29. Tuberculosis

Arash Maleki¹

(1)

Massachusetts Eye Research and Surgery Institution, Waltham, MA, USA

Keywords

TuberculosisUveitis

Overview

Definition
- An airborne communicable disease caused by Mycobacterium tuberculosis and three related mycobacterial species (M. bovis, M. africanum, and M. microti). Ocular tuberculosis (TB) is defined as infection in the eye, around the eye, or on its surface
- Two billion people are estimated to be latently affected with TB, 95% of whom are in developing countries
- Ocular disease occurs in 1–2% of patients infected with TB
Symptoms
- Highly variable, as it can affect any structure in the eye or around the eye. Symptoms range from very subtle, leading to delay in referral and diagnosis, to severe, sight-threatening complications
Laterality
- It can be unilateral or bilateral
Course
- Chronic course with an insidious onset
Age of onset
- All age groups may be affected
Gender/race
- M = F
- Patients are typically from TB endemic regions (especially Africa and South Asia) and/or of Asian or Indian ethnicity
Systemic association
- Ocular TB occurs as a consequence of primary infection, dissemination of systemic infection, or reactivation of latent TB, with host’s own immune response and hypersensitivity playing a role in propagating inflammation

Many patients with ocular TB have latent systemic disease, so there may not be any systemic symptom
Cough lasting >3 weeks, hemoptysis, chest pain, weight loss, fever, night sweats, chills, loss of appetite
Extrapulmonary TB occurs via hematogenous dissemination and can affect practically any organ
- Up to 60% of patients with extrapulmonary TB may have undiagnosed pulmonary disease
- Miliary TB: affects young children, elderly, and immunocompromised; bone marrow is frequently affected, with anemia, thrombocytopenia, and leukocytosis

OCT
- Macular thickening, cystoid changes, and epiretinal membrane
FA
- Vitreous haze, optic nerve head leakage, retinal vascular leakage or staining, and choroidal inflammation with no or mild early diffuse hyperfluorescence, which evolves into late intense hyperfluorescence
ICG
- Hypofluorescent spots in early and late phases if there is choroiditis

Chest x-ray
Identification of the organism by culture is the most reliable and definitive diagnostic method, but usually not possible when only ocular disease is present
Purified protein derivative (PPD): 5 mm or more in immunocompromised, 10 mm or more in immunocompetent, including children, and 15 mm or more in Bacillus Calmette–Guérin (BCG)–vaccinated
- Cheap and widely available
- Can help distinguish active vs. latent disease
- Subjective interpretation, false positive in BCG-vaccinated, and false negative in immunocompromised
IFN-γ release assays (QuantiFERON-TB Gold)
- More specific than PPD, not affected by BCG vaccination or other atypical mycobacteria
- Cannot distinguish active vs. latent disease
- Costly and not widely available in developing countries
PCR amplification of ocular fluids
- Allow for rapid analysis and can help identify drug-resistant strains
No single test offers high enough sensitivity and specificity to be used alone

In the USA, Centers for Disease Control and Prevention (CDC) suggests starting with RIPE therapy (rifampin, isoniazid, pyrazinamide, ethambutol) for 2 months, then rifampin/isoniazid double therapy is continued for an additional 4–7 months based on subsequent culture result (if obtainable), CXR findings, and HIV status
Generally, a 9-month treatment is effective for ocular TB
In case of drug resistance, second-line agents are used: streptomycin, cycloserine, P-aminosalicylic acid, ethionamide, and capremycin are all FDA-approved for TB
Off-label agents include amikacin, kanamycin, and fourth-generation fluoroquinolones
Corticosteroids may be used judiciously when there is persistent or even progressive ocular disease despite appropriate anti-TB therapy, as hypersensitivity reaction to TB bacilli plays an important role in ocular inflammation