Peripheral ulcerative keratitis secondary to tuberculosis: A case report and literature review.

RATIONALE: Compared with intraocular tuberculosis, ocular tuberculosis with ocular surface involvement is rare. Corneal involvement in ocular tuberculosis may include interstitial keratitis or peripheral ulcerative keratitis. We report a case of peripheral ulcerative keratitis directly caused by tuberculosis. PATIENT CONCERNS: A 20-year-old man complained of vision loss and pain in the left eye that had lasted for 1 week. A slit lamp examination of the left eye showed a corneal epithelial defect, interstitial corneal edema, and a white irregular infiltrative lesion and ulcer (with the dimension of 2 × 2.5 mm) in the inferior temporal region. DIAGNOSES: The corneal ulcer was scraped, and the Mycobacterium tuberculosis deoxyribonucleic acid polymerase chain reaction was positive. INTERVENTIONS AND OUTCOMES: After a month of oral antituberculosis treatment, the corneal ulcer resolved, and the intraocular inflammation improved. LESSONS: Peripheral ulcerative keratitis secondary to tuberculosis can be directly caused by M tuberculosis.

Host urinary biomarkers in HIV positive and HIV negative patients with tubercular uveitis and other uveitic diseases.

PURPOSE: To determine if host urinary biomarker profiles could distinguish between tubercular uveitis (TBU) and other uveitic diseases (OUD) in patients with and without HIV infection. METHODS: Concentrations of 29 different host biomarkers were measured in urine samples using the Luminex platform. Data were analyzed to describe differences between patients diagnosed with and without TBU and with and without HIV co-infection. RESULTS: One-hundred-and-eighteen urine samples were collected and 39% participants were diagnosed as TBU+. Mean age TBU+ was 39.3±13.6 years with 45.7% males. Anterior and panuveitis and unilateral involvement were most common. 32.6% were TBU+HIV+ (median CD4+=215) while 40.2% were OUD+HIV+ (median CD4+=234). Only sVEGF3 was decreased in TBU+ versus OUD+ (p=0.03), regardless of HIV status. Some biomarkers were significantly raised in HIV+ TBU+ compared to HIV- TBU+: sIL-6Rα, CD30, sRAGE , sTNFR I&-II, IP-10, MIP-1ß, sEGFR and Ferritin. HIV+ OUD+ had increased sVEGFR3, CD30, sIL-6Rα, IP-10, sTNFR I&-II, Ferritin and Haptoglobin compared to HIV- OUD+. VEGF-A (p = 0.04) was decreased in HIV+ OUD+ versus HIV- OUD+. CONCLUSION: Decreased urinary concentrations of VEGFR3 were observed in TBU+ compared to TBU-. HIV+ individuals demonstrated increased concentrations of multiple urinary analytes when compared to HIV- patients with uveitis.

Ocular TB in Western Australia.

This was a retrospective chart review in Western Australia, Australia.To describe the diagnosis, management, and treatment outcomes of ocular TB in Western Australia (WA).This was a retrospective review of ocular TB cases in WA from 2007 to 2018 with a minimum 2-year follow-up upon completion of anti-TB therapy (ATT).A total of 44 patients were referred to WA TB clinic. Ten were excluded from the analysis of treatment response; 34 met the inclusion criteria, of whom 97.1% were born overseas. No patients had symptomatic extraocular TB. Chest X-ray showed prior pulmonary TB in 11.7% of patients (n = 4). All patients were treated with three or four ATT drugs. The most common ocular TB manifestation was retinal vasculitis (23.5%). Full resolution of ocular inflammation following ATT occurred in 66.7% (n = 22), and reduced ocular inflammation requiring only topical steroid treatment was seen in 21.2% (n = 7). Treatment failure occurred in 12.1% (n = 4). Side effects were reported in 45.6% of patients, with gastrointestinal symptoms most common (27.2%).Our study is the first Australian study examining the management of ocular TB. Our study highlights the challenges in diagnosing TB ocular disease in a low-endemicity setting and the importance of the collaboration between uveitis and TB subspecialists..

Mycobacterium dormancy and antibiotic tolerance within the retinal pigment epithelium of ocular tuberculosis.

Tuberculosis (TB) is a leading cause of death among infectious diseases worldwide due to latent TB infection, which is the critical step for the successful pathogenic cycle. In this stage, Mycobacterium tuberculosis resides inside the host in a dormant and antibiotic-tolerant state. Latent TB infection can also lead to multisystemic diseases because M. tuberculosis invades virtually all organs, including ocular tissues. Ocular tuberculosis (OTB) occurs when the dormant bacilli within the ocular tissues reactivate, originally seeded by hematogenous spread from pulmonary TB. Histological evidence suggests that retinal pigment epithelium (RPE) cells play a central role in immune privilege and in protection from antibiotic effects, making them an anatomical niche for invading M. tuberculosis. RPE cells exhibit high tolerance to environmental redox stresses, allowing phagocytosed M. tuberculosis bacilli to maintain viability in a dormant state. However, the microbiological and metabolic mechanisms determining the interaction between the RPE intracellular environment and phagocytosed M. tuberculosis are largely unknown. Here, liquid chromatography-mass spectrometry metabolomics were used to illuminate the metabolic state within RPE cells reprogrammed to harbor dormant M. tuberculosis bacilli and enhance antibiotic tolerance. Timely and accurate diagnosis as well as efficient chemotherapies are crucial in preventing the poor visual outcomes of OTB patients. Unfortunately, the efficacy of current methods is highly limited. Thus, the results will lead to propose a novel therapeutic option to synthetically kill the dormant M. tuberculosis inside the RPE cells by modulating the phenotypic state of M. tuberculosis and laying the foundation for a new, innovative regimen for treating OTB. IMPORTANCE: Understanding the metabolic environment within the retinal pigment epithelium (RPE) cells altered by infection with Mycobacterium tuberculosis and mycobacterial dormancy is crucial to identify new therapeutic methods to cure ocular tuberculosis. The present study showed that RPE cellular metabolism is altered to foster intracellular M. tuberculosis to enter into the dormant and drug-tolerant state, thereby blunting the efficacy of anti-tuberculosis chemotherapy. RPE cells serve as an anatomical niche as the cells protect invading bacilli from antibiotic treatment. LC-MS metabolomics of RPE cells after co-treatment with H2O2 and M. tuberculosis infection showed that the intracellular environment within RPE cells is enriched with a greater level of oxidative stress. The antibiotic tolerance of intracellular M. tuberculosis within RPE cells can be restored by a metabolic manipulation strategy such as co-treatment of antibiotic with the most downstream glycolysis metabolite, phosphoenolpyruvate.

Tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment: a case report.

BACKGROUND: Ocular tuberculosis is a relatively rare extrapulmonary manifestation of tuberculosis. This vision-threatening disease is extremely challenging to diagnose, particularly because it can mimic other diseases. We report a case of tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment. CASE REPORT: A 52-year-old female presented with bullous retinal detachment in her left eye, and ultrasound biomicroscopy (UBM) verified the presence of a lesion with ciliary body granulomatous inflammation. The T-SPOT was positive, and the purified protein derivative (PPD) test was strongly positive (diameter of 20 mm). Following the administration of oral anti-tuberculosis regimen combined with prednisone, the retina gradually became reattached, the ciliary body granuloma became significantly reduced in size, and the visual acuity of the patient noticeably improved. CONCLUSIONS: Tuberculous ciliary body granulomas can cause bullous exudative retinal detachment and can be diagnosed with UBM. Early and full-course anti-tuberculosis treatment (ATT) combined with corticosteroid therapy can improve the patient prognosis.

Assessment of quality of life, psychosocial, and epidemiological aspects in patients diagnosed with tuberculous uveitis.

PURPOSE: To assess the quality of life in patients diagnosed as having tuberculous uveitis and its association with sociodemographic, clinical, and psychosocial aspects. METHOD: By conducting standardized interviews, clinical and demographic data were collected using a measure developed in this study. This measure was applied in addition to other measures, namely SF-12, Hospital Anxiety and Depression Scale, and NEI-VFQ-39, which were used to assess health-related quality of life, anxiety and depression symptoms, and visual functioning. RESULTS: The study included 34 patients [mean age: 46.5 ± 15.1 years, female patients: 21 (61.8%)]. The mean of the VFQ-39 score was 74.5 ± 16.6 and that of SF-12 physical and mental component scores were 45.8 ± 10.1 and 51.6 ± 7.5, respectively, for the health-related quality of life. Anxiety symptoms were the most prevalent compared with depression symptoms and were found in 35.3% of the participants. CONCLUSION: Tuberculous uveitis affects several scales of quality of life, thereby affecting a population economically active with a social, psychological, and economic burden.

Diagnostic Utility of QuantiFERON-Gold Testing in Patients with Ocular Inflammation in a Low-Endemic Tuberculosis Region.

PURPOSE: To evaluate the diagnostic value of QuantiFERON Gold (QFT-G) testing for ocular inflammation in a low prevalence tuberculosis (TB) area. DESIGN: Diagnostic utility analysis. METHODS: A review was performed for all uveitis patients who underwent QFT-G testing at the University of Colorado Eye Center from 2009 to 2022. Records were reviewed to assess QFT-G positivity rate and to identify which patients were tested for diagnostic purposes, defined as meeting the Standardization of Uveitis Nomenclature (SUN) criteria for tubercular uveitis (TBU): anterior uveitis with iris nodules, serpiginous-like choroiditis, choroidal nodule resembling a tuberculoma, multifocal choroiditis, or occlusive retinal vasculitis. RESULTS: A total of 388 patients with uveitis underwent QFT-G testing, of which 17 (4.38%) were positive. Only one (5.88%) patient had true TBU with anterior uveitis with iris nodules. The remaining 16 (94.1%) patients did not meet SUN criteria for TBU and were incidentally found to be QFT-G positive during laboratory work-up prior to immunosuppression. The positive predictive value was 100% when QFT-G testing was performed in patients who met SUN criteria for TBU, whereas the positive predictive value was 0% for QFT-G testing performed in patients who did not meet SUN criteria for TBU. CONCLUSION: In low prevalence areas, the majority of QFT-G positive tests in uveitis patients are coincidental and unrelated to their uveitic disease process. The diagnostic value of a TB test is likely to be minimal unless the SUN clinical criteria for tubercular uveitis are met.

Primary Orbital Tuberculosis with Cold Abscess: A Case Report.

Orbital tuberculosis is a rare form of extrapulmonary tuberculosis involving orbital soft tissue, periosteum, bones and lacrimal glands. This is a case report of a 6-year-old male child who presented with swelling of the right upper eyelid. He had normal visual acuity without signs of diplopia or ophthalmoplegia. The tuberculin skin test was reactive and the computed tomography scan showed peripherally enhancing collection with bony erosion and intracranial extension in the extraconal space of the superolateral right orbit. Orbital exploration was done which showed caseous material. The histological examination revealed necrotizing granulomatous tissue. The caseous material on Ziehl Neelsen staining confirmed acid-fast bacilli causing a tubercular abscess. The child is currently on anti-tubercular therapy planned for 12 months. Orbital tuberculosis might or might not be in association with pulmonary tuberculosis and should always be taken into consideration while dealing with chronic inflammatory orbital disease and an orbital mass. Keywords: case reports; orbit; tuberculosis.

Unilateral solitary choroidal tuberculoma as the presenting sign in disseminated tuberculosis in an immunocompetent patient.

INTRODUCTION: Tuberculosis can involve any organ in the body including ocular tissue of which the uveal tissue is most commonly infected. Choroidal involvement ranges from choroidal tubercles to granulomas. This is one of the few cases of a solitary choroidal granuloma with no other systemic symptoms in an immunocompetent child. METHOD: A case report. RESULTS: A 12-year-old female, presented with diminution of vision in the left eye for a month. The anterior segment of her left eye was normal. A fundus examination revealed an isolated orangish-yellow choroidal mass, 4 DD in size, involving the posterior pole with overlying subretinal exudation. CT scan of the thorax showed large pulmonary, cervical and pancreatic lymph nodes, along with lytic lesions of the thoracic vertebrae. Excision biopsy of the cervical lymph nodes showed caseating granulomas with no e/o malignancies on histopathology. The patient was started on anti-tubercular therapy. Six months after the treatment, the lesion had reduced in size and her vision had improved. CONCLUSION: Isolated choroidal tuberculomas can be present in eyes with little associated ocular inflammation and no other symptoms of systemic tuberculosis. High suspicion, early diagnosis and rapid initiation of medication are important for the treatment of ocular and systemic tuberculosis.

Indolent ulcer and discharging sinus on the eyelid of healthy Indian children and an adult: Orbital tuberculosis, a spot-diagnosis.

Five cases of tuberculous osteomyelitis of the fronto-zygomatic (F-Z) region presented with a non-healing ulcer or discharging sinus in the eyelid skin in healthy children and an adult. Lack of awareness about peri-ocular manifestations of extra-pulmonary tuberculosis and delayed referral to specialists, along with poor compliance to long-term ATT, could be the reason for its underreporting in India.

TUBERCULOUS CHORIORETINITIS: A CHALLENGING CASE OF AN OPHTHALMIC MIMIC.

PURPOSE: To report a challenging case of tuberculous chorioretinitis. METHODS: Case report of a 51-year-old woman from the Middle East, who was referred from an optometrist with a suspicious retinal lesion in her right eye. RESULTS: Clinical examination showed multifocal, pale, elevated lesions temporal to the right macula with no vasculitis or hemorrhages. Infective and inflammatory workup showed unremarkable results. B-scan ultrasound confirmed an 8 mm × 3 mm × 10 mm right focal chorioretinal thickening. Computed tomography scanning showed calcified lung hilar nodes supporting a prior granulomatous process, along with an enhancing nodule in the right globe. Magnetic resonance imaging of the brain and obits showed retinal thickening of the temporal surface of the right globe with subtle enhancement without retrobulbar extension or evidence for cerebral vasculitis. Subretinal lesion biopsy showed mononuclear inflammatory cells with granulomatous inflammation, including multinucleated giant cells but no neoplastic features. Interferon-gamma release assay testing for tuberculosis showed negative result, but a high index of suspicion lead to tuberculin skin testing and subsequent treatment for tuberculous chorioretinitis. CONCLUSION: Ocular tuberculosis presents in a variety of ways, making it a challenging diagnosis. Herein, we describe such case of tuberculous chorioretinitis.

Primer Consenso Chileno de Grupo de Estudio de Tuberculosis Ocular / First Chilean Consensus Document of the Ocular Tuberculosis Study Group

INTRODUCCIÓN: El tratamiento de la tuberculosis (TB) ocular es un tema que genera controversia en el mundo. Para el correcto manejo de estos pacientes, es necesario el desarrollo de guías que consideren la epidemiología de la TB ocular en cada nación. El objetivo de este consenso fue discutir de forma interdisciplinaria la epidemiología, fisiopatología, clínica, diagnóstico, estudio y tratamiento de los pacientes con TB ocular, para establecer un algoritmo de tratamiento y proponer qué pacientes deben ser tratados en Chile y con qué tratamiento. Además, se establecieron acuerdos para efectuar quimioprofilaxis de los pacientes con TB latente que tienen indicación de tratamiento inmunosupresor por enfermedades inflamatorias oculares.

The treatment of ocular tuberculosis (TB) remains controversial worldwide. The development of guidelines for ocular TB can facilitate the approach and management of these patients. These guidelines should be developed regionally, considering the local TB epidemiology. The objectives of this consensus are: to initiate an interdisciplinary discussion about the epidemiology, pathophysiology, clinical presentation, diagnosis, workup and treatment of patients with ocular TB, to establish a treatment algorithm and define which patients should be treated in Chile and how and, to analyze and discuss the published data regarding chemoprophylaxis for patients with latent TB who need to start immunosuppressive treatment due to inflammatory ocular conditions.

The immune response in tubercular uveitis and its implications for treatment: From anti-tubercular treatment to host-directed therapies.

Tubercular uveitis (TB-uveitis) remains a conundrum in the uveitis field, which is mainly related to the diverse clinical phenotypes of TB-uveitis. Moreover, it remains difficult to differentiate whether Mycobacterium tuberculosis (Mtb) is present in the ocular tissues, elicits a heightened immune response without Mtb invasion in ocular tissues, or even induces an anti-retinal autoimmune response. Gaps in the immuno-pathological knowledge of TB-uveitis likely delay timely diagnosis and appropriate management. In the last decade, the immunopathophysiology of TB-uveitis and its clinical management, including experts' consensus to treat or not to treat certain conditions with anti-tubercular treatment (ATT), have been extensively investigated. In the meantime, research on TB treatment, in general, is shifting more toward host-directed therapies (HDT). Given the complexities of the host-Mtb interaction, enhancement of the host immune response is expected to boost the effectiveness of ATT and help overcome the rising burden of drug-resistant Mtb strains in the population. This review will summarize the current knowledge on the immunopathophysiology of TB-uveitis and recent advances in treatment modalities and outcomes of TB-uveitis, capturing results gathered from high- and low-burden TB countries with ATT as the mainstay of treatment. Moreover, we outline the recent progress of HDT development in the pulmonary TB field and discuss the possibility of its applicability to TB-uveitis. The concept of HDT might help direct future development of efficacious therapy for TB-uveitis, although more in-depth research on the immunoregulation of this disease is still necessary.

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

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.

Ocular Tuberculosis in Pediatrics: A Case Report.

A 17-year-old male was taken to the emergency department for decreased left visual acuity and floaters beginning that same day. There was a history of exposure to pulmonary tuberculosis five years before (mother as index case) followed by a four-month period of isoniazid prophylaxis. The ophthalmic examination showed posterior and intermediate uveitis in the left eye. Laboratory tests were normal; IgG for herpes simplex 1 was positive and both the varicella-zoster virus and remaining serologic tests were negative. Chest radiography was normal. Two weeks later, an epiretinal membrane with risk of tractional retinal detachment was observed. The Mantoux tuberculin skin test showed an induration of 15 mm and the IGRA test was positive. Sputum and vitreous humor samples were collected. Quadruple therapy and prednisolone were started. Ten days later, a posterior vitreous detachment with underlying vitreous hematoma was observed. Posterior vitrectomy and peripheral endolaser were performed without complications. One month later, the microbiological results became available, with the identification of Mycobacterium tuberculosis. Corticosteroids were weaned progressively. Antituberculous drugs were maintained for six months. The patient made a full recovery.

Ocular tuberculosis presenting with a conjunctival granuloma.

An 18-year-old female patient was referred with complaints of tearing and redness in the left eye for 3 months after a mild ocular trauma with a turkey feather. She was treated with topical antibiotics and corticosteroids with no improvement. Slit-lamp examination of the left eye showed a vascularized lesion with a polypoidal appearance due to multiple contiguous micronodules on the temporal and inferior bulbar conjunctiva. Results of the anterior and posterior segment examination were unremarkable in both eyes. A biopsy specimen of the conjunctival mass showed multiple tuberculoid granulomas composed of epithelioid histiocytes with associated Langhan's type multinucleate giant cells and a necrotic nodule surrounded by histiocytes and giant cells. The Mantoux test was positive with induration of 15mm. The patient was prescribed antituberculosis therapy. Three months after treatment initiation, the conjunctival lesions had resolved. Mycobacterium tuberculosis should be considered in cases of unilateral chronic recalcitrant conjunctivitis. Biopsy of a conjunctival mass is of utmost importance to establish a definite diagnosis.