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Particulate matter (PM) exposure is known to induce significant ocular surface inflammation, necessitating effective therapeutic interventions. This study compared the efficacy of 2% rebamipide (REB) with 0.1% hyaluronic acid (HA) eye drops in investigating the anti-inflammatory and pathogen-clearance effects in a PM-induced ocular surface inflammation model using Sprague–Dawley (SD) rats. Parameters including clinical signs, histological changes, mucin secretions, inflammatory cytokines, mast cell degranulation, dysregulated cell proliferation, and cellular apoptosis were evaluated. 2% REB alleviated ocular surface inflammation by downregulating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inflammatory pathway and upregulating epidermal growth factor receptor (EGFR) signaling, thereby enhancing mucin secretion and promoting pathogen clearance. Histopathological analysis, western blot, and immunohistochemical staining revealed a marked reduction in inflammatory markers including MMP-9, IL-1β, TNF-α, IL-17, and CD-4, decreased mast cell degranulation, increased goblet cell density, and enhanced expression of mucins, including MUC5AC and MUC16, in the 2% REB-treated group compared to the 0.1% HA-treated and PM-exposed groups. Moreover, 2% REB demonstrated decreased apoptosis (TUNEL) and reduced uncontrolled cell proliferation (Ki67), indicating improved cellular integrity. In conclusion, 2% REB is a promising treatment option for PM-induced ocular surface inflammation in a rat model compared with 0.1% HA, offering the benefits of reducing inflammation, clearing pathogens, and protecting overall ocular health.

Dry eye disease (DED) has increasingly been linked to oxidative stress; however, the specific redox mechanisms underlying different clinical phenotypes remain incompletely understood. This study aimed to evaluate tear film oxidative stress profiles in patients with primary DED and sarcoidosis-associated DED (S-DED) by assessing lipid peroxidation, antioxidant enzyme activity, and total tear protein content, and to explore their relationship with clinical tear film dysfunction. Tear samples were analyzed for superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, as well as for malondialdehyde (MDA) and total protein levels, alongside standard clinical tests of tear film stability and secretion. Both DED groups exhibited significant oxidative alterations compared to controls, but with distinct redox signatures. Primary DED was characterized by markedly increased tear MDA levels, indicating predominant lipid peroxidation, whereas S-DED showed a more pronounced impairment of antioxidant defense, reflected by preserved or increased SOD activity in the context of significantly reduced GPx activity. Total tear protein levels were reduced in both groups, with evidence suggesting qualitative protein alterations in S-DED. The tear collection method significantly influenced the measured levels of several oxidative stress markers, underscoring the importance of sampling technique when interpreting tear-based redox profiles. Oxidative stress markers correlated with clinical measures of tear film dysfunction, supporting their physiological relevance. These findings demonstrate that DED encompasses heterogeneous oxidative stress mechanisms and that sarcoidosis acts as a modifier of ocular surface redox homeostasis. Distinct tear-based redox profiles differentiate primary from sarcoidosis-associated dry eye, highlighting the potential value of oxidative biomarkers for phenotyping DED beyond tear deficiency alone.

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.

To compare the short-term therapeutic effects of topical corticosteroids in patients with refractory dry eye disease (DED) according to the tear matrix metalloproteinase 9 (MMP-9) point-of-care positivity. This study was conducted on 137 patients who were referred from other eye clinics, complaining of irresponsive DED or acute DED flares despite routine treatment with topical cyclosporin or diquafosol. The patients received treatment with topical corticosteroids for 1 month. DED was evaluated by SANDE (Symptom Assessment in Dry Eye) questionnaire, tear film breakup time, ocular surface staining score, and meibomian gland dysfunction stage. The InflammaDry MMP-9 immunoassay was conducted in more symptomatic eyes of all patients. The changes in the subjective symptoms were additionally surveyed as symptom improvement score. The mean age of the patients was 57.8±13.4 years, and the tear MMP-9 positivity was 73.0%. Topical corticosteroids treatment showed significant improvement of symptoms and signs in the patients with refractory DED irrespective of the positivity of MMP-9 (each <0.001). The changes in SANDE score and OSS, and symptom improvement score were higher in the MMP-9 positive group than in the MMP-9 negative group ( =0.002/0.010/0.011). The overall rates of subjective symptoms improvement and SANDE reduction were 73.0% and 90.6% after topical corticosteroids treatment, respectively. Short-term topical corticosteroids had excellent therapeutic effects in patients with refractory DED or acute DED flares, irrespective of the tear MMP-9 level. Tear MMP-9 positivity may serve as a reliable response predictor of topical corticosteroids treatment in DED.

Dry eye disease (DED) is a prevalent ocular surface disease. Like with any chronic disease, patients with DED can experience episodic flares. There are many existing and upcoming treatments for the chronic treatment of DED, yet treatments for DED flares are limited. Loteprednol etabonate 0.25% is an FDA approved treatment modality for the short-term treatment of the signs and symptoms of DED. This medication is formulated with the customized mucus-penetrating particle (MPP) technology, which has a greater ability to penetrate the ocular surface and more effectively deliver the active steroid to the ocular surface tissues as compared with conventional steroid preparations. There is also increasing utility of loteprednol etabonate 0.25% in the treatment of DED before and/or after cataract or refractive surgery or as induction therapy prior to starting chronic immunomodulatory medication for DED.

Graft-versus-host disease (GVHD) is characterized by tissue inflammation in the host following an allogeneic hematopoietic cell transplantation (HCT). The pathophysiology is complex and only incompletely understood yet. Donor lymphocyte interaction with the histocompatibility antigens of the host plays a crucial role in the pathogenesis of the disease. Inflammation may affect multiple organs and tissues, e.g., the gastrointestinal tract, liver, lung, fasciae, vaginal mucosa, and the eye. Subsequently, alloreactive donor-derived T and B lymphocytes may lead to severe inflammation of the ocular surface (i.e., cornea and conjunctiva) and the eyelids. Furthermore, fibrosis of the lacrimal gland may lead to severe dry eye. This review focuses on ocular GVHD (oGVHD) and provides an overview of current challenges and concepts in the diagnosis and management of oGVHD. Ophthalmic manifestations, diagnostic procedures, grading of severity and recommendations for ophthalmic examination intervals are provided. Management of ocular surface disease with lubricants, autologous serum eye drops, topical anti-inflammatory agents and systemic treatment options are described based on the current evidence. Ocular surface scarring and corneal perforation are severe complications of oGVHD. Therefore, ophthalmic screening and interdisciplinary treatment approaches are highly relevant to improve the quality of life of patients and to prevent potentially irreversible visual loss.

Cathepsin S (CTSS) activity is increased in tears of Sjögren’s syndrome (SS) patients. This elevated CTSS may contribute to ocular surface inflammation. Human corneal epithelial cells (HCE-T cells) were treated with recombinant human CTSS at activity comparable to that in SS patient tears for 2, 4, 8, and 24 h. Acute CTSS significantly increased HCE-T cell gene and protein expression of interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) from 2 to 4 h, while matrix metalloproteinase 9 (MMP-9), CTSS, and protease-activated receptor-2 (PAR-2) were increased by chronic CTSS (24 h). To investigate whether the increased pro-inflammatory cytokines and proteases were induced by CTSS activation of PAR-2, HCE-T cells were transfected with PAR-2 siRNA, reducing cellular PAR-2 by 45%. Cells with reduced PAR-2 expression showed significantly reduced release of IL-6, TNF-α, IL-1β, and MMP-9 into culture medium in response to acute CTSS, while IL-6, TNF-α, and MMP-9 were reduced in culture medium, and IL-6 and MMP-9 in cell lysates, after chronic CTSS. Moreover, cells with reduced PAR-2 expression showed reduced ability of chronic CTSS to induce gene expression of pro-inflammatory cytokines and proteases. CTSS activation of PAR-2 may represent a potential therapeutic target for amelioration of ocular surface inflammation in SS patients.

Background The ocular surface microbiome (OSM) in patients with meibomian gland dysfunction (MGD) differs from that of healthy individuals. However, the precise role of OSM in MGD remains unknown. Therefore, we aimed to investigate the mechanism of OSM in the inflammation of MGD and the effects of topical sodium butyrate (SB) treatment in ApoE −/− mice. Methods ApoE −/− ( n  = 36) and wild-type C57BL/6J ( n  = 16) mice served as MGD models and healthy controls, respectively. MGD mice were treated with safety-confirmed concentrations of SB (1, 5, and 10 mM) and PBS for 3 weeks. OSM was analyzed by 16S rRNA gene sequencing (V3–V4). The slit-lamp biomicroscopy, tear cytokines, histopathology (oil red O/PAS/TUNEL staining), and TLR4/MyD88/NF-κB signaling (RT-qPCR, immunohistochemistry, and Western blotting) were evaluated. Results Five-month-old ApoE −/− mice exhibited typical clinical and histological features of MGD. These mice exhibited elevated tear levels of inflammatory cytokines and activation of the TLR4/NF-κB signaling pathway in the MGs and conjunctivae. Treatment with SB improved the corneal fluorescein staining score of MGD. The ApoE −/− mice demonstrated dysbiosis of OSM, characterized by an increase in Proteobacteria and a decrease in Bacteroidota . Additionally, the relative abundance of Muribacter and Muribacter muris increased in ApoE −/− mice, while that of Staphylococcus and Staphylococcus lentus decreased, and these alterations were restored by SB treatment. SB also reduced the expression of the TLR4/NF-κB p65 signaling pathway, inflammatory cytokines, and apoptosis in MGs and conjunctival tissues. Conclusion ApoE −/− mice exhibited characteristic features of MGD, accompanied by dysbiosis of OSM. Topical administration of SB modulated the OSM and reduced MGD-associated inflammation. 3uDHCn4-anMbfB6kqnAFHJ Video Abstract

Purpose To assess the functional and ocular surface anti-inflammatory outcomes of epithelium-off accelerated corneal cross-linking (ACXL) in adolescents with progressive keratoconus associated with allergic ocular surface disease and dry eye disease (DED) characterized by elevated tear matrix metalloproteinase-9 (MMP-9) concentrations. Methods Prospective interventional case series of 30 eyes from 15 patients (mean age 16.41 ± 2.36 years; Krumeich stage II) undergoing epi-off ACXL. Outcomes at baseline and 1, 3, 6, and 12 months included corrected distance visual acuity (CDVA), maximum keratometry (Kmax), minimum corneal thickness (MCT), computerized non-invasive tear break-up time (cBUT), Ocular Surface Disease Index (OSDI), and tear MMP-9 (point-of-care test). In vivo qualitative confocal microscopy (IVCM) investigation provided supportive imaging. Paired t-tests were used and results reported with 95% confidence intervals (CI). Results CDVA improved to 0.09 logMAR at 12 months (≈ 0.81 decimal; 95% CI: 0.10–0.08 logMAR; P  < 0.001). Kmax decreased from 55.00 to 53.75 D (95% CI: 53.55–53.95 D; Δ =  − 1.25 D; P  < 0.001), indicating ectasia stabilization. cBUT increased from 10.11 to 14.41 s (95% CI: 14.11–14.71; P  < 0.01). OSDI decreased to 12.15 (95% CI: 11.65–12.65). Tear MMP-9 levels diminished from 64.79 to 16.15 ng/mL ( P  < 0.0001) and the proportion < 38.6 ng/mL reached 86.7% of the study cohort at 12 months. IVCM documented disappearance of inflammatory infiltrates. No postoperative persistent adverse events occurred. Conclusions Epi-off ACXL stabilized ectasia, improving visual and ocular surface outcomes, markedly lowering tear MMP-9 levels. Although exploratory, these findings are consistent with a potential ocular surface anti-inflammatory and neuromodulatory role of ACXL, meriting validation in studies involving inflammatory DED beyond keratoconus.

To report the outcomes of using a sutureless human amniotic membrane dehydrated matrix (HAMDM) in the management of a range of ocular surface conditions utilizing a digital ocular surface disease assessment tool. Two UK NHS Trusts - Queen Victoria Hospital Foundation Trust (East Grinstead and Maidstone) and Tunbridge Wells Trust (Kent) - prospectively treated patients with ocular surface disease with sutureless HAMDM. The patient cohort was assessed for resolution of epithelial defects, ocular surface inflammation, and best-corrected visual acuity pre- and posttreatment. Measurements of ocular surface inflammation and epithelial defect size were assessed using AOS digital imaging software, a validated tool for objective grading of bulbar conjunctival redness and measurement of corneal epithelial defects. A total of 47 applications of sutureless HAMDM on 46 eyes of 46 patients (25 male, 21 female, age 9-94 years) were assessed across various etiologies for an average of 24.0±14.1 days. Patients with limbal stem-cell deficiency (n=17), persistent epithelial defects (n=16), neurotrophic corneal disease (n=7), filamentary keratitis (n=2), corneal erosion (n=1), corneal thinning (n=1), ocular surface inflammation (n=1), and traumatic corneal laceration (n=1) were included in the study. Across all patents, 63% of eyes showed complete healing of epithelial defects and 32.6% of eyes showed partial resolution. The average rate of healing (wound closure) was 0.36 mm per day across the overall patient cohort, and the rate of healing in cases with complete resolution of epithelial defects was 0.41 mm per day. Inflammation across all four quadrants of the ocular surface remained stable. Visual acuity across the patient cohort remained stable (61%) and improved in 26% of patients (0.06±0.51 logMAR). Sutureless HAMDM application can be accomplished in just a few minutes and effectively treat a range of ocular surface disease in a clinical, nonsurgical setting. The AOS imaging software offered a quantitative methodology for measuring epithelial defect size and inflammation state.