Ocular Immunology & Inflammation, 2015; 23(4): 353–357 Copyright ! Taylor & Francis Group, LLC ISSN: 0927-3948 print / 1744-5078 online DOI: 10.3109/09273948.2015.1056536 REVIEW ARTICLE Pathogenesis and Pathology of Intraocular Tuberculosis Soumyava Basu, MD 1 , Denis Wakefield, MD 2 , Jyotirmay Biswas, MD 3 , and Narsing A. Rao, MD 4 1 LV Prasad Eye Institute, Bhubaneswar, India, 2 Department of Pathology, School of Medicine Sciences, Faculty of Medicine, University of New South Wales, Inflammation and Infectious Research Center, Sydney, Australia, 3 Department of Uveitis and Ocular Pathology, Sankara Nethralaya, Chennai, Tamil Nadu, India, and 4 Deparment of Ophthalmology and Pathology, USC Eye Institute, USC Keck School of Medicine, University of Southern California, Los Angeles, California, USA ABSTRACT Intraocular tuberculosis (TB) is an extremely paucibacillary form of extrapulmonary TB. It likely results from bacterial dissemination to the eye from lungs, localization in ocular tissues, followed later by reactivation and appearance of clinical signs. These have been partly demonstrated in the guinea pig model of ocular TB. Alternative hypotheses have been suggested but are not supported by adequate evidence. Mycobacterial recognition by macrophages and dendritic cells probably leads to activation of several immune pathways, primarily the Th1 and Th17 pathways, as in other TB infections. Histopathology of bacteriologically proven ocular TB tissues reveals granulomatous inflammation with central caseous necrosis containing occasional acid- fast organisms. Recent reports have also demonstrated intraretinal granuloma in the vicinity of retinal vessels and T-cell infiltration of epiretinal membranes, in cases of TB retinal vasculitis. Keywords: Animal model, immunology, itraocular tuberculosis, ocular, pathogenesis, pathology Intraocular tuberculosis (TB) is unique among all forms of extrapulmonary TB for 2 reasons: first, it has several clinical manifestations within a single organ, and second, live Mycobacterium tuberculosis is rarely isolated from clinical samples accessible to the ophthalmologist. This has led to a protracted debate on respective roles of immune-mediated inflamma- tion and direct bacteria-mediated inflammation in the pathogenesis of intraocular TB. 1–2 The key differentiating factor between these two mechanisms is their association with latent and active TB, respectively. However, latent TB infection is char- acterized by the presence of a reactive tuberculin skin test or T-cell response to M. tuberculosis antigens in the absence of clinical or radiological findings of TB. 3 During latent TB, M. tuberculosis may exist in several different organs and cell types, but there cannot be any clinical (pulmonary or extrapulmon- ary) disease. 4 Thus the presence of clinical signs of active intraocular inflammation rules out any role of latent TB in such eyes. Recent developments support a more direct role of M. tuberculosis in the pathogenesis of intraocular TB. Polymerase chain reaction (PCR) has been used to amplify the M. tuberculosis genome from up to 70% of clinically suspected cases of intraocular TB. 5–7 Anti- TB therapy has been shown to significantly reduce recurrent inflammation in presumed ocular TB as compared to corticosteroid therapy alone. 8–10 We can therefore speculate that intraocular TB is likely to have pathogenic mechanisms similar to other forms of extrapulmonary TB. Thus if we extrapolate the patho- genesis of extrapulmonary TB to intraocular TB, these mechanisms can be divided into 3 different stages: dissemination of bacteria from the site of primary infection, i.e. lungs, to the eye; localization of bacteria in different ocular tissues, and bacterial reactivation and initiation of inflammation in those tissues. 11–12 Correspondence: Narsing A. Rao, Department of Ophthalmology and Pathology, USC Eye Institute, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. E-mail: narsing.rao@med.usc.edu Received 12 February 2015; revised 16 April 2015; accepted 12 May 2015; published online 4 August 2015 353 Downloaded by [Soumyava Basu] at 21:19 14 August 2015