics to treat cGAS-STING-related pathologies.

With global improvements in sociodemographic status and life expectancy, the burden of disease has progressively shifted from infectious diseases to non-communicable diseases and disabilities, with vision impairment emerging as a major global public health challenge [1]. The leading causes of vision impairment include refractive disorders, cataracts, glaucoma, age-related macular degeneration, near vision loss, and other […]

Anterior segment diseases are a major global cause of preventable blindness, especially in regions with limited access to specialized ophthalmic care. Diag

Introduction: Refractive error and dry eye are highly prevalent ocular conditions that significantly impair the quality of life and impose a substantial burden on individuals and society. Growing evidence suggests a correlation between these two conditions. This study aimed to develop and validate a machine learning (ML) model to accurately predict the risk of concurrent dry eye comorbidities in patients with refractive error. Methods: Data from Xiamen Eye Center outpatient database (1st January 2024 to 28th February 2025) were analyzed (n = 114,579). Hyperparameter optimization, Spearman correlation analysis, and logistic regression analyses were performed. The final feature set was determined using a Random Forest algorithm with the sequential forward selection technique. Eight ML algorithms were evaluated through ten-fold cross-validation. The optimal model was selected based on a comprehensive assessment of the receiver operating characteristic curve, precision-recall curve, and decision curve analysis. For the best-performing model, SHapley Additive exPlanations and partial dependence plots were utilized to interpret the importance and interactions of risk factors. Results: Baseline characteristics were comparable between the training set and the internal test set, while significant differences were observed in multiple baseline characteristics between dry eye group and non-dry eye group among subjects with refractive error. Based on ten selected feature variables, the tabular prior-data fitted network (TabPFN) model demonstrated the best performance, showing high screening efficacy with both specificity and accuracy reaching 0.945. The interaction analysis revealed that a longer duration of refractive error was associated with a higher risk of dry eye, a relationship that was particularly pronounced among older and female patients. Furthermore, an online web calculator was developed to deploy this diagnostic prediction model. Discussion: This study developed a high-performance and interpretable ML system based on a large-scale real-world clinical dataset for the early prediction of concurrent dry eye risk in patients with refractive error. The system holds significant potential as a predictive aid for clinical decision-making, enabling more timely and personalized patient management, thereby offering substantial clinical value and promising application prospects.

This study aimed to identify potential drugs associated with drug-related retinal fibrosis (RF) and to analyze their risk characteristics systematically. This study used a retrospective disproportionality analysis to identify significant drug signals associated with RF from over 17 million reports in the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. The identified drugs were categorized by therapeutic class, risk level, latency period, and key subgroups (e.g., age, gender, off-label use). Sixteen drugs showed a significant association with RF, including anti-neovascularization agents, corticosteroids, and immunosuppressants. Risk severity varied: Verteporfin, ranibizumab, and brolucizumab had the highest risk, and vigabatrin and sildenafil had a relatively lower risk. The latency periods differed significantly, ranging from a median of 950 days for fluocinolone acetonide to 13 days for triamcinolone. Subgroup analysis revealed that off-label use increased the risk of RF and uncovered distinct susceptibility patterns: Adolescents (0-17 years) faced a higher risk when using specific drug classes such as corticosteroids, whereas elderly patients (≥65 years) were more susceptible to RF when using anti-neovascularization agents. Females showed a higher risk associated with immunosuppressants. This study presents a list of drugs associated with RF, providing a valuable reference to guide rational drug use, preserve visual acuity, and prevent irreversible structural damage. Identifying specific drugs associated with RF is crucial for preventing drug-related RF and developing personalized monitoring strategies.