Uveitis

Jean Deschênes, MD, FRCSC

Professor of Ophthalmology

McGill University

Uveitis (intraocular inflammation)

Anterior uveitis

Intermediate uveitis

Posterior uveitis

Panuveitis

Etiology

Infectious

Non-infectious

800 consecutives cases

Incidence rate of 56 per 100,000 person-years.

Prevalence rate of 112 per 100,000 person-years.

July 1, 2004 to June 30, 2007. Incidence and prevalence rates calculated with

dynamic population model from the general ophthalmology clinic MUHC-RVH.

800 consecutives cases

AnteriorUveitisN= 434

(54.25%)

Intermediate Uveitis N= 206

(25.75%)

Posterior Uveitis N= 49

(6.12%)

Panuveitis

N= 111

(13.88%)

Total

N= 800

(100%)Mean age at presentationand Standard Deviation

41.73 18.76

42.98 19.75

40.04 18.74

47.50 21.57

Females240

(55.30%)

130

(63.11%)

33

(67.35%)

64

(57.66%)

467

(58.37%)

Males194

(44.70%)

76

(39.89%)

16

(32.65%)

47

(42.34%)

333

(41.63%)

800 consecutives cases

15

80

1

88.8

38.8

57.1

10.8

66.7

0

10

20

30

40

50

60

70

80

90

100

% P

ati

en

ts

ANTERIOR INTERMEDIATE POSTERIOR PANUVEITIS

INFECTIOUS NON-INFECTIOUS

Uveitis

Accounts for 10-15% of blindness

in Canada and USA

Acute anterior uveitis

Focal area of inflammation

S

I

CB

I

C

Systemic lupus erythematosus. This patient has

scleritis and an associated intraocular

inflammation with a fibrinous pupillary

membrane

SYSTEMIC ASSOCIATIONS OF UVEITIS

1. Spondylarthropathies

• Systemic features

• Ocular features

2. Juvenile idiopathic arthritis (JRA)

3. Sarcoidosis

4. Behçet disease 5

5. Vogt-Koyanagi-Harada syndrome 5

7. Tubulointerstitial nephritis and uveitis

6. Inflammatory bowel disease

• Ulcerative colitis

• Crohn disease

• Systemic features

• Ocular features

Spondylarthropathies

70% males 95% 30%

90% males 60% 20%

equal 30% 10%

Ankylosing

spondylitis

Reiter syndrome

Psoriatic arthritis

Gender Acute uveitis HLA-B27

Spondylarthropathies

Sacroiliitis Peripheral arthritis Bowel inflammation

100% 20% Common

60% 100% Uncommon

30% 100% Occasional

Ankylosing spondylitis

Reiter syndrome

Psoriatic arthritis

Clinical features of Reiter syndrome

Conjunctivitis Painless oral ulceration

Urethritis and circinate balanitis

Keratoderma blenorrhagica Nail dystrophy

Plantar fasciitis

Juvenile idiopathic arthritis Pauciarticular Polyarticular Systemic (60%) (20%) (20%)

< 5 > 4 Variable

< 6 years Variable Variable

Absent Mild or absent Severe

Joints no.

Onset

Systemic features

Positive ANA

Ant. uveitis 20% 5% Absent

75% 40% 10%

High risk factors for uveitis

• Girls

• Pauciarticular

• ANA +

• HLA-DR5

• Early onset

Complications of uveitis

Posterior synechiae - 30% Cataract -20%

Glaucoma due to PAS - 15% Band keratopathy - 10%

Sarcoidosis

Systemic Features of Sarcoidosis

1. Multisystem non-caseating granuloma

2. More common in blacks than whites

3. Presentation • Acute - third decade

• Insidious - fifth decade

4. Organ involvement

• Lungs - 95%

• Thoracic lymph nodes - 50%

• Skin - 30%

• Eyes - 30%

Acute sarcoidosis

Erythema nodosum

Hilar lymphadenopathy Parotid enlargement Facial palsy

Classification of sarcoid lung lesions

Stage 1

Hilar Lymphadenopathy

Stage 2

Hilar Lymphadenopathy

and parenchymal

infiltrates

Stage 3

Parenchymal

Infiltrates alone

Stage 4

Fibrosis and

Bronchiectasis

Sarcoid skin lesions

On face, buttocks and extremities

Indurated, purple-blue lesions

Granulomata Lupus pernio

Anterior segment lesions in sarcoidosis

Conjunctival granuloma Lacrimal gland involvement and dry eyes

Anterior uveitis in sarcoidosis

In young patients with acute sarcoid In older patients with chronic sarcoid

Acute non-granulomatous Chronic granulomatous

Posterior segment lesions in sarcoidosis

Subtle periphlebitis Candlewax drippings

Neovascularization Vitritis and snowballs

Fundus granulomata in sarcoidosis

Retinal and preretinal Choroidal Optic nerve head

Behçet Disease 5

1. Idiopathic multisystem disease

2. Presentation - third to fourth decade

3. Most prevalent in Mediterranean region and Japan

4. Associated with HLA-B5 in Turkey and Japan

5. Major diagnostic criteria

• Oral aphthous ulceration (100%)

• Genital ulceration (90%)

• Skin lesions (80%)

• Uveitis (70%)

Mucocutaneous ulceration in Behçet disease

Oral aphthous ulceration Genital ulceration

Skin lesions in Behçet disease

Erythema nodosum Acneiform

Lines after stroking skin (dermatographism)

Pustule after scratching skin (pathergy test)

Vascular lesions in Behçet disease

Migratory thrombophlebitis of extremities

Obliterative thrombophlebitis of major internal veins

Uveitis in Behçet disease

Acute anterior uveitis Retinitis

Diffuse leakage Occlusive periphlebitis

Signs of Vogt-Koyanagi syndrome

Granulomatous uveitis

Alopecia

Poliosis Vitiligo

Harada syndrome

Multifocal sensory retinal detachments

Multifocal choroiditis Exudative retinal detachment

Progression of Harada disease

Inflammatory bowel disease

Large bowel ulceration Stricture and ‘rose thorn’ ulceration

Crohn disease Ulcerative colitis

Uveitis - common Uveitis - uncommon

Tubulointerstitial nephritis and uveitis (TINU)

Hypersensitivity reaction to drugs • Good response to steroids

Most frequently affects women and children

Bilateral, recurrent anterior uveitis

• Proteinuria and renal failure

Renal histology Urine

Inactive syphilitic interstitial keratitis with ghost

vessels and diffuse corneal scarring.

Syphilis

• Uncommon, bilateral in 50%

Initially may be associated with dilated vessels (roseolae)

Becomes chronic unless treated

Anterior uveitis

• Infection with spirochaete Treponema pallidum

• Uveitis may occur during secondary and tertiary stages

Posterior syphilitic uveitis

• May be bilateral • Frequently juxtapapillary or central

Unifocal chorioretinitis

• May be bilateral

• Residual choroidal atrophy & RPE changes

Multifocal chorioretinitis

• Optic atrophy, vascular non-perfusion and RPE changes

Inactive neuroretinitis

• Usually unilateral • Disc oedema, macular star and cotton wool spots

Acute neuroretinitis

Treatment of Intraocular

Inflammation (Uveitis)

R/O infectious diseases

Prevent iatrogenic disease

Knowledge of immunology will

allow better treatment

C

S

I

CB

Corticosteroids

Intraocular implants

Toxicity from medications

Topical medications

have systemic effects!

Immunosuppressive Drugs

• Alkylating agents

– Cyclosphosphamide

– Chlorambucil

• Antimetabolites

– Azathioprine

– Mycophenolate Mofetil

– Methotrexate

• Antibiotics

– Cyclosporine

– 1-2 mg/kg/day, p.o., I.V.

– 0.1 mg /kg/day, p.o.

– 1-2.4 mg /kg/day, p.o.

– 1 g BID, p.O.

– 2.5-15 mg every 1-4

weeks.

– 2.5-5.0 mg /kg/day, p.o.

I.V. Immunoglobulins

1 gramme/Kg

Premedicate with

antihistaminic

Slow infusion

D5W

Biologic agents: Ethernacept, Remicade,

Humira, etc.

2004

2006

S.F.

Before and after Remicade

Efficacy of anti-TNF in AAU: A

retrospective study (Guignard et al. Ann Rheum Dis 2006; 65: 1631)

Mean No AAU Flares per 100

patient years

Pre-Tx Post-Tx

NNT [95%CI]

ETN 54.6 58.5

IFN 47.4 9.0** 3 [2-4]

ADA 60.5 0*

NNT Number needed to treat to avoid 1 AAU flare per patient per year.

NB. 2 patients developed first episodes of AAU whilst receiving ETN

Anti-TNF Structure – Clinical Considerations ?

Etanercept and Infliximab in Uveitis

Braun et al. Arthritis Rheum 2005; 52 (8):2447–51.

ETA vs IFX (P=0.08=NS)

15.6

7.9

3.4

6.8

-

5

10

15

20

Placebo ETA IFX All Anti-TNFs

Uve

itis

Fla

res

pe

r 1

00

Pt

Y

ea

rs

Anti-TNF mAntibodies Reduce Flares

of Uveitis in Spondyloarthropathy

Guignard et al. Ann Rheum Dis. 2006 ;65(12):6131-4.

P=0.03 P=0.92 P=0.0008

Mean # Uveitis flares per 100 patient years

51.8 50.654.6

21.4

6.8

58.5

0

10

20

30

40

50

60

70

80

All anti-TNFs

(n=46)

Anti-TNF

Antibodies (IFX +

Ada n=33)

Soluble TNF

Receptor

(Etanercept

n=13)

Prior Anti-TNF

During Anti-TNF

uveit

is f

lare

s /

100 p

t-yrs

15.2 yr

1.2 yr

16.7 yr

1.2 yr

11.5 yr

1.2 yr

Mean

Treatment

Duration

Before anti-TNF

After anti-TNF

New Acute Anterior Uveitis (AAU) Flares

in SpA Pts Treated with Anti-TNF

Ibanez. ACR 2006 Abstract 1118

0.417

0.095

0.6440.638

0.0

0.5

1.0

Infliximab Etanercept

Pre-RX Pre-RX Post-RX Post-RX

P=0.045

# of flares per patient pre-

and post-treatment

9.63

4.22

25

9.61

0.0

5.0

10.0

15.0

20.0

25.0

30.0

Infliximab Etanercept

Incidence of AAU / 100 pt-yrs

pre- and post-treatment

Infliximab SpA patients showed an improvement in the

frequency of AAU flares, this was not seen in patients

receiving etanercept

Pre-Rx Pre-Rx Post-Rx Post-Rx

Feeding of antigens

Antigens enter local

lymph nodes

through lymphatic

vessels

Antibody response

Interleukin 10 produced by Th 2

prevents expression of IFN

and decreases Th1 response

Suppression of DTH

IFN secreted by Th1 cell

prevents expression of

antibody response

Suppression of Th2 response

Uveitis (intraocular inflammation)

Anterior uveitis

Intermediate uveitis

Posterior uveitis

Panuveitis

Etiology

Infectious

Non-infectious