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Dry Eye Disease

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Dry Eye Disease. Core disease mechanisms, molecular and cellular pathways,...

2026-08-08
Asta MONDO:0006733 Model: Asta Scientific Corpus Retrieval 19 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Dry Eye Disease. Core disease mechanisms, molecular and cellular pathways,...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 19
  • Snippets retrieved: 20

Relevant Papers

[1] Interleukin-20 is involved in dry eye disease and is a potential therapeutic target

  • Authors: Hsiao-Hsuan Wang, Wei‐Yu Chen, Yi-Hsun Huang, S. Hsu, Y. Tsao et al.
  • Year: 2022
  • Venue: Journal of Biomedical Science
  • URL: https://www.semanticscholar.org/paper/975c97a82ceb1de42cb3a06c69f9310d97e6950e
  • DOI: 10.1186/s12929-022-00821-2
  • PMID: 35681232
  • PMCID: 9178884
  • Citations: 58
  • Summary: The functions of IL-20 were demonstrated in DED and presented a potential therapeutic option for this condition and the anti-IL-20 antibody 7E was established to neutralize IL- 20 activity.
  • Evidence snippets:
  • Snippet 1 (score: 0.552) > Dry eye disease (DED) is the most common disease in ophthalmology, affecting millions of people worldwide. Currently, the world's population is becoming an aging society, and DED may become a serious problem [1]. DED is characterized by a prolonged dry state of the cornea and conjunctiva of the outer layer of the eye, causing the eyes of patients to feel dry, red, itchy, and sensitive to external stimuli. The etiology and pathogenesis of DED are complex and multifactorial and may involve autoimmune diseases, contact lens use, hormonal changes, chronic inflammation, environmental factors, and infection. Patients with severe DED may even present with excessive eye watering, burning sensation, thick secretions, and blurred vision. Clinically, DED can be divided into two main types, aqueous tear-deficient dry eye and evaporative dry eye [2]. Aqueous tear-deficient dry eye can be subdivided into two categories, Sjögren's dry eye type and non-Sjögren's dry eye type. Evaporative dry eye has been subdivided to distinguish between those eyelid and ocular surface conditions that depend on intrinsic causes and those that arise from extrinsic influences. Studies have shown that many patients have both aqueous tear-deficient and evaporative dry eye, and both types share the common feature of inflammation [3]. It is essential to understand the pathogenesis and molecular mechanism of DED to facilitate drug development. Currently, no available drugs can effectively cure DED, and many cause negative side effects. Therefore, there is an urgent need to understand the pathogenesis of DED and to develop novel therapeutic strategies for DED treatment. > The cornea functions to protect the eyes from dust and bacteria and to focus vision. Normally, eyes are protected by the tear film outside the cornea. The tear film is mainly composed of three protein components, including the mucin layer (secreted by goblet cells on the conjunctiva), the aqueous layer (secreted by the lacrimal gland), and the lipid layer (secreted by the meibomian gland).

[2] Recent Developments About the Pathogenesis of Dry Eye Disease: Based on Immune Inflammatory Mechanisms

  • Authors: Lifei Yu, Chunjing Yu, He Dong, Yan-dong Mu, Rui Zhang et al.
  • Year: 2021
  • Venue: Frontiers in Pharmacology
  • URL: https://www.semanticscholar.org/paper/c11a61f7972873d2371f827b9ec72169fb6ef5b5
  • DOI: 10.3389/fphar.2021.732887
  • PMID: 34421626
  • PMCID: 8375318
  • Citations: 67
  • Influential citations: 6
  • Summary: This review will systematically review the previous research on the treatment of DED in immune inflammation, analyze the latest views and research hotspots, and provide reference for the prevention and treatment ofDED.
  • Evidence snippets:
  • Snippet 1 (score: 0.545) > Dry eye disease (DED) is newly defined as eye surface disease caused by a variety of factors, tear film instability, increased osmotic pressure, ocular surface inflammation and damage, and neurosensory abnormalities play a pathogenic role, characterized by the loss of tear film balance accompanied by eye symptoms. These include dryness, foreign body sensation, burning sensation, itching sensation, photophobia, red eyes, blurred vision, fluctuating vision, and visual fatigue. In severe cases, corneal epithelial exfoliation, filamentous adhesion, and conjunctival lesions may occur (Stapleton et al., 2017). The global prevalence of dry eye disease is 5-50%, while the incidence in China is 45%, which is a high incidence area (Guo et al., 2010;Farrand et al., 2017;Stapleton et al., 2017). With the popularity of electronic products, makeup, contact lenses, environmental pollution and other influences, the number of patients with dry eye disease will continue to rise at a rate of more than 10% per year, and tend to be younger. The pathogenesis of dry eye has not yet been fully elucidated, but the eye surface immune inflammatory response as the focus of the mechanism has been increasingly concerned. In the classification of etiology, Dry Eye Workshop II regards the imbalance of tear film homeostasis as the main feature of dry eye and the core of pathophysiology, whether it is water-based tear deficiency type or over-evaporation type (Nelson et al., 2017). This process is caused by the increase of Th17 and chemokines in the ocular surface of DED patients, which breaks the normal ocular surface immune balance and leads to the immune homeostasis in the tear membrane (Kodati et al., 2014). In the clinical treatment of DED, anti-inflammatory drugs represented by cyclosporine A and immunomodulatory drugs represented by lifitegrast can play a good ameliorative effect (Wan et al., 2015;Perez et al., 2016). Therefore, it is of strategic significance to further study the immune inflammatory mechanism of DED.

[3] Oxidative Stress in Dry Eye Disease: A Bibliometric Analysis

  • Authors: Yifan Lei, Xinyun Huang, Haodong Guo, Rongqing Huang, Yajun Shi et al.
  • Year: 2025
  • Venue: Clinical Ophthalmology (Auckland, N.Z.)
  • URL: https://www.semanticscholar.org/paper/2e69ebb670f20e4886d4a07c814449a2c2818aea
  • DOI: 10.2147/OPTH.S532001
  • PMID: 40689240
  • PMCID: 12276749
  • Citations: 2
  • Summary: This study provides the first bibliometric approach to hot topics and emerging trends in the field of oxidative stress in DED and explores prospective anti-oxidative stress strategies for future clinical interventions.
  • Evidence snippets:
  • Snippet 1 (score: 0.506) > Dry eye disease (DED) is a multifactorial ocular surface disease characterized by an imbalance in tear film homeostasis, leading to symptoms such as ocular discomfort and visual impairment. 1 The disease affects millions of people worldwide, particularly in the aged population, and the prevalence continues to rise due to population aging and increased exposure to screens. 2 While multiple factors contribute to the pathophysiology of DED, oxidative stress has emerged as one of the key drivers and one link to the central mechanisms of the disease. 3,4 Basically, it occurs due to the disrupted balance between the antioxidant and pro-oxidative systems. 3 5][6] At the same time, inflammatory pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) are activated, forming a vicious cycle of oxidation-inflammation, leading to reduced tear secretion, abnormal lipid composition, and decreased mucin expression, which ultimately exacerbate tear film instability and tear hyperosmolarity 7,8 Prolonged exposure of the ocular surface to environmental stresses such as ultraviolet radiation, air pollution, and dryness predisposes to oxidative damage. 9 Systemic factors such as diabetes mellitus, 10 autoimmune diseases, and aging can further exacerbate oxidative stress, leading to pathological changes such as decreased tear film stability and lipid layer abnormalities in patients with DED. 3 In recent years, there has been an explosion of research into the role of oxidative stress in the pathogenesis of DED, the identification of relevant biomarkers, and targeted therapeutic strategies. These studies span the interdisciplinary fields of molecular biology, epigenetics, clinical ophthalmology, and biomaterials. Despite the proliferation of papers, researchers still face significant challenges in integrating existing evidence and identifying future directions due to the heterogeneity of research models and difficulties in the clinical translation of oxidative damage markers. > Bibliometric methods allow researchers to systematically identify high-impact studies, core authors/institutions, and emerging topics in their field. Such analyses not only reveal the evolutionary pulse of the discipline but also provide a basis for prioritizing the allocation of resources.

[4] Recent developments on dry eye disease treatment compounds

  • Authors: B. Colligris, H. Alkozi, J. Pintor
  • Year: 2013
  • Venue: Saudi Journal of Ophthalmology
  • URL: https://www.semanticscholar.org/paper/e7bc127d66090092496177d6b498d9fdebff9677
  • DOI: 10.1016/j.sjopt.2013.12.003
  • PMID: 24526854
  • PMCID: 3923205
  • Citations: 54
  • Influential citations: 2
  • Summary: The corresponding literature and patents are revised assembling the new treatment approaches of novel and future pharmaceutical compounds destined for the dry eye disease treatment, with the most frequent categories of compounds presented are secretagogues and anti-inflammatory drugs.
  • Evidence snippets:
  • Snippet 1 (score: 0.463) > Current topical treatments for dry eye patients include the use of lubricants and anti-inflammatory drugs. However, lubricants only suppress negative symptoms temporarily, and chronic use of topical steroids is related to severe ocular side effects such as cataract and glaucoma. Further research is necessary toward the action mechanisms of new mucin and tear secretagogues compounds possibly possessing antiinflammatory properties. Additionally further research is needed on understanding the immunomodulatory and inflammatory mechanisms of the conjunctiva. > The deeper understanding of the cellular mechanisms implicated in dry eye is necessary not only to improve symptoms but also to restore the homeostasis of the ocular surface. The pursuit of effective dry eye treatment strategies is delayed by the absence of an accepted set of definitive criteria for evaluating disease severity. There is a lack of an objective test for the diagnosis of the severity of the disease, because symptoms' evaluation is insufficient as a measurement factor. There are several proposals for a novel objective testing such as molecular markers 86,87 or evaluation of the tear film osmolarity 88,89 but for the moment none of them advanced after the pre-clinical test.

[5] Animal models of dry eye: a critical assessment of opportunities and limitations.

  • Authors: S. Barabino, S. Barabino, Reza Dana
  • Year: 2004
  • Venue: Investigative ophthalmology & visual science
  • URL: https://www.semanticscholar.org/paper/33dec41e83bab9ab4778a591a43dcffcf07c1f4f
  • DOI: 10.1167/IOVS.03-1055
  • PMID: 15161821
  • Citations: 163
  • Influential citations: 9
  • Summary: It is shown that interruption of neuronal stimulation for tear secretion, defects in transmembrane and secretory mucin expression, and Meibomian gland dysfunction can all lead to various forms of KCS, and the pathogenic mechanisms in dry eye are not limited to those involved in lacrimal inflammation.
  • Evidence snippets:
  • Snippet 1 (score: 0.463) > Dry eye syndrome, or keratoconjunctivitis sicca (KCS), affects tens of millions of people worldwide, representing one of the most common ocular diseases. The National Eye Institute Industry Workshop on Clinical Trials in Dry Eyes produced a classification that essentially separates dry eye syndrome into two major types: tear-deficient forms (including Sjögren’s syndrome and non-Sjögren’s tear-deficient) and evaporative forms. Recently, it has become clear that the immunopathogenesis of dry eye is complex and multifactorial. Sjögren’s syndrome, which is the classic form of exocrine deficiency associated with KCS, is characterized by a chronic inflammatory infiltration of the lacrimal and salivary glands. The predominant cell type is CD4 T cells that appear to have a defect in Fas-mediated apoptosis, thereby rendering their infiltration into exocrine tissue damaging. However, exactly what factors incite the infiltration of glands by T cells remains unknown. Recently, the observation that lacrimal gland acinar cells may express class II major histocompatibility complex (MHC) molecules, cathepsins B and D, and ribonucleoprotein particle La/SSB proteins has provided some support (but no definitive proof) for the thesis that these cells may be involved in aberrant presentation of autoantigens, thereby potentially capable of priming autoreactive T cells. But the pathogenic mechanisms in dry eye are not limited to those involved in lacrimal inflammation. Indeed, interruption of neuronal stimulation for tear secretion, defects in transmembrane and secretory mucin expression, and Meibomian gland dysfunction can all lead to various forms of KCS. Numerous animal models have been developed to reflect the multiplicity of pathophysiologic mechanisms involved in KCS. Understanding the unique characteristics of these different models of dry eye, and their limitations, will provide a better insight into their use in mechanistic and therapeutic study design.

[6] Changes in human tear metabolome following topical 0.05% cyclosporine A on primary Sjögren’s syndrome

  • Authors: Yingsi Li, Meiting Huang, Luoying Xie, Xiaoming Yan, Wenjing Song
  • Year: 2025
  • Venue: Frontiers in Medicine
  • URL: https://www.semanticscholar.org/paper/36fbac55268fea8848cf5c22ce135cab4dc5fb15
  • DOI: 10.3389/fmed.2025.1653585
  • PMID: 41210869
  • PMCID: 12592072
  • Summary: Analysis of tear metabolome and the therapeutic impact of 0.05% cyclosporine A eye drops in patients with dry eye disease linked to primary Sjögren’s syndrome underscores significant alterations in tear metabolites at the ocular surface in pSS patients receiving 0.05% CsA.
  • Evidence snippets:
  • Snippet 1 (score: 0.459) > Dry eye disease (DED) is a chronic condition with multifactorial etiologies that affects millions globally (1,2). Sjögren's syndrome (SS) is an autoimmune disease that affects the lacrimal and salivary glands, significantly contributing to aqueous-deficient dry eye and resulting in severe ocular surface damage and visual impairment (3). Whether primary or secondary, the majority of SS cases exhibit meibomian gland dysfunction (MGD), characterized by palpebral margin epithelial metaplasia, obstruction of meibomian gland (MG) orifices, and deficiencies in meibum secretion (4). Inflammation plays a pivotal etiological role in the pathophysiology of DED (2). Chronic ocular surface inflammation increases pro-inflammatory cytokine release, leading to corneal and conjunctival tissue damage (5). Consequently, anti-inflammatory strategies are essential for the treatment of Cyclosporine A (CsA), a common immunomodulator, effectively treats DED and other ocular surface diseases by preventing T-cell infiltration, activation, and proliferation and by inhibiting the transcription of inflammatory cytokine genes such as interleukin-2 and interleukin-4 (6)(7)(8). Its mechanism involves forming a complex with cyclophilin to inhibit calcineurin activity, thereby preventing the nuclear translocation and activation of transcription factors in activated T cells (6,7). The application of topical CsA enhances tear production, preserves ocular surface integrity through its antiapoptotic and immunomodulatory properties, and mitigates ocular discomfort associated with DED (9)(10)(11). Tears, complex fluids containing proteins, lipids, electrolytes, and metabolites, are crucial for identifying biomarkers of ocular surface disorders. Metabolomics, an emerging analytical approach, offers the potential to identify biomarkers and elucidate disease pathways that are more closely aligned with biological phenotypes compared to proteomics.

[7] Differentially Expressed Tear Proteins in Sjögren's Syndrome Keratoconjunctivitis Sicca

  • Authors: Stephen P. Yoon, Zhiyuan Yu, S. Pflugfelder, C. D. de Paiva
  • Year: 2023
  • Venue: Translational Vision Science & Technology
  • URL: https://www.semanticscholar.org/paper/754616bb5eef76c12f8f5fe5b7cdb2b575c09740
  • DOI: 10.1167/tvst.12.6.8
  • PMID: 37310735
  • PMCID: 10275389
  • Citations: 13
  • Influential citations: 1
  • Summary: The results suggest tear protein concentrations are altered in patients with SS KCS compared to controls, and indicate that hundreds of factors can be assayed in tear proteins collected from a Schirmer strip.
  • Evidence snippets:
  • Snippet 1 (score: 0.454) > Sjögren's syndrome (SS) is an autoimmune disease affecting the exocrine lacrimal and salivary glands, which can lead to keratoconjunctivitis sicca (KCS) and xerostomia. Changes in tear composition combined with systemic factors contribute to an inflammatory cycle and ocular surface disease. 1 The activation of stress signaling pathways from desiccation triggers the production of inflammatory mediators, inflammatory cell recruitment, dendritic cell (DC) maturation, and the activation of an adaptive T-cell mediated response. 2 urrent methods of diagnosis for KCS focus on measures of eye irritation using symptom questionnaires and ocular surface dye staining. Patients with aqueous deficient dry eye typically have increased scores on symptom questionnaires (such as the Symptom Assessment Questionnaire in Dry Eye [SANDE]), corneal fluorescein (CF) staining, and conjunctival (CJ) lissamine green staining, and decreased tear break-up times (TBUT). 3 Identifying disease-relevant biomarkers in SS KCS could improve diagnostic sensitivity, specificity, and classification, and identify disease relevant therapeutic targets. > The mechanism(s) driving the pathophysiology of SS KCS are not completely understood. Genetic and proteomic analysis in SS may help identify key immune mediators involved in the pathogenesis of KCS and therapeutic targets. Our group has previously identified differentially expressed gene (DEG) pathways as possible biomarkers in SS KCS in cells obtained via conjunctival impression cytology. 4 These DEG biomarkers correlated with clinical markers for dry eye. In addition to changes in the conjunctiva, tear proteomic analysis in SS has shown dysregulated expression of proteins involved in inflammation, immunity, and oxidative stress. 5 Schirmer strips are widely available in clinical settings and provide an accessible method to sample tear fluid in patients with SS KCS for proteomics analysis. The purpose of this study was to compare levels of immune-related tear proteins of healthy subjects and patients with SS KCS collected by Schirmer strips using the RayBiotech L507 proteomic array.

[8] Metabolomic Alterations in the Tear Fluids of Patients With Superior Limbic Keratoconjunctivitis

  • Authors: Y. Zong, Chaofan Cheng, Kunke Li, R. Xue, Ziyan Chen et al.
  • Year: 2022
  • Venue: Frontiers in Medicine
  • URL: https://www.semanticscholar.org/paper/48dc312841e912115e635b294a226815110dcb6c
  • DOI: 10.3389/fmed.2021.797630
  • PMID: 35118093
  • PMCID: 8804220
  • Citations: 9
  • Summary: SLK has a specific metabolomic profile, of which some key elements can serve as potential biomarkers of SLK for diagnostic and prognostic purposes, and this study reveals that linoleic acid metabolism was the most significantly changed pathway.
  • Evidence snippets:
  • Snippet 1 (score: 0.450) > Metabolomics is focused on a comprehensive analysis of metabolites in a biological system and metabolic changes in response to pathophysiological stimuli, genetic modifications and/or environmental perturbations (12). The main analytical techniques adopted are nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-tandem mass spectrometry (GC-MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Metabolomics has been widely used to assess biological systems, providing molecular information related to phenotypes since metabolites are the ultimate product of gene, mRNA and protein activity (17). Moreover, in terms of the high-throughput profiling of the whole metabolome in a disease condition, identifying biomarkers becoming possible (18,19). With advances in technology, untargeted LC-MS metabolomic analysis of tear fluid has been applied in clinical and animal studies of several eye diseases, such as keratoconus (12,15,20), dry eye (13,21), and multiple sclerosis (16). Studies of metabolomics used in eye diseases have been summarized in a recent review article (12). As the reviewers suggested, to date, possible biomarker candidates for dry eye disease are lipid metabolites and androgens, and those for keratoconus are cytokeratins, urea, citrate cycle, and oxidative stress metabolites. In addition, palmitoylcarnitine, sphingolipids, vitamin-D-related metabolites, and steroid precursors may be related to glaucoma, and the dysregulation of amino acid and carnitine metabolism is critical in the development and progression of diabetic retinopathy (12). > In the present study, we analyzed tear samples obtained from a clinical cohort of 42 subjects and investigated the tear metabolomic differences between SLK patients and healthy controls. We aimed to identify the metabolites in tears that are pathologically relevant to SLK. In addition, we constructed a potential metabolite biomarker model to assist us in distinguishing SLK from a healthy status.

[9] Current Advances in Regenerative Strategies for Dry Eye Diseases: A Comprehensive Review

  • Authors: Basanta Bhujel, Seheon Oh, Chang-Min Kim, Ye-Ji Yoon, H. Chung et al.
  • Year: 2023
  • Venue: Bioengineering
  • URL: https://www.semanticscholar.org/paper/258d79070e0785ee699b011a1afb3234f345e10f
  • DOI: 10.3390/bioengineering11010039
  • PMID: 38247916
  • PMCID: 10813666
  • Citations: 16
  • Summary: This article specifically explores the different strategies reported so far for treating dry eye disease and discusses their potential as long-term cures while also considering the factors that limit their feasibility and effectiveness.
  • Evidence snippets:
  • Snippet 1 (score: 0.448) > The pathogenesis of dry eye is complex and not fully understood. Current research on the dry eye mechanism predominantly concentrates on the following areas:
  • Snippet 2 (score: 0.448) > The pathogenesis of dry eye is complex and not fully understood. Current research on the dry eye mechanism predominantly concentrates on the following areas:

[10] Poly(lactic-co-glycolic acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress

  • Authors: A. Ghosh, Rubina Thapa, H. N. Hariani, Michael Volyanyuk, S. D. Ogle et al.
  • Year: 2021
  • Venue: Pharmaceutics
  • URL: https://www.semanticscholar.org/paper/952fbcf295b69ca3e897e9019543ea851088c7d8
  • DOI: 10.3390/pharmaceutics13091362
  • PMID: 34575438
  • PMCID: 8471707
  • Citations: 24
  • Summary: Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced ocular surface damage and oxidative stress-associated DNA damage in corneal epithelial cells in the mouse desiccating stress/scopolamine model for dry eye disease in vivo.
  • Evidence snippets:
  • Snippet 1 (score: 0.447) > Dry eye disease is an umbrella term describing various subtypes of the disease. Dry eye disease poses a substantial burden on the affected individual and society as a whole. Existing pharmacologic management for dry eye disease targets T cell-mediated inflammatory pathways and in the United States consists of ophthalmic formulations of cyclosporine (Restasis ® or Cequa™) or the lymphocyte function-associated antigen 1 inhibitor, lifitegrast (Xiidra ® ). Both agents are associated with limited efficacy and adverse effects in up to 25% of patients [1][2][3], highlighting an urgent unmet clinical need for novel efficacious and well-tolerated therapeutics. > Previous studies have implicated the generation of reactive oxygen species (ROS) and the ensuing elevated levels of cellular oxidative stress as a key contributor to the pathophysiology of dry eye disease (reviewed in [4]). Specifically, elevated levels of oxidative stress have been identified in patients with dry eye disease [5,6], while hyperosmolar conditions cause oxidative stress in cultured corneal epithelial cells [7]. We have recently shown significant oxidative DNA damage in the corneal epithelium of mice exposed to dry eye-inducing conditions of desiccating environment with scopolamine [8]. Similarly, lacrimal gland dysfunction as a result of mitochondrial oxidative stress produces an ocular phenotype reminiscent of dry eye disease in mice [9,10]. > Notably, a mitochondrially-targeted antioxidant, SkQ1 (Visomitin), exerts anti-inflammatory effects in human conjunctival epithelial cells in vitro [11], and has shown therapeutic benefit in US Phase 2 clinical trials following approval in Russia in 2011 [12], providing proof-of-concept evidence supporting the development of therapeutic approaches using antioxidants to treat dry eye disease. > Major challenges associated with dry eye disease management are low patient satisfaction and poor compliance with dosing regimens [13]. Therefore, one important drug development consideration for topical ophthalmic formulations is to enhance ocular surface retention times that minimize the number of instillations.

[11] Diquafosol Improves Corneal Wound Healing by Inducing NGF Expression in an Experimental Dry Eye Model

  • Authors: Chieun Song, Hyemin Seong, Woong-Sun Yoo, Mee-Young Choi, Réka Dorottya Varga et al.
  • Year: 2024
  • Venue: Cells
  • URL: https://www.semanticscholar.org/paper/80aee03e77c076a735fc9e12ee5fa3893ccda857
  • DOI: 10.3390/cells13151251
  • PMID: 39120282
  • PMCID: 11311477
  • Citations: 7
  • Influential citations: 1
  • Summary: Treatment with cyclosporine or diquafosol restored cell viability and wound healing and reduced corneal damage by hyperosmolarity, and treatment with cyclosporine or diquafosol resulted in decreased apoptosis.
  • Evidence snippets:
  • Snippet 1 (score: 0.440) > Dry eye disease (DED) is a complex, multifactorial condition characterized by a loss of tear film homeostasis, ocular surface inflammation, and damage [2]. The condition can be classified into two primary types: aqueous tear-deficient dry eye, resulting from decreased tear production, and evaporative dry eye, caused by excessive tear evaporation. Both types lead to increased tear osmolarity, triggering inflammation and subsequent damage to the ocular surface [2,3]. Given the heterogeneous nature of DED, it is crucial to tailor treatments based on the specific clinical phenotypes of the disease [5]. Our study explored the therapeutic mechanisms of CsA and DQS in an experimental dry eye model induced by hyperosmolarity. Hyperosmolar stress is a key driver in DED pathogenesis, leading to an inflammatory cascade and corneal surface damage [5]. CsA is a potent immunomodulator that inhibits T-cell activation and downregulates several inflammatory cytokines, thereby reducing ocular surface inflammation. Its efficacy in treating inflammatory ocular surface diseases was first reported by Laibovitz et al. [7]. Topical CsA has been shown to reduce cell-mediated inflammatory responses, improving tear film stability and reducing ocular surface inflammation [8,9]. DQS, on the other hand, is a dinucleotide derivative that functions as an agonist of the purinergic P2Y2 receptor [11], stimulating mucin and water secretion from conjunctival epithelial cells and accessory lacrimal glands. This action helps to stabilize the tear film and protect the ocular surface from desiccation [12,13]. Our findings highlight that CsA and DQS exhibit distinct effects on DED, suggesting that their clinical applications should be differentiated based on the underlying pathophysiology and phenotype of the disease. > Our findings demonstrate that both CsA and DQS mitigate hyperosmolarity-induced cellular damage by modulating inflammatory responses and promoting corneal epithelial cell survival. As previously published papers have stated, both CsA and DQS decrease the cell viability of HCECs at higher concentrations [18,19].

[12] Recent advances and prospects of nanoparticle-based drug delivery for diabetic ocular complications

  • Authors: Siqi Wang, Hongyu Yang, Jiaying Zheng, Aiyang Tong, Sen Mu et al.
  • Year: 2025
  • Venue: Theranostics
  • URL: https://www.semanticscholar.org/paper/163a5e270633cb64dc21b5f88a0122037d30841a
  • DOI: 10.7150/thno.108691
  • PMID: 40093887
  • PMCID: 11905120
  • Citations: 16
  • Influential citations: 1
  • Summary: This review highlights several common ocular complications associated with DM, focusing on their pathogenesis and treatment strategies, and emphasis is placed on the innovative applications and potential of nanotechnology in treating diabetic ocular complications.
  • Evidence snippets:
  • Snippet 1 (score: 0.440) > The eye is a vital organ in the human body. Diabetic eye complications primarily result from chronic hyperglycemia, which affects multiple ocular structures and contributes significantly to various eye diseases [1]. The increasing prevalence of diabetes mellitus (DM) has led to a rise in the incidence of ocular complications. Prominent among these complications are diabetic keratopathy, diabetic retinopathy (DR), cataracts, and glaucoma. These ocular manifestations cause considerable physical discomfort for affected individuals and impose a substantial economic burden on patients and healthcare systems (Figure 1). > Following extensive research over the years, significant progress has been made in understanding the pathogenesis of diabetic ocular diseases; however, the mechanisms underlying diabetic dry eye and other ocular lesions remain incompletely understood, which hampers the development of effective clinical treatment strategies. Several common pathogenic mechanisms of hyperglycemia have been proposed, such as increased polyol pathway flux, overactivation of the hexosamine pathway, accumulation of intracellular advanced glycation end products (AGEs), activation of the protein kinase C (PKC) pathway, inflammatory responses, and oxidative stress [2,3]. These mechanisms are summarized below. Since the proposal of a unified mechanism for diabetic complications, growing evidence indicates that reactive oxygen species (ROS) activate multiple signaling pathways, with oxidative stress induced by ROS being a key pathogenic factor in DM and its complications [4] (Figure 2). > The most commonly employed treatment approaches can be categorized into three types [5,6]: > (1) Topical administration, primarily for anterior segment diseases; (2) Intraocular administration, which provides superior efficacy compared to topical Ivyspring International Publisher treatments; and (3) Oral administration, notable for its high patient compliance. These traditional drug delivery systems are cost-effective, convenient, and generally safe. However, the eye's complex physiological barriers and anatomical structures hinder the entry and penetration of drugs into intraocular tissues, often resulting in suboptimal therapeutic outcomes for ocular drug delivery. Tear turnover, blinking, and nasolacrimal drainage rapidly eliminate many topical eye drops [7].

[13] Ion Channels as Potential Drug Targets in Dry Eye Disease and Their Clinical Relevance: A Review

  • Authors: C. Harrell, V. Volarevic
  • Year: 2024
  • Venue: Cells
  • URL: https://www.semanticscholar.org/paper/94b706c0219cff096c0eda7f5707798410b5ff12
  • DOI: 10.3390/cells13232017
  • PMID: 39682765
  • PMCID: 11639998
  • Citations: 9
  • Influential citations: 1
  • Summary: Current knowledge about the molecular mechanisms responsible for the inflammation-induced modification of ion channels leading to tear hyperosmolarity and immune cell dysfunction in DED patients are summarized and d-MAPPS™ Hypo-Osmotic Ophthalmic Solution is emphasized, an important novel approach for DED treatment.
  • Evidence snippets:
  • Snippet 1 (score: 0.437) > Dry eye disease (DED) is a common eye condition affecting over half the world's population [1]. This multifactorial disorder, affecting both the lacrimal system and the ocular surface, is characterized by a deficiency in the quality and/or quantity of tear fluid [1]. DED has two primary subtypes: evaporative dry eye (EDE), caused by excessive evaporation of tear fluid, and aqueous tear-deficient dry eye (ADDE), characterized by the lacrimal glands' inefficiency or failure to produce tears [2,3]. In clinical settings, DED is often seen as a "combination" or "hybrid" form of these two types, where each type gains certain clinical characteristics from the other, initiating and worsening its pathology [2,3]. > Many factors, including aging, eye injury, surgical interventions, poor nutrition, environmental allergens, and chemical hazards, can cause dysfunction of ion channel proteins and generate a detrimental immune response, leading to the development and progression of DED [4,5]. Tear hyperosmolarity (caused by alterations in ion channels) and ocular inflammation (caused by enhanced activation of immune cells and massive production of inflammatory cytokines) create a vicious cycle, aggravating all main DED-related signs and symptoms (ocular discomfort, pain, and vision problems) [1,5,6]. > Accordingly, many experimental and clinical studies have focused on examining the ion channel-dependent effects on the development of DED-associated pathology [1,[3][4][5][6]. The delineation of signaling pathways which were elicited in eye-infiltrated immune cells during DED progression has paved the way for designing new immunoregulatory therapeutic agents capable of suppressing detrimental immunity, attenuating DED-related signs and symptoms [1]. > This manuscript summarizes current knowledge about the molecular mechanisms responsible for inflammation-induced modification of ion channels leading to tear hyperosmolarity and immune cell dysfunction in DED patients.

[14] Managing dry eye disease – a review of selected traditional Chinese medicine and some of their metabolites focusing on molecular mechanisms and signaling pathways

  • Authors: Yixuan Lu, Yuhang Li, Zhen-yu Zhao, Yue Liu, Jiadi Wang et al.
  • Year: 2026
  • Venue: Frontiers in Pharmacology
  • URL: https://www.semanticscholar.org/paper/4c4d84d535379ceba314cf562668325271bd63fd
  • DOI: 10.3389/fphar.2026.1693198
  • PMID: 41988530
  • PMCID: 13076346
  • Summary: The mechanisms by which TCM-derived metabolites, botanical drug extracts, and TCM formulas are reported to modulate interconnected pathological processes underlying DED are described to establish a theoretical framework for intervention optimization and offer a robust foundation for future clinical translation.
  • Evidence snippets:
  • Snippet 1 (score: 0.436) > Dry eye disease (DED) is a prevalent global health issue that negatively impacts quality of life. It is also associated with the risk of corneal ulceration, scarring, and even blindness in severe cases. The complex, multifactorial pathology of DED, often conceptualized as a vicious cycle involving tear film instability, hyperosmolarity, inflammation, and apoptosis, complicates treatment. Traditional Chinese Medicine (TCM) offers a potential therapeutic approach by targeting multiple components and pathways. This review systematically describes the mechanisms by which TCM-derived metabolites, botanical drug extracts, and TCM formulas are reported to modulate interconnected pathological processes underlying DED to establish a theoretical framework for intervention optimization. A systematic literature search was conducted on 23 April 2025, across seven electronic databases (PubMed, Web of Science, Embase, SinoMed, CNKI, Wanfang, and VIP) using a comprehensive strategy combining MeSH terms and keywords related to DED, TCM, and signaling pathways. DED involves alterations in several important signaling pathways associated with inflammation, oxidative stress, and apoptosis. These include PI3K/AKT, MAPK, NF-κB, NLRP3, Nrf2, SIRT, AMPK, and VEGF. TCM formulas represent a multi-target approach with an ability to simultaneously target single or multiple signaling pathways involved in DED pathology. This is proposed to counteract key interlinked processes of inflammation, apoptosis, and oxidative stress, and promotes tear film stability in cellular and animal models, thereby highlighting its pharmacological potential. The multi-component, multi-target, and multi-pathway approach of TCM may offer a strategic advantage for managing the multifactorial pathology of DED through the potential to simultaneously regulate multiple interactive signaling networks. This review describes the molecular mechanisms underlying these traditional treatment practices and offers a robust foundation for future clinical translation.

[15] A Practical Approach to Severity Classification and Treatment of Dry Eye Disease: A Proposal from the Mexican Dry Eye Disease Expert Panel

  • Authors: A. Rodríguez-Garcia, Alejandro Babayan-Sosa, A. Ramirez-Miranda, Concepcion Santa Cruz-Valdes, E. Hernández-Quintela et al.
  • Year: 2022
  • Venue: Clinical Ophthalmology (Auckland, N.Z.)
  • URL: https://www.semanticscholar.org/paper/f78081e5df4fdc77e341aee0a5047e40e2492984
  • DOI: 10.2147/OPTH.S351898
  • PMID: 35520107
  • PMCID: 9061212
  • Citations: 16
  • Summary: A practical DED classification system based on disease severity to help clinicians discriminate cases needing referral to subspecialty clinics from those they could attend and a systematic management approach and general management considerations to improve patients’ therapeutic outcomes according to disease severity are proposed.
  • Evidence snippets:
  • Snippet 1 (score: 0.427) > The Industry Workshop on Clinical Trials in DED, held in 1995 under the auspices of the National Eye Institute (NEI), shaped the first formal definition of DED. 16 Three major concepts are inherent to this definition, (1) the recognition that an abnormal tear film is the primary pathophysiological mechanism of DED; (2) the pathology arises from either an aqueous deficiency or excessive tear film evaporation; and (3) DED causes discomfort symptoms". 1,16 This report established a solid foundation that launched translational, clinical, and basic scientific research to improve the diagnosis and treatment. 1 However, the NEI workshop DED definition was incomplete, lacking critical aspects of the pathogenesis and symptomatology of the disease. > Due to the growing evidence concerning diagnosis and therapeutics of dry eye, the first Tear Film & Ocular Surface Dry Eye Workshop (TFOS DEWS) held in 2007 proposed a definition including its multifactorial origin, the increase in tear osmolarity, and inflammation of the ocular surface as crucial pathogenic findings, 17,18 and the presence of visual disturbances among relevant symptoms. 19 This definition recognized dry eye as a disease, resulting from a complex abnormal interaction between the tear film and the ocular surface, suggesting that DED results from an alteration in ≥1 portions of the intertwined "functional unit" comprised by the conjunctiva, cornea, accessory lacrimal and Meibomian glands, the main lacrimal gland, eyelids, and motor and sensory nerves. 20,21 he TFOS DEWS II (2017) produced an evidence-based definition, recognizing the loss of tear film homeostasis as the conveying element in DED, reasserting ocular symptoms as the central feature of DED, and expanding the pathophysiological understanding of the disease by adding the neurosensory abnormalities. 1,22 However, this definition does not account for differences in symptom duration. 20 For example, although patients with DED associated with Sjögren syndrome and those with recent refractive surgery may present similar dry eye symptoms, the former is unlikely to improve over time, while the latter is expected to exhibit significant improvement. 20

[16] Oxidative Stress in the Anterior Ocular Diseases: Diagnostic and Treatment

  • Authors: A. Dammak, Cristina Pastrana, Alba Martín-Gil, Carlos Carpena-Torres, Assumpta Peral Cerda et al.
  • Year: 2023
  • Venue: Biomedicines
  • URL: https://www.semanticscholar.org/paper/610ba39ffe207a56271f5612d5241950983950e3
  • DOI: 10.3390/biomedicines11020292
  • PMID: 36830827
  • PMCID: 9952931
  • Citations: 95
  • Influential citations: 2
  • Summary: The oxidative stress and inflammatory processes in the front of the eye is analysed to provide a better understanding of the pathomechanism, the importance of biomarkers for the diagnosis of eye diseases, and the recent treatment of anterior ocular diseases.
  • Evidence snippets:
  • Snippet 1 (score: 0.425) > The eye is a metabolically active structure, constantly exposed to solar radiations making its structure vulnerable to the high burden of reactive oxygen species (ROS), presenting many molecular interactions. The biomolecular cascade modification is caused especially in diseases of the ocular surface, cornea, conjunctiva, uvea, and lens. In fact, the injury in the anterior segment of the eye takes its origin from the perturbation of the pro-oxidant/antioxidant balance and leads to increased oxidative damage, especially when the first line of antioxidant defence weakens with age. Furthermore, oxidative stress is related to mitochondrial dysfunction, DNA damage, lipid peroxidation, protein modification, apoptosis, and inflammation, which are involved in anterior ocular disease progression such as dry eye, keratoconus, uveitis, and cataract. The different pathologies are interconnected through various mechanisms such as inflammation, oxidative stress making the diagnostics more relevant in early stages. The end point of the molecular pathway is the release of different antioxidant biomarkers offering the potential of predictive diagnostics of the pathology. In this review, we have analysed the oxidative stress and inflammatory processes in the front of the eye to provide a better understanding of the pathomechanism, the importance of biomarkers for the diagnosis of eye diseases, and the recent treatment of anterior ocular diseases.

[17] Síndrome de ojo seco asociado a fármacos sistémicos

  • Authors: E. O. G. Hernández, Jesús Guerrero Becerril
  • Year: 2020
  • Venue: Anales Médicos de la Asociación Médica del Centro Médico ABC
  • URL: https://www.semanticscholar.org/paper/85e3494d9ddcd1d5e3ff788e3bb9133fcd19ee36
  • DOI: 10.35366/97465
  • Summary: The purpose of this review is to briefly summarize the most common systemic medications and the possible mechanism related to dry eye disease.
  • Evidence snippets:
  • Snippet 1 (score: 0.423) > Dry eye syndrome is a very common cause of ophthalmological consultation, it is a condition characterized by high tear osmolarity, tear film instability and ocular surface inflammation. The main etiologies are age, feminine gender, meibomian gland dysfunction, contact lens use, environmental factors and systemic drugs. The main mechanisms that cause dry eye are reduction in tear production, alteration of the corneal nerves or a direct toxicity to the lacrimal gland. Many drugs are related to dry eye syndrome, this are important in daily medical practice due to the frequent use. Some of the group of drugs that have been related to dry eye syndrome are: NSAIDs (nonsteroidal anti-inflammatory drugs), gastric protector drugs, antihypertensive agents, anxiolytics, oral contraceptives, antidepressants, antipsychotics, antihistamines and drugs for treating Parkinson’s disease, among others. The purpose of this review is to briefly summarize the most common systemic medications and the possible mechanism related to dry eye disease.

[18] Classifying Dry Eye Disease Patients from Healthy Controls Using Machine Learning and Metabolomics Data

  • Authors: Sajad Amouei Sheshkal, Morten Gundersen, M. Riegler, Ø. Utheim, K. Gundersen et al.
  • Year: 2024
  • Venue: Diagnostics
  • URL: https://www.semanticscholar.org/paper/a813a14498d134a77d46cad08f48339a12ed6fbc
  • DOI: 10.3390/diagnostics14232696
  • PMID: 39682603
  • PMCID: 11640104
  • Citations: 10
  • Influential citations: 1
  • Summary: The results show that the logistic regression model with L2 regularization can outperform more complex models on an imbalanced data set with a small sample size and a high number of features, while also avoiding overfitting and delivering consistent performance across cross-validation folds.
  • Evidence snippets:
  • Snippet 1 (score: 0.420) > Dry Eye Disease (DED) is a multifaceted disorder characterised by a disruption in the composition, integrity, and stability of the tear film due to various internal and external factors. It is one of the most common reasons people seek eye care, with a severity spectrum ranging from minor, fleeting discomfort to severe, persistent pain and visual function impairment. This progression not only presents a substantial economic and healthcare challenge but also significantly impacts the quality of life of sufferers and the broader community. The incidence of DED notably increases following cataract surgery, highlighting the critical need for ophthalmologists to thoroughly evaluate for existing DED and to implement proactive treatment approaches. The presence of DED before surgery, can also complicate the precision of pre-surgical measurements, necessitate the reduction of intra-operative factors that could harm the ocular surface, and require the adoption of post-surgical care protocols to prevent the worsening of DED symptoms [1]- [6]. Clinical signs and symptoms are currently used to diagnose dry eye disease; however, the correlation between signs and symptoms is weak, leading to challenges in diagnosing and monitoring DED [7]. > Advancements in omics technologies allow researchers to explore the genome, transcriptome, proteome, and more, providing in-depth insights into the molecular mechanisms underlying diseases. Despite their utility, single omics approaches are insufficient for comprehensively understanding the intricate interactions between genes, RNA, proteins, and environmental factors. Metabolomics distinguishes itself by revealing how metabolites, the dynamic output of gene, mRNA, and protein function, respond to various internal and external stimuli. This makes metabolomics a crucial instrument for unraveling complex biological processes and deepening our understanding of the origins, progression, and treatment outcomes of diseases [1]. > In the context of DED, metabolomics holds the promise of identifying disease-specific metabolite profiles. These profiles can play an important role in enhancing the early diagnosis of DED, and in elucidating its etiology and pathology [1]. By identifying specific metabolic pathways and therapeutic targets, metabolomics can guide the choice of personalized treatment plans and improve the prediction of patient outcomes [1].

[19] Comparative evaluation of aqueous solution and oil emulsion formulations of 0.05% cyclosporine eye drops in dry eye disease – A randomized clinical trial

  • Authors: Ayesha A Salam, Seema Sen, N. Lomi, Noopur Gupta, M. Vanathi et al.
  • Year: 2025
  • Venue: Indian Journal of Ophthalmology
  • URL: https://www.semanticscholar.org/paper/654d0b1a651be983ac8cf834e80947c784d8222f
  • DOI: 10.4103/IJO.IJO_1850_24
  • PMID: 40146145
  • PMCID: 12097410
  • Citations: 1
  • Summary: Both aqueous solution and oil emulsion 0.05% cyclosporine formulations appear to be equally effective in the management of dry eye disease with a comparatively better response with oil emulsion formulations.
  • Evidence snippets:
  • Snippet 1 (score: 0.418) > Dry eye disease (DED), alternatively termed keratoconjunctivitis sicca, stands as a prevalent ocular surface ailment impacting millions of individuals globally. The prevalence of DED among adults worldwide ranges from 5% to 50%. [1] cording to the DEWS 2 (Dry Eye Workshop 2) report of 2017 -"Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles." [2] e main management modality for DED is the use of ocular lubricants. From numerous studies, we already know that tear hyperosmolarity plays a central mechanism in the pathophysiology of DED. [3] This in turn is said to damage the ocular surface by initiating inflammation (directly as well as indirectly). Thus, the primary focus for the management of DED lies in addressing the relentless inflammatory cycle. However, the use of topical steroids for a long period can be harmful because of the large number of adverse effects associated with it. Hence, the treatment of DED also entails the utilization of topical non-glucocorticoid immunomodulatory drugs like cyclosporine eyedrops which target the T cells and produce anti-inflammatory action by inhibiting the nuclear factor κB (NFκB) activation and also by inhibiting calcineurin thereby blocking the release of interleukin 2. > Different concentrations of topical cyclosporine are available in the market. For this study, we specifically selected a concentration of 0.05% of cyclosporine eye drops. This choice Cite this article as: Salam AA, Sen S, Lomi N, Gupta N, Vanathi M, Tandon R. Comparative evaluation of aqueous solution and oil emulsion formulations of 0.05% cyclosporine eye drops in dry eye disease -A randomized clinical trial. Indian J Ophthalmol 2025;73:577-81.

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.