Ocular Microbiome and Immune System in Dry Eyes

Study Overview
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Brief Summary
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The primary objectives of this study are the characterization of the ocular microbiome as well as of the local immune system in participants with and without dry eye disease. Secondary objectives are the identification of differences in the ocular microbiome as well as in the immune system between participants with and without dry eye disease to ultimately find associations between the ocular microbiome and the immune system in dry eye disease.

Detailed Description
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Although dry eye disease is considered to be one of the most common ocular surface diseases worldwide, treatment options are only very limited and severe side effects are common. However, recent studies showed that the ocular microbiome may be crucial for maintaining ocular surface homeostasis. Disruption of this homeostasis, called dysbiosis, may lead to inflammation that is a key component in the pathogenesis of dry eye disease. It has been suggested that bacteria are invasive in ocular mucosal tissue, thereby effectively hidden from clearance by the local immune system and rendering the inflammation chronic. Therefore, the investigators hypothesize that the ocular microbiome may induce changes in the mucosal immune system of the eye, which in turn may accelerate the development of dry eyes. Since there is a crucial role of both, the ocular microbiome and the local mucosal immune system, on several diseases, the overall aim of this project is to assess the associations of the mucosal immune system and the ocular microbiome in dry eye disease.

Official Title
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Associations of the Ocular Microbiome and the Immune System in Dry Eye Disease

Conditions
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Dry Eye Disease

Intervention / Treatment
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* Other: Ocular microbiome
* Other: Ocular immune system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to sign informed consent 18 years of age or older Exclusion Criteria: Not willing or able to sign informed consent Younger than 18 years Recent (3 month) history of use of systemic and/or topical antibiotics Usage of medical eye drops (Lacrycon and other moisturizing eye drops are allowed) Recent (3 month) history of ocular surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Dry eye disease<br>Patients with dry eye disease | Other: Ocular microbiome<br>* Taxonomical and functional characterization of the ocular microbiome<br>Other: Ocular immune system<br>* Functional characterization of the tear fluid proteome, histology of conjunctival tissue and molecular assays<br>|
| Healthy controls<br>Healthy controls without dry eye disease | Other: Ocular microbiome<br>* Taxonomical and functional characterization of the ocular microbiome<br>Other: Ocular immune system<br>* Functional characterization of the tear fluid proteome, histology of conjunctival tissue and molecular assays<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular microbiome and local immune system in controls | Qualitative and quantitative characterization of the ocular microbiome and the local immune system in participants with no signs of dry eye disease. The primary variable for the characterization of the ocular microbiome is the identification of microbial taxa and the functional analysis of the identified taxa using eye swabs and conjunctival tissue samples. The primary variable for the characterization of the immune system is the identification of components of the ocular mucosal immune system (i.e. immune cells, anti- and proinflammatory cytokines) using conjunctival tissue samples and tear fluid. Baseline factors such as age, sex, BMI, medication, risk factors for dry eyes such as smoking and contact lenses may have an influence on the ocular microbiome. | At baseline | 
| Ocular microbiome and local immune system in patients | Qualitative and quantitative characterization of the ocular microbiome and the local immune system in participants with clinical signs of dry eye disease. For primary variable for characterization see Outcome 1. The variables for grading of dry eyes are tear film osmolarity, split lamp examination, tear secretion and subjective measurement by the Ocular Surface Disease Index© (OSDI©) questionnaire. | At baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences of the ocular microbiome and the local immune system between patients and controls | Identification of differences of the ocular microbiome and the local immune system between patients and controls. The variables used for the differentiation of these two cohorts in terms of the microbiome are the relative abundances of identified microbial taxa and of corresponding functional features (i.e. genes and pathways) of the taxa. The variables used for the differentiation of the cohorts in terms of the immune system are quantitative values of cytokines and immune cells. | At baseline | 
| Correlations between the ocular microbiome and the local immune system | Identification of correlations between the ocular microbiome and the local immune system. For variables used see Outcome 3. | At baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiome, immune system