Journal presentation

1. Tubercular intermediate uveitis
: the importance of meticulous
multidisciplinary assessment
DR.PRAKRITI YAGNAM.K

2. Case :
- 27 year old
- Asian Indian female
- c/o repeated episode of redness in both eyes for
past one year
- Insidious in onset,with associated blurring of
vision,floaters and photophobia
- No H/O any medical illness

3. Systemic examination :
- 3.5*3cm. Lobulated nodule in superolateral
quadrant of left breast
- Diagnosed to have masquerade syndrome and
referred to higher centre
On Ocular Examination :
- Visual acuity distance 20/40 OU
- IOP OD – 18mm Hg ,OS - 19mm Hg

4. Slit lamp biomicroscopy :
- 1+ Flare
- 1+ cells and fine dusting on endothelial surface
- No posterior synechiae
- Posterior segment – OU –
Media clarity Grade 1
Normal disc and vessels with anterior
vitreous cells and large discrete snow balls
inferiorly

5. (a) Slit-lamp examination of the right eye using 90-D
lens shows large snow balls in the inferior vitreous
cavity. (b) Fundus photography shows media haze
due to vitritis, focal vascular sheathing involving the
venules of the inferior arcade, and large vitreous
snow balls. (c) The Mantoux test result shows a large
area of necrosis and induration

6. FFA :OU
- Focal vascular (perivenular) sheathing with
leakage along superior and inferior temporal
vascular arcades
Inv :
- Mantoux test
- QuantiFERON TB Gold
- CECT chest

7. Fluorescein angiography early phase (a and b) and
late phase (c and d) of both the eyes shows presence
of focal retinal vasculitis (especially seen involving
the large arcade venules in the left eye). There is focal
vascular leakage in the late phase from large venules
in the right eye along with leakage from small
capillary bed. Vascular leakage is also seen in the late
phase in left eye

8. - Mantoux and QuantiFERON positive with
20*25mm.necrosis
- CECT – 7*7mm. Pre tracheal and pre carinal lymph
nodes
12*11mm.subcarinal lymph nodes on right
side of esophagus and few axillary lymph nodes up to
22*15mm.
- No pleural effusion
- VDRL negative

9. Pulmonology opinion :
- Palpable enlarged lymphnodes in left axilla
fixed,discrete with hard consistency
- Biopsy : ill formed epithelial cells
Granulomas
Langhans giant cells
- Zeihl-Neelsen staining - positive
USG breast – B/L oval hypoechoic, well
circumscribed nodules
USG guided biopsy – Benign duct adenosis

10. Histopathological examination with acid-fast (Ziehl–
Neelsen) staining of the axillary lymph node (obtained
from a biopsy) showed presence of acid-fast bacilli (white
arrow) (a) The hematoxylin and eosin staining of the
lymph node in low magnification power shows ill-formed
epithelioid cells, granulomas, and giant cells (b) (white
arrows) consistent with granulomatous inflammation due
to tuberculosis

11. Treatment :
- ATT along with oral steroids given
- 2 months – Visual acuity improved to 20/20 OU with
quiescent anterior chamber and resolving vitritis
- Advised to continue ATT and steroids tapered

12. Discussion :
- Intermediate Uveitis can be associated with
TB,sarcoidosis,lyme disease,demylienating
diseases and tubuloinsterstitial nephritis
- Certain systemic malignancies are known to
present with vitreous inflammation along with
retinal vasculitis and can masquerade as
intraocular inflammation and intermediate
uveitis

13. - The above discussed case has been misdiagnosed
as breast cancer related uveitis
- Therefore careful detailed systemic investigations
for infectious etiologies must be taken place to
provide accurate diagnosis and thus treatment to
the patient
- Tuberculosis must be ruled out mainly in endemic
areas
- Association with physicians and other specialists is
necessary to establish a timely diagnosis

14. Intermediate Uveitis :
- Also known as Pars planitis
- Affects pars plana of ciliary body and
periphery of choroid
Clinical features :
- Children and young adults are affected
- Females > males
- Onset is insidious and bilateral in 80%

15. - Retinal periphlebitis with extravascular leakage
into vitreous and late development of exudates
in vitreous near ora serrata is seen
- Inflammation is non specific
- Cause is unknown in most cases
Symptoms :
- Floaters and vision deterioration due to
opacities in anterior vitreous

16. Signs :
- Minimal aqueous flare
- Occasional K.P’s(spill over anterior uveitis)
- Anterior vitritis
- White snow ball like exudates near ora
- Coalescent exudates giving appearance of a
snow bank
- Mild peripheral periphlebitis
- Macular edema,papillitis or disc edema
- Retrolenticular cyclitic membranes
- VH,TRD

17. DD :
- Tuberculosis
- Toxoplasmosis
- Syphilis
- Multiple sclerosis
- Sarcoidosis
- Resolves spontaneously or has a prolonged
course
- Most cases do not need treatment
- In chronic cases steroids or
immunosuppressants are helpful

18. TB Uveitis :
- Tuberculosis is a chronic infection caused by
Mycobacterium tuberculosis and can involve
any part of eye though uveitis appears to be
most common
- Characterized by formation of necrotizing
granulomas
- Bacteria infect alveolar macrophages from
where they are carried to reginal lymph nodes
and other parts including eye

19. - Diagnosis is largely presumptive and mainly
depends on
- Presence of suggestive clinical signs
- Evidence of past TB infection
- Exclusion of non TB entities
- Most patients with uveitis do not have evidence
of systemic TB (active/healed)
- Microbiological evidence of M.TB is rarely
found in ocular samples and clinical signs of
ocular TB are non specific and mimic other
infectious and non infectious uveitis

20. - Ocular TB is a paucibacillary infection
Ocular manifestations :
Anterior uveitis / iritis :
Granulomatous Non granulomatous
Miliary. Solitary Allergic Immunoinflammatory

21. Miliary :
- Small yellowish white nodules surrounded
numerous , small satellites near pupillary or
ciliary margin
- Seen in severely debilitated patients with
impaired immunological responsiveness
- Or in massive dissemination of bacilli
- Mutton fat KP’s,posterior synechiae Koeppe
iris nodules , hypopyon and iris or angle
granulomas can be seen

22. Anterior uveitis due to ocular TB. (Panel A)
Granulomatous keratic precipitates and posterior
synechiae in 12-year-old girl. (Panel B) Fundus
examination shows neuroretinitis in the right eye. (Panel
C) Fundus examination shows optic neuritis in the left eye.

23. Anterior chamber granuloma due to ocular TB. (Panel
A) Anterior chamber granuloma with granulomatous
keratic precipitates and hypopyon. Aspiration of the
granuloma demonstrated acid fast bacilli in Ziehl-Neelsen
stain. (Panel B) Following antituberculous treatment, the
posterior segment demonstrates healed pigmented scars
along the vasculature.

24. Iris granuloma due to tuberculosis followed by
immune recovery tuberculous uveitis. (A) Right eye of
a HIV patient with coexisting tubercular uveitis showing
iris granuloma and hypopyon. Anterior chamber aspiration
revealed acid-fast bacilli, confirming the diagnosis of
tuberculosis. (B) Severe form of immune recovery uveitis
resulting in perforation of the right eye following highly
active antiretroviral therapy (HAART) and antitubercular
treatment. Iris is seen prolapsed through the perforation
site at the limbus.

25. Solitary / conglomerate :
- Large yellowish white tumor seen
- Smaller satellite lesions may be present
- Nodules contain giant cells
Non granulomatous exudative :
- May be allergic or immunoinflammatory
- Recurrent or very chronic presentation
- Type 4 delayed hypersensitivity reaction to
Mycobacterial antigens elsewhere

26. Intermediate uveitis :
- Chronic low grade uveitis seen
- Snow ball opacities,peripheral vascular
sheathing,healed or active peripheral
chorioretinitis,cystoid macular edema are seen

28. Posterior and Pan uveitis :
- Multifocal serpiginous choroiditis
- Multifocal choroiditis
- Choroid tubercles
- Choroidal tuberculomas
- Retinal vasculitis
- Optic nerve head tuberculoma
- Subretinal abscess

29. Tuberculous Choroiditis :
Choroid tubercles Tuberculomas
- 0.3 to 3mm. - single large subretinal mass
(>20DD)
- mimics choroidal tumor

30. Choroidal tuberculomas.

31. (a, b) Case 1 showing large area of peripapillary
choroiditis before and after ATT; (c) Case 2 showing a
large choroidal tubercle; (d, e) Case 3 showing multifocal
choroiditis before and after ATT. (Straight arrows indicate
active lesions and curved arrows healed lesions.)

32. - Miliary tubercles are found in acute military
tuberculosis mainly tuberculous meningitis
- Ophthalmologically they appear as three or four
round , pale yellow spots usually near the disc
DD :
- Sarcoidosis , Behcet syndrome , Leprosy , syphilis
, cat scratch disease , leptospirosis , brucellosis

34. Pathogenesis :
cavernous pulmonary lesion
erodes BV/lymphatics
hematogenous spread of mycobacteria
choroid tubercles

35. On FFA –
- Hypofluorescent during dye transit
- Hyperfluorescent in late stages
- In healing stage pigmented and atrophic scars
seen
- In Posterior or panuveitis retinal vasculitis is also a
common manifestation
- Presents as retinal periphlebitis / occlusive
vasculitis associated with healed or active focal
chorioretinal lesions

36. occlusive vasculitis
retinal / disc neovascularization
VH/TRD
Multifocal serpiginous choroiditis :
- Recently recognized entity in TB endemic countries
- Typically show central healing and active ameboid
margins

37. Posterior uveitis due to ocular TB. (A) A 35-year-old
woman presented with massive subretinal abscess and
optic nerve granuloma with neovascularisation in her left
eye. Her mantoux test was positive and necrotic, and
ultrasonography demonstrated thickened choroid. (B)
Interval improvement was observed after one month of
antituberculous therapy (ATT). (C) Resolution of
funduscopic findings and choroidal thickening was
observed after three months of antituberculous therapy.

38. Retinal periphlebitis with active chorioretinitis
overlying bloodvessels

39. - Some appear healed and show active choriditis
features
- FAF is the quick diagnostic tool to monitor the
clinical course of these lesions
- Recently FAF+OCT+OCT – A is used
- Active lesions
FAF – hyperautofluorescence
OCT – hyperreflectivity in outer retina and RPE
OCT A – flow void areas in choriocapillaries

40. Healed lesions :
FAF – hypoautofluorescence
OCT A – tangled meshwork of vessels

41. Serpiginous-like choroiditis due to ocular TB.

42. (a) Fundus photograph of the left eye showing
multifocal choroidal lesions of varying shape and size
and at various stages of resolution in a patient with
serpiginous-like choroiditis and (b) autofluorescence
of the left eye showing variegated pattern of
hypoautofluorescence and hyperautofluorescence
(yellow arrow). Note the healed choroiditis lesions
(white arrows) characterized by total
hypoautofluorescence area with sharp borders

43. Color fundus photograph (a) and early (b and d) and
late-phase (c and e) fundus fluorescein angiography
and indocyanine green angiography pictures of a 32-
year-old male with serpiginous-like choroiditis, who
presented with reactivation of choroiditis in fovea.
Active choroiditis appears as hypofluorescence with
fuzzy, irregular borders in early phase (b), followed by
profuse leakage of the dye leading to
hyperfluorescence in late phase of fundus fluorescein
angiography (c). Active lesions in indocyanine green
angiography show blockage of the dye beginning
from the early phase (d) to the late phase (e)

44. (a) Color fundus photo of right eye showing active
edge of serpiginous choroiditis encroaching fovea
with temporal healed lesion and (b) optical coherence
tomography angiography at choriocapillaris
segmentation of the area in the dotted square in (a)
showing flow void area corresponding to the active
edge and loss of choriocapillaris at the healed areas
with high reflectivity from underlying medium-sized
choroidal vessels

46. DD for granulomatous uveitis :
- Sarcoidosis
- Syphilis
- Herpes simplex
- Varicella zoster
- Leprosy
- VKH disease
- Sympathetic Ophthalmia

47. DD for choroidal granulomas or chorioretinitis :
- Syphilis
- Sarcoidosis
- Fungal lesions
- Cryptococcus
- Toxoplasmosis
- Serpiginous choroidopathy

48. Sarcoidosis.

49. Syphilitic chorioretinitis.

50. Cryptococcal chorioretinitis. Active toxoplasmic retinochoiditis.

51. Serpiginous choroidopathy.

52. Other ocular structures which can be infected
- Orbit – most commonly in children
- Eyelid
- Lacrimal gland
- Conjunctiva
- Keratoconjunctivitis
- Sclera

53. Sclerokeratitis due to ocular TB. (A) Recurrent
sclerokeratitis resulting in corneal thinning and melt with
adjacent active scleritis. (B) Chest computed tomography
(CT) revealed enlarged lymph nodes with necrosis
involving pretracheal, paratracheal, and subcarinal
groups, with the largest lymph node measuring 1.89 x
1.35 cm.

54. Investigations :
- Mantoux dermal reaction
Positive – Value in children but does not prove
condition is tubercular
Negative – diagnosis of allergic tuberculosis is
unlikely
- Allergy to tubercular protein occurs in patiens
suffering from sarcoidosis,hodgekins disease
,immunodeficient states
- QuantiFERON gold test

55. - Other presumptive tests – CXR , therapeutic trial
with isoniazid
- Definitive tests– HPE , culture , PCR on sample
from ocular tissues
- Pathology :
Central caseous necrosis surrounded by epitheloid
cells,Langerhans giant cells,lymphocytes and
plasma cells
- In immunocompromised patients – purulent
infection that revelas necrosis and neutrophils
mixed with macrophages
- Lesions contain numerous bacteria

56. Treatment :
- ATT four drug regimen
Isoniazid – 5mg/kg/day
6 months
Rifampicin – 450mg/kg/day
Ethambutol – 15mg/kg/day
2
Pyrazinamide – 25mg/kg/day

57. - Ethambutol may lead to optic neuropathy with
decreased visual acuity , blurring and red green
color blindness
- Visual symptoms are rare if dose is
<15mg/kg/day and more if >25mg/kg/day
- Rifampicin has been shown to increase plasma
clearance of prednisolone by 45% and reduce
bioavailability by 66% which may lead to
progressive inflammation

58. Corticosteroids :
- Topical for anterior uveitis (+/- periocular )
- Periocular for intermediate (+/- systemic )
- Oral for posterior and pan uveitis (+/-
intravenous )
- Oral dosage starts with 1mg/kg bodywt.
- Immunosuppressants whenever necessary
- Steroids are tapered over 6- 12 weeks

59. Reasons for progressive ocular inflammation
following TT in presumed ocular TB :
- Defined as two step increase in inflammation (
anterior chamber /vitreous ) or appearance of
new lesions following initiation of ATT
1. Paradoxical worsening Jarisch – Herxheimer
reaction due to release of mycobacterial
antigens following ATT

60. - Strengthening of host immune response
- Decrease in immunosuppression mechanism
- Treatment is by increasing corticosteroid
dosage
2. Non compliance to ATT
3.Non TB uveitis

61. THANK YOU!!!