Ocular Microbiome and Immune System in Dry Eyes

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

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.

Study Overview

• Status: Recruiting
• Conditions: Dry Eye Disease
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Martin Zinkernagel, Prof. Dr. Dr.; Phone Number: +41 31 632 95 65; Email: martin.zinkernagel@insel.ch
• Study Contact Backup: Name: Denise Zysset, PhD; Phone Number: +41 31 632 85 10; Email: denise.zysset@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Department of Ophthalmology, Inselspital
    • Contact: Martin Zinkernagel, Prof. Dr. Dr.; Phone Number: +41 31 632 95 65; Email: martin.zinkernagel@insel.ch
    • Contact: Denise Zysset, PhD; Phone Number: +41 31 632 85 10; Email: denise.zysset@insel.ch
    • Principal Investigator: Martin Zinkernagel, Prof. Dr. Dr.
    • Sub-Investigator: Denise Zysset, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• 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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stability of the ocular surface microbiome	Sequential sample collection of eye swabs	3-6 months after baseline

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Collaborators: Stiftung OPOS; Fondation Bertarelli
• Investigators: Principal Investigator: Martin Zinkernagel, Prof. Dr. Dr., Department of Ophthalmology, Inselspital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (Actual): December 8, 2020

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: immune system; microbiome
• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca
• Other Study ID Numbers: BASEC 2020-00775

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No