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.

Various Spectrum Of Ocular Tuberculosis.

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

Animal Models of Ocular Tuberculosis: Implications for Diagnosis and Treatment.

The pathogenesis of ocular tuberculosis (TB) has remained unclear due to the challenges of performing mechanistic studies on clinical samples. Animal models have the potential to bridge these gaps by providing information about ocular dissemination and localization of mycobacteria, innate and adaptive immune response, and granuloma formation in the eye. Here, we critically review various animal models of ocular TB from the early 20th century to date and derive novel insights into pathogenesis of ocular TB that have direct implications on the diagnosis and treatment of this disease. Future directions on experimental approaches to understanding pathogenesis of ocular TB are also discussed.

Program-wide review and follow-up of erythema Induratum of Bazin and tuberculosis-associated ocular inflammation management in a TB low-incidence setting: need for improved treatment candidate selection, therapy standardization, and care collaboration.

BACKGROUND: Erythema induratum of Bazin (EIB) - nodular vasculitis associated with Mycobacterium tuberculosis (TB) - and Tuberculosis-Associated Ocular Inflammation (TB-AOI) represent uncommon manifestations of TB. There is limited data and a lack of diagnostic and treatment standards for these conditions. METHODS: Eleven-year retrospective review of EIB and TB-AOI cases managed in a provincial TB program with prospective phone-based follow-up of anti-tubercular therapy (ATT) recipients. Presumptive TB-AOI and EIB diagnoses were determined by ophthalmologist or dermatologist assessments correlated with positive tuberculin skin test and/or QuantiFERON-TB Gold, along with pathologic criteria in EIB cases. RESULTS: Of 21 EIB and 20 TB-AOI cases that received ATT, 13 and 11, respectively, were reached for follow-up. The majority of EIB and TB-AOI cases were female and immigrated from TB high-burden countries. Median durations of pre-diagnosis symptoms were 2 and 0.8 years (IQR 2.5 & 1.1) for EIB and TB-AOI cases, respectively. Overall, 14 different ATT regimens were used for a median duration of 6 months (range 5-9). ATT related adverse events resulting in treatment discontinuation occurred in 14% of EIB and 10% of TB-AOI cases. On last follow-up, 76% of EIB and 42% of TB-AOI had improvement or resolution of disease. CONCLUSION: EIB and TB-AOI were uncommon presentations receiving variable therapy. While treatment response was modest for EIB cases, TB-AOI cases had sub-optimal treatment outcomes. The unique diagnostic and management challenges presented by these conditions in TB low-incidence settings highlight a need for improved treatment candidate selection, therapy standardization, and cross-specialty medical collaboration.

Primary tubercular dacryocystitis - a case report and review of 18 cases from the literature.

Tuberculosis is an airborne communicable disease primarily affecting lungs. Primary tuberculosis of the lacrimal sac is very rare. A 15-year-old girl presented with bilateral epiphora for 8 months. Examination revealed bilateral nasolacrimal duct obstruction. During dacryocystorhinostomy, bone over lacrimal sac was found partially eroded. Lacrimal sac was found filled with caseous white material. Biopsy from the lacrimal sac revealed tubercular granulomas. Patient improved after anti-tubercular therapy. Abbreviations: PCR: polymerase chain reaction; NAAT: nucleic acid amplification test.

[Ocular tuberculosis]. / Tuberculose oculaire.

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

[The study of ocular tuberculosis during the 19th and early 20th century].

During the 19th and early 20th century the achievements in the study of ocular tuberculosis were of great significance. The development of pathological anatomy in those years helped physicians to understand the histological image and the pathophysiology of the disease and allowed the scientists to detect the specific anatomical structures of the eye, where the disease could be present. The physicians of those years tried to describe the clinical image of the disease and to give value information, in order to facilitate the diagnosis. Despite major efforts made in the field of clinical approach to ocular tuberculosis, the treatment of the disease in those years was not very effective. Nevertheless, the physicians of the time used every new pharmacological or not pharmacological treatment to fight the disease.

Ocular Tuberculosis.

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

[Eales' disease]. / La maladie de Eales.

The syndrome of recurrent vitreous hemorrhages in young men was described for the first time by Henry Eales in 1880. The association with a clinical manifestation of ocular inflammation was reported 5years later. Eales disease affects young adults who present with ischemic retinal vasculitis, with the peripheral retina most commonly affected. Most cases have been reported in South Asia. Although the etiology of this abnormality is unknown, it may be related to an immune sensitivity to Mycobacterium tuberculosis antigens. Its pathogenesis is related to extensive ischemia that affects the retina, secondary to an obliterative retinal vasculopathy with release of angiogenic factors of the VEGF type. Involvement of the retina is the hallmark of the disease, which manifests as follows: periphlebitis, retinal capillary ischemia most often affecting the periphery with secondary proliferative retinopathy and retinal and/or papillary neovascularization, recurrent vitreous hemorrhages and tractional retinal detachment. These complications are potentially blinding. The natural history of Eales disease varies, with temporary or permanent remission in some cases and continuous progression in others. Progression is often bilateral, which necessitates regular follow-up. The treatment of Eales disease depends on the stage of the disease and is not well defined. Observation only, pars plana vitrectomy surgery and/or intravitreal injections of anti-VEGF are recommended in cases of vitreous hemorrhage, associated with corticosteroids when retinal vasculitis is present. Laser pan-retinal photocoagulation is necessary when neovascularization is present.

OCULAR AND OSTEOARTICULAR TUBERCULOSIS IN A YOUNG PATIENT. CASE REPORT.

CASE REPORT: A young healthy patient, health-care worker in a state hospital, presented in the eye department complaining of pain and blurred vision in the left eye for approx. 2 weeks. Examination revealed a VA of 12/20 in the left eye, an interstitial keratitis, some signs of vitreal inflammation and two chorioretinal mass lesions (at echography appearing cystic) in the affected eye. She also mentioned a chronic pain in the right wrist. No systemic association was found. Based on the orthopaedic examination, biopsy, and surgical intervention, a strong suspicion of ocular tuberculosis was made and the patient was advised to start tuberculostatic treatment for 12 months and ocular steroidian treatment for 4 months. The ocular manifestations regressed totally after 3 months of treatment, the VA of the left eye improving at 20/ 20. CONCLUSION: Tuberculosis can present many manifestations, with multi systemic involvement. Ocular tuberculosis is a difficult diagnosis and thus requires thorough multi-disciplinary investigations.

Orbital tuberculosis in a paediatric population.

PURPOSE: To report the clinical profile and management of orbital tuberculosis (TB) in children. METHODS: Eight cases were studied retrospectively. RESULTS: Ages in the range of 3-16 years. Three cases presented with discharging sinus in upper lid, three with a cystic mass and two with lid necrosis. Underlying bony changes were found in five patients. Drainage and curettage was done for five patients, needle drainage of fluid was done in one patient and in two patients local debridement was done. Polymerase chain reaction for tuberculosis was positive in four cases and acid fast bacilli (AFB) were isolated on culture in three cases. On histopathology, six cases had granulomatous inflammation with caseating necrosis in one, though AFB could not be found. A favourable response to anti-tubercular treatment was achieved in all cases. CONCLUSION: High index of suspicion is required for diagnosis of orbital TB. Microbiological and pathological diagnosis may not be achieved in all cases.

Mycobacterial ocular inflammation: delay in diagnosis and other factors impacting morbidity.

IMPORTANCE: The reported outcomes of ocular mycobacterial infection are commonly unfavorable. This study is among the first to elucidate factors associated with poor outcomes, as well as highlight the continued controversies in therapy, particularly the role of oral corticosteroids. OBJECTIVE: To describe presentations and outcomes of mycobacterial ocular disease in the Midwestern United States. DESIGN Retrospective case series. SETTING: A university-based uveitis clinic. PARTICIPANTS: Twenty-six eyes of 17 patients with mycobacterial ocular inflammatory disease seen at University of Illinois at Chicago from 1995 to 2010. MAIN OUTCOME MEASURES: Bivariate and regression analyses were performed to assess factors associated with delay in referral, relapse, and irreversible visual acuity loss (≤ 20/200). RESULTS: Of 17 patients, 13 had isolated ocular disease, 1 had miliary tuberculosis (TB), 2 had TB lymphadenopathy, and 1 had active pulmonary TB. Fourteen had Mycobacterium tuberculosis and 3 had nontuberculous mycobacterial infection. Chest imaging was consistent with granulomatous disease in 46.7%. Average delay from ocular disease onset to uveitis service referral was 755.3 days. Posterior uveitis and non-Hispanic white race were associated with increased delay. A relapsing course was observed in posterior uveitis (odds ratio [OR], 20.0; 95% CI, 1.39-287; P = .03) and those treated with systemic steroids for eye disease (OR, 10.1; 95% CI,1.60-64.0; P = .01). Disease control was achieved in 81%, although 38.5% had profound visual loss, associated with age older than 50 years and delay in diagnosis. Patients diagnosed after 500 days from initial ocular symptoms were more likely to lose vision (OR, 20.0; 95% CI, 1.41-282; P = .03). CONCLUSIONS: Ocular mycobacterial infection occurs in nonendemic areas and cannot be ruled out with negative chest imaging. Tuberculosis and atypical mycobacterial infection should be in the differential diagnosis of ocular inflammation, regardless of patient ethnicity. Significant delays exist in instituting antimicrobial treatment, associated with increased morbidity. Early referral is necessary for patients not responding appropriately to anti-inflammatory therapy.

Clinical presentation, treatment, and outcomes in presumed intraocular tuberculosis: experience from Newcastle upon Tyne, UK.

PURPOSE: To report the clinical manifestations and treatment outcomes of patients with presumed intraocular tuberculosis (TB) seen at the Newcastle Uveitis Service, Royal Victoria Infirmary, Newcastle upon Tyne, UK over a 10-year period. METHODS: Retrospective review of case notes. RESULTS: A total of 21 patients were identified. Occlusive retinal vasculitis was the commonest ophthalmological presentation (12 patients). Eight patients (38%) were found to have underlying active systemic TB (four with mediastinal lymphadenopathy, three with pulmonary TB, one with cutaneous TB). Constitutional or respiratory symptoms, elevated inflammatory markers, and an abnormal chest radiograph were poor indicators of active TB. Two patients had inactive intrathoracic TB. Eleven patients had latent TB. Eighteen patients received anti-tuberculous treatment. Final visual acuity was better than or equal to initial visual acuity in 14 out of 16 patients who completed at least 6 months of standard anti-tuberculous treatment. CONCLUSIONS: Most patients with presumed intraocular TB have latent TB, but a significant minority has hitherto undetected active TB. Our series suggests that either proven or presumed intraocular TB occurs frequently in the absence of constitutional or respiratory symptoms, elevated inflammatory markers, or an abnormal chest radiograph. A minimum of 6 months standard anti-tuberculous treatment provides good visual outcomes in the majority of patients.

[Tolerance of porous polyethylene orbital implants in children]. / Tolérance des implants orbitaires en polyéthylène poreux chez l'enfant.

INTRODUCTION: The purpose of our study is to determine the incidence of orbital complications that occurred after insertion of orbital porous polyethylene implant in children under the age of 15 years. MATERIAL AND METHODS: We report a series of 21 eyes of 21 patients younger than 15 years and in which a porous polyethylene implant is used for reconstruction of the orbital cavity after enucleation between January 2003 and December 2008.All patients were operated on by the same surgeon using the same technique. RESULTS: These 11 boys and 10 girls, whose average age is 5.7 years. Histopathologic diagnoses after enucleation are dominated by the retinoblastoma (10 eyes) and phthisis bulbi (6 eyes). After a mean follow up of 23 months it was observed two cases of implant extrusion in children enucleated for retinoblastoma. No cases of orbital cellulitis or enucleated syndrome have been reported. DISCUSSION: The most common complication of porous polyethylene implants in children is exposure. Risk factors may be related to surgical technique, infection, the implant, use of wrapping material and the association with adjuvant chemotherapy. Using a porous polyethylene implant uncovered remains an appropriate technique in children under 15 years for the reconstruction of the anophthalmic cavity, provided a rigorous surgical technique.

Tuberculous scleritis in a patient with rheumatoid arthritis.

UNLABELLED: Scleritis is an ocular inflammatory disorder commonly associated with systemic autoimmune diseases. We report a case of nodular scleritis with an etiological diagnosis of tuberculosis wherein diagnosis was possible only after histopathological examination of the enucleated eye. METHOD OF STUDY: A 52 year female patient was referred as a case of nodular scleritis not responding to topical and oral anti-inflammatory agents. She was being treated with immunosuppressives for rheumatoid arthritis by her rheumatologist. Scleritis improved initially but worsened in few months with development of complications. Eye was enucleated and histopathological examination revealed tuberculous bacilli in retinal pigment epithelial cells. CONCLUSION: Infective scleritis should be suspected in cases of scleritis which progress despite treatment. Reactivation of latent Mycobacterium tuberculosis may occur especially in patients on long term systemic immunosuppressive treatment. Early detection and aggressive treatment is necessary for preventing morbidity or mortality due to these infections.