18/4/2018 https://www.medscape.com/viewarticle/772189_print https://www.medscape.com/viewarticle/772189_print 1/12 www.medscape.com Reema Bansal; Aman Sharma; Amod Gupta Expert Rev Ophthalmol. 2012;7(4):341-349. Abstract and Introduction Abstract Intraocular involvement by Mycobacterium tuberculosis is common in the absence of systemic evidence of tuberculosis. It can have protean manifestations with certain clinical signs that differentiate it from nontubercular causes of uveitis. Retinal vasculitis and serpiginous-like choroiditis have typical presentations. The diagnosis is usually presumptive and corroborated by laboratory tests such as positive tuberculin skin test or IFN-g release assays, or radiographic evidence on chest x-ray or PET/computer-assisted tomography. Definitive diagnosis by histopathological demonstration of mycobacteria is extremely rare, although PCR is increasingly being performed on intraocular samples. Antitubercular therapy effectively reduces the rate of recurrence of inflammation when administered in a timely manner along with corticosteroids. Introduction Tuberculosis (TB), a multisystem infectious disease caused by Mycobacterium tuberculosis (MTB), primarily affects the lungs and causes significant morbidity and mortality worldwide. TB, however, may affect other organs, including the eye. Intraocular TB is usually not associated with clinical evidence of pulmonary TB, as up to 60% of extrapulmonary TB patients may not have pulmonary TB. [1] In recent years, there is a growing concern for TB as a major public health problem, increasing the prevalence of tuberculous eye disease. Epidemiology Diagnosis and treatment of TB remains a challenge especially in the developing world, which bears the majority of the global disease burden. [2] There are increasing reports of TB as a cause of uveitis from various regions of the world. [3–5] In the Sverdlovsk region of Russia, intraocular TB ranked fourth among extrapulmonary TB, following involvement of the urinary tract, peripheral lymph nodes, and bones and joints. [6] Ocular involvement in patients with systemic TB is uncommon and only 1.2–1.39% of patients with pulmonary TB may have intraocular TB. [7,8] However, in a series of 100 randomly selected patients with culture-proven systemic TB seen in a university hospital in Spain, 18 (18%) were found to have intraocular TB. [9] On the other hand, in a series of 494 patients with presumed intraocular TB, only 15 (3.03%) patients showed evidence of concurrent systemic TB disease. [10] Prevalence of TB as an etiology of uveitis has varied from 0.39% in South India, [11] 0.5% in the USA, [12] 4% in China, [13] 6.31% in Italy, [14] 6.9% in Japan, [4] 9.86% in North India [3] and 10.5% in Saudi Arabia. [15] Studies from the same institute in South India at different time periods have revealed changing patterns of uveitis. [16] Pathogenesis of Intraocular TB The pathogenesis of intraocular TB is not clear. In the absence of isolation of MTB from the ocular sites by either smear or cultures, pathogenesis of uveitis associated with TB has at best remained speculative. Pleural TB is believed to be caused by delayed type of hypersensitivity response to mycobacterial antigens and release of inflammatory cytokines by activated pleural cells. [17] If a similar mechanism is involved in tuberculous uveitis, it is difficult to prove due to the lack of opportunities of choroidal biopsy. In an enucleated eye of uveitis, Rao et al. documented the presence of MTB in the necrotic retinal pigment epithelium (RPE)which was confirmed by quantitative PCR. [18] They found 1.7 × 10 6 copies of MTB genome in the microdissected RPE cells. This location of the MTB may explain the nature of clinical lesions seen in patients with tuberculous uveitis. MTB is known to be a facultative intracellular parasite and multiplies in nonactivated macrophages. [19] The RPE cells that are known to express Toll-like receptors may actively phagocytose MTB that reaches the inner choroid via the hematogenous route. Once the intracellular MTB reaches a sufficient number in the macrophages, a cytotoxic cell-mediated response leads to destruction of the macrophages and surrounding tissue, and the formation of the caseum. [19] A similar mechanism may be operative in the eye as well. Rao et al. developed a model of intraocular TB by way of MTB aerosol infection in guinea pigs to mimic human infection. [20] MTB delivered via aerosol resulted in dissemination of the organisms to the eye besides the lungs. In the untreated animals, uveal TB developed in 42% of eyes, with the presence of acid-fast bacilli (AFB) and MTB DNA in uveal granulomas. Interestingly, in the animals given anti-TB drugs, none showed the presence of AFB but showed mild nongranulomatous inflammation. [20] In another study, Thayil et al. reported microbiological evidence of ocular TB within at least 4 weeks of aerosol infection. [21] Simultaneous with their appearance in the spleen and other organs, the organisms could be cultured form the eyes at 28 days after aerosol infection, thereby indicating that the ocular infection takes place by a hematogenous route. The resultant tuberculous granuloma lesions in the choroid were hypoxic, and the RPE and photoreceptors showed increasing levels of VEGF similar to what has been observed in the granulomas of lung TB. [21] While it is known that genotypic variations determine the clinical manifestations of TB, [22] there is as yet complete absence of data on the genetic types of MTB that cause various manifestations of intraocular TB. Intraocular Tuberculosis