Search Results (204)

Background: Dry Eye Disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability and inflammation. Cyclosporine A, an immunomodulator, and Diquafosol sodium, a mucin secretagogue, represent two distinct therapeutic pathways. However, current evidence directly comparing their clinical efficacy is inconsistent. This meta-analysis aimed to compare treatment outcomes and efficacy between 0.05% Cyclosporine A and 3% Diquafosol sodium in patients with moderate-to-severe DED. Methods: In January 2026, we conducted a systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library for randomized controlled trials directly comparing 0.05% Cyclosporine A to 3% Diquafosol sodium in adult patients with moderate-to-severe DED. For the meta-analysis, we used R 4.5.0 with R Studio 2024.12.1+563. Results: We included six RCTs with a total of 859 patients. No significant differences were found between Cyclosporine A and Diquafosol sodium in Tear Break-Up Time (TBUT) at 4, 8, or 12 weeks. Cyclosporine A showed a suggestive greater improvement in Schirmer test scores at 4 weeks (SMD = 0.35, 95% CI 0.07 to 0.63). A modest benefit in symptom scores favoring Diquafosol sodium was observed at 12 weeks (SMD = 0.23, 95% CI 0.06 to 0.41). Subgroup analysis suggested this symptomatic benefit may be more pronounced in patients with severe disease, although subgroup interaction tests were not statistically significant. There were no significant differences in corneal or conjunctival staining at any time point. The risk of adverse events did not differ significantly between treatments. Conclusions: Early improvement in tear production showed a potential benefit for Cyclosporine A, while longer-term symptomatic relief showed a potential benefit for Diquafosol sodium, with suggestive evidence in severe disease. However, these findings should be interpreted cautiously, given the methodological limitations and inconclusive TSA evidence for several outcomes. Future large-scale, standardized trials with extended follow-up are warranted to confirm these findings. Full article

Chronic diseases such as cardiovascular disorders, diabetes, neurological conditions, and kidney disease continue to rise worldwide. These conditions create a growing demand for continuous, non-invasive, and personalized health monitoring technologies. Wearable biosensors meet this need by enabling real-time physiological and biochemical measurements outside traditional clinical settings. Among wearable biosensors, those based on biofluids like sweat, tears, and saliva provide a painless alternative to blood sampling. These fluids also grant access to metabolites, electrolytes, hormones, proteins, and disease related biomarkers that reflect systemic health status. Advanced sensing technology allow us to continuously track health status by analyzing key biomarkers in these accessible biofluids. This review summarizes recent advances in non-invasive wearable biosensors and focuses on their sensing principles which includes biorecognition elements, signal transduction mechanisms, and data acquisition strategies. We also discussed key sensing modalities, including electrochemical, optical, thermal, and piezoelectric approaches, highlighting their advantages for wearable integration and performance in biofluid sensing. Finally the review also outlines recent developments and applications of these systems in biofluid sensing. In the end we highlights existing challenges, potential solutions, and future directions toward clinically deployable, AI-assisted precision healthcare systems. Full article

Background/Objectives: Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability and decreased tear secretion, largely driven by chronic ocular surface inflammation. Although current therapies primarily target inflammation and tear film stabilization, their clinical efficacy is often limited by insufficient ocular surface retention. In this study, we explored a drug repositioning strategy for DED by developing a nanocrystalline formulation of troxipide (TRO), a gastric mucosal protective agent with cytoprotective properties. Methods and Results: A TRO nanosuspension (TRO-NPs) was successfully prepared by wet bead milling, yielding particles with a mean diameter of approximately 100 nm. Physicochemical characterization revealed that the crystalline structure, solubility, viscosity, pH, and osmolarity of the nanosuspension were comparable with those of the conventional TRO microsuspension (TRO-MPs). In contrast, the TRO-NPs exhibited markedly improved dispersion stability, maintaining particle suspension for at least 1 month after preparation. Repeated topical instillation of the TRO-NPs did not induce corneal toxicity or inflammation in rabbits, and resulted in significantly higher drug retention in the tear fluid than that observed for the TRO-MPs. Furthermore, in an N-acetylcysteine-induced rabbit dry eye model, repetitive instillation of the TRO-NPs significantly increased tear volume and mucin levels, leading to improved tear film stability. Conclusions: These findings demonstrate that nanosuspension-based formulations can enhance ocular surface retention and therapeutic efficacy of TRO. TRO-NPs therefore represent a promising nanomedicine-based repositioned therapy for the treatment of DED. Full article

Background and Objectives: Sjögren’s disease (SjD) is a chronic autoimmune disorder in which the immune system attacks the glands that produce tears and saliva, leading to symptoms such as dry eyes and dry mouth. If left untreated, SjD can also cause inflammation and damage to other parts of the body, including the skin, lungs, kidneys, and nervous system, and increase the risk of developing lymphoma. The human leukocyte antigen (HLA) class II molecule HLA-DR3 is strongly associated with SjD. Materials and Methods: To investigate how post-translational modifications (PTMs) influence the presentation of SjD-associated autoantigens by HLA-DR3, we employed a computational framework to determine the binding of PTM-mimic peptides to HLA-DR3. We further supported the in-silico results with in-vitro experiments. Results: Our analysis revealed that PTM-mimic substitutions at canonical anchor positions rarely improved predicted binding affinity using the Stabilized Matrix Method, with most modifications resulting in reduced affinity. However, a comprehensive analysis of full-length SjD-associated autoantigen sequences (Ro60, Ro52, La) identified discrete regions with high densities of PTM-eligible anchor sites, specifically, the Ro60 HEAT solenoid, Ro52 RING/B-box/PRY-SPRY modules, and the La motif-RRM1 region, suggesting that PTMs may alter epitope presentation in a sequence-dependent manner. Experimental validation of selected PTM-mimic peptides showed enhanced T cell responses, which were associated with increased binding affinity to HLA-DR3. Structural modeling of a representative complex revealed that PTM-mimic peptides adopt a slightly shifted backbone orientation and altered side-chain positioning, leading to a larger peptide–DR3 interaction interface. Conclusions: These findings provide new insights into the role of PTMs in shaping the immunogenicity of SjD-associated autoantigens and highlight the potential for PTM-mimic peptides to modulate T cell responses in SjD. Full article

Dry eye disease (DED) is a chronic inflammatory disorder of the ocular surface, characterized by tear film homeostasis imbalance, with aging being identified as a crucial independent risk factor. Oxidative stress, which refers to the excessive production of reactive oxygen species (ROS) and reactive nitrogen substances during mitochondrial metabolism and the weakened protective effect of antioxidants, plays a central role in this process. With aging, the mitochondrial function of ocular surface tissues, such as the corneal epithelium, meibomian glands, and lacrimal glands, declines. Concurrently, the activity of endogenous antioxidant enzymes (such as superoxide dismutase and glutathione peroxidase) decreases, and the levels of tear antioxidants such as lactoferrin also decrease. These age-related changes collectively lead to excessive accumulation of ROS, triggering oxidative stress that directly damages biomacromolecules in ocular surface cells and impairs the stability of the tear film. Furthermore, we have summarized the current therapeutic strategies for oxidative stress in DED, including both conventional antioxidants and emerging approaches such as eye drops based on nanoenzymes, thermosensitive hydrogels, intense pulsed light therapy, and drug-eluting contact lenses. By combining the new progress in the delivery systems of biomaterials-based drugs with mechanism-guided interventions, this review systematically establishes the intimate functional linkages between mitochondrial dysfunction, oxidative stress, and the pathogenesis of DED and focuses on elaborating the translational potential of advanced biomaterials-based antioxidant regimens, aiming to provide novel foundations and insights theoretical for the development of more effective and precise therapeutic strategies for DED. Full article

Dry eye disease (DED) is a complex ocular surface disorder characterized by tear film instability, chronic inflammation, and epithelial damage, for which current treatments remain limited. Marine-derived bioactive oligosaccharides have attracted increasing interest due to their diverse pharmacological activities and favorable safety profiles. In this study, we investigated the therapeutic potential of neoagarotetraose (NA4), a marine oligosaccharide derived from red algal agar, in a murine model of DED. DED was induced in eight-week-old female C57BL/6 mice by topical instillation of 0.2% benzalkonium chloride for seven consecutive days. NA4 was administered topically at concentrations of 125, 250, and 500 mg/L. Therapeutic outcomes were evaluated by tear secretion, corneal fluorescein staining, histopathological analysis, immunofluorescence staining for Ki67, F4/80, IL-1β, IL-6, and TNF-α, TUNEL assay for apoptosis, and ELISA for cytokine levels. NA4 treatment significantly improved tear secretion and reduced corneal fluorescein staining scores. Histological analysis revealed that NA4 preserved corneal epithelial thickness and restored conjunctival goblet cell density. Immunofluorescence analysis revealed that NA4 reversed inflammation-associated epithelial hyperproliferation and attenuated macrophage infiltration. Moreover, NA4 markedly suppressed the expression and tissue levels of IL-1β, IL-6, and TNF-α, and attenuated corneal epithelial apoptosis, with the 500 mg/L NA4 group showing no significant difference in efficacy compared to the positive control 0.1% sodium hyaluronate. These findings demonstrate that NA4, a marine-derived oligosaccharide, exerts multi-targeted protective effects against DED by improving tear film stability, preserving ocular surface integrity, suppressing inflammation, and reducing apoptosis. Our study highlights the potential of marine oligosaccharides such as NA4 as promising candidates for ocular surface disease management and supports the further exploration of marine resources for ophthalmic therapeutic applications. Full article

Background: Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability, inflammation, and neurosensory abnormalities. Current therapies remain limited by slow onset and suboptimal efficacy. Teriflunomide, an immunomodulatory agent approved for multiple sclerosis, has shown therapeutic potential in DED, but its multi-target mechanisms remain unclear. Methods: We employed an integrated computational and transcriptomic framework combining ADMET profiling, multi-dataset transcriptomic integration, and single-cell RNA sequencing (scRNA-seq) to identify disease-relevant targets. Candidate genes were further refined through molecular docking and 50 ns molecular dynamics (MD) simulations. The AetherCell virtual cell model was applied to evaluate both the concordance between target perturbation and drug-induced responses and the potential mechanistic roles of candidate targets. Results: Transcriptomic integration identified 16 consensus genes across heterogeneous DED models, which were further localized to disease-relevant epithelial and immune cell populations by scRNA-seq. Molecular simulations prioritized three core targets—CTSS, STAT1, and PTGS1—based on binding stability and affinity. AetherCell simulations demonstrated that perturbation of these targets not only recapitulated teriflunomide-induced transcriptional and pathway changes but also revealed their distinct mechanistic contributions, including epithelial barrier regulation (CTSS), microvascular and lipid homeostasis (PTGS1), and inflammation suppression coupled with tissue repair (STAT1). Conclusions: Teriflunomide exerts therapeutic effects in DED through coordinated multi-target regulation involving inflammation control, barrier restoration, and tissue repair. This study provides a rationale for novel therapeutic targets in dry eye disease, establishes a paradigm for applying virtual cell modeling to elucidate drug mechanisms, and offers a bioinformatics framework for validating drug repositioning outcomes. Full article

Dry eye disease (DED) is a common ocular surface disorder characterized by instability of the tear film, inflammatory responses, and epithelial damage, and therapeutic interventions directed at these fundamental pathogenetic processes are still insufficient. This research aimed to evaluate the medicinal efficacy of glycyrrhizic acid (GA) and to unravel the underlying molecular pathways through which it exerts its protective role in DED. A benzalkonium chloride-induced mouse model and a hyperosmolarity-induced human corneal epithelial cell model were established. Corneal epithelial injury, tear secretion, and goblet cell density were evaluated in vivo, while cellular responses and related signaling pathways were examined using RT-qPCR, Western blotting, flow cytometry, and immunofluorescence. GA treatment alleviated corneal epithelial damage, increased tear secretion, and improved goblet cell density in mice. In vitro, GA reduced inflammatory responses, as evidenced by decreased tumor necrosis factor-α (TNF-α) expression, and helped preserve epithelial barrier integrity, accompanied by reduced matrix metalloprotease 9 (MMP9) levels. Further analysis suggested that GA suppressed pyroptosis through regulation of the high mobility group box 1 (HMGB1)/lysosomal membrane permeabilization (LMP)/cathepsin B (CTSB) pathway and attenuated oxidative stress via activation of the nuclear factor erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD (P)H:quinone oxidoreductase 1 (NQO1) axis. In addition, GA improved mitochondrial function, as indicated by decreased reactive oxygen species levels, restored membrane potential, and enhanced adenosine triphosphate (ATP) production. Taken together, these findings indicate that GA may alleviate hyperosmolarity-induced DED by modulating inflammation, oxidative stress, mitochondrial dysfunction, and epithelial barrier damage, underscoring its viability as a remedial candidate. Full article

Smartphone-based portable slit lamp microscopes are increasingly used as low-cost tools for anterior segment imaging in teleophthalmology, yet the literature combines heterogeneous study designs, comparator standards, and deployment contexts. Because the evidence base spans engineering reports, basic science, clinical validation studies, implementation research, and case-based telemedicine, we structured a narrative review rather than a pooled meta-analysis. We searched PubMed/MEDLINE, Embase, Scopus, Web of Science, Google Scholar, Cochrane Library, ScienceDirect, and DOAJ for literature available on or before 28 February 2026, supplemented by manual reference list screening and targeted retrieval of relevant technical standards. Peer-reviewed English original studies formed the core evidence base; contextual non-English and gray literature sources were retained only when explicitly labeled as non-core. To improve interpretability, the results were grouped by synthesis domain, clinical task, comparator standard, telemedicine scenario, and artificial intelligence (AI) dataset/validation characteristics. The highest-confidence evidence concerned nuclear cataract grading, tear film breakup time and corneal staining assessment, anterior chamber depth screening, tear meniscus height measurement, allergic conjunctival grading, and selected corneal disorders. Agreement with conventional slit lamp examination or anterior segment optical coherence tomography was generally moderate to high within task-specific comparisons, and telemedicine deployment was feasible for screening, follow-up, remote consultation, emergency triage, house visits, and outreach. However, illumination reporting remains inconsistent, explicit ISO-aligned dosimetry is sparse, and most AI studies remain retrospective, single-center, and device family-specific. Current evidence, therefore, supports smartphone-based portable slit lamp microscopes primarily as adjunctive teleophthalmology tools rather than replacements for comprehensive in-clinic microscopy. The synthesis clarifies where conclusions are supported by comparative validation data, where they remain exploratory, and which methodological gaps should be prioritized in future multicenter studies. Full article

Craniofacial and corneal neuropathic pain are disabling conditions characterized by persistent pain that is frequently refractory to conventional pharmacologic and interventional therapies. These disorders arise from complex interactions between peripheral nerve injury, neuroinflammation, and maladaptive central sensitization within trigeminal pathways, features that span neuropathic and nociplastic pain mechanisms as defined by the International Association for the Study of Pain, thus emphasizing the need for mechanism-based, patient-stratified treatment strategies. Regenerative medicine offers a paradigm shift from symptom suppression toward structural nerve repair and functional restoration. This narrative review examines the pathophysiological mechanisms underlying craniofacial and corneal neuropathic pain and critically evaluates emerging regenerative therapies, including autologous biologics (autologous serum tears and platelet-rich plasma), mesenchymal stem cells and their derivatives, exosomes and extracellular vesicles, and neurotrophic peptides. Particular emphasis is placed on corneal neuropathic pain as a translational model, given the cornea’s dense sensory innervation and the ability to non-invasively quantify nerve regeneration using in vivo confocal microscopy as an objective biomarker of treatment response. Clinical evidence across regenerative modalities varies by indication: cenegermin has demonstrated robust efficacy and regulatory approval for neurotrophic keratitis, while platelet-rich plasma shows growing evidence in temporomandibular disorders, myofascial pain, and occipital neuralgia. Cell-based and cell-free therapies demonstrate strong preclinical promise but remain limited by heterogeneous protocols and a paucity of large-scale randomized trials. Key barriers to translation include regulatory uncertainty, lack of standardized outcome measures, and workforce and implementation challenges. Advancing regenerative therapies for craniofacial and corneal neuropathic pain will require rigorous clinical trials, biomarker-driven patient selection, and multidisciplinary collaboration. Sex as a biological variable remains underexplored across all regenerative modalities and represents a priority for future research. Full article

Corneal neovascularization (CNV) in dogs causes chronic ocular surface inflammation, which may disrupt tear film stability and meibomian gland function. As bevacizumab inhibits abnormal vessel growth and affects tear composition, it may benefit dogs with ocular surface disorders. The aim of this pilot study was to evaluate the effects of bevacizumab eye drops on the ocular surface in dogs with chronic CNV. Fourteen eyes from nine client-owned dogs were included. Dogs received either preserved (B_BAC-group) or unpreserved (B-group) 0.25% bevacizumab eye drops twice daily for 28 days. Re-examinations occurred one week after treatment initiation, at the end of treatment, and three months later. An ocular surface analyzer was used to assess tear composition and meibomian glands via interferometry, tear meniscus height, and meibography. Ocular and systemic toxicities were monitored, and clinical signs were scored. Serum VEGF levels were measured via ELISA before and after treatment. No statistically significant changes in intraocular pressure, tear production, or systemic VEGF levels were observed. Statistically significant improvements were noted in conjunctival hyperemia and chemosis in both groups, ocular discharge in the B_BAC-group, and fluorescein uptake in the B-group. Both formulations were safe and well tolerated. These preliminary findings suggest that topical bevacizumab may have potential benefits for CNV and ocular surface disorders in dogs, although larger studies are needed. Full article

Thyroid eye disease (TED) is an autoimmune inflammatory disorder primarily affecting orbital tissues, but ocular surface and adnexal involvement represent a frequent and clinically significant component of disease burden. Beyond mechanical exposure resulting from eyelid retraction and proptosis, TED-associated ocular surface disease arises from complex interactions between immune activation, epithelial stress, glandular dysfunction, and altered neuro-epithelial signaling. Increasing use of systemic immunomodulatory therapies, biologics, and orbital radiotherapy has improved control of orbital inflammation; however, their molecular and cellular effects on ocular surface homeostasis remain incompletely defined. This review summarizes current evidence on the cellular and molecular mechanisms underlying ocular surface dysfunction in TED and examines how disease-modifying therapies influence epithelial integrity, tear film stability, meibomian and lacrimal gland function, and local immune signaling. Key pathways discussed include cytokine-mediated inflammation, thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor crosstalk, pro-fibrotic signaling, neuro-inflammatory mechanisms, and epithelial stress responses involving mitogen-activated protein kinase and nuclear factor kappa B pathways. We further highlight the challenge of disentangling therapy-induced molecular effects from persistent exposure-related mechanical stress. Understanding how TED therapies modulate ocular surface and adnexal homeostasis is essential for optimizing integrated management strategies that address both orbital inflammation and long-term ocular surface stability. Full article

Background/Objectives: Anterior segment optical coherence tomography (AS-OCT) and optical coherence tomography angiography (AS-OCTA) have enhanced the evaluation of the cornea, ocular surface, and ocular surface diseases (OSD), offering high-resolution structural and anterior segment vascular imaging. This review summarizes recent advances in these modalities and their clinical applications. Methods: A comprehensive literature search was conducted using PubMed, Web of Science, and Google Scholar with the terms OCT, OCTA, anterior segment, and ocular surface disease. Studies published in the past five years were included, emphasizing more recent developments such as ultra-high-resolution AS-OCT (UHR-AS-OCT) and swept-source AS-OCTA technologies. Results: UHR-AS-OCT provides non-invasive, sub-micron imaging of the cornea and the ocular surface, including tear film morphology and epithelial thickness to correlate with clinical tests such as tear break-up time, and fluorescein staining. Advances in AS-OCTA allow dye-free, depth-resolved imaging of corneal and conjunctival vasculature. These vascular biomarkers have shown promising utility in conditions such as limbal stem cell deficiency, chemical ocular injury, and ocular surface squamous neoplasia. Improvements in image acquisition, motion correction, and segmentation algorithms have enhanced accuracy and repeatability, supporting broader clinical translation. Conclusions: AS-OCT and AS-OCTA have become useful adjunctive imaging tools for the cornea and ocular surface evaluation. Their non-invasive, quantitative, and reproducible metrics may enable earlier diagnosis, objective staging, and longitudinal monitoring of OSD. Integration of OCT-based imaging with artificial intelligence and multimodal data, including tear proteomics and meibography, may optimize personalized treatment for ocular surface disorders. Full article

Dry eye disease (DED) is an ocular surface disorder characterized by tear film instability, inflammation, epithelial damage, and neurosensory abnormalities. Due to its multifactorial etiology and pathophysiology, conventional therapies that focus on lubrication and immunosuppression often fall short in addressing the neuropathic component of ocular pain experienced by a growing subset of patients. Recent developments in sensory neuroscience have highlighted the pivotal role of ion channels in mediating ocular surface homeostasis, pain signaling, and inflammation. This review examines the role of the following major ion channel families in the pathophysiology of DED and neuropathic ocular pain: transient receptor potential (TRP) channels, voltage-gated sodium (Nav) channels, and purinergic P2X receptors. The review details their anatomical distribution, molecular function, and responses to environmental stimuli such as heat, cold, osmolarity, and injury. Current treatments, such as artificial tears, anti-inflammatory drops, and systemic neuromodulators, are also reviewed in relation to their effects on ion channel modulation. Additionally, emerging therapies that directly target sensory transduction pathways are introduced. This review highlights the therapeutic potential of ion channel modulation in personalizing treatment for patients with ocular surface pain, particularly those with neuropathic features unresponsive to standard care. Full article

Duropathies represent a spectrum of disorders associated with spinal dural tears and cerebrospinal fluid (CSF) leaks. Diagnosis and treatment is often complicated by overlapping clinical manifestations. This review aims to synthesize current literature on duropathies, focusing on their clinical, neuroradiological, and pathophysiological features. A comprehensive literature review was conducted, analyzing various conditions classified as duropathies, including spontaneous intracranial hypotension (SIH), superficial siderosis (SS), spinal cord herniation, and, as added issue, arachnoid webs. The review emphasized the importance of imaging techniques such as MRI and CT myelography in diagnosing these conditions. Duropathies can arise from congenital anomalies, trauma, and degenerative changes, with SIH being characterized by orthostatic headaches and neurological deficits. Imaging typically reveals specific patterns, such as a widened dorsal subarachnoid space and ventral displacement of the spinal cord. Syringomyelia was frequently associated with arachnoid webs, and complications like SS and bibrachial amyotrophy were noted in patients with persistent ventral spinal CSF leaks. The unifying concept of duropathies is proposed, emphasizing the need for timely intervention to mitigate long-term neurological consequences. Enhanced diagnostic strategies are crucial for improving patient outcomes, and a multidisciplinary approach is recommended for the management of these complex disorders. Further research is warranted to clarify the pathophysiological mechanisms underlying duropathies and to establish standardized treatment protocols. Full article