Paradoxical Reaction in Intraocular Tuberculosis: Report of Three Cases.

PURPOSE: To present paradoxical reaction (PR) in three cases with ocular tuberculosis (OTB) treated with antitubercular therapy (ATT), highlighting diagnostic challenges and treatment strategies. METHODS: We retrospectively reviewed clinical records of three OTB patients presenting with paradoxical worsening after ATT initiation at two Brazilian university hospitals. RESULTS: The patients (2 males, 1 female) experienced worsening clinical presentation (increased inflammation, vision loss) within two to three weeks after initiating ATT. One patient who was HIV-positive with unilateral multifocal choroiditis developed PR soon after starting antiretroviral therapy. The second patient presented with a choroidal tuberculoma in both eyes. The third patient also had multifocal choroiditis and developed a localized choroidal elevation with a double-layer sign as a manifestation of PR. All patients were maintained on ATT therapy in association with corticosteroids and experienced improvement of inflammatory signs. CONCLUSION: This case series highlights the potential for PR in OTB patients. Close monitoring and prompt therapeutic adjustments are crucial for management success.

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.

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.

Ocular Tuberculosis Diagnosis Through Biomarkers: Clinical Relevance of Serum C1q and Whole Blood Interferon Gene Signature Score.

PURPOSE: To assess the clinical relevance of pathophysiology-based biomarkers, specifically serum C1q and whole blood interferon gene signature score (IGSS), in ocular tuberculosis (OTB) diagnosis by conducting an integrative analysis of clinical presentations and treatment response. METHODS: This retrospective cohort study analysed data from 70 patients with suspected OTB at a tertiary care uveitis practice in Indonesia. Serum C1q levels and whole blood IGSS were quantified. Patients were categorized into four quadrants based on their biomarker profiles: quadrant 1 (high C1q & low IGSS), quadrant 2 (high C1q & high IGSS), quadrant 3 (low C1q & high IGSS), and quadrant 4 (low C1q & low IGSS). Characteristics of clinical presentations, work-up results, and treatment outcomes were explored according to the predefined quadrants. RESULTS: We identified that the majority of OTB patients diagnosed with concurrent active pulmonary TB were in quadrant 1, 2, or 3 (20/23, 87.0%). Twenty-seven patients (27/47, 57.4%) with clinically undifferentiated uveitis were in quadrant 4 (p < 0.001). Among patients in quadrants 1, 2, and 3, completion of a full course of antitubercular treatment (ATT) was associated with a lower number of patients showing persistence or recurrence of ocular inflammation compared to those who were not fully treated with ATT (14.3% vs 85.7%, p = 0.001). CONCLUSIONS: Based on the analysis of clinical features and treatment outcomes, patients with elevated levels of either or both serum C1q and whole blood IGSS may reflect active TB disease in the eye, necessitating full ATT management.

Primary Tubercular Chorioretinitis Without a Pulmonary Focus: A Case Report.

Ocular tuberculosis (TB) can affect various eye structures and may manifest independently of systemic TB. Typically, it arises from hematogenous dissemination from a primary focus; however, in exceptional instances, it may originate as a primary infection after epithelial injury. Diagnosing TB in an extrapulmonary site presents a significant clinical challenge. We present the case of a 33-year-old Bangladeshi female who presented with a deteriorating loss of vision in her left eye. A thorough neurologic examination and serological tests, the tuberculin skin test, a CT scan of the chest, ocular fundus photography, and optical coherence tomography were performed. Based on the clinical features and the outcome of appropriate tests, a presumptive diagnosis of ocular TB was made and later confirmed after initiating antitubercular therapy, which resulted in a marked improvement in the patient's vision a week later. This case is an illustration of the rare nature and unusual presentation of extrapulmonary TB in the form of tubercular chorioretinitis, diagnosed in a resource-limited setting. Tubercular chorioretinitis, characterized by inflammation of the choroid and retina due to TB infection, presents a diagnostic challenge, especially in resource-limited environments where access to advanced diagnostic tools may be restricted. Therefore, this case highlights the importance of considering TB as a potential cause of ocular manifestations, even in settings where TB prevalence might not be high, and underscores the need for increased awareness and diagnostic capacity for extrapulmonary TB in resource-limited areas. This case exemplifies the infrequent occurrence and atypical manifestation, presenting a learning opportunity for future clinicians.

Clinical Features and Predictors of Treatment Outcome in Patients with Ocular Tuberculosis from the Netherlands and Indonesia: The OculaR TB in Low versus High Endemic Countries (ORTEC) Study.

PURPOSE: To describe and compare clinical features, treatment approaches, and treatment outcomes of ocular tuberculosis (OTB) patients in the Netherlands, a low tuberculosis (TB)-endemic country, and Indonesia, a high TB-endemic country. We also aimed to identify predictors of treatment outcomes. METHODS: A medical chart review of 339 OTB patients (n = 93 from the Netherlands and n = 246 from Indonesia) was performed. The primary outcome was response to treatment, whether with or without anti-tubercular treatment, after six months of treatment initiation (good versus poor responders). RESULTS: Indonesian OTB patients displayed a higher prevalence of chest radiograph findings indicative of TB infection (p < 0.001) and concurrent active systemic TB (p = 0.011). Indonesian cohort exhibited a more acute and severe disease profile, including uveitis duration ≤ 3 months (p < 0.001), blindness (p < 0.001), anterior chamber (AC) cells ≥ 2+ (p < 0.001), and posterior synechiae (p < 0.001). Overall proportions of good responders to treatment were 67.6% in the Netherlands and 71.5% in Indonesia. Presence of AC cell ≥ 2+ (adjusted odds ratio (aOR): 2.12, 95% CI: 1.09-4.14), choroidal lesions other than serpiginous-like choroiditis (SLC) or tuberculoma (aOR: 4.47, 95% CI: 1.18-16.90), and retinal vasculitis (aOR: 2.32, 95% CI: 1.10-4.90) at baseline were predictors for poor response to treatment. CONCLUSIONS: Despite a more severe initial clinical presentation in the Indonesian cohort, the overall treatment outcomes of OTB was comparable in both cohorts. Three baseline clinical features were identified as predictors of treatment outcomes.

Clinical manifestation and long-term follow-up of presumed ocular tuberculosis in China.

Background: This study aimed to report the clinical manifestations of presumed ocular tuberculosis (OTB) and the treatment response after anti-tuberculosis therapy (ATT) in a Chinese population. Methods: Clinical data, including general characteristics, ocular lesions, visual acuity at baseline, and final follow-up of patients with presumed OTB from 2006 to 2022 in two eye clinics in China, were retrospectively analyzed. Results: The study included 84 eyes of 52 patients. The following ocular manifestations were observed: anterior uveitis (4.8%), posterior uveitis (34.5%), panuveitis (11.9%), retinal vasculitis (40.5%) and optic neuropathy (8.3%). After ATT, the vision improved by varying degrees in 48 eyes (57.1%), remained stable in 34 eyes (40.5%) and decreased in 2 eyes (2.4%). Conclusions: OTB is likely to be misdiagnosed as other infectious uveitis and optic neuropathy. Clinical features must be interpreted in conjunction with topical and general laboratory findings and in collaboration with other subspecialties to make a final diagnosis.

Ocular manifestations and diagnosis of tuberculosis involving the uvea: a case series.

BACKGROUND: Ocular tuberculosis (TB) affects 1-2% of patients with TB, with TB uveitis being the most common. This series aims to look at different manifestations of tuberculosis associated uveitis and the different tests used to make a presumptive or definitive diagnosis. METHODS: Patients diagnosed with TB related uveitis in Hong Kong SAR between 2017 and 2020 were reviewed. Demographics, clinical features, investigations and treatments of patients were collected. RESULTS: Fifteen eyes in 10 patients with a mean age 57.30 ± 10.17 years were included. The ocular manifestations on presentation included anterior uveitis (50%), posterior uveitis (40%) and panuveitis (10%), where 70% of them were unilateral and 30% were bilaterally infected; on subsequent visits the manifestations further developed into posterior uveitis (40%), panuveitis (40%) and anterior uveitis (20%), where 50% of them were unilateral and 50% bilateral infected. Tuberculosis tests were positive in 5 out of 7 Mantoux tests, 4 out of 4 T-SPOT TB tests, 3 out of 4 QuantiFERON-TB gold tests, 1 out of 1 lymph node biopsy, 0 out of 9 chest x-rays, and no aqueous fluid polymerase chain reaction (PCR) was tested. Vision impairing complications were seen in 6 patients where retinal vasculitis was most commonly seen. With anti-TB treatment prescribed in 9 patients, side effects occurred in 5 patients, including ocular hypertension, disc swelling, and hepatitis. CONCLUSIONS: Ocular TB infections may manifest in various forms, and can involve different parts of the eye. Bilateral involvement of TB is commonly presented, and both eyes should be evaluated at every follow up. When TB is suspected in a patient, diagnostic confirmation requires multimodal investigations where a negative chest x-ray is not useful in ruling out ocular TB infections, especially in an endemic region like Hong Kong. In these patients, it is crucial to have a high index of suspicion for TB, even when they do not demonstrate classical respiratory signs and symptoms of TB.

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.

Bilateral interstitial keratitis in a patient with presumed brain tuberculoma / Ceratite intersticial bilateral em um paciente com tuberculoma cerebral presumido

ABSTRACT Interstitial keratitis is an inflammation of the corneal stroma without epithelium or endothelium involvement. The underlying causes are mostly infectious or immune mediated. Brazil has one of the highest incidence rates of tuberculosis in the world. Tuberculosis is considered one of the causes of interstitial keratitis. Malnutrition and anemia are risk factors of the disseminated disease. This is a case report of a 10-year-old child who presented with decreased visual acuity and a clinical diagnosis of bilateral interstitial keratitis and sclero-uveitis. The patient had been treated with topical steroids with partial improvement. Examinations revealed severe iron deficiency anemia, negative serologies for human immunodeficiency virus and syphilis, positivity for cytomegalovirus- and herpes simplex-specific IgG, and purified protein derivative of 17 mm. During the follow-up, the patient presented with tonic-clonic seizures, and magnetic resonance imaging findings suggested a central nervous system tuberculoma. Interstitial keratitis improvement was observed after specific tuberculosis treatment. This is the first case report describing the association of interstitial keratitis and central nervous system tuberculoma.

RESUMO A ceratite intersticial é uma inflamação do estroma corneano sem envolvimento epitelial ou endotelial causada principalmente por doenças infecciosas e imunomediadas. O Brasil tem altas taxas de tuberculose que deve ser lembrada como causa de ceratite intersticial. Desnutrição e anemia são fatores de risco da forma disseminada da tuberculose. Este é um relato de uma criança de 10 anos com redução de acuidade visual e diagnóstico clínico de ceratite intersticial bilateral e esclerouveíte. O paciente obteve melhora parcial da ceratite com corticoide tópico. Exames laboratoriais mostraram anemia ferropriva grave, sorologias negativas para HIV e sífilis; IgM negativo e IgG positivo para citomegalovírus e herpes simplex e PPD positivo (17 mm). Ele evoluiu com crises tônico-clônicas e a ressonância nuclear magnética revelou tuberculoma do sistema nervoso central. A melhora da ceratite intersticial foi observada após tratamento para tuberculose. Este é o primeiro caso que descreve a associação de ceratite intersticial e tuberculoma do sistema nervoso central.

Surgically induced scleral necrosis associated with concomitant tuberculosis infection: a diagnostic challenge.

Objective: Surgically induced scleral necrosis (SISN) is a potentially blinding sequela that may occur after any ocular procedure. SISN in the context of active tuberculosis is seldom seen. We report a case of a patient with asymptomatic tuberculosis who developed SISN after pterygium surgery. Methods: A 76-year-old Mexican-mestizo woman from Veracruz, Mexico, was referred to our clinic because of severe disabling pain and scleral thinning in her right eye. Results: Tubercular-related SISN was finally diagnosed and managed successfully with antitubercular therapy, topical and systemic corticosteroids. Conclusion: Tuberculosis must be considered as a differential diagnosis of high-risk patients in the context of refractory SISN in endemic countries.

A propósito de un caso pediátrico de tuberculosis oftálmica y drogorresistencia / Presentation of a Pediatric Case of Ocular Tuberculosis and Drug Resistance

El compromiso ocular es una forma extrapulmonar de tuberculosis. Puede comprometer cualquier componente del sistema visual. Las manifestaciones oculares pueden ser causadas por una infección activa que invade el ojo o por una reacción inmunológica de hipersensibilidad retardada. Las presentaciones clínicas más comunes son uveítis anterior crónica, coroiditis y esclero-queratitis. A pesar de la existencia de herramientas moleculares altamente sensibles, arribar al diagnóstico de formas poco frecuentes o no pensadas como la TB ocular en un niño sigue siendo un gran reto y se basa en la presentación clínica, evaluación sistémica y la respuesta terapéutica. El tratamiento implica el uso de antifímicos y, muchas veces, esteroides. El objetivo fue presentar una forma de tuberculosis endoftálmica, pulmonar miliar y meníngea, en el marco de la drogorresistencia.

Eye engagement is an extrapulmonary form of tuberculosis. It can compromise any component of the visual system. Eye manifestations can be caused by an active infection that invades the eye or by a delayed hypersensitivity immune reaction. The most com mon clinical presentations are: chronic anterior uveitis, choroiditis and sclero-keratitis. Despite the existence of highly sensitive molecular tools, arriving at diagnosis in rare or undeceived ways with eye tuberculosis in a child remains a major challenge, based on clinical presentation, systemic evaluation and therapeutic response. Treatment involves the use of antiphymics and often steroids. The objective was to present a form of endophthalmic tuberculosis, miliary pulmonary and meningeal, in the framework of drug resistance.

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)

Role of Interferon-Gamma Release Assay for the Diagnosis and Clinical Follow up in Ocular Tuberculosis.

PURPOSE: To assess the performance of interferon-gamma release assay (IGRA) associated with tuberculosis skin test (TST) for ocular tuberculosis (OTB) diagnosis and therapeutic decision making. METHOD: One hundred and ninety-one patients with ocular inflammation were prospectively followed-up. Patients with clinical signs highly suspected of OTB, TST≥10 mm, and/or IGRA≥0.35 IU/mL received antitubercular therapy (ATT). Sensitivity (Se), specificity (Sp), and area under the curve (AUC) were assessed. RESULTS: Seventy-two (37.7%) patients received ATT for presumed OTB. Combining TST and IGRA had Se=89.6%, Sp=99.2%, and AUC (0.98) significantly higher compared to TST (0.85, Z=6.3, p<.001) or IGRA (0.95, Z=2.5, p=.01). Prior history of corticosteroids or immunosuppressant with concomitantly oral prednisone and baseline IGRA> 2.0 IU/mL was associated significantly with more recurrences in ATT patients (p=.01)      . CONCLUSION: Considering TST and IGRA together was more effective in assessing OTB diagnosis. The real value of the IGRA test to predict recurrences needs further studies.

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.

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.

Antigen-Specific Intraocular Cytokine Responses Distinguish Ocular Tuberculosis From Undifferentiated Uveitis in Tuberculosis-Immunoreactive Patients.

PURPOSE: To compare antigen-specific intraocular immune responses between different clinical phenotypes of tuberculin skin test (TST)-positive and TST-negative uveitis. DESIGN: Single center, retrospective cross-sectional study. METHODS: Patients requiring diagnostic or therapeutic vitrectomy for the management of intraocular inflammation were divided into 3 groups based on Standardization of Uveitis Nomenclature (SUN) classification criteria for tubercular uveitis. Group 1 included patients with ocular tuberculosis (OTB; n = 23) who were TST-positive patients, met the SUN criteria, and/or had a polymerase chain reaction (PCR)-positive test for TB. Group 2 included patients with uveitis of unknown origin (UNK; n = 24) who were undifferentiated TST-positive patients who had not met SUN criteria. Group 3 included non-TB uveitis patients (n = 24) who were TST-negative either with or without a well-defined non-TB diagnosis. Total vitreous cells were activated with Mycobacterium tuberculosis-specific Early Secreted Antigenic Target-6 (ESAT-6) or the retinal autoantigen, interphotoreceptor retinoid-binding protein peptide (pIRBP 1-20), stained for intracellular interferon gamma (IFNγ), tumor necrosis factor-alfa (TNFα), and interleukin 17 (IL-17), and analyzed by flow cytometry. Antigen-specific single and dual (polyfunctional) cytokine responses to ESAT-6 and IRBP were compared between the 3 groups. RESULTS: All cytokine responses to ESAT-6 were higher in the UNK group compared with the non-TB control subjects, while all except IL-17 were comparable between the OTB and non-TB groups. Polyfunctional responses-IFNγ/IL-17 (P = .002), TNFα/IL-17 (P = .02), and TNFα/IFNγ (P = .01)-were significantly greater for UNK than the OTB group. Polyfunctional cells also produced more cytokine per cell than respective monofunctional cells. IRBP cytokine responses were comparable between different groups and were not affected by the clinical phenotype or duration of disease. CONCLUSION: The intraocular polyfunctional cytokine response is stronger in undifferentiated TST-positive uveitis than in OTB patients, likely representing an exaggerated anti-TB immune response rather than active infection.

Colombian ocular infectious epidemiology study (COIES): presumed ocular tuberculosis incidence and sociodemographic characterization, 2015-2020.

PURPOSE: This study aims to describe the incidence and geographical distribution of presumed ocular tuberculosis (POTB) in Colombia between 2015 and 2020 based on the Colombian Ministry of Health and Social Protection data. METHODS: We conducted a claims-based study using the Integrated Social Protection Information System database from the Colombian Ministry of Health. We used the specific code of the International Classification of Diseases for Ocular Tuberculosis (A18.5) and tuberculosis from 2015 to 2020 to estimate the incidence and the demographic status of the disease in Colombia. We used STROBE guidelines. RESULTS: During the 6 years of study, the crude unadjusted incidence was 0.2 new cases of POTB in one million consulting patients and 55 new cases of POTB in 100,000 patients with TB showing a decreasing pattern of the disease. From the 28 new cases, the mean age of presentation was 41.4 years (SD ± 25.3) with a female predominance (60.7% of the cases). Distribution by age shows a higher proportion of cases in groups 15-19 (14%), 20-24 (11%), 55-59 (11%), and 60-64 (11%) years of age. The geographic analysis showed a higher number of cases in Andean region, followed by the Caribbean and Pacific regions. CONCLUSIONS: This is the first study that determines the incidence of POTB in a developing country from Latin America. POTB incidence in Colombia is lower than the reported worldwide. It could be attributed to a low burden of Tuberculosis in Colombia, underdiagnosis, and a low rate of immigration from countries with a high burden of TB.

Infectious Sclerouveitis in an Immunocompetent Patient: A Probable Case of Simultaneous Ocular Tuberculosis and Toxoplasmosis.

Simultaneous infections of tuberculosis and toxoplasmosis are uncommon in immunocompetent patients. We report a case of a 30-year-old male who presented with right eye redness and blurring of vision for one month. The visual acuities were hand movement and Snellen 20/30 in the right and left eyes, respectively. Panuveitis and scleritis were found in the right eye, together with dense vitritis and a large choroidal lesion that extended from the inferonasal to the superotemporal quadrants. B-scan ultrasonography of the right eye showed a choroidal detachment with scleral thickening and subtenon fluid. His IgM anti-Toxoplasma antibody was detected, and his QuantiFERON Gold testing was positive. Magnetic resonance imaging (MRI) of the orbit revealed an enhancing intraocular mass at the lateral and inferior aspects of the right globe. The diagnosis of right eye sclerouveitis with presumed tuberculosis and toxoplasmosis co-infections was made. He was treated with a course of oral azithromycin and anti-tubercular therapy along with systemic prednisolone and a topical steroid. The treatment reduced the inflammation; however, the patient suffered from a sequela of chronic uveitis with prolonged hypotony. Medical treatment alone may be insufficient in treating severe infective sclerouveitis, hence surgical intervention might be warranted to provide favorable clinical outcomes.