Background:

- Uveitis is a general term describing a group of inflammatory diseases of the eye. The causes of uveitis are not fully understood. Researchers want to look at bacteria in the body that might be related to the inflammation. They will study the natural bacteria present in the gut and intestines of people with and without uveitis to understand their potential role in these diseases.

Objectives:

- To study the intestinal bacteria in people with and without uveitis or ocular inflammatory disease.

Eligibility:

• Individuals at least 18 years of age who have uveitis or ocular inflammatory disease.
• Individuals at least 18 years of age without uveitis or ocular inflammatory disease to serve as healthy controls.

Design:

• Participants may have more than one study visit (approximately 2-4) to assess possible changes in microbiome composition associated with treatment or disease activity.
• At each visit, participants will have a full eye examination, including vision and eye pressure tests. They will provide blood samples for testing. Participants will also be provided a stool collection kit to take home. The samples may be sent or brought back to the clinic.
• Treatment will not be provided as part of this study.

Objective: What precipitates ocular inflammatory episodes remains unknown, but a possible potentiating factor is the microbiome. The microbiome has become increasingly studied with the advent of new techniques, but these have not been applied to uveitis. We wish to evaluate microbiome composition in patients with the ocular inflammatory diseases uveitis who may be on standard therapy or receiving orally-administered tolerizing antigen therapy.

Study Population: A total of 200 participants may be enrolled in this study. Of those participants, the goal is to enroll 50 healthy controls and 150 with various types of uveitis.

Design: This is an observational, prospective, single-center study. Participants will receive a complete ocular examination with clinical testing as determined clinically and will provide stool and blood samples using a standardized method. Participants may have multiple visits and may provide multiple samples in order to evaluate changes in microbiota composition with disease status or treatment.

Outcome Measures: Alterations in bacterial diversity, microbiota composition and changes in relative abundance of various taxa or species will be analyzed between healthy volunteers and participants and between various types of uveitis. In addition, comparisons will be made between these findings and the immunome and metabolome.

• INCLUSION CRITERIA:

Inclusion Criteria for Uveitis Participants

1. Participant must be 18 years of age or older.

2. Participant must have a diagnosis of:

   Uveitis (or ocular inflammatory disorder)

3. Participant must be able to undergo slit lamp biomicroscopy.

4. Participant must understand and sign the protocol s informed consent document.

Inclusion Criteria for Healthy Volunteers

1. Participant must be 18 years of age or older.
2. Participant must be able to undergo slit lamp biomicroscopy.
3. Healthy controls will be age-and sex-matched individuals with no personal history of uveitis or other rheumatologic/autoimmune diseases (such as arthritis, inflammatory bowel disease, type 1 diabetes mellitus, psoriasis, Sjorgren s syndrome or multiple sclerosis) and no current use of corticosteroids, disease modifying antirheumatic drugs (DMARDs) including those with antibiotic properties (e.g., gold salts, sulfasalazine, hydroxychloroquine, minocycline) or any immunomodulatory drugs.
4. Participant must understand and sign the protocol s informed consent document.

EXCLUSION CRITERIA:

Exclusion Criteria for Uveitis Participants

1. Participants who are unable to provide informed consent.
2. Recent (<3 months prior) use of any antibiotic therapy
3. Current consumption of probiotics
4. Current extreme diet (parenteral nutrition, macrobiotic diet, etc.)
5. Known gastrointestinal (GI) tract neoplasm
6. Recent GI tract infection (gastroenteritis, colitis, diverticulitis, appendicitis) within the last month
7. Chronic unexplained diarrhea
8. Participant has or had a significant active infection (an infection requiring treatment as determined by the investigator) that required systemic antibiotic treatment within the past three months
9. Participant has any GI tract surgery leaving permanent residua (e.g., gastrectomy; bariatric surgery; colectomy)
10. Participant has inflammatory bowel disease (IBD)
11. Participant is pregnant or lactating.

Exclusion Criteria for Healthy Volunteers

1. Recent (<3 months prior) use of any antibiotic therapy
2. Current consumption of probiotics
3. Current extreme diet (parenteral nutrition, macrobiotic diet, etc.)
4. Known gastrointestinal (GI) tract neoplasm
5. Recent GI tract infection (gastroenteritis, colitis, diverticulitis, appendicitis) within the last month
6. Chronic unexplained diarrhea
7. Participant has or had a significant active infection (an infection requiring treatment as determined by the investigator) that required systemic antibiotic treatment within the past three months
8. Participant has any GI tract surgery leaving permanent residua (e.g., gastrectomy; bariatric surgery; colectomy)
9. Participant has inflammatory bowel disease (IBD)
10. Participant is pregnant or lactating.

200 participants: 150 with uveitis; 50 healthy controls