Ocular syphilis and tuberculosis

Ocular Syphilis: "The Great Mimicker"

Ocular syphilis is caused by the spirochete Treponema pallidum. It can arise at any stage of syphilitic infection (primary, secondary, latent, or tertiary) and has earned the title of "The Great Mimicker" due to its ability to imitate virtually any known clinical pattern of anterior, intermediate, posterior, or panuveitis.

Clinical Spectrum

• Anterior Segment: Interstitial keratitis (deep stromal vascularization with "salmon patches" and ghost vessels), granulomatous anterior uveitis, and iris roseola (dilated, hyperaemic vascular tufts on the iris sphincter, highly suggestive of secondary syphilis).
• Posterior Segment:
  • Acute Syphilitic Posterior Placoid Chorioretinitis (ASPPC): characteristic placoid, circular or oval, yellowish-white outer retinal/RPE lesions located in the macula or juxtapapillary area, demonstrating a characteristic granular fade in the center with hyperfluorescent borders on fluorescein angiography and disruption of the ellipsoid zone on SD-OCT.
  • Retinal Vasculitis: Severe, occlusive retinal arteriolitis or phlebitis with vitreous haemorrhage and exudation.
  • Neuroretinitis & Optic Nerve Disease: Papillitis, optic perineuritis (sheath inflammation with intact central visual acuity and peripheral field constriction), and neuroretinitis with a complete macular star.

Laboratory Diagnostics

Dual serological testing is mandatory:

1. Treponemal Serological Tests (EIA, CLIA, TPHA, TPPA, FTA-ABS): Detect antibodies directed against specific T. pallidum antigens. Highly sensitive and specific; usually remain positive long-term regardless of past treatment. A negative result lowers the likelihood, but early infection, immune status and assay limitations matter. With a strong compatible history or phenotype, coordinate repeat or alternative testing rather than treating one negative result as definitive exclusion.
2. Non-Treponemal Serological Tests (VDRL, RPR): Detect antibodies to cardiolipin-lecithin-cholesterol antigens. Quantified as a titer; reflects active, ongoing disease and tracks treatment response (a 4-fold decrease in titer indicates successful cure). Can be falsely negative in late neurosyphilis, early primary infection, or due to the prozone phenomenon (antibody excess in secondary syphilis causing false-negative un-diluted testing).

Ocular Tuberculosis

Ocular tuberculosis is caused by Mycobacterium tuberculosis, an acid-fast bacillus. Intraocular disease may result from active hematogenous dissemination from an extraocular site or from a delayed-type hypersensitivity (Type IV) response to circulating mycobacterial antigens in an individual with latent infection.

Clinical Manifestations

• Granulomatous Panuveitis: Indolent, chronic panuveitis with mutton-fat KPs, Koeppe/Busacca iris nodules, and broad-based posterior synechiae.
• Choroidal Manifestations:
  • Choroidal Tubercles: Small, multiple, greyish-white or pale yellow, circumscribed nodules (typically 0.5 to 1.5 mm) located in the posterior pole; characteristic of acute hematogenous miliary tuberculosis.
  • Solitary Choroidal Tuberculoma: A large, elevated, yellowish subretinal mass often exceeding 4 mm in thickness, accompanied by exudative retinal detachment; mimics an amelanotic choroidal melanoma or metastatic carcinoma.
  • Tuberculous Serpiginous-Like Choroiditis (TB-SLC): Multifocal, non-contiguous, yellowish-white choroidal lesions with active amoeboid creeping edges and central pigmented atrophic clearing. Unlike classical autoimmune serpiginous choroidopathy (which originates at the peripapillary margin and progresses continuously), TB-SLC is multifocal, can arise anywhere in the posterior pole, and frequently involves the vitreous with prominent cells.
• Retinal Vasculitis & Eales Disease Phenotype: Severe, obliterative retinal periphlebitis characterized by heavy vascular sheathing, extensive peripheral capillary non-perfusion, secondary retinal neovascularisation elsewhere (NVE), and recurrent vitreous haemorrhage.

Diagnostic Approach and Anti-Tubercular Therapy (ATT)

• Investigations: High-resolution chest CT (evaluates apical scarring, calcified Ghon complexes, and lymphadenopathy); Interferon-Gamma Release Assay (IGRA: QuantiFERON-TB Gold) provides high specificity unconfounded by prior BCG vaccination; positive Tuberculin Skin Test (TST / Mantoux induration $\ge 10\text{ mm}$ in immunocompetent or $\ge 5\text{ mm}$ in immunocompromised); PCR of aqueous/vitreous for the IS6110 insertion sequence.
• Treatment Protocol:
  • Standard Multi-Drug ATT: Intensive phase comprising four drugs for 2 months: Rifampicin (RIF), Isoniazid (INH), Pyrazinamide (PZA), and Ethambutol (EMB). Followed by a continuation phase comprising two drugs for 4 to 7 months: Rifampicin and Isoniazid (total treatment duration: 6 to 9 months).
  • Pyridoxine (Vitamin B6, $25\text{--}50\text{ mg/day}$) co-administered with INH to prevent peripheral neuropathy.
  • Systemic Corticosteroids: Oral prednisolone ($0.5\text{--}1.0\text{ mg/kg/day}$) introduced exclusively under full ATT coverage to control destructive tissue hypersensitivity.

Treatment Boundaries in Toxoplasmosis and Necrotising Retinitis

Small peripheral toxoplasma lesions in immunocompetent patients may be observed in selected circumstances; location, size, immune status and visual threat guide antimicrobial treatment. Corticosteroids, when used, require appropriate antimicrobial coverage and specialist timing. A negative IgG can be misleading early or in immune compromise. For ARN, begin antiviral therapy promptly, obtain supportive PCR without waiting for it, adjust systemic treatment to renal function and assess the fellow eye. Preventive laser or early vitrectomy is considered individually; evidence does not establish compulsory 360-degree laser for every eye. PORN typically has rapid outer-retinal involvement and little inflammation in severe immunosuppression, but inflammation need not be completely absent. Coordinate HIV and immune-restoration care.