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.

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.

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.

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.

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 – A Portuguese Portrait of This Rare and Challenging Problem / Tuberculosis ocular: un retrato portugués de este problema raro y desafiante

Objectives: Although threatening there is not enough awareness for ocular tuberculosis, hence we intend to study and characterize the ocular tuberculosis observed on a Portuguese specialized pulmonology diagnostic center. Materials and Methodologies: Retrospective study of individuals diagnosed with ocular tuberculosis and followed up from 1st January2016 until 31th December 2018. Results: We studied 38 patients with presumed ocular tuberculosis, with mean age 53,315,7 years old, whose 55,3% were females. Only one patient had known immunosuppression, seven patients had history of previous tuberculosis and only two patients reported a known risk contact. None had extraocular disease. All patients had at least one positive immunologic test, either tuberculin skin test (63,2%) or Interferon Gamma Release Assay test (86,8%). Most patients presented bilateral ocular tuberculosis (44,7%). The standard four-drug regimen was the treatment of choice and corticosteroids were administered to 55,3% patients with no differences in treatment outcomes. The mean length of treatment was 8,6 months and among the patients who completed treatment, 72,4% presented clinical improvement or remission of the ocular manifestations. Conclusions: Ocular tuberculosis, despite a rare condition, carries a huge burden in health care centers. Delay in starting proper treatment can result in permanent blindness and impairment of life’s quality. This condition is probably underdiagnosed and, to our knowledge, there are no recent studies characterizing the latest trend of ocular tuberculosis in Portugal. (AU)

Objetivos: Aunque amenazante, no hay suficiente conciencia sobre la tuberculosis ocular, por lo que pretendemos estudiar y caracterizar los casos de tuberculosis ocular observados en un centro portugués de diagnóstico especializado en neumología. Materiales y Metodologías: Estudio retrospectivo de individuos con tuberculosis ocular seguidos desde 1 de enero de 2016 hasta 31 de diciembre de 2018. Resultados: Se estudiaron 38 pacientes, con una edad media de 53,3±15,7 años, de los cuales el 55,3% eran mujeres. Solo un paciente tenía inmunosupresión iatrogénica, siete pacientes tenían antecedentes de tuberculosis previa y dos pacientes reportaron un contacto de riesgo conocido. Ninguno tenía enfermedad extraocular. Todos los pacientes tenían al menos una prueba inmunológica positiva, ya sea prueba cutánea de tuberculina (63,2%) o prueba de interferón gamma (86,8%). La mayoría de los pacientes presentaron patología bilateral (44,7%). El régimen de cuatro fármacos fue el tratamiento de elección y se administraron corticoides al 55,3% de los pacientes sin diferencias en los resultados. La duración del tratamiento fue de 8,6 meses y entre los que completaron tratamiento, 72,4% presentó mejoría clínica o remisión. Conclusión: La tuberculosis ocular, aunque una condición rara, sobrecarga los centros de salud. El retraso en el inicio del tratamiento puede provocar ceguera y deterioro de la calidad de vida. Esta condición probablemente está subdiagnosticada y, hasta donde sabemos, no hay estudios que caractericen su evolución en Portugal. (AU)

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.

Correlation of angiogenic growth factors and inflammatory cytokines with the clinical phenotype of ocular tuberculosis.

PURPOSE: To determine the correlation of angiogenic growth factors and inflammatory cytokines with the clinical phenotype of ocular tuberculosis (OTB). METHODS: Vitreous fluid was analysed for cytokines in patients with OTB and non-OTB uveitis using multiplex fluorescent bead-based flow cytometric assay. The clinical phenotypes were recorded and correlated with vitreous biomarkers. RESULTS: Vitreous humour from OTB patients had elevated levels of interleukin-10 (IL-10), IL-17-A, interferon-gamma (IFN-γ), and tumour necrosis factor-alpha (TNF-α). Angiopoietin (Ang-2) levels were higher in the panuveitis phenotype. OTB posterior uveitis phenotype had relatively higher vascular endothelial growth factor (VEGF) levels and lower fibroblast growth factor (FGF) levels. Additionally, eyes with choroiditis and vasculitis had elevated levels of VEGF and Ang-2 with FGF downregulation. Both IFN-γ and IL-10 were upregulated in the choroiditis phenotype of OTB. CONCLUSION: Angiogenic growth factors and inflammatory cytokines were altered in the vitreous humour of OTB patients. IFN-γ, VEGF, and IL-10 levels are increased in choroiditis and vasculitis phenotypes. Receiver operating characteristic (ROC) curve analysis further emphasized the importance of the IFN-γ assay in the diagnosis of OTB.

Anti-tubercular therapy in the treatment of tubercular uveitis: A systematic review and meta-analysis.

We quantitatively evaluated the efficacy of antitubercular therapy (ATT) in tubercular uveitis (TBU) patients. Main outcome measures include inflammation recurrence, inflammation reduction, complete resolution of inflammation, improved visual acuity (VA), ability to taper corticosteroids to < 10 mg/day without inflammatory progression, and use of adjunctive immunosuppressants while on ATT. This review is prospectively registered in PROSPERO (CRD42020206845). Forty-nine studies reporting data for 4,017 TBU patients were included. In comparative studies, the odds ratio (OR) of inflammatory recurrence was 0.33 (95%CI:0.19-0.60) for TBU patients treated with ATT±corticosteroid versus no ATT. For TBU patients treated with ATT±corticosteroid, the pooled absolute incidences of inflammatory recurrence, inflammatory reduction, complete resolution of inflammation, and visual acuity improvement were 13% (n=310/2,216; 95%CI:9-18), 81% (n=217/276; 95%CI: 62-95), 83% (n=1,167/1,812; 95%CI: 77-89), and 65% (n=347/542; 95%CI:51-78), respectively. Corticosteroids were tapered to <10 mg/day without inflammatory progression in 91% (n=326/395; 95%CI:78-99) of patients, 9% (n=121/1,376; 95%CI:6-13) of whom were administered concomitant immunosuppressive agents alongside ATT. We conclude that treatment of TBU with ATT±corticosteroid is associated with a high level of control or improvement of inflammation. More prospective studies with detailed reporting of ATT regimens, patient subgroups, and outcomes are required to better evaluate ATT effectiveness.

The Collaborative Ocular Tuberculosis Study (COTS) calculator-a consensus-based decision tool for initiating antitubercular therapy in ocular tuberculosis.

OBJECTIVE: To introduce the Collaborative Ocular Tuberculosis Study (COTS) Calculator, an online clinical scoring system for initiating antitubercular therapy (ATT) in patients with ocular tuberculosis (TB). METHOD: The COTS Calculator was derived from COTS Consensus (COTS CON) data, which has previously published consensus guidelines. Using a two-step Delphi method, 81 experts evaluated 486 clinical scenario-based questions, ranking their likelihood of initiating ATT in each specific scenario. Each scenario was a permutation of the results and/or availability of five following components-clinical phenotype, endemicity, two immunological (tuberculin skin test, interferon-γ release assay) and one radiological (chest X-Ray) test results-and a sixth component further stratifying three of the clinical phenotypes. The median scores and interquartile ranges (IQR) of each scenario were tabulated, representing the expert consensus on whether to initiate ATT in that scenario. The consensus table was encoded to develop the COTS Calculator. RESULTS: The COTS Calculator can be accessed online at: https://www.oculartb.net/cots-calc . The attending physician can select the conditions present in the patient, which will generate a median score from 1 to 5. 114 out of 486 scenarios (24%) deliberated had a median score of 5 indicating expert consensus to initiate ATT. CONCLUSION: The COTS Calculator is an efficient, low-cost, evidence and experience-based clinical tool to guide ATT initiation. While it holds substantial promise in improving standard-of-care for ocular-TB patients, future validation studies can help to as certain its clinical utility and reliability.

Differences in biomarker concentrations in serum and urine of patients with Ocular Tuberculosis - A prospective descriptive study.

PURPOSE: To describe biomarker concentrations in serum and urine of South African patients with ocular tuberculosis (OTB). METHODS: A prospective study to compare 29 urine and serum biomarkers in 14 OTB patients at a tertiary eye clinic. RESULTS: Median age of participants (7 male and 7 female) was 38.5 years (range 25-73) Most biomarker concentrations were significantly higher in serum than in urine (p < 0.01). Only 2 (IL-1RA and IL-2) showed higher concentrations in urine than serum (p < 0.01). Three biomarkers (sIL-2Ra, sTNFRI and IFNγ) showed no difference in concentration between urine and serum (p > 0.05). CONCLUSIONS: Most biomarkers tested showed significant differences in concentration between serum and urine and therefore these 2 biofluids cannot be used interchangeably when studying biomarker profiles. One notable exception is IFNγ as its concentration did not differ between serum and urine.

Presumed tuberculosis-related scleritis.

AIMS: To evaluate the clinical characteristics and therapeutic outcome of patients with recurrent scleritis of unknown demonstrable aetiology and positive QuantiFERON-TB Gold In-Tube test (QFT). METHODS: Retrospective chart review of the demographic, clinical, laboratory and therapeutic outcome data of 15 patients. Clinical characteristics as well as remission rate after standard antituberculous therapy (ATT) were assessed. RESULTS: There were 9 men and 6 women with a mean age of 48.9 years (range, 32-73). Scleritis was diffuse in 10 patients (66.6%) and nodular in 5 patients (33.3%), 1 of them with concomitant posterior scleritis. It was bilateral in 7 patients (46.6%) and recurrent in all of them. Scleritis appeared after prior uveitis (10 patients, 66.6%) and/or with concomitant uveitis (5 patients, 33.3%) or peripheral keratitis (5 patients, 33.3%). Previous ocular surgery was found in 7 patients (46.6%). Previous extraocular tuberculosis (TB) infection or previous TB contact was detected in 11 patients (73.3%). No radiologic findings of active extraocular TB were detected. ATT was used in 15 patients, sometimes with the addition of systemic corticosteroids (5 patients) and methotrexate (1 patient); 14 patients achieved complete remission (93.3%). CONCLUSION: Presumed TB-related scleritis may appear in recurrent scleritis of unknown origin and positive QFT. It may occur after prior uveitis and/or concomitantly with uveitis or peripheral keratitis, and it may be triggered by previous ocular surgery. No patients had evidence of concurrent active extraocular infection, although many had previous TB infection or TB contact. ATT was effective, sometimes with the addition of systemic corticosteroids and methotrexate.