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10.5005/jp-journals-10028-1085
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Intraocular Tuberculosis
Intraocular Tuberculosis
Swapnil Parchand, Vishali Gupta, Amod Gupta, Aman Sharma
ABSTRACT
Intraocular tuberculosis remains a major diagnostic challenge
and it is extremely important to establish the diagnosis as the
specific treatment helps in reducing the recurrences, thus
reducing ocular morbidity. The present review aims to describe
the global epidemiology and pathogenesis of intraocular
tuberculosis with clinical spectrum and different presentations.
The challenges in establishing the diagnosis with role of
conventional tests like PPD skin test as well as current
diagnostic tests including interferon gamma release assay and
molecular diagnostic tests are discussed. The treatment
requires anti-tuberculosis therapy with the use of concomitant
corticosteroids and carries good prognosis provided the
treatment is started in the early stage.
Keywords: Intraocular tuberculosis, Granulomatous uveitis, Antituberculosis treatment, Serpiginous-like choroiditis, Tubercles.
How to cite this article: Parchand S, Gupta V, Gupta A,
Sharma A. Intraocular Tuberculosis. J Postgrad Med Edu Res
2013;47(4):193-201.
Source of support: Nil
Conflict of interest: None declared
INTRODUCTION
Tuberculosis (TB) is a common infectious disease caused
by Mycobacterium tuberculosis (MTB) with nearly onethird of the world’s population infected with it.1 India is
endemic for TB with prevalence of 256 cases/100,000
population.2 Reported incidence for all forms of TB in India
was 185 with death rate of 26 in 2010.2
Nearly 80% of TB occurs in the lungs, but other organs
including eyes may be infected and there is a recent increase
in extrapulmonary TB in patients with HIV/AIDS. 3
Tuberculosis can affect the anterior and posterior segment
of the eye as well as ocular adnexa with remarkable
pleomorphism of the lesions. The large variation in the
clinical presentation and lack of uniformity in diagnostic
criteria make diagnosis of intraocular tuberculosis difficult.
However establishing the diagnosis of intraocular TB is of
utmost importance, as specific therapy needs to be instituted.
The current review focuses on various clinical manifestations,
diagnostic modalities including the newer ones and treatment
recommended for ocular TB.
EPIDEMIOLOGY OF OCULAR TB
There is no reliable data on prevalence of ocular tuberculosis
because of wide spectrum of presentation, lack of uniformity
in the diagnostic criteria and difficulty in confirming the
diagnosis. First attempt was made in 1967 when Donahue4
reviewed the ophthalmic record of 10,524 patients with
primarily pulmonary tuberculosis and found 154 (1.4%)
patients having clinical signs of ocular tuberculosis.
However, in 1997, Bouza et al5 reported a higher incidence
of ocular tuberculosis in Spain; of 100 randomly selected
patients with culture proven systemic tuberculosis seen in a
university hospital, 18 were found to have ocular lesions,
including choroiditis, papillitis, retinitis, vasculitis,
dacryoadenitis and scleritis. In a report from South India,
Biswas et al6 reported 0.39% of total cases from their clinic
being caused by TB between 1992 and 1994. However; this
study did not elaborate the diagnostic criteria for diagnosis
of ocular TB. We reported that 9.8% of total uveitis cases
at our referral eye clinic were caused by TB between the
years 1996 and 2001.7 The discrepancy in the incidence
reported between two large centers in India could be due to
the fact that we had used molecular biologic techniques
including polymerase chain reaction (PCR) assay from
intraocular fluids for diagnosing intraocular tuberculosis
which was not done in the study from South India.
Persons living with HIV are more likely to progress from
latent tuberculosis infection to TB, to have atypical
presentations, including extrapulmonary TB, and are more
difficult to diagnose.8 Extrapulmonary TB can be seen in
as many as 70% of patients with concomitant HIV and TB
infections. 9 Babu et al reported 1.95% incidence of
concurrent ocular TB in patients with HIV/AIDS in India,
while the reported incidence from US was 5%.10,11
PATHOGENESIS OF OCULAR TB
Rao et al12 developed an experimental guinea pig model to
understand the pathogenesis of ocular tuberculosis and to
reproduce natural route of infection through lungs. Their
observations indicate that guinea pigs when infected with
M. tuberculosis via an aerosol route showed development
of pulmonary TB in all animals and ocular lesions developed
in 42%. Histological analysis of the pulmonary and ocular
lesions revealed granulomatous inflammation and presence
of acid-fast bacilli (AFC) similar to those observed in humans
with TB. This model reiterates the belief that intraocular TB
results from hematogenous spread from the primary complex
or from post primary reactivated lung lesions.12 Bacilli in
the ocular tissue, as in other extrapulmonary sites, may
remain dormant in RPE for years before they are activated.13
CLINICAL SPECTRUM OF INTRAOCULAR TB
The most common clinical presentation appears to be
posterior uveitis (42%), followed by anterior uveitis (36%),
panuveitis (11%) and intermediate uveitis (11%).14,15
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CLINICAL FEATURES
1. Anterior segment: Patients may present with localized
nodule in the eyelid simulating chalazion or as localized
granuloma in orbital or lacrimal gland.8 Phlyctenulosis
more frequently observed in children with malnutrition
can present with extreme photophobia, irritation, tearing
and blepharospasm but responds well to topical
steroids.16 Tuberculosis may cause interstitial keratitis
with stromal infiltration. 8 Scleral involvement in
tuberculosis is usually anterior, and may present as focal
elevated nodules of the sclera that may undergo necrosis
leading to scleromalacia and ultimately perforation or
less commonly as diffuse scleritis (Figs 1A to D).
Tuberculosis is a well-known cause of acute or
chronic granulomatous anterior uveitis (Fig. 2) that may
be associated with iris or angle granulomas (Fig. 3) with
mutton-fat keratic precipitates and posterior synechiae
(Fig. 4).17 In the acute miliary form of tuberculosis,
patients may present with anterior chamber inflammation
associated with small grayish-yellow or reddish nodules
near the iris root. In severe cases, hypopyon may be seen
in association with iris lesions. Clinically, these nodules
first appear as small gray elevations that, if left untreated,
could grow up to 3 mm in size. Overtime, the color
changes from gray to yellow, and the nodules become
vascularized. Tubercular anterior uveitis may also
present as a mild or moderate recurrent iridocyclitis.
During relapses, mutton-fat keratic precipitates may
develop, along with extensive broad-based posterior
synechiae, complicated cataract and vitritis.
2. Intermediate uveitis (IU): In the large clinical series of
intermediate uveitis from North India, TB was the most
common underlying etiology seen in 57 (46.7%) of 122
patients with IU.18 Presenting sign was vitritis (95 eyes),
snow balls (82 eyes) (Figs 5A to D), snow banking
(16 eyes), vascular sheathing (14 eyes) and healed
choroiditis (10 eyes). IU can be complicated by cystoid
macular edema (CME) (Figs 5A to D).
3. Posterior uveitis: In tuberculous posterior uveitis, the
ocular changes include choroidal tubercles, tuberculoma,
subretinal abscess, serpiginous-like choroiditis,
endophthalmitis, neuroretinitis and retinal vasculitis.
Choroidal tubercle: Multifocal choroidal tubercles
are the most characteristic clinical presentation of the
tubercular posterior uveitis developing from hematogenous
spread of tubercular bacilli from pulmonary or other
sites.19 A study from India reporting 60% cases with
mycobacterial sepsis showing ocular involvement;
choroidal tubercles being the most common
presentation.20 Usually, they are multiple and less than
A
B
C
D
Figs 1A to D: A 34-year-old, who was receiving ATT for serpiginous like choroiditis presented with recurrence
of uveitis in form of diffuse scleritis; (A and B), Aqueous tap PCR for M. tuberculosis was positive and
patient was started on category II ATT regimen and frequent topical betamethasone drops 0.1%. Same
patient at the 2 weeks showing resolution of scleritis (C and D)
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Intraocular Tuberculosis
5 in number, appearing as grayish white to yellowish in
color, discrete with indistinct borders lying deep in the
choroid (Figs 6A to D). These lesions are mainly seen
Fig. 2: Acute anterior granulomatous uveitis in a patient with ocular
TB showing mutton fat keratic precipitates (black arrow) and iris
nodule at papillary margins (white arrow)
Fig. 3: A 19-year-old female presented with blurring of vision in
right eye since 1 month. On examination, anterior segment revealed
granuloma at superonasal quadrant of the angle in right eye.
Granuloma after biopsy was subjected to multiplex PCR
for TB which came out to be positive. Patient received ATT for
12 months without any further recurrence
Fig. 4: A 21-year-old female with pulmonary TB showing typical broadbased posterior synechiae in healed tubercular anterior uveitis
in the posterior pole but can be seen in the mid-periphery
as well. The size may vary from a quarter disk to several
disk diameters with an overlying serous detachment. The
choroidal tubercles heal over 12 to 14 weeks with pale
atrophic, sharply demarcated areas with variable
pigmentation. Histologically, the choroidal tubercles are
similar to the tubercles elsewhere in the body.21 On
fluorescein angiography, the lesions are hypofluorescent
in the dye transit and become hyperfluorescent in the
late frames. 14 In patients with acquired immune
deficiency syndrome (AIDS), the tubercles may be
asymptomatic with little overlying vitritis and detected
on routine examination.22 These choroidal tubercles
responds very well to antitubercular therapy (ATT) with
oral corticosteroids and surgical intervention should be
avoided in such cases.23
Solitary choroidal tuberculoma/subretinal abscess:
In patients with miliary tuberculosis/disseminated
tuberculosis and those with depressed T-cell immunity
including HIV-infected individuals, ocular TB may
present as solitary yellowish elevated mass-like lesion
(tuberculoma), measuring from 4 to 14 mm in size,
resulting from a progressive, liquefied caseation necrosis
with rapid multiplication of tubercular bacilli and tissue
destruction (Figs 7A and B). They may be accompanied
by exudative retinal detachment and may show rapid
progression at times breaking into the vitreous cavity or
even ocular perforation.21,22,24 Ultrasonography may
show a low internal reflectivity on A-scan but may show
a solid elevated mass lesion on B-scan.
Serpiginous-like choroiditis: We first described the
clinical presentation of serpiginous-like choroiditis.25
Two morphologic patterns are seen: (a) progressive
multifocal choroiditis where lesions begin as yellowishwhite, well-defined round lesions, measuring one-fourth
to 1 disk diameter in size with raised edges. Fluorescein
angiography shows initial hypofluorescence with late
hyperfluorescence (Figs 8A to D). Over a period of the
next 1 to 4 weeks, these lesions progress, become
confluent, and show a wave-like progression with an
advancing edge that is hypofluorescent in the early phase
with late hyperfluorescence. On ICG, the lesions are
hypofluorescent throughout, (b) The lesion may start
more diffusely as a plaque-like lesion with an active
progressive serpiginous like edge, whereas the center is
less elevated with pigmentary changes, indicating the
process of healing in the center of the lesion. The
fluorescein angiography shows central mixed
fluorescence, with advancing edge showing initial hypoand late hyperfluorescence. Recently, we reported the
role of fundus autofluorescence in identifying the areas
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Swapnil Parchand et al
A
B
C
D
Figs 5A to D: The right of patient with intermediate uveitis showing snow balls inferiorly (black arrow in
Figure A), vascular leakage in periphery (white arrow in Figure C) and cystoids macular edema (white arrow
in Figure D) in late phase of fundus fluorescein angiography. UBM picture of same patient showing exudates
at pars plana area (white arrow in Figure B)
A
B
C
D
Figs 6A to D: A 23-year-old female presented with choroidal granuloma (black arrow) with exudative retinal
detachment (red arrow demarcating the extent of detachment) in posterior pole area of right eye (A).
On fundus fluorescein angiography (B) the lesion is hypofluorescent in early stage. In late stage (C and D),
the lesion becomes more hyperfluorescent with leakage of dye marking the extent of surrounding exudative
detachment. X-ray showed right sided pleural effusion with calcified lymph node in perihilar region. Mantoux
test was 35 × 25 mm. Quantiferon gold for TB was positive. She was started on ATT with oral corticosteroids
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of disease activity which shows increase autofluorescence
and also for monitoring the course of lesions by
identifying four patterns in serpiginous- like choroiditis.26
Patients may show multiple recurrences on oral
corticosteroids/immunosuppressants and recurrences can
be significantly reduced after initiating antituberculosis
chemotherapy in this group of patients.
Endophthalmitis: Rarely, ocular tuberculosis may
present as acute onset endogenous endophthalmitis
due to rapidly progressive disease, which does not
respond to antitubercular therapy.21 This may occur due
to rapid multiplication of bacilli or in patients who
receive corticosteroid therapy without concomitant
antitubercular drugs.
Tubercular neuroretinitis: Tuberculous optic
neuropathy is usually seen as a retrobulbar optic neuritis
complicating tubercular meningitis.27
Tubercular retinal vasculitis: Active retinal vasculitis
due to TB typically present with moderate vitritis, severe
perivascular cuffing with infiltrates, and extensive
peripheral capillary nonperfusion leading to formation
of new vessels in the periphery or even on the optic disk
(Figs 9A to C). 28 Snowball opacities may be seen
inferiorly in the vitreous cavity. In nearly half of the
patients, it is associated with active or healed choroiditis
patches, typically seen under the retinal vessels. 28
A
B
Figs 7A and B: A 35-year-old female presented with large subretinal
abscess in temporal quadrant with surrounding exudative retinal
detachment involving the center of fovea of right eye (A). Same
patient at 15-month after receiving ATT with corticosteroid showing
resolution of abscess with formation of scar (B)
A
B
C
D
Figs 8A to D: A 28-year-old male presented with serpiginous- like choroiditis in right eye (A). Note the
choroiditis lesions with central healing with grayish-white elevated active edges (arrow) (A). Fundus
fluorescein angiography showing transmission defects in the healed areas of choroiditis and intense
hyperfluorescence of the active edges in the late frames (B and C). Same patient at 1 year after completing
the course of ATT showing healed choroiditis lesions with pigmentary changes (D)
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B
A
C
Figs 9A to C: A 35-year-old male presented with retinal vasculitis with hemorrhages (black arrow) and
perivascular choroiditis lesion (white arrow) (A), Fundus fluorescein angiography shows perivascular staining
in temporal retinal (B), Same patient following ATT, oral steroids and scatter laser showing healed perivascular
choroiditis lesion with occluded vessels (C)
Neuroretinitis characterized by optic disk edema and
macular star may be commonly associated with
tubercular retinal vasculitis. Tubercular vasculitis causes
extensive peripheral retinal ischemia and leads to retinal
vascularization, necessitating scatter laser photocoagulation in majority of affected eyes, a few requiring pars
plana vitrectomy for removal of nonclearing vitreous
hemorrhage or relief of tractional retinal detachment.
Thus, tuberculous uveitis has varied presentation and
can involve any structure of eye and several other
diseases, like syphilis, sarcoidosis, etc. mimic the clinical
presentation of TB. We analyzed these ocular signs
which could be predictive of ocular TB.29 In the retrospective study, we found four clinical signs very specific
for TB: broad-based posterior synechiae (93%), retinal
vasculitis without choroiditis (97%), retinal vasculitis
with choroiditis (99%) and serpiginous-like choroiditis
(98%). Thus, if any one of these four clinical signs is
present in an undiagnosed patient, further TB testing is
warranted, especially in endemic areas, such as India.
DIAGNOSIS
The gold standard in the diagnosis of TB has been detection
of M. tuberculosis in the lesions by histological methods or
by culture using Lowenstein-Jensen media.30 But isolation
of M. tuberculosis through culture often proves challenging
because of the paucibacillary and focal nature of the
infection in eye. Also, it is impractical, as it may take several
weeks before culture results become available for starting
specific therapy for a sight-threatening lesion and also
obtaining biopsy specimens from intraocular tissues for
making a confirmatory histopathological diagnosis is not
198
without unjustifiable risks. In this setting, at best, a diagnosis
of presumed ocular TB can be made.
The tuberculin test (Mantoux test) is based on a classic
type-IV delayed-type hypersensitivity (DTH) response and
quantifies the induration produced 48 to 72 hours following
intradermal injection of 5 tuberculin units (TU) of PPD.
Any induration less than 5 mm is considered a negative
result and between 5 and 10 mm is positive in persons with
HIV infection, close contact with an infectious patient with
tuberculosis, and those showing healed lesions of
tuberculosis in chest radiographs. A test result more than
10 mm is considered positive for patients living in high
incidence areas, those with high-risk behavior and those
who are residents of long-term care facilities. Any result
more than 15 mm is considered a positive result.14,31 Falsepositive tests may result from prior exposure to nontuberculous mycobacterium and BCG vaccination, although
BCG-induced TST responses are generally small and believed
to wean off and usually do not persist after 10 years.32
Importantly, TST results may be negative in 20 to 30% of
patients with active TB, and the negative predictive value
is further decreased in HIV-infected patients.33
Lungs being the primary site of infection, radiography
has a major role in diagnosis and evaluation of TB. Primary
TB can involve any lung segment whereas reactivated TB
most often involves the upper lobe or the superior segment
of the lower lobes. In patients with normal immune
responses, reactivation disease is characterized by focal or
patchy heterogeneous consolidation involving the apical and
posterior segments of the upper lobes or the superior
segments of the lower lobes, with or without cavitation.
Calcified hilar lymph nodes or pulmonary nodules characterize
the inactive disease. Computer-assisted tomography (CT)
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Intraocular Tuberculosis
scans of the chest provide increased sensitivity and
specificity and should be considered in all patients with
inconclusive chest X-rays.34 Recently, cases of TB detected
by 18F-fluorodeoxyglucose positron emission tomography/
computer-assisted tomography (18F-FDG-PET/CT) were
reported in patients with malignant diseases and immunocompromised subjects, where clinical manifestations were
atypical and morphological abnormalities were not
detectable with conventional imaging.35,36 Doycheva et al37
found 18F-FDG-PET/CT beneficial in identifying
metabolically active lymph nodes, appropriate for biopsy
in patients with presumed TB-induced intraocular
inflammation, and thereby helps to establish the diagnosis
and appropriate therapy, especially in the case of
latent infection.
Interferon gamma release assays (IGRA) are in vitro
assays, which measure the interferon- (INF) released by
sensitized T cells after stimulation by very specific MTB
antigen, ESAT-6 and CFP-10,9.38,39 They trigger no cross
reactivity with BCG vaccine and, usually, no cross reactivity
with the non-M. tuberculosis complex. QuantiFERON-TB
Gold identifies latent TB infection better than the tuberculin
skin test in a population vaccinated by BCG.40-42 It could
thus be a useful tool for identifying more accurately those
patients who may benefit from full anti-TB treatment in the
management of presumed TB-related uveitis. Studies of
IGRAs in patients with uveitis from multiple centers have
suggested comparable sensitivity, but improved specificity,
relative to TST.41,42 Although the IGRA cannot replace
conventional methods to diagnose active TB, they may play
a role in certain patient population, including immunocompromised patients, young children who cannot produce
a sputum sample, patients with smear-negative pulmonary
TB, and those with extrapulmonary disease, especially in
highly endemic areas.43
PCR is a sensitive and highly specific technique that
can amplify mycobacteial DNA several-fold for easy
detection. PCR can be performed with very small sample
that can be aqueous humor, vitreous humor, subretinal fluid
or, rarely, tissue obtained by chorioretinal biopsy. The
reported PCR-positivity for M. tuberculosis is 33.3% of
cases in retinal vasculitis and 66.6% in granulomatous
panuveitis.44 Use of ATT in PCR positive patients resulted
in resolution of symptoms and elimination of recurrences.45
Nested PCR of ocular fluid may be more sensitive and
specific than other types of PCR. Nested PCR using MPB64
is 100% specific and 10,000 times more sensitive than using
the IS6110 primer.46,47 However, major concerns exist with
regard to false positivity as a result of less than rigorous
laboratory procedures.48 Recently, quantitative PCR or real
time PCR has been used in confirming the diagnosis of
tubercular uveitis.49,50 It allows better quantification of
nucleic acid and also facilitates the monitoring of the
progress of a PCR reaction in real time. Sharma et al reported
4.53 × 104 – 1.43 × 105 numbers of copies of MTB genomes
in vitreous fluid sample by real time PCR in patients
presumed to have tuberculous uveitis.49
In view of a wide spectrum of the clinical presentations
of ocular TB and infrequent positive laboratory tests to
establish systemic the following guidelines may be used to
arrive at confirmed or presumed diagnosis of ocular TB in
endemic areas14,15 (Table 1).
TREATMENT OF OCULAR TB
Ocular TB is treated as other forms of extrapulmonary TB
with the first-line combination regimen comprising isoniazid
5 mg/kg/d (maximum dose of 300 mg/d), rifampicin
10 mg/kg/d (maximum dose of 600 mg/d), pyrazinamide
20 to 25 mg/kg (maximum dose of 1500 mg/d) and
Table 1: Guidelines for the diagnosis of intraocular TB
A Clinical signs
• Cellular reaction in the anterior chamber and/or vitreous with or without posterior synechiae.
• Vitreous snowball opacities in the inferior vitreous.
• Perivascular cuffing of inflammatory exudates.
• Solitary or multiple choroidal granulomas with/without exudative retinal detachment.
• Optic disk granuloma with or without neuroretinitis.
• Subretinal abscess.
B Ocular investigations
• Demonstration of AFB/culture of M. tuberculosis from the ocular fluids.
• Positive polymerase chain reaction from ocular fluids for IS6110 or other conserved sequences in M. tuberculosis genome.
C Systemic investigations
• Positive Mantoux reaction.
• Evidence of healed or active tubercular lesion on radiography of chest.
• Evidence of extrapulmonary TB diagnosed by demonstration of tubercular granuloma/AFB/culture of M. tuberculosis.
D Therapeutic test
• A positive response to antitubercular therapy over a period of 4 to 6 weeks.
Any one or more of the clinical signs (A), (Table 1) with any of the positive tests in (B) could be confirmatory of ocular TB. Any one or
more of the clinical signs (A) with any of the positive tests in (C) or a positive therapeutic trial (D) could be considered suggestive of
presumed ocular TB that would merit a full course of antitubercular treatment provided other infective uveitis have been excluded
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Swapnil Parchand et al
ethambutol 15 mg/kg/d (maximum dose of 1000 mg/d).
During the first 2 months, known as the intensive phase of
treatment, all four drugs are given, followed by 10 to 12
months with two drugs (usually isoniazid and
rifampin).14,15,51 Pyridoxine 10 mg orally per day should be
given to prevent INH neurotoxicity. These drugs being
hepatotoxic monitoring of liver function test is important.
Anti-TB treatment significantly helps in reducing the
recurrences in both latent as well as manifest TB.52,53 In a
large retrospective series, we have demonstrated superior
clinical outcomes following concurrent treatment with
steroids and anti-TB treatment in patients with uveitis
relative to patients who received steroids alone.52 Similarly,
Anq et al showed 11 fold reduction in the likelihood of
recurrence when patients with uveitis and latent TB are
treated with ATT for more than 9 months duration. 53
However, the treatment should be instituted in consultation
with an infectious disease specialist because of potential
for drug interactions in a multiple drug regimen, significant
side effects, risk of multidrug-resistant TB and paradoxical
reactions in patients with HIV infections.
Recently, we reported progression of choroiditis lesions
in 14% of patients after initiating anti-TB treatment.54 The
worsening of these lesions was believed to be mediated by
the host’s immune system because of a combination of
factors including enhanced delayed hypersensitivity of the
host, decreased suppressor mechanisms, and increased
exposure to the mycobacterial antigens or a response to
mycobacterial antigens, such as tuberculoproteins. Hence,
the concomitant use of short course of corticosteroids along
with antitubercular treatment is recommended. It is
important to be aware of this phenomenon so that one does
not interrupt anti-TB treatment and think of drug-resistant
tubercular serpiginous-like choroiditis or investigate for
other possible nontubercular etiologies. Similar approach
of concomitant use of steroids with antitubercular treatment
has been found useful in patients with tubercular meningitis
and pericarditis.55-57
Topical therapy for tuberculous anterior uveitis consists
of betamethasone 0.1% eye drops and cycloplegic/
mydriatics. Antiglaucomatous therapy in the form of betablockers and carbonic anhydrate inhibitors may be given
for patients with secondary glaucoma. Surgery for cataract
and glaucoma can be performed if indicated when the
inflammatory reaction is brought under control and the eye
has been quiet for a minimum period of 3 months.
REFERENCES
1. CDC. Data and statistics tuberculosis 2010. US Department of
Health and Human Services, CDC 2010.
2. WHO report. Tuberculosis control in South-East Asia Region,
WHO 2012.
200
3. CDC. Tuberculosis cases and percentages by pulmonary and
extrapulmonary disease. Atlanta, GA: States, US Department
of Health and Human Services, CDC 2005.
4. Donahue HC. Ophthalmologic experience in a tuberculosis
sanatorium. Am J Ophthalmol 1967;64:742-748.
5. Bouza E, Merino P, Munoz P, et al. Ocular tuberculosis.
A prospective study in a general hospital. Medicine (Baltimore)
1997;76:53-61.
6. Biswas J, Narain S, Das D, et al. Pattern of uveitis in a referral
uveitis clinic in India. Int Ophthalmol 1996;20:223-228.
7. Singh R, Gupta V, Gupta A. Pattern of uveitis in a referral eye
clinic in north India. Indian J Ophthalmol 2004;52:121-125.
8. Tabbara KF. Ocular tuberculosis: anterior segment. Int
Ophthalmol Clin 2005;45:57-69.
9. Harries AD. Tuberculosis and human immunodeficiency virus
infection in developing countries. Lancet 1990;335:387-390.
10. Babu RB, Sudharshan S, Kumarasamy N, Therese L, Biswas J.
Ocular tuberculosis in acquired immunodeficiency syndrome.
Am J Ophthalmol 2006;142:413-418.
11. Jabs DA. Ocular manifestations of HIV infection. Trans Am
Ophthalmol Soc 1995;93:623-683.
12. Rao NA, Albini TA, Kumaradas M, et al. Experimental ocular
tuberculosis in guinea pigs. Arch Ophthalmol 2009;127:1162-1166.
13. Rao NA, Saraswathy S, Smith RE. Tuberculous uveitis:
distribution of Mycobacterium tuberculosis in the retinal pigment
epithelium. Arch Ophthalmol 2006;124:1777-1779.
14. Gupta A, Gupta V, Rao NA. Intraocular tuberculosis—an update.
Surv Ophthalmol 2007;52:561-587.
15. Gupta A, Gupta V. Tuberculosis posterior uveitis. Int Ophthalmol
Clin 2005;45:71-88.
16. Valentina C, Mircla C. Phlyctenular keratoconjunctivitis and
lymph node tuberculosis. Oftalmologia 1999;48:15-18.
17. Finnoff WC. The relation of tuberculosis to chronic uveitis. Am
J Ophthalmol 1931;14:1208-1227.
18. Parchand S, Tandan M, Gupta V, Gupta A. Intermediate uveitis
in Indian population. J Ophthal Inflamm Infect 2011;1:65-70.
19. Massaro D, Katz S, Sachs M. Choroidal tubercles: a clue to
hematogenous tuberculosis. Ann Intern Med 1964;60:231-241.
20. Mehta S. Ocular lesions in acute disseminated tuberculosis. Ocul
Immunol Inflamm 2004;12:311-315.
21. Biswas J, Madhwan HB, Gopal L, et al. Intraocular tuberculosis.
Clinicopathologic study of five cases. Retina 1995;15:461-468.
22. DiLoreto DA Jr, Rao NA. Solitary nonreactive choroidal
tuberculoma in a patient with acquired immune deficiency
syndrome. Am J Ophthalmol 2001;131:138-140.
23. Gupta V, Gupta A, Sachdeva N, Arora S, Bambery P. Successful
management of tubercular subretinal granulomas. Ocul Immunol
Inflamm 2006;14:35-40.
24. Demirici H, Shields CL, Shields JA, et al. Ocular tuberculosis
masquerading as ocular tumors. Surv Ophthalmol 2004;49:
78-89.
25. Gupta V, Gupta A, Arora S, et al. Presumed tubercular serpiginous
like choroiditis: clinical presentation and management.
Ophthalmology 2003;110:1744-1749.
26. Gupta A, Bansal R, Gupta V, Sharma A. Fundus Autofluorescence in serpiginous- like choroiditis. Retina 2012;32:814-825.
27. Miller BW, Frenkel M. Report of a case of tuberculous
retrobulbar neuritis and osteomyelitis. Am J Ophthalmol 1971;
71:751-756.
28. Gupta A, Gupta V, Arora S, et al. PCR-positive tubercular retinal
vasculitis: Clinical characteristics and management. Retina
2001;21:435-444.
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Intraocular Tuberculosis
29. Gupta A, Bansal R, Gupta V, Sharma A, Bambery P. Ocular
signs predictive of tubercular uveitis. Am J Ophthalmol 2010;
149:562-570.
30. CDC. Reported Tuberculosis in the United States 2002. Atlanta,
GA: US Department of Health and Human Services, CDC 2003.
31. Centers for Disease Control. Screening for tuberculosis and
tuberculous infection in high-risk population and the use of
preventive therapy for tuberculosis infections in the United
States. Recommendations of the Advisory Committee for
Elimination of Tuberculosis. MMWR Recomm Rep 1990;39:
1-12.
32. Centers for disease control and prevention: Screening for
tuberculosis infection in high-risk population recommendations
of the advisory council for the elimination of tuberculosis.
MMWR Morb Mortal Wkly Rep 1995;11:18-34.
33. Abrams J, Schlaegel TF, Jr. The tuberculin skin test in the
diagnosis of tuberculous uveitis. Am J Ophthalmol 1983;96:
295-298.
34. Lee KS, Hwang JW, Chung MP, Kim H, Kwon OJ. Utility of
CT in the evaluation of pulmonary tuberculosis in patients
without AIDS. Chest 1996;110:977-984.
35. Bakheet S, Powe J, Ezzat A, et al. F-18-FDG uptake in
tuberculosis. Clin Nucl Med 1998;23:739-42.
36. Mehta S, Jiandani P. Fluorine-18 Fluorodeoxyglucose Positron
Emission Tomography in the Evaluation of a Patient with
Presumed Ocular Tuberculosis Ocular Immunology and
Inflammation 2010;18:192-193.
37. Doycheva D, Deuter C, Hetzel J, et al. The use of positron
emission tomography/CT in the diagnosis of tuberculosisassociated uveitis. Br J Ophthalmol 2011;95:1290-1294.
38. Andersen P, Munk ME, Pollock JM, Doherty TM. Specific
immune-based diagnosis of tuberculosis. Lancet 2000;
356(9235):1099-1104.
39. Van Pinxteren LA, Ravn P, Agger EM, et al. Diagnosis of
tuberculosis based on the two specific antigens ESAT-6 and
CFP10. Clin Diagn Lab Immunol 2000;7:155-160.
40. Mazurek GH, Jereb J, Lobue P, Iademarco MF, Metchock B,
Vernon A. Guidelines for using the QuantiFERON-TB Gold
test for detecting Mycobacterium tuberculosis infection, United
States. MMWR Recomm Rep 2005;54(RR-15):49-55.
41. Ang M, Htoon HM, Chee SP. Diagnosis of tuberculous uveitis:
clinical application of an interferon-gamma release assay.
Ophthalmology 2009;116:1391-1396.
42. Cordero-Coma M, Calleja S, Torres HE, et al. The value of an
immune response to Mycobacterium tuberculosis in patients with
chronic posterior uveitis revisited: utility of the new IGRAs.
Eye (Lond) 2010;24:36-43.
43. Mackensen F, Becker MD, Wiehler U, Max R, Dalpke A,
Zimmermann S. QuantiFERON TB-gold—a new test
strengthening long-suspected tuberculous involvement in
serpiginous-like choroiditis. Am J Ophthalmol 2008;146:761-766.
44. Arora SK, Gupta V, Gupta A, et al. Diagnostic efficacy of
polymerase chain reaction in granulomatous uveitis. Tuber Lung
Dis 1999;79:229-233.
45. Gupta V, Arora S, Gupta A, et al. Management of presumed
intraocular tuberculosis: possible role of the polymerase chain
reaction. Acta Ophthalmol Scand 1998;76:679-682.
46. Madhavan HN, Therese KL, Gunisha P, Jayanthi U, Biswas J.
Polymerase chain reaction for detection of Mycobacterium
tuberculosis in epiretinal membrane in Eales’ disease. Invest
Ophthalmol Vis Sci 2000;41:822-825.
47. Das S, Paramasivan CN, Lowrie DB, Prabhakar R, Narayanan
PR. IS6110 restriction fragment length polymorphism typing
of clinical isolates of Mycobacterium tuberculosis from patients
with pulmonary tuberculosis in Madras, south India. Tuber Lung
Dis 1995;76:550-554.
48. Biswas J, Shome D. Choroidal tubercles in disseminated
tuberculosis diagnosed by the polymerase chain reaction of
aqueous humor: a case report and review of the literature. Ocul
Immunol Inflamm 2002;10:293-298.
49. Sharma P, Bansal R, Gupta V, Gupta A. Diagnosis of tubercular
uveitis by quantitative polymerase chain reaction. J Ophthal
Inflamm Infect 2010 Nov 11;1(1):23-27.
50. Singh R, Toor P, Parchand S, et al. Quantitative polymerase
chain reaction for mycobacterium tuberculosis in so-called Eales’
Disease. Ocul Immunol Inflamm 2012;20:153-157.
51. Patterson PE, Kimerling ME, Bailey WC, et al. Chemotherapy
of tuberculosis. In: Schlossberg D, editors. Tuberculous and
Nontuberculous Mycobacterial Infections. 4th edition. Philadelphia,
PA: WB Saunders 1999;71-82.
52. Bansal R, Gupta A, Gupta V, Dogra MR, Bambery P, Arora SK.
Role of anti-tubercular therapy in uveitis with latent/manifest
tuberculosis. Am J Ophthalmol 2008;146:772-779.
53. Ang M, Hedayatfar A, Wong W, Chee SP. Duration of antitubercular therapy in uveitis associated with latent tuberculosis:
a case-control study. Br J Ophthalmol 2012;96:332-336.
54. Gupta V, Bansal R, Gupta A. Continuous progression of
tubercular serpiginous-like choroiditis after initiating
antituberculosis treatment. Am J Ophthalmol 2011;152:857-863.
55. Girgis N, Farid Z, Kilpatrick M, et al. Dexamethasone adjunctive
treatment for tuberculous meningitis. Pediatr Infect Dis 1991;
10:179-183.
56. Strang JIG, Kakaza HHS, Gibson DG, et al. Controlled clinical
trial of prednisolone as adjuvant in treatment of tuberculous
constrictive pericarditis in Transkei. Lancet 1987;2:1418-1422.
57. Dooley DP, Carpenter JL, Rademacher S. Adjunctive
corticosteroid therapy for tuberculosis; a critical reappraisal of
the literature. Clin Infect Dis 1997;25:872-887.
ABOUT THE AUTHORS
Swapnil Parchand
Senior Resident, Department of Ophthalmology, Postgraduate Institute
of Medical Education and Research, Chandigarh, India
Vishali Gupta (Corresponding Author)
Additional Professor, Department of Ophthalmology, Advanced
Eye Centre, Postgraduate Institute of Medical Education and
Research, Sector 12, Chandigarh, India, Phone: +91-1722747837
Fax: +91-1722747837, e-mail: [email protected],
[email protected]
Amod Gupta
Dean, Professor and Head, Department of Ophthalmology, Advanced
Eye Centre, Postgraduate Institute of Medical Education and Research
Chandigarh, India
Aman Sharma
Assistant Professor, Department of Internal Medicine, Postgraduate
Institute of Medical Education and Research, Chandigarh, India
Journal of Postgraduate Medicine, Education and Research, October-December 2013;47(4):193-201
201