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UVEITIS AND OCULAR IMMUNOLOGY by Wendy Smith MDCOPE ID 31562-SDLecture Series 12th Visionary Ophthalmology
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WENDY M SMITH, MDSENIOR STAFF FELLOW,
UVEITIS AND OCULAR IMMUNOLOGYNATIONAL EYE INSTITUTE
NATIONAL INSTITUTES OF HEALTH
Uveitis
a generic term for intraocular inflammation.does not indicate site of inflammationdoes not indicate the cause: autoimmune or infectious
Uveitis: Definition
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 52.4/100,000U.S. Prevalence 115.3/100,0003 times higher than previous estimatePrevalence 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 yrsMean age of onset is 37.2 yearsRange 20-50 years
151,200322,000
2,400,000
U.S. Prevalence WorldwideU.S. Incidence
IUSG Classification of Uveitis
Anterior uveitisiris and pars plicata (CB)
Intermediate uveitispars plana and vitreous
Posterior uveitisretina + choroid
Panuveitis
Cells per high-power field in 1x1 mm slit beam0 = < 1 cell/hpf0.5+ = 1 - 5 cells1+ = 6 - 152+ = 16 - 253+ = 26 - 504+ = > 50
Flare0 = none1+ = faint2+ = moderate, (iris/lens details clear)3+ = marked(iris/lens hazy)4+ = intense (fibrin or plastic aqueous)
SUN Grading system for AC cell and flare
Number of Cells* Description Grade0-1 clear 02-20 few opacities trace21-50 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)
0 = Clear
0.5+/trace = Trace
1+ = Few opacities,mild blurring
2+ = Significantblurring but stillvisible
3+ = Optic nervevisible, no vessels seen
4+ = Dense opacityobscures opticnerve head
National Eye Institute Grading System for Vitreous Haze (adopted by SUN Working Group)
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?
Anterior Uveitis: ~60% of all uveitis
Idiopathic
HLA-B27 associatedInflammatory bowel disease
Ankylosing spondylitis
Psoriatic arthritis
JIA (Juvenile Idiopathic Arthritis) associated
Sarcoidosis
Syphilis
Glaucomatocyclitic crisis
Masquerade syndromes
Anterior uveitisprevalence: 81/100,000 (Gritz et al)
Differential Diagnosis of Stellate Keratic Precipitates:Fuchs heterochromia (rubella, herpes, toxoplasmosis)
Viral
Toxoplasmosis
Differential Diagnosis of hypopyon:HLA-B27 associated
Low back pain, ethnicity, GI symptoms, ulcers, joints
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 yrsNo correlation betw joint and eye
Frequently asymptomaticUveitis before joint disease poor pxBK/PS/cataract/ON hyperemia/CME common
Complications Treatment
Posterior synechiaeCataract Inflammation-relatedSteroid-induced
Secondary glaucomaSteroid responseAngle closure
Cystoid macular edemaBand keratopathymore common in children
Topical corticosteroidsCycloplegicsGlaucoma gttsNSAIDs (gtt or PO)
Periocular steroids
Systemic steroidsSystemic immunosuppression
Anterior Uveitis
Intermediate Uveitis: ~15% of all uveitis
Most common causes:Sarcoidosis
Pars planitis syndrome (idiopathic)
Multiple sclerosis
Masquerade Syndromes
Infection Toxoplasma, Lyme, Toxocara, Syphilis, TB
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
Posterior & Panuveitis: 10-15% of all uveitis
Focal choroiditis/retinitis: Toxocariasis
Tuberculosis
Nocardiosis
Masquerade syndrome
Multifocal Retinitis:SyphilisHerpes simplex virus, CMVSarcoidosisMasquerade syndromesCandidiasisMeningococcus
Multifocal Choroiditis:SOVKHSarcoidosisSerpiginousBirdshot
Histoplasmosis/TBMasquerade syndrome
PANuveitis:SyphilisSarcoidosisVKH
disease Sympathetic OphthalmiaInfectious endophthalmitis
Posterior (Pan) Uveitis
Inflammation involving retina/choroid
Optic nerve:ON Edema, papillitis, granulomaFA features hot?
Retinal vasculature:Staining, leakage, capillary dropoutInvolves mainly veins vs arteriesPeripheral vs central
Chorioretinal lesions:Dalen-fuchs nodulesSize, age of lesion (old atrophic vs new elevated with substance to it)
Sarcoidosis
Sarcoidosis is a multisystem granulomatous disorder lungs (90-95%), lymph nodes, skin, eyes, CNSTypically affects young adults
More commonly seen in African Americans and Caucasians of Northern European descentIn 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 presentationUveitis occurs in 25-50% of pts20-50 yrs, typically bilateral (98%)
Sarcoidosis: Dalen-
30 yo AAM: Referred for endogenous candida endophthalmitisAlso has recent onset of headache, mood changes, gait abnormalities
Slit-like third ventricle
Enlarged lateral ventricles
Transependymal CSF flow
Diagnosis: Biopsy-Proven Neurosarcoidosis
75 yo WF with recent onset blurry visionCarried dx of SLE for >20 yrs
CBC: slightly elevated WBCNeg or wnl: Lyme, RPR, FTA ABS, PPD HLA B27 neg, UA & Chem 20 wnl
Diagnostic vitrectomy:Nests of macrophages & giant cellsSmall and reactive lymphocytesFurther work-up: hilar LAD on CT and PET scan
Diagnosis: Presumed Ocular Sarcoidosis
Modified Japanese Criteria:Major criteria (skin, oral, genital, eye)Minor criteria (arthritis, GI, epididymitis, neuropsychiatric etc)
ClassificationComplete (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)
retinitis
VKH: Common in pigmented ethnic groupsBilateral panuveitisVitiligo, alopecia, poliosis, (10-60%)Dysacusia, tinnitus (75% auditory problems)Meningitis (80% have CSF lymphocytic pleocytosis)
ON edema & hyperemia, Serous RDDalen-Fuchs nodulesSunset-glow fundusSigiura sign (perilimbal vitiligo)HLA DR4 (esp Japanese), DR1
24 yo Latino male with VKH:
Sudden onset blurred visionHeadacheTinnitus & hearing loss
One month after presentation
Ten months after presentation
End-stage VKH with diffuse RPE loss and subretinal fibrosis
Systemic Lupus ErythematosusRetinopathy is an important marker of systemic activity esp CNS vasculitis-75%
Polyarteritis Nodosa (PAN)
Untreated: 90% mortalityWegener granulomatosis Necrotizing granulomatosis of upper & lower resp tract -esp paranasal sinusesGlomerulonephritis (85%), peripheral neuropathy Untreated: 80% mortality
Retinal Vasculitis
52 yo MAcute onset of blurred vision & photophobia OS
Non-granulomatous anterior uveitis OS > OD
Vitritis OS > OD
BRAO and retinitis OD
HIV+ not on HAARTRPR+ 1:2048, Syphilis IgG+
Syphilis-related panuveitisResponded to IV Penicillin x 4 wks
Serpiginous choroidopathyRelationship w/TB?Treated with immunosuppressivesHLA-B07>30% VA <20/200
APMPPE: Acute posterior multifocal placoid pigment epitheliopathy
Bitten by a lab animalPreceding flu-like symptoms
Early hypo, late hyper on FA(White Dot Syndromes)
Hypofluorescent spots on ICGCNS vasculitisBenign course20% Visual Sequelae
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
Work-up
CBC with diff,Chem 20, UA, ESR, CRPTB (PPD+anergy panel)+Chest X-raySyphilis (both RPR and Sy IgM, IgG)HIVAdditional:ACE, lysozyme, Ca sarcoidosisUA-> TINU, Wegener, SLEANA, anti-DNA, RF, anti-CCP, ENA panel connective tissue disordersANCAs (c-ANCA=PR3;; p-ANCA=MPO) Wegener, PANHypercoagulability panel (ACA, LAC, Factor V Leiden mut) occlusive vasculitis
High Resolution Chest CT TB, sarcoidosisPFT/pulm consult sarcoidosisHearing test VKH, sarcoidosisLP MS, VKH, PIOL/CNSLHLA panel Birdshot, HLA-B27, Behçet, MS, sarcoidSinus CT WLumbosacral XR/MRI HLAB27 associated uveitidesColonoscopy IBD, Behçet, malignancy work-up
Anterior chamber and/or vitreous tap for PCR, cultures, cytokines
Despite a million dollar work-up-> 40% still idiopathic
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 endothel ium
Mononuclear phagocytes Chemotaxis Clearance of antibody coated particles Production of Il-1 and TNF
Lymphocytes Redistribution of T lymphocytes(CD4 > CD8) Inhibit T lymphocyte activation proliferation and lymphokine production Inhibit Ig production by B cells (high dose)
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, ChlorambucilBiologics: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
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
Thank you!