Download 8/4/14 1 “Doc I have eyeritis” Uveitis front to back Brian E. Mathie

8/4/14 1
“Doc I have eyeritis”
Uveitis front to back
Brian E. Mathie. OD, FAAO
2
Demographics
•  Most commonly in patients 20-59 years old
•  5-10% in pts<16yo
•  Males = Females
•  All races affected equally
•  Ocular history—prior episodes and their treatment; surgery;
trauma
3
Uveitis
•  3rd most common preventable cause of blindness in US
•  Anterior uveitis most common form (8:100,000)
•  Anterior uveitis etiology known in 50% of cases
4
Etiologies
85 causes
•  50% idiopathic conditions
•  20% trauma
•  20% systemic
•  10% local (H Zoster, Toxoplasmosis, etc)
5
Etiologies
6
Idiopathic
•  Implies that all other potential causes have been evaluated and
appropriately ruled out
7
Symptoms
•  Redness
•  Aching pain
•  Photophobia
•  Tearing
•  Pain with accommodative tasks
•  Browache
1 •  Implies that all other potential causes have been evaluated and
appropriately ruled out
7
Symptoms
•  Redness
•  Aching pain
•  Photophobia
•  Tearing
•  Pain with accommodative tasks
•  Browache
8/4/14 •  download immunologic history form at http://www.uveitis.org/
Enhanced/Review/ques.htm
8
Clinical Findings
•  Circumlimbal injection, not always present
•  Eyelids may be involved
•  Corneal precipitates and edema
•  Fixed and/or irregular pupil
•  Varying IOP
• initial decrease due to inflammation of ciliary body
• possible future increase due to decreased outflow
• no change in pressure
•  Cells and/or flare, rarely a hypopion
•  Band keratopathy, cataract
•  Posterior synechia
•  Retina-r/o detachment, cystoid macular edema (CME)
9
Summed Ocular Inflammation Score (SOIS)
Anterior chamber cell grading:
0 for 0 cells,
0.5 for 1-5(trace)
1 for 6-15,
2 for 16-25,
3 for 26-50, and
4 for >50
10
Masquerade syndromes
•  Pigment dispersion syndrome
•  Pseudoexfoliation
•  Acute angle closure—also has corneal edema, IOP, pupil
irregularity
•  Intraocular melanoma
•  Intraocular/Orbital lymphoma
2 4 for >50
10
Masquerade syndromes
8/4/14 •  Pigment dispersion syndrome
•  Pseudoexfoliation
•  Acute angle closure—also has corneal edema, IOP, pupil
irregularity
•  Intraocular melanoma
•  Intraocular/Orbital lymphoma
•  Corneal ulcers
•  Retinal detachment—AC cells imply subacute or chronic
timeframe
11
Classification
•  Timing
– Acute vs Chronic or insidious
•  Course
– Limited (<3 months)
– Persistent(>3 months)
12
Timing
•  Acute
– Sudden onset and limited duration
•  Recurrent
– Repeated events > 3 months between occurrence
•  Chronic
– Persistent
– Relapses after < 3 months off treatment
13
Classification
Anatomical Location
•  Anterior (Anterior Chamber)
– Usually idiopathic or HLA B27 (-)
•  Intermediate (Ciliary Body)
•  Posterior (Retina and Choroid)
•  Panuveitis (All structures)
14
New Treatment
The FDA has granted AbbVie’s adalimumab (Humira) orphan drug
designation for the treatment of non-infectious intermediate,
posterior, or pan-uveitis, or chronic non-infectious anterior uveitis.
•  AbbVie is investigating the efficacy and safety of the drug for the
treatment of non-infectious uveitis, which is currently in phase III
development.
•  The drug is not currently approved to treat any form of uveitis.
3 •  Panuveitis (All structures)
14
New Treatment
8/4/14 The FDA has granted AbbVie’s adalimumab (Humira) orphan drug
designation for the treatment of non-infectious intermediate,
posterior, or pan-uveitis, or chronic non-infectious anterior uveitis.
•  AbbVie is investigating the efficacy and safety of the drug for the
treatment of non-infectious uveitis, which is currently in phase III
development.
•  The drug is not currently approved to treat any form of uveitis.
MAY 27, 2014
15
Anatomical Classification
•  Based on where the primary cause is located- edema of optic
nerve or CME doesn’t count
16
Classification
•  Granulomatous
– Mutton Fat keratic precipitates
– Often involves systemic or autoimmune conditions, syphilis,
Lyme disease, TB, toxo, sarcoid, herpetic
– Nodules-Koeppe, Bussaca and Berlin
•  Nongranulomatous
– Anterior chamber
– Small cells, small KP
– Idiopathic
– HLA B27
– sarcoid, herpetic, Fuchs
17
IOP/ Iris Clues
•  Decreased in acute phase
•  Increased in herpetic etiologies
o HSV-diffuse iris atrophy
o HZO-sectoral iris atrophy
o Fuch’s-pigment loss on iris
o Rubella Virus?
18
Exam
•  Look posterior to cells
•  Lens-cataract
•  Vitreous-cells, debris, haze
•  Retina-infiltrates, necrosis, retinitis, detachment
•  Choroid-infiltrates, scarring
•  Optic Nerve-edema is common
4 o Fuch’s-pigment loss on iris
o Rubella Virus?
18
Exam
•  Look posterior to cells
•  Lens-cataract
•  Vitreous-cells, debris, haze
•  Retina-infiltrates, necrosis, retinitis, detachment
•  Choroid-infiltrates, scarring
•  Optic Nerve-edema is common
19
Treatment
•  Topical Steroid
– 1% prednisolone acetate is the gold standard
– Q15min to Q1h
– Need night time coverage (gel, ung)
– Soft steroids only ones approved for iritis but not 1st choice
– Taper 2-4 weeks, at least as long as presentation
– Durezol: half dosing vs prednisolone acetate
– Lotemax: for very long tapering
20
Treatment
Based on classification of uveitis
8/4/14 •  Anterior Uveitis=Iritis=Anterior Cyclitis-idiopathic
•  Intermediate-peripheral retina, pars plana and vitreous, only 4-8%
of uveitis cases
– 69% idiopathic, 22% Sarcoid
•  Posterior- highest risk of vision loss
21
NSAIDs
•  Topical NSAID
– May help with pain, reduce CME
– Nevenac (nepafenac0.1%) TID
– Xibrom (bromfenac) BID
– Bromday (bromfenac) QD
22
Cycloplegics
•  Cycloplegics
– 5% homatropine BID or TID
– 0.25% scopolamine BID
– 1% atropine –avoid in most all cases to avoid synechia
5 8/4/14 22
Cycloplegics
•  Cycloplegics
– 5% homatropine BID or TID
– 0.25% scopolamine BID
– 1% atropine –avoid in most all cases to avoid synechia
23
Glaucoma medications
•  Alphagan/alpha agonists favored
•  CAI’s only fair;
•  Beta blockers often contraindicated
•  Avoid prostaglandins and pilocarpine
24
Treatment
•  Uveitic Glaucoma
– 0.5% timolol BID (Betimol, Istalol, Timoptic (XE))
– 0.1 % brimonidine TID (Alphagan)
•  Contraindicated Treatment
– Pilocarpine
– Prostaglandin Analogs
25
NSAIDs
•  Topical NSAID may help in pain management
•  May also reduce CME
26
Steroid injections
•  Subtenon Triamcinolone
•  .5cc Kenalog
– repository
– Side Effects
• infection
• cataract (17.5%)
• ocular hypertension (36%)
• hemorrhage
• retinal detachment
•  Intraocular Steroid Injection
27
Orals
•  Orals—ibuprofen 600-800mg t.i.d. acutely;
•  consider Celebrex for prophylaxis in chronic or recurrent cases;
•  Refer for oral steroids IF systemic
~ 60 mg/day baseline dosage
6 • cataract (17.5%)
• ocular hypertension (36%)
• hemorrhage
• retinal detachment
•  Intraocular Steroid Injection
27
Orals
•  Orals—ibuprofen 600-800mg t.i.d. acutely;
•  consider Celebrex for prophylaxis in chronic or recurrent cases;
•  Refer for oral steroids IF systemic
~ 60 mg/day baseline dosage
28
If Advanced
•  Immunosuppressives
– Methotrexate, cyclosporine et al.
•  Injectable cytokine blockers
– Remicade, Enbrel, and Humira (newer) use is increasinging
from systemic to ocular arena in sight threatening cases.
Zenapax (newest)
29
When to order testing
•  Recurrent
•  Bilateral presentation
•  Positive findings with review of systems
•  Granulomatous findings
•  Involvement of the posterior aspect
•  Severe
30
Lab testing for systemic disease
•  CBC - Complete Blood Count
•  CRP - C Reactive Protein
•  ESR - Erythrocyte Sedimentation Rate
•  HLA B-27 - Human Leukocyte Antigen
•  ANA - Anti-Nuclear Antibody (Lupus)
•  RPR - Rapid Plasma Reagin (Syphilis)
•  FTA- ABS - Fluorescent treponemal antibody absorbtion test
(Syphilis)
•  ACE - Angotenesin converting enzyme (Tuberculosis)
•  PPD - Purified protein derivative (Tuberculosis)
•  RF - Rheumatoid factor (Rheumatoid Arthritis)
31
Etiologies
•  idiopathic
•  ocular trauma
•  ocular surgery
8/4/14 7 •  PPD - Purified protein derivative (Tuberculosis)
•  RF - Rheumatoid factor (Rheumatoid Arthritis)
31
Etiologies
•  idiopathic
•  ocular trauma
•  ocular surgery
•  systemic inflammatory disease
32
Systemic disease
Clues
•  repeating cases
•  abnormally aggressive
•  unresponsive to treatment
•  bilateral
•  alternating unilateral recurrences
33
Systemic Diseases
•  HLA – B27
– ankylosing spondylitis
• 80% male
• Sacroilitis –bamboo sign on spine
• Upper lung fibrosis
– Reiter’s syndrome (Reactive Hans Conrad Reiter)
• Cant see, cant pee, cant climb a tree
– psoriatic arthritis
34
HLA-B27
– Behcet’s
• oral and genital ulcers
• 81% Asians, 13% Caucasians
• 86% develop eye disease (in Japan)
• Findings-hypopion, vitritis, ION, retinal vasculitis
• Diagnosis criteria
– Recurrent oral ulcers (3x in 1 yr) and 2 of……
» Ocular inflamation
» Skin lesions
» Recurrent genital warts
» Pathergy test
35
Systemic Diseases
•  Sarcoidosis
8/4/14 8 • Findings-hypopion, vitritis, ION, retinal vasculitis
• Diagnosis criteria
– Recurrent oral ulcers (3x in 1 yr) and 2 of……
» Ocular inflamation
» Skin lesions
» Recurrent genital warts
» Pathergy test
35
Systemic Diseases
•  Sarcoidosis
•  Multiple Sclerosis (MS)
•  Syphilis
•  Lyme Disease
•  Histoplasmosis
•  Rheumatoid Arthritis
•  Juvenile Rheumatoid Arthritis
36
Rheumatoid Arthritis
•  75% female, esp. Anglo-Saxons
•  1-3% of Americans
•  JRA now called JIA (juvenile idiopathic arthritis), follow children
more closely if younger than age 7, +ANA , HLA-DR5 +
•  antigen-antibody reaction of rheumatoid factor against IgG
triggers release of cytokine TNF-alpha
•  joint inflammation of synovial membrane and cartilage
37
Rheumatoid Arthritis
•  Check for rheumatoid factor=antibody to IgG; HLA-DR4 and/or
HLADR5
•  surface antigens present in 80% of all RA patients
•  X-rays
•  Treatment options—NSAIDS, DMARDS (disease-modifying
antirheumatologic agents) such as steroids, plaquenil, gold,
sulfasalazine, and Remicade
38
Herpes Simplex
•  Number one cause of infectious uveitis
•  85% unilateral
•  Disciform keratitis presents extra risk for uveitis…..watch IOP!
•  HSV’s big three:
– unexplained corneal scarring
– corneal desensitivity
– iris atrophy
8/4/14 9 38
Herpes Simplex
8/4/14 •  Number one cause of infectious uveitis
•  85% unilateral
•  Disciform keratitis presents extra risk for uveitis…..watch IOP!
•  HSV’s big three:
– unexplained corneal scarring
– corneal desensitivity
– iris atrophy
•  Oral treatment of herpes simplex uveitis:
– 400 mg acyclovir 5x dailyfor 7-10 days
– 500 mg valacyclovir t.i.d. for 7-10 days
– 250 mg famcyclovir t.i.d. for 7-10 days.
39
Herpes Simplex
•  Herpetic Eye Disease Study (HEDS)—prophylactic antiviral
dosing, esp. valacyclovir 500mg qd to bid for > 1 year in keratitis
and keratouveitis. Advocate oral treatment!
•  Polymerase chain reaction (PCR) to amplify and identify viral
DNA from small specimens, e.g. aqueous humor
•  Other—keratitis, blepharoconjunctivitis, trabeculitis, scleritis
40
Herpes Zoster
•  vesicular eruption along V1 by varicella virus
•  systemic treatment—Zovirax and prodrugs Valtrex and Famvir
•  topical antivirals ineffective, steroids are therapeutic cornerstone
•  monitor closely, treat aggressively—uveitis may be rapid onset,
severe
•  extra vigilance if corneal findings of spk/mucoid plaques
41
Inflammatory bowel disease
•  Crohn’s disease, ulcerative colitis
•  2 million Americans, >50% female
•  chronic intestinal inflammation mediated by TNF-alpha
UC less likely to cause uveitis than Crohn’s
•  3-10% have ocular involvement, mainly episcleritis and uveitis
•  granulomatous uveitis may be bilateral, posterior, and chronic
•  50% risk for uveitis if arthritic!
42
Seronegative spondyloarthropathies
•  ~ 350,000 Americans
•  RF negative, but HLA-B27 positive
•  Ankylosing spondylitis, reactive arthritis (formerly Reiter’s),
psoriatic arthritis, and undifferentiated form
•  Morning back pain , improved with exercise
10 •  3-10% have ocular involvement, mainly episcleritis and uveitis
•  granulomatous uveitis may be bilateral, posterior, and chronic
•  50% risk for uveitis if arthritic!
42
8/4/14 Seronegative spondyloarthropathies
•  ~ 350,000 Americans
•  RF negative, but HLA-B27 positive
•  Ankylosing spondylitis, reactive arthritis (formerly Reiter’s),
psoriatic arthritis, and undifferentiated form
•  Morning back pain , improved with exercise
•  Usually acute, unilateral uveitis
•  most common cause of hypopyon uveitis
•  most common cause of uveitis (30%) that is confirmed
43
Sarcoidosis
•  A series of inflammatory nodules, mostly lung but also eyes, joints,
skin, liver, lymphatics, spleen, and kidney; unknown origin
•  More prevelant in African-Americans and European whites
•  Often dx’d by chest x-ray and physical exam (lymphadenopathy,
fever, respiratory problems)
•  angiotensin converting enzyme (ACE), serum calcium + lysosyme,
and biopsy (characteristic coffin-shaped inflammatory cell).
•  +ACE may specify sarcoid’s presence but –ACE does not rule it
out
•  Classically bilateral
•  Frequently involves posterior segment
44
Sarcoidosis
•  Tx: steroids!
•  20% show ocular involvement: uveitis tends to be chronic,
unilateral, granulomatous, and more likely anterior/intermediate
•  Beware of EOM dysfunction, optic neuropathy, and retinal
vasculitis (candlewax drippings)
45
Fluoroquinolones
•  Association considered “probable”
•  Mean time to onset of anterior uveitis is 13 days
•  Resolves with fluoroquinolone discontinuation
46
47
11 •  Mean time to onset of anterior uveitis is 13 days
•  Resolves with fluoroquinolone discontinuation
8/4/14 46
47
48
Case 1
•  29 YOWM
•  C/O pain OD x 1 day after being hit by wire, blurry vision and
photophobia
•  SLE-injection 1+ diffuse, SPK OD, cells 1+ OD
49
Traumatic Iritis
May have photophobia in other eye
Immediate tx: cycloplegic
Testing: IOP, measure cell and flare, retinal evaluation
Prescribe: steroid if severe, cycloplegic, sunglasses
50
Longstanding Iritis
51
Post Cataract Surgical Iritis
Anterior Uveitis
•  Day 1 Gr rare to Gr 1
•  Day 7 Gr rare to trace
•  Day 28
0
52
Glaucoma and Uveitis
•  TM blocked by inflammatory cells, debris
•  TM inflamed (Posner Schlossman Syndrome)
•  Anterior synechiae
•  Posterior synechiae
•  CB inflamed
•  Steroid induced
53
Other consequences of uveitis
•  Retinal damage
•  Macular Edema
•  Cataract
54
Case presentation
June 15, 2010 – Visit #1
•  18-year-old Caucasian female
•  red and swollen right eye for 3 days
12 53
Other consequences of uveitis
•  Retinal damage
•  Macular Edema
•  Cataract
54
Case presentation
June 15, 2010 – Visit #1
•  18-year-old Caucasian female
•  red and swollen right eye for 3 days
•  throbbing pain, tearing, light sensitivity
•  POHx: contact lens wear OD only
•  PMHx: ovarian infection treated with cephalexin 500 mg PO TID
•  FMHx: (+)hypertension and diabetes
•  SHx: (+)smoking and alcohol consumption
•  Allergies: NKDA
55
Young Iritis
18YOWF Visit #1
•  VA: 20/70-1 OD, 20/20 OS
•  SLE:
– I+ - II conjunctival and episcleral injection OD
– II+ cells, I+ flare OD
– cornea clear OD/OS
– unremarkable OS
56
Young Iritis
June 15, 2010 – Visit #1
•  Assessment: Anterior Uveitis OD
•  Plan:
– Pred Forte Q 1HR OD
– Xibrom BID OD
– Follow up 1 week with DFE
57
Not So Obvious
22 YOWM
•  Mentally retarded, noncommunicative
•  Reduced vision and eye rubbing noticed by care givers
•  Clinical Findings
– Conjunctival injection GII+ circumlimbal
– Cells G III
– Flare G II+
– Ta 28 OD and 19 OS
58
Treatment
•  Pred Forte OD Q1 hr
8/4/14 13 •  Mentally retarded, noncommunicative
•  Reduced vision and eye rubbing noticed by care givers
•  Clinical Findings
– Conjunctival injection GII+ circumlimbal
– Cells G III
– Flare G II+
– Ta 28 OD and 19 OS
58
Treatment
•  Pred Forte OD Q1 hr
•  Homatropine OD BID
•  F/U in 2 days-slightly better
•  F/U in 1 week- much better, taper over 3 weeks
•  F/U 3 weeks-full blown iritis return,
59
APPROPRIATE Diagonosis
•  Retinal detachment OD with a high myope
•  Anterior and posterior uveitis secondary to retinal detachment
•  Refer to retinologist for RD repair
60
When to work up
•  Bilateral
•  Recurrent
•  Granulomatous
•  Severe
•  Posterior Synechiae
•  + Systemic involvement
•  + Physical exam findings
61
Thank You
Brian Mathie, OD, FAAO
[email protected]
8/4/14 14