This document discusses various infectious causes of uveitis, including viruses, fungi, protozoa, helminths, and bacteria. It covers specific infectious etiologies such as herpesviridae family members, toxoplasmosis, toxocariasis, syphilis, Lyme disease, tuberculosis, and endogenous infectious endophthalmitis. For each condition, it describes clinical features, diagnostic testing, treatment approaches, and prognosis. Infectious uveitis remains an important consideration in uveitis evaluation and management.

1. Clinical Aspects of Infectious
Uveitis
H. Nida en, MD, MHS
Director, Uveitis and Ocular Immunology Fellowship Program
National Eye Institute, National Institutes of Health
Associate Clinical Professor, Dept of Ophthalmology
The George Washington University
Washington DC, 20037
Visionary Ophthalmology, September 18, 2011

2. Infectious uveitides
Viral uveitis
Hepesviridae family
HIV
HTLV
Other (Rubella, west nile, measles, LCV)
Fungal uveitis
OHS, Candida, Aspergillosis, Cryptococcosis
Protozoal Uveitis
Toxoplasma
Helminthic uveitis
Toxocara, cysticercosis, DUSN, onchocerciasis
Bacterial uveitis
Syphilis, Lyme, Tuberculosis, Bartonella, leptospirosis,
nocardiosis
Infectious Endophthalmitis
Postoperative, posttraumatic, endogenous endophthalmitis

3. Viral Uveitis-Herpesviridae family
(HSV I/II, CMV, VZV and EBV)
Anterior uveitis
R/o viral retinitis esp immunocompromised host
Treatment:
topical steroids and cycloplegics (topical antivirals not useful
except to prevent recurrence of keratitis if present)
Oral antivirals in severe recurrent cases
400 bid acycl/500qd valacycl for HSV, 800bid acycl/1000qd
valacycl for VZV

5. Herpesviridae family
Retinitis
Acute Retinal Necrosis (ARN)
Described in 1971 (Urayama et al)
Typically in otherwise healthy immune-competent adults , starts
unilateral (2nd eye involvement in up to 36%)
M=F, 5th to 7th decades
VZV HSV CMV (+-EBV)
Genetic predisposition:
HLADQw7, Bw62, DR4 (caucasian), Aw33, B44, DRw6 (japanese)
Clinical criteria (AUS):
Peripheral retinal necrosis with discrete borders with circumferential
spread
typically full-thickness lesions that are white or cream colored
Rapid progression w/out tx
Occlusive vasculopathy with arteriolar involvement
Prominent vitritis and AC inflammation
Complications: Retinal breaks and RD (~75%), NV and VH
Dx: clinical + PCR from ocular fluid

6. ARN

7. ARN treatment
Treatment:
Antivirals: induction + maintanance (3 mo)
iv acyclovir (?PO)
decreases risk of bilateral involvement
Treatment with antivirals does not reduce the risk of RD
intravitreal gancyclovir/foscarnet injection
+ steroids
Vitrectomy/RD repair for complications
? Prophylactic laser barricade
Prognosis:
Guarded
Regardless of complications visual outcome is poor

8. Herpesviridae family
Retinitis-PORN
Progressive outer retinal necrosis (PORN)
primarily in immunocompromised individuals (in contrast to ARN)
Advanced stages of HIV (CD4<50)
Also described post-transplant
Clinical characteristics:
Differs multiple patchy areas of outer retinal whitening
little or no inflammatory component
from
spares the retinal vasculature
ARN progression to confluent full thickness retinal necrosis occurs more rapidly (hence
the name ““progressive””)
can involve the posterior pole early
more likely to progress to bilateral involvement (~70%)
Virus: VZV most common (HSV also reported)
Diagnosis: clinical +PCR (quantitative helps in determining tx response)
Complications: RRD (75%)

9. No inflammation
Vessels spared
Early post pole involvement

11. PORN-treatment
Treatment:
anti-HIV (HAART) + i.v antiviral + intravitreal
ganciclovir+foscarnet
Ganciclovir implant
Immune reconstitution
Surgery for complications
Prognosis:
Poor visual outcome despite antiviral treatment
No light perception in 67% of eyes

12. CMV retinitis
Typically in imunocompromised patients with HIV/AIDS
CD4 counts of less than 50-100 cells/ L
most common ocular opportunistic infection in patients with AIDS
Less since HAART
Can occur after renal transplantation or primary immune deficiencies
Two classical clinical appearances to CMV retinitis:
1. Perivascular inflammation with irregular patches of necrotizing retinitis
with hemorrhage
2. Granular lesion with central clearing and stippled retinal pigment
epithelium.
Other features: frosted branch angiitis, CME,
retinitis progresses at the edge of previous retinal lesions (250 m per
week)
Complications:
RRD (20%)
IRU (20% to 90%) risk w/larger area
vitritis, anterior uveitis, macular edema
Believed to represent recovery of CMV-specific immunity
topical, periocular,or oral steroids (reactivation!)

13. 59 yo moroccan male with h/o leukemia s/p
chemotherapy
Patient with HIV
28 yo F with angioimmunoblastic T-cell lymphoma
s/p chemo

14. 20/20= 20/25
43 yo jamaican female c h/o HTLV-1 associated adult lymphoma/leukemia s/p
6 cycles of EPOCH-FR recently started on EPOCH-Campath (Alemtuzumab)

16. CMV retinitis-treatment
Treatment:
ganciclovir, foscarnet, cidofovir (Vistide, Gilead), fomivirsen
(Vitravene, Novartis), and valganciclovir (Valcyte, Roche)
FDA
Iv ganciclovir (5 mg/kg bid) for 2 weeks (induction) once a day
approved
(maintanance)
replaced by oral valganciclovir
Intravitreal injection (ganciclovir/foscarnet)
Intravitreal implant (ganciclovir)
6-8 month (x4 concentration than iv ganc)
HAART/Immune recovery
without HAART 50% reactivation despite anti-CMV therapy
Prognosis:
It may take 2-6 wks for progression to halt
vision loss due to macular or optic nerve involvement OR CME

17. 4.5 mg gancyclovir, releases 1.4ug/hr

18. CMV retinitis-treatment resistance
Phenotypic and genotypic resistance to
gancyclovir can occur
most often secondary to mutations in the CMV
UL97 gene (viral phosphotransferase)
UL54 (viral DNA polymerase)
The rate of resistance has declined dramatically
with HAART therapy(28% to ~9%)
Can be overcome with higher doses (intravitreal
injection or implant)

19. 52F HIV+ F from Ethiopia referred
for recurrent CMV retinitis OS
while on Valganciclovir x 5 mo &
HAART (CD4 135)
Anterior chamber tap (aqueous)
and blood CMV PCR
genotypic resistance to
ganciclovir in blood but not in
ocular fluids

20. Toxoplasmosis
Infects at least 500 million persons The disease is caused by the obligate
worldwide ~50% in US intracellular protozoan Toxoplasma gondii.
A survey of ophthalmologists in
the US: 55% of those who
responded saw 1 active ocular
toxoplasmosis cases in last 2
years
93% of those who responded
had seen inactive cases in the
last 2 years. West:
In the United Kingdom the 17.5% North East:
Mid West: 29.2%
estimated lifetime risk for ocular 20.5%
toxoplasmosis ~ 18/100 000 South:
22.8%

21. Definitive
host
Toxoplasmosis Infection
Congenital: transplacental
transmission to the fetus
chorioretinitis, encephalitis, other birth defects
(TORCHS)
Acquired:
Ingestion of contaminated,
undercooked lamb or pork (cysts)
Ingestion of oocysts from soil, milk,
water or unwashed vegetables
rarely contaminated blood
transfusions, organ transplants etc
Acute infection: a flu-like illness with
lymphadenopathy, fatigue, fever and
malaise (~3-7%)
Recurrent infections: chorioretinitis,
lymphadenitis, myocarditis,
polymyositis

22. Ocular toxoplasmosis
Ocular disease can occur after
both congenital and acquired
disease.
Clinically: anterior uveitis,
vitritis with a prominent haze
(headlight in the fog) and
necrotizing chorioretinitis
Recurrent disease frequently is
seen as a satellite lesion.
Immunodeficient patients are at
risk

23. Courtesy of Rubens Belfort, MD

24. Courtesy of Rubens Belfort, MD, MBA
Sao Paulo, Brazil

25. Treatment and Prognosis
Treatment: There are no randomized, controlled large-scale
clinical trials to guide therapeutic choice of agents.
Pyrimethamine, sulfadiazine are used with or without
prednisone.
prednisone recommended to start 24 to 48 hours after the
antibiotics are started. periocular or intraocular steroid
injections are not recommended
Bactrim (trimethoprim/sulfamethoxazole), clindamycin
Atovaquone and Azithromycin.
Bactrim prophylaxis?
Silveira et al: 1998-2000, 7% recurrence in bactrim group vs
24% recurrence in control group. Complications: foveal
involvement, ERM, CNV, BRAO, BRVO, cataract, glaucoma
and CME
Prognosis; Complications may result in permanent visual loss.
Most patients retain good vision

26. Toxocariasis
Human toxocariasis is a helminth zoonosis due to the
infestation of humans by ascarid larvae belonging to the genus
Toxocara.
Toxocara canis and T. cati causative agents of human
disease
Seroprevalence: 2-5% in western world to 60-80% in
tropical countries
Adult form lives in the upper digestive tract of their
definitive hosts (cats/dogs) and eggs are passed in the feces
Can be passed via the placenta in dogs only, milk for cat
Primarily soil transmitted
Pica, poor personal hygiene, raw vegetables, raw meat, exposure to
puppies and kittens

27. Ocular Toxocariasis
Result of migration of larva to the eye ““ocular larva migrans””
Primarily in young patients
Ocular toxocariasis: ~1.0% uveitis patients
Most patients report a history of recent exposure to puppies
Unilateral
50% - a granuloma in the peripheral retina (age: 6-40)
25% - a granuloma in the macula (age:6-14)
25% - endophthalmitis (age: 2-8)
Diagnosis:
Serum ELISA: NEGATIVE in up to 50% ! OR
AC/Vitreous tap
Peripheral blood eosinophilia (may be absent in ocular toxocara)
Serum total IgE , LFTs
Imaging for liver, lung, CNS involvement
Complications: TRD, CME, Vitritis
Vitritis 52.6%, CME 47.4%, TRD 36.8%

29. Ocular toxocariasis
Treatment:
Albendazole 10mg/kg PO BID x 5-14d (better tolerated
and larger decrease in eosinophilia)
Thiabendazole 25mg/kg PO BID x 5-14d
Prednisone
Ivermectin
Not very effective and not recommended

30. Syphilis
May affect all ocular tissue; uveitis is most common, Bilateral in 50% of the
cases
Great masquarader Anterior, intermediate, posterior and panuveitis,
retinitis, retinal vasculitis, papillitis and neuroretinitis
Tests for syphilis fall into four categories
1. Direct microscopy when lesions are present
2. Nontreponemal tests: VDRL, RPR
Clumping of cardiolipin ( lecithin and cholesterol)
False Negative in 30%
False positive in SLE and other autoimmune disorders, tissue damage, liver
diseases, pregnancy, other Treponema- Lyme disease, Leptospirosis
3. Treponemal tests
FTA-ABS (Fluorescent Treponemal Antibody absorption test) detects antibody to
T. pallidum after serum treated with nonpathogenic treponemal antigen; High
sensitivity and specificity
MHA-TP (Hemagglutination tests):
15% + in SLE and can be + in Lyme disease
4. Direct antigen and the bacterial DNA detection, research
HIV TEST !

33. Syphylis-treatment
Ocular Inflammation secondary to syphilis should be treated as
neurosyphilis (AAO), Lumbar puncture
Routine RPR or VDRL and FTA-ABS or MHA-TP
HIV testing
Chao JR, Khurana RN– and Rao NA. Syphilis: reemergence of an old adversary. Ophthalmology 2006:
113: 2074-2079
Aldave AJ et al (2001) Current Opinion in Ophthal. 12: 433-441

34. Lyme Disease
It is most frequent tick-born infectious disease in certain
regions of US and Europe
US: Coastal North-East, North west California and Great
lakes regions
The causative pathogen is Borrelia burgdorferi
The tick must feed for at least 36 hours for transmission of the
agent
Three stages of the disease
Early localized infection (stage 1):
erythema migrans, fever, malaise, fatigue, headache,
myalgias, arthralgias, conjunctivitis
Early disseminated infection (stage 2: occurring days to
weeks later)
neurologic, musculoskeletal or cardiovascular and uveitis
Late disseminated infection (stage 3)
Arthritis +-uveitis
neuropathy or encephalopathy
Dx: clinical+ Isolation of organism from advancing margin
of the erythema migrans; ELISA; IgG and IgM and
Western blot

35. 20/20 OD 20/80 OS
A 27 year old male from California, an avid hiker c/o scotoma, photopsia in the left
eye. Reported fever, generalized 20/20 20/20
malaise and some joint discomfort for 1mo
ANA, RF, CXR, PPD and Sy serology (-), Laboratory work up was significant for
After iv ceftriaxone treatment for 3 wks
positive ELISA Lyme antibody titers 3.4 Western blot was positive for Lyme IgG
Prophylaxis: A single dose of doxycycline 200mg orally
(prevention should be emphasized)
Courtesy of Narsing Rao, MD

36. OCT-tuberculous granulomas?

37. Presumed tubercular serpiginous-like choroiditis
Gupta et al. Ophthalmology 2003
Serpiginous choroiditis relapsing despite corticosteroids and CSA
Highly positive PPD. PCR from aqueous and vitreous in 4 samples was (+) positive for
Mtb. No more relapse after anti-TB therapy.
Follow-up : 3 y and without Rx

38. AIDS or other immunecomprimising
diseases-particular concern
Brevundimonas endogenous endophthalmitis
Aspergillus enendophthalmitis in CLL s/p chemo
coccidioidomycosis

39. When to suspect an infectious agent?
1- Clinical presentation may be helpful but
non specific
2- Systemic manifestations (immune-
compromise (HIV/AIDS), fever, neutropenia)
3- Steroid-resistance or -dependence
4- No evidence for a specific auto-
inflammatory condition (JIA, VKH, SO,
Behçet) or a malignant disease
5- Epidemic outbreak!

40. Diagnostic strategy
Infectious agent Diagnostic strategy
HSV, CMV, VZV PCR > GW
EBV, HHV-8 PCR
Toxoplasmosis GW > PCR
Toxocariasis WB
Tuberculosis PPD/Chestx-ray
nPCR
Whipple PCR
Fungal Culture/PCR

41. Summary
All atypical forms of uveitis deserve further
investigations to exclude an infectious
etiology
prednisone or other uveitis treatment can cause significant
worsening
Early Dx remains the best way to propose a
specific Rx and achieve long-term remission
or healing

42. Thank you
Special thanks to:
Dr Chan and our clinical fellows