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OCULAR MANIFESTATIONS OF TUBERCULOSIS
YUZBASHEVA NIHAL 221B
INTRODUCTION
 Tuberculosis (TB) is the leading cause
of death worldwide due to an
infectious agent, the problem
being aggravated by the human
immunodeficiency virus (HIV)
pandemic and the recent increasing
incidence of microbial resistance to
antibiotics
 The recurrence of TB as a major public
health problem raises the possibility
that ophthalmologists may encounter
an increasing number of ocular
complications.
 Ocular TB may affect various regions
of the eye and cause severe visual loss
if not treated properly
HISTORY
 In 1711, Maitre-Jan reported the earliest description of ocular
tuberculosis, an iris lesion that eventually lead to corneal
perforation
 Gueneau de Mussy recognized the first choroidal tubercle in
miliary tuberculosis in 1830 (Wecker 1874) and in 1867, Cohnheim
showed that choroidal tubercles seen clinically were identical to
tubercles elsewhere in the body.
 The tubercle bacillus was discovered by Koch in 1882 (Koch 1882),
and the diagnosis of ocular tuberculosis was further proved when
von Michel identified tubercle bacilli in the eye one year later
DAMAGES CAUSED BY TUBERCULOSIS
Anterior segments
Posterior segments
MANIFESTATION
Anterior
Segment
Anterior uveitis Diffuse scleritis Nodular scleritis Keratoconjuctivitis
Posterior
Segment
Posterior uveitis Neuroretinitis Optic neuropathy
PATHOGENESIS
 Ocular manifestations associated with
TB are either caused by:
- Active infection
- Immunological reaction in the absence
of any infectious agent, which is
related to delayed hypersensitivity and an
aseptic reaction
ACTIVE INFECTION
Primary No other systemic
lesions
Usually associated
with lesions on
conjuctiva and cornea
Secondary
Infection resulting
from contagious or
hematogenous spread
Usually associated
with intraocular
lesions
CLINICAL
FEATURES
 TB may involve any part of the eye and
appear in different clinical forms
 The clinical manifestations of ocular TB are
non-specific and protean.
 The most common manifestation of ocular TB
in patients with pulmonary TB is choroiditis.
 Anterior uveitis, choroid tubercles, retinal
vasculitis, vascular occlusion, dense vitritis,
and papillitis may also occur
 The incidence of TB in patients with the
acquired immunodeficiency syndrome (AIDS)
is almost 500 times the incidence in the
general population
 Unfortunately, early diagnosis of TB in HIV-
positive persons is not easy as the clinical and
radiological features are often atypical
and resemble those caused by other HIV-
related infections
 A 70-year-old man with a
painless tumor in his left
lower lid. a Pathology
findings of the lid mass
showed
chronic granulomatous
inflammation with caseous
necrosis (H&E, x1S0).
(Reprinted from Sheu et al.
2001, with permission from
Elsevier Science) b Acid-fast
stain showed acid-fast bacilli
(Kinyoun's crystal Fuchsin
acid-fast stain, x198)
 A 58-year-old man presenting
with a recurrent corneal ulcer in
the right eye. a Slit-lamp
biomicroscopy showed a corneal
ulcer with descemetocele. b
Nested peR from corneal scraping
showed a positive result for
Mycobacterium
tuberculosis (Reprinted from Sheu
et al. 2001, with permission from
Elsevier Science)
 A 54-year-old woman
presenting with bilateral
choroidal tuberculosis. a
Right eye b Left eye
 Fundus montage showed 50
to 60 ill-defined yellowish-
white elevated nodules
mostly over the posterior
pole. Some hemorrhage was
noted over the macular area
and the optic disc margin
was blurred
 At the late phase of
fluorescein angiography,
allthe nodular lesions
became hyperfluorescent,
and mild dye leakage from
the disc was also noted.
 After anti-TB medication,
the disc margin cleared and
the nodular lesion became
more well-defined.
Choroidal
neovascularization develope
d in the macula of both eyes
 A47-year-old man
presenting with a right
temporal headache, fever
and loss of vision in the left
eye. TB meningitis was
suggested by his TB history
and typical CSF findings,
(although the culture was
negative).
 a Fundus
examination showed
remarkable vitreous opacity.
 b Fundus examination, one
week later, showed several
yellowish-white subretinal
nodule at posterior pole
 Panophthalmitis in a 75-
year-old woman with
pulmonary TB.
 a Slit-lamp biomicroscopy
at presentation
showed ciliary congestion
and dense anterior chamber
reaction (Reprinted from
Sheu et aI. 2001, with
permission from Elsevier
Science).
 b Acid-fast stain of bronchial
biopsy showed acid-fast
bacilli (Kinyoun's crystal
Fuchsin acid-fast stain,
xI000).
 Endophthalmitis in a 68-
year-old man with miliary
TB. a Slit-lamp
biomicroscopy at
presentation
showed pigmented keratic
precipitates, corneal stroma
edema, exudate in the
anterior chamber. c Acid-fast
stain showed acid-fast bacilli
in the area of caseous
necrosis (Kinyoun's crystal
Fuchsin acid-fast stain,
x1000) (Reprinted from Sheu
et al. 2001, with
permission from Elsevier
Science)
DIAGNOSIS
A high degree suspicion is essential for the early diagnosis of TB
The past medical history of patients and their families is a major consideration
Complex diagnostic invetigation to detect tuberculosis of lung or other internal
organs
Ophtolmological investigation of eye lids, lacrimal glands, sclera, conjuctiva,
cornea
Investigation of retina by fluorecent angiography
Optical coeherence tomographyy and ultrasound investigation
SMEARS AND CULTURES
 A presumptive diagnosis is commonly based on the finding of
acid-fast bacilli during microscopic examination (acid-fast bacilli
microscopy) of a diagnostic specimen, such as a vitreous aspirate
or aqueous smear
 A definitive diagnosis is dependent on a positive culture of the
organism from a diagnostic specimen
 Lowenstein-Jensen medium is widely used for the isolation of M
tuberculosis
 Normally, treatment should be started before the culture
results are available.
TUBERCULIN
SKIN TEST
 This reaction is an immunologic
process based on delayed
hypersensitivity.
 A positive skin test result is detectable
3- -8 weeks after the primary infection.
 An intense skin reaction can become
necrotic.
 There is no specific amount of
induration that confirms TB and a
negative test result does not exclude
the diagnosis.
 Active disease may be associated with
a weak or negative reaction, especially
in older patients, the malnourished,
immunosuppressed, or those
patients undergoing corticosteroid
treatment
 A 44-year-old woman
presenting with presumed
tuberculous neuroretinitis. a
Fundus showed severe disc
swelling and hyperemia as
well as multiple placoid
exudative retinal detachment
in the posterior pole. b
Tuberculin skin test
resulted in an intense
reaction with necrosis
MOLECULAR
TECHNIQUES
 These methods include the
polymerase chain
reaction (PCR), which uses a
heat-stable DNA
polymerase to amplify
mycobacterial DNA from
clinical samples (Musial et al.
1988).
 PCR has been used in ocular
specimens to diagnose M.
tuberculosis infection (Kotake
et al. 1994; Gupta et al. 1998).
 PCR is a rapid diagnostic test
with high sensitivity and
specificity.
CHALLENGES
WE MAY FACE
DURING
DIAGNOSING
PATIENTS
 The manifestations of ocular TB are
nonspecific and protean. The ocular
findings can be seen with other ocular
and systemic diseases.
 Ocular TB diagnosis is complicated by
the difficulties associated with ocular
sampling
 And the bacteriological investigetion
of taken materials are rarely giving
positive results
 Tuberculin test and IGRA test is not
useful in detection active and latent
forms of tuberculosis
 The final decision are solely based on
positive result from treatment
TREATMENT
Ethambutol is not advisable
Streptomycin is recommended drug
2HRZS/4HR
Surgery is advised in case of adverse outcomes
TOXICITY OF
ANTI-TB
CHEMOTHERAPY
 The most common adverse reaction of significance is hepatitis.
Patients should be instructed to discontinue medication and
seek medical assistance on developing any signs of hepatitis.
 The drugs can be reintroduced one at a time after liver
function has returned to normal.
 Hypersensitivity reactions usually require discontinuation of all
drugs and re-assessment to determine which agent is
responsible.
 Similarly, the occurrence of optic neuritis with ethambutol
(and rarely isoniazid), as well as the development of
eighth nerve damage with streptomycin require permanent
discontinuation of these drugs.
THANK YOU
FOR
ATTENTION!

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Ocular TB Manifestations Guide

  • 1. OCULAR MANIFESTATIONS OF TUBERCULOSIS YUZBASHEVA NIHAL 221B
  • 2. INTRODUCTION  Tuberculosis (TB) is the leading cause of death worldwide due to an infectious agent, the problem being aggravated by the human immunodeficiency virus (HIV) pandemic and the recent increasing incidence of microbial resistance to antibiotics  The recurrence of TB as a major public health problem raises the possibility that ophthalmologists may encounter an increasing number of ocular complications.  Ocular TB may affect various regions of the eye and cause severe visual loss if not treated properly
  • 3. HISTORY  In 1711, Maitre-Jan reported the earliest description of ocular tuberculosis, an iris lesion that eventually lead to corneal perforation  Gueneau de Mussy recognized the first choroidal tubercle in miliary tuberculosis in 1830 (Wecker 1874) and in 1867, Cohnheim showed that choroidal tubercles seen clinically were identical to tubercles elsewhere in the body.  The tubercle bacillus was discovered by Koch in 1882 (Koch 1882), and the diagnosis of ocular tuberculosis was further proved when von Michel identified tubercle bacilli in the eye one year later
  • 4. DAMAGES CAUSED BY TUBERCULOSIS Anterior segments Posterior segments
  • 5. MANIFESTATION Anterior Segment Anterior uveitis Diffuse scleritis Nodular scleritis Keratoconjuctivitis Posterior Segment Posterior uveitis Neuroretinitis Optic neuropathy
  • 6. PATHOGENESIS  Ocular manifestations associated with TB are either caused by: - Active infection - Immunological reaction in the absence of any infectious agent, which is related to delayed hypersensitivity and an aseptic reaction
  • 7. ACTIVE INFECTION Primary No other systemic lesions Usually associated with lesions on conjuctiva and cornea Secondary Infection resulting from contagious or hematogenous spread Usually associated with intraocular lesions
  • 8. CLINICAL FEATURES  TB may involve any part of the eye and appear in different clinical forms  The clinical manifestations of ocular TB are non-specific and protean.  The most common manifestation of ocular TB in patients with pulmonary TB is choroiditis.  Anterior uveitis, choroid tubercles, retinal vasculitis, vascular occlusion, dense vitritis, and papillitis may also occur  The incidence of TB in patients with the acquired immunodeficiency syndrome (AIDS) is almost 500 times the incidence in the general population  Unfortunately, early diagnosis of TB in HIV- positive persons is not easy as the clinical and radiological features are often atypical and resemble those caused by other HIV- related infections
  • 9.  A 70-year-old man with a painless tumor in his left lower lid. a Pathology findings of the lid mass showed chronic granulomatous inflammation with caseous necrosis (H&E, x1S0). (Reprinted from Sheu et al. 2001, with permission from Elsevier Science) b Acid-fast stain showed acid-fast bacilli (Kinyoun's crystal Fuchsin acid-fast stain, x198)
  • 10.  A 58-year-old man presenting with a recurrent corneal ulcer in the right eye. a Slit-lamp biomicroscopy showed a corneal ulcer with descemetocele. b Nested peR from corneal scraping showed a positive result for Mycobacterium tuberculosis (Reprinted from Sheu et al. 2001, with permission from Elsevier Science)
  • 11.  A 54-year-old woman presenting with bilateral choroidal tuberculosis. a Right eye b Left eye  Fundus montage showed 50 to 60 ill-defined yellowish- white elevated nodules mostly over the posterior pole. Some hemorrhage was noted over the macular area and the optic disc margin was blurred
  • 12.  At the late phase of fluorescein angiography, allthe nodular lesions became hyperfluorescent, and mild dye leakage from the disc was also noted.
  • 13.  After anti-TB medication, the disc margin cleared and the nodular lesion became more well-defined. Choroidal neovascularization develope d in the macula of both eyes
  • 14.  A47-year-old man presenting with a right temporal headache, fever and loss of vision in the left eye. TB meningitis was suggested by his TB history and typical CSF findings, (although the culture was negative).  a Fundus examination showed remarkable vitreous opacity.  b Fundus examination, one week later, showed several yellowish-white subretinal nodule at posterior pole
  • 15.  Panophthalmitis in a 75- year-old woman with pulmonary TB.  a Slit-lamp biomicroscopy at presentation showed ciliary congestion and dense anterior chamber reaction (Reprinted from Sheu et aI. 2001, with permission from Elsevier Science).  b Acid-fast stain of bronchial biopsy showed acid-fast bacilli (Kinyoun's crystal Fuchsin acid-fast stain, xI000).
  • 16.  Endophthalmitis in a 68- year-old man with miliary TB. a Slit-lamp biomicroscopy at presentation showed pigmented keratic precipitates, corneal stroma edema, exudate in the anterior chamber. c Acid-fast stain showed acid-fast bacilli in the area of caseous necrosis (Kinyoun's crystal Fuchsin acid-fast stain, x1000) (Reprinted from Sheu et al. 2001, with permission from Elsevier Science)
  • 17. DIAGNOSIS A high degree suspicion is essential for the early diagnosis of TB The past medical history of patients and their families is a major consideration Complex diagnostic invetigation to detect tuberculosis of lung or other internal organs Ophtolmological investigation of eye lids, lacrimal glands, sclera, conjuctiva, cornea Investigation of retina by fluorecent angiography Optical coeherence tomographyy and ultrasound investigation
  • 18. SMEARS AND CULTURES  A presumptive diagnosis is commonly based on the finding of acid-fast bacilli during microscopic examination (acid-fast bacilli microscopy) of a diagnostic specimen, such as a vitreous aspirate or aqueous smear  A definitive diagnosis is dependent on a positive culture of the organism from a diagnostic specimen  Lowenstein-Jensen medium is widely used for the isolation of M tuberculosis  Normally, treatment should be started before the culture results are available.
  • 19. TUBERCULIN SKIN TEST  This reaction is an immunologic process based on delayed hypersensitivity.  A positive skin test result is detectable 3- -8 weeks after the primary infection.  An intense skin reaction can become necrotic.  There is no specific amount of induration that confirms TB and a negative test result does not exclude the diagnosis.  Active disease may be associated with a weak or negative reaction, especially in older patients, the malnourished, immunosuppressed, or those patients undergoing corticosteroid treatment
  • 20.  A 44-year-old woman presenting with presumed tuberculous neuroretinitis. a Fundus showed severe disc swelling and hyperemia as well as multiple placoid exudative retinal detachment in the posterior pole. b Tuberculin skin test resulted in an intense reaction with necrosis
  • 21. MOLECULAR TECHNIQUES  These methods include the polymerase chain reaction (PCR), which uses a heat-stable DNA polymerase to amplify mycobacterial DNA from clinical samples (Musial et al. 1988).  PCR has been used in ocular specimens to diagnose M. tuberculosis infection (Kotake et al. 1994; Gupta et al. 1998).  PCR is a rapid diagnostic test with high sensitivity and specificity.
  • 22. CHALLENGES WE MAY FACE DURING DIAGNOSING PATIENTS  The manifestations of ocular TB are nonspecific and protean. The ocular findings can be seen with other ocular and systemic diseases.  Ocular TB diagnosis is complicated by the difficulties associated with ocular sampling  And the bacteriological investigetion of taken materials are rarely giving positive results  Tuberculin test and IGRA test is not useful in detection active and latent forms of tuberculosis  The final decision are solely based on positive result from treatment
  • 23. TREATMENT Ethambutol is not advisable Streptomycin is recommended drug 2HRZS/4HR Surgery is advised in case of adverse outcomes
  • 24. TOXICITY OF ANTI-TB CHEMOTHERAPY  The most common adverse reaction of significance is hepatitis. Patients should be instructed to discontinue medication and seek medical assistance on developing any signs of hepatitis.  The drugs can be reintroduced one at a time after liver function has returned to normal.  Hypersensitivity reactions usually require discontinuation of all drugs and re-assessment to determine which agent is responsible.  Similarly, the occurrence of optic neuritis with ethambutol (and rarely isoniazid), as well as the development of eighth nerve damage with streptomycin require permanent discontinuation of these drugs.