CLASSIFICATION:

Anterior and Intermediate Uveitis Anatomic Location

 Anterior Uveitis
– Iritis, anterior cyclitis, iridocyclitis
 Intermediate Uveitis
– Pars planitis, posterior cyclitis, hyalitis, basal
retinochoroiditis
May 1, 2009  Posterior Uveitis
Pauline T. Merrill, MD – Focal, multifocal, or diffuse choroiditis,
chorioretinitis, retinochoroiditis, or neurouveitis
 Panuveitis

Pattern of Disease CLASSIFICATION

 Onset  Granulomatous vs. nongranulomatous

– Sudden vs Insidious
 Unilateral vs. bilateral
 Duration
 Patient demographics
– Limited: < 3 months
– Persistent: > 3 months  Associated signs & symptoms
 Course  Response to prior therapy
– Acute: Sudden / limited
– Recurrent: > 3 mos quiescence between episodes
– Chronic: Persistent, < 3 mos quiescence

3
4

Uveitis Questionnaire ANTERIOR UVEITIS

 Symptoms: Acute
– Pain
– Photophobia
– C j
Conjunctival
i l injection
i j i
– Decreased vision
 Chronic
– Decreased vision

5 6
 Anterior Chamber Cells
Exam: Cornea
SUN Working Group Grading
 Keratic Precipitates Grade # Cells in 1x1mm slit beam
– Granulomatous vs non
non--granulomatous 0 <1
– Pigmented vs non-
non-pigmented
0.5+
0.5+ 1–5
– Distribution
1+
1+ 6–15
• Diffuse, stellate KP – Fuchs, Toxo
2+
2+ 16––25
16
3+
3+ 26––50
26
4+
4+ >50

7
8

Anterior Chamber Flare

Exam: Iris
SUN Working Group Grading
Grade Description  Heterochromia
0 None  Nodules
1+
1+ Faint – Koeppe
2+
2+ Moderate (iris and lens details clear) – Busacca

3+
3+ Marked (iris and lens details hazy)  Synechiae

4+
4+ Intense (fibrin or plastic aqueous) – PAS
– Posterior
 Neovascularization

9 10

Slit Lamp Exam Slit Lamp Exam

Exam–– Don’t Forget . . .

 Lens  Lacrimal gland

– Cataract  Conjunctiva: nodules
• Inflammation
• Steroids
 Anterior Vitreous Cells
– white vs. pigmented
– trace – 4+

11 12
 Gonioscopy: Angle ACUTE ANTERIOR UVEITIS

 Nodules  HLA--B27
HLA
 Neovascularization – 2-6% population
 Anterior synechiae – 50
50--60% acute iritis
 Retained lens material patients
or foreign body – Males > females
– May have isolated iritis,
without systemic disease

13 14

ACUTE ANTERIOR UVEITIS: ACUTE ANTERIOR UVEITIS:

HLA--B27
HLA HLA--B27
HLA
 Ankylosing spondylitis  Reiter’s syndrome
– Low back stiffness/pain – May follow non-
non-gonococcal urethritis, or dysentery
– 5% aortitis, conduction • Chlamydia
– Sacroiliitis
defects • Ureaplasma
• Shigella
• Salmonella
• Yersinia

15 16

HLA--B27: Reiter’s syndrome

HLA HLA--B27: Reiter’s syndrome
HLA

 Major criteria:  Major criteria:

– Conjunctivitis / iritis – Keratoderma blennorrhagicum
– Urethritis – Circinate balanitis
– Polyarthritis
P l h ii

17 18
 HLA--B27: Reiter’s syndrome
HLA HLA--B27: Reiter’s syndrome
HLA

 Minor criteria:  Minor criteria:

– Oral mucosal lesions – Rash

19 20

ACUTE ANTERIOR UVEITIS:

HLA--B27: Reiter’s syndrome
HLA
HLA--B27
HLA
 Minor criteria:  Psoriatic arthritis
– Fasciitis, tendonitis, sacroiliitis, spondylitis
– Cystitis, prostatitis

Plantar fasciitis.
Pepose Holland Wilhelmus 96 21 22

ACUTE ANTERIOR UVEITIS:

ACUTE ANTERIOR UVEITIS
HLA--B27
HLA
 Inflammatory bowel  Sarcoidosis
disease

23 24
 Tubulointerstitial Nephritis and
ACUTE ANTERIOR UVEITIS
Uveitis Syndrome (TINU)
 Behcet’s  Bilateral, sudden onset, non
non--granulomatous,
– Hypopyon iritis recurrent, anterior uveitis and acute
interstitial nephritis
– Nephritis
N h iti precedes
d uveitis,
iti self-
self
lf-limited
li it d
– Uveitis prolonged, recurrent
 Second most common cause of uveitis in
children in Japan
 Female predominance (3:1), mean age onset 15 yo
 Systemically ill: fever, myalgias, fatigue
25
 Variable vitritis 26

Tubulointerstitial Nephritis and

ACUTE ANTERIOR UVEITIS
Uveitis Syndrome (TINU)
 High sed rate, anemia, mildly abnormal LFTs  Kawasaki disease
 Transient abnormal urinalysis – Mucocutaneous lymph node syndrome
 Elevated urinary beta
beta--2 microglobulin
 BUN normal, creatinine may be elevated
 Treatment
– Topical and /or systemic steroids
– Cyclosporine, methotrexate, or azathioprine for
steroid resistant / dependent uveitis
– Good prognosis Coronary Aneurysms
27 28

ACUTE ANTERIOR UVEITIS ACUTE ANTERIOR UVEITIS

 Medications  Herpes Simplex

– Rifabutin, Cidofovir, Fomiversen  Varicella Zoster

29 30
 ACUTE ANTERIOR UVEITIS ACUTE ANTERIOR UVEITIS

 Lens--induced uveitis
Lens  Posner-Schlossman syndrome
Posner-
– Phacolytic glaucoma (Glaucomatous cyclitic crisis)
– Phacoantigenic glaucoma
– Phacotoxic
Ph i glaucoma
l

 Idiopathic (~ 50%)

Macrophages & lens protein

31 32

CHRONIC ANTERIOR UVEITIS:

ACUTE ANTERIOR UVEITIS
Juvenile Idiopathic Arthritis
 Treatment  Systemic: usually pauciarticular JRA
 Highest risk (screen q3-
q3-4mos) :
– Specific treatment of any associated disorder – Girls
– ANA +
– Topical steroids – Pauciarticular
 Also at risk:
– Cycloplegia – Boys
– Pauciarticular
– HLA
HLA--B27+ (less chronic)

33 34

JIA--Associated Iridocyclitis:
JIA Juvenile Idiopathic Arthritis
Clinical Features
 Ocular symptoms: often none
 Presentation  Signs
– Asymptomatic, chronic, bilateral, NGAU – Moderate cells, chronic flare
– Band keratopathy (46%)
– Peak onset: 6 months to 4 yyears of age
g
– Posterior synechiae (58%)
– 90% following articular onset (2
(2--4 years) – Glaucoma (20%), hypotony (10%)
– 10% may precede onset of arthritis – Cataract (64%)
– Systemic/ocular inflammatory activity independent – CME, macular scar (26%)
– Optic nerve edema

Ophthalmol 2006;
113:1874-7
36
CHRONIC ANTERIOR UVEITIS: CHRONIC ANTERIOR UVEITIS:
Juvenile Idiopathic Arthritis Fuchs’ Heterochromic Iridocyclitis
 Treatment  Symptoms: none, or decreased acuity
– AC cells (do not treat flare):  Signs:
• Topical or periocular steroids
– Iris heterochromia
• NSAIDS
– Mild cell/flare
• Immunosuppressives
– Methotrexate
– Biologics: Infliximab; Adalimumab
– Band keratopathy: EDTA chelation
– Glaucoma: meds/surgery
– Cataracts: quiet 3 months
• anterior vs. pars plana approach
37 38

CHRONIC ANTERIOR UVEITIS: CHRONIC ANTERIOR UVEITIS:

Fuchs’ Heterochromic Iridocyclitis Fuchs’ Heterochromic Iridocyclitis
 Signs:  Treatment
– Diffuse stellate KP – Topical steroids (often unnecessary)
– Abnormal angle vessels – Cataract surgery – usually do well
– C
Cataract – Glaucoma
Gl may be
b difficult
diffi l to controll
– Glaucoma
– Vitritis
– Chorioretinal scars (?)
– 7 – 15% bilateral

39 40

Chronic Anterior Uveitis:

Sarcoidosis
Sarcoidosis
 Multisystem granulomatous disease  Organs most commonly involved:
 African--American > Caucasian in US (?)
African – Lungs
 Age 20 – 60 typical – Thoracic lymph nodes
– African Americans younger at presentation – Skin
Ski

 Also consider in:

– Children
– Older white females

Ophthalmol 2007;114:325-333
41 42
 Sarcoidosis: Skin lesions Sarcoidosis: Skin lesions

 Erythema nodosum  Erythema nodosum

 Nodules  Nodules
 Plaques  Plaques
 Maculopapular  Maculopapular
eruptions eruptions
 Lupus pernio  Lupus pernio

43 44

Sarcoidosis: Skin lesions Sarcoidosis: Skin lesions

 Erythema nodosum  Erythema nodosum

 Nodules  Nodules
 Plaques  Plaques
 Maculopapular  Maculopapular
eruptions eruptions
 Lupus pernio  Lupus pernio

45 46

Sarcoidosis: Skin lesions Sarcoidosis: Rheumatologic

 Erythema nodosum  Joints involved 5% of cases

 Nodules  Lytic/cystic lesions
 Plaques
 Maculopapular
eruptions
 Lupus pernio
– Indurated, violaceous

47 48
 Neurosarcoidosis Sarcoidosis: Systemic

 Anemia

 Altered liver function

 Splenomegaly

49 50

Sarcoidosis Sarcoidosis: Anterior Segment

 Ocular disease (25 - 80% of patients)  Usually granulomatous iritis

– Usually bilateral – May be nongranulomatous, esp. 1st episode
• May be very asymmetric • 67% in Doheny study
– Lacrimal involvement - dry eye  M tt -fat
Mutton-
Mutton f t KP
– Anterior uveitis most common (50 – 60%)

51 52

Sarcoidosis: Anterior Segment Sarcoidosis: Laboratory

 Koeppe & Busacca nodules – Definitive diagnosis: biopsy

• Non-
Non-caseating epithelioid granulomas
 Nodules in angle
• Conjunctiva, lacrimal gland, skin, transbronchial,
 Posterior synechiae mediastinal

 Cataract
 Glaucoma
 Hypotony

53 54
 Sarcoidosis: Laboratory Sarcoidosis: Laboratory

– CXR: hilar adenopathy – Gallium scan:

• Chest CT may be helpful in atypical cases • Increased uptake in lacrimal & salivary glands (panda sign), lungs

– ACE elevated
• Also in DM, TB, EtOH, cirrhosis, PCP, thyroid dz, burns,
histo
– Lysozyme
– Calcium
– Pulmonary Function Tests
• Decreased diffusing capacity (DLCO)
– Skin testing
• Anergy
55 • Kveim test 56

Sarcoidosis: Treatment Sarcoidosis: Treatment

 Indications:  Cataract surgery

– Uveitis
– Symptomatic pulmonary disease – Eye quiet 3 mos pre-
pre-op
 Corticosteroids
– Local – High doses systemic steroids perioperatively
• Topical, periocular, intravitreal (injection / implant)
– Systemic – Pars plana vs. anterior approach
 Other immunosuppressives
– Cyclosporine, methotrexate, chlorambucil,
azathioprine, mycophenolate mofetil
57 58

Syphilis:
Syphilis: “The Great Imitator”
Acquired
 Congenital  Primary
– Interstitial keratitis – Chancre
• Age 5 – 25 • Painless
• Bilateral  S
Secondary
d
– Chorioretinopathy – Rash (palms/soles), fever, weight
• “Salt and pepper”
loss, arthralgias
– 10% ocular involvement – iritis,
chorioretinitis

59 60
 Syphilis: Syphilis:
Acquired Acquired
 Latent – 70% untreated patients  Ocular findings
 Tertiary – Blepharitis, madarosis
– Benign (gumma) – Argyll--Robertson pupil
Argyll
– Cardiovascular – O l
Oculomotor palsies
li
– Neurosyphilis – 5-10% untreated patients – Unilateral IK
– Iritis, iris nodules
– Lens dislocation

61 62

Syphilis:
Syphilis: Laboratory
Acquired
 Ocular findings  Treponemal tests:
– Chorioretinitis, vasculitis, vitritis, CME – Positive for all stages
– Neuroretinitis, exudative RD, CNV • FTA-
FTA-ABS
• MHA
MHA--TP
– Pseudo
P d -RP
Pseudo-
 Non--treponemal tests
Non
– Often negative in tertiary syphilis, & after Rx
• RPR
• VDRL
 CSF VDRL
 Check HIV
63 64

Syphilis: Treatment CHRONIC ANTERIOR UVEITIS

 Treat uveitis as neurosyphilis  Bacterial endophthalmitis (P. acnes)

 IV Penicillin G  Anterior segment ischemia
– 2 – 4 million units q 4 hrs x 10d  Corneal allograft rejection

7/02 8/02
HM 20/40

65 66
CHRONIC ANTERIOR UVEITIS CHRONIC ANTERIOR UVEITIS

 Masquerade syndromes:  Masquerade syndromes:

– Leukemia – Leukemia
– Lymphoma – Lymphoma
– R i bl
Retinoblastoma – R i bl
Retinoblastoma
– Foreign body – Foreign body
– Caterpillar or tarantula – Caterpillar or tarantula
hair hair

67 68

INTERMEDIATE UVEITIS INTERMEDIATE UVEITIS

 Symptoms: blurred vision, floaters

 Signs:
– Vitreous cells
– Snowballs

70

INTERMEDIATE UVEITIS INTERMEDIATE UVEITIS

 Signs:  Signs:
– Snowbanks – CME

71 72
 INTERMEDIATE UVEITIS:
INTERMEDIATE UVEITIS
Differential Diagnosis
 Signs:  Sarcoidosis
– Perivasculitis
 Lyme disease
– Peripheral NV
– Vi
Vitreous hemorrhage
h h  I fl
Inflammatory
t bowel
b l disease
di
– Retinal detachment
 Intraocular lymphoma – older patients
– Cataract, glaucoma
– Kids: more AC inflammation, optic disc edema

73 74

INTERMEDIATE UVEITIS: INTERMEDIATE UVEITIS:

Differential Diagnosis Differential Diagnosis
 Toxocariasis – young, unilateral  Multiple sclerosis – granulomatous KP

75 76

INTERMEDIATE UVEITIS:
Pars Planitis
Differential Diagnosis
 Idiopathic  Epidemiology:
– “Pars planitis” if snowbank present – Teens - adults, white
– Up to 25% of children with uveitis
 Course:
– Chronic (permanent remissions rare)
– 20
20--30% mild, 40-
40-50% moderate, 20
20--40% severe
 70 – 80% bilateral at presentation

77 78
 Pars Planitis: Treatment Pars Planitis: Treatment

 None for mild disease (> 20/40, no/minimal

 Surgery
CME, no NV of snowbanks)
– Cryotherapy or laser for vascularized snowbanks
 Corticosteroids
– Topical not usually effective in phakic patients – Pars
P plana
l vitrectomy
i – dense
d vitreous
i d
debris,
b i
– Periocular – unilateral disease, children (may persistent vitreous hemorrhage
require general anesthesia)
– Systemic – Cataract extraction – pre
pre-- and post-
post-op oral steroids,
– Intravitreal steroid; Fluocinolone implant close F/U
 Other immunosuppressives • IOL may increase inflammation

– Cyclosporine, methotrexate, azathioprine,

cyclophosphamide, mycophenolate, biologics 79 80

Intravitreal Injection

81 82

83 84
 SEVERE UVEITIS
Treatment
MULTICENTER UVEITIS • Corticosteroids + immunosuppression
STEROID TREATMENT TRIAL effective
• Systemic side effects largely reversible with
dose reduction or discontinuation
Supported by the
• Rates of side effects acceptably low
National Eye Institute,
• Rates of cataract & glaucoma each
The National Institutes of Health estimated at 7 to 10%/PY
Revised 3/1/08
86

FLUOCINOLONE ACETONIDE FLUOCINOLONE ACETONIDE

IMPLANT IMPLANT
• Implanted into vitreous
• Releases drug for 2.5 to 3 years
• FDA-approved for intermediate, posterior
& panuveitis fluocinolone
acetonide implant
ganciclovir implant

• Effective (RCT v taper treatment)

• No systemic side effects
• Ocular side effects: cataracts & elevated
IOP
87 88

FLUOCINOLONE ACETONIDE FLUOCINOLONE ACETONIDE

IMPLANT IMPLANT
Outcome Time Implant Fellow eye Outcome Time Implant Fellow eye
Recurrence 1 year prior 60% 25%
2 yrs post 11% 50% Topical Rx for Enrollment 14% 11%
elevated IOP
P-value
P value <0.0001 <0.0001
2 yrs post 54% 20%
Topical corticosteroids enrollment 36% 25%
2 yrs post 28% 36% P-value <0.0001 0.002
P-value 0.05 0.0008
Filtering surgery 2 yrs post 31% 0.4%
Periocular corticosteroid 1 year prior 68% 30%
3 yrs post 40%
injections 2 yrs post 10% 45%
Cataract surgery 3 yrs post 93% 20%
P-value <0.0001 <0.0001
89 90
 MUST TRIAL MUST TRIAL
Specific Aims Design
• Compare visual outcomes between • Multicenter randomized clinical trial
implant & systemic therapy • Randomization 1:1
• Compare
p efficacy
y of two treatment
strategies • Randomized by patient (all eligible eyes
receive assigned treatment)
• Compare rates of both ocular & systemic
side effects • 125 patients per group
• Compare quality of life between treatment • Common study close out
strategies – Enrollment completed Dec 2008
– 2 years follow-up minimum
91 92

MUST TRIAL
Systemic Therapy MUST TRIAL Clinical Centers
• Prednisone 1 mg/kg/day up to 60 mg/day
• Treat until uveitis quiet or 1 month
p
• Standardized tapering g protocol
p to target
g
maintenance dose of < 10 mg/day
• Immunosuppressive agent (if needed)
individualized & chosen by clinician
• Standardized approach to using each agent &
monitoring for side effects
93 94

UVEITIS UVEITIS
Drug Costs Drug Costs
Drug Dose Annual cost ($) Drug Dose Annual cost ($)
prednisone 10 mg/day 60
adalimumab 40 mg/2 weeks 13,588
methotrexate 17.5 mg/week 394
azathioprine 150 mg/day 1 436
1,436 daclizumab infusion/4 weeks 5 817
5,817
mycophenolate 2 gm/day 8,646 infliximab infusion/4 weeks 8,991
cyclosporine (Neoral) 300 mg/day 6,699
implant 50% bilateral, lasts 2.5 years 10,950
tacrolimus 4 mg/day 5,581
80% bilateral, lasts 2.5 years 13,140
cyclophosphamide 150 mg/day 4,454
chlorambucil 8 mg/day 2,896 80% bilateral, lasts 3.0 years 10,950

95 96