ocular TB manifestations,diagnostic tests, treatment

1. DR.JAHIDUR RAHMAN
FCPS COURSE STUDENT
NIO&H,DHAKA
OCULAR TUBERCULOSIS
CHAIRMAN : MODERATOR:
DR.BISWANATH GHOSH DR.MEJBAHUL ALOM

2. • Tuberculosis (TB) is the most important systemic
infectious disease usually caused by the bacterium
Mycobacterium tuberculosis (MTB).
• Presently, one-third of the world's population is thought
to be infected with TB.
• Tuberculosis primary involves lung but can also affect
other parts of the body.
• Secondary ocular TB is a common presenting form

3. • Most infections - latent tuberculosis
• About 10% of latent infections → active disease
• More than 95% of deaths occurred in developing countries
• The classic symptoms of active TB are ~
a chronic cough with blood-containing sputum
fever
night sweats and
weight loss

4. CAUSES:
• The main cause of TB is Mycobacterium tuberculosis
(MTB), a small,obligate aerobic,nonmotile acid fast
bacillus.
• The M. tuberculosis complex (MTBC) includes four other
TB-causing mycobacteria:
 M. bovis
 M. africanum
 M. canetti and
 M.microti.

5. CAUSES:
• Other known pathogenic mycobacteria include –
M. leprae
M. avium
M. kansasii.
• The latter two species are classified as"nontuberculous
mycobacteria" (NTM).
• NTM cause neither TB nor leprosy, but they do cause lung
diseases that resemble TB.

6. TRANSMISSION OF INFECTION:
• Primary airborne disease
• Spreads person to person : by cough or sneezing,rarely by direct
contact & by blood.
• Droplets measuring 1 to 5 micron suspended in air for several hours
can harbour the bacteria
• Usually 5 to 200 inhaled bacteria : sufficient for infection
• About 90 % of infected patients : asymptomatic
• Approximately 80% pulmonary TB & 20% extrapulmonary TB

7. EXTRA PULMONARY TB :
• Extrapulmonary TB occurs more commonly in people with a
compromised immune system and young children.Notable
diseases are-
• The pleura ( tuberculous pleurisy)
• The central nervous system (tuberculous meningitis)
• The lymphatic system (scrofula of the neck)
•

8. EXTRA PULMONARY TB :
• The genitourinary system ( urogenital tuberculosis)
• The bones and joints ( Pott disease of the spine)
• The eye (Ocular tuberculosis)

9. OCULAR TB :
• Results from 1)Active infection or
2) An immunological reaction to the organism.
• 2 types :
A.Primary ocular TB -in which the eye is the primary portal of
entry manifests mainly as conjunctival,corneal & scleral disease.
B.Secondary ocular TB - occurs by virtue of hematogenous
dissemination or by contiguous spread from adjacent structures &
manifests mainly as uveitis.

10. CLINICAL MANIFESTATION :
• A) Adnexal manifestation
• B) Anterior segment manifestation
• C) Posterior segment manifestation
• D ) Neuro ophthalmic manifestation
• E) Drug related ocular toxicity

11. ANTERIOR UVEITIS
• Acute or Chronic granulomatous
uveitis
• May be associated with iris or angle
granuloma
• Mutton fat KPs
• Posterior synechiae –broad based

12. ANTERIOR UVEITIS
• Iris findings
• Nodules at pupillary margin( Koeppe nodule),
• Busacca nodules small gray nodules at iris root –miliary TB

13. ANTERIOR UVEITIS
• Iris atrophy may be seen in some cases
• May present as mild to moderate recurrent iridocyclitis
• Severe cases, hypopyon may be seen
• Complications : cataract ,glaucoma, vitritis

14. INTERMEDIATE UVEITIS :
• Low-grade, chronic uveitis
• Vitritis with
- snowball opacities
- snow banking,
- peripheral vascular
sheathing,
- peripheral granuloma

15. INTERMEDIATE UVEITIS :
• Complications :
• Cystoidmacular oedema
• Epiretinal membrane
• Peripheral neovascularization
• Retinal detachment
• Vitreous haemorrhage
• Cataract

16. POSTERIOR SEGMENT MANIFESTATIONS :
• Choroidal tubercles
• Choroidal tuberculoma
• Serpiginous like choroiditis
• Subretinal abscess
• Vasculitis retinae
• Progressive ocular inflammation followed by ATT

17. CHOROIDAL TUBERCLE :
• Most common manifestation of intra-
ocular tuberculosis
• Hematogenous spread
• Less than 5mm, upto 50 in number
• Unilateral or bilateral
• Grayish white to yellow in color
• Indistinct borders
• Mostly in the posterior pole

18. CHOROIDAL TUBERCLE :
• Seen in miliary tuberculosis and central nervous system
tuberculosis (meningitis)
• On fluorescein angiography, they are hypofluorescent in early
stage and hyperfluorescent in late stage
• 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.

19. CHOROIDAL TUBRRCULOMA :
• May occur in immunocompetent patients and in
patients with disseminated tuberculosis
• Presents as a large (4-14 mm) solitary yellowish mass
• May have overlying hemorrhages, retinal folds and
surrounding exudative retinal detachment.

20. • On ultrasonography, these lesions are solid, elevated
masses with moderate to low internal reflectivity

21. SERPIGINOUS LIKE CHOROIDITIS :
• Chronic, progressive and recurrent
inflammation that primarily involves
the choroid and
• choriocapillaris and progresses to
involve the retina secondarily .
• These lesions begin in the peri
papillary area and spread
centrifugally.

22. SERPIGINOUS LIKE CHOROIDITIS :
• On progression, acquires an active
advancing edge
• It represents an immune-mediated
hypersensitivity reaction with
progression despite administration of
antitubercular treatment.

23. SERPIGINOUS LIKE CHOROIDITIS :
• Antituberculosis treatment in conjunction with oral
corticosteroids/immunosuppressive agents may reduce the
number of recurrences.
• Results following liquefaction of caseous material in the
granuloma.

24. SUBRETINAL ABSCESS :
• Yellowish 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

26. TUBERCULAR RETINAL VASCULITIS :
• Involves mainly the veins
• Characteristic feature is
Periphlebitis.
• Associated features:
- vitreous infiltrates (vitritis),
- perivascular cuffing,
- retinal haemorrhages,
- neo- vascularization
- neuro-retinitis.

27. NEURO-OPHTHALMIC MANIFESTATIONS :
• The optic neuropathy develops either from direct infection induced
by the mycobacteria or from a hypersensitivity to the infectious
agent.The involvement may manifest as -
• An optic nerve tubercle
• Papillitis
• Retrobulbar neuritis
• Neuroretinitis
• Papillodema

28. • a Fundus photograph. Posterior pole of the left eye demonstrates marked
swelling of the optic disc with peripapillary hemorrhage. b Fundus
photograph. Posterior pole of the left eye 2 weeks after initiation of
antimycobacterial therapy shows marked resolution of the optic disc swelling.

29. ADNEXAL MANIFESTATIONS :
• 1) Lupus Vulgaris
• 2) Eyelid Tuberculous Granuloma

30. ANT. SEGMENT INVOLVEMENT :
• 1) Tuberculous conjunctivitis.
• 2) Conjunctival granuloma.
• 3) Phlyctenular keratoconjunctivitis.
• 4) Tuberculous Scleritis
• 5) Interstitial keratitis
• 6) Iridocyclitis

31. DRUG RELATED TOXICITY :
1) Ethambutol :
• optic neuropathy
• Acquired red green dyschromatopsia
• Central scotoma
• Disc oedema, disc hyperemia
• Toxicity is dose- and duration dependent
• Daily dose >25 mg/kg

32. DRUG RELATED TOXICITY :
• 2) Isoniazid
• Optic neuropathy
• Steven Johnson syndrome involving lids and
conjunctiva
• 3) Rifampicin -orange-red discoloration of tears

33. INVESTIGATIONS :
Corroborative evidence :
• Mantoux test
• Chest X RAY / CT Scan
• Serodiagnosis
• Interferon Gamma Release Assays (IGRA )
Direct evidence :
• Smear and Culture of AFB
• PCR

34. INVESTIGATIONS :
Ocular Investigations
• FFA and ICG
• OCT
• USG
• UBM

36. MANTOUX TEST :
• Intradermal 5 TU of PPD is given
• Test is read at 48 to 72 hours
• < 5 mm : negative
• 5 – 10 mm : positive in HIV infected person
• > 10 mm : high risk persons
• >15 mm : positive result

37. DISADVANTAGES :
• False negative : severe TB
• Dose dependent test
• Cross reaction with BCG vaccination / non TB
Mycobacteria
• Cannot distinguish active from latent TB

38. CHEST X RAY/ CT SCAN
Can provide evidence of active , healed or reactivated TB
Lesions :
• Consolidation
• Cavitation
• Fibrosis
• Hilar or paratracheal lymph node enlargement
• Multiple millet like opacities

39. SERODIAGNOSIS :
• Detects antibody or antigen
• Middlebrook Dubos test : Hemagglutinin test between sheep
RBC and with polysaccharides from M.Tuberculosis and sera of
patient
• High false positive results

40. NEW DIAGNOSTIC ASSAYS
• Interferon-gama release assays (IGRA)
• Based on the in vitro assays that measure interferon-gama
released by sensitized T cells after stimulation by
Mycobacterium tuberculosis antigens.
• Antigens used are -
A. Early secreted antigen target (ESAT ) 6
B. Culture specific protein ( CSP ) 10

41. INTERFERON GAMA RELEASE ASSAY
• Immunospot test : T-SPOT.TB test
• ELISA : QunatiFERON –TB Gold
• QunatiFERON Test two types:
1.QuantiFERON -TB Gold ( QFTG )
2.QuantiFERON-TB Gold in tube (QFTGIT )

42. QUANTIFERON TB GOLD
Advantages
• Results in 24 hours
• No reader bias
• No cross reaction with BCG

43. QUANTIFERON TB GOLD
Disadvantages –
• Sample to be used in 12 hours
• False positive with other types of Mycobacterium
• Cannot distinguish latent from active TB
• Costly

44. DIRECT EVIDENCE
Smear and staining :
• Organism required are 10 ^ 6 /ml of sputum
• Low yield from intraocular specimens
Culture and sensitivity :
• Lowenstein –Jenson medium
• Prolonged process – 8 weeks
• Low yield from intraocular specimen

45. POLYMERASE CHAIN REACTION ( PCR )
• DNA Amplification and detection technique
• Small amount of sample needed
• Aqueous , vitreous humor , chorioretinal biopsy can be used
• Positive in 33.33 % : retinal vasculitis
• Positive in 66.6 % : granulomatous panuveitis

46. DIAGNOSIS OF OCULAR TUBERCULOSIS
• Diagnosis is difficult & mostly presumptive
• Difficult to get tissue sample
• Low bacterial load
• Inadequacy of tissue/fluid
• Mimics other ocular disease

47. Low mass of ocular tissue
Can’t stimulate body’s immune system
Can’t raise serum level of immune
mediators to an adequate level.
No alteration of the conventional
serological or immunological tests

48. D/D:
Infectious Disorders Noninfectious Disorders
Syphilis
Toxoplasmosis
Toxocariasis
Candidiasis
Brucellosis
Leprosy
Nocardiasis
Coccidiomycosis
Leptospirosis
Cat scratch disease
Lyme disease
Sarcoidosis
Behçet's disease
Metastasis
Tumors
Autoimmune vasculitis

49. TREATMENT :
• Based on evidence - Clinical
- Indirect and direct evidence
• ATT –extrapulmonary TB regimen(CNS TB)
• Corticosteroids – Concomitant use
• Prolonged and difficult in MDR TB, RR-TB &XDR-TB

50. TREATMENT
ATT Adult dose Pediatric dose
Isoniazid 5mg/kg
PO;not>300mg/d
10-20mg/kg/d
PO;not>300mg/d
Rifampicin 600mgPO/IV OD 10-20mg/kg Po/IV
not>600mg
Ethambutol 15mg/kg PO OD <13yrs:15-20mg/kg/d;
>13yrs:as in adult
Pyrazinamide 15-30mg/kg PO OD As in aduit

51. TREATMENT :
• 2HREZ/7-10HR3 means isoniazid, rifampicin, ethambutol and
pyrazinamide daily for two months, followed by 7-10 months of
isoniazid and rifampicin given three times a week.
• Two new drugs which are now used for the treatment of drug
resistant TB are bedaquiline and delamanid.

52. INDICATION OF STEROID:
• Uveitis
• Vitritis
• Vasculitis retinae
• Lesion involving optic disc,macula, large retinal vessels
• Lesion close to macula ,optic disc
• A large lesion in the retina
• Serpiginous choroiditis

53. • Systemic corticosteroids used for the first 4–8 weeks, together
with ATT, limit damage to ocular tissues .
• However, one should avoid using corticosteroids alone without
concomitant ATT as the corticosteroids may promote
multiplication of bacilli, leading to panophthalmitis or they may
cause a flare-up of systemic tuberculosis by activating a latent
infection.
• Topical steroids also used for uveitis.

54. SUMMARY
• Ocular tuberculosis involves almost all the ocular structures
except lens
• Commonest manifestation is in the posterior segment.
• Diagnosis depends on clinical findings and suspicion of TB
• Newer diagnostic modalities, IGRA and PCR are better tools in
diagnosis and providing support to initiate antitubercular
treatment