Trial Summary
What is the purpose of this trial?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.
Is the treatment MDS, Standard of Care (SOC) a promising treatment for intraocular infections?Yes, MDS, Standard of Care (SOC) is a promising treatment for intraocular infections because it helps accurately identify the germs causing the infection, which is crucial for effective treatment and preventing blindness.13478
What safety data is available for metagenomic deep sequencing in intraocular infections?The provided research does not directly address safety data for metagenomic deep sequencing (MDS) in intraocular infections. The studies focus on the efficacy and diagnostic utility of MDS in identifying pathogens in intraocular infections, such as uveitis and endophthalmitis. They highlight the potential of MDS to accurately detect pathogens and provide actionable information for infectious disease management. However, specific safety data or adverse effects related to the use of MDS in these contexts are not discussed in the abstracts.12578
Do I have to stop taking my current medications for this trial?The trial protocol does not specify whether you need to stop taking your current medications. It is best to consult with the trial coordinators for specific guidance.
What data supports the idea that Deep Sequencing Test for Intraocular Infections is an effective treatment?The available research shows that Deep Sequencing Test for Intraocular Infections, also known as metagenomic deep sequencing (MDS), is effective because it can accurately detect pathogens in eye infections. This is important because about half of these infections are hard to diagnose with traditional methods. The studies highlight that MDS can identify both common and rare pathogens, which helps in providing the right treatment sooner. Compared to traditional methods, MDS has a higher success rate in finding the cause of the infection, which can lead to better outcomes for patients.16789
Eligibility Criteria
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.
I am suspected to have an eye infection after surgery.
Exclusion Criteria
I am unable to give consent by myself.
I am under 18 years old.
Treatment Details
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: MDSExperimental Treatment1 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 CareActive Control1 Intervention
Patients enrolled in the trial and randomized to the standard of care (SOC) arm will undergo standard of care testing.
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of California San Francisco (UCSF)San Francisco, CA
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Who is running the clinical trial?
University of California, San FranciscoLead Sponsor
University of California, Los AngelesCollaborator
University of UtahCollaborator
University of California, DavisCollaborator
University of NebraskaCollaborator
References
Illuminating uveitis: metagenomic deep sequencing identifies common and rare pathogens. [2023]Ocular infections remain a major cause of blindness and morbidity worldwide. While prognosis is dependent on the timing and accuracy of diagnosis, the etiology remains elusive in ~50 % of presumed infectious uveitis cases. The objective of this study is to determine if unbiased metagenomic deep sequencing (MDS) can accurately detect pathogens in intraocular fluid samples of patients with uveitis.
Genomics-Based Identification of Microorganisms in Human Ocular Body Fluid. [2019]Advances in genomics have the potential to revolutionize clinical diagnostics. Here, we examine the microbiome of vitreous (intraocular body fluid) from patients who developed endophthalmitis following cataract surgery or intravitreal injection. Endophthalmitis is an inflammation of the intraocular cavity and can lead to a permanent loss of vision. As controls, we included vitreous from endophthalmitis-negative patients, balanced salt solution used during vitrectomy and DNA extraction blanks. We compared two DNA isolation procedures and found that an ultraclean production of reagents appeared to reduce background DNA in these low microbial biomass samples. We created a curated microbial genome database (>5700 genomes) and designed a metagenomics workflow with filtering steps to reduce DNA sequences originating from: (i) human hosts, (ii) ambiguousness/contaminants in public microbial reference genomes and (iii) the environment. Our metagenomic read classification revealed in nearly all cases the same microorganism that was determined in cultivation- and mass spectrometry-based analyses. For some patients, we identified the sequence type of the microorganism and antibiotic resistance genes through analyses of whole genome sequence (WGS) assemblies of isolates and metagenomic assemblies. Together, we conclude that genomics-based analyses of human ocular body fluid specimens can provide actionable information relevant to infectious disease management.
Comparison of Intraocular Antibody Measurement, Quantitative Pathogen PCR, and Metagenomic Deep Sequencing of Aqueous Humor in Secondary Glaucoma Associated with Anterior Segment Uveitis. [2022]To identify viral pathogens in patients with secondary glaucoma associated with anterior segment uveitis and compare metagenomic deep sequencing (MDS) with enzyme-linked immunosorbent assay (ELISA) combined with Witmer-Desmonts coefficient (WDC) evaluation and real-time quantitative polymerase chain reaction (qPCR) on investigating pathogens in aqueous humor.
[Identification of pathogens in the vitreous of patients with infectious uveitis by metagenomic sequencing]. [2020]Objective: To investigate the role of metagenomic sequencing in the diagnosis of infectious uveitis. Methods: Cross-sectional study. A total of 19 vitreous specimens of patients with suspected infectious uveitis from March 2016 to July 2018 in Beijing Tongren Hospital were collected, including 8 males and 11 females, 19 to 68 years old. There were 10 cases in the right eye, 8 cases in the left eye and 1 case in both eyes. Acute retinal necrosis was clinically diagnosed in 8 patients (9 eyes), and the diagnosis was unknown in 11 patients (11 eyes). About 1 ml of the vitreous fluid was reserved for each specimen, 800 μl for metagenomic sequencing and 200 μl for real-time fluorescence quantitative PCR verification. The TIANamp Micro DNA Kit was used to extract the sample DNA for metagenomic sequencing, and the ultrasonic fragment was broken to 200-300 bp. The BGISEQ-500 platform was used for sequencing. The data with low quality and length less than 35 bp were cleared from the sequencing data to obtain high-quality data. Through biological authentication software, the reference human genome sequence and low complexity were removed from high-quality data. The data obtained were compared with a special microorganism database regarding the percentage of microbial sequences, the number of unique sequences, coverage and sequencing depth, so as to determine positive sequencing parameters, which were classified into bacteria, viruses, fungi and parasites. Real-time fluorescence quantitative PCR was performed to validate the accuracy. Results: A variety of microorganisms were detected by metagenomic sequencing in 19 specimens, including 3 cases of varicella zoster virus, 2 cases of Candida albicans, 1 case of Propionibacterium acnes and 1 case of Haemophilus parainfluenzae. The percentage of microbial sequences was 77.93% （1 794/2 302）, 99.98% （12 843/12 845） and 98.88%（5 733/5 798）, and the number of unique sequences was 1 794, 12 843 and 57 33 in varicella zoster virus cases, respectively. The verification of varicella zoster virus by PCR was consistent with that by metagenomic sequencing. Conclusion: Metagenomic sequencing can be used as an alternative method for laboratory diagnosis of infectious uveitis. (Chin J Ophthalmol, 2020, 56: 519-523).
A Genomic Approach to Investigating Ocular Surface Microorganisms: Monitoring Core Microbiota on Eyelid Margin with a Dot hybridization Assay. [2021]A sound ocular surface microbiota has been recognized as a part of ocular surface health following a growing body of evidence from next-generation sequencing technique and metagenomic analysis. However, even from the perspective of contemporary precision medicine, it is difficult to directly apply these new technologies to clinical practice. Therefore, we proposed a model based on dot hybridization assay (DHA) to bridge conventional culture with a metagenomic approach in investigating and monitoring ocular surface microbiota. Endophthalmitis, mostly caused by bacterial infection, is the most severe complication of many intraocular surgeries, such as cataract surgery. Hazardous microorganisms hiding and proliferating in the ocular surface microbiota not only increase the risk of endophthalmitis but also jeopardize the effectiveness of the preoperative aseptic procedure and postoperative topical antibiotics. The DHA model enables the simultaneous assessment of bacterial bioburden, detection of target pathogens and microorganisms, and surveillance of methicillin/oxacillin resistance gene mecA in the ocular surface microbiota. This assay revealed heavier bacterial bioburden in men, compatible with a higher risk of endophthalmitis in male patients who underwent cataract surgery. No occurrence of endophthalmitis for these patients was compatible with non-hazardous microorganisms identified by specific dots for target pathogens. Moreover, the mecA dot detected oxacillin-resistant strains, of which culture failed to isolate. Therefore, the DHA model could provide an alternative genomic approach to investigate and monitor ocular surface microorganisms in clinical practice nowadays.
Impact of Sample Collection Order on the Diagnostic Performance of Metagenomic Deep Sequencing for Infectious Keratitis. [2023]The purpose of this article was to evaluate the impact of sample collection order on the diagnostic yield of metagenomic deep sequencing (MDS) for determining the causative pathogen in infectious keratitis.
METAGENOMIC NEXT-GENERATION SEQUENCING DETECTS PATHOGENS IN ENDOPHTHALMITIS PATIENTS. [2022]To investigate the utility of metagenomic next-generation sequencing (mNGS) in identifying the pathogens in endophthalmitis.
Application of metagenomic next-generation sequencing in suspected intraocular infections. [2023]To evaluate the efficacy of metagenomic next-generation sequencing (mNGS) and to explore its value in the diagnosis of intraocular infection.
IDENTIFICATION OF PATHOGENS IN THE INTRAOCULAR FLUID SAMPLES OF PATIENTS WITH ENDOGENOUS ENDOPHTHALMITIS USING RAPID NANOPORE TARGETED SEQUENCING. [2023]Nanopore targeted sequencing showed a higher positivity rate and a shorter turnaround time than did traditional culture in identifying pathogens in the intraocular fluid samples of patients with endogenous endophthalmitis.