OCULAR TUBERCULOSIS

1. INTRODUCTION & EPIDEMIOLOGY

2. PRIMARY vs. SECONDARY OCULAR TB

3. CLINICAL MANIFESTATIONS

A. EYELID TB

• Starts as a red papule → indurated nodule/plaque → chronic painless ulcer
• Lupus vulgaris of the face may spread to the eyelid producing the classic "apple-jelly" nodule on diascopy
• TB of the tarsal plate simulates recurrent chalazion; eventually causes its destruction
• Regional lymphadenopathy accompanies most cases

B. CONJUNCTIVAL TB

• Primary: unilateral nodular or ulcerative conjunctivitis with regional lymphadenopathy — mainly affects children
• Conjunctival TB is a cause of Parinaud's oculoglandular syndrome (infectious conjunctivitis + regional lymph node enlargement)
• Types of granulomas: ulcerative, nodular, polypoid/hyperplastic
• Phlyctenulosis: hypersensitivity reaction to tuberculoprotein — small nodule with surrounding hyperaemia at the limbus → ulcerates → heals without scarring (unlike corneal phlyctenulosis)
• Mtb demonstrated in only one-fourth of patients with conjunctival TB

C. CORNEAL TB

• Manifestations: phlyctenulosis, interstitial keratitis, ulceration, and infiltrations
• Corneal phlyctenules arise from the limbus and heal with variable scarring and vascularisation
• TB interstitial keratitis is more intense and has more scarring/vascularisation in deeper layers compared to syphilitic IK; it tends to be unilateral and involves the lower cornea preferentially
• Corneal ulcers due to TB are indolent and refractory to treatment

D. SCLERAL TB

• Most common presentation: focal necrotising anterior scleritis; diffuse form also occurs
• Nodular lesion develops due to direct infection or spread from conjunctiva/uveal tract/haematogenous route
• Scleral nodules may undergo caseation necrosis → ulceration → perforation

E. LACRIMAL SYSTEM TB

• TB dacryoadenitis: gradual, painless enlarging swelling; may cause proptosis and restriction of upward gaze
• Abscess formation with chronic draining fistula in the upper lid can occur
• Regional lymphadenopathy is a prominent feature

F. ORBITAL TB

• First described by Abadie in 1881
• Forms: periostitis, tuberculomas, myositis
• Occurs via haematogenous spread or extension from paranasal sinuses
• Typically unilateral, first two decades of life
• TB periostitis: insidious onset, painless inflammation of malar bone → cold abscess → fistula → regional lymphadenitis
• Tuberculomas mimic benign/malignant tumours and orbital pseudotumours

G. UVEAL TRACT (Most Important)

1. Choroidal tubercles / disseminated choroiditis ← most common
2. Choroidal mass/abscess
3. Chronic granulomatous iridocyclitis
4. Intermediate and panuveitis
5. Rarely: panophthalmitis

H. CHOROIDAL TB (Most Common Ocular Manifestation)

• Results from haematogenous dissemination (choroid is highly vascular)
• 28%–60% of miliary TB patients have choroidal tubercles on ophthalmoscopy
• Clinically: solitary or multiple yellowish-grey elevated nodules with overlying vitreal inflammation; most often in the posterior pole; up to 60 tubercles described but usually <5
• B-mode ultrasonography showing a central hypoechoic zone in a moderately reflective choroidal mass is suggestive of TB abscess
• Choroidal granulomas are NOT diagnostic alone — can occur in sarcoidosis, cryptococcosis

I. TB IRITIS AND IRIDOCYCLITIS

• Historically considered an important cause of granulomatous uveitis (declined after identifying sarcoidosis, toxoplasmosis)
• Classic features: mutton fat keratic precipitates, early dense synechiae, iris nodules of Koeppe or Bussaca
• These must be distinguished from sarcoid nodules (larger, more pink)
• Non-granulomatous anterior uveitis may also occur as an immune reaction

J. RETINAL TB

• Isolated direct retinal involvement is extremely rare; retina more commonly affected secondarily from choroidal lesions
• Eale's disease: idiopathic inflammatory vasculitis of retinal vasculature attributed to hypersensitivity to tuberculoprotein
  • Affects 2nd–3rd decade, males more than females
  • 90% become bilateral within a few years
  • Presents with painless sudden visual loss due to vitreous haemorrhage
  • Pathophysiology: retinal periphlebitis → capillary non-perfusion → hypoxia → neovascularisation → vitreous haemorrhage → retinal detachment
  • PCR positivity for TB in vitreous samples reported

4. PATHOLOGY

5. DIAGNOSIS

A. INDEX-TB Guidelines — Diagnostic Categories

B. Investigations

• Tuberculin Skin Test (TST): Positive TST in granulomatous uveitis = positive evidence of ocular TB; does NOT confirm active disease. Patient with uveitis + positive TST has only 1% probability of active TB (Rosenbaum & Wernick)
• IGRAs: Cannot differentiate LTBI from active TB; WHO/RNTCP do not encourage for active TB diagnosis
• Serology (ELISA): WHO strongly recommends against use for TB diagnosis
• PCR: Most promising tool for definitive diagnosis; multitargeted PCR > Gene Xpert > LPA on vitreous samples; LPA (MTBDRplus) also detects rifampicin resistance
• CXR / HRCT chest: Must be done to rule out pulmonary TB; CT superior to CXR in miliary TB
• Abdominal USG: Detects ascites, retroperitoneal lymphadenopathy (abdominal TB)
• B-mode USG of eye: Hypoechoic zone in choroidal mass → TB abscess
• Biopsy: From accessible sites (eyelid, conjunctiva, lacrimal gland, sclera) — demonstrates caseating granulomas with Langhans' giant cells

6. TREATMENT

Standard Regimen (INDEX-TB Guidelines):

Adjunctive Treatment:

Surgical Indications (INDEX-TB Guidelines):

1. Complications of retinal vasculitis (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, glaucoma)

7. ATT-INDUCED OCULAR TOXICITY

Ethambutol (Most Common)

• Three types of optic neuritis: axial, periaxial, mixed
• Dose-related: 45% toxicity at 60–100 mg/kg/day; <2% at <15 mg/kg/day
• Manifestations: visual loss, colour vision defects, pericentral/peripheral scotoma, quadrantic field defects
• British JTC Guidelines: Avoid in renal impairment; do not exceed recommended dose; baseline visual acuity + colour vision; monthly questioning about vision; avoid in children; stop if visual disturbance
• Monitoring: VA + monocular colour vision monthly if dose >15–20 mg/kg for >2 months or renal insufficiency

Isoniazid

• Causes optic neuritis at doses 200–900 mg/day; symptoms as early as day 10
• Pyridoxine is beneficial in treatment and prophylaxis; discontinue INH at first sign of ocular toxicity

Streptomycin

• Rare; retrobulbar optic neuritis reported

Rifampicin

• Most common: conjunctivitis; produces orange-coloured tears (stains contact lenses)
• Rifabutin: endophthalmitis-like response (hypopyon uveitis)

Clofazimine

• Brown discolouration of conjunctiva; brown swirls in cornea; bull's eye maculopathy → macular degeneration

Newer/MDR-TB drugs

• Linezolid: optic neuritis (usually reversible if early); periodic ophthalmic evaluation required
• Capreomycin: optic neuritis

SUMMARY TABLE