Tuberculosis and the Eye

Ocular tuberculosis results from haematogenous spread of Mycobacterium tuberculosis, a delayed hypersensitivity reaction to mycobacterial antigens, or occasionally direct inoculation. It can occur with or without active pulmonary or systemic disease, and it is a major cause of infectious uveitis in endemic regions (up to 10 to 25 percent of uveitis in high burden countries).

• Ocular manifestations:
  • Uveitis: granulomatous or non-granulomatous anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis.
  • Choroid: choroidal tubercles (miliary tuberculosis), choroidal granuloma (tuberculoma), tuberculous multifocal serpiginous like choroiditis.
  • Retina: retinal vasculitis (periphlebitis, occlusive, with neovascularisation and vitreous haemorrhage), Eales disease (a presumed hypersensitivity related periphlebitis), and subretinal abscess.
  • Cornea and sclera: phlyctenular keratoconjunctivitis, interstitial keratitis, scleritis.
  • Orbit and lids: tuberculous dacryoadenitis and lupus vulgaris, orbital abscess, and preseptal disease.
  • Neuro ophthalmic: optic neuritis, papillitis, tuberculoma, and basal meningitis with cranial neuropathies and papilloedema.
• Anti-tuberculous drug toxicity: ethambutol (optic neuropathy), isoniazid (optic neuropathy), rifabutin (uveitis), and streptomycin (cranial nerve VIII toxicity).

• Variable and chronic: blurred vision, floaters, redness, pain, and photophobia. Granulomatous keratic precipitates, iris nodules, posterior synechiae, vitritis, snowballs, retinal vasculitis with perivascular sheathing, peripheral non-perfusion, neovascularisation, vitreous haemorrhage, and choroidal lesions (creamy yellow, 0.25 to 1 disc diameter, miliary tubercles).
• Serpiginous like choroiditis: multifocal, spreads from the edge of the lesions with a "wagon wheel" pattern, differing from the true serpiginous pattern around the disc.
• Systemic signs: cough, weight loss, night sweats, fever, lymphadenopathy, previous contact, immunosuppression, HIV, and endemic exposure.
• Phlyctenular disease: nodules at the limbus in children with tuberculosis infection.

• Ocular examination with slit lamp, dilated fundus examination, optical coherence tomography, fluorescein and indocyanine green angiography, and widefield imaging.
• Immunological tests: interferon gamma release assay (preferred) or tuberculin skin test (induration above 10 mm; above 5 mm in HIV); these show exposure, not active disease.
• Chest radiograph and CT chest for mediastinal lymphadenopathy, parenchymal disease, and calcification; sputum smear, culture and nucleic acid amplification when indicated; other samples (urine, lymph node biopsy).
• Aqueous or vitreous polymerase chain reaction for the mycobacterial genome (IS6110, MPB64); biopsy of lesions; exclusion of other causes (sarcoidosis, syphilis, toxoplasmosis, viral retinitis, lymphoma, HLA-B27 disease).
• HIV test, full count, liver function, and renal function before treatment.
• Diagnosis of probable ocular tuberculosis is made by compatible ocular signs, positive immunological test or evidence of tuberculosis, exclusion of other causes, and response to antitubercular therapy.

• Antitubercular therapy with an infectious disease or chest physician for 6 to 12 months (many centres use 9 to 12 months for ocular disease):
  • Initial phase (2 months): isoniazid 5 mg/kg (maximum 300 mg), rifampicin 10 mg/kg (maximum 600 mg), pyrazinamide 25 mg/kg (maximum 2 g), ethambutol 15 mg/kg, all daily, with pyridoxine 10 to 25 mg daily.
  • Continuation phase (4 to 10 months): isoniazid 5 mg/kg (maximum 300 mg) and rifampicin 10 mg/kg (maximum 600 mg) daily.
  • Monitor liver function monthly initially (stop for transaminases above 5 times the upper limit or above 3 times with symptoms), and screen vision (acuity, colour vision) monthly during ethambutol treatment; stop ethambutol for any visual change.
• Corticosteroids as adjuncts, started 2 to 3 days after antitubercular therapy: oral prednisolone 1 mg/kg daily (60 to 80 mg), tapered over 6 to 8 weeks; topical prednisolone acetate 1 percent and cycloplegia (cyclopentolate 1 percent three times daily) for anterior uveitis; periocular or intravitreal triamcinolone for macular oedema.
• Retinal vasculitis with ischaemia: panretinal photocoagulation; intravitreal anti-VEGF for neovascularisation or oedema; vitrectomy for non-clearing haemorrhage or tractional detachment.
• Immunosuppressive steroid sparing therapy (methotrexate 15 to 25 mg weekly, azathioprine 2 mg/kg, adalimumab 40 mg every 2 weeks) only after antitubercular therapy has been established for recurrent inflammation.
• Monitor for paradoxical reactions (worsening after starting therapy), drug resistance (multidrug resistant regimens by specialists), adherence, and recurrence for at least 2 years.
• Contact tracing and screening of household contacts; BCG and public health measures.