Ocular Microbiome and Immune System in Dry Eyes

• ClinicalTrials.gov Identifier: NCT04658238
• Recruitment Status: Recruiting
• First Posted: December 8, 2020
• Last Update Posted: April 28, 2021
• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Stiftung OPOS; Fondation Bertarelli
• Information provided by (Responsible Party): University Hospital Inselspital, Berne

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Dry Eye Disease	Other: Ocular microbiome; Other: Ocular immune system

Detailed Description:

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 600 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Associations of the Ocular Microbiome and the Immune System in Dry Eye Disease
• Actual Study Start Date: October 1, 2020
• Estimated Primary Completion Date: October 1, 2023
• Estimated Study Completion Date: October 1, 2023

Groups and Cohorts

Group/Cohort	Intervention/treatment
Dry eye disease; Patients with dry eye disease	Other: Ocular microbiome; Taxonomical and functional characterization of the ocular microbiome; Other: Ocular immune system; Functional characterization of the tear fluid proteome, histology of conjunctival tissue and molecular assays
Healthy controls; Healthy controls without dry eye disease	Other: Ocular microbiome; Taxonomical and functional characterization of the ocular microbiome; Other: Ocular immune system; Functional characterization of the tear fluid proteome, histology of conjunctival tissue and molecular assays

Outcome Measures

Primary Outcome Measures :

1. Ocular microbiome and local immune system in controls [ Time Frame: At baseline ]
   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.
2. Ocular microbiome and local immune system in patients [ Time Frame: At baseline ]
   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.

Secondary Outcome Measures :

1. Differences of the ocular microbiome and the local immune system between patients and controls [ Time Frame: At baseline ]
   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.
2. Correlations between the ocular microbiome and the local immune system [ Time Frame: At baseline ]
   Identification of correlations between the ocular microbiome and the local immune system. For variables used see Outcome 3.

Other Outcome Measures:

1. Stability of the ocular surface microbiome [ Time Frame: 3-6 months after baseline ]
   Sequential sample collection of eye swabs

Biospecimen Retention:   Samples With DNA

DNA isolated from swabs frozen conjunctival tissue frozen tear fluid

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

Consecutive ongoing recruitment of subjects attending routine follow-ups through the involved investigators in daily clinical practice at Department of Ophthalmology, Inselspital, Bern

Criteria

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

Contacts and Locations

Contacts

Contact: Martin Zinkernagel, Prof. Dr. Dr.; +41 31 632 95 65; martin.zinkernagel@insel.ch

Contact: Denise Zysset, PhD; +41 31 632 85 10; denise.zysset@insel.ch

Locations

Switzerland

Department of Ophthalmology, Inselspital; Recruiting

Bern, Switzerland, 3010

Contact: Martin Zinkernagel, Prof. Dr. Dr. +41 31 632 95 65 martin.zinkernagel@insel.ch

Contact: Denise Zysset, PhD +41 31 632 85 10 denise.zysset@insel.ch

Principal Investigator: Martin Zinkernagel, Prof. Dr. Dr.

Sub-Investigator: Denise Zysset, PhD

Sponsors and Collaborators

University Hospital Inselspital, Berne

Stiftung OPOS

Fondation Bertarelli

Investigators

• Principal Investigator: Martin Zinkernagel, Prof. Dr. Dr.; Department of Ophthalmology, Inselspital

More Information

• Responsible Party: University Hospital Inselspital, Berne
• ClinicalTrials.gov Identifier: NCT04658238
• Other Study ID Numbers: BASEC 2020-00775
• First Posted: December 8, 2020
• Last Update Posted: April 28, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital Inselspital, Berne:

microbiome; immune system

Additional relevant MeSH terms:

Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases