Ocular Tuberculosis

Adeel Mushtaq

Introduction

Tuberculosis is an infection caused by Mycobacterium tuberculosis, which can manifest in multiple organs, most commonly the lungs, but can also affect the eye. The unique aspect of infection by M. tuberculosis is the complex interplay that occurs with the host immune system, leading to chronicity of the infection. When initial infection occurs, it promotes a type IV hypersensitivity reaction leading to the recruitment of alveolar macrophages that attempt to phagocytose and destroy the bacilli. However, when they fail, the bacteria multiplies within the intracellular matrix and bursts out, leading to the recruitment of more macrophages and a domino effect ensues. Lymphocytes are then recruited and form a granuloma to contain the infection. In immunocompetent individuals, this can lead to resolution of infection or indefinite latency. In the setting of immunocompromised patients, the disease can progress to active TB (1).

The term “ocular TB” refers to the involvement of any part of the eye and adnexa. This can be primary or secondary; the later referring to hematogenous seeding of the infection from a primary site or contiguous seeding of infection.

Epidemiology

In 2017, there was estimated to be 1.4 million deaths worldwide attributed to tuberculosis, making this compete with HIV as the leading cause of death from infectious diseases (2). Extra-pulmonary TB can manifest anywhere in the body; and does not require the co-existence of pulmonary TB to exist. The most common extra-pulmonary manifestation is within the skeletal system (3), with approximately 1-2% of patients with systemic TB developing ocular manifestations.

Clinical Manifestations

Ocular tuberculosis has a wide variety of presentations, as it can affect almost all structures within and around the eye. Anterior segment manifestations may include chronic iritis, keratitis, conjunctivitis and episcleritis. Posterior segment involvement can cause choroiditis, retinal vasculitis, and optic nerve complications (4).

As a result, patients would report a variety of symptoms including reduced visual acuity, ocular pain, photophobia, floaters and ocular redness. This outline the importance of comprehensive ophthalmological and systemic evaluation key in the work-up for these patients (5).

Diagnostic Approach

Diagnosing ocular tuberculosis requires a comprehensive clinical history, focusing on prior/childhood exposure risk factors, previous treatment, immunisation status, systemic features of disease such as fever, night sweats, malaise, and geographical and occupational risk factors (6).

The mainstay serology studies used in suspected TB cases are interferon-gamma release assays (IGRAs) and tuberculin-skin test (T-Spot). Both have been shown to have a sensitivity of above 80% and specificity above 79% (7). Other serological studies include specific antibody panels, mainly to rule out vasculitis as a cause of the symptoms, and inflammatory markers.

Intraocular fluid analysis provides definitive diagnostic insights through techniques such a Polymerase Chain Reaction (PCR), culture studies and Acid-Fast Bacilli (AFB) smear examination, all of which are very sensitive to TB.

Advanced imaging modalities are required in both diagnostics and, after diagnosis has been established, to examine for other seeding of disease. Ocular imaging includes optical coherence tomography (OCT), which can directly visualise a choroidal tuberculoma or indirectly image areas of non-perfusion of the retina, and fluorescein angiography. This can better evaluate retinal vascular leakage and active choroidal disease (8).

Differential Diagnosis

As explored, the clinical presentation of ocular TB mimics several other inflammatory and infectious conditions, presenting significant diagnostic challenge (9). Close differentials with practical tips are listed below:

Sarcoidosis

Distinguishing features:

  • Sarcoidosis typically presents with bilateral granulomatous inflammation
  • Unlike TB, sarcoidosis shows characteristic bilateral hilar lymphadenopathy on chest imaging
  • Serum angiotensin-converting enzyme (ACE) levels are often elevated in sarcoidosis
  • TB lesions tend to be more asymmetrical and have a more variable presentation
  • Specific tests include:
    • Kveim-Siltzbach test
    • Chest X-ray comparison
    • Serum ACE level measurements

Syphilis

Diagnostic differentiation:

  • Syphilitic uveitis often demonstrates more pronounced vascular involvement
  • Specific serological markers:
    • Fluorescent treponemal antibody absorption (FTA-ABS) test
    • Rapid plasma reagin (RPR) test
    • Venereal Disease Research Laboratory (VDRL) test
  • Syphilis typically shows more prominent secondary signs of systemic infection
  • Treponema pallidum particle agglutination (TPPA) test can provide definitive diagnosis

Viral Uveitis

Key distinguishing characteristics:

  • Viral uveitis often has a more acute onset
  • Specific viral markers can be detected through:
    • Polymerase chain reaction (PCR)
    • Specific antibody titres
  • Herpes-related uveitis typically shows characteristic dendritic keratitis
  • Cytomegalovirus (CMV) uveitis more common in immunocompromised patients
  • More pronounced inflammatory response with less granulomatous formation

Fungal Infections

Differentiation strategies:

  • Fungal infections often show more indolent progression
  • Specific diagnostic approaches:
    • Detailed fungal culture
    • Specific antibody testing
    • Microscopic examination of intraocular fluid
  • Characteristic retinal infiltrates with distinct morphological features
  • More common in immunocompromised patients
  • Specific staining techniques (KOH preparation, calcofluor white stain)

Toxoplasmosis

Diagnostic considerations:

  • Typically presents with more defined, discrete chorioretinal lesions
  • Specific serological markers:
    • Toxoplasma-specific IgG and IgM antibodies
    • Sabin-Feldman dye test
  • Often shows characteristic chorioretinal scars
  • More prevalent in patients with compromised immune systems
  • Distinct pattern of inflammatory response

Lymphoma

Critical differentiation points:

  • Requires advanced diagnostic techniques
  • Cytological examination of intraocular fluid
  • Immunohistochemical studies
  • Flow cytometry analysis
  • Molecular studies for specific genetic markers
  • Typically shows more uniform cellular infiltration
  • Less inflammatory response compared to infectious causes

Behçet’s Disease

Distinguishing features:

  • Characterized by recurrent oral and genital ulcers
  • More pronounced systemic inflammatory manifestations
  • Specific diagnostic criteria including mucocutaneous findings
  • HLA-B51 genetic marker associated with higher prevalence
  • More frequent in specific geographical regions

Treatment Strategies

Management of ocular TB is generally treated under the same guidelines as active pulmonary or extra-pulmonary TB. Standard anti-TB antibiotic regime involves: 8 weeks of triple therapy (Rifampicin, Isoniazid and Ethambutol) with pyrazinamide to avoid complications of treatment; and then 18 weeks of dual therapy (Rifampicin and Isoniazid). It is becoming more common to see single-drug or even multi-drug-resistant TB affecting populations across the world, so culture reports including sensitivities on a broad range of antibiotic is paramount in adequately covering these patients. Additional corticosteroid, either topical or oral, can help alleviate inflammation which can be triggered by initiation of therapy by a Jarisch-Herxheimer reaction.

References

  1.  Tobin EH, Tristram D. Tuberculosis. [Updated 2024 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441916/
  2.  Semin Respir Crit Care Med 2013; 34(01): 003-016. DOI: 10.1055/s-0032-1333467
  3. Pang Y, An J, Shu W, Huo F, Chu N, Gao M, Qin S, Huang H, Chen X, Xu S. Epidemiology of Extrapulmonary Tuberculosis among Inpatients, China, 2008-2017. Emerg Infect Dis. 2019 Mar;25(3):457-464.
  4. Dutta Majumder P, et al. Ocular tuberculosis. Surv Ophthalmol. 2020;65(4):517-538.
  5. Kawali A, et al. Ocular manifestations of tuberculosis. Curr Opin Pediatr. 2017;29(1):67-74.
  6. Koirala S, et al. Diagnostic approach to ocular tuberculosis. J Ophthalmic Inflamm Infect. 2018;8(1):7.
  7. Sester M, Sotgiu G, Lange C, Giehl C, Girardi E, Migliori GB, Bossink A, Dheda K, Diel R, Dominguez J, Lipman M. Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis. European Respiratory Journal. 2010 Dec 30;37(1):100-11.
  8. Marchese A, et al. Imaging in ocular tuberculosis. Clin Radiol. 2015;70(10):1140-1147.
  9. Moshfeghi DM. Differential diagnosis of ocular inflammatory disease. Curr Opin Ophthalmol. 2018;29(3):269-275.

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