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©2014 MFMER | slide-1

TB and the Eye

Wendy M. Smith, M.D. Assistant Professor of Ophthalmology

Mayo Clinic, Rochester, MN USA


Disclosure

• No financial disclosures


TB and the Eye

Outline

• Introduction

• Ocular TB manifestations

• Case Examples

• Diagnosis

• Treatment

Objectives

• Identify the variety of manifestations of ocular tuberculosis

• Describe the challenges associated with diagnosing ocular tuberculosis


Pre-test Questions

• True or False: Mycobacterium tuberculosis is usually isolated from ocular specimens in cases of suspected TB uveitis.

• True or False: The presence of M. tuberculosis DNA is evidence of active infection.

• True or False: TB uveitis is only treated with anti-TB drugs.


Tuberculosis = Mycobacterium tuberculosis

• Worldwide distribution

• ~1/3 latently infected

• Incidence >9 million active TB cases/yr

• Special populations

• People living in or immigrating from endemic regions

• Immunocompromised people (HIV, elderly, diabetics, those on immunosuppressive medications)


TB and the Eye

• Ocular disease is rare

• May affect any ocular tissue

• Direct invasion, hematogenous dissemination

• Hypersensitivity reaction to bacillus infection outside the eye

Mittal R et al. Ophthalmology. 2013 May; 120(5): 1103.e1-4


Ocular TB Epidemiology

• Varies worldwide

• U.S. 1.4% of those with primarily pulm TB

• Spain: 18% of randomly selected patients with culture-proven TB

• Italy: 20% of newly diagnosed TB cases (only 5% with ocular symptoms)

• Subgroups of TB (reviewed in Cutrufello et al. 2010)

• tubercular meningitis (16.2%), tubercular lymphadenopathy (23.2%), pediatric tubercular meningitis (~70%)


Ocular TB

• Tuberculosis of the conjunctiva and eyelids

• Tuberculous chancre and gumma of eyelids atypical chalazion

• Mucopurulent conjunctivitis with regional lymphadenopathy

• Chronic blepharitis

• Interstitial keratitis

• Phlyctenular conjunctivitis

Mittal R et al. Ophthalmology. 2013 May; 120(5): 1103.e1-4

Babu RB et al. Am J Ophthalmol. 2006

Sep;142(3):413-8.


Ocular TB

• Scleritis (most often anterior necrotizing or non-necrotizing, less often posterior)

• Orbital or adnexal disease Biswas J et al. Ocul Immunol

Inflamm. 2012 Feb;20(1):49-52.

Madge SN et al. Orbit. 2008;27(4):267-77.


Intraocular TB

• Tuberculoma

• Granulomatous uveitis

• Granulomatous choroiditis

• Retinal vasculitis

• Retinal or vitreous hemorrhages (Eales disease)

• Papilledema

• Optic neuritis, neuroretinitis


Most common presentations of ocular TB

• Demirci et al: review of 92 published case reports

• Choroidal mass +/-inflammatory signs (34%)

• Choroiditis/chorioretinitis (27%)

• Vitritis (24%)

• Iridocyclitis/anterior chamber reaction (13%)

• Panuveitis (11%)


TB Uveitis

• Uveitis = inflammation of the uveal tract (iris, ciliary body, retina/choroid)

• Uveitis attributed to TB:

• Once considered the most common cause of uveitis (up to 40% of granulomatous uveitis)

• Now relatively rare:

• US ~1%, China 4%, Italy 6%, Japan 7%, India up to 10%, Saudi Arabia 16%


IUSG Classification of Uveitis

• Anterior uveitis

• iris and pars plicata (CB)

• Intermediate uveitis

• pars plana and vitreous

• Posterior uveitis

• retina + choroid

• Panuveitis

“front”

“back”


ANTERIOR UVEITIS Granulomatous or Non-granulomatous

Keratic

precipitates

Posterior

synechia

Iris nodule

Rathinam SR, Lalitha P. Eye 2007 May;21(5):667-8.


http://www.reviewofophthalmology.com/content/d/retinal_insider/i/1206/c/22740/

http://www.eyecalcs.com/DWAN/pages/v5/ch033/016f.html

Choroidal tubercle with miliary TB

Choroidal

Tuberculoma

©2014 MFMER | slide-16 Bansal R et al. Ophthalmology. 2012 Nov;119(11):2334-42.

Serpiginous-like Choroiditis


M Ishaq, A H Feroze, M Shahid, M A Baig, S

S Ameen, S H Feroze and R A Chishti. Eye 2007

Sandeep Saxena http://www.ejournalofophthalmology.com/ejo/ejo21.html

Eales Disease

Idiopathic peripheral

perivasculitis

proliferative vascular

retinopathy,

recurrent vitreous

hemorrhages, and

tractional retinal

detachment

Young, otherwise

healthy men, 20-40 yrs

India, PPD+

TB identified by PCR

on aqueous, vitreous,

ERM


Case: 28 yo M from Kenya, in US x 8 yrs

• 2 months earlier: clouding in peripheral vision

• Then, black spot in vision, not a floater

• A week ago: awoke with red, painful eye

• In college, PPD rxn left scar on his arm

• 2009: PPD 25mm

• 2013: nml CXR


38 sec

1 min

5 min VA cc: 20/50 OU, Ta 10, 9

K OU: inferior subepithelial

opacification, neovascularization,

pigmented KPs, endothelial debris

AC OU: 3+ cell, 1+ flare

Vit OU: 2+ cell, 1+ haze, veils


5 min

58 sec • CRP 14.5

• Quantiferon positive

• ANA low positive 1.1

• wnl/neg: CBC (except low MCV), diff, Cr, UA, ESR, ACE, lysozyme, dsDNA, RF, CCP, toxoplasma IgG/M, Lyme abs, HepB/C, Syphilis IgG, HIV

• 28 yo M from Kenya

• Bilateral panuveitis

• Keratitis

• Anterior uveitis

• Vitritis

• Posterior uveitis/choroiditis


Chest CT

• Calcified granuloma in the superior segment of the left lower lobe

• Scattered tiny indeterminant pulmonary nodules with an upper lung predominance

• These may all represent old granulomas, and are consistent with the diagnosis of prior TB lung infection, but can be seen with other granulomatous processes


Presumed TB Uveitis • ID consult:

• requested AC tap neg acid fast smear and culture

• Quadruple drug tx (ethambutol, isoniazid, pyrazinamide, rifampin for 6 months

• Oral prednisone taper

• One month after finishing prednisone and anti-TB meds, no active uveitis


Case: 45 yo F from Pakistan, U.S. x 11 yr Sudden onset of “wavy lines” in vision

Aunt had tuberculosis, but no

direct exposure

Yearly PPD for work (teacher)

Chest x-ray: normal

Quantiferon: indeterminate,

but she was on systemic

immunosuppression


35 sec

5 min

42 sec

5 min


Serpiginous vs Serpiginous-like Choroiditis

Differences from Classic Serpiginous:

• From TB endemic region

• More likely unilateral

• Multifocal lesions involve posterior pole, mid-periphery,

periphery and spare juxtapapillary region (unlike

classic serpig)

• Inflammation in anterior chamber & vitreous

• Inflammation stops in response to anti-TB meds


Diagnosis of Ocular TB

Clinical context + clinical findings

• immigration from or travel to TB endemic region

• exposure to active TB

• healthcare worker

• worker or resident of nursing home or prison

• Immunocompromised (HIV+, iatrogenic, chronic disease)

• Homeless, elderly


Diagnostic Testing

• Assessments for other uveitis etiologies including HIV

• Chest imaging (x-ray, CT, PET/CT)

• TST/PPD

• False negative in 20-30% active TB

• Low positive predictive value in non-endemic areas

• Interferon-gamma release assay

• In vitro test using M tb antigens to stimulate release of IFNg from peripheral blood cells

• Biopsy, Smear, Culture, PCR


Challenges in Ocular TB Diagnosis

• Limited specimen

• aqueous – 150-200 uL

• Morbidity of obtaining specimen

• Vitrectomy

• Chorioretinal biopsy

• Low DNA yield, and presence of DNA not necessarily indicative of active disease

• Inflammation might be response to extraocular infection (no organism in the eye)

Van der Lelij A, Rothova A. Br J Ophthalmol.

1997 Nov;81(11):976-9.


Ocular TB - Treatment

• Report to local health department

• Coordinate care with infectious diseases specialist

• Confirmed and Presumed Ocular TB

• Both: quadruple drug tx x 6-12 mo

• Longer if increased risk of relapse (cavitary pulm disease, sputum cx + after 2 months)

• Concurrent corticosteroids

• Therapy efficacy: 40-70%

• Enucleation rate up to 30%


Delayed diagnosis/treatment: Sight- and/or life-threatening consequences

Patel et al. JAMA Ophth 2013:

• Midwestern U.S. cohort of 14 patients

• Average delay from ocular disease onset to uveitis referral: 755.3 days

• Non-Hispanic white race, posterior uveitis

• Vision loss associated with diagnosis after 500 days, age >50 yrs

Kesen MR. Arch Ophthalmol. 2009 Aug;127(8):1079-80.

Corneoscleral perforation

Choroiditis affecting macula, optic nerve

Choroidal neovascular membrane

Endophthalmitis


Post-test Questions

• True or False: Mycobacterium tuberculosis is usually isolated from ocular specimens in cases of suspected TB uveitis.

• True or False: The presence of M. tuberculosis DNA is evidence of active infection.

• True or False: TB uveitis is only treated with anti-TB drugs.


References 1. Alvarez GG, Roth VR, Hodge W. Ocular tuberculosis: diagnostic and treatment challenges. Int J

Infect Dis. 2009 Jul;13(4):432-5. 2. Babu RB, Sudharshan S, Kumarasamy N, Therese L, Biswas J. Ocular tuberculosis in acquired

immunodeficiency syndrome. Am J Ophthalmol. 2006 Sep;142(3):413-8. 3. Bansal R, Gupta A, Gupta V, Dogra MR, Sharma A, Bambery P. Tubercular serpiginous-like

choroiditis presenting as multifocal serpiginoid choroiditis. Ophthalmology. 2012 Nov;119(11):2334-42. 4. Biswas J, Aparna AC, Annamalai R, Vaijayanthi K, Bagyalakshmi R. Tuberculous scleritis in a patient

with rheumatoid arthritis. Ocul Immunol Inflamm. 2012 Feb;20(1):49-52. 5. Bodaghi B, LeHoang P. Ocular tuberculosis. Curr Opin Ophthalmol. 2000 Dec;11(6):443-8. 6. Cutrufello NJ, Karakousis PC, Fishler J, Albini TA. Intraocular tuberculosis. Ocul Immunol Inflamm.

2010 Aug;18(4):281-91. 7. 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. 8. Ishaq M, Feroze AH, Shahid M, Baig MA, Ameen SS, Feroze SH, Chishti RA. Intravitreal steroids

may facilitate treatment of Eales' disease (idiopathic retinal vasculitis): an interventional case series. Eye (Lond). 2007 Nov;21(11):1403-5.

9. Kesen MR, Edward DP, Rao NA, Sugar J, Tessler HH, Goldstein DA. Atypical infectious nodular scleritis. Arch Ophthalmol. 2009 Aug;127(8):1079-80.

10. Madge SN, Prabhakaran VC, Shome D, Kim U, Honavar S, Selva D. Orbital tuberculosis: a review of the literature. Orbit. 2008;27(4):267-77.

11. Mittal R, Tripathy D, Sharma S, Balne PK. Tuberculosis of eyelid presenting as a chalazion. Ophthalmology. 2013 May;120(5):1103.e1-4.

12. Nazari Khanamiri H, Rao NA. Serpiginous choroiditis and infectious multifocal serpiginoid choroiditis. Surv Ophthalmol. 2013 May-Jun;58(3):203-32.

13. Patel SS, Saraiya NV, Tessler HH, Goldstein DA. Mycobacterial ocular inflammation: delay in diagnosis and other factors impacting morbidity. JAMA Ophthalmol. 2013 Jun;131(6):752-8.

14. Rathinam SR, Lalitha P. Paradoxical worsening of ocular tuberculosis in HIV patients after antiretroviral therapy. Eye (Lond). 2007 May;21(5):667-8.

15. Sheu SJ, Shyu JS, Chen LM, Chen YY, Chirn SC, Wang JS. Ocular manifestations of tuberculosis. Ophthalmology. 2001 Sep;108(9):1580-5.

16. Van der Lelij A, Rothova A. Diagnostic anterior chamber paracentesis in uveitis: a safe procedure? Br J Ophthalmol. 1997 Nov;81(11):976-9.


Thank you!

TB and the Eye - Mayo Clinic Center for Tuberculosiscenterfortuberculosis.mayo.edu/uploads/2/3/8/6/... · TB and the Eye •Ocular disease is ... •Tuberculous chancre and ... •worker

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