Assessment of the Ocular Microbiome in Health and Disease

The objective of this application is to illustrate the core constituents of the ocular surface microbiome, describe factors that promote colonization, and assess the ocular microbiome's role in the health of the anterior segment. We will conduct a prospective, observational cohort study, including a longitudinal analysis of the ocular microbiome in adults.

Study Overview

• Status: Recruiting
• Conditions: Eye Diseases; Microbial Colonization; Ophthalmopathy

Detailed Description

The microbiome is defined as a community of microbial organisms that reside in a specific host niche. There is a growing body of literature on the association between gut microbiome and disease entities such as inflammatory bowel disease, colon cancer and presumably an association that might influence response to treatment in some patients.

Recent data suggest the existence of a resident ocular microbiota that may play a protective role in corneal infections [1-4]. However, not much is known about the ocular microbiome and its association with disease or response to treatment. The National Eye Institute (NEI) recently hosted a symposium to discuss challenges to characterize the ocular microbiome and its role in promoting or preventing ocular diseases. One of the major challenges discussed is the lack of a normative population- based database describing the ocular microbiome.

In response the NEI as part of the Anterior segment initiative put out an RFA requesting proposals on methods of collection of biological samples and associated clinical data (e.g. demographic, residence, medications, allergies); processing of samples to extract analytes (e.g., DNA, RNA, protein, metabolites) and characterizing microorganisms in a low biomass niche, specifically the ocular surface using16S rRNA marker gene, whole metagenome sequencing (WMS), and metatranscriptomics approaches.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Amber Wren; Phone Number: 16153228920; Email: amber.wren@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Sapna Gangaputra, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

We anticipate there will be approximately 20% failure rate due to the low bacterial load in these samples and so we will have to collect more samples to account for the loss of data.

We estimate that 20 patients in each cohort of eyes with ocular disease - 100 total patients and 500 normal eyes will give us sufficient power to explore this topic.

Description

Inclusion Criteria:

We will include subjects who meet all of the following criteria:

• 18 years of age or older
• Provide informed consent
• Cohort A - normal eyes with no ocular disease
• Cohort B - primary open angle glaucoma/Ocular hypertension defined as mild glaucoma which is well controlled with no more than one drop of prostaglandin use daily for the past 6 months
• Cohort C - non-infectious keratopathy not using any prescription medication (OTC artificial tears are acceptable)
• Cohort D - Dry AMD (age related macular degeneration)
• Cohort E - Wet AMD
• Cohort F - diabetic retinopathy

Exclusion Criteria:

We will exclude subjects who meet all of the following criteria:

• Prior ocular disease either of the anterior or posterior segment
• Any medical comorbidities except well controlled DH and HTN
• Unable to follow up with study procedures as described

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort
Cohort A; normal eyes with no ocular disease
Cohort B; primary open angle glaucoma/Ocular hypertension defined as mild glaucoma which is well controlled with no more than one drop of prostaglandin use daily for the past 6 months
Cohort C; non-infectious keratopathy not using any prescription medication (OTC artificial tears are acceptable)
Cohort D; Dry AMD (age related macular degeneration)
Cohort E; Wet AMD
Cohort F; diabetic retinopathy, any stage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normal Ocular Microbiome	Number of patients in middle Tennessee with a normal ocular microbiome by development of a normative database.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole Metagenome Sequencing Methods	Number of ocular microbial species in different age and ethnic groups by the development of whole metagenome sequencing methods optimized for low biomass samples to characterize the ocular surface (anterior segment) microbiome.	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Novel Metatranscriptomics Analysis	Number of active microbial pathways and host epithelial gene expression profiles by novel metatranscriptomics analysis.	3 years

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: May 19, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 10, 2022

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: September 14, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Eye Diseases
• Other Study ID Numbers: 10001 (Disarm Therapeutics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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