Tuberculosis and the Eye

a seminar presented at
Birminham &
 Tuberculosis and the Eye
a seminar presented at Birmingham &
Midland Eye Centre, 2003
John O’Shea
 Tuberculosis and the Eye-
Epidemiology
 About one third of the world's population has latent
tuberculosis, caused by Mycobacterium tuberculosis.
 From this pool, roughly 9 million cases of active
tuberculosis emerge annually, resulting in 2-3 million
deaths.
 Most new cases occur in the most populated nations. India
and China, but the highest rates of disease are seen in sub-
Saharan Africa, the Indonesian and Philippine archipelagos,
Afghanistan, Bolivia, and Peru. In these regions case rates
typically exceed 300 cases per 100 000 per year fection.
 The incidence of tuberculosis has increased in England and
Wales over the past few years, with a current annual rate of
5000 to 6000 cases. For the year 2000, the Public Health
Laboratory Service has had a 10.6% increase in notifications
over 1999
Tuberculosis and the Eye-
Epidemiology
 Tuberculosis and the Eye-
Contemporary Issues
 Although the incidence of tuberculosis declined in North
America and western Europe throughout most of the latter
half of the 20th century, case rates have increased over the
past 10 years mainly because of immigration, HIV/AIDS,
and the neglect of tuberculosis control programmes.
 It is recommended that all patients with tuberculosis
undergo a test for HIV.
 Health workers are at risk of tuberculosis
 Treatment of active Tuberculosis gives cure rates above
95% provided that the strain of Mycobacterium tuberculosis
is not multidrug resistant and that compliance is adequate.
Non-adherence to treatment may decrease cure rates to 79%
and increase the prevalence of multidrug resistant strains
Tuberculosis and the Eye-
Contemporary Issues
 In 1992 the New York Post ran
the headline: "TB timebomb.
Homeless contaminate public
areas in city."
 In April 1993 increasing rates of
tuberculosis led to the World
Health Organization declaring a
global emergency.
 Tuberculosis has enjoyed a
resurgence, allied as it is to
economic and social fractures and
the HIV epidemic.
 Tuberculosis and the Eye-
Contemporary Issues
 Globally, the most common opportunistic infection and the leading cause of death related
to HIV infection is tuberculosis. The two main approaches to tuberculosis control are
casefinding combined with treatment of active cases, and prevention of disease in infected
people.
 A recent trial conducted in Zaire compared a six month therapeutic regimen (daily
rifampin, isoniazid, pyrazinamide, plus ethambutol for two months followed by twice
weekly rifampin plus isoniazid for four months) with a 12 month regimen
 The rate of relapse was higher after the shorter regimen, but survival was comparable.
 Prophylaxis of active disease with isoniazid for patients infected with HIV and
tuberculosis is effective, but widespread implementation of such an approach in
developing countries may not be feasible.
 The United States saw a resurgence of tuberculosis in the late 1980s and early 1990s that
highlighted the devastating consequences of cutbacks in the infrastructure of tuberculosis
control programmes.
 Several outbreaks of multidrug resistant tuberculosis occurred, primarily affecting people
infected with HIV.
 In some areas, like New York city, as many as 19% of the cases of tuberculosis were
attributable to multidrug resistant tuberculosis.
 Renewed attention to tuberculosis control has begun to deal with the problem in the USA.
 Tuberculosis and the Eye-
Contemporary Issues
HEALTH WORKERS
 Health and hospital workers vary in their risk of contracting and
disseminating tuberculosis. Staff working with children or
immunocompromised patients should have a chest radiograph
before starting work.
 Mortuary workers, microbiology staff, and those caring for patients
with tuberculosis should have a pre-employment chest radiograph
and tuberculin test.
 Those who are tuberculin negative should be given BCG.
 Routine chest radiography during employment is not
recommended.
 Other health workers should be given BCG vaccination, if
indicated.
 Other specific precautions need not be taken.
 Tuberculosis and the Eye-
Pathology
 The tubercle bacillus was
discovered by Robert Koch
in 1882
 Mycobacteria are Gram-
positive, although they are
not easily stained by this
method. They are resistant to
decolorization by mineral
acids after staining with
arylmethane dyes such as
carbol fuchsin, hence the
term acid-fast.
 Tuberculosis and the Eye-
Pathology
 Immune responses in tuberculosis
may be either protective, leading to
resolution of disease, or tissue
destroying, leading to the
pathological characteristics of active
disease
 Both types of response are cell-
mediated and there has been
considerable controversy about
whether protective and
immunopathological responses are
manifestations of the same
mechanism, differing only in degree
 The characteristic histological lesion
of tuberculosis is the granuloma,
which consists of a chronic, compact
aggregate of activated macrophages
(epithelioid cells), some of which
fuse to form multinucleate giant cells
 Tuberculosis and the Eye-
Pathology
 Mycobacterium tuberculosis uses a
trick to invade cells.
 The body's immune system normally
tags any invading bacteria with
proteins that alert macrophages to
consume it. One of these proteins,
C2a, then floats in the blood with no
known function.
 M tuberculosis manages to associate
with this discarded C2a protein and
use it to create a new label that helps
the bacteria adhere to the macrophage
and enter it.
 Once inside the macrophage, the
mycobacteria multiply until the cell
ruptures and the bacteria are then
released to repeat the process
 Tuberculosis and the Eye- Pathology
 The initial pulmonary lesion,
the Ghon focus, together with
the hilar lymphadenopathy,
forms the primary complex of
Ranke.
 Some bacilli are disseminated
through lymphatics and
blood, leading in some cases
to meningeal, bone, and renal
involvement.
 Tuberculosis and the Eye-Standard
Investigations
 CXR
 CultureSputum / urine culture / stain for
AAFB (acid and alkali fast bacilli).Ziehl
Neelsen stain or auramine-phenol fluorescent
test are confirmatory
 Tuberculin hypersensitivity
 Mantoux
 Old Tuberculin = PPD (purified protein
derivative)
 Biopsy
Tuberculosis and the Eye-Standard
Investigations Chest X Ray
Reactivation tuberculosis
 Tuberculosis and the Eye-Standard
Investigations
 Radiological changes,
though sensitive, are rather
non-specific. Tuberculosis
may cause virtually any
radiological abnormality
and atypical pictures are
not uncommon, especially
in HIV-positive and other
immunocompromised
persons.
 Bacteriological
confirmation should always
be sought.  
 SARCOIDOSIS AND
TUBERCULOSIS
 Sarcoidosis and tuberculosis have several clinical and pathological features
in common. Sarcoid often features cutaneous anergy.
 Both diseases are characterised by the formation of granulomas. These are
usually caseating in tuberculosis, but areas of necrosis can occur in
sarcoidosis.
 This overlap makes it difficult to distinguish between the two conditions in
some cases, such as that of our patient. In addition, there are occasional
well characterised cases in which both diseases seem to coexist,eading to
suggestions that the association is causal.
 Moreover tuberculosis may become apparent after the treatment of
sarcoidosis with corticosteroids, but this association is relatively rare.
 Isolation of mycobacterial DNA from sarcoid tissue using the polymerase
chain reaction has been reported, but these data have not been consistently

replicated and their significance remain uncertain.
Winterbauer RH, Kraemer KG. The infectious complications of sarcoidosis. Arch Intern Med 1976;136:1356-62. [Medline]
 Fidler HM, Rook GA, Johnson NM, McFadden J. Mycobacterium tuberculosis DNA in tissue affected by sarcoidosis. BMJ 1993;306:546-9. [Medline]
 Bocart D, Lecossier D, De Lassence A, Valeyre D, Battesti JP, Hance AJ. A search for mycobacterial DNA in granulomatous tissue from patients with sarcoidosis using the polymerase chain reaction. Am Rev Respir Dis 1992;145:1142-8. [Medline]
 SARCOIDOSIS AND
TUBERCULOSIS
 Neurosaroid- Meningeal biopsy by small
burr hole and the use of the operating
microscope is a procedure of low morbidity
 Tuberculosis and the Eye- Ocular
Manifestations
 Uveitis commonest
 Systemic disease is often apparent
 Eyelids- lupus vulgaris (nodules surrounded by erythema)
 Orbit- cellulitis, dacryoadenitis, dacryocystitis, osteomyelitis,
abscess
 Conjunctiva- rarely affected, phlyctenular conjunctivitis
described in some texbooks as allegic manifestation along
with erythema nodosum.
 Cornea- phlyctenular keratoconjunctivitis, interstitial
keratitis (unilateral, sectorial, superficial vascularisation)
  Sclera- episcleritis, nodular scleritis
 Uveitis- chronic granulomatous anterior uveitis, multifocal
choroiditis, exudative retinitis,
 Vasculitis, optic nerve oedema, papilloedema
 Tuberculosis and the Eye- Ocular
Manifestations
 Phlyctenular conjunctivitis, which may
occur in some children within 1 year of the
primary infection, consists of small,
multiple, yellow or grey conjunctival
nodules near the limbus, with a sheaf of
dilated vessels.
 Tuberculosis and the Eye- Case
Presentation
 DOB 1974, 31 Years, male
 Pulmonary Tuberculosis
 Presented with recurrent vitreous
haemorrhage R and L,
 Referred from Wolverhampton
 Rx Rifampicin, Isoniazid, Pyridoxine
 Tuberculosis and the Eye- Case
Presentation
 VA RE 6/5 LE6/5
 Bilateral vitreous haemorrhages
 No obvious new vessels
 FFA and ICG 12/11/2002
 Bilateral PRPs following angiography
 Now non complaint
Right Fundus
Left Fundus
Colour Fundus photography-
multiple vascular lesions associated with vitreous
haemorrhage
 Flourescein Angiography
 RE NV’S AND
VASCULAR
LEAKAGE,
VASCULAR
REMODELLING, NO
CMO, DISC
HYPERFLOURESEN
-CE
 LE MULTIPLE
NV’S-NO CMO
Flourescein Angiography
 Tuberculosis and the Eye- Case
Presentation
 ICG-delayed choroidal
filling
 THERAPEUTICS
 It is recommended that all patients with tuberculosis undergo a test for
HIV.
 Supplements of pyridoxine (vitamin B6)not to exceed a daily dose of
50 mgare suggested for patients taking isoniazid to prevent peripheral
neuritis. Particular attention should be given to patients at risk of
neuropathy, including patients who are malnourished or pregnant. Baseline
liver function tests and periodic and regular monitoring are advocated in
view of the potential hepatotoxicity of isoniazid, rifampicin, and
pyrazinamide. The risk of major liver damage is less than 1%, but mild
asymptomatic increases in transaminase blood concentrations are seen in
up to 20% of patients.
 Doses of ethambutol should be carefully adjusted in patients with renal
impairment.
 Patients taking ethambutol should have their visual acuity checked initially
and serially monitored (Snellen acuity and Ishihara colour). They should be
instructed to report promptly any perceived disturbances in their vision.
 ETHAMBUTOL

 Ethambutol is bacteriostatic for M. tuberculosis in the dosages that can safely

be given, and is used to prevent the emergence of strains resistant to other
drugs. It should be avoided in the treatment of patients with impaired renal
function as it may accumulate and cause serious ocular toxicity. It should not
be given to young children or any patient unable to report early symptoms of
ocular toxicity.
 The British Thoracic Society recommends that renal function and visual acuity
should be assessed before the drug is prescribed, the recommended dosage
should not be exceeded, any history of eye disease should be recorded, the
patient should be told that the drug may rarely affect vision and drugs should
be stopped immediately should vision become impaired, patients complaining
of visual disturbance during chemotherapy should be referred to an
ophthalmologist for detailed examination, and the family practitioner should
be told what information and instructions have been given to the patient. All
these precautions and pieces of advice to the patient should, of course, be
recorded in the case notes.
 EALE’S DISEASE
  Obliterative vasculitis affecting the peripheral retina
 M>F, 30-40yrs
 India, Pakistan and Middle East
 50% have TB or have been exposed to TB bacillus. No definite
cause but there is a definite association with the Tubercle bacillus
perhaps mediated by a hypersensitivity to tuberculin protein.
 Presents with vitreous haemorrhages or floaters.
 Sheathed vessels especially veins with peripheral non- perfusion
and NVE, NVD and rarely rubeosis
 Anterior chamber activity, vitritis and CMO
 Associated vestibuloauditory dysfunction
– 
 Outcome

 The overall mortality for all forms of tuberculosis in Great

Britain is about 8 per cent, varying from under 1 per cent
for children and young adults to over 30 per cent in those
aged 75 years or more.
 Mortality is higher for patients with extensive disease,
smear positivity and cavitation. Mortality appears to be the
same in both sexes, even though males are twice as likely
to develop pulmonary disease.
 Most deaths occur early in treatment: a recent study
showed that over two-thirds of deaths due to pulmonary
tuberculosis occurred within 4 weeks of starting
chemotherapy.