Tuberculosis and the Eye Miles Stanford Euretina Uveitis Course Hamburg 2013
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
Prevalence of ocular disease in patients with TB – reported case series 1% USA, 4% China, 6% Italy, 7% Japan, Saudi Arabia 16%
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
Pathophysiology: Hypotheses • Direct infection with mycobacterium • Delayed type hypersensitivity reaction • Mycobacterium sequestered in RPE
Ocular TB – Anterior segment • • Eyelids Conjunctiva Phlyctenulosis IK or sclerokeratitis
Lid granuloma and old necrotising scleritis
Diffuse scleritis in a 35 year old Nigerian with a history of fever, night sweats, weight loss and raised inflammatory markers
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
Acute presumed TB retinal vasculitis (Eales disease) in a 32 year old Sri Lankan woman
Clear signs of old ocular disease in her other eye
Kyrieleis periarteritis in a patient with presumed TB
TB presenting as ampiginous choroiditis
Patient subsequently developed classical Eales disease
Eales disease: inflammatory stage
24 year old caucasian with occlusive vasculitis
Eales Disease: pre-proliferative stage
Presumed ocular TB presenting with vitreous haemorrhage
Choroidal tubercles in a patient with TBM
Massive tuberculous choroidal granuloma
A 13 year old Somali girl with miliary TB – Optic nerve head TB abscess
Serpiginous – like choroiditis
Ocular TB – differential diagnosis • • • Sarcoidosis Behcet’s disease Idiopathic ischaemic retinal vasculitis Choroidal infection – pneumocystis, etc Choroidal tumour
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
CXR Ghon complex/cavities Mediastinal/hilar LAD Calcified LNs
Mantoux test • Specificity confounded by BCG vaccination • Read at 48 - 72 hrs: +ve if – >5 mm in HIV pt – >10 mm in high-risk (from endemic area) – >15 mm in all – US suggests cut off at 5 mm and ignoring previous BCG for screening
Gamma Interferon Tests • Immunological test against antigens found in mycobacterium TB • Antigens NOT in BCG • Quanti-feron TB Gold/in tube, T-SPOT, ELISPOT
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
M. TB from a vitreous smear
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
Treatment of TB - India • • - Retrospective interventional case series Inclusion criteria Complete clinical records Documented positive skin test (>10 mm) Evidence of active uveitis All other infect/non-infect causes ruled out Minimum 1 year follow up
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
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
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
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
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