Uveitis - McGill University · Uveitis (intraocular inflammation) Anterior uveitis Intermediate...
Transcript of Uveitis - McGill University · Uveitis (intraocular inflammation) Anterior uveitis Intermediate...
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