Deep Sequencing Test for Intraocular Infections

(OPTICS Trial)

Overseen By Jessica Shantha, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Disqualifiers: Pregnancy, Age < 18, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new test, metagenomic deep sequencing (MDS), can improve outcomes for people with certain eye infections compared to usual testing methods. Participants will receive either the MDS test along with standard tests or only the standard tests to guide their treatment. The study will assess whether participants receive the correct treatment and if their eye condition improves. Individuals dealing with specific types of eye inflammation or infections, such as uveitis or post-surgery eye infections, may be suitable for this study. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could enhance future diagnostic methods for eye infections.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What prior data suggests that metagenomic deep sequencing is safe for intraocular infections?

Research shows that metagenomic deep sequencing (MDS) helps diagnose difficult eye infections. Studies indicate that MDS has led to better health outcomes for some patients with these infections. No reports have shown MDS causing harm, suggesting it is quite safe. MDS allows doctors to identify infections more accurately, leading to better treatment options. This technique is a new tool in the fight against eye infections and appears effective without causing problems for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the potential of deep sequencing tests for diagnosing intraocular infections. Unlike the standard of care, which typically relies on culturing pathogens—a process that can be slow and sometimes inconclusive—deep sequencing offers a faster and potentially more comprehensive way to identify infectious agents. This method can detect a wide array of pathogens by analyzing their genetic material, even if they are present in very low quantities. The hope is that this approach could lead to quicker, more accurate diagnoses, enabling timely and targeted treatments for patients.

What evidence suggests that this trial's treatments could be effective for intraocular infections?

Research has shown that metagenomic deep sequencing (MDS), which participants in this trial may receive, serves as a powerful tool for diagnosing complex eye infections. Studies have found that MDS can detect unusual germs in eye fluid samples that other tests might miss, enabling doctors to choose better treatments more quickly. In some cases, patients who received MDS results experienced modest health improvements. MDS proves especially helpful when the infection doesn't seem typical, allowing doctors to better understand the situation. Participants in the trial will be randomized to either the MDS arm or the standard of care (SOC) arm, with those in the SOC arm undergoing standard testing procedures. ^{3 6 7 8 9}

Who Is on the Research Team?

Thuy Doan, MD PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 with suspected infectious uveitis or post-operative endophthalmitis, which are types of eye infections. It's not suitable for those who can't consent, don't have enough specimen for MDS testing, are under 18, or are pregnant.

Inclusion Criteria

I have an eye infection affecting the front, middle, back, or all parts of my eye.

Unilateral or bilateral

I am suspected to have an eye infection after surgery.

Exclusion Criteria

Insufficient specimen for MDS

I am unable to give consent by myself.

I am under 18 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomization and Initial Follow-up

Participants are randomized to receive MDS testing results or not, followed by initial follow-up visits

3-6 weeks

Visits at week 2 and week 3-6

Follow-up

Participants are monitored for safety and effectiveness after randomization

4 weeks

Visit at 4 weeks after randomization

What Are the Treatments Tested in This Trial?

Interventions

• MDS
• Standard of Care (SOC)

Trial Overview The study compares the effectiveness of Metagenomic Deep Sequencing (MDS) to standard tests in improving treatment outcomes for eye infections. Participants will be randomly assigned to either receive MDS test results or not alongside regular care.

How Is the Trial Designed?

Group I: MDS Experimental Treatment 1 Intervention

Patients enrolled in the trial and randomized to the MDS arm will undergo standard of care testing and MDS testing.

Group II: Standard of Care Active Control 1 Intervention

Patients enrolled in the trial and randomized to the standard of care (SOC) arm will undergo standard of care testing.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

University of California, Davis

Collaborator

Trials

958

Recruited

4,816,000+

University of Nebraska

Collaborator

Trials

563

Recruited

1,147,000+

Published Research Related to This Trial

The dot hybridization assay (DHA) model allows for effective monitoring of ocular surface microbiota, helping to identify hazardous microorganisms that could lead to endophthalmitis, particularly in male patients undergoing cataract surgery.

The DHA model can detect antibiotic resistance genes, such as mecA, in bacteria that traditional culture methods might miss, enhancing the ability to prevent infections and improve surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Genomic Approach to Investigating Ocular Surface Microorganisms: Monitoring Core Microbiota on Eyelid Margin with a Dot hybridization Assay. Kuo, MT., Chao, TL., Kuo, SF., et al.[2021]

In a study of 31 patients with secondary glaucoma linked to anterior segment uveitis, viral pathogens were identified in 61.3% of cases using real-time qPCR and WDC evaluation, highlighting the role of viruses like HCMV and VZV in this condition.

Metagenomic deep sequencing (MDS) successfully detected HCMV DNA in three patients, suggesting that MDS could be a valuable tool for diagnosing intraocular viral infections in secondary glaucoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Intraocular Antibody Measurement, Quantitative Pathogen PCR, and Metagenomic Deep Sequencing of Aqueous Humor in Secondary Glaucoma Associated with Anterior Segment Uveitis. Wang, L., Wang, Z., Ma, J., et al.[2022]

In a study of 15 patients with suspected intraocular infections, metagenomic next-generation sequencing (mNGS) successfully identified pathogens in 8 samples, confirming its efficacy in diagnosing these infections.

Despite 7 samples returning negative mNGS results, 4 were still diagnosed with intraocular infections through clinical evaluation and other tests, highlighting the need for optimized mNGS protocols to better detect intracellular pathogens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of metagenomic next-generation sequencing in suspected intraocular infections. Qian, Z., Zhang, Y., Wang, L., et al.[2023]

Nanopore targeted sequencing (NTS) identified pathogens in 89.28% of intraocular fluid samples from 27 patients with endogenous endophthalmitis, significantly outperforming traditional microbial culture, which detected pathogens in only 35.71% of samples (P < 0.001).

NTS provided results much faster, with an average detection time of just 1.11 days compared to 2.50 days for microbial culture, and it was particularly effective in identifying fungal infections, showing a positivity rate of 46.43% versus 7.14% for culture (P = 0.002).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IDENTIFICATION OF PATHOGENS IN THE INTRAOCULAR FLUID SAMPLES OF PATIENTS WITH ENDOGENOUS ENDOPHTHALMITIS USING RAPID NANOPORE TARGETED SEQUENCING. Hao, X., Wang, M., Yuan, M., et al.[2023]

Unbiased metagenomic deep sequencing (MDS) effectively detected pathogens in intraocular fluid samples from patients with uveitis, accurately identifying known pathogens like Cryptococcus neoformans and Toxoplasma gondii, as well as a previously unknown rubella virus infection in one patient.

The study suggests that MDS can reveal chronic infections in the eye, highlighting its potential as a diagnostic tool for ocular infections that are often difficult to identify, which could improve treatment outcomes and understanding of pathogen reservoirs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Illuminating uveitis: metagenomic deep sequencing identifies common and rare pathogens. Doan, T., Wilson, MR., Crawford, ED., et al.[2023]

This study highlights the potential of genomics to improve the diagnosis of endophthalmitis by analyzing the microbiome of vitreous fluid from patients, which could lead to better management of this serious eye condition.

By developing a metagenomics workflow and a curated microbial genome database, the researchers were able to accurately identify microorganisms and their antibiotic resistance genes, providing critical information for treating infections effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomics-Based Identification of Microorganisms in Human Ocular Body Fluid. Kirstahler, P., Bjerrum, SS., Friis-Møller, A., et al.[2019]

Metagenomic next-generation sequencing (mNGS) identified pathogens in 88.89% of endophthalmitis cases, significantly outperforming traditional culture methods, which only had a positive rate of 27.78%.

mNGS not only detected common pathogens like Staphylococcus epidermidis and Klebsiella pneumoniae but also revealed antibiotic resistance genes in 9 cases, highlighting its potential for improving treatment strategies and understanding visual prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

METAGENOMIC NEXT-GENERATION SEQUENCING DETECTS PATHOGENS IN ENDOPHTHALMITIS PATIENTS. Zhu, J., Xia, H., Tang, R., et al.[2022]

Metagenomic sequencing successfully identified a variety of microorganisms in 19 vitreous specimens from patients with suspected infectious uveitis, including varicella zoster virus and Candida albicans, demonstrating its efficacy in diagnosing complex infections.

The results from metagenomic sequencing were validated by real-time PCR, confirming its reliability as an alternative diagnostic method for infectious uveitis, which could enhance patient management and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Identification of pathogens in the vitreous of patients with infectious uveitis by metagenomic sequencing]. Zhang, MX., Peng, XY., Hu, F., et al.[2020]

Metagenomic deep sequencing (MDS) was able to identify pathogens in 76% of subjects with infectious keratitis, showing a high diagnostic yield compared to traditional culture methods, which had a 74% agreement with MDS results.

The order of sample collection did not affect the overall yield of MDS; however, collecting MDS samples after other diagnostic tests reduced the agreement with culture results, suggesting potential contamination issues or differences in sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Sample Collection Order on the Diagnostic Performance of Metagenomic Deep Sequencing for Infectious Keratitis. Redd, TK., Lalitha, P., Prajna, NV., et al.[2023]

Citations

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Metagenomic next-generation sequencing Results. The study included three patients with novel presentations of intraocular infections, manifesting with atypical clinical manifestations ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41139156/

a game-changer in the diagnosis of unique intraocular ... Metagenomic next-generation sequencing has an important role in the diagnosis of challenging intraocular infections.

3. ajo.com ajo.com/article/S0002-9394(25)00350-2/fulltext

The Effect of Metagenomic Sequencing on Patient Clinical ... Having access to metagenomic sequencing results modestly improved clinical outcomes in a subset of patients with suspected intraocular ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002939425003502

The Effect of Metagenomic Sequencing on Patient Clinical ... Having access to metagenomic sequencing results modestly improved clinical outcomes in a subset of patients with suspected intraocular ...

5. genomemedicine.biomedcentral.com genomemedicine.biomedcentral.com/articles/10.1186/s13073-016-0344-6

Illuminating uveitis: metagenomic deep sequencing identifies ... The objective of this study is to determine if unbiased metagenomic deep sequencing (MDS) can accurately detect pathogens in intraocular fluid samples of ...

6. frontiersin.org frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.940818/full

Clinical Metagenomic Next-Generation Sequencing for ... We compared the sensitivity and specificity of qPCR and Metagenomic Next-Generation Sequencing (mNGS) in the aqueous humor of patients with suspected CMV ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41139156/?utm_source=FeedFetcher&utm_medium=rss&utm_campaign=None&utm_content=10MSL6XygFtCE0XpaQpog-pEt8342fXkY9lzrR7q6H0wVRyEa2&fc=None&ff=20251026072217&v=2.18.0.post22+67771e2

a game-changer in the diagnosis of unique intraocular ... Metagenomic next-generation sequencing has an important role in the diagnosis of challenging intraocular infections.

8. mdpi.com mdpi.com/1999-4915/17/6/757

Metagenomic Next-Generation Sequencing for the ... Infectious uveitis is a serious intraocular inflammatory condition that can cause severe vision impairment and blindness if not promptly identified and treated.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40653257/

The Effect of Metagenomic Sequencing on Patient Clinical ... Conclusions: Having access to metagenomic sequencing results modestly improved clinical outcomes in a subset of patients with suspected ...