Search Results (819)

Background: Long-duration spaceflight (LDSF) poses unique challenges to ocular health as microgravity, radiation, and environmental changes can cause lasting visual and structural impairments that affect astronaut performance. Objective: This review synthesises current evidence on in- and post-flight ocular complications. It integrates clinical findings, terrestrial analogues, animal studies, and theoretical models to characterise the pathophysiology, risk factors, and countermeasures associated with spaceflight-induced ocular changes. Methods: A review of peer-reviewed literature was conducted, focusing on dry eye disease, corneal edema, ocular biometric shifts, spaceflight associated neuro-ocular syndrome (SANS), and radiation-induced cataractogenesis. Data from in-flight imaging, post-flight assessments, and ground-based analogues were analysed. Results: Spaceflight induces multifactorial ocular changes, including tear film instability, optic disc edema, posterior globe flattening, and hyperopic refractive shifts. These effects are thought to result from cephalad fluid shifts compartmentalised cerebrospinal fluid pressure, venous congestion, and impaired glymphatic system. Long-term risks, such as cataractogenesis, are linked to radiation exposure and genetic susceptibility. Although several countermeasures are being explored, no single approach fully prevents these complications. Conclusions: Ocular complications during LDSF remain a significant challenge for astronaut health and mission performance. A multimodal approach combining mechanical, nutritional, and diagnostic strategies will be essential for future exploration-class missions. Further research is needed to refine countermeasures and preserve astronauts’ visual function. 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/Objectives: This study compared choroidal morphological changes, including choroidal vascularity index (CVI) and layer-specific choroidal thickness, between aflibercept 8 mg and faricimab-svoa in treatment-naïve polypoidal choroidal vasculopathy (PCV) and pachychoroid neovasculopathy (PNV). Methods: This retrospective study included 66 eyes treated with aflibercept 8 mg (n = 32) or faricimab-svoa (n = 34). Following three monthly loading injections, a pro re nata regimen was employed for 6 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachment (PED) height, and CVI were assessed. Results: Both groups demonstrated significant improvements in BCVA, CMT, SFCT, and PED height at 6 months (all p < 0.05), with no between-group differences. Dry macula rates were 75.0% and 79.4%, respectively. Faricimab-svoa was associated with a significantly greater CVI increase (0.037 vs. 0.018, p = 0.003), driven by a numerically greater reduction in choriocapillaris/Sattler’s layer thickness (−18.9 ± 16.4 μm vs. −13.8 ± 15.8 μm, p = 0.153). Conclusions: Both agents achieved comparable functional and anatomical outcomes in treatment-naïve PCV and PNV. Faricimab-svoa was associated with a greater CVI increase, reflecting differential choroidal remodeling. CVI may serve as a biomarker for differentiating the choroidal effects of second-generation anti-VEGF therapies in pachychoroid spectrum disease. Full article

Background: Immune checkpoint inhibitors (ICIs) can induce a sicca-like syndrome that differs from primary Sjögren’s disease in both immunopathogenesis and clinical phenotype. Despite growing recognition of this entity, data describing real-world management and outcomes, particularly in the context of ICI discontinuation and rechallenge, remain limited. Methods: Patients with new onset of sicca syndrome or exacerbation of previous symptoms following ICI therapy were retrospectively identified and assessed. Results: Fifty-nine patients with diverse malignancies (including melanoma, gastrointestinal, genitourinary, etc.) and sicca syndrome following treatment with ICIs (most often pembrolizumab or nivolumab +/− ipilimumab) were evaluated. Acute-onset dry mouth, primarily CTCAE v6.0 grades 1 (n = 24, 40.7%) and 2 (n = 34, 57.6%), occurred at a median of 104 days after ICI initiation, sometimes with associated dry eye (n = 8, 13.6%). Most were managed conservatively with behavioral modification and over-the-counter therapies alone (n = 37, 62.7%) while others received sialagogues (n = 9, 15.3%), dexamethasone oral rinse (n = 11, 18.6%), and/or systemic corticosteroids (n = 16, 27.1%). Additional management strategies included de-escalation to ICI monotherapy (n = 5, 8.5%) or discontinued ICI (n = 6, 10.2%). Half of patients treated with corticosteroids demonstrated subjective improvement in symptoms while 75% improved following ICI discontinuation. Four patients underwent rechallenge after a median interruption of 564 days; all (n = 4) demonstrated sicca recurrence. Conclusions: In this largest cohort to date of ICI-associated sicca syndrome, we confirm frequent improvement with steroids and/or supportive care and suggest a greater than previously appreciated risk of recurrence with rechallenge. 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

Regulatory T cells (Tregs, CD4⁺ CD25⁺ Foxp3⁺) play a crucial role as a core cell subset in maintaining immune homeostasis in the ocular immune-privileged microenvironment. This review systematically summarizes the stage-specific regulatory mechanisms of Treg cells in common inflammatory diseases such as keratitis, uveitis, and dry eye syndrome, including intercellular interactions, signal pathway mediation, and cytokine network regulation, as well as key experimental evidence (animal/cell models and clinical sample data) and research progress in targeted therapy. Studies have shown that Treg cells maintain ocular immune balance by secreting anti-inflammatory cytokines (such as IL-10 and TGF-β), regulating signaling pathways (STAT, PI3K/AKT, SIRT1, etc.), and interacting with immune cells (macrophages, dendritic cells). Their functions are regulated by multiple factors such as cytokine networks, epigenetic modifications, and delivery vectors. Targeted interventions based on Treg cells (cell therapy, drug intervention, and signaling pathway regulation) and combined treatment strategies have shown good anti-inflammatory potential. This article, in light of current research limitations (such as insufficient analysis of cell heterogeneity and the disconnect between basic and clinical research), proposes future research directions, providing a theoretical basis for the understanding of the pathogenesis of inflammatory eye diseases and the development of new immunomodulatory therapies, and establishing a complete research framework of “mechanism–evidence–treatment”. Full article

Purpose: To evaluate the anatomical and functional efficacy of photobiomodulation (PBM) therapy in patients with dry age-related macular degeneration (AMD) and to investigate structural predictors of visual response. Methods: This retrospective study included 47 eyes of 30 patients with dry AMD treated with PBM. Best-corrected visual acuity (BCVA) was recorded as Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, and visual change (ΔBCVA) was calculated. Spectral-domain optical coherence tomography parameters—central retinal thickness (CRT), central macular volume (ETDRS 9-subfield central zone), and photoreceptor layer integrity (external limiting membrane [ELM], ellipsoid zone [EZ], and interdigitation zone [IZ])—were assessed pre- and post-treatment. Age-Related Eye Disease Study (AREDS) stage was graded per eye. Because both eyes from some patients were included, generalized estimating equation (GEE) models with patient-level clustering were used to account for inter-eye correlation. Effect estimates were reported as unstandardized coefficients with 95% confidence intervals. Results: Visual acuity improved following PBM therapy, with mean ETDRS letter scores increasing from 75.0 ± 14.1 to 78.0 ± 12.1 letters. In the GEE model accounting for patient-level clustering, the estimated mean gain was 2.97 ETDRS letters (95% CI: 1.15 to 4.79; p = 0.001). Mean CRT showed no significant change following PBM therapy (210.32 ± 48.61 µm vs. 211.23 ± 50.27 µm; GEE estimate: +0.91 µm; 95% CI: −5.52 to 7.35; p = 0.780). Central macular volume likewise remained stable (0.1913 ± 0.030 vs. 0.1919 ± 0.033 mm³; GEE estimate: +0.0006 mm³; 95% CI: −0.0054 to 0.0067; p = 0.836). Photoreceptor layer integrity demonstrated limited structural change, with no significant time effect for EZ or IZ integrity in binary GEE models and no observed pre–post change in ELM integrity. In multivariable GEE analysis, baseline BCVA (p < 0.001), ELM integrity (p < 0.001) and central macular volume (p = 0.041) were associated with change in ETDRS letter score, whereas AREDS category, EZ integrity, and IZ integrity were not. Conclusions: PBM therapy demonstrated limited short-term anatomical change but variable functional outcomes in dry AMD. Baseline BCVA emerged as the primary determinant of visual response, suggesting that treatment benefit may be influenced predominantly by pre-treatment functional reserve. Full article

Purpose: To evaluate the clinical efficacy and safety of eye drops containing lyophilized amniotic membrane (AM) in the treatment of dry eye disease (DED), with a focus on tear film stabilization and epithelial–immune balance. Methods: In this prospective cohort study, 40 patients (80 eyes) with DED were followed over six visits. The primary outcome was tear break-up time (TBUT). Secondary outcomes included corneal and conjunctival staining graded by the Oxford scale, meibomian gland parameters, corneal sensitivity (Cochet–Bonnet esthesiometry), best-corrected visual acuity, intraocular pressure (IOP), and Schirmer I test. Continuous variables were analyzed using repeated-measures ANOVA with Greenhouse–Geisser correction and Bonferroni post hoc testing; ordinal outcomes were analyzed using the Friedman test with Dunn–Bonferroni correction. Results: TBUT increased significantly in both eyes (OD: +5.3 s; OS: +4.9 s; both p < 0.001; ηp² ≈ 0.33). Corneal and conjunctival staining scores decreased (p < 0.001), meibomian gland quality and expressibility improved (p < 0.001), and corneal sensitivity increased (p < 0.001), while visual acuity and IOP remained stable. Schirmer I values showed no significant change. The combined pattern of changes (TBUT ↑, staining ↓, meibum/expressibility ↑, sensitivity ↑) indicates tear film stabilization and ocular surface improvement with a preserved safety profile. Conclusions: Lyophilized AM eye drops significantly prolong TBUT and improve clinical signs of DED, presumably by restoring the extracellular matrix (ECM) niche and the heavy-chain hyaluronan/pentraxin 3 (HC-HA/PTX3) complex, reducing proteolytic burden, and promoting a pro-resolving immune balance, with potential neurotrophic effects. These findings support the adjunctive use of AM-derived eye drops within contemporary TFOS DEWS II-based management algorithms for dry eye disease. Full article

Background/Objectives: To explore potential dry eye-related ocular surface functional alterations in women at the time of first diagnosis of endometriosis or adenomyosis in a real-world clinical setting. Methods: This was a cross-sectional case–control study. Patients were evaluated at the time of initial diagnosis, prior to initiation of any hormonal therapy, to reflect real-world clinical conditions. Participants underwent a standardized ocular surface assessment comprising the Ocular Surface Disease Index (OSDI) questionnaire, Schirmer test, and multimodal TearCheck^® analysis, including Non-Invasive Break-Up Time (NIBUT), Tear Film Stability Evaluation (TFSE), Meibography, and Abortive Blinking^®. Results: A total of 71 women were included: 41 with endometriosis or adenomyosis and 30 without known gynecological disease. Patients reported significantly higher OSDI scores than controls (p < 0.05). Objective testing demonstrated lower Schirmer values, reduced tear film stability, and more pronounced Meibomian gland dropout in the patient group (all p < 0.05). Differences were consistently observed across both subjective and objective parameters. Conclusions: Women with endometriosis and/or adenomyosis exhibited significantly altered ocular surface parameters compared with women without known gynecological disease. These findings suggest a possible association between gynecological disease and ocular surface dysfunction. Greater awareness of potential ocular involvement may encourage closer collaboration between gynecology and ophthalmology in the care of affected patients. Full article

Background: Dry eye disease (DED) is a multifactorial disease. Numerous risk factors might cause DED, including indoor air pollution, such as incense. Incense (Bakhoor) is widely used in many cultures, including Saudi Arabia, although its smoke contains toxic chemicals that pose serious health hazards. This research investigates the link between the Schirmer II test and tear fluid proteins in DED patients. The study focuses on identifying the ocular examinations, hypothesizing that incense smoke, particularly from synthetic types, exacerbates DED. Methods: This pilot cross-sectional study was conducted at King Abdulaziz Medical City (KAMC) in Jeddah, Saudi Arabia. Participants were recruited from the Cornea and Ophthalmology Clinics. Eye assessments analyzed tear protein concentrations, including tear collection using Schirmer II test strips and tear break-up time (TBUT). The study included DED patients who used incense. Tear fluid from the Schirmer test of 20 randomly selected patients was used for protein analysis of total protein, lactoferrin, and Immunoglobulin E. Inclusion criteria were male and female subjects aged 18 years or older, diagnosed with DED, and using incense. The sample size was 55 participants, selected via convenience sampling. Subjective data were collected through questionnaires, as well as objective data from the tear test and the sample and analyzed with SPSS. Descriptive and inferential statistics were used, with statistical significance set at p-value < 0.05. Results: The Ocular Comfort Index (OCI) categories showed that 21.8% had no symptoms, 40.0% had low symptoms, 30.9% had moderate symptoms, and 7.3% reported high symptoms. TBUT values and Schirmer test scores decreased with increasing OCI severity, with no statistical significance. The mean (SD) of total protein in the right and left eyes for high OCI was 7.19 (1.39) and 7.42 (0.91), respectively, with no statistical significance. The immunoglobulin E levels in the right and left eyes for high OCI were 301.71 (55.97) and 301.71 (47.14), respectively, with no statistical significance. The mean (SD) of lactoferrin in the right and left eyes for high OCI was 163.77 (10.42) and 159.43 (1.68), respectively, with no statistical significance. Conclusions: The study findings demonstrate alignment in incense-using patients between subjective OCI symptom scores and objective clinical diagnostic measures. Specifically, higher OCI scores are associated with lower TBUT and Schirmer II test values, as well as changes in tear biomarkers such as IgE and lactoferrin. These findings emphasize the potential of using simple screening methods combined with bioanalytical markers for early detection of ocular surface disease. This highlights the potential health risks associated with incense exposure, particularly for individuals predisposed to DED. The urgency for further research to explore the long-term effects of incense on ocular health and to raise awareness about its potential impact on populations with high incense usage cannot be overstated. Full article

Background/Objectives: This study aimed to evaluate the relationship between cumulative occupational exposure and ocular surface alterations in Colombian tomato farm workers, using data collected through a cross-sectional survey. In addition, the study sought to explore how occupational exposure duration may support risk stratification and targeted preventive strategies in this vulnerable population. Methods: A cross-sectional observational study was conducted involving 72 tomato farm workers in Colombia. Participants were grouped according to duration of agricultural work experience (<15 years vs. ≥15 years). Clinical assessments included slit lamp examination, tear film break-up time (BUT), Schirmer test, and fluorescein staining. Subjective symptoms were evaluated using the McMonnies Dry Eye Questionnaire. Ocular surface alterations, including conjunctival changes and Meibomian gland dysfunction, were documented and statistically analyzed between groups. Results: Workers with ≥15 years of experience reported significantly higher dry eye symptom scores (McMonnies mean = 8.19 ± 2.54) than those with <15 years (mean = 6.59 ± 2.61; p = 0.006). Schirmer test scores were lower in the experienced group (16.30 ± 11.48 mm vs. 22.71 ± 11.20 mm; p = 0.018), indicating reduced tear production. Bulbar conjunctival alterations and Meibomian gland obstruction were significantly more frequent in the experienced group (p = 0.002 and p = 0.013, respectively). No significant differences were found in BUT or eyelid findings. Conclusions: Long-term agricultural work was associated with increased dry eye-related symptoms and clinical signs of ocular surface compromise among Colombian tomato farm workers. From a personalized medicine perspective, occupational exposure duration may represent a useful risk-stratification factor to identify workers who could benefit from targeted screening, preventive counseling, protective interventions, and individualized follow-up. These findings support the implementation of tailored occupational eye health strategies to reduce cumulative ocular surface damage in vulnerable rural populations. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and newer dual-incretin therapies have become central to the treatment of diabetes mellitus and obesity, with benefits extending beyond glycemic control. Their expanding use has prompted growing interest in their potential ocular effects. Experimental data support plausible protective mechanisms, including reduction in oxidative stress and neuroprotective effects on retinal and optic nerve tissues. Clinical evidence, however, remains heterogeneous. In diabetic retinopathy, the main concern appears to be transient early worsening associated with rapid glycemic improvement rather than direct retinal toxicity. A potential semaglutide-associated signal for non-arteritic anterior ischemic optic neuropathy has raised concern, although the absolute risk appears low and causality remains unproven. Emerging studies also suggest possible beneficial associations with glaucoma, ocular surface diseases, and certain retinal vascular outcomes, whereas the evidence regarding age-related macular degeneration and cataract remains conflicting or preliminary. Overall, ocular outcomes associated with incretin-based therapies seem to reflect a complex interplay among drug-specific pharmacology, systemic metabolic changes, and individual patient susceptibility rather than a class effect. Baseline ophthalmic assessment and individualized follow-up may be advisable in selected high-risk patients. Further prospective ophthalmology-focused studies are needed to clarify long-term safety and identify the patients most likely to benefit or develop adverse events. 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