“Anti-tuberculous therapy in a real-life clinical setting significantly reduced the number of flare-ups and enabled long-term remission in patients with presumed ocular tuberculosis.”
Tuberculosis (TB) remains a global health challenge: The World Health Organization (WHO) estimates that 10.4 million cases and 1.3 million deaths were recorded worldwide in 2016. And although Mycobacterium tuberculosis typically affects pulmonary tissue, the infection may present a myriad of extra-pulmonary manifestations. Intraocular tuberculosis presenting as posterior uveitis may be difficult to recognize by physicians working outside TB-endemic countries, as it mimics a variety of uveitis entities.
Currently, there are no standardized diagnostic criteria for ocular tuberculosis. Instead, confirmation relies on known clinical symptoms’ patterns, tuberculin skin testing and culture, or DNA PCR of MTB in intraocular samples. Interferon gamma release assays (IGRA) are highly specific for MTB infection, but cannot differentiate between latent and active tuberculosis, thereby worsening the controversy.
“While ocular TB, a recognized form of extra-pulmonary TB, is associated with high rates of morbidity, there is little clinical information or standard guidelines for its diagnosis,” shared Dr. Rupesh Agrawal, Adjunct Assistant Professor and Consultant Ophthalmologist, National Healthcare Group Eye Institute NHGEI), Tan Tock Seng Hospital (TTSH), Singapore, shedding light on the ocular TB dilemma. The absence of a unified guide thus poses a challenge in the diagnosis and management of the disease, emphasized Dr. Agrawal.
The Collaborative Ocular Tuberculosis Study (COTS), a first-of-its-kind, multicenter global initiative, according to Dr. Agarwal, was established to address the challenges ocular TB care faces via cloud computing and big data.
“Through this study, we aim to construct a predictive model to identify diagnostic clinical features to not only enhance the care outcomes and treatment combinations for this disease but also create an international database of its own kind,” he explained.
COTS is led by Prof. Rupesh Agrawal from NHGEI Singapore, Prof. Carlos Pavesio from Moorfields Eye Hospital, London, United Kingdom, and Prof. Vishali Gupta from PGIMER, Chandigarh, India, and has uveitis experts from 25 multinational ophthalmology centers.
The team has recently published its first report in JAMA Ophthalmology1 and has several other reports under consideration at various renowned journals.2
“With the support from the scientific fraternity, we can take the study to the next exciting phase of identifying novel biomarkers and transcripts for the diagnosis of this neglected disease [ocular TB],” said. Dr. Agrawal.
Diagnosis isn’t the only hurdle doctors and patients face when it comes to ocular TB – how to best treat it remains a dilemma as well. Recent reports support the use of anti-tuberculous therapy (ATT) in patients with a consistent uveitic phenotype and positive TB investigation. However, there is a lack of consensus on treatment indications, regimens and durations, as well as investigation protocols and what exactly constitutes a successful outcome.
A recent publication in the Journal of Ophthalmic Inflammation and Infection by Damato and colleagues reported the outcomes of ATT in a cohort of patients treated for presumed ocular tuberculosis, based on clinical findings, systemic assessment and specific testing for tuberculosis.3 In this retrospective study, patients diagnosed with tuberculous uveitis and who received ATT over a four-year period (2010-2014) were selected. The authors included only patients who completed a course of treatment and were followed up for at least 12 months. Data on baseline clinical and demographic characteristics were collected. All patients had full ophthalmic examinations, systemic workups, chest radiographs, Mantoux testing and interferon gamma release assays (IGRAs).
Presumed ocular TB was defined as a consistent ocular phenotype, with findings on chest imaging and/or positive T-spot or Mantoux testing after the exclusion of other causes of uveitis. Majority of patients were referred for ATT for ocular TB mainly based on a positive Mantoux and/or IGRA result, with normal chest X-ray imaging and no systemic symptoms. Flare rates pre- and post-treatment and time-to-flares were reported.
Of the 54 patients in whom treatment was recommended, 7 (13%) patients did not comply. Forty-seven (47) patients received a course of ATT. Treatment duration ranged from 4 to 12 months with a mean of 6.8 months. Treatment regimens varied, and 94% and 86% of patients were flare-free at 6 and 12 months, respectively.
However, the study had some limitations. It was conducted in a real-life clinical setting, with patients unavoidably lost to follow-up or non-compliant with their treatment. Furthermore, flare rate was used as a measure of disease activity – which may not accurately reflect disease in patients with ongoing pathology, where uveitis is chronically uncontrolled, or in patients receiving corticosteroid therapy.
The key message from this study is that ATT in a real-life clinical setting significantly reduced the number of flare-ups and enabled long-term remission in patients with presumed ocular tuberculosis. The authors therefore concluded that despite the unresolved controversies regarding diagnosis, the relevance of IGRAs and definition of ocular tuberculosis, if patients have a consistent uveitis phenotype and other uveitic causes are excluded, then ATT is likely to be beneficial.
1 Agrawal R, Gunasekeran DV, Grant R, et al; Collaborative Ocular Tuberculosis Study (COTS)- 1 Study Group. Clinical Features and Outcomes of Patients With Tubercular Uveitis Treated With Antitubercular Therapy in the Collaborative Ocular Tuberculosis Study (COTS)-1. JAMA Ophthalmol. 2017;135(12):1318-1327.
2 Agarwal A, Agrawal R, Gunasekaran DV, et al. The Collaborative Ocular Tuberculosis Study (COTS)-1 Report 3: Polymerase Chain Reaction in the Diagnosis and Management of Tubercular Uveitis: Global Trends. Ocul Immunol Inflamm. 2017; 20:1-9 [Epub ahead of print].
3 Damato EM, Dawson S, Liu X, et al. A retrospective cohort study of patients treated with anti-tuberculous therapy for presumed ocular tuberculosis. Journal of Ophthalmic Inflammation and Infection. 2017;7:23