Uveitis is a general term for intraocular inflammation that does not indicate the specific site or cause of inflammation. It can be caused by autoimmune or infectious processes. Uveitis is a common cause of visual impairment and blindness worldwide. It is classified based on the site of inflammation - anterior, intermediate, posterior or panuveitis. Developing a differential diagnosis involves considering factors such as acuity of onset, laterality, associated symptoms and response to previous therapies. Common etiologies include idiopathic disease, infections like tuberculosis, and autoimmune diseases like sarcoidosis and Behcet's disease. Treatment involves corticosteroids and immunosuppressive therapies.

1. Fritz Allen, MD
Visionary Eye Doctors
Review of Uveitis

2. • A generic term for intraocular inflammation.
• Does not indicate site of inflammation
• Does not indicate the cause:
Autoimmune or Infectious
Uveitis: Definition

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
 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
 Mean age of onset is 37.2 years
 Range 20-50 years
151,200
322,000
2,400,000
U.S. Prevalence WorldwideU.S. Incidence

4. IUSG Classification of Uveitis
Anterior uveitis
 iris and pars plicata (CB)
Intermediate uveitis
 pars plana and vitreous
Posterior uveitis
 retina + choroid
Panuveitis
“front”
“back”

5. 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)
SUN Grading system for AC cell and flare

6. 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
National Eye Institute Grading System for Vitreous Cell
(No SUN Working Group Consensus)

7. 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
National Eye Institute Grading System for Vitreous Haze
(adopted by SUN Working Group)

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
disease
 Ankylosing spondylitis
 Reiter’s syndrome
 Psoriatic arthritis
JIA (Juvenile Idiopathic
Arthritis) associated
Behçet’s disease
Fuchs’ heterochromia
Sarcoidosis
Syphilis
Glaucomatocyclitic crisis
Masquerade syndromes

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
 Behçet’s disease
 Low back pain, ethnicity, GI symptoms,
ulcers, joints

13. JIA-associated uveitis
 <16 yo,>6 mo 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-, pauci-articular 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. Complications Treatment
Posterior synechiae
Cataract
 Inflammation-related
 Steroid-induced
Secondary glaucoma
 Steroid response
 Angle closure
Cystoid macular edema
Band keratopathy
 more common in children
Topical corticosteroids
Cycloplegics
Glaucoma gtts
NSAIDs (gtt or PO)
Periocular steroids
Systemic steroids
Systemic
immunosuppression
Anterior Uveitis

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:
Toxocariasis
Tuberculosis
Nocardiosis
Masquerade syndrome
Multifocal Retinitis:
Syphilis
Herpes simplex virus, CMV
Sarcoidosis
Masquerade syndromes
Candidiasis
Meningococcus
Multifocal Choroiditis:
SO
VKH
Sarcoidosis
Serpiginous
Birdshot
Wegener’s, SLE
Histoplasmosis/TB
Masquerade syndrome
PANuveitis:
Syphilis
Sarcoidosis
VKH
Behçet’s disease
Sympathetic Ophthalmia
Infectious endophthalmitis

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, HLA-B8,
HLA-DRB1) 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-Fuch’s Nodules

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

23. 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
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

24. Behçet’s Disease
 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. Behçet’s 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.  Systemic Lupus Erythematosus
 Retinopathy is an important marker of systemic activity esp CNS vasculitis-75%
 Polyarteritis Nodosa (PAN)
 M>F; HBs+, polyneuropathy, Raynaud’s, coronary arteritis
 Untreated: 90% mortality
 Wegener granulomatosis
 Necrotizing granulomatosis of upper & lower resp tract -esp paranasal sinuses
 Glomerulonephritis (85%), peripheral neuropathy
 Untreated: 80% mortality
 Behçet’s Disease
Retinal Vasculitis

30. 52 yo M
Acute onset of blurred
vision & photophobia OS
Non-granulomatous
anterior uveitis OS > OD
Vitritis OS > OD
BRAO and retinitis OD
HIV+ not on HAART
RPR+ 1:2048, Syphilis IgG+
Syphilis-related panuveitis
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
24 yo WM with “flashes of light” and blurry vision that developed overnight

33. Posterior/Panuveitis complications
Cataract
Epiretinal membrane
Secondary glaucoma
Hypotony
Chronic cystoid macular
edema
Subretinal fibrosis
Atrophy of retina/RPE
Choroidal
neovascularization
Retinal ischemia
Retinal
neovascularization
Optic nerve atrophy
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
 ANCAs (c-ANCA=PR3; p-ANCA=MPO)  Wegener, PAN
 Hypercoagulability panel (ACA, LAC, Factor V Leiden mut) occlusive vasculitis
 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  Wegener’s
 Lumbosacral XR/MRIHLAB27 associated uveitides
 Colonoscopy  IBD, Behçet, malignancy work-up
 Anterior chamber and/or vitreous tap for PCR, cultures, cytokines
Despite a million dollar work-up->
40% still idiopathic

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
Mononuclear phagocytes Chemotaxis
Clearance of antibody coated particles
Production of Il-1 and TNFα
Lymphocytes 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!)
Treatment: don’t wait too long to move beyond
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!