Uveitis unplugged:anterior uveitis

Hobart 2017Peter McCluskey

Save Sight Institute

Sydney Eye Hospital

Sydney Medical School

University of Sydney

Sydney Australia

No financial or proprietary interest in any material discussed

2

Financial Disclosures

maintaining academicintegrity:

I work in inflammatory eyedisease,

Financial Disclosures

maintaining academicintegrity:

I work in inflammatory eyedisease,

therefore

I have no financial disclosures

…..…… but I live the dream

Ferrari F430

Uveitis Classification

• anterior

• intermediate

• posterior

• panuveitis

Standardisation of Uveitis Nomenclature

Uveitis Classification

Background

• commonest form of uveitis

• up to 90% of patients

• inflammation of iris and ciliary body

• most frequently episodic andrecurrent

• may be chronic & persistent

• wide range of causes

Anterior Uveitis

…….at least 27 recognisable inflammatory & infectious uveitis phenotypes

Anterior Uveitis

Clinical Features

• sudden onset, limited duration

• red painful photophobic

• AC flare, cells & KPs

• fibrin, synechiae, hypopyon

• fundus normal

• self limited disease with goodprognosis

• low rate of vision threateningcomplications

Acute Anterior Uveitis

Chronic Anterior Uveitis

Clinical Features

• insidious onset, persistent• blurred vision• AC flare, cells & KPs• fundus normal

• variable prognosis

• multiple complications –synechiae, cataract, ↑IOP, CME

• loss of vision common

How to sort out patients with Uveitis• clinical assessment of uveitis

- comprehensive history

- detailed examination

- extra history & review of systems

- directed extra ocular physical examination

• define diagnosis- syndrome recognition

- differential diagnosis

- selective investigations

- determine cause of any vision loss

• plan treatment

Anterior Uveitis

History:

• determine clinicalphenotype

• systemic disease

• all medications & drugs

• ocular trauma

• travel history

• at risk behaviour

- IVDU

- at risk sexual activity

• immunocompromised

- immunosuppressive drugs

- immunosuppressive illness

- organ transplant

- cancer therapy

- HIV infection

- past history of malignancy+

• review of systems – espjoints, skin, GIT, G/U, resp

Anterior Uveitis

Anterior Uveitis

phenotype infectious inflammatory ocularunilateralrecurrent

herpeticPSS

HLA B27 relatedBehcets

unilateralalternating

HLA B27 related

bilateral acute SarcoidBehcets

unilateralchronic

herpetic JIAsarcoid

Fuchs

bilateral chronic JIASarcoidTINU

Clinical phenotypes of anterior uveitis

NB: syphilis can mimic any phenotype of uveitis

Anterior Uveitis Signs:

• signs mostly non specific

• useful signs - KPs, iris and pupil

• the most important fundamental rule:

can’t diagnose anterior uveitis without a normalfundus on dilated exam

Anterior Uveitis

Cells & Flare

• flare: protein in aqueous

• cells: WBC, RBC, pigment

• SUN grading system

Anterior Uveitis

Keratic Precipitates

• location

• distribution

• morphology

Fuchs – pan corneal

HerpeticToxoSevere IU

180°0°Others - Arlt’s triangle

Anterior Uveitis

Iris stroma Vs IPE loss

• Fuchs cyclitis, PSS

• anterior stromal atrophy

• pupil normal; no PS

• herpetic uveitis

• iris pigment epithelialatrophy – sector

• pupil usually abnormal

Stroma

Pigment Epithelium

Anterior Uveitis

Idiopathic 505 (50%)• idiopathic 419

• Fuchs 26

• WDS 55

Inflammatory 308 (35%)• HLA B27 188

(+systemic B27) 46

• sarcoid 56

• Behcets 23

Infective 203 (20%)

• Herpetic 105

- anterior 83

- posterior 22

• TB 40

• Toxoplasmosis 38

• syphilis 10 (25)

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Uveitis in Sydney

Idiopathic 505 (50%)• idiopathic 419

• Fuchs 26

• WDS 55

Inflammatory 308 (35%)• HLA B27 188

(+systemic B27) 46

• sarcoid 56

• Behcets 23

Infective 203 (20%)

• Herpetic 105

- anterior 83

- posterior 22

• TB 40

• Toxoplasmosis 38

• syphilis 10 (25)

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Uveitis in Sydney

Anterior Uveitis

HLA B27 related diseases

• acute anterior uveitis

• ankylosing spondylitis

• psoriatic

- spondylo-arthritis subgroup

• reactive arthritis

• inflammatory bowel disease

- Crohn’s disease

- ulcerative colitis

(Reiter’s syndrome)

Anterior Uveitis

Enthesitis DactylitisAcute anterior

uveitis

Plaque psoriasis Crohn’s Disease Ulcerativecolitis

Anterior Uveitis

HLA B27, AAU and Inflammatory Disease

• definable restricted pattern of B27 associated disease• HLA B27 associated with AAU & RAAU• strong association: > 50% AAU/RAAU B27 +ve

• 50% HLA B27+ve AAU AAU is the B27 association

• 50% HLA B27+ve AAU systemic B27 disease

• up to 25% systemic B27 disease AAU

• 1-2% HLA B27 +ve B27 related illness

Anterior Uveitis

Systemic HLA B27 related diseases

Axial SpA Peripheral SpA

PsA

ReA

IBD-SpA

AS

Non-radiographicAxial SpA

UndifferentiatedPeripheral SpA

Raychaudhuri SP and Deodhar A.J Autoimmun. 2014;48–49:128–133

Anterior Uveitis

Systemic HLA B27 related diseases

Axial SpA Peripheral SpA

PsA

ReA

IBD-SpA

AS

Non-radiographicAxial SpA

UndifferentiatedPeripheral SpA

AAU/RAAU

Raychaudhuri SP and Deodhar A.J Autoimmun. 2014;48–49:128–133

Anterior Uveitis

Anterior Uveitis

DUET study (Dublin Uveitis Evaluation Tool)

• 173 consecutive patients with AAU presenting toRoyal Victoria Eye & Ear Hospital Dublin EmergencyDepartment

• 40% patients presenting with AAU had undiagnosedSpA by ASAS criteria

Haroon M, O’Rourke M, Ramasamy P et al. A novel evidence based detection ofundiagnosed spondyloarthritis in patients presenting with acute anterior uveitis.Ann Rheum Dis 2015; 74:1990-95

Recent studies of HLA B27 AAU

Anterior Uveitis

SENTINEL study Spain

• multicentre, prospective clinical study• 2008 - 2013• 798 consecutive patients with AAU• 60% B27 +ve; 40% B27 –ve• ASAS diagnostic criteria• 50.2% undiagnosed axial SpA• 17.5% undiagnosed peripheral SpA• B27 +ve Vs B27 –ve:

• axial SpA: 69.8% Vs 27.3%• peripheral SpA 21.9% Vs 11.1%

Juanola X, Santamaria EL, Cordero-Coma M et al. Descriptionand prevelance of spondyloarthritis in patients with anterioruveitis. Ophthalmol 2016; 123:1632-36

ie ~ 60% hadundiagnosed SpA

Anterior Uveitis

Inflammatory back pain

• usually onset < age 35 - 40• persistent > 3 months• worse at rest, at night & early AM• back stiffness lasts > 1 hour• improves with activity/exercise

• opposite to mechanical back pain• often multiple previous diagnoses and

treatments

DUET Study

Anterior Uveitis

or joint pains requiring GP consultationor inflammatory back pain + psoriasis

Anterior Uveitis

What does this mean???• potentially we can diagnose a large

number of patients withpreviously undiagnosed SpA

- history of back pain critical

- evidence of peripheral disease

- other B27 related disease

• SpA now highly treatable

• ASAS criteria aim to diagnoseSpA before significant jointdamage

Anterior Uveitis

Juvenile Idiopathic Arthritis (JIA)

AKA -Childhood arthritis, JCA, JRA

• onset age < 16 years

• girls > boys

• autoimmune

• ANA, RF & HLA B27 may be useful

• risk factors for uveitis:

- young age at onset

- arthritis < 4 years

- ANA positive

Anterior Uveitis

Oligoarticular(50%)≤4 joints80% ANA +ve

Polyarticular(20%)>5 jointsRF +ve (<20%)50% ANA +ve

EnthesitisRelated Arthritis(15%)Sacroilitis, IBD80% HLA-B27

Psoriatic Arthritis(5-10%)50% ANA35% HLA-B27

JIA Classification Criteria

Anterior Uveitis

JIA uveitis• white eye & asymptomatic

• atypical presentations common

• insidious onset & persistent

• bilateral

• anterior uveitis

• band keratopathy, synechiae,cataract, or IOP, CME

• screening critical

• medical & surgical managementhas changed significantly

JIA Uveitis Screening

Clinical guideline for the diagnosis and management of juvenile arthritis (August 2009)Royal Australian College of General Practitioners- www.racgp.org.au/guidelines/juvenileidiopathicarthritis

Anterior Uveitis

Herpes Simplex

Clinical Features

• usually after onset of cornealdisease

• may occur in absence ofcorneal activity or disease

• IPE changes common

• typically recurrent clinicalcourse

• elevated IOP and cataractcommon

VZV Clinical Features

• uveitis in up to 40% of patientswith HZO

• onset after rash and cornealdisease

• variable often chronic clinicalcourse

• iris and pupil changes common

• elevated IOP and cataractcommon

• anti-VZV therapy => uveitis

• co-existing HIV infection

Anterior Uveitis

VZV sine herpete• acute onset

• decreased corneal sensation

• florid anterior uveitis

• severe iris changes

- non reactive dilated pupil

- sectorial iris atrophy

- widespread pigment loss

• persistent recalcitrant course

• elevated IOP & glaucoma

• cataract

Anterior Uveitis

Posner-Schlossman Syndrome /

CMV anterior uveitis• uncommon

• ↑ in Asian ethnicity – esp Chinese

• recurrent acute or chronicanterior uveitis + endotheliitis

• acute or chronic ↑ IOP

• severe IOP mediated damage

• increasing evidence PSS due toCMV infection

• ??characteristic clinical signs

small & medium KPs+ pigment deposits

anterior iris stromal atrophy

Anterior Uveitis

Fuch’s Heterochromic Cyclitis

Clinical Features• females > males

• any age group (20 - 50)

• ill defined onset or asymptomatic

• clinical presentations:

- routine examination

- acute PVD

- floaters

- reduced vision

- cataract

- elevated IOP

Fuch’s Heterochromic Cyclitis

Clinical Features• white eye

• typical KPs – white, stellate &pan-corneal

• anterior stromal iris changes

• no synechiae

• angle vascularisation – Amsler’s• IOP/glaucoma

• PSC cataract

• vitreous cells & syneresis

• no response to topical steroids

Viruses & Anterior Uveitis• HSV, VZV – often corneal disease; can be CAU/RAAU

• sector iris atrophy + age < 40 > 90% HSV;

+ age > 60 > 90% VZV

• CMV anterior uveitis

- PSS/CAU - > 50% CMV +ve

- ↑ in Asian ethnicity – esp Chinese

• FHC 70% +ve rubella PCR; 20 - 30% +ve CMV PCR;occasional Toxoplasmosis

• diagnosis confirmed by viral PCR

Anterior Uveitis

Vision Loss & Anterior Uveitis

Inflammatory Mediated

• cystoid macular oedema• optic disc swelling

Non-Inflammatory

• posterior synechiae

• elevated intraocular pressure

• cataract

• band keratopathy

• hypotony

Anterior Uveitis

• Chest X Ray / CT chest

• + ACE level

• Qfn gold/Mantoux

• Syphilis serology

• Lyme serology

• Chlamydia serology

• Yersinia serology

• HLA B 27

• X Ray/MRI Sacroiliacjoints

• aqueous tap – PCR,culture, cytology

• medical consultation

Potential Range of Investigations

Anterior Uveitis

Anterior Uveitis

• Chest X Ray / CT chest

• no ACE level

• Qfn gold/Mantoux

• Syphilis serology

• Lyme serology

• Chlamydia serology

• Yersinia serology

• HLA B 27

• X Ray/MRI Sacroiliacjoints

• aqueous tap – PCR,culture, cytology

• medical consultation

review of systems

Potential Range of Investigations

Anterior Uveitis

Principles of treatment

• similar despite diverse aetiologies

• Rx determined by cause & severity of a threat to vision

• inflammatory visual loss => anti inflammatory Rx

• specific Rx for non inflammatory complications

• topical corticosteroid therapy controls majority

• treat infectious uveitis with specific antimicrobialtherapy & judicious use of corticosteroids

Anterior Uveitis

Indication Treatment

initial therapy topical steroids

cycloplegics

severe inflammation periocular steroids

cystoid macular oedema

severe inflammation systemic steroids

cystoid macular oedema

frequently recurrent oral methotrexate

or chronic

Anterior Uveitis

Indications for systemic steroids

• uncontrolled severe acute anterior uveitis withmaximum topical Rx

- continuing pain

- progressing signs

• very severe acute HLA B27 related AAU

• hypopyon

• cystoid macular oedema and decreased vision

• intraocular surgery

Managing JIA uveitis

• control of intraocular inflammation is essential

• adequate systemic immunosuppression is critical

- minimise topical steroid therapy

- must get topical steroids down to < 2/day

- stepwise use of systemic IMT – MTX, (MFM), biologic

• rapid taper any systemic steroids; increasing dosemethotrexate

• no improvement over 3-6 months => biologic agent

- adalimumab or infliximab

Anterior Uveitis

Uveitis Screening

Adalimumab plus methotrexate for uveitis in juvenile idiopathic arthritisRamanan AV, Dick AD, Jones AP, McKay A et al. NEJM 2017; 376: 1637-46

Sycamore Study

Anterior Uveitis

Managing HSV & VZV Uveitis

• often no active corneal disease

• AC tap for viral PCR to confirm diagnosis

• intensive topical steroids + atropine

• oral acyclovir 400mgs X 5/day for 5 days orvalacyclovir 1gram X3/day for 5 days

• suppressive dose for 3-6 months (ACV 800mg orval-ACV 500mg)

• consider long term suppressive Rx in I/C patients(ie ongoing/permanent)

HEDS & Herpetic Uveitis

HEDS 4: iritis

- oral acyclovir probablyminimises treatment failure

- ACV 400mgs X 5/day for 5 days

HEDS 5: prevention

- prophylaxis halves recurrencerate over 1 year

- ACV 400mgs BD

• valtrex Vs acyclovir

Anterior Uveitis

Managing CMV Uveitis

• AC tap for viral PCR to confirm diagnosis

• no consensus

• multiple treatment regimens

• topical ganciclovir gel X 4-5 / day + topical steroids

• + 3 weeks oral valganciclovir 900mgs BD

• consider longer term oral suppressive Rx in I/Cpatients

Anterior Uveitis

Take Home Messages:

• AAU/RAAU commonly associated with SpA

• JIA uveitis

- treat aggressively systemically; minimise topical Rx

- biologics have made big difference

- use IOLs in older, well controlled patients

• herpetic uveitis

- commoner than previously thought

- diagnosis by AC tap for viral PCR

- overlap with FHC

- specific topical & oral therapy of benefit

Anterior Uveitis

Take Home Messages:

• acute anterior uveitis

- relatively benign disease with good prognosis

- high frequency of associated disease – B27

- discharge AAU patients once attack resolved

• chronic anterior uveitis

- persistent, severe disease with poorer prognosis

- herpetic uveitis, JIA, idiopathic

- multiple complications => long term clinic F/U