Infectious Disease, Uveitis
Conditions
Keywords
Uveitis, Metagenomic deep sequencing, Intraocular infection, MDS
Brief summary
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.
Interventions
DEVICEMetagenomic Deep Sequencing (MDS)
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.
DIAGNOSTIC_TESTStandard of Care (SOC)
SOC includes any available diagnostic tests, such as Gram stain, cultures, PCRs, that are considered the appropriate testing based on the clinical findings.
Sponsors
University of California, San Francisco
University of Nebraska
University of Utah
University of California, Davis
University of California, Los Angeles
Research to Prevent Blindness
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Improvement 2-step Decrease in the Level of Inflammation or Decrease to Grade 0; Inflammatory Retinal/Choroidal Lesions Reducing in Size; 20% Improvement of CST on Optical Coherence Tomography, a > 10- Letter Improvement in Visual Acuity, | 4-week after randomization | Dichotomous variable (Y/N) as assessed by a masked evaluator |
| Appropriate Therapy | 4-week after randomization | Dichotomous variable (Y/N) as determined by an independent expert panel |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Provider Certainty of Belief | 4-week after randomization | Provider certainty of belief that the patient has an infection (continuous variable from 0 to 100%, 0% signifying uncertain and 100% signifying certain) |
| Patient Quality of Life | 4-week after randomization | As measured by National Eye Institute Vision Function Questionnaire (min = 0, max = 100; higher means better vision function) |
| Comparative Sensitivity of the Physician, Conventional Diagnostics, and MDS Using Latent Class Analysis | Conclusion of study. 4 weeks after randomization. | Latent Class Analysis (LCA) was used to estimate the sensitivity of three diagnostic approaches: (1) clinical diagnosis by the treating physician at presentation, (2) conventional diagnostics, and (3) MDS. LCA was performed on all randomized participants with infection status, evaluating the diagnostic performance of treating physicians, conventional diagnostics, and MDS. A total of 100 participants were enrolled in Phase l of the OPTICS trial. |
| Comparative Specificity of the Physician, Conventional Diagnostics, and MDS Using Latent Class Analysis | Conclusion of study. 4 weeks after randomization | Latent Class Analysis (LCA) was used to estimate the specificity of three diagnostic approaches: (1) clinical diagnosis by the treating physician at presentation, (2) conventional diagnostics, and (3) MDS. LCA was performed on all randomized participants with infection status, evaluating the diagnostic performance of treating physicians, conventional diagnostics, and MDS. A total of 100 participants were enrolled in Phase l of the OPTICS trial. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORThuy Doan, MD, PhD
University of California, San Francisco
Participant flow
Recruitment details
Participants with presumed intraocular infection were enrolled at 6 sites: University of California, San Francisco; University of California, Los Angeles; University of California, Davis; University of Utah; University of Nebraska Medical Center; Khon Kaen University. Recruitment took place from May 2022 through January 2024.
Pre-assignment details
The trial involved two phases with two distinct inclusion criteria. Participants moved onto phase II, where they were randomized to two arms, if they met the following inclusion criteria: active inflammation in at least one eye and/or active retinal or choroidal inflammation and/or macular edema. Participants were excluded from randomization if: pathogen identified that was consistent with clinical findings, complete resolution of inflammation, or no light perception (NLP) vision.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62.0 years |
| Race/Ethnicity, Customized African American, African, or Afro-Caribbean | 9 Participants |
| Race/Ethnicity, Customized Asian | 26 Participants |
| Race/Ethnicity, Customized Caucasian | 45 Participants |
| Race/Ethnicity, Customized Hispanic ethnicity | 21 Participants |
| Sex: Female, Male Female | 57 Participants |
| Sex: Female, Male Male | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 100 | 0 / 12 | 0 / 9 |
| other Total, other adverse events | 0 / 100 | 0 / 12 | 0 / 9 |
| serious Total, serious adverse events | 0 / 100 | 0 / 12 | 0 / 9 |
Outcome results
None listed