How do you approach a patient who has anterior uveitis and is referred for evaluation of ocular TB with a positive Quantiferon gold (as part of their workup) in countries with low TB incidence?

It is a frustrating problem and is expected to increase without solid evidence. Until then, management should involve an interdisciplinary collaborative approach and a shared decision-making process.

I see the following issues. 

1. I feel ophthalmologists follow the diagnostic criteria for TB uveitis used in the COTS-1 (Agrawal et al., PMID 29075752) study. The criteria used in the study were based on expert consensus. Were the criteria validated? 
2. Is it possible to demonstrate the presence of mycobacteria or its genome in ocular fluids/tissues? Ocular inflammation in Latent TB is likely from an immune response to previously acquired Mtb infection, unlike the invasion of the eye by Mtb bacteria in Ocular TB. These tests might suffer from sensitivity issues when there is a low bacterial burden.
3. The literature suggests phenotypic differences in disease expression between endemic and non-endemic countries. The association between positive tests and uveitis might be circumstantial in non-endemic countries, and the etiology of uveitis might be idiopathic. 
4. Should we institute conventional TB therapy or therapy for latent TB in nonendemic countries? 

I often see patients diagnosed with uveitis and have a Positive QuantiFERON TB test with no systemic symptoms suggestive of TB/CXR evidence of TB infection/negative workup for other etiologies. There is usually a time lag between initial ophthalmology and outpatient ID evaluations. They end up on topical or systemic corticosteroids before ID evaluation, depending on the severity of the uveitis. 

I tend to choose conventional ATT with a four-drug regimen if they have:

1. Characteristic eye findings such as granulomatous uveitis, serpiginous choroiditis, choroidal tubercle, choroidal granuloma, subretinal abscess, serpiginous choroiditis or retinal vasculitis irrespective of their TB risk factors.
2. TB risk factors and severe disease not responding to immunosuppressive therapy or requiring escalation in treatment.

I choose therapy for latent TB if the patients do not have TB risk factors and have severe disease. If the patient has anterior uveitis requiring topical steroids and is improving, I would repeat the test to rule out false positives and consider treatment for latent TB accordingly.

This is an increasing problem in the US, and very frustrating, as most of the time there is a plan to start high-dose steroids for the uveitis. We have more cases of ocular TB now diagnosed than any other form of X-pulm TB in our area.

After a good history rules out TB risk factors, and the exam and CXR show no evidence of active TB anywhere else, I will discuss with the Ophthalmologist as to how strong their suspicion is for the uveitis being due to active TB. Often it has been going on for years, and someone just did the TB test, and it is thus unlikely to be from TB. However, if they are going to be on prolonged courses of high-dose steroids, I usually treat them for TB infection, even if I think it is a false positive. Unfortunately, we have had to treat with multidrug treatment sometimes as there is no way to prove this is not active TB.