Clinical features and outcomes of patients with tubercular uveitis treated with antitubercular therapy in the collaborative ocular tuberculosis study (COTS)-1

IMPORTANCE Eradication of systemic tuberculosis (TB) has been limited by neglected populations and the HIV pandemic. Whereas ocular TB often presents as uveitis without any prior evidence of systemic TB, the existing uncertainty in the diagnosis of TB uveitis may perpetuate missed opportunities to address systemic TB. OBJECTIVE To examine the clinical features of TB uveitis and the associations with response to antitubercular therapy (ATT). DESIGN, SETTING, AND PARTICIPANTS This retrospective multinational cohort study included patients from 25 ophthalmology referral centers diagnosed with TB uveitis and treated with ATT from January 1, 2004, through December 31, 2014, with a minimum follow-up of 1 year. MAIN OUTCOMES AND MEASURES Treatment failure, defined as a persistence or recurrence of inflammation within 6 months of completing ATT, inability to taper oral corticosteroids to less than 10mg/d or topical corticosteroid drops to less than 2 drops daily, and/or recalcitrant inflammation necessitating corticosteroid-sparing immunosuppressive therapy. RESULTS A total of 801 patients (1272 eyes) were studied (mean [SD] age, 40.5 [14.8] years; 413 [51.6%] male and 388 [48.4%] female; 577 [73.6%] Asian). Most patients had no known history (498 of 661 [75.3%]) of systemic TB. Most patients had bilateral involvement (471 of 801 [58.8%]). Common clinical signs reported include vitreous haze (523 of 1153 [45.4%]), retinal vasculitis (374 of 874 [42.8%]), and choroidal involvement (419 of 651 [64.4%]). Treatment failure developed in 102 of the 801 patients (12.7%). On univariate regression analysis, the hazard ratios (HRs) associated with intermediate uveitis (HR, 2.21; 95%CI, 1.07-4.55; P = .03), anterior uveitis (HR, 2.68; 95%CI, 1.32-2.35; P = .006), and panuveitis (HR, 3.28; 95%CI, 1.89-5.67; P < .001) were significantly higher compared with posterior distribution. The presence of vitreous haze had a statistically significant association (HR, 1.95; 95%CI, 1.26-3.02; P = .003) compared with absence of vitreous haze. Bilaterality had an associated HR of 1.50 (95%CI, 0.96-2.35) compared with unilaterality (HR, 1 [reference]), although this finding was not statistically significant (P = .07). On multivariate Cox proportional hazards regression analysis, the presence of vitreous haze had an adjusted HR of 2.98 (95%CI, 1.50-5.94; P = .002), presence of snow banking had an adjusted HR of 3.71 (95%CI, 1.18-11.62; P = .02), and presence of choroidal involvement had an adjusted HR of 2.88 (95%CI, 1.22-6.78; P = .02). CONCLUSIONS AND RELEVANCE A low treatment failure rate occurred in patients with TB uveitis treated with ATT. Phenotypes and test results are studied whereby patients with panuveitis having vitreous and choroidal involvement had a higher risk of treatment failure. These findings are limited by retrospectivemethods. A prospectively derived composite clinical risk score might address this diagnostic uncertainty through holistic and standardized assessment of the combinations of clinical features and investigation results that may warrant diagnosis of TB uveitis and treatment with ATT

Global variations and challenges with tubercular uveitis in the collaborative ocular tuberculosis study

Purpose: The aim of this study was to examine regional variation management practices and outcomes for tubercular uveitis (TBU). Methods: In this retrospective multinational cohort study, patients from 25 international eye care centers diagnosed with TBU with a minimum follow-up of 1 year were included. The geographic variation in treatment outcomes on survival analysis in patients with TBU were analyzed. Treatment failure is defined as a persistence or recurrence of inflammation within 6 months of completing antitubercular therapy, the inability to taper oral corticosteroids to less than 10 mg/d or topical corticosteroid drops to less than 2 drops daily, and/or recalcitrant inflammation necessitating corticosteroid-sparing immunosuppressive therapy. Results: Records of 945 patients (1485 eyes) with TBU were analyzed. The mean age was 41.3 ± 15.0 years (range, 4-90 years), with more males (52.9%, n = 500/945) and predominant Asian ethnicity (74.4%, n = 690/927). Most patients had no symptoms (92.0%, n = 655/712) or history (76.7%, n = 604/787) suggestive of pulmonary tuberculosis (TB). Some patients had evidence of inactive pulmonary TB on chest X-rays (26.9%, n = 189/702) or chest computed tomography (68.6%, n = 109/159). Patients with western geographic origin (log-rank = 6.47, P = 0.010), African or Hispanic ethnicity (log-rank = 19.9, P < 0.001), and positive immigrant status (log-rank = 4.89, P = 0.027) had poorer survival outcomes. Conclusions: This is a first-ever multinational analysis of TBU that highlights regional differences in treatment outcomes for this elusive form of extrapulmonary TB. Our findings will help in the design of future collaborative studies together with internists to develop best practice guidelines for this early opportunity to address TB infection and strategies to target at-risk groups such as immigrants

Global variations and challenges with tubercular uveitis in the collaborative ocular tuberculosis study

Purpose: The aim of this study was to examine regional variation management practices and outcomes for tubercular uveitis (TBU). Methods: In this retrospective multinational cohort study, patients from 25 international eye care centers diagnosed with TBU with a minimum follow-up of 1 year were included. The geographic variation in treatment outcomes on survival analysis in patients with TBU were analyzed. Treatment failure is defined as a persistence or recurrence of inflammation within 6 months of completing antitubercular therapy, the inability to taper oral corticosteroids to less than 10 mg/d or topical corticosteroid drops to less than 2 drops daily, and/or recalcitrant inflammation necessitating corticosteroid-sparing immunosuppressive therapy. Results: Records of 945 patients (1485 eyes) with TBU were analyzed. The mean age was 41.3 ± 15.0 years (range, 4-90 years), with more males (52.9%, n = 500/945) and predominant Asian ethnicity (74.4%, n = 690/927). Most patients had no symptoms (92.0%, n = 655/712) or history (76.7%, n = 604/787) suggestive of pulmonary tuberculosis (TB). Some patients had evidence of inactive pulmonary TB on chest X-rays (26.9%, n = 189/702) or chest computed tomography (68.6%, n = 109/159). Patients with western geographic origin (log-rank = 6.47, P = 0.010), African or Hispanic ethnicity (log-rank = 19.9, P < 0.001), and positive immigrant status (log-rank = 4.89, P = 0.027) had poorer survival outcomes. Conclusions: This is a first-ever multinational analysis of TBU that highlights regional differences in treatment outcomes for this elusive form of extrapulmonary TB. Our findings will help in the design of future collaborative studies together with internists to develop best practice guidelines for this early opportunity to address TB infection and strategies to target at-risk groups such as immigrants

Global variations and challenges with tubercular uveitis in the collaborative ocular tuberculosis study

10.1167/iovs.18-24102Investigative Ophthalmology and Visual Science59104162-4171IOVS

Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis—Report 1: Guidelines for Initiating Antitubercular Therapy in Tubercular Choroiditis

Topic: An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. Clinical Relevance: The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. Methods: An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. Results: Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. Discussion: Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Review of 165 Patients with Tubercular Anterior Uveitis

Purpose: The Collaborative Ocular Tuberculosis Study (COTS) Group sought to address the diagnostic uncertainty through retrospective cohort analysis of treatment regimens and therapeutic outcomes for patients with tubercular Anterior Uveitis (TAU) across international centers. Methods: Multicentre retrospective analysis of&nbsp;patients diagnosed with TAU between January 2004 to December 2014 that had a minimum follow-up of 1 year. Results: One hundred and sixty-five patients were included. One hundred and seven subjects received antitubercular therapy (ATT) (n&nbsp;=&nbsp;107/165; 64.9%) with all the patients receiving topical steroid therapy. Treatment failure was noted in 17 patients (n&nbsp;=&nbsp;17/165; 10.3%), more frequently described in patients that received ATT (n&nbsp;=&nbsp;13/107, 12.2%), than those that did not receive ATT (n&nbsp;=&nbsp;4/58, 6.9%). Conclusion: In this retrospective study, addition of ATT did not have any statistically significant impact on outcome in patients with TAU

Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis—Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis

Topic: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). Clinical Relevance: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. Methods: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. Results: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. Discussion: The COTS consensus guidelines were generated based on the evidence from published literature, specialists’ opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis

Tubercular Uveitis: Nuggets from Collaborative Ocular Tuberculosis Study (COTS)-1

Background: Tuberculosis (TB) is a major infection that can affect the eye as first and sole presentation without features of systemic disease. Controversy exists regarding diagnosis and management of tubercular uveitis (TBU), further compounded by regional variations in disease expression. Purpose: Collaborative Ocular Tuberculosis Study (COTS)-1 aims to address knowledge deficits through collaboration amongst uveitis specialists across the globe by sharing the data of patients with TBU presented at participating centers from January 2004 to December 2014. Methods: Data collection was facilitated by a novel method of real-time encrypted web-based data entry allowing regular updates as new data and recommendations become available. Results: Information on clinical features, investigation findings, management, and treatment outcomes were reviewed to get an idea about real world scenario. Conclusion: The current review aims to focus on methodology and briefing of published reports from COTS group in COTS-1 study to highlight key messages from this large data. © 2019 Taylor & Francis Group, LLC

The Collaborative Ocular Tuberculosis Study (COTS)-1: A Multinational Description of the Spectrum of Choroidal Involvement in 245 Patients with Tubercular Uveitis

Purpose: To contribute a global description of the spectrum of choroidal involvement in tubercular uveitis (TBU). Methods: Retrospective cohort study of TBU patients with choroidal involvement from 25 centers between January 2004 and December 2014. Medical records of patients with a minimum follow-up of 1 year were reviewed. Results: 245 patients were included. The phenotypic variations included serpiginous-like choroiditis (SLC) (46%), tuberculoma (13.5%), multifocal choroiditis (MFC) (9.4%), ampiginous choroiditis (9%), among others. 219 patients were treated with anti-tubercular therapy (ATT) (n = 219/245, 89.38%), 229 patients with steroids (n = 229/245, 93.47%) and 28 patients with immunosuppressive agents (n = 28/245, 11.42%). Treatment failure was noted in 38 patients (n = 38/245, 15.5%). Patients with SLC and ampiginous choroiditis appeared to have superior outcomes on survival analysis (p = 0.06). Conclusion: This study provides a comprehensive description of choroidal involvement in TBU. Patients with SLC and ampiginous choroiditis may have better clinical outcomes. ©, Taylor & Francis Group, LLC