uveitis unplugged: anterior uveitis - conference design · background • commonest form of uveitis...
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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