Various Spectrum Of Ocular Tuberculosis.

Mycobacterium Tuberculosis may infect any organ in the body, when it affects ocular tissue symptoms are vague and hence diagnosis is challenging, through a number of cases reported in our clinic it is emphasized to make quantiferon test as part of routine investigation for cases of presenting with uveitis thus leading to timely diagnosis and accurate treatment.

Imaging in Tubercular Choroiditis: Current Concepts.

PURPOSE: Ocular tuberculosis has protean clinical manifestations. Because of its varied clinical presentation, multimodal imaging is very important to characterize the disease activity, presence of inflammation, determining therapeutic response, and detection of complications. METHODS: Narrative review. RESULTS: In this review, various imaging modalities employed in the management of ocular tuberculosis including fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) have been reviewed. Not only do these imaging tools complement each other in providing a comprehensive assessment of the pathology, they also help in gaining valuable insights regarding the evolution of the disease. CONCLUSIONS: Fundus imaging plays a vital role in the diagnosis and management of patients with posterior uveitis due to tuberculosis. Fundus imaging may have a useful role in defining clinical endpoints for ocular tuberculosis in the future.

Clinical Profile and Treatment Response of Patients with Ocular Inflammation due to Presumed Ocular Tuberculosis: A Retrospective Study

Objectives: Ocular tuberculosis is an extrapulmonary tuberculous infection and has varying manifestations which pose a huge challenge to diagnosis and treatment. The purpose of this study is to describe the various clinical manifestations of ocular inflammations due to tuberculosis and to assess the response to treatment following antituberculous therapy (ATT) and corticosteroids in these patients. Materials and Methods: We performed a retrospective analysis of 29 patients with presumed ocular tuberculosis who were started on ATT and completed follow-up of at least 6 months after ATT was initiated. The data collected were: age at presentation, sex, laterality, presence or absence of pulmonary/extrapulmonary tuberculosis, history of exposure to tuberculosis, site of ocular involvement and duration of illness, visual acuity at presentation and at 6-month follow-up, and response to treatment. Results: Most of the patients were of economically productive age, between 21-60 years. This most common presentation in our study population was unilateral nongranulomatous anterior uveitis. In spite of the delay between symptom onset and start of therapy, favorable response was noted in 79.3% of patients at completion of 6 months of ATT. The various reasons for the delay in start of therapy were also evaluated. Conclusion: In this case series, we presented the various ocular manifestations and the difficulties faced in the diagnosis of presumed ocular tuberculosis. Outcomes of ATT were favorable in most of our patients. Thus, the clinician should exercise a very high degree of suspicion and should not withhold a trial of ATT.

The blinding bug found in the eye.

Tubercular uveitis is a common manifestation of tuberculosis (TB) in TB-endemic countries. Due to lack of gold standard diagnostic tests for confirming intraocular TB, it is often either underdiagnosed or rarely over diagnosed. We report a case of a 28-year-old woman with diminution of vision in the left eye. She was started on antitubercular treatment (ATT) and steroids but she did not comply with the treatment. She developed progressive painful loss of vision consequently and was treated with vitrectomy and silicone oil tamponade. After a complete course of ATT, she recovered, salvaging of eye and restoration of some vision was possible. Mycobacterium tuberculosis is rarely demonstrated in the ocular fluid samples of the suspected cases of TB due to the paucibacillary nature of the disease. A vitreous sample can be obtained from these patients. Surgical intervention in the form of vitrectomy and silicone oil tamponade can help in avoiding enucleation/evisceration.

Enhanced Depth Imaging by High-Resolution Spectral Domain Optical Coherence Tomography in Tubercular Multifocal Serpiginoid Choroiditis.

Purpose: To report the choroidal changes by enhanced depth imaging optical coherence tomography (EDI-OCT) in tubercular multifocal serpiginoid choroiditis (MSC). Methods: Prospective study of 20 patients (23 eyes) with active MSC who underwent simultaneous fundus autofluorescence and EDI-OCT imaging at regular visits. Results: Eyes with acute lesions demonstrated diffuse choroidal thickening at presentation, which decreased significantly as the lesions healed. Additionally, the region of (thickened) choroid just beneath the active choroiditis lesion demonstrated a localized area of mixed reflectivity (a central hyperreflectivity surrounded by a zone of hyporeflectivity), suggesting choroidal involvement deeper to choriocapillaris. Once the lesions healed, the choroid under the scar showed a localized thinning, along with outer retinal layers loss. Conclusion: EDI-OCT highlighted diffuse and localized choroidal structural changes in MSC as the lesions evolved from acute to healed stage, providing an adjunct to clinical examination for monitoring response to therapy.

Transcriptional Profile of Mycobacterium tuberculosis in an in vitro Model of Intraocular Tuberculosis.

Background: Intraocular tuberculosis (IOTB), an extrapulmonary manifestation of tuberculosis of the eye, has unique and varied clinical presentations with poorly understood pathogenesis. As it is a significant cause of inflammation and visual morbidity, particularly in TB endemic countries, it is essential to study the pathogenesis of IOTB. Clinical and histopathologic studies suggest the presence of Mycobacterium tuberculosis in retinal pigment epithelium (RPE) cells. Methods: A human retinal pigment epithelium (ARPE-19) cell line was infected with a virulent strain of M. tuberculosis (H37Rv). Electron microscopy and colony forming units (CFU) assay were performed to monitor the M. tuberculosis adherence, invasion, and intracellular replication, whereas confocal microscopy was done to study its intracellular fate in the RPE cells. To understand the pathogenesis, the transcriptional profile of M. tuberculosis in ARPE-19 cells was studied by whole genome microarray. Three upregulated M. tuberculosis transcripts were also examined in human IOTB vitreous samples. Results: Scanning electron micrographs of the infected ARPE-19 cells indicated adherence of bacilli, which were further observed to be internalized as monitored by transmission electron microscopy. The CFU assay showed that 22.7 and 8.4% of the initial inoculum of bacilli adhered and invaded the ARPE-19 cells, respectively, with an increase in fold CFU from 1 dpi (0.84) to 5dpi (6.58). The intracellular bacilli were co-localized with lysosomal-associated membrane protein-1 (LAMP-1) and LAMP-2 in ARPE-19 cells. The transcriptome study of intracellular bacilli showed that most of the upregulated transcripts correspond to the genes encoding the proteins involved in the processes such as adherence (e.g., Rv1759c and Rv1026), invasion (e.g., Rv1971 and Rv0169), virulence (e.g., Rv2844 and Rv0775), and intracellular survival (e.g., Rv1884c and Rv2450c) as well as regulators of various metabolic pathways. Two of the upregulated transcripts (Rv1971, Rv1230c) were also present in the vitreous samples of the IOTB patients. Conclusions:M. tuberculosis is phagocytosed by RPE cells and utilizes these cells for intracellular multiplication with the involvement of late endosomal/lysosomal compartments and alters its transcriptional profile plausibly for its intracellular adaptation and survival. The findings of the present study could be important to understanding the molecular pathogenesis of IOTB with a potential role in the development of diagnostics and therapeutics for IOTB.

Diminished TLR2-TLR9 mediated CD4+ T cell responses are associated with increased inflammation in intraocular tuberculosis.

Intraocular tuberculosis (IOTB) is amongst the leading causes of uveitis in tropical countries. Despite reports on involvement of proinflammatory cytokines, studies on innate immune responses in disease pathogenesis are lacking. Reports from animal models and patients with pulmonary tuberculosis indicate that defects in toll like receptor (TLR)2 and TLR9 signalling predispose them to tuberculosis. In this context, we investigated the role of TLR2, TLR4 and TLR9 in generation of CD4+ T effector (Teff) cell responses during IOTB. Firstly, the cells in vitreous fluids showed lower expression of TLR2 and TLR9 in IOTB as compared to non-uveitis and non-TB uveitis groups. Next, peripheral CD4+ Teff cells of subjects with IOTB showed decreased proliferative responses and lower induction of Tregs following TLR2 and TLR9 stimulation. Further, TLR9 ligation resulted in increased IFN-γ and IL-17a but decreased expression of IL-10 and TGF-ß. Lastly, lower expression of genes involved in TLR9 signalling after direct TLR9 ligation was observed in IOTB. Collectively, our results show that a subdued response to direct TLR2 and TLR9 stimulation in CD4+ T cells is associated with increased proinflammatory responses in IOTB. These findings reveal an important link between innate immune signalling and ensuing adaptive immune responses in IOTB with implications in other forms of extrapulmonary tuberculosis.

[Ocular tuberculosis]. / Tuberculose oculaire.

Despite extensive investigations, including the use of Interferon-gamma release assays (IGRA), the diagnosis of intraocular tuberculosis (TB) remains challenging. Ocular evidence of Mycobacterium tuberculosis in low endemic countries for TB is extremely rare, leading mostly to a TB-related ocular inflammation presumptive diagnosis. This present work aims: to highlights the main clinical patterns suggestive of ocular TB; and the latest recommended guidelines for diagnosing ocular TB to clarify interferon-gamma release assay (IGRA) contribution and accuracy to the management of intraocular TB and its diagnosis, in addition to other available diagnostic tools, such as tuberculin skin test, bacteriologic and histologic analysis from intra/extra ocular sample and radiographic investigations; to define the accuracy of these diagnostic tools according to the endemic TB prevalence; and finally to identify therapeutic strategies adapted to the main clinical presentations of ocular TB. Our review of the literature shows that management of suspected ocular TB differs significantly based on whether patients are from high or low TB prevalence countries since accuracy of chest X-ray, tuberculin skin test and IGRA is significantly different. Taking into account these discrepancies, distinct guidelines should be determined for managing patients with suspected ocular TB, taking into consideration home prevalence of TB-patients.

Optical Coherence Tomography Features of Tuberculous Serpiginous-like Choroiditis and Serpiginous Choroiditis.

OBJECTIVE: To investigate optical coherence tomography (OCT) characteristics of tuberculous serpiginous-like choroiditis (Tb-SLC) and serpiginous choroiditis (SC) and to perform OCT to differentiate between these conditions. METHODS: This retrospective, case-control study examined consecutively enrolled patients with active Tb-SLC or SC. Patients underwent comprehensive ocular examinations and imaging (OCT, color fundus photography, autofluorescence imaging, fluorescein angiography, and indocyanine green angiography). Findings were examined and compared between eyes with SC and Tb-SLC. RESULTS: Nine patients with active Tb-SLC (14 eyes) and 8 with active SC (12 eyes) were included. The following OCT findings were observed significantly more often in the Tb-SLC group than in the SC group: vitreal hyper-reflective spots [5 Tb-SLC eyes (36%), no SC eyes; P = 0.02], intraretinal edema [11 Tb-SLC eyes (79%), 3 SC eyes (25%); P = 0.01], sub-retinal pigment epithelium (RPE) drusenoid deposits [11 Tb-SLC eyes (79%), 2 SC eyes (17%); P < 0.01], and choroidal granulomas [8 Tb-SLC eyes (57%), 2 SC eyes (17%); P = 0.03]. A hyporeflective, wedge-shaped band was observed more often in the SC group [5 Tb-SLC eyes (36%), 9 SC eyes (75%); P = 0.045] than in the Tb-SLC group. The incidence of other OCT signs did not differ between the groups and included outer nuclear layer hyper-reflection, outer retinal tabulation, and choriocapillaris point-like hyper-reflection. CONCLUSION: Vitreal hyper-reflective spots, intraretinal fluid, sub-RPE drusenoid deposits, and choroidal granulomas on OCT images may indicate Tb-SLC. Additionally, a hyporeflective, wedge-shaped band may indicate SC. Therefore, OCT is likely helpful in differentiating between Tb-SLC and SC.

A zebrafish model for ocular tuberculosis.

Ocular tuberculosis (TB) commonly causes severe inflammation and vision loss in TB-endemic countries. The mechanism by which tuberculous infection becomes established in the eye is poorly understood. We have developed the zebrafish larva infected with Mycobacterium marinum as a model to study the early pathogenesis of ocular TB. We find that hematogenous bacterial seeding of the eye occurs despite a functional blood retinal barrier. Prototypical early granulomas form in response to bacteria in the eye. These granulomas involve the retinal vasculature and retinal pigment epithelium-choroid complex which are characteristic locations for human ocular TB. We find that peripheral blood monocytes are recruited to the nascent ocular granuloma further suggesting that the immune privileged nature of the eye is breached by this inflammatory focus.

Orbital tuberculosis with involvement of the eyelid: An unusual presentation.

Although cases of ocular tuberculosis (TB) are increasing, involvement of the eyelid and orbit are unusual. These cases occur secondary to the presence of TB elsewhere in the body, usually pulmonary TB. The primary infection of orbit or eyelid is a rare occurrence. We report a 4-year-old child with primary orbital TB and involvement of the eyelid. The diagnosis of TB should not be missed in patients with ocular symptoms (especially in India) as it is a treatable condition and delays in diagnosis or incorrect diagnosis can lead to serious sequelae.

Autoreactive T Cells in Immunopathogenesis of TB-Associated Uveitis.

Purpose: Intraocular inflammation in tuberculosis-associated uveitis (TBU) is usually widespread, and responds unpredictably to treatment. Herein, we analyze the intraocular T-cell response in TBU for its surface phenotype, antigenic specificity, and functional characteristics to explain the above observations. Methods: We isolated T cells from vitreous humor samples of patients with TBU and non-TB uveitis (controls). These were directly stained for surface markers CD4, CD8, CD45RO, CD45RA, CCR7, as well as intracellular cytokines IFN-γ, TNF-α, and IL-17 and analyzed on flow cytometry. Antigenic specificity was determined by activating with Mycobacterium tuberculosis-specific antigen Early Secreted Antigenic Target-6 (ESAT-6) or retinal crude extract (RCE). Activation-induced cell death (AICD) characteristics of each T-cell population were analyzed by staining for PI-Annexin V, Fas-FasL, phospho-Akt, and phospho-Erk1/2. Results: Immunophenotyping of vitreous humor samples demonstrated polyfunctional effector and central memory CD4+ T helper cells coexpressing IFN-γ, TNF-α, and IL-17. Both ESAT-6 and RCE (autoreactive) specificity was found in T cells extracted from TBU samples; however, the mycobacterial and autoreactive T-cell populations differed in their sensitivity to AICD. Autoreactive T cells appeared to resist AICD through decreased expression of apoptotic markers, FasL and caspase-3, sustained phosphorylation of Akt, and lowered Erk1/2 activity. Conclusions: Autoreactive T cells are present in TBU eyes and are relatively resistant to AICD. An understanding of this epiphenomenon could be crucial in planning treatment of TBU patients, and interpreting response to anti-TB therapy.

LONGITUDINAL FOLLOW-UP OF CHOROIDAL GRANULOMAS USING ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To assess the ability of enhanced depth imaging optical coherence tomography (EDI-OCT) in detecting variations in the structure and size of choroidal granulomas in response to treatment and to compare these findings with indocyanine green angiography (ICGA). METHODS: EDI-OCT and ICGA images of choroidal granulomas in eyes of patients diagnosed with tubercular or sarcoid uveitis were obtained at baseline and follow-up visits. Two independent masked observers analyzed the lesions to compare changes in their structural features such as shape, reflectivity, and margins, among others, through time. The size of each lesion was manually measured on EDI-OCT and ICGA images at all the visits. In addition, longitudinal assessment of choroidal area was performed on the EDI-OCT images during the course of follow-up. RESULTS: Twenty-eight granulomas (16 tubercular and 12 sarcoid; 7 patients) were included in the study. Using EDI-OCT, significant decrease in the mean size of lesions could be appreciated after 1 month of treatment (0.29 mm at baseline vs. 0.18 mm at 1 month; P < 0.001). However, ICGA did not reveal significant decrease in lesion size at 1 month compared with baseline (0.94 vs. 0.76 mm; P = 0.07). The granulomas followed a characteristic healing pattern in which the antero-posterior extent (depth) decreased first, followed by decrease in their lateral extent. Apart from size, the choroidal granulomas did not show significant changes in their morphological features on EDI-OCT with treatment. CONCLUSION: EDI-OCT may be more sensitive than ICGA in detecting early variations in the size of choroidal granulomas. Morphometric analyses of choroidal granulomas on EDI-OCT may be very useful in monitoring the response to treatment in patients with choroidal granulomas.

Ocular Tuberculosis.

Ocular tuberculosis is an extrapulmonary mycobacterial infection with variable manifestations. The reported incidence of ocular involvement varies considerably, depending on the criteria used for diagnosis and the population sampled. However, tuberculosis is thought to affect the lungs in 80% of patients, with the remaining 20% being affected in other organs, such as the eye. It is imperative for physicians to consider this diagnosis in their differential, as ocular tuberculosis can present in a fashion similar to that of more common conditions causing ocular inflammation. In addition, prompt recognition of the clinical signs and symptoms leads to quicker initiation of antituberculosis therapy.