uveitis classification & clinical features 1
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UVEITIS CLASSIFICATION & CLINICAL FEATURES
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• Uvea consists of the middle, pigmented vascular structures of the eye & includes the iris, ciliary body & choroid
• Uveitis is broadly defined as inflammation of the uvea
• Since uveitis is frequently associated with systemic disease, a thorough history, physical examination & workup is needed to categorize it
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CLASSIFICATION• BASED ON ANATOMY• CLINICAL COURSE• ETIOLOGY• HISTOLOGY
• STANDARDIZATION OF UVEITIS NOMENCLATURE (SUN) WORKING GROUP IN 2005 DEVELOPED ANATOMICAL CLASSIFICATION, DESCRIPTORS, STANDARDISED GRADING SYSTEM AND TERMINOLOGY
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BASED ON ANATOMY
• ANTERIOR UVEITIS• INTERMEDIATE UVEITIS• POSTERIOR UVEITIS• PANUVEITIS
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ANTERIOR UVEITIS• AC is the primary site of inflammation• Inflammation confined to the anterior
chamber is called iritis• If it spills over to retrolental space, it is
called iridocyclitis• If it involves cornea, its called
keratouveitis• If it involves sclera and uveal tract, its
called sclerouveitis
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INTERMEDIATE UVEITIS• The major site of inflammation is the
vitreous• Inflammation of the middle
portion(posterior ciliary body, pars plana) of the eye manifests primarily as floaters affecting vision; the eye frequently appears quiet externally
• Visual loss is primarily a result of CSME or less commonly cataract formation
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POSTERIOR UVEITIS• Intraocular inflammation primarily involving retina &/or
choroid• Inflammatory cells may be observed diffusely throughout
the vitreous cavity, overlying foci of active inflammation, or on the posterior vitreous face
• Ocular examn reveals focal, multifocal or diffuse areas of retinitis or choroiditis with varying degrees of vitreous cellular activity
• Macular edema, retinal vasculitis and retinal or choroidal neovascularisation are structural complications of certain uveitic entities & not considered essential to the anatomical classification
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PANUVEITIS
• Primary sites are AC, vitreous & retina or choroid
• Many systemic infectious & noninfectious diseases associated with uveitis may produce diffuse intraocular inflammation with concomitant iridocyclitis & posterior uveitis
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TYPE PRIMARY SITE OF INFLAMMATION
INCLUDES
ANTERIOR UVEITIS ANTERIOR CHAMBER IRITISIRIDOCYCLITISANTERIOR CYCLITIS
INTERMEDIATE UVEITIS
VITREOUS PARS PLANITISPOSTERIOR CYCLITISHYALITIS
POSTERIOR UVEITIS RETINA OR CHOROID FOCAL, MULTIFOCAL OR DIFFUSE CHOROIDITISCHORIORETINITISRETINOCHOROIDITISRETINITISNEURORETINITIS
PANUVEITIS AC, VITREOUS & RETINA OR CHOROID
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DESCRIPTORSCATEGORY DESCRIPTOR COMMENTONSET SUDDEN
INSIDIOUSDURATION LIMITED
PERSISTENT<or=3 MONTHS>3 MONTHS
COURSE ACUTE
RECURRENT
CHRONIC
SUDDEN ONSET & LIMITED DURATIONREPEATED EPISODES SEPARATED BY PERIODS OF INACTIVITY WITHOUT Rx >or=3 MONTHSPERSISTENT UVEITIS WITH RELAPSE IN <3 MONTHS AFTER DISCONTINUING Rx
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ACTIVITY OF UVEITIS TERMINOLOGY
TERM DEFINITION
INACTIVE GRADE 0 CELLS(AC)
WORSENING ACTIVITY 2 STEP INCREASE IN LEVEL OF INFLAMMATION(eg. AC CELLS, VITREOUS HAZE) OR INCREASE FROM GR 3+ TO 4+
IMPROVED ACTIVITY 2 STEP DECREASE IN LEVEL OF INFLAMMATION OR DECREASE TO GR 0
REMISSION INACTIVE DS FOR >or=3 MONTHS AFTER DISCONTINUING ALL Rx FOR EYE DISEASE
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CATEGORISATION BY CLINICAL COURSE
• As acute; chronic; or recurrent• Whether severe or low grade can
influence categorisation & prognosis• Inflammatory process may occur in 1 or
both eyes or it may alternate between them
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HISTOLOGY-GRANULOMATOUS OR NONGRANULOMATOUS
• Ocular examination offers a unique opportunity to determine the type of infiltrating inflammatory cells involved without taking a biopsy
• In anterior uveitis, inflammatory cells attach to the corneal endothelium in conglomerates called keratic precipitates(KPs)
• Appearance of KPs can be used to classify it as granulomatous & non granulomatous
• Non granulomatous characterised by fine white collections of lymphocytes, plasma cells & pigment. These can form in any disease. It only alerts that anterior inflammatory disease has occurred
• Granulomatous KPs are large greasy appearing collections of lymphocytes, plasma cells & giant cells called ‘mutton fat’ KPs is a useful diagnostic clue
• Other ocular findings suggestive of granulomatous inflammation are iris nodules & choroidal granulomas
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CAUSES OF GRANULOMATOUS INFLAMMATION
• Sarcoidosis• Sympathetic ophthalmia• Uveitis associated with multiple sclerosis• Lens induced uveitis• Intraocular FB• VKH syndrome• Syphilis• Tb• Other infectious agents
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UNILATERAL VS BILATERAL
Most cases are bilateral although one eye maybe affected 1st
Disease that frequently involve a single eye even after months or years of the disorder are
• Sarcoidosis• Postsurgical uveitis• Intraocular FB• Parasitic disease• Acute retinal necrosis• Behcet disease
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FLOWCHART FOR EVALUATION OF UVEITIS PATIENT
ACUTE, SEVERE WITH OR WITHOUT FIBRIN MEMBRANE OR HYPOPYON
ARTHRITIS, BACKPAIN, GI/GU SYMPTOMS
SERONEGATIVE SPONDYLOARTHROPATHIES
HLA-B27, SACROILIAC FILMS
APHTHOUS ULCERS
BEHCET DS HLA-B5, -B51
POSTSURGICAL, POSTTRAUMATIC
INFECTIOUS ENDOPHTHALMITIS
VITREOUS CULTURE, VITRECTOMY
NONE IDIOPATHIC POSSIBLY HLA-B27
ANTERIOR UVEITIS
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MODERATE SEVERITY(RED, PAINFUL)
SHORTNESS OF BREATH, AFRICAN DESCENT
SARCOIDOSIS SERUM ACE, LYSOZYME, CHEST X-RAY, GALLIUM SCAN, BIOPSY
POSTTRAUMATIC
POSTTRAUMATIC IRITIS
INCREASED IOP GLAUCOMATOCYCLITIC CRISIS, HERPETIC IRITIS
POOR RESPONSE TO STEROIDS
SYPHILIS RPR, VDRL, FTA-ABS
POST CATARACT EXTRACTION
LOW GRADE ENDOPHTHALMITIS, IOL RELATED IRITIS
CONSIDER VITRECTOMY, CULTURE
NONE IDIOPATHIC
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Chronic, minimal redness pain
Child especially with arthritis
JIA-related iridocyclitis
ANA, ESR, rheumatoid factor
Heterochromia, diffuse kp, u/l
Fuchs heterochromic iridocyclitis
None
Postsurgical Low grade endophthalmitis(eg. Propionibacterium acnes); iol related
Consider vitrectomy, capsulectomy, with culture
None Idiopathic
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INTERMEDIATE UVEITISMild to moderate Shortness of
breath, african descent
Sarcoidosis As above
Tick exposure, erythema chronicum migrans rash
Lyme disease Elisa
Neurologic symptoms
Multiple sclerosis MRI brain
Over age 50 Intraocular lymphoma
Vitrectomy, cytology
None Pars planitis
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POSTERIOR UVEITIS-CHORIORETINITIS WITH VITRITIS
Focal Adjacent scar, raw meat ingestion
Toxoplasmosis ELISA
Child, history of geophagia
Toxocariasis ELISA
HIV infection CMV retinitis
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Multifocal Shortness of breath
Sarcoidosis As above
Tuberculosis Ppd, cxr
Peripheral retinal necrosis
Acute retinal necrosis,Progressive outer retinal necrosis if immunocompromised
Vzv, hsv titres(elisa) possibly vitrectomy/retinal biopsy
Aids Syphilis, toxoplasmosis
As above
Iv drug abuse, hyperalimentation, immunosupression
Candida, aspergillus infection
Blood, vitreous cultures
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Visible, intraocular parasite, from Africa or Central/South America
CysticercosisOnchocerciasis
Age over 50 Intraocular lymphoma
As above
None Birdshot retinochoroidopathy
HLA-A29, fluorescein angiography(FA)
Multifocal choroiditis with panuveitis
Rule out TB, sarcoidosis, syphilis
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Diffuse Dermatological/CNS symptoms
VKH syndrome FA, LP to document CSF pleocytosis
Postsurgical/traumatic; bilateral
Sympathetic ophthalmia
FA
U/L Infectious endophthalmitis
As above
Child; History of geophagia
Toxocariasis As above
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CHORIORETINITIS WITHOUT VITRITIS
Focal None, history of carcinoma
Neoplastic Metastatic workup
Multifocal Ohio/Missisippi Valley
Ocular Histoplasmosis
FA if macula involved
Lesions confined to posterior pole
White dot syndrome(eg. APMPPE, MEWDS, PIC)
FA
Geographic pattern of scars
Serpiginous choroiditis
FA
Diffuse From Africa, Central/South America
Onchocerciasis
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VASCULITISAphthous ulcers, hypopyon
Behcet disease As above
Malar rash, Female, arthralgias
SLE ANA
c/c sinusitis with hemorrhagic rhinorrhoea, dyspnoea, renal insufficiency, purpura
Wegeners granulomatosis
c-ANCA
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POSTERIOR UVEITIS WITH RETINITIS
FOCAL RETINITIS MULTIFOCAL RETINITISToxoplasmosis Syphilis
Onchocerciasis HSV
Cysticercosis VZV
Masquerade syndrome CMV
DUSN(Diffuse unilateral subacute neuroretinitis)Candida infn
Sarcoidosis
Cat scratch disease
Masquerade syndrome
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POSTERIOR UVEITIS WITH A FOCAL(SOLITARY) CHORIORETINAL LESION
WITH VITREAL CELLS WITHOUT VITREAL CELLSToxocariaasis Tumour
Sarcoidosis Serpiginous choroiditis
Tuberculosis
Nocardia
Cats-cratch disease
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POSTERIOR UVEITIS WITH MULTIFOCAL CHORIORETINAL LESIONS
WITH VITREAL CELLS WITHOUT VITREAL CELLSBirdshot retinochoroidopathy OHS(Ocular histoplasmosis syndrome)
MCP(Multifocal choroiditis & panuveitis) PIC(Punctate inner choroiditis)
SFU(Subretinal fibrosis) syndrome PORT(Punctate outer retinal toxoplasmosis)
Sympathetic ophthalmia Acute retinal pigment epithelitis
VKH syndrome Subacute sclerosing panencephalitis*
Sarcoidosis
West nile virus
Cat scratch disease
Malignant masquerade syndromes
Rubella measles*
MEWDS*
APMPPE*(Acute posterior multifocal placoid pigment epitheliopathy)
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POSTERIOR UVEITIS WITH RETINAL VASCULITIS
PRIMARILY ARTERITIS PRIMARILY PHLEBITIS ARTERITIS & PHLEBITIS
SLE Sarcoidosis Toxoplasmosis
PAN Multiple sclerosis Relapsing polychondritis
Syphilis Behcet disease Wegeners granulomatosis
HSV Birdshot retinochoroidopathy
Crohns disease
VZV HIV paraviral syndrome Frosted branch angitis
IRVAN(Idiopathic retinal vasculitis, aneurysms & neuroretinitis)
Eales disease
Churg strauss syndrome
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CLINICAL FEATURES
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SYMPTOMS• Depends on which part is inflammed, rapidity of onset,
duration of disease & course of the disease• Acute onset anterior uveitis causes pain, photophobia,
redness & blurred vision.• Pain results due to acute onset inflammation of iris or from
secondary glaucoma• Pain associated with ciliary spasm in iritis may be a reffered
pain that seems to radiate over areas severed by trigeminal nerve
• Epiphora, redness & photophobia are usually present when inflammation involves the iris, cornea or iris-ciliary body
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• Chronic iridocyclitis in patients with juvenile idiopathic arthritis maynot be associated with any symptoms at all
• But with c/c iridocyclitis blurred vision may result as a result of calcific band keratopathy, cataract or CME
• Intermediate uveitis produces symptoms of floaters & blurred vision
• Floaters result from shadows cast by vitreous cells on the retina
• Blurred vision may be due to CME or vitreous opacities in the visual axis
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• Presenting symptoms in posterior uveitis include painless decreased visual aquity, floaters, photopsia, metamorphopsia, scotoma, nyctalopia, or a combinaton of these
• This blurred vision maybe due to the primary effects of uveitis such as retinitis &/or choroiditis directly affecting macular functions, or to the complication of inflammation such as CME, epiretinal membrane, retinal ischemia & choroidal neovascularisation
• It may also result from refractive error such as myopic or hyperopic shift associated with macular edema, hypotony or a change in lens position
• Other causes are opacities in visual axis from inflammatory cells, fibrin or protein in the anterior chamber; KPs; secondary cataract; vitreous debris; macular edema; & retinal atrophy
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SYMPTOMS OF UVEITIS• Redness• Pain• Photophobia• Epiphora• Visual disturbances Diffuse blur, causedby:
Myopic or hyperopic shiftInflammatory cellsCataract Scotomata(central or peripheral) Floaters
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SIGNS ANTERIOR PORTION• KPs• Inflammatory cells• Flare• Fibrin• Hypopyon• Pigment dispersion• Pupillary miosis• Iris nodules• Synechiae, both anterior & posterior• Band keratopathy(in long standing uveitis)
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SIGNS OF UVEITIS• Eyelid & skin
VitiligoNodules
• ConjunctivaPerilimbal or diffuse injectionNodules
• Corneal endotheliumKPsFibrinPigment(nonspecific)
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• AC/PCInflammatory cellsFlare(proteinaceous influx)Pigment(nonspecific)
• IrisNodulesPosterior synechiaeAtrophyHeterochromia
• AnglePeripheral anterior synechiaeNodulesVascularization
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• Intraocular pressureHypotonySecondary glaucoma
• VitreousInflammatory cells(single/clumped)Traction bands
• Pars planaSnowbanking
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• RetinaInflammatory cellsInflammatory cuffing of blood vesselsEdemaCMERetinal pigment epithelium: hypertrophy/clumping/lossEpiretinal membranes
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• ChoroidInflammatory infiltrateAtrophyNeovascularization
• Optic nerveEdema(nonspecific)Neovascularization
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• Chemical mediators of acute stage of inflammation include serotonin, complement & plasmin
• Leukotrienes, kinins & prostaglandins modify 2nd phase of acute response
• Polymorphonuclear leukocytes, eosinophils & mast cells contribute to inflammatory signs, but lymphocyte is the predominant inflammatory cell in the innner eye in uveitis
• These mediators result in vascular dilatation(ciliary flush), increased vascular permeability(aqueous flare), & chemotaxis of inflammatory cells into the eye( aqueous & vitreous cellular reaction)
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• Perilimbal vascular engorgement(ciliary flush) or diffuse injection of the conjunctiva, episclera or both is typical with acute anterior uveitis
• The AC reaction can be described as• Serous(aqueous flare caused by protein influx)• Purulent(PML & necrotic debris causing hypopyon)• Fibrinous(plasmoid or intense fibrinous exudate)• Sanguinoid(inflammatory cells with erythrocytes
manifested by hypopyon mixed with hyphema)
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• SUN grading of Cells & Flare• AC cells• Graded according to number of cells seen
in a 1mm*1mm high-powered beam at full intensity at 45deg to 60 deg
• Flare may be graded similarly
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GRADE CELLS CELLS IN FIELD0 <1
0.5+ 1-5
1+ 6-15
2+ 16-25
3+ 26-50
4+ >50
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FLAREGRADE DESCRIPTION0 NONE
1+ FAINT
2+ MODERATE(IRIS & LENS DETAILS CLEAR)
3+ MARKED(IRIS & LENS DETAILS HAZY)
4+ INTENSE(FIBRIN OR PLASMOID AQUEOUS)
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• Iris involvement may manifest as either anterior or posterior synechiae, iris nodules(Koeppe nodules at the pupillary border, Busaca nodules within the iris stroma & Berlin nodules in the angle), iris granulomas, heterochromia(eg, Fuchs heterochromic iridocyclitis) or stromal atrophy(eg, herpetic uveitis)
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• With involvement of ciliary body & trabecular meshwork, IOP is often low secondary to decreased aqueous production or increased alternative outflow
• But IOP may increase if meshwork becomes clogged by cells or debris or if trab meshwork itself is the site of inflammation(trabeculitis)
• Pupillary block with iris bombe & secondary angle closure may also lead to an acute rise in IOP
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INTERMEDIATE SEGMENT• Vitreal inflammatory cells graded as
• NIH grading for vitreous haze has been adopted by SUN group. With this standardized photos are used for comparison
GRADE NO. OF CELLS0 NO CELLS
0.5+ 1-10
1+ 11-20
2+ 21-30
3+ 31-100
4+ >100
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• Other changes are• Snowball opacities- common with sarcoidosis or
intermediate uveitis• Exudates over pars plana(snowbank). Active
snowbanks have a fluffy or shaggy appearance; if it becomes inactive the pars plana appears gliotic or fibrotic & smooth(not reffered as snowbanks)
• Vitreal strands• Chronic uveitis may be associated with cyclitic
membrane formation, secondary ciliary body detachment & hypotony
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POSTERIOR SEGMENT• Retinal or choroidal inflammatory infiltrates• Inflammatory sheathing of arteries or veins• Exudative, tractional or rhegmatogenous retinal
detachment• RPE hypertrophy or atrophy• Atrophy or swelling of retina, choroid or optic nerve
head• Preretinal or subretinal fibrosis• Retinal or choroidal neovascularisation
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