Abstract

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. To examine the clinical features of TB uveitis and the associations with response to antitubercular therapy (ATT). 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. Treatment failure, defined as a persistence or recurrence of inflammation within 6 months of completing ATT, 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. 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). 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 retrospective methods. 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.

Highlights

  • 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

  • A low treatment failure rate occurred in patients with TB uveitis treated with antitubercular therapy (ATT)

  • Results suggested that accurate diagnosis of TB uveitis required a multipronged approach considering clinical features and investigations as a whole. Meaning These results suggest a lack of comprehensive evidence for diagnostic approaches for TB uveitis, with regional inconsistencies in the workup of patients possibly affected

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Summary

Methods

COTS-1 is an exploratory retrospective cohort study of patients diagnosed with TB uveitis from January 1, 2004, through December 31, 2014, conducted by 25 multinational centers. Participating centers were as follows: National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; Moorfields Eye Hospital, London, England; Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India; LV Prasad Eye Institute, Hyderabad, India; Singapore National Eye Centre, Singapore; Department of Clinical Ophthalmology & Eye Health, Central Clinical School, Save Sight Institute, The University of Sydney, Sydney, Australia; Ocular Immunology Unit, Department of Ophthalmology, Arcispedale-IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; Sankara Nethrayala, Chennai, India; Shroff Eye Centre, New Delhi, India; Dr Shroff’s Charity Eye Hospital Daryaganj, New Delhi, India; Narayana Nethralaya, Bangalore, India; Department of Ophthalmology, Fattouma Bourguiba University Hospital, Faculty of Medicine, University of Monastir, Tunisia; University of Manchester, United Kingdom; Istanbul Faculty of Medicine, Department of Ophthalmology, Istanbul University, Turkey; Prabha Eye Clinic & Research Centre, Vittala International Institute of Ophthalmology, Bangalore, India; LV Prasad Eye Institute, Bhubaneswar, India; Bristol Eye Hospital, Bristol, England; King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia; University of Pierre and Marie Curie, Paris, France; Luigi Sacco Hospital, University of Milan, Italy; Department of Ophthalmology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois; Centre for Ophthalmic Specialised Care & University of Laussane, Laussane, Key Points.

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