Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis.

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.

/pdf/diagnosis-and-biomarkers-for-ocular-tuberculosis-from-the-3eep297i.pdf

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

The Collaborative Ocular Tuberculosis Study (COTS) Group sought to address the diagnostic uncertainty through retrospective cohort analysis of treatment regimens and therapeutic outcomes for patien...

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 165 Patients with Tubercular Anterior Uveitis

Tuberculosis (TB)-associated uveitis is a common cause of infectious uveitis in the developing world. Diagnosis of TB uveitis remains a challenge. The role of interferon gamma release assays (IGRAs) is uncertain. Herein we summarise the available literature on the utility of IGRAs in the diagnosis and management of TB uveitis. We searched PubMed database from 1 August 2010 to 31 July 2020 using the following keywords alone and in combination: 'interferon-gamma release assay', 'QuantiFERON', 'T-SPOT.TB', 'TB uveitis', 'serpiginous like choroiditis', 'tuberculoma', 'TB vasculitis', 'TB panuveitis' and 'ocular tuberculosis'. Data from 58 relevant studies were collated. The review is focused on currently marketed versions of IGRA tests: QuantiFERON-TB Gold In-Tube assay, QuantiFERON-TB Gold Plus assay (QFT-Plus) and T-SPOT.TB. We found limited evidence regarding the diagnostic utility of IGRA in patients with uveitis. No study was identified evaluating the newer QFT test-the QFT-Plus-in patients with uveitis. Similarly, there is lack of data directly comparing QFT-Plus with T-SPOT.TB specifically for the diagnosis of TB uveitis.

/pdf/role-of-interferon-gamma-release-assay-in-the-diagnosis-and-2e0yt1vdpq.pdf

Role of interferon gamma release assay in the diagnosis and management of Mycobacterium tuberculosis-associated uveitis: a review.

Purpose: To report a case of a choroidal neovascularization (CNV) secondary to ocular toxocariasis treated with intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents.Methods: A 66-year-old woman presented with decreased vision (20/40) and metamorphopsia in the right eye. Fundus examination revealed inferotemporal retinal whitish lesion and subretinal hemorrhage in the right eye.Results: She was diagnosed with ocular toxocariasis based on the clinical features and positive serological anti-toxocara antibody test result. Ophthalmic examination revealed classic CNV formation adjacent to a retinal granuloma. She was treated with intravitreal ranibizumab and bevacizumab injections combined with oral albendazole. Her vision decreased to 20/100 following CNV recurrence. However, after additional bevacizumab treatment, the CNV became inactive and her vision recovered to 20/40.Conclusions: CNV can be combined with retinal granuloma due to ocular toxocariasis. Repeated intravitrea...

Intravitreal Administration of Ranibizumab and Bevacizumab for Choroidal Neovascularization Secondary to Ocular Toxocariasis: A Case Report.

Tuberculosis (TB) is the single most common cause of morbidity and mortality worldwide, but it is also the most cost-effective disease to treat [1,2,3]. TB is caused by Mycobacterium tuberculosis (MTB), which causes chronic and indolent systemic illness in multiple organs of the body [4]. Most patients with TB remain symptom-free, and illness occurs in only 3% to 5% of infected people. The incidence of TB-related uveitis (TRU) in patients with intraocular inflammation varies between 0.6% and 10.5%, depending on the country [4].

Cases of TRU are generally chronic and progress slowly. As MTB requires oxygen to grow, it tends to remain in the choroid and ciliary body. However, it can be present in any part of the eye and thus, the condition presents in variable ways. TRU most commonly manifests as anterior uveitis, multifocal choroiditis, panuveitis, or vasculitis. The most accurate diagnostic tool to confirm TRU is the acid-fast smear/culture combination, followed by polymerase chain reaction of an ocular fluid sample. Unfortunately, obtaining an ocular fluid sample of sufficient volume is difficult in most cases and these tests are not highly specific. Although the current gold standard for TB diagnosis is a positive tuberculin skin test (TST) combined with appropriate clinical findings, thi s test has somewhat limited accuracy. The TST can have a high false-positive rate in Korea, which has an intermediate TB burden and a large number of Bacille Calmette-Guerin (BCG)-vaccinated individuals [2,5].

Among other diagnostic tests, the interferon-gamma release assay (IGRA) has been reported to be useful for detecting TB infections [5,6]. Kang et al. [5] showed that 95.7% of Korean subjects had received the BCG vaccine, and that 51% and 4% of subjects had a positive TST and IGRA, respectively, even though the study group had no identifiable risk factors for TB. This result indicates that IGRA is a better TB test than the TST in Korea. Interestingly, Ang et al. [7] found that IGRA was more specific than TST, and the high TST false-positive rate in BCG-vaccinated subjects favors the use of IGRA. Itty et al. [6] also suggested that IGRA is useful in detecting TRU, especially in immunocompromised or BCG-vaccinated patients.

However, the IGRA has a high cost, technical limitations, and a limited ability to differentiate between active and latent TB. Although several studies have shown the usefulness of IGRA in detecting TRU, few studies have investigated which patients should be tested with IGRA. Clinical factors may affect IGRA results, including age (≥46 years) and TB history, both of which are independent risk factors for false-positive outcomes [8]. However, a recent study by Critselis et al. [9] showed that a positive IGRA result was not associated with age in children investigated for latent TB infections.

The aim of the present study was to evaluate the usefulness of IGRA for diagnosing TRU in Korean patients with intraocular inflammation, and to assess the effect of clinical factors, including age, on IGRA results. Clinical factors were compared between patients with and without positive IGRA results as well as between patients with and without presumed TRU. Furthermore, positive IGRA rates were compared among subgroups created based on specific clinical factors. Lastly, associations between clinical factors and IGRA results were assessed using multiple regression analyses.

/pdf/the-usefulness-of-interferon-gamma-release-assay-for-rvhtz3qi75.pdf

The Usefulness of Interferon-gamma Release Assay for Diagnosis of Tuberculosis-related Uveitis in Korea

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The Usefulness of Interferon-gamma Release Assay for Diagnosis of Tuberculosis-related Uveitis in Korea