Dry Eye DiseaseNCT04658238
Ocular Microbiome and Immune System in Dry Eyes
An observational study of Dry Eye Disease, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Dry Eye Disease
- What is being tested?
- Ocular microbiome and Ocular immune system
- How many people
- 600 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Oct 2020to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Who may be able to join
- Willing to sign informed consent
- 18 years of age or older
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
Department of Ophthalmology, Inselspital
Bern, 3010
Martin Zinkernagel, Prof. Dr. Dr., +41 31 632 95 65, martin.zinkernagel@insel.ch
Denise Zysset, PhD, +41 31 632 85 10, denise.zysset@insel.ch
About this study
Official title: 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.
Read the 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.
- Conditions
- Dry Eye Disease
- Being tested
- Ocular microbiome, Ocular immune system
- Keywords
- microbiome, immune system
- Medical subject headings
- Dry Eye Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ocular microbiomeOther
Taxonomical and functional characterization of the ocular microbiome
Ocular immune systemOther
Functional characterization of the tear fluid proteome, histology of conjunctival tissue and molecular assays
| Study group | Role | What they receive |
|---|---|---|
| Dry eye disease | Patients with dry eye disease Receives: Other: Ocular microbiome; Other: Ocular immune system | |
| Healthy controls | Healthy controls without dry eye disease Receives: Other: Ocular microbiome; Other: Ocular immune system |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: At baseline
Secondary outcomes (2)
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.
Measured: 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.
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2020
- Study start1 Oct 2020
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Dry Eye DiseaseStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- Stiftung OPOS, Fondation Bertarelli
- Responsible party
- Sponsor
- Investigators
- Martin Zinkernagel, Prof. Dr. Dr., Principal investigator, Department of Ophthalmology, Inselspital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04658238
- Sponsor's protocol ID
- BASEC 2020-00775
- Status last verified
- Mar 2025
- First submitted
- 1 Dec 2020
- Last updated
- 1 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Sporri L, Studer JM, Kreuzer M, Rotzetter J, Scharer D, Largiader CR, Jaggi D, Zinkernagel MS, Zysset-Burri DC. Linking the microbiome to the complement system in geographic atrophy. NPJ Genom Med. 2026 Feb 2;11(1):14. doi: 10.1038/s41525-026-00550-7.
PubMed 41629364
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Associations of the Ocular Microbiome and the Immune System in Dry Eye Disease
- ClinicalTrials.gov ID
- NCT04658238
- Acronym / sponsor ID
- BASEC 2020-00775
- Conditions
- Dry Eye Disease
- Keywords
- microbiome, immune system
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- Stiftung OPOS, Fondation Bertarelli
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 8 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dry eye disease | – | Other: Ocular microbiome, Other: Ocular immune systemPatients with dry eye disease |
| Healthy controls | – | Other: Ocular microbiome, Other: Ocular immune systemHealthy controls without dry eye disease |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (2 listed)
- Willing to sign informed consent
- 18 years of age or older
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ocular microbiomeTaxonomical and functional characterization of the ocular microbiome | Other | Dry eye disease, Healthy controls |
| Ocular immune systemFunctional characterization of the tear fluid proteome, histology of conjunctival tissue and molecular assays | Other | Dry eye disease, Healthy controls |
Primary outcome
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.
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.
2 secondary outcomes
Differences of the ocular microbiome and the local immune system between patients and controls
Time frame: At baseline
Correlations between the ocular microbiome and the local immune system
Time frame: At baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2025.
- Derived from this study: PubMed 41629364Sporri L, Studer JM, Kreuzer M, Rotzetter J, Scharer D, Largiader CR, Jaggi D, Zinkernagel MS, Zysset-Burri DC. Linking the microbiome to the complement system in geographic atrophy. NPJ Genom Med. 2026 Feb 2;11(1):14. doi: 10.1038/s41525-026-00550-7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Martin Zinkernagel, Prof. Dr. Dr. principal investigator
Department of Ophthalmology, Inselspital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Dry Eye Disease, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Martin Zinkernagel, Prof. Dr. Dr. (+41 31 632 95 65, martin.zinkernagel@insel.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ocular microbiome and local immune system in controls (time frame: At baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04658238, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2025.