What is the recommended protocol for diagnosing and treating ocular tuberculosis?

Protocol for Ocular Tuberculosis

Diagnostic Approach

Screen for tuberculosis in any patient presenting with uveitis of unknown etiology, recurrent uveitis, or uveitis not responding to conventional therapy, as well as in cases with ocular findings highly suggestive of TB. 1

Essential Diagnostic Workup

• Tuberculin skin testing (TST) and interferon-gamma release assay (IGRA) should be performed as the primary screening tools for ocular TB. 1
• Complete medical history focusing on TB exposure, prior TB infection, immunosuppression status, and HIV status. 1, 2
• Comprehensive ophthalmologic evaluation including slit-lamp biomicroscopy, indirect ophthalmoscopy, and fluorescein angiography to characterize the pattern of ocular involvement. 2, 3
• Chest imaging (chest X-ray or CT) to identify pulmonary or mediastinal TB, though ocular TB frequently occurs without active pulmonary disease. 1, 3
• Attempt microbiological confirmation when feasible through acid-fast bacilli microscopy, culture on Löwenstein-Jensen medium, or PCR from ocular specimens (aqueous/vitreous fluid, tissue biopsy). 2, 3

Common Clinical Presentations

• Anterior segment: Granulomatous or nongranulomatous anterior uveitis, keratitis, scleritis (focal, nodular, or diffuse). 4, 3
• Posterior segment: Vitritis, choroiditis, choroidal tubercles, serpiginous-like choroiditis, posterior uveitis. 2, 3
• Severe presentations: Panophthalmitis, endophthalmitis (particularly in immunocompromised or HIV-infected patients). 2, 3

Treatment Protocol

All patients with presumed or confirmed ocular tuberculosis should receive standard four-drug antituberculous therapy for 6-9 months, consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol. 1

Standard Antituberculous Regimen

Initial Intensive Phase (2 months)

• Isoniazid (INH): 5 mg/kg daily (maximum 300 mg/day). 5
• Rifampicin (RIF): 10 mg/kg daily (maximum 600 mg/day). 5
• Pyrazinamide (PZA): 25-35 mg/kg daily. 5
• Ethambutol (EMB): 15-25 mg/kg daily. 5

Continuation Phase (4-7 months)

• Isoniazid + Rifampicin daily for an additional 4-7 months (total treatment duration 6-9 months). 1, 5

Critical Pre-Treatment Screening for Ethambutol

Visual acuity must be tested by Snellen chart before prescribing ethambutol, and patients must be counseled to stop the drug immediately and report if visual symptoms occur. 5

• Ethambutol should only be used in patients with reasonable visual acuity who can appreciate and report visual changes. 5
• Document in the medical record that the patient has been warned about ocular toxicity. 5
• Inform the patient's primary care physician of this risk. 5
• In patients with pre-existing visual impairment or inability to report symptoms, consider alternative fourth-line agents. 5

Essential Adjunctive Therapy

• Pyridoxine (Vitamin B6) 10-25 mg daily should be given to patients at increased risk of isoniazid-induced neuropathy, including diabetics, HIV-positive patients, those with chronic renal failure, malnutrition, or alcohol use disorder. 5

Corticosteroid Therapy

Adjunctive corticosteroids should be used in conjunction with antituberculous therapy to control intraocular inflammation. 4, 1

• Corticosteroids are initiated after starting antituberculous therapy to prevent paradoxical worsening of inflammation. 4, 1
• Topical, periocular, or systemic corticosteroids may be used depending on the site and severity of inflammation. 4, 1
• Taper corticosteroids gradually based on clinical response while continuing full antituberculous therapy. 4, 1

Pre-Treatment Laboratory Monitoring

• Renal function should be checked before starting streptomycin or ethambutol; avoid these drugs in renal failure or monitor serum drug concentrations with dose reduction. 5
• Liver function tests should be checked before treatment, with monitoring protocols based on baseline results:
  • If AST/ALT <2× normal: repeat at 2 weeks, then only if symptoms develop. 5
  • If AST/ALT 2-5× normal: monitor weekly for 2 weeks, then every 2 weeks until normal. 5
  • If AST/ALT >5× normal or bilirubin elevated: stop rifampicin, isoniazid, and pyrazinamide. 5

Treatment Monitoring and Follow-Up

• Review patients at 2 months (end of intensive phase) to assess treatment response and medication tolerance. 1
• Review at 6-9 months (end of treatment) to confirm resolution and assess for relapse risk. 1
• Monitor visual acuity monthly in patients receiving ethambutol who can cooperate with testing. 5
• Favorable response is expected in approximately 79% of patients despite delays in diagnosis, with improvement in inflammation and visual acuity. 4

Critical Pitfalls to Avoid

• Do not delay treatment while awaiting microbiological confirmation; presumptive treatment should be initiated based on clinical suspicion and positive screening tests, as delayed diagnosis can result in irreversible vision loss. 4, 1, 2
• Do not use ethambutol without baseline visual acuity testing or in patients unable to report visual symptoms. 5
• Do not use corticosteroids alone without concurrent antituberculous therapy, as this can lead to progression of infection. 4, 1
• Do not use a 6-month regimen for CNS involvement; if there is any suspicion of CNS tuberculosis (including optic nerve or chiasmal involvement), extend treatment to 12 months. 6, 7
• Do not forget drug interactions in HIV-positive patients on protease inhibitors; rifampicin significantly reduces protease inhibitor levels through CYP3A enzyme induction. 5
• Do not withhold treatment in patients with negative microbiological studies if clinical suspicion remains high; ocular TB diagnosis is often presumptive based on clinical findings, positive screening tests, and response to therapy. 4, 1