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| Name | Class |
|---|---|
| University of Nebraska | OTHER |
| University of Utah | OTHER |
| University of California, Davis | OTHER |
| University of California, Los Angeles |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard of Care | Active Comparator | Patients enrolled in the trial and randomized to the standard of care (SOC) arm will undergo standard of care testing. |
|
| MDS | Experimental | Patients enrolled in the trial and randomized to the MDS arm will undergo standard of care testing and MDS testing. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metagenomic Deep Sequencing (MDS) | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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, | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Provider Certainty of Belief | Provider certainty of belief that the patient has an infection (continuous variable from 0 to 100%, 0% signifying uncertain and 100% signifying certain) | 4-week after randomization |
| Patient Quality of Life |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thuy Doan, MD, PhD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Francisco (UCSF) | San Francisco | California | 94158 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40653257 | Derived | Shantha JG, Moussa K, Laovirojjanakul W, Yeh S, Tsui E, Chen JL, Vitale AT, Shakoor A, Larochelle M, Niemeyer K, Mentreddy A, Livnat I, Safo M, Ao W, Choo C, Yan D, Zhong L, Chen C, Da Silva K, Reddy AK, Lee J, Sura A, Crowell EL, Qian Y, Sharon Y, Hinterwirth A, Porco T, Arnold BF, Gonzales J, Acharya NR, Lietman TM, Doan T; OPTICS Study Group. The Effect of Metagenomic Sequencing on Patient Clinical Outcomes for Intraocular Infections: A Multicenter Randomized Controlled Trial. Am J Ophthalmol. 2025 Nov;279:100-109. doi: 10.1016/j.ajo.2025.07.003. Epub 2025 Jul 11. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase I | Patients enrolled with presumed infectious inflammatory eye disease. |
| FG001 | Phase II: Standard of Care | Patients enrolled in the trial and randomized to the standard of care testing arm. |
| FG002 | Phase ll: Metagenomic Deep Sequencing (MDS) Testing | Patients enrolled in the trial and randomized to the MDS arm. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase 1 |
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| Phase 2 |
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Of the 21 patients that proceeded to Phase II of the study, 9 were randomized to receive MDS results and 12 were randomized to not receive MDS results.
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase I | Patients enrolled into Phase I. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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, | Dichotomous variable (Y/N) as assessed by a masked evaluator | One participant in the Standard of Care group was lost to follow-up post randomization. | Posted | Count of Participants | Participants | 4-week after randomization |
|
From enrollment until end of follow-up, 4 weeks after randomization.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase l | Patients enrolled with presumed infectious inflammatory eye disease. |
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79% of patients did not proceed to randomization. Participants were predominantly recruited in the U.S. and thus limited study interpretations to other geographic areas. Only patients with presumed infectious intraocular inflammation were assessed - the use of MDS for other types of ocular infections may require a different trial. Lastly, uveitis is a heterogeneous group of inflammatory diseases which can make clinical outcome assessment difficult when designing clinical trials.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thuy Doan | UCSF F. I. Proctor Foundation | 415-476-6939 | thuy.doan@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_ICF | Yes | No | Yes | Study Protocol and Informed Consent Form | Apr 22, 2022 | Sep 4, 2025 | Prot_ICF_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 5, 2024 | Sep 4, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D014605 | Uveitis |
| D003141 | Communicable Diseases |
| ID | Term |
|---|---|
| D014603 | Uveal Diseases |
| D005128 | Eye Diseases |
| D007239 | Infections |
| D020969 | Disease Attributes |
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| OTHER |
| Research to Prevent Blindness | OTHER |
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| Standard of Care (SOC) | Diagnostic Test | SOC includes any available diagnostic tests, such as Gram stain, cultures, PCRs, that are considered the appropriate testing based on the clinical findings. |
|
As measured by National Eye Institute Vision Function Questionnaire (min = 0, max = 100; higher means better vision function)
| 4-week after randomization |
| Comparative Sensitivity of the Physician, Conventional Diagnostics, and MDS Using Latent Class Analysis | 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. | Conclusion of study. 4 weeks after randomization. |
| Comparative Specificity of the Physician, Conventional Diagnostics, and MDS Using Latent Class Analysis | 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. | Conclusion of study. 4 weeks after randomization |
| NOT COMPLETED |
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Participants had the option to select more than 1 race and/or ethnicity. | Number | Participants |
|
Patients enrolled in the trial and randomized to the MDS arm will undergo standard of care testing and MDS testing.
|
|
|
| Primary | Appropriate Therapy | Dichotomous variable (Y/N) as determined by an independent expert panel | One participant in the Standard of Care group was lost to follow-up post randomization. | Posted | Count of Participants | Participants | 4-week after randomization |
|
|
|
|
| Secondary | Provider Certainty of Belief | Provider certainty of belief that the patient has an infection (continuous variable from 0 to 100%, 0% signifying uncertain and 100% signifying certain) | One participant in the Standard of Care group was lost to follow-up post randomization. | Posted | Median | Inter-Quartile Range | Percent | 4-week after randomization |
|
|
|
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| Secondary | Patient Quality of Life | As measured by National Eye Institute Vision Function Questionnaire (min = 0, max = 100; higher means better vision function) | Posted | Median | Inter-Quartile Range | Quality of Life composite score | 4-week after randomization |
|
|
|
|
| Secondary | Comparative Sensitivity of the Physician, Conventional Diagnostics, and MDS Using Latent Class Analysis | 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. | Posted | Number | 95% Confidence Interval | Percentage of Cases | Conclusion of study. 4 weeks after randomization. |
|
|
|
| Secondary | Comparative Specificity of the Physician, Conventional Diagnostics, and MDS Using Latent Class Analysis | 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. | Posted | Number | 95% Confidence Interval | Percentage of Cases | Conclusion of study. 4 weeks after randomization |
|
|
|
| 0 |
| 100 |
| 0 |
| 100 |
| 0 |
| 100 |
| EG001 | Phase ll: Standard of Care | Patients enrolled in the trial and randomized to the standard of care (SOC) arm will undergo standard of care testing. | 0 | 12 | 0 | 12 | 0 | 12 |
| EG002 | Phase ll: Metagenomic Deep Sequencing (MDS) Testing | Patients enrolled in the trial and randomized to the MDS arm will undergo standard of care testing and MDS testing. | 0 | 9 | 0 | 9 | 0 | 9 |
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| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Superiority |