Diagnosis and biomarkers for ocular tuberculosis: From the present into the future

Zhang Ludi, Ashita Ashish Sule, Ramar Perumal Samy, Ikhwanuliman Putera, Benjamin Schrijver, Paul Edward Hutchinson, Jayantha Gunaratne, Indu Verma, Amit Singhal, Rina La DIstia Nora, P. Martin Van Hagen, Willem A. Dik, Vishali Gupta, Rupesh Agrawal*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

8 Citations (Scopus)
21 Downloads (Pure)

Abstract

Tuberculosis is an airborne disease caused by Mycobacterium tuberculosis (Mtb) and can manifest both pulmonary and extrapulmonary disease, including ocular tuberculosis (OTB). Accurate diagnosis and swift optimal treatment initiation for OTB is faced by many challenges combined with the lack of standardized treatment regimens this results in uncertain OTB outcomes. The purpose of this study is to summarize existing diagnostic approaches and recently discovered biomarkers that may contribute to establishing OTB diagnosis, choice of anti-tubercular therapy (ATT) regimen, and treatment monitoring. The keywords ocular tuberculosis, tuberculosis, Mycobacterium, biomarkers, molecular diagnosis, multi-omics, proteomics, genomics, transcriptomics, metabolomics, T-lymphocytes profiling were searched on PubMed and MEDLINE databases. Articles and books published with at least one of the keywords were included and screened for relevance. There was no time limit for study inclusion. More emphasis was placed on recent publications that contributed new information about the pathogenesis, diagnosis, or treatment of OTB. We excluded abstracts and articles that were not written in the English language. References cited within the identified articles were used to further supplement the search. We found 10 studies evaluating the sensitivity and specificity of interferon-gamma release assay (IGRA), and 6 studies evaluating that of tuberculin skin test (TST) in OTB patients. IGRA (Sp = 71-100%, Se = 36-100%) achieves overall better sensitivity and specificity than TST (Sp = 51.1-85.7%; Se = 70.9-98.5%). For nuclear acid amplification tests (NAAT), we found 7 studies on uniplex polymerase chain reaction (PCR) with different Mtb targets, 7 studies on DNA-based multiplex PCR, 1 study on mRNA-based multiplex PCR, 4 studies on loop-mediated isothermal amplification (LAMP) assay with different Mtb targets, 3 studies on GeneXpert assay, 1 study on GeneXpert Ultra assay and 1 study for MTBDRplus assay for OTB. Specificity is overall improved but sensitivity is highly variable for NAATs (excluding uniplex PCR, Sp = 50-100%; Se = 10.5-98%) as compared to IGRA. We also found 3 transcriptomic studies, 6 proteomic studies, 2 studies on stimulation assays, 1 study on intraocular protein analysis and 1 study on T-lymphocyte profiling in OTB patients. All except 1 study evaluated novel, previously undiscovered biomarkers. Only 1 study has been externally validated by a large independent cohort. Future theranostic marker discovery by a multi-omics approach is essential to deepen pathophysiological understanding of OTB. Combined these might result in swift, optimal and personalized treatment regimens to modulate the heterogeneous mechanisms of OTB. Eventually, these studies could improve the current cumbersome diagnosis and management of OTB.

Original languageEnglish
Pages (from-to)2088-2113
Number of pages26
JournalTheranostics
Volume13
Issue number7
DOIs
Publication statusPublished - 2023

Bibliographical note

Funding Information:
RA is supported by a grant from the National Medical Research Council (NMRC) by Ministry of Health, Singapore, for the Clinician Scientist Award (CSA) from 2020 to 2023. He has not received funding for his work in this publication. AS is supported by A*STAR ID Labs. RLDN is supported by a grant from RisetInovatifProduktif - Lembaga Pengelola Dana Pendidikan (RISPRO LPDP). The open access publication of this study is supported by Riset Inovatif Produktif - Lembaga Pengelola Dana Pendidikan (RISPRO LPDP) grant number: RISPRO/KI/B1/KOM/5/15219/2020.

Funding Information:
RA is supported by a grant from the National Medical Research Council (NMRC) by Ministry of Health, Singapore, for the Clinician Scientist Award (CSA) from 2020 to 2023. He has not received funding for his work in this publication. AS is supported by A*STAR ID Labs. RLDN is supported by a grant from RisetInovatifProduktif – Lembaga Pengelola Dana Pendidikan (RISPRO LPDP).

Funding Information:
The open access publication of this study is supported by Riset Inovatif Produktif – Lembaga Pengelola Dana Pendidikan (RISPRO LPDP) grant number: RISPRO/KI/B1/KOM/5/15219/2020.

Publisher Copyright:
© The author(s).

Fingerprint

Dive into the research topics of 'Diagnosis and biomarkers for ocular tuberculosis: From the present into the future'. Together they form a unique fingerprint.

Cite this