Current capabilities and limitations for the diagnosis of etiology of ocular tuberculosis: a review

Abstract

Ocular tuberculosis (OTB) remains one of the most diagnostically challenging extrapulmonary forms of tuberculosis in terms of determining the etiology. The paucibacillary nature of the disease, small quantity of intraocular samples, and pathogenetic heterogeneity significantly complicate the direct confirmation of Mycobacterium tuberculosis (MBT) in ocular tissue and fluid samples. This paper reviewed current capabilities and limitations for the diagnosis of etiology of OTB. Molecular gene methods for direct detection of MBT, including polymerase chain reaction (PCR), automated molecular platforms and studies on cell-free DNA analysis, were considered. Despite advances in these methods, they still do not have enough sensitivity for negative results to rule out OTB. Special attention was given to the methods allowing indirect confirmation of MBT infection, tuberculin skin test (TST) and interferon-gamma release analysis (IGRA), particularly, QuantiFERON. A positive IGRA result indicates the presence of a specific immune response to MBT, but does not localize the infectious process or independently confirm a causal relationship between MBT infection and intraocular inflammation. The absence of an independent and sufficiently sensitive reference standard for OTB detection is a major issue in the assessment of diagnostic accuracy of current OTB detection methods. Future research should be aimed not only at increasing the sensitivity of direct diagnostic methods, but also focused on the search for, and independent validation of  markers that will allow differentiation between etiologically MBT-related intraocular inflammation from concomitant latent infection.