Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review

Pardo, Isabele; Finamor, Luciana P. S.; Marra, Pedro S.; Ferreira, Julia Messina G.; Gutfreund, Maria Celidonio; Hsieh, Mariana Kim; Li, Yimeng; Pinho, João Renato Rebello; Rizzo, Luiz Vicente; Kobayashi, Takaaki; Diekema, Daniel J.; Edmond, Michael B.; Bispo, Paulo J. M.; Marra, Alexandre R.

doi:10.3390/v17060757

Open AccessReview

Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review

by

Isabele Pardo

^1,*

,

Luciana P. S. Finamor

²,

Pedro S. Marra

³

,

Julia Messina G. Ferreira

⁴,

Maria Celidonio Gutfreund

¹,

Mariana Kim Hsieh

⁵

,

Yimeng Li

³

,

João Renato Rebello Pinho

^1,6

,

Luiz Vicente Rizzo

⁴,

Takaaki Kobayashi

^7,8,

Daniel J. Diekema

⁷,

Michael B. Edmond

⁹

,

Paulo J. M. Bispo

¹⁰ and

Alexandre R. Marra

^1,7

¹

Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, Brazil

²

Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo 05508-090, SP, Brazil

³

University of California San Francisco, San Francisco, CA 94143, USA

⁴

Hospital Israelita Albert Einstein, Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo 05652-900, SP, Brazil

⁵

The Program of Hospital Epidemiology, University of Iowa Health Care, Iowa City, IA 52242, USA

⁶

LIM03/07, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, SP, Brazil

⁷

Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA

⁸

Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, KY 40536-0298, USA

⁹

Department of Medicine, School of Medicine, West Virginia University, Morgantown, WV 26506-9111, USA

¹⁰

Department of Ophthalmology, Harvard Medical School, Infectious Disease Institute, Massachusetts Eye and Ear, Boston, MA 02114, USA

^*

Author to whom correspondence should be addressed.

Viruses 2025, 17(6), 757; https://doi.org/10.3390/v17060757

Submission received: 18 April 2025 / Revised: 17 May 2025 / Accepted: 20 May 2025 / Published: 26 May 2025

(This article belongs to the Special Issue Ocular Diseases in Viral Infection)

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Abstract

Background: Infectious uveitis is a potentially sight-threatening condition that requires timely and accurate pathogen identification to guide effective therapy. However, conventional microbiological tests (CMTs) often lack sensitivity and the inclusiveness of pathogen detection. Metagenomic next-generation sequencing (mNGS) offers an unbiased approach to detecting a broad range of pathogens. This review evaluates its diagnostic performance in detecting infectious uveitis. Methods: A systematic search across multiple databases identified studies assessing the use of mNGS for diagnosing infectious uveitis. The included studies compared mNGS to CMTs, including polymerase chain reaction (PCR), culture, serology, and the IGRA (Interferon-Gamma Release Assay). The study characteristics; the detection rates; and the sensitivity, specificity, and predictive values were extracted. The sensitivity and specificity of mNGS were calculated using CMTs as a reference. Results: Twelve studies comprising 859 patients were included. The sensitivity of mNGS compared to that of CMTs ranged from 38.4% to 100%, while specificity varied between 15.8% and 100%. The commonly detected pathogens included varicella-zoster virus, cytomegalovirus, Toxoplasma gondii, and herpes simplex virus. In some cases, mNGS outperformed PCR in viral detection, aiding diagnosis when the standard methods failed. However, contamination risks and inconsistent diagnostic thresholds were noted. Conclusions: mNGS enables the diagnosis of infectious uveitis, particularly for viral causes, but its variable performance and standardization challenges warrant further investigation.

Keywords: systematic literature review; metagenomic NGS; infectious uveitis; diagnostic methods

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MDPI and ACS Style

Pardo, I.; Finamor, L.P.S.; Marra, P.S.; Ferreira, J.M.G.; Gutfreund, M.C.; Hsieh, M.K.; Li, Y.; Pinho, J.R.R.; Rizzo, L.V.; Kobayashi, T.; et al. Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review. Viruses 2025, 17, 757. https://doi.org/10.3390/v17060757

AMA Style

Pardo I, Finamor LPS, Marra PS, Ferreira JMG, Gutfreund MC, Hsieh MK, Li Y, Pinho JRR, Rizzo LV, Kobayashi T, et al. Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review. Viruses. 2025; 17(6):757. https://doi.org/10.3390/v17060757

Chicago/Turabian Style

Pardo, Isabele, Luciana P. S. Finamor, Pedro S. Marra, Julia Messina G. Ferreira, Maria Celidonio Gutfreund, Mariana Kim Hsieh, Yimeng Li, João Renato Rebello Pinho, Luiz Vicente Rizzo, Takaaki Kobayashi, and et al. 2025. "Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review" Viruses 17, no. 6: 757. https://doi.org/10.3390/v17060757

APA Style

Pardo, I., Finamor, L. P. S., Marra, P. S., Ferreira, J. M. G., Gutfreund, M. C., Hsieh, M. K., Li, Y., Pinho, J. R. R., Rizzo, L. V., Kobayashi, T., Diekema, D. J., Edmond, M. B., Bispo, P. J. M., & Marra, A. R. (2025). Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review. Viruses, 17(6), 757. https://doi.org/10.3390/v17060757

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Metagenomic Next-Generation Sequencing for the Diagnosis of Infectious Uveitis: A Comprehensive Systematic Review

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