Ocular Pathogen and Transcriptome Investigation Using Comprehensive Sequencing

Study Overview
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Brief Summary
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This is a multi-center randomized controlled evaluator-masked trial designed to compare metagenomic deep sequencing (MDS) versus standard of care testing for improvement of outcomes for intraocular infections. Patients with presumed intraocular infections who meet the eligibility criteria will be randomized to receive MDS testing results or not to receive MDS testing results. All patients will receive standard-of-care testing to guide management. Enrolled patients will be followed at week 2, week 3-6 (randomization visit), and at 4 weeks after the randomization visit. The proportions of patients who received the appropriate therapy and the proportions of patients with improved outcome will be compared between arms. Patient quality of life, MDS performance, and the provider certainly of belief will be collected.

Official Title
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Ocular Pathogen and Transcriptome Investigation Using Comprehensive Sequencing

Conditions
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Uveitis, Infectious Disease

Intervention / Treatment
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* Device: Metagenomic Deep Sequencing (MDS)
* Diagnostic Test: Standard of Care (SOC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presumed infectious anterior uveitis, or intermediate uveitis, or posterior uveitis, or panuveitis Presumed post-operative endophthalmitis Unilateral or bilateral 18 years and older Exclusion Criteria: Insufficient specimen for MDS Age < 18 years of age Pregnancy Unable to consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care<br>Patients enrolled in the trial and randomized to the standard of care (SOC) arm will undergo standard of care testing. | Diagnostic Test: Standard of Care (SOC)<br>* SOC includes any available diagnostic tests, such as Gram stain, cultures, PCRs, that are considered the appropriate testing based on the clinical findings.<br>|
| Experimental: MDS<br>Patients enrolled in the trial and randomized to the MDS arm will undergo standard of care testing and MDS testing. | Device: Metagenomic Deep Sequencing (MDS)<br>* MDS is an RNA-seq based testing of ocular fluid or tissue to identify potential infectious pathogens including bacteria, fungi, parasites, and DNA and RNA viruses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical improvement | Dichotomous variable (Y/N) as assessed by a masked evaluator | 4-week after randomization | 
| Appropriate therapy | Dichotomous variable (Y/N) as determined by an independent expert panel | 4-week after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Provider certainty of belief | Provider certainty of belief that the patient has an infection (continuous variable from 0 to 100%) | 4-week after randomization | 
| Patient quality of life | As measured by National Eye Institute Vision Function Questionnaire (min = 0, max = 100; higher means better vision function) | 4-week after randomization | 
| Infection status | Estimated through latent class analysis that compares MDS with traditional tests for presumed ocular infections. Sensitivity and specificity will be reported as percentage (%) | 4-week after randomization | 
| Provider quality of care | As measured by the World Health Organization Quality of Life Abbreviated Questionnaire (min = 0, max = 100; higher means better quality of life). | 4-week after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDS, Uveitis, Metagenomic deep sequencing, Intraocular infection