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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.

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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.

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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.

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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.

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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.

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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.

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Ocular tuberculosis is often a challenging diagnosis with extremely diverse clinical manifestations and, most times, impractical bacilli isolation. Here we describe an unprecedented case of presumed ocular tuberculosis presenting with bilateral pseudoretinitis pigmentosa and retinal vasculitis.

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PURPOSE: To evaluate the clinical features and management of presumed ocular tuberculosis (OTB). METHOD: A prospective 3-year follow-up study of patients with ocular inflammation that performed Interferon-gamma release assay (IGRA) and tuberculin skin test (TST) was conducted in a tertiary referral center in Brazil. Patients with clinical signs highly suspect of OTB with a positive TST and/or IGRA with other causes ruled out were prescribed anti-tuberculosis therapy (ATT) during 9 months. Clinical features and treatment outcomes were recorded. RESULTS: Seventy-two patients (mean age 48.3 ± 15.7 years) were included in the study, and most were female (65.3%, n = 47). Posterior uveitis (43.1%, n = 31) was the main clinical feature. Multifocal choroiditis (25%, n = 18) was the most common choroidal involvement. Concomitant oral prednisone (45.8%, n = 33) during ATT was associated with more recurrences (p = 0.04). A significant difference (p < 0.001) between initial and final best-corrected visual acuity after ATT conclusion was observed. Cure or remission was observed in 58 (85.3%) patients that completed follow-up (n = 68). CONCLUSION: In our cohort some variation in demographics and ocular phenotypes of presumed OTB was observed. The high rates of cure or remission of our patients strongly support the ATT in presumed OTB. Oral corticosteroids during ATT were associated with higher recurrences rates.

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BACKGROUND: Bovine tuberculosis is a chronic inflammatory disease that causes granuloma formation mainly in retropharyngeal, tracheobronchial, mediastinal lymph nodes and lungs of bovines. The presence of these lesions in other tissues such as the eyeball is very rare and difficult to diagnose. This study describes macroscopic and microscopic pathological findings in a calf with ocular and meningeal tuberculosis. CASE PRESENTATION: March 2019, an eight-month-old Holstein Friesian calf was identified in a dairy farm located in central Mexico with a clinical cough, anorexia, incoordination, corneal opacity and vision loss. At necropsy, pneumonia, lymphadenitis, meningitis, and granulomatous iridocyclitis were observed. The histopathological examination revealed granulomatous lesions in lung tissue, lymph nodes, meninges and eyes with the presence of acid-fast bacilli associated with Mycobacterium spp. CONCLUSION: To the best of our knowledge, this is the first report that describes macroscopic and microscopic pathological findings of ocular tuberculosis in cattle. This report highlights the importance of considering bovine tuberculosis in the differential diagnosis of corneal opacity and loss of vision in cattle.

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Introducción: se presenta el caso de un paciente de 36 años, a quien se le realizó el diagnostico de tuberculoma coroideo, otorgando tratamiento sin mejoría de los síntomas. Posteriormente fallece dilucidándose el diagnóstico de adenocarcinoma de pulmón con metástasis a coroides. Objetivo: informar el diagnóstico de metástasis coroidea como manifestación inicial, de adenocarcinoma de pulmón, en un paciente joven. Diseño de estudio: reporte de caso. Resumen del caso: masculino de 36 años de edad, antecedente de tuberculosis en la infancia, tabaquismo positivo no significativo. Presenta baja visual de ojo derecho, siendo diagnosticado con tuberculoma coroideo, asociado a sudoración nocturna, lumbalgia, tos y QuantiFERON-TB positivo. Se inicia tratamiento antituberculosis. Posterior, presenta deterioro respiratorio y neurológico requiriendo intubación orotraqueal, ulteriormente fallece. La autopsia elucida el diagnóstico de adenocarcinoma de pulmón con metástasis a coroides, hígado y riñón. Conclusión: las metástasis coroideas conllevan un mal pronóstico visual y sistémico, se requiere un alto índice de sospecha en pacientes menores de 50 años sin factores de riesgo. Se convierten en un reto diagnóstico, sobre todo en países donde predominan las enfermedades infecciosas. El papel del oftalmólogo es realizar el diagnóstico oportuno y correcto, evitando así retrasar el tratamiento.

Background: the case of a 36 year-old patient is presented, who was diagnosed with choroidal tuberculoma, giving treatment without improvement. Then, the diagnosis of pulmonary adenocarcinoma and choroidal metastases was elucidated. Objective: to report the diagnosis of metastasis as the initial manifestation of lung adenocarcinoma in a young patient. Study design: case report. Case summary: male, 36 years old, history of tuberculosis in childhood, positive smoking, but not significant. He presented visual loss of the right eye, being diagnosed with a choroidal tuberculoma, associated with night sweats, cough and positive QuantiFERON-TB test, treatment for tuberculosis was initiated. Later he had respiratory and neurological deterioration requiring orotracheal intubation, but unfortunately he died. Autopsy reveals lung adenocarcinoma with choroidal, liver and kidney metastases. Conclusion: choroidal metastases lead to poor visual and systemic prognosis, a high suspicion is required in patients under 50 years of age without risk factors. They become a diagnostic challenge, especially in countries where infectious diseases are predominat. The ophthalmologist's role is to make the diagnosis timely and correctly, thus avoiding delaying treatment.

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Resumo Objetivo: Descrever aspectos clínicos e esquema terapêutico dos pacientes com tuberculose ocular presumida tratados em um centro de referência em tuberculose de São Paulo. Métodos: Estudo retrospectivo descritivo. O teste exato de Fisher foi realizado quando apropriado. Resultados: A queixa mais comum foi baixa acuidade visual (83,1%), seguida por dor ocular generalizada (25,3%) e visão turva (22,8%). A uveíte posterior foi a apresentação mais comum (35,7%). O tratamento consistiu no esquema atualmente recomendado de rifampicina, isoniazida, pirazinamida e etambutol (RHZE). A prednisona oral foi incluída no tratamento de 37 pacientes, para tratamento da inflamação aguda, embora não tenha diminuído a prevalência de complicações crônicas, em comparação com a recuperação completa (p = 0,1). O diagnóstico precoce (<70 dias) foi associado a maiores taxas de recuperação total (p = 0,005). Não houve significância estatística quando se comparou a terapia de 6 a 9 meses (p = 0,7). Conclusão: A uveíte tuberculosa pode ser tratada por uma terapia com duração de seis meses. Um breve curso de esteroides melhora os sintomas agudos, embora não reduza as complicações a longo prazo.

Abstract Purpose: To analyze and describe the therapy used in presumed ocular tuberculosis in a referral center in São Paulo, Brazil. Methods: Retrospective, descriptive study. Fisher's exact test was performed when appropriate. Results: The most common complaint was low visual acuity (83.1%), followed by generalized ocular pain (25.3%) and blurred vision (22.8%). Posterior uveitis was the most common presentation (35.7%). Treatment consisted of the currently recommended association of rifampin, isoniazid, pyrazinamide, ethambutol (RHZE) regimen. Oral prednisone was included in the treatment of 37 patients for acute inflammation, although it did not significantly decrease the prevalence of chronic complications compared to full recovery (p = 0,1). Early diagnosis (< 70 days) was associated with higher rates of full recovery (p = 0.005). No statistical significance was observed when comparing 6 to 9-month therapy (p = 0.7). Conclusion: Tuberculous uveitis can be treated with a 6-month duration RHZE therapy. A brief course of steroids may improve acute symptoms, although it did not reduce long-term disabilities.

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PURPOSE: To characterize the clinical features in patients with presumed ocular tuberculosis (TB) and determine prognostic factors of visual outcomes and complications in this disease. MATERIAL AND METHODS: Retrospective case series of 35 patients (29 females, 6 males) with presumed ocular TB from referral centers in Chile and Spain between 2002 and 2012. Medical records were reviewed, and data regarding clinical features, complications, best-corrected visual acuity (BCVA), duration of disease, extraocular manifestations, and therapy were retrieved. Prognostic factors for low vision (BCVA 20/50 or less), legal blindness (BCVA 20/200 or less), and complications (cataract, glaucoma, and macular lesion) were evaluated. To calculate correlations, we used Spearman's rank correlation test. To determine clinical predictors, we used the binary logistic regression test. RESULTS: Anterior and non-granulomatous uveitis was the most common types of inflammation. Only 2 (5.7%) patients had respiratory symptoms, and 6 (17.1%) patients had an abnormal chest X-ray at diagnosis. All patients received combined antitubercular therapy with a mean duration of 6.9 ± 2.3 months. A longer duration of symptoms at diagnosis was associated with both low vision and legal blindness. Older patients had a higher risk of legal blindness. A longer duration of symptoms as well as anterior inflammation demonstrated an increased risk for cataract formation. The duration of the symptoms and baseline BCVA had a positive correlation with the final BCVA. Prognostic factors of macular lesions were not found. CONCLUSIONS: The diagnosis of ocular TB can be difficult due to the lack of extraocular manifestations and the broad spectrum of ocular features. A longer duration of symptoms at diagnosis was associated with poorer visual outcomes and cataracts. Therefore, efforts should be made to avoid a delay in the diagnosis of ocular TB and to identify prognostic factors for visual outcomes and complications.

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PURPOSE: To determine the performance of T-SPOT.TB, an interferon gamma release assay test, in patients with ocular tuberculosis (TB) in a BCG-vaccinated, non-endemic population. METHODS: We employed a nested case-control design. In total, 45 subjects were enrolled (23 patients with ocular tuberculosis and 22 patients with other causes of uveitis). A blood sample was collected from each subject, and T-SPOT.TB was executed. Laboratory professionals were blinded to the disease status of each subject. RESULTS: Five patients were excluded because of indeterminate results. The calculated sensitivity and specificity were 0.80 and 0.85, respectively. The positive likelihood ratio was 5.33 and the negative likelihood ratio was 0.23. The overall accuracy of the test was 0.83. CONCLUSIONS: T-SPOT.TB adequately diagnosed ocular TB. This technique is particularly useful in populations where BCG vaccinations are still mandatory.

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Pulmonary tuberculosis (TB) is the most common type of TB in children. Extrapulmonary tuberculosis is also prevalent (about 30-40 percent of cases) and it can occur in a variety of anatomical sites. This study presents a review of the literature on the main clinical manifestations of extrapulmonary tuberculosis in children, its diagnosis and treatment. At the end, some reflections on the importance of BCG for prevention are presented.

La tuberculosis (TB) pulmonar es el tipo más común de TB en niños. La tuberculosis extrapulmonar también es frecuente (alrededor de 30-40 por ciento de los casos) y se puede presentar en una gran variedad de sitios anatómicos. Se hace una revisión de la literatura sobre las principales manifestaciones clínicas extrapulmonares de la tuberculosis en niños, su diagnóstico y su tratamiento. Al final se hacen algunas reflexiones sobre la importancia de la BCG para su prevención.

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Tuberculosis (TB) is considered a public health problem in several countries. This disease is classified as either pulmonary or extrapulmonary. Within the extrapulmonary disease, ocular involvement is uncommon but it is important to recognize it because its incidence has been reported up to 1 percent. Ocular TB cases can be divided in primary and secondary. These manifestations can be caused by an active infection that invades the eye or by an immunologic reaction of delayed hypersensitivity in absence of the infectious agent. The most common clinical presentations are: chronic anterior uveitis, choroiditis and sclerokeratitis. Despite the existence of highly sensitive molecular diagnostic techniques, the diagnosis of ocular tuberculosis continues to be presumptive, based upon clinical presentation, systemic evaluation and response to treatment. For the treatment we use four drugs during a two month period (isoniazid, rifampin, pyrazinamide and ethambutol) and two drugs for four additional months.

La tuberculosis (TBC) es considerada un problema de salud pública en varios países del mundo. Esta enfermedad se clasifica en pulmonar y extra pulmonar. Dentro de la forma extra pulmonar, el compromiso ocular es poco común, pero es importante conocerlo ya que su incidencia puede llegar hasta 1 por ciento. Los casos de TBC ocular se dividen en primarios y secundarios. Las manifestaciones oculares pueden ser causadas por una infección activa que invade el ojo o por una reacción inmunológica de hipersensibilidad retardada, en ausencia del agente infeccioso. Las presentaciones más comunes son: uveítis anterior crónica, coroiditis y esclero-queratitis. A pesar de la existencia de herramientas moleculares altamente sensibles, el diagnóstico de TBC ocular continúa siendo presuntivo, basándose en la presentación clínica, evaluación sistémica y la respuesta terapéutica. Para el tratamiento se utilizan cuatro fármacos por dos meses (isoniacida, rifampicina, pirazinamida y etambutol) y dos fármacos por cuatro meses adicionales.

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