Ocular tuberculosis

OCULAR TB-UVEITIS

1. OCULAR TUBERCULOSIS

2. INTRODUCTION Prevalence- 0.39 to 9.86% in the south and north Indian uveitis clinic population respectively Tuberculosis is caused by Mycobacterium tuberculosis which is an obligate aerobic, slow growing, nonspore forming, nonmotile bacterium Humans are only natural host End organs with high oxygen tension (apices of the lungs, kidneys, bones, meninges, eye) are typically infected In eye , Choroid and Ciliary body are mainly affected The hallmark of extra-pulmonary TB is caseating granuloma and necrosis spread by small airborne droplets from infected patients.

3. Once the droplet nuclei are inhaled, the bacilli settle in the airways. If the infection is not contained by the immune system, in around 3–8 weeks, local spread and spread to regional lymph nodes in the lungs occurs. Subsequent spread to other organs results in extrapulmonary tuberculosis. In a susceptible host, the alveolar macrophages are overwhelmed and destroyed by the multiplying tubercular bacilli with the release of various cytokines and chemokines to attract circulating monocytes which although phago cytose the bacilli are incapable of destroying them.

4. A delayed type of hypersensitivity (DTH) response destroys the bacteria-laden macrophages with attendant tissue destruction and formation of an epithelioid cell granuloma with central area of necrosis containing the acid-fast bacilli (AFB) surrounded by activated and nonactivated macrophages, giant cells and T lymphocytes. The activated macrophages representing the cell mediated immunity (CMI) serve to contain the infection. However, inactivated macrophages containing bacilli may escape via the lymphatic channels and circulation and reach the extrapulmonary organ(s) where these may remain dormant. Later, it is the reactivation of these dormant lesions at some stage of life that may cause active TB infection.

5. ANTERIOR UVEITIS Acute or Chronic granulomatous uveitis May be associated with iris or angle granuloma Mutton fat KPs, The keratic precipitates may be few or diffuse, occupying inferior half of the corneal endothelium Posterior synechiae –broad based

6. Iris findings Nodules at pupillary margin -Koeppe nodule, Bussaca nodules on the surface of the iris Sometimes nodules in angle Iris atrophy may be seen in some cases

7. May present as mild to moderate recurrent iridocyclitis Severe cases, hypopyon may be seen Complications : cataract, glaucoma, vitritis Inadequate treatment may be complicated by band shaped keratopathy and iris neovascularisation 10 yrs old boy-hypopyon uveitis with exudates behind the lens. In view of poor response to steroid therapy, UBM examination was done which revealed a granuloma in the ciliary body He was subjected to pars plana lensectomy and vitrectomy. PCR from vitreous sample was positive for the Mycobacterium tuberculosis genome. He received ATT

8. INTERMEDIATE UVEITIS Spill over of inflammatory cells into the anterior vitreous from the anterior uveitis Vitritis with snowball opacities snow banking, peripheral vascular sheathing, peripheral granuloma.

9. COMPLICATIONS Cystoid macular edema Cataract Epiretinal membrane, raised intraocular pressure, optic disc pallor Peripheral neovascularization, retinal detachment and vitreous hemorrhage. In eyes with media opacity, ultrasound biomicroscopy can assist in detecting the presence of a granuloma in the ciliary body region.

10. POSTERIOR UVEITIS Choroidal tubercles granulomas located deep in the choroid result from hematogenous spread usually less than 5, up to 50 in number, Unilateral or bilateral Most commonly situated in the posterior pole, greyish-white to yellowish in colour, discrete with indistinct borders, and typically elevated in the centre. may or may not be associated with subretinal fluid

11. Active Choroidal tubercles usually respond well to ATT and generally take up to 3 to 4 months to heal. On healing, the tubercles result in pigmented and atrophic scars.

12. CHOROIDAL TUBERCULOMA Choroidal tubercle continues to grow, it forms a solitary mass known as tuberculoma Present as a solitary, yellowish, subretinal mass with surrounding exudative retinal detachment , mimicking a choroidal tumor. May be located anywhere Measure from 4 to 14 mm in size

13. May occur in immunocompetent patients and in patients with disseminated tuberculosis, may have overlying hemorrhages, retinal folds, and surrounding exudative retinal detachment On ultrasonography, these lesions are solid, elevated masses with moderate to high internal reflectivity

14. Large choroidal infiltrate inferotemporal to disc B scan -a choroidal mass with high internal reflectivity

15. SUBRETINAL ABSCESS A yellowish, solitary, elevated subretinal mass-like lesion It develops as a result of progressive, liquefied caseation necrosis with rapid multiplication of bacilli and tissue destruction. Very often these patients would have evidence of systemic disseminated tuberculosis Lesions associated with overlying vitritis , retinal haemorrhages and serous retinal detachments. Show tendency to develop retinal angiomatous proliferation over a period of time Rarely, these lesions can rupture into the vitreous cavity and may lead to endophthalmitis or panophthalmitis

16. Serpiginous like choroiditis Tubercular serpiginous like choroiditis is seen at a younger age, accompanied by mild vitritis and is bilateral in majority. It is more common in men. Multifocal discrete lesions may be the initial presentation which show a wave-like progression and then become confluent. These lesions begin as yellowish-white, well-defined round lesions, ¼ to 1 disc diameter in size with raised edges. On fundus fluorescein angiography, they show initial hypo fluorescence, followed by hyperfluorescence in the late stages.

17. (3) It may manifest as diffuse, larger, yellowish-white, plaque-like lesion. The edges are elevated, and the centre is less elevated and shows pigmentary changes, indicating the process of healing. The fundus fluorescein angiography shows mixed fluorescence; the advancing edge initial hypofluorescence and late hyperfluorescence. (4) Another pattern could be a mixed pattern, with discrete lesions in one eye and diffuse, plaque-like lesion in the opposite eye. (5) A less common type is seen as a reactivation at the edge of an old scar of serpiginous like choroiditis.

18. RETINAL VASCULITIS Involves mainly the veins Characteristic feature is periphlebitis Associated features - Vitreous infiltrates ( vitritis ), - Perivascular cuffing, - Retinal haemorrhages, - Neo- vascularization - Neuro-retinitis - Focal choroiditis lesions

19. DIAGNOSIS Criteria- Positive Montoux test or CXR s/o active TB Any one of the following Aqueous /vitreous PCR positive for MTB Sputum positive for AFB Histological evidence of MTB from biopsy(cervical/ parahilar lymph nodes) Response to ATT

20. Tuberculin Skin Test Tuberculin is sterilised concentrated culture of tuberculi bacilli Also known as Montoux test and Purified protein derivative test tuberculin is injected intradermally and then skin induration is measured at 24–48 h based on a host type IV Hypersensitivity reaction.

21. limited by poor inter-reader reliability (e.g., 9 mm negative vs. 10 mm positive), low specificity (e.g., prior BCG vaccination), it requires patient reliability to return to read the test

22. Interferon gamma release assays These tests are ELISA assays that measure the interferon gamma produced when the patient’s peripheral blood leukocytes are purified and mixed with three different tuberculosis antigens from a whole blood sample. There are currently two FDA approved tests the Quantiferon TB-gold test T-SPOT TB test Quantiferon test –more reliable Useful for poorly reliable patients or immigrants from endemic areas that may have a false positive PPD from previous BCG vaccination Cost is an issue

23. TREATMENT Oral isoniazid, rifampicin, ethambutol, and pyrazinamide in their usual standard doses. Pyrazinamide and ethambutol are stopped after 2 to 3 months and treatment with isoniazid and rifampin is continued for 9 to 12 months ATT is given in combination with oral corticosteroids (0.8-1.0 mg/kg/day), which are gradually tapered over 3-4 months. The response to treatment is usually evident within 4 to 6 weeks.