UVEITIS CLASSIFICATION & CLINICAL FEATURES

• 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

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

BASED ON ANATOMY

• ANTERIOR UVEITIS• INTERMEDIATE UVEITIS• POSTERIOR UVEITIS• PANUVEITIS

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

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

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

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

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

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

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

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

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

CAUSES OF GRANULOMATOUS INFLAMMATION

• Sarcoidosis• Sympathetic ophthalmia• Uveitis associated with multiple sclerosis• Lens induced uveitis• Intraocular FB• VKH syndrome• Syphilis• Tb• Other infectious agents

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

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

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

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

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

POSTERIOR UVEITIS-CHORIORETINITIS WITH VITRITIS

Focal Adjacent scar, raw meat ingestion

Toxoplasmosis ELISA

Child, history of geophagia

Toxocariasis ELISA

HIV infection CMV retinitis

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

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

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

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

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

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

POSTERIOR UVEITIS WITH A FOCAL(SOLITARY) CHORIORETINAL LESION

WITH VITREAL CELLS WITHOUT VITREAL CELLSToxocariaasis Tumour

Sarcoidosis Serpiginous choroiditis

Tuberculosis

Nocardia

Cats-cratch disease

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)

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

CLINICAL FEATURES

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

• 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

• 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

SYMPTOMS OF UVEITIS• Redness• Pain• Photophobia• Epiphora• Visual disturbances Diffuse blur, causedby:

Myopic or hyperopic shiftInflammatory cellsCataract Scotomata(central or peripheral) Floaters

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)

SIGNS OF UVEITIS• Eyelid & skin

VitiligoNodules

• ConjunctivaPerilimbal or diffuse injectionNodules

• Corneal endotheliumKPsFibrinPigment(nonspecific)

• AC/PCInflammatory cellsFlare(proteinaceous influx)Pigment(nonspecific)

• IrisNodulesPosterior synechiaeAtrophyHeterochromia

• AnglePeripheral anterior synechiaeNodulesVascularization

• Intraocular pressureHypotonySecondary glaucoma

• VitreousInflammatory cells(single/clumped)Traction bands

• Pars planaSnowbanking

• RetinaInflammatory cellsInflammatory cuffing of blood vesselsEdemaCMERetinal pigment epithelium: hypertrophy/clumping/lossEpiretinal membranes

• ChoroidInflammatory infiltrateAtrophyNeovascularization

• Optic nerveEdema(nonspecific)Neovascularization

• 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)

• 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)

• 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

GRADE CELLS CELLS IN FIELD0 <1

0.5+ 1-5

1+ 6-15

2+ 16-25

3+ 26-50

4+ >50

FLAREGRADE DESCRIPTION0 NONE

1+ FAINT

2+ MODERATE(IRIS & LENS DETAILS CLEAR)

3+ MARKED(IRIS & LENS DETAILS HAZY)

4+ INTENSE(FIBRIN OR PLASMOID AQUEOUS)

• 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)

• 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

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

• 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

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