Definitive diagnosis of TB requires direct evidence of mycobacteria in bodily fluids or tissues. In many cases of ocular TB, this confirmation is not possible, and the diagnosis is instead presumptive, based on indirect evidence. A positive result on a tuberculin skin test using PPD (purified protein derivative of Mycobacterium bovis) test or an interferongamma release assay is indicative of prior exposure to TB but not necessarily of active systemic or ocular infection.
In the United States, an induration of 5 mm or more, read 48–72 hours after intradermal injection of the standard 5-tuberculin-unit (5-TU), or intermediate-strength, test dose is considered a positive result in individuals with HIV infection, those exposed to active TB, or those whose radiographs are consistent with healed tuberculous lesions. An induration of 10 mm or more is considered indicative of a positive result for other high-risk individuals, including patients with diabetes mellitus or renal failure, those on immunomodulatory therapy (IMT), health care workers, and recent immigrants from high-prevalence countries. Patients with no known risks for tuberculosis are considered to have a positive test result if induration is 15 mm or more.
False-negative skin testing results may occur at a rate of up to 25% because of patients with profound acute illness or immune compromise, which can stem from corticosteroid use, advanced age, poor nutrition, and sarcoidosis. False-positive results may arise from patients infected with atypical mycobacteria, immunized with BCG vaccine, and treated with intraluminal BCG injections for bladder carcinoma. Individuals recently immunized with BCG vaccine may have an induration measuring around 10 mm at presentation, but the reaction is usually not sustained and tends to decrease with time compared with the reaction following the skin test after more recent systemic TB exposure. A Bayesian analysis predicts that routine screening of uveitis patients for TB has a low probability of detecting disease in settings where the prevalence of TB is low. It is recommended, therefore, that testing be selectively used for patients in whom the index of suspicion has been heightened by a careful history, review of systems, and clinical examination. Testing for TB is required in patients being considered for treatment with tumor necrosis factor inhibitors or other biologic agents.
A history of recent exposure to TB or a positive TB test result warrants a concerted search for systemic infection, using chest imaging (radiography, computer-assisted tomography and positron emission tomography scanning), and/or microbiologic analysis of sputum, urine, or gastric aspirates, or a cervical lymph node biopsy for acid-fast bacilli. Failure to demonstrate systemic disease does not, however, exclude the possibility of intraocular infection.
For cases of suspected ocular TB in which the results of the above-mentioned testing for systemic infection are negative, the patient is asymptomatic, or the infection is thought to be extrapulmonary, definitive diagnosis may require intraocular fluid analysis or tissue biopsy. Nucleic acid amplification techniques, with either transcription-mediated amplification of 16S ribosomal RNA or PCR amplification of unique DNA sequences of M tuberculosis, have been successfully used in some cases to diagnose intraocular TB, though the yield may be low because of a thick cell wall and possibly low bacterial load in the vitreous. Chorioretinal biopsy used in conjunction with PCR testing and routine histologic examination may be necessary in atypical cases where the differential diagnosis and therapeutic options are widely divergent. Recently, antibodies against purified cord factor, the most antigenic and abundant cell wall component of tubercle bacilli, have been detected by ELISA and may be useful for rapid serodiagnosis of pulmonary TB, in addition to providing supportive data for the diagnosis of ocular infection.
Ang M, Vasconcelos-Santos DV, Sharma K, et al. Diagnosis of ocular tuberculosis. Ocul Immunol Inflamm. 2018;26(2):208–216.
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Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017; 64(2):111–115.
Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.