Normalised quantitative polymerase chain reaction for diagnosis of tuberculosis-associated uveitis

Barik, Manas Ranjan; Rath, Soveeta; Modi, Rohit Ramesh; Rana, Rajkishori; Reddy, Mamatha M.; Basu, Soumyava

doi:10.1016/j.tube.2018.03.005

Cited by 10 publications

(6 citation statements)

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“…Furthermore, the difficulty of culturing mycobacteria and the limitations of molecular diagnostic tests from No. and virulence of bacilli x allergy Resistance ocular fluid samples [74], present a challenge in clearly delineating infection and immunemediated mechanisms at a given time point, in the course of disease. Despite these limitations, data from experimental animal models and more recently, from human OTB can provide useful insights into the existence of the indirect mechanisms.…”

Section: Lesion Is Directly Proportional Tomentioning

confidence: 99%

Pathogenesis of ocular tuberculosis: New observations and future directions

2020

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Ocular tuberculosis (OTB) encompasses all forms of intra-and extra-ocular inflammation associated with Mycobacterium tuberculosis (Mtb) infection. However, the organism is rarely found in ocular fluid samples of diseased eyes, rendering the pathomechanisms of the disease unclear. This confounds clinical decision-making in diagnosis and treatment of OTB.Here, we critically review existing human and animal data related to ocular inflammation and TB pathogenesis to unravel likely pathomechanisms of OTB. Broadly there appear to be two fundamental mechanisms that may underlie the development of TB-associated ocular inflammation: a. inflammatory response to live/ replicating Mtb in the eye, and b. immune mediated ocular inflammation induced by non-viable Mtb or its components in the eye. This distinction is significant as in direct Mtb-driven mechanisms, diagnosis and treatment would be aimed at detection of Mtb-infection and its elimination; while indirect mechanisms would primarily require anti-inflammatory therapy with adjunctive anti-TB therapy. Further, we discuss how that most clinical phenotypes of OTB likely represent a combination of both mechanisms, with one being predominant than the other.

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Section: Lesion Is Directly Proportional Tomentioning

confidence: 99%

Pathogenesis of ocular tuberculosis: New observations and future directions

2020

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“…Interpretation of the results of molecular assays to detect miliary tuberculosis (MTB) DNA from ocular fluids is thus challenging. Barik et al 25 have offered a novel solution to rule out cases with bystander MTB DNA by normalizing the MTB DNA copy numbers to the host genome copy numbers. They propose a cut-off value of this ratio and suggest that cases having a higher ratio only have significant MTB DNA in ocular fluids to cause tubercular uveitis and cases with a lower cut-off value might be only having bystander MTB DNA.…”

Section: Discussionmentioning

confidence: 99%

Tubercular DNA PCR of ocular fluids and blood in cases of presumed ocular tuberculosis: a pilot study

Chawla

Singh

et al. 2022

Ophthalmol Eye Dis

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Background: The definitive diagnosing of ocular tuberculosis (TB) is difficult; therefore, there is a need of better understanding of investigating TB DNA in presumed ocular TB patients. Objectives: The aim of this study is to correlate tubercular DNA PCR of aqueous/vitreous and blood in cases of presumed ocular TB. Design: A prospective study. Methods: DNA was extracted from aqueous of cases of choroidal tuberculoma (group 1) and serpiginous choroiditis (group 2) and from vitreous of cases of vasculitis (group 3) and macular hole/retinal detachment (group 4). Gel-based PCR and real-time PCR amplification were performed using IS6110 primer on ocular fluids. The same was also performed on the blood samples of cases in which tubercular DNA was detected in the ocular fluids. Results: Overall, 31 cases were analysed in our study. Tubercular DNA was detected in ocular fluids of seven cases: group 1, two cases (67%); group 2, one case (17%); group 3, four cases (27%); and no case of group 4. Blood samples of six of these seven patients were positive for tubercular DNA. Of these six patients, four had evidence of systemic TB and were on ATT. Two cases had no evidence of active systemic TB, yet PCR was positive from blood and ocular fluids. Conclusion: Tubercular DNA detected from ocular fluids may possibly be due to bystander DNA and may not indicate primary ocular tubercular infection. Thus, caution must be exercised prior to labelling a case of uveitis as being tubercular based on the results of molecular assays on ocular fluids alone. The results of PCR on ocular fluids should be correlated with PCR on blood and systemic findings.

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“…(Mohan et al, 2014;Sudheer et al, 2018). Thus, the presence of MTb could not directly attribute to the clinical manifestation as an inflammatory load of aqueous/vitreous samples increase the probability of so-called "bystander" MTb DNA, especially in an endemic setting (Barik et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, experts agreed to start ATT based on several criteria, not merely depend on Mtb found in the ocular samples (Agarwal et al, 2019a;Agrawal et al, 2020;Testi et al, 2020). The sensitivity and specificity of PCR from ocular samples often being calculated back using the clinical diagnosis of presumptive ocular TB (Barik et al, 2018).…”

Section: Introductionmentioning

confidence: 99%