Role of the infectious disease consultant in management of patients with Tuberculosis-associated ocular inflammation

Tuberculosis (TB), the second leading cause of death from an infectious disease, poses serious complications for those infected. In 2013 alone, an estimated 9 million people were diagnosed and 1.5 million died as a result of TB [1]. Approximately one third of the world's population is suspected to be infected with Mycobacterium tuberculosis (MTB), with approximately 10% expected to develop tuberculous disease during their lifetime [2]. Within the United States, the Centers for Disease Control and Prevention (CDC) reported the disease prevalence as 3 cases per 100 000 persons in 2013 with foreign-born persons having nearly 13 times higher rates of disease [3]. Additional risk factors include homelessness, low socioeconomic status, detainment in correctional facilities, and human immunodeficiency virus (HIV) infection [4]. The true prevalence may be underreported, because there remains difficulty in confirming the diagnosis in many patients. Tuberculosis is typically associated with pulmonary infection, but in up to 20% of cases pulmonary involvement is absent [5]. Extrapulmonary TB can involve almost any site of the body, including the eye. Tuberculosis-associated ocular inflammation (TB-AOI) is the presence of infection and/or inflammation involving the eye as a result of direct infection of the eye or in association with extraocular TB. Tuberculosis-AOI may present with a variety of ophthalmic clinical findings involving almost any structure of the eye, often mimicking other inflammatory conditions. Pathology evaluation typically reveals granulomatous inflammation [6]. Eye manifestations of TB are categorized based on the primary anatomical location of the inflammation in accordance with the Standardization of Uveitis Nomenclature Working Group [7]. Anterior uveitis describes inflammation involving the iris and ciliary body. Other anterior structures that may be involved are the cornea and sclera. Symptoms suggestive of an anterior process are a red, painful eye with or without decreased vision. Inflammation involving primarily the vitreous is called intermediate uveitis. Posterior uveitis describes inflammation of the choroid and/or retina. Symptoms suggestive of a posterior process are blurry vision, mild or absent pain, and floaters. Panuveitis involves both anterior and posterior segments. Optic neuropathy is primary involvement of the optic nerve. Posterior uveitis is traditionally regarded as the most common site of ocular involvement and predominantly involves the choroid [8]. Gupta et al [2] described 158 patients in India with TB-AOI, which were classified as posterior uveitis (42%), anterior uveitis (36%), intermediate uveitis (11%), and panuveitis (11%). Recent data suggest bilateral disease occurs in 53% to 73% of cases of isolated TB-AOI [6, 9]. Diagnosis of TB-AOI poses a significant challenge to clinicians due to limited diagnostic capabilities. There remains lack of uniform diagnostic criteria agreed upon by infectious disease (ID) specialists and ophthalmologists. Guidelines for the diagnosis of TB-AOI have been proposed to categorize patients as definitive or presumed infection using supportive clinical ocular findings, ocular microbiologic specimens, corroborative evidence (positive tuberculin skin test, interferon gamma release assay, and chest radiography), and exclusion of other causes [2, 10]. In one study of presumed TB-AOI in India, they identified 3 clinical findings specific for TB: broad-based posterior synechiae, retinal vasculitis with or without choroiditis, and serpiginous-like choroiditis [11]. However, these criteria are yet to be evaluated and validated in lower prevalence regions. Pathology and microbiologic testing (acid-fast smear [AFB], tissue culture, polymerase chain reaction [PCR] for MTB DNA) to confirm the presence of TB infection provides a more conclusive diagnosis, but the yield from such studies has been relatively low [6]. In one study, the sensitivity for PCR in vitreous samples ranged from 33.3% to 46.9% [12], and in another study only 3.8% of suspected cases were positive [13]. Moreover, positive tissue-based PCR results have been obtained in up to 11% of controlled patient groups that had been assumed not to have TB-AOI [14]. The added risk of ocular morbidity while obtaining a specimen must be weighed against what has seemed low benefit. In addition to inadequate diagnostic capabilities, there is also speculation that many ocular manifestations are immune-mediated hypersensitivity reactions secondary to TB infection in other sites of the body, as opposed to active ocular infection [15, 16]. Without direct evaluation for TB from ocular specimens, differentiating infection from inflammation may be impossible [8]. The role for early evaluation and management by an ID specialist has been well described [2, 14, 17–19]. There are limited data in the literature regarding clinical approach taken by the ID specialist with these complicated cases. We present a large series of patients referred to an academic ID clinic for evaluation of presumed TB-AOI.