Uveitis is an intraocular inflammation that can lead to vision loss and is a significant cause of blindness worldwide. Various classifications and grading systems are used to diagnose and categorize uveitis, with treatment options including corticosteroids and immunosuppressive therapies. Understanding the underlying causes and identifying the specific type of uveitis is critical for appropriate management and improving patient outcomes.

1. Uveitis
W E N D Y M S M I T H , M D
S E N I O R S T A F F F E L L O W ,
U V E I T I S A N D O C U L A R I M M U N O L O G Y
N A T I O N A L E Y E I N S T I T U T E
N A T I O N A L I N S T I T U T E S O F H E A L T H

2. Uveitis: Definition
a generic term for intraocular inflammation.
does not indicate site of inflammation
does not indicate the cause: autoi mmune or infectious

3. How Common is Uveitis?
10-­15% of severe visual handicap in the U.S.
3rd leading cause of blindness in the world
U.S. Incidence 52.4/100,000
U.S. Prevalence 115.3/100,000 2,400,000
3 times higher than previous estimate
Prevalence higher in women (1:1.4)
Common in older patients
Gritz and Wong. Ophthalmology 2004
Worldwide prevalence ~2.4 million
~5-­10% of cases in children <16 yrs 322,000
151,200
Mean age of onset is 37.2 years
Range 20-­50 years
U.S. Incidence U.S. Prevalence Worldwide

4. IUSG Classification of Uveitis
Anterior uveitis
iris and pars plicata (CB)
Intermediate uveitis
pars plana and vitreous
Posterior uveitis
retina + choroid
Panuveitis

5. SUN Grading system for AC cell and flare
Cells per high-­power field in 1x1 mm slit beam
0 = < 1 cell/hpf
0.5+ = 1 -­ 5 cells
1+ = 6 -­ 15
2+ = 16 -­ 25
3+ = 26 -­ 50
4+ = > 50
Flare
0 = none
1+ = faint
2+ = moderate,
(iris/lens details clear)
3+ = marked
(iris/lens hazy)
4+ = intense (fibrin or plastic aqueous)

6. National Eye Institute Grading System for Vitreous Cell
(No SUN Working Group Consensus)
Number of Cells* Description Grade
0-­1 clear 0
2-­20 few opacities trace
21-­50 scattered opacities 1+
51-­100 moderate opacities 2+
101-­250 many opacities 3+
>250 dense opacities 4+
*cells are counted using a Hruby, 90 or 78 diopter lens

7. National Eye Institute Grading System for Vitreous Haze
(adopted by SUN Working Group)
0 = Clear
0.5+/trace = Trace
1+ = Few opacities,
mild blurring
2+ = Significant
blurring but still
visible
3+ = Optic nerve
visible,
no vessels seen
4+ = Dense opacity
obscures optic
nerve head

8. Developing a Differential Diagnosis
Is the disease acute or chronic?
Where is the inflammation located in the eye?
Unilateral or bilateral?
Granulomatous or non-­granulomatous?
What are the demographics of the patient?
Associated symptoms?
Associated signs on physical exam?
How did the disease respond to previous therapy?

9. Anterior Uveitis: ~60% of all uveitis
Idiopathic
HLA-­B27 associated
Inflammatory bowel Sarcoidosis
disease Syphilis
Ankylosing spondylitis
Glaucomatocyclitic crisis
Masquerade syndromes
Psoriatic arthritis
JIA (Juvenile Idiopathic
Arthritis) associated

10. Anterior uveitis
prevalence: 81/100,000 (Gritz et al)

11. Differential Diagnosis of Stellate Keratic Precipitates:
Fuchs heterochromia (rubella, herpes, toxoplasmosis)
Viral
Toxoplasmosis

12. Differential Diagnosis of hypopyon:
HLA-­B27 associated
Low back pain, ethnicity, GI symptoms,
ulcers, joints

13. JIA-­associated uveitis
<16yo,>6mo disease
Pauci-­articular: 25%
Type 1=Ana+ young girls
Type 2=Older boys B27+
Poly-­articular: ~15%
Systemic onset: 1-­5%
Most at risk:
ANA+, RF-­, pauciarticular
girls
Uveitis develops within 5-­7 yrs
No correlation betw joint and eye
Frequently asymptomatic
Uveitis before joint disease poor px
BK/PS/cataract/ON hyperemia/CME common

14. Anterior Uveitis
Complications Treatment
Posterior synechiae Topical corticosteroids
Cataract Cycloplegics
Inflammation-­related Glaucoma gtts
Steroid-­induced NSAIDs (gtt or PO)
Secondary glaucoma
Steroid response Periocular steroids
Angle closure
Cystoid macular edema Systemic steroids
Band keratopathy Systemic
more common in children immunosuppression

15. Intermediate Uveitis: ~15% of all uveitis
Most common causes:
Sarcoidosis
Pars planitis syndrome (idiopathic)
Multiple sclerosis
Masquerade Syndromes
Infection
Toxoplasma, Lyme, Toxocara, Syphilis, TB

16. Intermediate Uveitis
Vitritis +/-­ periphlebitis
Snowballs, snowbanking
(more severe disease process)
Pars planitis: PP exudates
(HLA-­DR15)
~15% of patients with pars
planitis will develop MS
CME is the main vision
threatening complication

17. Posterior & Panuveitis: 10-­15% of all uveitis
Focal choroiditis/retinitis: Multifocal Retinitis:
Toxocariasis Syphilis
Herpes simplex virus, CMV
Tuberculosis
Sarcoidosis
Nocardiosis Masquerade syndromes
Masquerade syndrome Candidiasis
Meningococcus
Multifocal Choroiditis:
SO PANuveitis:
VKH Syphilis
Sarcoidosis Sarcoidosis
Serpiginous
VKH
Birdshot
disease
Sympathetic Ophthalmia
Histoplasmosis/TB
Infectious endophthalmitis
Masquerade syndrome

18. Posterior (Pan) Uveitis
Inflammation involving retina/choroid
Optic nerve:
ON Edema, papillitis, granuloma
FA features hot?
Retinal vasculature:
Staining, leakage, capillary dropout
Involves mainly veins vs arteries
Peripheral vs central
Chorioretinal lesions:
Dalen-­fuchs nodules
Size, age of lesion (old atrophic vs new elevated with substance to it)

19. Sarcoidosis
Sarcoidosis is a multisystem granulomatous disorder
lungs (90-­95%), lymph nodes, skin, eyes, CNS
Typically affects young adults
More commonly seen in African Americans and Caucasians of
Northern European descent
In US 8-­10x more common in AA
AA: 35 to 82/100,000 Caucasians: 8 to 11/100,000
Etiology unknown but believed to be immune mediated:
genetic predisposition (familial aggregation, monozygotic twins, HLAB8,
HLADRB1) and environmental factors (environmental allergens and
infectious agents) have been suggested.
Ocular disease most common extra-­pulmonary presentation
Uveitis occurs in 25-­50% of pts
20-­50 yrs, typically bilateral (98%)

21. Sarcoidosis: Dalen-­

22. Slit-like third ventricle
Transependymal CSF flow
Diagnosis: Biopsy-­Proven Neurosarcoidosis
30 yo AAM: Referred for endogenous candida endophthalmitis
Also has recent onset of headache, mood changes, gait abnormalities
Enlarged lateral ventricles

23. Diagnostic vitrectomy:
Nests of macrophages & giant cells
Small and reactive lymphocytes
Further work-up: hilar LAD on CT and PET scan
Diagnosis: Presumed Ocular Sarcoidosis
75 yo WF with recent onset blurry vision
Carried dx of SLE for >20 yrs
CBC: slightly elevated WBC
Neg or wnl: Lyme, RPR, FTA ABS, PPD
HLA B27 neg, UA & Chem 20 wnl

24. Modified Japanese Criteria:
Major criteria (skin, oral, genital, eye)
Minor criteria (arthritis, GI, epididymitis, neuropsychiatric
etc)
Classification
Complete (4 major), Incomplete (3 major OR ocular
disease+1 major), Suspect (2 major nonocular),
Possible (1 major)
International Study Group for BD recurrent
oral ulcers is a must (+2 other criteria)

25. retinitis

26. VKH: Common in pigmented ethnic groups
Bilateral panuveitis
Vitiligo, alopecia, poliosis, (10-­60%)
Dysacusia, tinnitus (75% auditory problems)
Meningitis (80% have CSF lymphocytic pleocytosis)
ON edema & hyperemia, Serous RD
Dalen-­Fuchs nodules
Sunset-­glow fundus
Sigiura sign (perilimbal vitiligo)
HLA DR4 (esp Japanese), DR1

27. 24 yo Latino male with VKH:
Sudden onset blurred vision
Headache
Tinnitus & hearing loss
One month after presentation
Ten months after presentation

28. End-­stage VKH with diffuse RPE loss and subretinal fibrosis

29. Retinal Vasculitis
Systemic Lupus Erythematosus
Retinopathy is an important marker of systemic activity esp CNS vasculitis-­75%
Polyarteritis Nodosa (PAN)
Untreated: 90% mortality
Wegener granulomatosis
Necrotizing granulomatosis of upper & lower resp tract -­esp paranasal sinuses
Glomerulonephritis (85%), peripheral neuropathy
Untreated: 80% mortality

30. HIV+ not on HAART
52 yo M RPR+ 1:2048, Syphilis IgG+
Acute onset of blurred
vision & photophobia OS
Non-­granulomatous
anterior uveitis OS > OD
Vitritis OS > OD
Syphilis-­related panuveitis
BRAO and retinitis OD Responded to IV Penicillin x 4 wks

31. Serpiginous choroidopathy
Relationship w/TB?
Treated with immunosuppressives
HLA-­B07
>30% VA <20/200

32. APMPPE:
Acute posterior multifocal placoid pigment epitheliopathy
Bitten by a lab animal
Preceding flu-­like symptoms
Early hypo, late hyper on FA
(White Dot Syndromes)
Hypofluorescent spots on ICG
CNS vasculitis
Benign course
20% Visual Sequelae

33. Posterior/Panuveitis complications
Cataract Choroidal
Epiretinal membrane neovascularization
Secondary glaucoma Retinal ischemia
Hypotony Retinal
neovascularization
Chronic cystoid macular
edema Optic nerve atrophy
Subretinal fibrosis
Atrophy of retina/RPE Retinal detachment
Phthisis bulbi

34. Work-­up
CBC with diff,Chem 20, UA, ESR, CRP
TB (PPD+anergy panel)+Chest X-­ray
Syphilis (both RPR and Sy IgM, IgG)
HIV
Additional:
ACE, lysozyme, Ca sarcoidosis
UA-­> TINU, Wegener, SLE
ANA, anti-­DNA, RF, anti-­CCP, ENA panel connective tissue disorders
Despite a million dollar work-­up-­>
ANCAs (c-­ANCA=PR3;; p-­ANCA=MPO) Wegener, PAN
Hypercoagulability panel (ACA, LAC, Factor V Leiden mut) occlusive vasculitis
40% still idiopathic
High Resolution Chest CT TB, sarcoidosis
PFT/pulm consult sarcoidosis
Hearing test VKH, sarcoidosis
LP MS, VKH, PIOL/CNSL
HLA panel Birdshot, HLA-­B27, Behçet, MS, sarcoid
Sinus CT W
Lumbosacral XR/MRI HLAB27 associated uveitides
Colonoscopy IBD, Behçet, malignancy work-­up
Anterior chamber and/or vitreous tap for PCR, cultures, cytokines

35. Treatment:
Corticosteroids have been the mainstay since 1970s
Neutrophils Inhibit neutrophil migration
neutrophil adherence to vascular
endothelium
bactericidal activity of neutrophils
Local effects on the endothelium
Mononuclea r phagocytes Chemotaxis
Clearance of antibody coated particles
Production of Il-1 and TNF
L ymphocytes Redistribution of T lymphocytes(CD4 > CD8)
Inhibit T lymphocyte activation
proliferation and lymphokine production
Inhibit Ig production by B cells (high dose)

36. Immunosuppressive Therapy
Antimetabolites:
Methotrexate (anti-­folate), Azathioprine (purine inhibitor),
Mycophenolate Mofetil (pu) (Cellcept), Leflunomide (pyrim inh)
T-­cell Inhibitors:
Cyclosporine, Tacrolimus (cacineurin), Sirolimus(mtor)
Alkylating agents:
Cyclophosphamide, Chlorambucil
Biologics:
Anti-­TNF( *infliximab, etanercept, adalimumab, golimumab,
certolizumab)
Anti-­IL2R (*daclizumab, basiliximab)
Anti-­IL1 (anakinra)
Anti-­B cell (*Rituximab, Ocralizumab)
million dollar treatment ?effect on outcome

37. Summary
Diagnosis: what, where, when, who
Differential: use to guide testing
rule out etiologies that must be treated before
immunosuppression (infections!)
corticosteroid treatments (Please refer!)
If not responding to treatment, consider another diagnosis
Goals: Prevent complications, minimize side effects
of treatment, PRESERVE VISION

38. Thank you!