OCULAR TUBERCULOSIS

1. INTRODUCTION & EPIDEMIOLOGY

• TB uveitis accounts for 2–30% of uveitis cases in India (large variation due to diagnostic criteria).
• In a US sanatorium study, 1.4% of 10,524 TB patients had ocular TB.
• The choroid is the most commonly infected intraocular structure.
• Ocular TB is paucibacillary and shows multiple clinical manifestations.
• Ocular TB is usually not associated with systemic TB manifestations.
• Can cause moderate-to-severe visual impairment in up to 40% of affected eyes (Index-TB Guidelines).

2. PRIMARY VS SECONDARY OCULAR TB

3. CLINICAL MANIFESTATIONS

A. Eyelid TB

• Spread from face, lymph nodes, or haematogenous route
• Begins as a red indurated papule → nodule/plaque → chronic painless ulcer with regional lymphadenopathy
• Lupus vulgaris of the face may extend to eyelid → characteristic "apple-jelly" nodule on diascopy, atrophic scars, ectropion
• TB of tarsal plate simulates recurrent chalazion
• Tuberculids of eyelid: small, multiple, papular, chronic lesions (hypersensitivity reaction)

B. Conjunctival TB

• Primary: unilateral nodular/ulcerative conjunctivitis with regional lymphadenopathy; mostly in children
• Secondary: more common in older patients, may be bilateral
• Can cause Parinaud's oculoglandular syndrome (infectious conjunctivitis + regional lymphadenopathy)
• Types: ulcerative, nodular, polypoid, hyperplastic
• Phlyctenulosis: hypersensitivity reaction to tuberculoprotein; involves limbal region most commonly; heals without scarring (unlike corneal phlyctenules which leave scars)

C. Corneal TB

• Manifestations: phlyctenulosis, interstitial keratitis, ulceration, infiltrations
• TB interstitial keratitis: unilateral, more intense scarring/vascularisation in deeper layers, propensity to involve lower cornea
• Corneal phlyctenules: intense photophobia, pain, blepharospasm; heal with scarring and vascularisation
• Sclerosing keratitis: triangular/tongue-shaped opacity with base towards limbus

D. Scleral TB

• Focal necrotising anterior scleritis is the most common form
• Scleral nodules may undergo caseation necrosis, ulceration, even perforation
• Regional lymphadenopathy (preauricular, submandibular) may be present

E. Lacrimal System TB

• TB dacryoadenitis: haematogenous or spread from conjunctiva/cornea
• Presents as gradual, painless enlarging swelling
• May cause eyelid oedema, pseudoproptosis, abscess with chronic draining fistula

F. Orbital TB (described first by Abadie, 1881)

• Forms: periostitis, tuberculomas, myositis
• Haematogenous or extension from paranasal sinuses
• Typically unilateral, first two decades of life
• Tuberculomas → gradual painless proptosis; mimic benign/malignant tumours, orbital pseudotumours, fungal infections
• TB periostitis: insidious, most commonly involves malar bone → cold abscess, fistula, cicatrisation

G. Tuberculosis of the Uveal Tract (most important)

• Most common intraocular manifestation
• Results from haematogenous dissemination (choroid is highly vascular)
• Choroidal tubercles: yellowish-grey elevated nodules, posterior pole, usually <5 but up to 60 described
• Choroidal tuberculoma: large solitary mass; may cause surrounding retinal detachment
• 28–60% of miliary TB patients have choroidal tubercles on ophthalmoscopy
• B-mode ultrasonography: central hypoechoic zone in moderately reflective mass → suggestive of TB abscess
• Blurred vision may be the only symptom; some patients are asymptomatic

• Classic features: mutton fat keratic precipitates, early dense synechiae formation, iris nodules of Koeppe or Busacca (distinguish from sarcoid nodules which are larger and more pink)
• Non-granulomatous anterior uveitis may also occur as immune reaction

• Eale's disease: idiopathic inflammatory vasculitis attributed to hypersensitivity to tuberculoprotein
• Affects second and third decade, males > females, becomes bilateral in 90% within few years
• Presents with painless sudden visual loss due to vitreous haemorrhage
• Pathology: retinal periphlebitis → capillary non-perfusion → retinal hypoxia → neovascularisation → vitreous haemorrhage → retinal detachment
• Evidence linking TB: increased tuberculoprotein hypersensitivity, concurrent pulmonary TB, PCR positivity for TB from vitreous samples, response to anti-TB treatment in some

4. PATHOLOGY

• Phlyctenules: dense lymphocytes, histiocytes, plasma cells; absence of giant cells and eosinophils; Mtb seldom seen
• Choroidal tubercles: caseating or non-caseating granulomas; characteristic giant cells may be absent
• TB endophthalmitis: marked caseation necrosis and exudation (contrast to choroidal tubercles)

5. DIAGNOSIS

Only 25% of patients with ocular TB have a history of TB; ~50% have normal chest radiographs. A high degree of clinical suspicion is key.

A. Definitive Diagnosis

B. Tuberculin Skin Test (TST / Mantoux)

• Positive TST in granulomatous uveitis = supportive evidence
• Does not reflect disease activity; a patient with uveitis + positive TST has only 1% probability of active TB (Rosenbaum & Wernick)
• Recent TST conversion favours active TB
• Systemic corticosteroids can interfere with TST interpretation

C. IGRAs (Interferon-Gamma Release Assays)

• Cannot differentiate latent TB infection from active TB
• WHO and RNTCP do not recommend IGRAs for diagnosing active TB

D. Molecular Methods (PCR)

• Most promising tool for definitive diagnosis
• PCR of vitreous/aqueous specimens using MPB64 protein sequence specific for Mtb
• Multi-targeted PCR, Gene Xpert MTB/RIF, LPA (MTBDRplus) can be used
• LPA from vitreous fluid: effective for rapid diagnosis of drug-resistant intraocular TB
• Presence of mycobacterial DNA alone does not confirm active TB

E. Imaging

• Chest X-ray: mandatory in all suspected cases
• HRCT chest: superior to plain X-ray for active TB lesions (miliary pattern)
• Ultrasonography abdomen: ascites, retroperitoneal lymphadenopathy
• Ocular imaging: fundus photography, fluorescein angiography, optical coherence tomography (OCT), multimodal imaging

6. DIAGNOSTIC CATEGORIES (INDEX-TB GUIDELINES / Table 24.1)

Possible Ocular TB

• [i] ≥1 clinical sign suggestive of ocular TB (other aetiology excluded)
• [ii] Chest X-ray/CT not consistent with TB; no extraocular TB
• [iii] Documented exposure to TB and/or immunological evidence (positive TST/IGRA)
• [iv] Molecular evidence of Mtb infection

Clinically Diagnosed (Probable) Ocular TB

• [i] ≥1 clinical sign of ocular TB (other aetiologies excluded)
• [ii] Chest X-ray consistent with TB or extraocular TB evidence or microbiological confirmation from sputum/extraocular site
• [iii] Documented exposure to TB and/or immunological evidence

Bacteriologically Confirmed Ocular TB

• ≥1 clinical sign of ocular TB + microbiological (smear/culture) or histopathological confirmation of Mtb from ocular fluids/tissues

7. TREATMENT

A. Anti-TB Treatment (ATT)

• Regimen: 2RHZE / 4RHE (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol for 2 months, then RHE for 4–7 months)
• Total duration: 6–9 months
• All patients (possible, probable, or confirmed) require ATT

B. Adjunctive Therapy

• Systemic steroids: for choroidal granulomas and panuveitis — start 48–72 hours after initiating ATT
• Topical corticosteroids + cycloplegics: for TB phlyctenulosis
• Local astringents: for mild conjunctival symptoms
• Topical antibiotics (streptomycin, amikacin, isoniazid): tried in TB scleritis

C. Surgical Indications (Index-TB Guidelines)

1. Complications of retinal vasculitis: retinal neovascularisation, vitreous haemorrhage, tractional/combined retinal detachment, epiretinal membrane
2. Diagnostic vitrectomy when conventional methods fail
3. Non-resolving vitreous inflammation
4. Visually significant vitreous floaters after completing medical therapy
5. Complications of uveitis: cataract and glaucoma

D. Treatment Response Definitions

• Remission: inactive disease for ≥3 months after discontinuing all therapy
• Treatment failure: no decrease or <2-step decrease in inflammation after 3 months ATT
• Relapse: ≥2-step increase in inflammation after complete remission

8. ATT-INDUCED OCULAR TOXICITY

1. Avoid in impaired renal function
2. Do not exceed recommended dose/duration
3. Pretreatment visual acuity and colour vision documentation mandatory
4. Inform patient about possibility of visual effects; document in records
5. Routine visual acuity testing not recommended during treatment
6. Avoid in children and adults in whom visual assessment is difficult
7. Any visual disturbance → refer immediately to ophthalmologist; discontinue ethambutol pending evaluation

SUMMARY BOX (Key Points for Exam)