Search Results (207)

Sjögren’s Disease (SjD) is an autoimmune disorder characterized by sicca symptoms arising from impaired salivary and lacrimal gland function and accompanying extraglandular involvement. SjD is recognized as an illness of female dominance for which the 2002 American–European Consensus Group Classification Criteria and the American College of Rheumatology/European Alliance of Associations for Rheumatology 2016 classification criteria are utilized for inclusion in clinical trials, and treatment recommendations from countries belonging to the American College of Rheumatology or the European Alliance of Associations for Rheumatology are globally recognized. It is presumed that there are geographical differences among female sufferers, and unique diagnostic criteria and recommendations are used in clinical practice in Japan. In addition to the items included in the classification criteria, several methods to measure saliva secretion, serum biomarkers, and artificial intelligence tools have recently been reported to be useful for the assessment of SjD. While symptomatic therapies including tear drops, artificial saliva, and muscarinic agonists are still the mainstay for treating SjD, several kinds of molecular targeted drugs, such as biological drugs and Janus kinase inhibitors, that are expected to improve the prognosis of SjD have been tested in recent clinical trials. Full article

Background/Objectives: The purpose of this study was to clinically characterize the lacrimal functional unit (LFU) of patients with chronic ocular pain associated with dry eye disease (DED). Methods: Ninety-three participants were included in this cross-sectional study: 28 patients with chronic ocular pain associated with DED (pain-DED), 35 patients with DED but no pain (no pain-DED), and 30 subjects without DED or ocular pain (controls). The following examinations were performed: symptom questionnaires, visual function assessment, tear meniscus, ocular surface evaluation, meibography, corneal sensitivity, Schirmer test, and in vivo corneal confocal microscopy. Results: Both DED groups presented increased DED-related symptoms (p < 0.001), corneal staining (p < 0.001), Meibomian gland loss (p < 0.010), and dendritic cell density (p < 0.001) compared with controls. Comparing both DED groups, the pain-DED group showed higher DED-related symptoms (p < 0.002) and increased microneuroma density (p < 0.001). Additionally, significant positive correlations were observed between symptom questionnaires and corneal staining (vs. OSDI: r = 0.514, p < 0.001; vs. m-SIDEQ: r = 0.504, p < 0.001; vs. NRS: r = 0.361, p < 0.001; vs. WBFPRS: r = 0.317, p = 0.002), dendritic cell density (vs. OSDI: r = 0.429, p < 0.001; vs. m-SIDEQ: r = 0.440, p < 0.001), and microneuroma density (vs. NRS: r = 0.405, p < 0.001; vs. WBFPRS: r = 0.416, p < 0.001). Conclusions: Differences in the LFU, especially in the morphology of sub-basal corneal nerves, are related to the presence of DED and chronic ocular pain and, along with ocular clinical questionnaires, can help phenotype these patients. Full article

Sjögren’s syndrome (SS) is a chronic autoimmune disease primarily affecting the lacrimal and salivary glands, characterized by ocular and oral dryness. Beyond exocrine dysfunction, SS may also involve multiple organs and systems, contributing to systemic complications that impair a patient’s quality of life. Among these, ocular inflammation represents a significant clinical challenge, manifesting as dry eye disease and other vision-affecting complexities. Despite advances in SS understanding, the inflammatory mechanisms driving ocular manifestations remain incompletely elucidated. This review aims to clarify the key inflammatory pathways underlying ocular complications in SS and the clinical implications. Additionally, it discusses both conventional and novel therapeutic strategies focusing on mitigating SS-associated ocular inflammation, including targeted immunomodulatory agents, regenerative medicine, and innovative drug delivery systems. By integrating current knowledge from recent studies, this review attempts to provide researchers and clinicians with a comprehensive resource for optimizing SS treatment approaches. The advancement of targeted therapies and emerging mitigation strategies holds promise for improving patient outcomes and enhancing SS management. Full article

Background and Objectives: Robotic surgery represents one of the most significant innovations in the field of surgery, offering new opportunities for the treatment of complex pathologies that require greater accuracy and precision. It is a technology that has become widely used in general, urologic, gynecologic, and cardio-thoracic surgery, but has a limited evidence in the head and neck region. This review explores the use of robotic surgery in orbital pathology, focusing on its applications, benefits, and limitations. Materials and Methods: A cross-sectional search method was performed in multiple databases to answer the following question: “What are the applications of robotic surgery in the management of orbital pathologies?” Studies were carefully reviewed by two simultaneous researchers, and, in case of disagreement, a third researcher was engaged. Care was taken to identify the surgical hardware (robotic station) used to perform the surgical procedure. Results: Out of 491 records, eight studies met the inclusion criteria. These included cadaveric, preclinical, in vitro, and early clinical investigations assessing robotic approaches for fronto-orbital advancement, tumor resection, orbital decompression, and other surgical procedures such as lacrimal gland dissection and biopsy, medial and lateral orbital wall dissections, enucleation, and lid-sparing orbital exenteration. The robotic systems evaluated included the Da Vinci Xi, Da Vinci SP, Medineering Robotic Endoscope Guiding System, and a modular multi-arm concentric tube robot, each with specific advantages and limitations. Conclusions: Robotic surgery provides significant advantages for orbital pathologies such as improved precision, visualization, and tissue preservation, with reduced complications and faster recovery, although some limitations still exist. Future advancements, such as smaller instruments and AI integration, promise to improve outcomes, making robotic surgery more effective in treating orbital conditions. Full article

Background/Objectives: Dry eye disease (DED) is a multifactorial inflammatory disease that disrupts the ocular surface, causing tear film instability, epithelial damage, and chronic inflammation. Mesenchymal stem cell-derived exosomes (MSC-exos) are promising therapeutics with immunomodulatory and regenerative properties. This study investigates the therapeutic effects of umbilical cord MSC-derived exosomes (UCMSC-exos) in a severe dry eye model, induced by a surgical resection of the infra-orbital (ILG) and extra-orbital lacrimal gland (ELG) in rats. Methods: Clinical evaluations, including tear volume measurement, slit lamp biomicroscopy, fluorescein staining, and spectral domain optical coherence tomography (SD-OCT), were performed to assess corneal neovascularization, corneal abrasion, and epithelial/stromal thickness. Histopathological analysis, immunohistochemistry, and mRNA gene expression were conducted to evaluate corneal tissue changes and inflammatory marker expression. Results: The results show that the treatment group exhibited significantly reduced corneal neovascularization compared to the control group (p = 0.030). During the first month, the Exo group also had a significantly lower corneal fluorescein staining area (p = 0.032), suggesting accelerated wound healing. SD-OCT analysis revealed that the corneal epithelial thickness in the treatment group was closer to normal levels compared to the control group (p = 0.02 and p = 0.006, respectively). UCMSC-exos treatment also modulated the expression of α-SMA and apoptosis in the cornea. Additionally, the gene expression of inflammatory cytokines (IL-1β and TNF-α) were downregulated. Conclusions: These findings suggest that MSC-exosome therapy offers a novel, cell-free regenerative approach for managing severe DED, modulating inflammatory response. Full article

Vascular endothelial growth factor (VEGF) is a key mediator of exudative age-related macular degeneration (eAMD), yet non-invasive biomarkers for disease monitoring remain limited. This study evaluates VEGF levels in human tear fluid as a potential biomarker for eAMD and investigates the molecular dynamics of VEGF in a laser-induced choroidal neovascularization (lCNV) mouse model. Tear VEGF levels were quantified using proximity qPCR immunoassays in eAMD patients (n = 29) and healthy controls (n = 21) and correlated with optical coherence tomography (OCT) findings. Molecular analyses, including immunohistochemistry, gene expression profiling, and phosphorylation assays, were conducted on choroid–retinal pigment epithelium (RPE) and lacrimal gland (LG) tissues from lCNV mice (n = 25). Tear VEGF levels were significantly elevated in eAMD patients, correlating with disease severity. Females exhibited higher VEGF levels, a pattern not replicated in the mouse model. In lCNV mice, VEGF overexpression originated from the choroid–RPE, driven by hypoxic and inflammatory signaling, with no significant LG contribution. Increased VEGF, IL-6, and vimentin expression, along with NF-κB and STAT3 activation, were observed. These findings suggest that tear VEGF is a promising non-invasive biomarker for eAMD, warranting further validation for clinical application in disease monitoring and treatment optimization. Full article

Sexual dimorphism significantly impacts the lacrimal gland’s structure, function, and ageing processes, playing an important role in dry eye disease (DED) pathophysiology. This multifactorial disorder, characterised by tear film instability, inflammation, and visual impairment, disproportionately affects women, especially after menopause. It highlights the interplay between sex steroid hormones, lacrimal gland function, and environmental factors. Systemic and local androgens are vital for maintaining lacrimal gland health and tear production, while the role of oestrogens remains less clear. Evidence suggests dose and context-dependent effects on inflammation and glandular function. Histopathological and molecular studies reveal significant sex differences in the lacrimal gland, with women exhibiting more pronounced age-related degenerative changes, including fibrosis and acinar atrophy, contributing to their increased susceptibility to DED. Despite these findings, the underlying mechanisms connecting sex steroid hormones, receptor expression, and local tissue regulation to these disparities remain poorly understood, highlighting the need for further research. This review synthesises the current knowledge of sex-specific differences in the lacrimal gland, emphasising the importance of integrating systemic and local biomarkers, histological data, and molecular insights into personalised therapeutic strategies. By tailoring treatments to patients’ unique hormonal and molecular profiles, personalised medicine has the potential to transform DED management, addressing unmet clinical needs and improving outcomes. Full article

Background: While intratumoral microbiota have been identified in various cancers, their presence and clinical significance in lacrimal gland tumors remain largely unexplored. This study investigates the existence, composition, and potential clinical significance of intratumoral bacteria in lacrimal gland tumors. Methods: High-throughput 16S rDNA sequencing was performed on tumor DNA extracted from 89 paraffin-embedded tissues from patients with lacrimal gland tumors. Diversity analysis and LEfSe differential analysis were conducted to identify tumor-type-specific bacterial taxa. LASSO regression and the Cox proportional hazards models were used to analyze the relationship between intratumoral microbiota and prognosis. Results: Significant differences in the β diversity of intratumoral microbiota were observed across adenoid cystic carcinoma (ACC), carcinoma ex pleomorphic adenoma (CXPA), pleomorphic adenoma (PA), and IgG4-related disease (IgG4-RD) patients. After FDR correction, Garicola, Prevotella, Polaribacter, and Helicobacter were notably enriched in the tumors of ACC, CXPA, PA, and IgG4-RD patients, respectively. Importantly, patients with malignant lacrimal gland tumors who experienced relapse, distant metastasis, or death had significantly higher α diversity within their tumors. Furthermore, specific genera, such as Roseburia and Alloprevotella, were particularly associated with poorer prognosis in patients with malignant lacrimal gland tumors. Conclusions: This study provides a comprehensive analysis of microbial profiles in lacrimal gland tumors, highlighting distinct microbial characteristics across tumor types. Our findings suggest that intratumoral bacterial diversity and specific genera may serve as potential prognostic markers for malignant lacrimal gland tumors. Full article

Over 2.2 billion people across the globe face significant barriers to accessing essential ophthalmic care, with elderly, rural, and refugee populations being disproportionately affected, deepening existing disparities in eye care. Three-dimensional printing is a novel technology that has the potential to transform the field and improve access by alleviating many patient-specific barriers. This article delves into the evolution of 3D printing within ophthalmology, highlighting its current applications and future potential. It explores various 3D printing techniques and numerous biomaterials discussing their effectiveness in creating advanced solutions such as bioengineered corneas, ocular prosthetics, and innovative treatments for dry eye syndrome, from punctal plugs to lacrimal gland models. Additionally, 3D printing has revolutionized drug delivery systems for conditions like glaucoma, retinal diseases, and ocular brachytherapy. Whether through 3D printed contact lens-based drug delivery systems or polycaprolactone implants that biodegrade and provide sustained drug release without adverse effects, these systems hold immense potential in the field. Despite its promise, the integration of 3D printing into clinical practice presents challenges, which the article addresses alongside strategies for overcoming them. By mapping out the technological advancements and challenges, this review offers a roadmap for enhancing global eye care accessibility and improving patient outcomes on a global scale. Full article

IgG4–related disease (IgG4–RD) is an autoimmune condition marked by IgG4–positive plasma cell infiltration, causing inflammation, fibrosis, and tumor–like lesions, especially in the lacrimal gland (LG). Current diagnostic criteria, based primarily on serum IgG4 levels, face limitations in predicting clinical outcomes and treatment responses. To address this, we conducted a multiplex immaunohistochemical analysis of LG tissues to assess immune checkpoint interactions and immune cell distribution in relation to mass size, fibrosis, and treatment response. Our findings revealed that PD–L1 (Programmed Death–Ligand 1), an immune checkpoint molecule, plays a key role in shaping an immunosuppressive environment that varies by clinical group. In non–responsive patients, increased co–expression of PD–L1 and CD11c+ dendritic cells (DCs) suggested a link to treatment resistance. Spatial analysis highlighted more active immune responses in non–fibrotic areas, while fibrotic regions exhibited stabilized immune interactions driven by PD–L1 expression. These results indicate that PD–L1 contributes to immune regulation and disease progression in IgG4–RD and emphasize its potential as a therapeutic target. This study provides new insights into the immunological landscape of IgG4–RD and paves the way for the development of personalized treatment strategies. Full article

Tearing and salivation are wholly dependent on the activity of exocrine (lacrimal and salivary) glands, whereas vaginal moisture and secretion rely on a combination of exudation and exocrine secretion. Exocrine gland disorders impact millions, and women with Sjögren’s Syndrome often experience dry eye and mouth as well as vaginal dryness. Cannabis users’ complaints of dry eye and ‘cottonmouth’ are well-known, but some female cannabis users also report vaginal dryness. The regulation of vaginal secretion by the cannabinoid signaling system is essentially unstudied. We recently reported that despite their small size and nocturnal nature, laboratory mice have measurable basal vaginal moisture and pheromone-stimulated secretory responses that are regulated by circadian and estrous factors. We tested the regulation of vaginal moisture by cannabinoid CB1 receptors in this model. We now report that the cannabinoid receptor agonist CP55940 does not alter baseline vaginal moisture but prevents a stimulated secretory response due to a local peri-vaginal effect. Chronic intermittent CP55940 reduces basal vaginal moisture but also unmasks or induces a potentiating effect for CP55940, suggesting multiple sites of action. The acute and chronic effects likely occur via CB1 receptors. Δ⁹-tetrahydrocannabinol (THC), the chief psychoactive ingredient of cannabis, a partial agonist at CB1, has no acute or chronic effects. In summary, strong acute activation of CB1 receptors in a murine model does not reduce vaginal moisture but does prevent a pheromone-stimulated vaginal secretory response. In contrast, chronic intermittent CB1 activation reduces baseline vaginal moisture. The extent to which these findings translate to humans remains to be determined. Full article

Neurolymphomatosis (NL) is a rare manifestation of hematologic malignancies, characterized by a neoplastic infiltration of the peripheral nervous system and cranial nerves (CNs). Non-Hodgkin lymphomas (NHLs) account for 90% of NL cases, while acute leukemia represents 10% of the cases. NL can occur as the first manifestation of a malignancy (primary), or as a relapse or progression of a previously treated disease (secondary). Herein, we report a unique case of NL involving the left orbit and CNs in a 74-year-old female with primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL). Our patient developed secondary neurolymphomatosis involving the left orbit and CNs II, III, V, and VI, supported by clinical, radiologic, and histologic findings. The lacrimal gland enhancement was histopathologically proven to be caused by the direct spread of CNS DLBCL to the lacrimal nerve, a branch of CN V, identifying NL as one of the conditions that can affect this organ. The lacrimal gland could be considered as a more accessible biopsy site when the involvement of CN V is suspected. Full article

Background: Sjögren’s disease (SD) is an autoimmune condition causing progressive salivary and lacrimal glands dysfunction following lymphocytic infiltration in the glandular tissue. SD patients are more prone to oral health impairment due to a reduction in salivary flow. This study evaluated the relationship between oral health, functional tests, and patient reported outcomes in a cohort of SD patients. Methods: Patients diagnosed with SD underwent complete dental examination, with the recording of the decayed–missing–filled teeth index (DMFT), probing pocket depth (PPD), full mouth bleeding score (FMBS), and full mouth plaque score (FMPS). Hyposalivation was assessed using the unstimulated whole saliva flow rate (UWS). Patients were administered the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Patient Reported Index, EULAR Sjögren’s syndrome disease activity index, Oral Health Impact Profile-14 (OHIP-14), Patient Acceptable Symptom State questionnaires, and a visual analog scale for xerostomia (VASx). Results: Fifty patients in total were enrolled. Reduced UWS was associated with higher DMFT, FMBS, and FMPS. Significant correlation was observed for UWS with VASx and OHIP-14 (p < 0.05). Conclusions: Quality of life and oral health appear mildly impaired in SD patients as an effect of reduced salivary flow, with higher DMFT and tendency towards gingival inflammation and plaque accumulation. Full article

In Manchega sheep, correlations between temperatures across various body regions, including the udder, under differing environmental conditions, stages of lactation, and states of mammary gland health have not been extensively explored. To address this, a group of 108 Manchega sheep was evaluated monthly over a period of six months. Ambient, rectal, lacrimal, perianal, and udder surface temperatures, alongside mammary gland health status indicators such as somatic cell count (SCC) and microbiological milk culture, were recorded. This study investigated the correlations between these temperature measurements and SCC levels. Mammary glands were classified based on their SCC (greater or lesser than 400,000 cells/mL) and the results of the microbiological cultures (more or less than five colonies in 20 µL of milk). This study found no correlation between body surface temperatures and rectal temperatures. SCC showed a low negative correlation with udder surface temperatures. Notably, mammary glands with SCC levels exceeding 400,000 cells/mL exhibited lower udder surface temperatures. This research underscores the Manchega breed’s ability to adapt to varying ambient temperatures and the necessity for further studies to better elucidate the relationship between inflammation and temperature changes in the udder during intramammary infections. Full article

Hashimoto’s thyroiditis (HT) is an autoimmune thyroid disease with characteristic lymphocytic infiltration and fibrosis. Chronic autoimmune changes that occur in the thyroid gland in HT may also affect the lacrimal gland. Objectives: This study aimed to analyze tear biomarkers and explore correlations between these biomarkers and clinical ocular parameters in patients with HT. Methods: A total of 150 participants were divided into three groups: HT (N = 50), non-HT DED (N = 50), and healthy controls (N = 50). The participants underwent a series of diagnostic tests for DED, including the Ocular Surface Disease Index, Tear Break-Up Time, Lid-Parallel Conjunctival Folds, Schirmer test without anesthetic, lissamine green and fluorescein staining. Tear samples were analyzed for cytokine and enzyme levels (interleukin 1β, tumor necrosis factor α, interleukin 6 (IL-6), interleukin 8, interleukin 10 (IL-10), interleukin 17A, matrix metalloproteinase 9 (MMP-9)) using ELISA and multiplex immunoassay. Statistical analyses were conducted to compare groups and assess biomarker correlations. Results: Dry eye disease was observed in more than half of the study group (27/50), with severe symptoms observed in 48.15% of the DED HT subgroup. IL-6 levels were significantly elevated in the DED HT subgroup compared to the non-HT DED group (p = 0.010), suggesting specificity for HT-associated DED. MMP-9 was elevated in both the HT and non-HT DED groups (p < 0.001) but lacked specificity for HT (p = 0.059). The DED HT subgroup exhibited significantly lower IL-10 levels (p = 0.008). Lissamine green staining and LIPCOF were significantly higher in the DED HT subgroup (p < 0.001). Conclusions: Dry eye disease is common in euthyroid HT patients without signs of TAO. This study highlights the potential role of IL-6. Lissamine green staining and LIPCOF are valuable diagnostic tools for assessing the ocular surface in DED HT patients. Full article