Uveitis Uveitis Clinician/ Academic View Clinician/ Academic View - - PowerPoint PPT Presentation

Uveitis Uveitis Clinician/ Academic View Clinician/ Academic View

Manfred Zierhut Manfred Zierhut Centre of Ophthalmology Centre of Ophthalmology University of Tuebingen University of Tuebingen Germany Germany

Definition Definition „ „Uveitis Uveitis“ “

• Inflammation of tissue inside

Inflammation of tissue inside the eye: the eye: Uvea, Retina Uvea, Retina

Classifications of Uveitis

• Localisation
• Morphology
• Etiology
• Course

Localisation Localisation

• Anterior Uveitis

Anterior Uveitis

• Iritis

Iritis

• Iridocyclitis

Iridocyclitis

Localisation Localisation

• Anterior Uveitis

Anterior Uveitis

• Iritis

Iritis

• Iridocyclitis

Iridocyclitis

• Intermediate Uveitis

Intermediate Uveitis

• Vitr.

Vitr.-

• and AC

and AC-

• cells

cells

Localisation Localisation

• Anterior Uveitis

Anterior Uveitis

• Iritis

Iritis

• Iridocyclitis

Iridocyclitis

• Intermediate Uveitis

Intermediate Uveitis

• Vitr. and AC
• Vitr. and AC-
• cells

cells

• Posterior Uveitis

Posterior Uveitis

• Chorioretinitis,

Chorioretinitis,

• Retinochoroiditis

Retinochoroiditis

Localisation Localisation

• Anterior Uveitis

Anterior Uveitis

• Iritis

Iritis

• Iridocyclitis

Iridocyclitis

• Intermediate Uveitis

Intermediate Uveitis

• Vitr. and AC
• Vitr. and AC-
• cells

cells

• Posterior Uveitis

Posterior Uveitis

• Chorioretinitis,

Chorioretinitis,

• Retinochoroiditis

Retinochoroiditis

• Panuveitis

Panuveitis

• AC cells

AC cells

• posterior uveitis

posterior uveitis

Etiology and Laterality Etiology and Laterality

unilateral unilateral bilateral bilateral

Herpes simplex/Zoster

• juv. Idiopathic Arthritis

Fuchs’ Heterochromic cyclitis HLA-B27-associated postsurgical Sarcoidosis foreign body Multiple Sclerosis APMPPE

Morphological Classification Morphological Classification

granulomatous granulomatous vs non non-

• granulomatous

granulomatous

speckled precipitates Koeppe-nodules Snowballs Choroidal Granuloma

Classification based on Morphology Classification based on Morphology

granulomatous granulomatous non non-

• granulomatous

granulomatous

Sarcoidosis JIA Multiple Sclerosis HLA-B27- associated Sympathetic Ophthalmia Behcet´s Disease VKH ARN Infection: Syphilis CMV Retinitis Tuberculosis Birdshot Choroidopathy Herpes Candida

Classification following Etiology Classification following Etiology

Uveitis Uveitis

Infections Infections: :

• Tuberculosis

Tuberculosis

• Syphilis

Syphilis

• Lyme

Lyme´ ´s Disease s Disease

• Herpes

Herpes-

• Virus

Virus

• Toxoplasmosis

Toxoplasmosis

• Taxocariasis

Taxocariasis

• Candida

Candida

Non Non-

• infectious:

infectious:

without ass. disease without ass. disease

• idiopathic

idiopathic

• Fuchs

Fuchs

• Pars planitis

Pars planitis

• Birdshot

Birdshot

• Serpiginosa

Serpiginosa

• Symp. Ophthalmia
• Symp. Ophthalmia

with ass. disease: with ass. disease:

• ankylosing Spondylitis

ankylosing Spondylitis

• JIA

JIA

• Behcet

Behcet´ ´s Disease s Disease

• Sarcoidosis

Sarcoidosis

• Multiple Sclerosis

Multiple Sclerosis

• Collagenosis

Collagenosis Traumatic Traumatic Masquerade Syndrome Masquerade Syndrome

SUN Criteria SUN Criteria

• Onset

Onset

• sudden

sudden

• insidious

insidious

• Duration

Duration

• limited:

limited: up to 3 months up to 3 months

• persistent:

persistent: longer than 3 months longer than 3 months

SUN Criteria SUN Criteria

• Course

Course

• acute:

acute: sudden onset with limited duration sudden onset with limited duration

• recurrent:

recurrent: multiple episodes, in between multiple episodes, in between intervals without inflammation without therapy, intervals without inflammation without therapy, at least 3 months at least 3 months

• chronic:

chronic: persistent uveitis with recurrences with persistent uveitis with recurrences with less than 3 months free of recurrences after stop less than 3 months free of recurrences after stop

• f therapy
• f therapy

Epidemiology of Uveitis Epidemiology of Uveitis Incidence Incidence

• Uveitis total: 35

Uveitis total: 35-

• 50/100.000 inhabitants

50/100.000 inhabitants

• Anterior Uveitis:

Anterior Uveitis:

• app. 50 %
• app. 50 %
• Intermediate Uveitis:

Intermediate Uveitis:

• app. 30 %
• app. 30 %
• Posterior Uveitis:

Posterior Uveitis:

• app. 20 %
• app. 20 %

Epidemiology of Uveitis Epidemiology of Uveitis Prevalence Prevalence

• Uveitis total: 100/100.000 inhabitants

Uveitis total: 100/100.000 inhabitants

• subgroups are unknown

subgroups are unknown

Uveitis in Childhood Uveitis in Childhood Epidemiology Epidemiology

• 5

5-

• 10 % of all uveitis patients

10 % of all uveitis patients

Evaluating Signs and Symptoms Evaluating Signs and Symptoms Goal Goal

To identify etiology and ass. disorders Best for an effective treatment But: adequate diagnostics!

How to evaluate Symptoms How to evaluate Symptoms

• History, eg. by questionnaire (symptoms)

History, eg. by questionnaire (symptoms)

• Quality of Life (NEI VFQ

Quality of Life (NEI VFQ-

• 25)

25)

• no optimal uveitis

no optimal uveitis „ „Evaluation of Symptoms Evaluation of Symptoms“ “ questionnaire questionnaire

How to evaluate Signs How to evaluate Signs

• clinical investigation

clinical investigation

• prob. new targeted history
• prob. new targeted history
• add. investigations
• add. investigations
• FLA, ICG, OCT, Visual fields, ERG, CT, MRI

FLA, ICG, OCT, Visual fields, ERG, CT, MRI

• t

targeted (lab argeted (lab-

• ) diagnostics

) diagnostics

Clinical Investigation Clinical Investigation

visual acuity slip lamp, intraocular presssure funduscopy

Slit Lamp Slit Lamp

conjunctiva sclera cornea endothelial precipitates anterior chamber Tyndall, cells lens cataract anterior vitreous cells, haze

Funduscopy Funduscopy

vitreous snowballs, cells retina and choroid infiltrates, granuloma macula edema, gliosis

• ptic disc

edema, excavation retinal vessels hemorrhages, sheething, neovascularisation

Additional Investigations Additional Investigations

Depending on clinical findings Laser Flare Photometry (LFP) Optical Coherence tomography (OCT) Fluorescein angiography Indocyanin-Green-angiography Perimetry Ultrasound Electrophysiology

Optical Coherence Tomography (OCT) Optical Coherence Tomography (OCT)

Macula Edema Gliosis Traction

Fluorescein Angiography Fluorescein Angiography

Retinal vessels vasculitis

• bliterations

neovascularisation non-perfusion-areas Macula edema RPE-changes

Perimetry Perimetry

unclear reduction of the visual acuity secondary glaucoma

Ultrasound Ultrasound

sclera posterior scleritis vitreous bleeding, infiltrations, adhesions retina detachment choroid tumor, granuloma

Electrophysiology Electrophysiology

• Retinal Function

How to reach a Diagnosis

History Findings

Working diagnosis (name it) Differential- diagnosis

Anatomy Morphology Course

Differential- diagnosis

• Add. Invest.

Anatomy Morphology Course

Diagnosis

Diagnostic Criteria

• Behcet

Behcet´ ´s Disease (Int. Study Group for BD 1990) s Disease (Int. Study Group for BD 1990)

• Acute retinal necrosis (Holland et al. 1994)

Acute retinal necrosis (Holland et al. 1994)

• Vogt

Vogt-

• Koyanagi

Koyanagi-

• Harada Syndrome (Read et al. 2001)

Harada Syndrome (Read et al. 2001)

• Birdshot chorioretinopathy (Levinson et al. 2006)

Birdshot chorioretinopathy (Levinson et al. 2006)

• Sarcoidosis (Herbort et. al 2009)(validation ongoing)

Sarcoidosis (Herbort et. al 2009)(validation ongoing)

• Vasculitis (International Uveitis Study Group, ongoing)

Vasculitis (International Uveitis Study Group, ongoing)

• Tuberculosis (Indian Uveitis Society, ongoing)

Tuberculosis (Indian Uveitis Society, ongoing)

Diagnostic Criteria Diagnostic Criteria

• SUN

SUN-

• Project

Project

• purpose: development of a structured terminology

purpose: development of a structured terminology for classification for classification

• to standardize terms and criteria

to standardize terms and criteria

• 28 entities

28 entities

• worldwide project

worldwide project

• Douglas Jabs, NYC, and the SUN

Douglas Jabs, NYC, and the SUN-

• Working Group

Working Group

Grading Systems Grading Systems

• SUN

SUN -

• various parameters

various parameters

• AC cells

AC cells – – IUSG, SUN IUSG, SUN

• AC flare

AC flare – – Laser Laser-

• flare

flare-

• photometry (not validated)

photometry (not validated)

• vitreous haze

vitreous haze

• NIH grading scale

NIH grading scale

• Janet Davis photographically

Janet Davis photographically

• macular edema

macular edema – – OCT (not evaluated) OCT (not evaluated)

• Disease activity Scores

Disease activity Scores

• Behcet

Behcet´ ´s Disease (Ben Ezra et al) s Disease (Ben Ezra et al)

Treatment Options Treatment Options

• Corticosteroids

Corticosteroids

• topical (anterior uveitis, AC cells)

topical (anterior uveitis, AC cells)

• subconjunctival (massive anterior uveitis)

subconjunctival (massive anterior uveitis)

• parabulbar (all uveitis, macular edema)

parabulbar (all uveitis, macular edema)

• intravitreal (mostly intermediate/posterior uveitis)

intravitreal (mostly intermediate/posterior uveitis)

• systemic (all uveitis, macular edema)

systemic (all uveitis, macular edema)

Treatment Options Treatment Options

• Immunosuppressives (systemic) (most off label)

Immunosuppressives (systemic) (most off label)

• Cyclosporine A

Cyclosporine A

• Methotrexate

Methotrexate

• Azathioprine

Azathioprine

• Mycophenolate mofetil, Mycophenolic acid

Mycophenolate mofetil, Mycophenolic acid

• various others (Tacrolimus, Cyclophosphamide)

various others (Tacrolimus, Cyclophosphamide)

Treatment Options Treatment Options

• Biologicals (often off label)

Biologicals (often off label)

• anti

anti-

• TNF

TNF-

• alpha (Etanercept, Infliximab, Adalimumab)

alpha (Etanercept, Infliximab, Adalimumab)

• Rituximab (anti

Rituximab (anti-

• CD 20)

CD 20)

• Daclizumab (anti

Daclizumab (anti-

• IL2

IL2-

• receptor, anti

receptor, anti-

• CD25)

CD25)

• Canalimumab and Anakinra (anti

Canalimumab and Anakinra (anti-

• IL

IL-

• 1, autoinflamm., JIA)

1, autoinflamm., JIA)

• Interferons

Interferons

• alpha

alpha-

• interferon 2a (esp. Behcet

interferon 2a (esp. Behcet´ ´s Disease, CME) s Disease, CME)

• beta

beta-

• interferon (intermediate uveitis, MS ass.)

interferon (intermediate uveitis, MS ass.)

Problems of current Medication Problems of current Medication

• very few on label (steroids, CsA, Osurdex)

very few on label (steroids, CsA, Osurdex)

• Side effects

Side effects

• corticosteroids (but: intravitreal appl., receptor

corticosteroids (but: intravitreal appl., receptor-

• specific)

specific)

• immunosuppressives

immunosuppressives

• costs

costs

• not well established for children

not well established for children

Unmet medical Needs Unmet medical Needs

• no optimal treatment against macular edema

no optimal treatment against macular edema

• better outcome measures

better outcome measures

• more specific for the uveitis entity

more specific for the uveitis entity

• lab parameters (regulatory T

lab parameters (regulatory T-

• cells, interleukin levels?)

cells, interleukin levels?)

• is more specific (targeted) treatment really effective?

is more specific (targeted) treatment really effective?

• more immunosuppressives on label

more immunosuppressives on label

• steroid alternative for anterior uveitis

steroid alternative for anterior uveitis

• topical monoclonal ab

topical monoclonal ab´ ´s (?) s (?)

Endpoints (EP) for Uveitis Studies Endpoints (EP) for Uveitis Studies

When is suppression of inflammation judged When is suppression of inflammation judged clinically meaningful? clinically meaningful?

• anterior uveitis

anterior uveitis

• reduction of 2 steps (e.g. 3+ to 1, 2+ to 0.5)

reduction of 2 steps (e.g. 3+ to 1, 2+ to 0.5)

• intermediate and posterior uveitis

intermediate and posterior uveitis

• vitreous haze: 2 steps reduction

vitreous haze: 2 steps reduction

• macular edema

macular edema

• reduction (amount not defined, complete resolution optimal)

reduction (amount not defined, complete resolution optimal)

• all types of uveitis

all types of uveitis

• visual acuity: improvement for 2

visual acuity: improvement for 2-

• 3 lines (15 letters)

3 lines (15 letters)

• sparing of steroids (10 mg of prednisolone or less)

sparing of steroids (10 mg of prednisolone or less)

EPs for anterior Uveitis EPs for anterior Uveitis

• primary EP

primary EP

• active: AC

active: AC-

• cells (3 months)

cells (3 months)

• inactive: recurrence rate (optimal 1 year!)

inactive: recurrence rate (optimal 1 year!)

• secondary EP

secondary EP

• visual acuity

visual acuity

• AC

AC-

• cells (6 months), AC

cells (6 months), AC-

• flare (Laser

flare (Laser-

• Flare

Flare-

• Photometry)

Photometry)

• sparing of steroids

sparing of steroids

• macular edema (OCT, FLA)

macular edema (OCT, FLA)

• Quality of Life (NEI VFQ

Quality of Life (NEI VFQ-

• 25)

25)

EPs for intermediate/posterior Uveitis EPs for intermediate/posterior Uveitis

• primary EP

primary EP

• active: vitreous haze (3 months)

active: vitreous haze (3 months)

• inactive: recurrence rate (6 months, optimal 1 year!)

inactive: recurrence rate (6 months, optimal 1 year!)

• secondary EP

secondary EP

• visual acuity

visual acuity

• sparing of steroids

sparing of steroids

• macular edema (OCT, FLA)

macular edema (OCT, FLA)

• AC

AC-

• cells (3, 6 months),

cells (3, 6 months),

• Quality of Life (NEI VFQ

Quality of Life (NEI VFQ-

• 25)

25)

Conclusion Conclusion

• „

„Uveitis Uveitis“ “ is a heterogenous group of diseases is a heterogenous group of diseases

• features, treatment and prognosis depend on the

features, treatment and prognosis depend on the etiology etiology

• treatment primarily based on steroids or off

treatment primarily based on steroids or off label immunosuppressives (side effects) label immunosuppressives (side effects)

• better definition of entities and endpoints

better definition of entities and endpoints

• more randomized controlled trials

more randomized controlled trials

• growing interest in uveitis studies

growing interest in uveitis studies

Our Wishes for Studies Our Wishes for Studies

• Well defined uveitis entities for inclusion

Well defined uveitis entities for inclusion

• so probably specific endpoints dep. on etiology

so probably specific endpoints dep. on etiology

• longer follow up studies (recurrences: 1 year)

longer follow up studies (recurrences: 1 year)

• children should also be involved in studies

children should also be involved in studies

• EP: OCT, Laser

EP: OCT, Laser-

• Flare

Flare-

• Photometer (validation needed)

Photometer (validation needed)

• Study reembursement should reflect the work we do

Study reembursement should reflect the work we do

Our Message Our Message

• Damage tends to develop with

Damage tends to develop with inflammatory activity inflammatory activity

• Control of this is the most important goal

Control of this is the most important goal

• f our treatment
• f our treatment
• Endpoints should reflect activity of

Endpoints should reflect activity of inflammation inflammation

• Visual acuity is not always a good EP

Visual acuity is not always a good EP

Thanks to Thanks to

• Ilknur Tugal

Ilknur Tugal-

• Tutgun, Istanbul

Tutgun, Istanbul

• Marc DeSmet, Lausanne

Marc DeSmet, Lausanne

• Andrew Dick, Bristol

Andrew Dick, Bristol

• Carlos Pavesio, London

Carlos Pavesio, London

• Denis Wakefield, Sydney

Denis Wakefield, Sydney

• Aniki Rothova, Amsterdam

Aniki Rothova, Amsterdam

• Doug Jabs, New York City

Doug Jabs, New York City