Tuberculosis and the Eye

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

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