1. Tuberculosis and the Eye Miles Stanford Euretina Uveitis Course Hamburg 2013

2. Epidemiology of TB One third of the world’s population has been infected with TB: 1 new infection every second 1:10 with latent TB will get active disease <5% are associated with HIV infection but this rises to 100% in some areas Multidrug resistant disease is increasing (approx 0.5 million) 58 countries have XDR TB cases

3. Prevalence of ocular disease in patients with TB – reported case series 1% USA, 4% China, 6% Italy, 7% Japan, 16% Saudi Arabia

4. Epidemiology of TB in the UK Current incidence 13.8/100,000 Higher in patients from India (36%) and sub- Saharan Africa (24%) Current rate 11/100,000 in the North of England 40/100,000 in Manchester

5. Pathophysiology: Hypotheses Direct infection with mycobacterium Delayed type hypersensitivity reaction Mycobacterium sequestered in RPE

6. Ocular TB – Anterior segment Eyelids Conjunctiva Phlyctenulosis IK or sclerokeratitis

7. Lid granuloma and old necrotising scleritis

8. Diffuse scleritis in a 35 year old Nigerian with a history of fever, night sweats, weight loss and raised inflammatory markers

9. Posterior segment manifestations of TB Posterior uveitis in 42%; panuveitis in 11% Usually: –Intermediate uveitis (11%) –Retinal vasculitis +/- choroiditis –Serpiginous-like choroiditis Gupta A, Bansal R, Gupta V, Sharma A, Bambery P. Ocular signs predictive of tubercular uveitis. Am J Ophthalmol. 2010 Apr;149(4):562-70

10. Acute presumed TB retinal vasculitis (Eales disease) in a 32 year old Sri Lankan woman

11. Clear signs of old ocular disease in her other eye

12. Kyrieleis periarteritis in a patient with presumed TB

13. TB presenting as ampiginous choroiditis

14. Patient subsequently developed classical Eales disease

15. Eales disease: inflammatory stage

16. 24 year old caucasian with occlusive vasculitis

17. Eales Disease: pre-proliferative stage

18. Presumed ocular TB presenting with vitreous haemorrhage

19. Choroidal tubercles in a patient with TBM

20. Massive tuberculous choroidal granuloma

21. A 13 year old Somali girl with miliary TB – Optic nerve head TB abscess

22. Serpiginous – like choroiditis

23. Ocular TB – differential diagnosis Sarcoidosis Behcet’s disease Idiopathic ischaemic retinal vasculitis Choroidal infection – pneumocystis, etc Choroidal tumour

24. Presumed ocular TB - diagnosis No pathognomic clinical features Ask about TB contact, recent travel, etc Check CXR Mantoux skin test γ interferon testing Response to anti-TB treatment

25. Ghon complex/cavities Mediastinal/hilar LAD Calcified LNs CXR

26. Mantoux test Specificity confounded by BCG vaccination Read at 48 - 72hrs: +ve if –>5mm in HIV pt –>10mm in high-risk (from endemic area) –>15mm in all –US suggests cut off at 5mm and ignoring previous BCG for screening

27. Gamma Interferon Tests Immunological test against antigens found in mycobacterium TB Antigens NOT in BCG Quanti-feron TB Gold/in tube, T-SPOT, ELISPOT

28. Current NICE guidance (2011) For Latent TB - Offer Mantoux to household contacts of patients with active TB and non- household contacts (eg workplace) - Consider IGRA for those with +ve Mantoux and those who have had BCG - Mantoux inconclusive, refer to TB specialist - In immunocompromised offer both tests

29. M. TB from a vitreous smear

30. Ocular TB- Therapy Rifampicin, isoniazid, pyrizinamide, ethambutol for 2 months Rifampicin and isoniazid for 4 months Will need longer if active TB detected Prednisolone as required but double the dose when on rifampicin because of liver enzyme induction

31. Treatment of TB - India Retrospective interventional case series Inclusion criteria -Complete clinical records -Documented positive skin test (>10mm) -Evidence of active uveitis -All other infect/non-infect causes ruled out -Minimum 1 year follow up

32. Treatment of TB - India 360 patients studied 216 received anti TB treatment and steroids 144 received steroids alone Recurrences were reduced in the first goup (15.7%) compared to the second (46%) – p<.001 at median follow up of 24 and 31 months AJO 2008 146;772-9

33. Presumed tuberculous uveitis:diagnosis management and outcome Retrospective study of 27 patients 4/27 caucasian >1/2 had history of contact with a patient treated for TB All received 6 months of anti-TB therapy 19/27 required systemic steroids as well Inflammation resolved after TB therapy in 70% Eye 2011 25:475-80

34. Ocular TB – how long should we treat? Retrospective case series from Singapore 46 >6 months ATT, 18 <6 months Patients with > 9 months treatment were less likely to relapse (OR 0.09, p=0.02) Patients with uveitis and latent TB treated for 9 months had an 11 fold reduction in the likelihood of relapse Br J Ophthalmol 2012 96:332-6

35. Ocular TB - Summary TB is on the increase as is the ocular disease associated with it All patients with ampiginous/serpiginous choroiditis should be screened for latent TB Consider the diagnosis especially in patients presenting with occlusive retinal vasculitis If all else fails and clinical suspicion is still high, try anti tuberculous therapy