Pathogenesis Of Dry Eye Syndrome Research Articles

Clinical features, diagnosis, and treatment of dry eye syndrome in children

AIM: To investigate the etiopathogenesis and clinical features of dry eye syndrome in children, methods for diagnosing the disease, and the treatment algorithm.
 MATERIAL AND METHODS: One hundred eighty-seven children with dry eye syndrome aged 3 to 17 yr were examined. To diagnose dry eye syndrome in children, the following research methods were used: biomicroscopy of the anterior part of the eye under diffuse illumination and with a cobalt filter after instillation of vital dyes; examination of the height of the lacrimal meniscus; identification of a characteristic discharge in the conjunctival sac, xerosis of the ocular surface; and evaluation of tear production (Schirmer I test) and stability of the tear film.
 RESULTS: We found that the links in the pathogenesis of dry eye syndrome in children were as follows: diseases of the ocular surface and appendage of the eye, contact correction of ametropia, and surgical operations on the conjunctiva and oculomotor muscles; otogenic neuritis of the facial nerve; rheumatoid arthritis; endocrine ophthalmopathy; lagophthalmos; and thermal and chemical burns. It is now always possible to evaluate tear production and tear film stability in preschool and primary school-aged children. In this case, the main diagnostic method is biomicroscopy. We identified objective clinical symptoms of dry eye syndrome in children using biomicroscopy. Dry eye syndrome was classified into four degrees of severity: mild, moderate, severe, and extremely severe. The subjective and objective clinical signs of each disease severity are described.
 An individual approach and personalized therapy are required to treat dry eye syndrome in children, focusing on the individual tolerability and effectiveness of the drug. Maximum medical alertness and early and accurate clinical differential diagnosis between dry eye syndrome and infectious inflammatory pathology of the anterior part of the eye are required.
 CONCLUSION: The features of the etiopathogenesis of dry eye syndrome in children with various nosologies are examined, and the characteristic clinical symptoms and severity of dry eye syndrome, diagnostic methods, and algorithm for treating dry eye syndrome in children are described. The clinical and diagnostic features of dry eye syndrome in children described by us contribute to its early diagnosis, allowing for the initiation of personalized tear replacement and reparative therapy on time, preventing the development of a chronic course of the disease, the occurrence of complications, and the preservation and/or restoration of visual acuity.

Protective Effect of Allyl Isothiocyanate in an Experimentally Induced Rat Model for Dry Eye Syndrome

PurposeGrowing evidence emphasizes the role of inflammation and oxidative stress in the pathogenesis of Dry Eye Syndrome (DES). Concordantly, the importance of agents targeting the inflammatory cascade and oxidative stress in the treatment is also progressively increasing. Herein, the study has investigated the protective effects and underlying mechanism of allyl isothiocyanate (AITC) on the ocular surface in a benzalkonium chloride (BAC)-induced dry eye rat model.MethodsA total of twenty-one Wistar albino rats were used to form the following three groups: Control, BAC, BAC + AITC. DES was established by topical application of BAC (four times daily for two weeks) in two groups, of which one group was treated with AITC (10 mg/kg BW daily oral dosage) for four weeks. Rats were monitored by dry eye diagnostic tests during the study period, and eventually, corneal tissues were used to evaluate for histopathologic analyzes and inflammatory and oxidative status.ResultsA significant improvement was observed in various histopathologic and ophthalmologic findings, including tear volume, tear film integrity, ocular surface damage, ocular inflammatory signs, corneal thickness, and edema through AITC supplementation. AITC prominently balanced the inflammatory status and oxidative stress by lowering key proinflammatory mediators (NF-κB, TNF-α, IL-1β, IL-6, and IL-8) and increasing the activities of antioxidant enzymes (SOD, GSH-Px). Also, levels of protective tear proteins, including Muc1, Muc4, and Muc5 were recovered with AITC supplementation.ConclusionAITC alleviates clinical and histopathologic signs related to DES. Antioxidative and anti-inflammatory properties of AITC play a significant role in the mechanism of action.

In Vivo Anti-Inflammation Potential of Aster koraiensis Extract for Dry Eye Syndrome by the Protection of Ocular Surface.

Dry eye syndrome (DES) is a corneal disease often characterized by an irritating, itching feeling in the eyes and light sensitivity. Inflammation and endoplasmic reticulum (ER) stress may play a crucial role in the pathogenesis of DES, although the underlying mechanism remains elusive. Aster koraiensis has been used traditionally as an edible herb in Korea. It has been reported to have wound-healing and inhibitory effects against insulin resistance and inflammation. Here, we examined the inhibitory effects of inflammation and ER stress by A. koraiensis extract (AKE) in animal model and human retinal pigmented epithelial (ARPE-19) cells. Oral administration of AKE mitigated DE symptoms, including reduced corneal epithelial thickness, increased the gap between lacrimal gland tissues in experimental animals and decreased tear production. It also inhibited inflammatory responses in the corneal epithelium and lacrimal gland. Consequently, the activation of NF-κB was attenuated by the suppression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Moreover, AKE treatment ameliorated TNF-α-inducible ocular inflammation and thapsigargin (Tg)-inducible ER stress in animal model and human retinal pigmented epithelial (ARPE-19) cells. These results prove that AKE prevents detrimental functional and histological remodeling on the ocular surface and in the lacrimal gland through inhibition of inflammation and ER stress, suggesting its potential as functional food material for improvement of DES.

LIN Guo-hua's experience in treating dry eye syndrome with Lingnan fire needling

Professor LIN Guo-hua is the representative inheritor of Lingnan fire needling therapy. He proposed that the clinical application of Lingnan fire needling is mainly based on pattern differentiation according to eight priciples, as well as in coordination with the theories of meridians and zang-fu organs. He believes that dry eye syndrome can be treated from the aspects of deficiency of liver and kidney, heart yin deficiency, and qi and yin deficiency. Through deeply digging the connotation of ancient classics, and combined his clinical practice using Lingnan fire needling, professor LIN created a unique therapy that select "Neichengqi"as the main acupoint combined with Xialeidian, Dagukong (EX-UE 5), Xiaogukong (EX-UE 6) and Shaoze (SI 1) in the treatment of dry eye syndrome. In this paper, from the etiology and pathogenesis of dry eye syndrome and therapeutic characteristics of Lingnan fire needling, the thoughts of syndrome differentiation and characteristics of acupoints selection of professor LIN were analyzed by a typical case, and it is expect to enrich the clinical treatment plan for dry eye syndrome.

Integrated Tear Proteome and Metabolome Reveal Panels of Inflammatory-Related Molecules via Key Regulatory Pathways in Dry Eye Syndrome.

Dry eye syndrome (DES) is a growing public health concern with a high global prevalence; however, the fundamental processes involved in its pathogenic mechanisms remain poorly understood. In the present study, we applied nanoscale liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (nanoLC/Q-TOF-MS/MS) and ultraperformance LC/Q-TOF-MS/MS technologies on tear samples obtained from 18 dry eye patients and 19 healthy controls for integrated proteomic and metabolomic analyses. Overall, 1031 tear proteins were detected, while 190 proteins were determined to be significantly expressed in dry eye patients. Further functional analysis suggested that various biological processes were highly expressed and involved in the pathogenesis of DES, especially immune and inflammatory processes. In total, 156 named metabolites were identified, among which 34 were found to be significantly changed in dry eye patients. The results highlighted the key elements, especially inflammatory-related proteins and metabolites that played important roles in the development of DES. Further, the regulatory roles of primary pathways, including complement and coagulation cascades, glycolysis/gluconeogenesis, and amino acid metabolism, were also identified as processes involved in DES. Collectively, our work not only provided insight into the potential biomarkers of DES for diagnostic and prognostic purposes but extended our knowledge of the physiopathology of this syndrome.

Expression of mucins MUC5AC and MUC19 on the ocular surface in dry eye syndrome model of ovariectomized female rabbits.

Dry eye syndrome (DES) is a common symptom of tear film instability and ocular surface damage due to an abnormal quality and quantity of tears, including the sensation of foreign objects and blurred vision. Among all factors for tear film stability, MUC5AC and MUC19 are very important; the levels of both mucins are associated with the pathogenesis of DES. The aim of this study was to explore the expression of MUC5AC and MUC19 on the ocular surface in a DES model of ovariectomized female rabbits. Healthy female New Zealand white rabbits (n = 18; age: 1 year, weight: 2.5 ±0.6 kg) were randomly assigned to a test group and a control group. The DES model was constructed in ovariectomized female rabbits. Indicators of ocular surface injury, such as Schirmer's test, corneal fluorescence staining, a conjunctival imprinting cytology test, and the expression of MUC5AC and MUC19 in conjunctival tissues were evaluated by immunohistochemistry in week 1, week 2 and week 4. Both the length of soaked test paper and the total scores of corneal fluorescence staining at all time-points were significantly lower in the test group than in the control group, and they decreased over time (p < 0.05). The grades of imprinted cells at all time-points were significantly higher in the test group than in the control group, and they increased over time (p < 0.05). The percentage of goblet cells was significantly lower in the test group than in the control group, and it decreased over time (p < 0.05). The percentages of cells with a positive expression of MUC5AC and MUC19 at all time-points were significantly lower in the test group than in the control group, and they decreased over time (p < 0.05). The pathogenesis of DES is associated with an increased grade of imprinted cells, decreased goblet cells, and a decreased expression of MUC5AC and MUC19.

Mesenchymal Stem/Stromal Cells Protect the Ocular Surface by Suppressing Inflammation in an Experimental Dry Eye

Dry eye syndrome (DES) is one of the most common ocular diseases affecting nearly 10% of the US population. Most of the currently available treatments are palliative, and few therapeutic agents target biological pathway of DES. Although DES is a multifactorial disease, it is well-known that inflammation in the ocular surface plays an important role in the pathogenesis of DES. Mesenchymal stem/stromal cells (MSCs) have been shown to repair tissues by modulating excessive immune responses in various diseases. Therefore, we here investigated the therapeutic potential of MSCs in a murine model of an inflammation-mediated dry eye that was induced by an intraorbital injection of concanavalin A. We found that a periorbital administration of MSCs reduced the infiltration of CD4(+) T cells and the levels of inflammatory cytokines in the intraorbital gland and ocular surface. Also, MSCs significantly increased aqueous tear production and the number of conjunctival goblet cells. Subsequently, corneal epithelial integrity was well-preserved by MSCs. Together, the results demonstrate that MSCs protect the ocular surface by suppressing inflammation in DES, and suggest that MSCs may offer a therapy for a number of ocular surface diseases where inflammation plays a key role.

Comparative Anatomy of the Human and Canine Efferent Tear Duct System – Impact of Mucin MUC5AC on Lacrimal Drainage

Purpose: To investigate the histomorphology of the canine tear drainage system and to show the distribution of mucin MUC5AC within the tissue.Methods: Conjunctiva and tear drainage systems of 19 long-nosed dogs were investigated histologically and ultrastructurally. The tissues were stained with eight different antibodies reactive against less glycosylated and highly-glycosylated MUC5AC. Results were compared with findings in human tissue received from 12 body donors.Results: Except for a distinctly longer nasolacrimal duct and several accessory openings of the duct into the nasal cavity, the morphology of the canine tear drainage system is very similar to that of humans. MUC5AC in less- and highly-glycosylated forms was present in the conjunctival tissue of dogs as well of humans. Within the tear sac and the nasolacrimal duct only less-glycosylated MUC5AC could be found in dogs and in human.Conclusions: These findings demonstrate that the canine tear drainage system is very similar to its human equivalent. In particular the distribution of MUC5AC, supposed to play an important role within the pathogenesis of dry eye syndrome (DES), is the same as in humans. Therefore the canine model seems to be an appropriate model for further DES research.

Investigating the Relationship between Serum Interleukin-17 Levels and Systemic Immune-Mediated Disease in Patients with Dry Eye Syndrome

PurposeTo investigate the association between dry eye syndrome (DE) and serum levels of interleukin (IL)-17 in patients with systemic immune-mediated diseases.MethodsIL-17 and IL-23 levels were measured in the sera of patients whose tear production was <5 mm on the Schirmer test. Subjects included patients with chronic graft-versus-host disease (GVHD), rheumatoid arthritis (RA), Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), and no systemic disease. Corneal/conjunctival fluorescein staining was scored and the correlation between the score and the IL-17 level was evaluated.ResultsA strong correlation existed between IL-17 level and the type of systemic disease. IL-17 was significantly elevated in patients with chronic GVHD compared to those with RA and SS. IL-17 was not detectable in patients with SLE or in those without systemic disease. IL-23 was not detected in any of the subjects. IL-17 was significantly increased in patients with high fluorescein staining scores.ConclusionsOur data suggest that IL-17 is involved in the pathogenesis of DE in patients with systemic immune-mediated diseases.

CCL4/MIP-1β Levels in Tear Fluid and Serum of Patients with Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive genetic disorder. The disease affects all secretory epithelia including the eye and belongs to the group of ocular surface epithelial diseases, termed keratoconjunctivitis sicca that develop in dry eye. In the pathogenesis of dry eye, inflammation plays a crucial role. The aim of this study was to assess the potential role of MIP-1beta in the pathogenesis of dry eye syndrome in patients with CF. We assayed MIP-1beta levels in tear fluid and serum of 28 patients with CF and 27 controls by ELISA. The ophthalmic examinations including the tests for dry eye were used to study the ocular surface. The tear levels of MIP-1beta in the CF patients were significantly higher than those in the controls. Dry eye syndrome was observed in 10 (36%) CF patients. The tear fluid levels of MIP-1beta were significantly raised in CF patients with dry eye syndrome compared with CF patients without dry eye symptoms. Our results suggest a crucial role of CCL4/MIP-1beta in the development of dry eye syndrome in CF patients and immunopathogenesis of ocular surface changes in this disease. Clarification of the role of CCL4/MIP-1beta in the pathogenesis of ocular findings in CF patients will be useful in establishing immunotherapeutic strategies for this disease.

Treatment of chronic dry eye: focus on cyclosporine

To review the current treatment of chronic dry eye syndrome, focusing on cyclosporine A (CsA), a systematic literature search was performed using PubMed databases in two steps. The first step was oriented to articles published for dry eye. The second step was focused on the use of CsA in dry eye. A manual literature search was also undertaken based on citations in the published articles. The knowledge on the pathogenesis of dry eye syndrome has changed dramatically during the last few years. Inflammation and the interruption of the inflammatory cascade seem to be the main focus of the ophthalmologic community in the treatment of dry eye, giving the anti-inflammatory therapy a new critical role. The infiltration of T-cells in the conjuctiva tissue and the presence of cytokines and proteasis in the tear fluid were the main reason introducing the use of immunomodulator agents such as corticosteroids, cyclosporine, and doxycicline in order to treat dry eye syndrome. CsA emulsion is approved by the FDA for the treatment of dry eye, while clinical trials of this agent have demonstrated efficacy and safety of CsA. CsA seems to be a promising treatment against dry eye disease. New agents focused on the inflammatory pathogenesis of this syndrome in combination with CsA may be the future in the quest of treating dry eye. More studies are needed to determine the efficacy, safety, timing, and relative cost/effect of CsA.

Changes in the tear film and ocular surface from dry eye syndrome.

Dry eye syndrome (DES) refers to a spectrum of ocular surface diseases with diverse and frequently multiple aetiologies. The common feature of the various manifestations of DES is an abnormal tear film. Tear film abnormalities associated with DES are tear deficiency, owing to insufficient supply or excessive loss, and anomalous tear composition. These categorizations are artificial, as in reality both often coexist. DES disrupts the homeostasis of the tear film with its adjacent structures, and adversely affects its ability to perform essential functions such as supporting the ocular surface epithelium and preventing microbial invasion. In addition, whatever the initial trigger, moderate and severe DES is characterized by ocular surface inflammation, which in turn becomes the cause and consequence of cell damage, creating a self-perpetuating cycle of deterioration. Progress has been made in our understanding of the aetiology and pathogenesis of DES, and these advances have encouraged a proliferation of therapeutic options. This article aims to amalgamate prevailing ideas of DES development, and to assist in that, relevant aspects of the structure, function, and production of the tear film are reviewed. Additionally, a synopsis of therapeutic strategies for DES is presented, detailing treatments currently available, and those in development.