Posterior uveitis-

BACTERIAL

PRESENTER – DR ARNAV S. SAROYA

MODERATOR – DR SUGANDHA GOEL
 CLASSIFICATION OF UVEITIS- Standardization of Uveitis Nomenclature
(SUN) Working Group and the International Uveitis Study Group.
-
• Anterior uveitis - Anterior chamber, Iritis,
Iridocyclitis, Anterior cyclitis

• Intermediate uveitis – Vitreous, Pars planitis,

Posterior cyclitis, Hyalitis

• Posterior uveitis - Retina or choroid, Focal,

multifocal, or diffuse choroiditis, Chorioretinitis,
Retinochoroiditis, Retinitis, Neuroretinitis

• Panuveitis - Anterior chamber, vitreous, and retina or

choroid
Posterior uveitis includes….

• Focal, multifocal, or diffuse choroiditis

• Chorioretinitis

• Retinochoroiditis

• Retinitis

• Neuroretinitis
 POSTERIOR UVEITIS- ETIOLOGY
VIRAL HERPESVIRIDAE-HSV, VZV, CMV, EBV
RUBELLA
LYMPHOCYTIC CHORIOMENINGITIS VIRUS
RUBEOLA
WEST NILE VIRUS
OTHERS

FUNGAL HISTOPLASMOSIS
CANDIDIASIS
ASPERGILLUS

PROTOZOAL TOXOPLASMOSIS
HELMINTHIC TOXOCARIASIS
CYSTICERCOSIS
DIFFUSE UNILATERAL SUBACUTE NEURORETINITS
ONCHOCERCIASIS

BACTERIAL SYPHILIS
TUBERCULOSIS
BARTONELLA (CAT-SCRATCH DISEASE)
BORRELIA
Pathogenesis
• Choroid & outer retinal layers involved.
• Granulomatous (lymphocytes, plasma cells)
• Non- granulomatous (leucocytes, macrophages, epitheloid cells)
• Early stages- fluid passes – retina cloudy
• Exudates pass- vitreous opacities
• Later stages- leucocytes in vitreous & retina
• Exudates organize- fibrosis- choroid & retina fuse
SYMPTOMS
• Painless loss of vision
• Retinitis or choroiditis affecting macular function or complications like CME,
ERM, retinal ischemia, CNV, refractive error, opacities in visual axis
• Scotoma (central or peripheral)
• Floaters
• Photopsias
• Metamorphopsia
• Nyctalopia
SIGNS
RETINITIS INFLAMMATORY INFILTARATES
RPE HYPERTROPHY OR ATROPHY
PRE- OR SUBRETINAL FIBROSIS
RETINAL DETACHMENT
(EXUDATIVE,TRACTIONAL,RHEGMATOGENOUS)
NEOVASCULARIZATION

CHOROIDITIS INFLAMMATORY INFILTRATES

ATROPHY OR SWELLING
NEOVASCULARIZATION

VASCULITIS INFLAMMATORY SHEATHING

PERIVASCULAR CUFFING
(ACTIVE-YELLOWISH OR GREY-WHITE, PATCHY CUFFING
QUIESCENT- PERIVASCULAR SCARRING)
Entities for this class
• TB
• Syphilis
• Lyme
• Cat scratch
• Leptospirosis
Tuberculosis

• Caused by mycobacterium tuberculosis

• Described as a systemic disease

• Majority of cases involve the lungs

• Definition of a case of TB depends on clinical criteria or laboratory

confirmation.

• Commonly seen as an opportunistic infection in HIV patients

Epidemiology of IOTB
• In India, Biswas et al studied 1005 active pulmonary Tb patients in
south India- found 1.39% prevalence, though did not mention on
diagnostic criteria

• Singh et al in North India found 30% cases with infective etiology of

the 602 cases studied, 2/3rd of which were presumed to be IOTB
 Transmission of infection
• Airborne infection

• Inhalation of droplets (1-5µm)

• 5-200 inhaled bacilli required to cause infection

• 90% never develop clinical disease

• 5% develop disease within 1st few years

• Rest 5% develop as a reactivation of latent TB

• IOTB results from hematogenous seeding from primary complex or postprimary

reactivated lung lesion
 Posterior uveitis
A) Choroidal tubercles
o Most commmon manifestation

o Suggests hematogenous spread

o Appear as small nodules, unilateral or bilateral

o Grayish white to yellow with indistinct margins

o Most patients DONOT have Anterior Segment or Vitreous inflammation

o Located mostly in posterior pole

o May continue to grow into a solitary mass called tuberculoma

o On healing- surrounding pigmentation and margins become distinct

B) Choroidal Tuberculoma

o Rarely found

o Present as a large solitary

mass mimicking a tumour, 4-
14 mm size

o Can be seen anywhere in

choroid

o May be associated with

overlying retinal detachment
in later stages
C) Subretinal abscess

o Multiplication of bacilli in caseous material

of granuloma, leading to liquefaction
necrosis and abscess formation

o Overlying vitreous inflammation is not

significant

o Yellow in color with overlying retinal

haemorrhages

o Lesions heal with Akt with chances of good

visual recovery
D) Serpiginious – like Choroiditis

o Seprpiginious choroiditis is a chronic recurrent inflammation primarily

involving the choroid and choriocapillaris, later retina secondarily.

o Autoimmune in nature, beginning in peripapillary region and progressing

centrifugally

o Tubercular choroiditis can start as multifocal choroiditis (discrete and non

contiguous), which progresses to discrete and contiguous variety with an
active advancing edge that resembles serpiginious choroiditis
o Exact mechanism is unknown

o Believed to be an immune
mediated hypersensitivity reaction
in the presence of bacteria in
choroid or RPE.

o Treatment includes steroids with

Akt

o Paradoxical reactions are common

 Retinitis and retinal vasculitis
• Isolated retinal involvement is rare
• Tubercular vasculitis predominantly affects veins
• Knox described perivascular accumulation of whitish material as
characteristic
• Other feature are vitritis, retinal haemorrhages, neovascularisation,
neuroretinitis.
• Diagnosis is presumptive as there may be no confirmatory evidence of TB in
these patients
• Unproven whether vasculitis per se is infective or it represents a
hypersensitivity response to tb antigen
• Treatment involves laser, Akt and
oral steroids
• Can be differentiated from Eales
disease
• Quiet eye
• No choroiditis patches
• Young adult male
Neuroretinitis and optic neuropathy
• Results from contiguous spread from choroid or hematogenous
spread from other foci
• Optic neuropathy is due to direct infection of bacteria or due to
hypersensitivity response
• Nerve involvement may manifest as ON tubercle, papillitis, disc
edema, optic neuritis, retrobulbar neuritis, neuroretinitis
Endophthalmitis and panophthalmitis

• Has acute onset and shows rapid progression

• Anterior chamber filled with purulent material
• In choroid large subretinal abscess present, which can eventually
burst into vitreous.
Ocular imaging studies in IOTB
1) FFA

o Choroidal tubercles – early hypo and later hyper

o Choroidal tuberculomas – early hyper with progressive increase in late

phase and also pooling in late phase corresponding to exudative RD

o Choroiditis – early hypo and late hyper

healed lesions show blocked fluorosence due to RPE proliferation

o Vasculitis – staining and leakage from vessel wall. Look for cnp also
2) Indocyanine green angiography
o To detect subclinical choroidal lesions in presumed IOTB
o Lesions are hypo in early and intermediate phases, may become iso in late phase.
o ICG changes are reversible and maybe used to monitor response to therapy

3) OCT
o Can detect retinal pathologies such as subretinal neovascular membrane and CME

4) USG / UBM
o can help differentiate granulomas (low internal reflectivity) from retinoblastoma/
melanoma etc
o Helps studying pars plana region – granulomas, cyclitic membrane
Pathology

o Tubercles involve all layers of choroid

o Choroidal blood vessels are obliterated

o Overlying RPE is normal in early stages and disrupted as lesion progresses

o Surrounding choroid is essentially normal

o Granulomas have a typical tubercular histology

o Acid fast bacilli have also been found in giant cells

Diagnosis
• Diagnosis of IOTB is difficult because of variable clinical presentation and lack of uniformity in
diagnostic criteria

• Direct evidence of the presence of bacilli in ocular tissue would be ideal for establishing a
diagnosis

a) Clinical indicators

b) Corroborative evidence

c) Direct evidence
Corroborative evidence
a) PPD / Montoux test

o 5 TU is injected intradermal on left forearm ventrally.

o Induration is read in 48-72 hrs

o <5 mm is negative

o 5-10mm – considered positive in HIV patients, those with healed lesion on chest xray and those
in close contact with infectious case

o >10 mm – considered positive in TB endemic regions, HCW

o >15 mm – positive for all

Probabilty that reaction is due to M. tuberculosis and not due to BCG
increases

a) With increase in size of reaction

b) H/O contact is positive

c) Patient from high endemic region

d) Increasing interval between vaccination and skin test

Vaccination induced reaction wane with time and unlikely to persist for more than 10 years
b) Chest radiography and CT

o IOTB can occur without an active pulmonary disease.

c) Serodiagnosis

o Middlebrook-dubos test was used

o Hemagglutinin reaction between sheep RBC and sera of TB

patient

o Currently not preferred because of low sensitivity and high false

positive results
d) Interferon gamma release assay
o Based on measuring interferon gamma released by sensitized T-
cells after stimulation with M. tuberculosis antigen

o Antigens used for stimulating T-cells are early secreted antigen

target (ESAT) 6, culture filtrate protein (CFP) 10

o These antigens are not shared by BCG vaccine strain or other

species of Mycobacterium.

o Two kits comercially available – T-SPOT.TB test and Quantiferon –TB

gold
DIRECT EVIDENCE
a) Examination of smear and staining for AFB
o For detection on 10(6) organisms/ml of fluid
o Yield of org from intraocular fluid is low

b) Culture
o LJ medium shows growth in 6-8 weeks
o Prolonged and cumbersome process
o Low yield from intraocular fluid

c) PCR
o Amplify bacteria several fold
o Thus can be performed on a small sample
• For diagnosis LTBI has to be demonstrated as very few patients have
ocular involvement with active TB
• LTBI indirectly detected by demonstrating the hypersensitivity
generated.
inaccurate as degree of hypersensitivity can vary unpredictably.
Endemic area majority will have LTBI

• But a heightened hypersensitivity can suggest possible etiology

• 2 common test for hypersensitivity are TST or QTG

TST
• False positive in BCG, NTB, improper technique
• False negative -
- window period (within 8-10 weeks of exposure)
-Immunosuppressed /sarcoidosis
-Recent viral infections/live virus vaccination (measles)
-Overwhelming infection-Disseminated TB
-Malnutrition/old age
-Incorrect technique
• Anergic in endemic areas-may suggest sarcoid uveitis
• Montoux drawbacks
1. Subjective
2. 2 step procedure
3. High False positives and False negatives
4. Low specificity-Esp in areas with high BCG coverage and NTM exposure (endemic)
5. Mod sensitivity- but low in pts with depressed immunity or overwhelming
infection
• Advantages if IGRA
1. One step procedure
2. Less subjective
3. Faster results
4. Higher specificity
5. High sensitivity for active disease
6. Can be done in BCG vaccinated pts
7. Malnourished/immunocompromised
Suggested guidelines for diagnosis of iotb

CONFIRMED CASE
• clinical sign + ocular investigation

PRESUMED CASE
• clinical sign + systemic inv
Or
• positive therapeutic trial + exclusion of
other causes
Treatment
A) Medical management
o 4 drug regimen in intensive phase followed by 2 or 3 drug regimen in
continuation phase
o Duration recommended by various authors is 9-12 months,
depending on clinical response which is usually evident by 4-6 weeks.
o System steroids 0.5-1 mg/kg/day also started simultaneously, for 6-8
weeks
o MDR cases- additional agents like rifabutin, fluoroquinolones,
linezolid are added and treatment lasts for 18-24 months
o Ethambutol toxicity should be looked for
o Usually if dose is >15mg/kg/day for 3-6 months
o Toxicity is dose related
o Toxicity due to decreased ATPase activity and mitochondrial
homeostasis
o High dose patients should be evaluted monthly
Syphilis
• Spirochaete Treponema pallidum
• Incidence has ↓ with accurate diagnostic techniques & penicillin
therapy

• Eye involvement mainly in secondary and tertiary stages, occasionally

seen in primary syphilis.
Presentation
• Decreased vision
• Unseeing newborn infant-
Hutchinson’s triad- Hutchinson’s teeth, interstitial keratitis, deafness-
pathognomonic but rare
 Syphilis
• Anterior uveitis
• Iridocyclitis (4% of patients with secondary syphilis and is bilateral in
50%).
• Iritis with dilated iris capillaries (roseolae) – few cases
• Localized papules  larger yellowish nodules  iris atrophy.
Syphilis - Posterior uveitis
• Chorioretinitis
• Multifocal, bilateral
• Salt & pepper type
( congenital )

• Acute posterior placoid

chorioretinitis - large, solitary,
placoid, pale-yellowish
subretinal lesions

Syphilis though uncommon in HIV, pursues a more aggressive course & respond less well to
conventional therapy - test all patients with ocular syphilis for HIV and vice-versa.
Clinical features
• Vitritis • Nectrotizing retinitis
• Neuroretinitis
• Untreated  secondary optic • Serous retinal detachment
atrophy + replacement of retinal
vessels by white strands.

• Periphlebitis may be occlusive.

 Diagnosis
oVDRL & RPR (nontreponemal tests) cardiolipin antibodies in response to
membrane lipids of T.pallidum

oFalse +ve in pregnancy, other spirochaetal infections & mononucleosis

oVDRL in CSF- for neurosyphilis

oFTA-ABS & MHA-TP (anti-T.pallidum Ab)

oFalse +ve in rheumatoid arthritis, SLE, biliary cirrhosis

 Treatment
• Conventional doses of penicillin are inadequate
• The therapeutic regimen is the same as for neurosyphilis
(should be ruled out by lumbar puncture).

• One of the following regimens may be used:

• Intravenous aqueous penicillin G 12-24MU (mega units) daily for
10-15 days.
• Intramuscular procaine penicillin 2.4MU daily, supplemented with
oral probenecid (2g daily), for 10-15 days.
• Oral amoxicillin 3g b.d. for 28 days.
LYME DISEASE
• Lyme disease is a systemic tick-borne illness with protean manifestations,
including dermatologic, rheumatologic, neurologic and cardiac abnormalities.
• While Borrelia burgdorferi causes Lyme disease, it is now known that there are
several genospecies included in the group called Borrelia burgdorferi sensu
lato.
• Three genospecies cause the majority of cases of Lyme borreliosis: Borrelia
burgdorferi sensu stricto, Borrelia andersonii and Borrelia bissetti.
• Once a person is bitten by an infected tick, the typical skin lesion, erythema
migrans, a ring-like erythematous reaction of at least 5 cm, develops in about
50 percent of patients. Systemic symptoms of malaise, fatigue, fever,
headache, myalgias and lymphadenopathy may also develop.
• Ocular symptoms
• Lyme disease has been divided into three stages: early localized, early
disseminated and late disseminated.
• Ocular involvement has been reported during all stages of Lyme
disease. During early Lyme disease, within the first weeks of infection, a
nonspecific self limited follicular conjunctivitis has been described as
occurring in about 10 percent of patients.
• Photophobia has been reported during this stage, as has periorbital
edema.
• During early disseminated and late disseminated Lyme disease,
keratitis, iridocyclitis, vitritis, multifocal choroiditis, exudative retinal
detachment and panophthalmitis have all been reported.
• Neuro-ophthalmic manifestations include optic neuritis, disc edema and
oculomotor palsy.
CAT SCRATCH DISEASE
• two forms of CSD as it relates to the eye:
1.Parinauds Ocularglanduar Syndrome: consisting of lymphadenopathy and
follicular conjunctivitis
2.Neuroretinitis: consisting of lymphadenopathy and granulomatous
inflammation of the retina and optic nerve with classic optic nerve
swelling, macular star (neuroretinitis), and possible vasculitis.
• Signs
• The most common presentation is regional lymphadenopathy.
• Pre-auricular, submandibular, or cervical lymph nodes
• Conjunctival epithelium ulcerations, and necrosis are commonly seen
producing a purulent discharge in severe cases.
• Erythematous overlying skin, showing signs of suppuration from involved
lymph nodes. Careful examination; evidence of cutaneous inoculation in
the form of a nonpruritic, slightly tender pustule or papule.
• Parinaud oculoglandular syndrome (conjunctival inflammation with
preauricular adenopathy) may be seen in about 2-7% of patients with cat-
scratch disease.
 intraocular presentations
• Neuroretinitis with optic nerve edema, macular star formation, and discrete
white retinal or choroidal lesions.
• Vascular leakage from the optic nerve head results in the macular star
formation, which may persist for months despite resolution of the
neuroretinitis.
• In more recent studies, discrete white retinal, and chorioretinal lesions were
a more common finding than the ‘classic’ macular star, and neuroretinitis.
• More sight-threatening presentation includes intermediate uveitis, retinal
vasculitis, vascular occlusions (artery and venous) , and retinitis.
• Less common posterior segment findings include granulomas, choroiditis,
angiomatoisis lesions, and local serous retinal detachments.
• Symptoms
• Patients typically present with unilateral decline in vision (20/80) with
systemic symptoms present in 67%.
• Unilateral conjunctiva injection, foreign body sensation, and epiphora.
• Malaise and headache in fewer than one third of patients.
• Others may present with a scotoma if the optic nerve is involved.

• Clinical diagnosis
• Typical history of prodromal symptoms, lymphadenopathy, and cat
exposure helps strengthen the diagnosis, especially when presenting in
young adults or children.
• It more commonly presents in the younger ages in the late summer and
fall months.
• Diagnostic procedures
• Visual field testing sometimes shows cecocentral scotoma.
• Fluorescein angiography often shows optic nerve leakage or can show
artery/venous occlusions.
• Optical coherence tomography (OCT) can display the degree of subretinal
fluid, retinal thickening, and exudates.
• OCT angiography may be able to show neovascularization within an area of
chorioretinitis.
• Biopsy: classically shows granulomatous inflammation.
• Warthin-Starry silver stain on biopsy can identify the bacteria.
• Culture: B. henselae is a fastidious, slow-growing, gram-negative rod that
requires specific culture techniques for tissue or blood such as up to 1
month incubation period, enriched agar with 5% CO2 at 32-35 degrees
Celsius.
Medical therapy

• Doxycycline (100 mg twice daily) has good intraocular, and central

nervous system penetration.
• However, in patients less than 12  years of age, erythromycin is
recommended due to the risk of tooth discoloration.
• Azithromycin -rapid resolution of lymphadenopathy.
• Corticosteroids -systemic and ocular therapy.
• Intravitreal anti-VEGF therapy -for the treatment of choroidal
neovascularization as well as macular edema in the setting of CSD