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TB or not TB? The perennial question
  1. EMMETT T CUNNINGHAM, JR
  1. The Pearl and Samuel J Kimura Ocular Immunology Laboratory, The Francis I Proctor Foundation and the Department of Ophthalmology, UCSF, Medical Center, San Francisco, California, USA
  2. Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, Tamil Nadu, India
  1. S R RATHINAM
  1. The Pearl and Samuel J Kimura Ocular Immunology Laboratory, The Francis I Proctor Foundation and the Department of Ophthalmology, UCSF, Medical Center, San Francisco, California, USA
  2. Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, Tamil Nadu, India
  1. Dr Emmett T Cunningham, Jr, The Pearl and Samuel J Kimura Ocular Immunology Laboratory The Francis I Proctor Foundation, UCSF, Medical Center, San Francisco, CA 94143–0944, USAemmett{at}itsa.ucsf.edu

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Tuberculosis is the leading infectious cause of morbidity and mortality worldwide.12 The World Health Organization (WHO) currently estimates that nearly two billion people, or one third of the world's population, are infected by tuberculosis, and that roughly 10% of these infected people will develop clinical disease at some point during their lifetime. This enormous pool of infected individuals results in 8–10 million new cases of tuberculosis and nearly three million deaths due to infection each year. Countries in the developing world, particularly in Africa and South East Asia, bear the brunt of the burden, with more than 95% of new infections and 98% of infection related deaths occurring in these regions. The situation is made even more difficult by the growing human immunodeficiency virus (HIV) epidemic, since simultaneous infection by HIV greatly increases the risk of developing active tuberculosis.3 At present, 5–10% of all patients with tuberculosis worldwide are also infected with HIV, and in many developing countries tuberculosis is now the most common opportunistic infection in HIV positive patients. These factors, together with poverty, limited resources, and the widespread emergence of multidrug resistant strains of tuberculosis, have led the WHO to declare tuberculosis a global emergency.

Ocular complications of tuberculosis, although less common than systemic involvement,45 are well recognised. Virtually any ocular tissue may be affected, including the ocular adnexa, the cornea, the conjunctiva, the sclera, the uveal tract, the retina, and the optic nerve.67 Uveitis, particularly when accompanied by choroiditis, appears to be the most frequent ocular manifestation of infection. Other findings that can support the diagnosis of tuberculous uveitis include, however, the presence of large keratic precipitates or iris nodules, so called “granulomatous” findings, and retinal vasculitis, which is frequently ischaemic in nature.8

The diagnosis of ocular tuberculosis is often problematic.67 The physical findings mentioned above are suggestive but non-specific. Culture or direct histopathological examination of infected tissue can provide definitive proof of ocular infection9-11 but is often impractical given the risks of intraocular biopsy, particularly in the setting of active inflammation. Polymerase chain reaction based assays performed on ocular fluids provide strong evidence of infection10-15 but are not well standardised, and are available only at selected centres.16-18 This leaves chestx ray and purified protein derivative (PPD) skin testing, which, although useful, particularly in patients at high risk of infection,5 have limited sensitivity and specificity.1117-19

The paper by Sakai and associates that appears in this issue of theBJO (p 130) is of great interest, therefore, because it describes the use of a rapid serological test to help support the diagnosis of ocular tuberculosis. The authors studied 15 patients with uveitis and retinal vasculitis—nine with evidence of previous exposure to Mycobacterium tuberculosis, all of whom had a positive PPD, one of whom had active pulmonary tuberculosis, and four of whom had radiographic evidence of previous pulmonary tuberculosis; three patients with sarcoidosis; and three patients with Behçet's disease. Each of these patients was tested for the presence of serum antibodies directed against purified cord factor (trehalose-6,6′-dimycolate or TDM), the most antigenic and abundant cell wall component ofM tuberculosis. All of the patients with presumed ocular tuberculosis but none of the control patients had antipurified cord factor antibodies in their serum. In addition, those patients who had not had previous antituberculosis treatment tended to have higher antibody titres than those patients who had had previous treatment, suggestions that antibody titres might, in some cases, be useful for monitoring response to therapy. These results confirm previously published findings from the same group describing the usefulness of serum antipurified cord factor antibodies to both diagnose and monitor treatment responses in patients with pulmonary tuberculosis.20 There is some hope, therefore, that such serological assays, if more widely available, could both simplify and improve our ability to diagnose ocular tuberculosis. For now, however, most ophthalmologists will have to depend upon their own clinical skills supported by the time honoured and judicious use of chestx ray and PPD testing.

Acknowledgments

This work was supported in part by a career development award from Research to Prevent Blindness, Inc, New York, USA.

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