Great talk about uveitis anterior uveitis and posterior uveitis for those who may have missed it or are not members of American Academy of Ophthalmology Meeting. Kudos to Dr. Lowder

1. How to Evaluate a Patient With Uveitis
Senior Instructor: Careen Yen Lowder MD PhD
Course: 238
Sunday, October 16, 2016
2:00 PM - 4:15 PM
Room: N139
Published: 10-11-16 11:44 AM
Join the conversation: #aao2016
© 2016 American Academy of Ophthalmology. All rights reserved.

2. 2016 American Academy of Ophthalmology Annual Meeting
Course Number: 238
Room: N139
Course Title: How to Evaluate a Patient with Uveitis
Instructors:
Introduction to Uveitis: James P. Dunn, MD
Anterior Uveitis: Debra A. Goldstein, MD
Intermediate Uveitis: Debra A. Goldstein, MD
Infectious Posterior Uveitis: Sunil K. Srivastava, MD
White Dot Syndromes: Emilio M. Dodds, MD
Masquerade Syndromes: Janet L. Davis, MD
Panuveitis: Careen Y. Lowder MD, PhD

3. Annual Meeting of the American Academy of Ophthalmology
2016
How to evaluate a patient with uveitis?
Careen Y. Lowder, MD, PhD
Course Outline
Sypnosis:
This course will focus on the step-by-step evaluation and differential diagnoses of
patients with uveitis by using Case Presentations to illustrate specific uveitis entities. The
course will begin with a general overview of uveitis and the Standardized Uveitis
Nomenclature (SUN) Classification system. Each course instructor will present
interesting cases as unknowns for discussion by the panel of instructors. The rationale for
ordering laboratory evaluations/ancillary tests and for the treatment plan will be
explained in detail. Attendees will have ample opportunity to participate in this
interactive course and will experience how a uveitis specialist analyzes each patient.
Presentations will include both infectious and noninfectious uveitis entities, in patients
with anterior, intermediate, posterior and pan-uveitis. Special emphasis will be given to
the newest treatment modalities. The handout will contain a detailed summary of each
instructor's presentation.
Case presentations of the following will be presented:
1. Anterior Uveitis
The clinical findings, tailored laboratory evaluation and appropriate
treatment will be described for infectious and non-infectious anterior
uveitis such as herpetic keratouveitis and HLA-B27 associated uveitis.
The rational use of topical antiviral agents, corticosteroids and
cycloplegics will be explained. The audience will learn when to use
systemic antiviral agents, immunosuppressive therapy and the newer
therapies such as anti-tumor necrosis factors.
2. Intermediate Uveitis
The differential diagnoses, laboratory evaluation and treatment of patients
with infectious and non-infectious intermediate uveitis will be reviewed.
The audience will also learn about the risks of patients with pars planitis
(intermediate uveitis without systemic associations) for development of
multiple sclerosis and sarcoidosis.

4. 3. Posterior Uveitis
Infectious
Case presentations will illustrate the different clinical presentations of the
various necrotizing retinitis syndromes. Diagnostic tests and treatment
modalities such as intravenous antiviral therapy, intravitreal implants and
oral therapy will be reviewed in detail.
White Dot Syndromes
The audience will learn to distinguish between the various white dot
syndromes through clinical examples. Prognosis and treatment of the
various entities will be discussed.
4. Panuveitis
The differential diagnosis of panuveitis will be discussed with presentation of
the most common entities such as syphilis and sarcoidosis. Case presentations
will illustrate the wide range of clinical manifestations and presentations of
these two entities. The appropriate laboratory evaluations and treatment will
be discussed.
5. Masquerade Syndromes
The masquerade syndromes are disorders that are often misdiagnosed as
chronic uveitis. Because many of the masquerade syndromes are due to
malignant processes, it is important that these syndromes be diagnosed
and promptly treated. Diagnostic and treatment modalities for primary
central nervous system lymphoma will be discussed. Other masquerade
syndromes such as intraocular foreign body, infectious entities and retinal
detachment simulating uveitis will be presented.
Panel Discussion
A panel discussion format will provide the audience with a variety of opinions from a
panel of uveitis experts. The audience will learn how to develop a differential diagnosis,
how to tailor the laboratory evaluations and why a specific treatment is chosen. This
interactive format will also allow for and encourage audience participation.

5. AAO Course 238:
Introduction to Uveitis
James P. Dunn, M.D.
Director, Uveitis Unit
Wills Eye Hospital
Philadelphia, PA

6. Disclosures
• Speakers Bureau (Abbvie, Inc.)

7. • Learn the definition of uveitis along with the
clinical signs and symptoms of uveitic
syndromes
• Learn the diagnostic approach and prognosis
for uveitic syndromes
Objectives

8. What is uveitis?
• Collection of >30 diseases characterized by
intraocular inflammation
• Technically, includes only
iritis/iridocyclitis/choroiditis
• Practically, includes
scleritis/keratouveitis/vitritis/retinitis/endopht
halmitis/even some optic neuritis and orbital
inflammation
• Multiple causes and disease associations

9. Causes of/Associations with Uveitis
• Infectious
• Genetic
• Autoimmune
• Systemic inflammatory diseases
• Neoplastic
• Post-traumatic
• “Idiopathic” (undifferentiated)

10. • Incidence: 17-52 cases/100,000 population
per year in US
• Prevalence: 57-204 persons/100,000
population
• Increases with age
• Studies limited by database, geography, and
ethnicity
Epidemiology

11. Epidemiology (con’t)
• Anterior >panuveitis>posterior>intermediate
• 50% of patients have an associated systemic
disease
• In U.S., 80% of uveitis is non-infectious
• Accounts for 10-15% of all cases of blindness
in the US

12. SUN Anatomic Classification of Uveitis

13. Demographic considerations
• age
• race
• gender
• ethnic background
• recent travel history

14. Manifestations of uveitis (anterior)
• Sclera: scleritis, episcleritis
• Conjunctiva: ciliary flush
• Cornea: edema, KP, PUK
• Anterior chamber: cells, flare, hypopyon,
heme
• Iris: synechiae, nodules, TID, atrophy, NVI,
membranes
• Angle: PAS, NVA, nodules
• Lens: cataract, phacodonesis, subluxation

15. Manifestations of uveitis (posterior)
• Vitreous: snowballs, snowbanks, cells, haze
• Retina: CME, vasculitis, necrosis, ischemia,
occlusion, scarring, NVE, detachment, atrophy
• Choroid: infiltrates, ischemia, granulomata,
CNV, folds
• Disc: glaucoma, ischemia, atrophy, edema,
NVD
• Other: glaucoma, hypotony

16. Type Primary Site Inflammation Includes
Anterior uveitis Anterior Chamber Iritis
Iridocyclitis
Anterior cyclitis
Intermediate uveitis Vitreous Pars planitis
Posterior cyclitis
Hyalitis
Posterior uveitis Retina or Choroid Focal, multifocal, or diffuse
choroiditis
Chorioretinitis
Retinochoroiditis
Retinitis
Neuroretinitis
Panuveitis Anterior chamber, vitreous,
and retina or choroid
Classification of Uveitis
From: The SUN Working Group. Am J Ophthalmol. 2005;140:510.

17. • Incidence and prevalence vary widely based
on race, age, and geography
– Behçet: Turkey and China
– Birdshot retinochoroidopathy: Western Europe
– VKH: China
– Tuberculosis and leptospirosis: India
– Viral uveitis: Middle East and France
– Toxoplasmosis: Brazil, Middle East, and France
Geography Impacts Disease
Sengun A et al. Ocul Immunol Inflamm 2005;13:45-
Rathinam SR et al. Indian J Ophthalmol 2007;55:173

18. JAMA Ophthalmol. 2013;131(11):1405-1412.
Age Impacts Disease

19. JAMA Ophthalmol. 2013;131(11):1405-1412. doi:10.1001/jamaophthalmol.2013.4237
Race Impacts Disease

20. Symptoms/signs
• pain
• redness
• photophobia
• blurred vision
• floaters
• metamorphopsia
• scotomata

21. Clinical features
• Location (anterior, intermediate,
posterior, panuveitis)
• pattern (acute, acute/recurrent, or
chronic)
• unilateral or bilateral
• granulomatous or non-granulomatous
• associated symptoms
• previous episodes
• previous therapy and degree of
response

22. Category Descriptor Comment
Onset Sudden
Insidious
Hours to days
Weeks to months
Duration Limited
Persistent
≤ 3months’ duration
> 3 months’ duration
Course Acute
Recurrent
Chronic
Sudden onset and limited duration
Repeated with episodes of inactivity without treatment ≥3
months
Persistent with relapse in <3 months after d/c treatment
Descriptors in Uveitis
The SUN Working Group. Am J Ophthalmol. 2005;140:511.

23. Grade AC Cells* AC Flare Intermediate Cell**
0 <1 None none
0.5+ 1-5 n/a 1-10
1+ 6-15 Faint 11-20
2+ 16-25 Moderate (iris & lens details clear) 21-30
3+ 26-50 Marked (iris & lens details hazy) 31-100
4+ >50 Intense (fibrin or plasmoid aqueous >100
Grading Scheme for Cells
*measured in 1x1 mm beam high intensity ** no consensus for this method
SUN Working Group. Am J Ophthalmol 2005;140:512.

24. c/o Emmett Cunningham, M.D.

25. NIH Grading of Vitreous Haze

26. Term Definition
Inactive Grade 0 cells (AC)
Worsening Activity 2-step increase in level of inflammation (AC cells, vitreous haze) or
increase from grade 3+ to 4+
Improved Activity 2-step decrease in level of inflammation or decrease to grade 0
Remission Inactive disease for ≥3months after discontinuing all treatments for
eye disease
Activity of Uveitis Terminology
From: The SUN Working Group. Am J Ophthalmol. 2005;140:513.

27. Other ways to classify uveitis
• Ocular vs. systemic
• Infectious vs. non-infectious
• Granulomatous vs. non-granulomatous
• Vision-threatening vs. non-vision-
threatening

28. • Based on history and clinical examination
– Likelihood should be in 50-65% range
• General principles:
– Do not order tests if the result will not
change your therapy
– Emphasize diagnosis of specifically
treatable diseases (especially rapidly-
progressive diseases)
– Recognize that uveitis is often idiopathic
General Principles of Workup

29. “Meaningful Use”
• Using consultations from inside and outside
your field to improve patient care); e.g., how
to
–co-manage uveitis and glaucoma
–help in systemic workup of a patient
–co-manage ocular and systemic disease

30. Non-invasive diagnostic tests
• Chest x-ray and CT scan (sarcoid/TB)
• OCT (macular edema)
• Fundus autofluorescence
• Ultrasound (if no view of posterior pole)
• Most valuable tests: careful history and exam

31. Invasive diagnostic tests
• Serology
–QuantiFERON® TB Gold in –tube test (TB)
–EIA treponemal testRPR (syphilis)
–Lyme (IgG and IgM)
–ANA (JIA)
• F/A, ICG (vasculitis, macular edema, choroidal
inflammation, CNV)
• Anterior chamber tap/vitreous biopsy
–PCR, cultures, stains (infections &
malignancy)
• Endoretinal/chorioretinal biopsy

32. Ocular Causes of Anterior Uveitis
Non-infectious
• Post-traumatic
• Post-surgical
• IOL-induced
• Lens-induced
• Fuchs iridocyclitis
• Retained IOFB
• Sympathetic ophthalmia
• Malignancy (primary)
Infectious
• Viral
– CMV
– HSV
– VZV
• Exogenous endophthalmitis
• Acute post-surgical
endophthalmitis
• Delayed-onset pseudophakic
endophthalmitis

33. Systemic Causes of Anterior Uveitis
Non-infectious
• HLA B27-associated
• JIA-associated
• Sarcoidosis
• Behcet’s disease
• V-K-H disease
• MS
• Drug-induced
• TINU
• Kawasaki disease
• Malignancy (RB, leukemia,
CNS lymphoma, mets)
Infectious
• Syphilis
• TB
• Lyme borreliosis
• Endogenous
endophthalmitis
• Post-viral
• Leprosy
• Coccidiomyocosis
• Brucellosis

34. Clinical Entity Diagnostic Tests
Idiopathic (pars planitis) None
Sarcoidosis ACE, chest radiography, biopsy (possibly), chest CT
Multiple sclerosis
MRI and neurologic consultation if history of
neurologic symptoms or optic neuritis, HLA-DR2
Lyme disease
Lyme serology (immunoglobulin [Ig]G/IgM Western
immunoblot testing) if from endemic area and/or
presence of systemic signs
Syphilis EIA, RPR
Inflammatory bowel disease GI consultation
Whipple disease GI consultation
Lymphoma
Vitreous cytology with immunophenotyping, lumbar
puncture for cytology, neuroimaging
Diseases Associated with Intermediate Uveitis

35. Diseases associated with
posterior/panuveitis
• Sarcoidosis
• V-K-H disease
• Behcet’s disease
• Retinal vasculitis
• Infectious uveitis

36. Term Definition
Inactive Grade 0 cells (AC)
Worsening Activity 2-step increase in level of inflammation (AC cells, vitreous
haze) or increase from grade 3+ to 4+
Improved Activity 2-step decrease in level of inflammation or decrease to grade
0
Remission Inactive disease for ≥3months after discontinuing all
treatments for eye disease
Activity of Uveitis Terminology
From: The SUN Working Group. Am J Ophthalmol. 2005;140:513.

37. Treatment options: corticosteroids
• Topical*
• Periocular/intravitreal injections*
• Sustained-release intravitreal implants*
• Oral*
• Intravenous*
* Indicates FDA approval

38. Treatment options: IMT
Antimetabolites
• methotrexate (oral, i.v., injectable)
• mycophenolate
• azathioprine

39. Treatment options: IMT
T-cell inhibitors
• Tacrolimus
• Sirolimus
• Cyclosporine

40. Treatment options: IMT
Cytotoxic agents
• Cyclophosphamide
• Chlorambucil

41. Treatment options: IMT
Biologics
• Anti-TNF
– Infliximab
– Adalimumab*
• Anti-CD20 (rituximab)
• Interferons
• Other
– Anti-IL-6R, IL-17A, CD80/86, IL-2R

42. Adjunctive therapy
• Anti-VEGF agents (macular edema)

43. Anterior uveitis
AAO 2016
Debra A Goldstein
Northwestern University
Chicago, Illinois

44. Disclosures
• No relevant disclosures
• I have served as a consultant for or received research support or honoraria from:
• Bausch and Lomb
• Allergan
• Abbott
• GSK
• Santen
• XOMA
• Clearside
• pSivida

45. What is uveitis?
• Heterogeneous collection of diseases
• Depending on classification, the term describes anywhere from 30 to a few
hundred different conditions
• How do we make sense of uveitis?

46. Classification of uveitis
• Anatomic
• Onset and course (acute vs. chronic)
• Infectious vs. “immune” vs malignant
• Granulomatous vs. non-granulomatous
• Isolated ocular disease or associated with a systemic diagnosis

47. Anatomic classification
• Anterior uveitis
• Primary site of inflammation is anterior chamber
• Iritis
• Iridocyclitis: cells in anterior vitreous

48. Anatomic Classification
• Intermediate uveitis
• Primary site of inflammation is vitreous
• Includes pars planitis (idiopathic)
• Posterior uveitis
• Primary site of inflammation is retina or choroid
• Panuveitis
• No predominant site of inflammation
• Inflammation in anterior chamber, vitreous and retina and/or choroid
SUN. AJO 2005;140(3):509-516

49. Anatomic classification of uveitis
• Based on site of inflammation
• Not structural complications, such as CME or disc edema
• Can occur with anterior, intermediate, posterior or pan-uveitis
AJO 2005;140(3):509-516

50. Classification of uveitis: timing
• Onset
• Sudden
• Insidious
• Course
• Limited – less than 3 months
• Persistent – greater than 3 months

51. Classification of uveitis: timing
• Characterization
• Acute
• Characterized by sudden onset and limited duration
• e.g. HLA-B27-associated
• Recurrent
• Repeated episodes activity separated by period of inactivity, off treatment, of > 3
months
• Chronic
• Persistent uveitis
• Relapse with d/c therapy
AJO 2005;140(3):509-516

52. Classification of uveitis
• Toxoplasmosis
• Herpes (including ARN and PORN)
• Syphilis
• TB
• Endophthalmitis
• Post-op or post-trauma
• Metastatic
• Immune mediated
• Malignant masquerades
• Non-malignant masquerades
Infectious Non-infectious

53. Classification of uveitis
Non-granulomatous
• Small KP
• May have small Koeppe nodules
• No Busacca nodules
• DDx includes HLA-B27,
sarcoidosis, Herpes, Fuchs’
Granulomatous
• Mutton fat KP (may leave “ghost KP”)
• Large Koeppe nodules
• Busacca nodules
• DDx includes sarcoidosis, TB, VKH, Herpes,
Toxoplasmosis

54. Case 1
• 32 year old Caucasian male
• Pain, redness, photophobia OS 7 days
• Prednisolone acetate Q2hrs for 3 days
• No improvement
• VA 20/20, 20/200

55. DDX severe, acute iritis with hypopyon
• Infectious
• ARN
• Metastatic endophthalmitis
• Post-operative endophthalmitis
• Syphilis
• Non-infectious
• HLA B-27
• Idiopathic
• Behcet’s disease

56. Case 1
• No ocular surgery or trauma, no previous episodes
• Healthy, no meds
• ROS: low back pain, worse in morning or after inactivity
• IOP 10, fundus examination limited; no retinitis
• Treatment
• Pred Forte hourly (shake well)
• Short course of PO prednisone 60 mg/day
• Work-up: HLA-B27 positive, FTA-ABS negative
• Diagnosis: HLA- B27 acute iridocyclitis, possible ankylosing spondylitis

57. HLA-B27+ iridocyclitis
• Ankylosing spondylitis
• Reactive arthritis
• Psoriatic arthritis
• IBD
• Isolated uveitis
• HLA-B27 disease is the most common identified cause of hypopyon uveitis in
North America

58. HLA-B27+ iridocyclitis
• Tends to be very severe and fibrinous
• Hypopyon common
• Typically unilateral, may alternate between eyes
• Ankylosing spondylitis more common in males
• Low back pain and stiffness, worse with inactivity
• Reactive arthritis Possible triggers: Chlamydia, Salmonella, Shigella, Yersinia

59. Inflammatory bowel disease
• Uveitis and IBD
• Ulcerative colitis: 5 – 12%
• Crohn’s disease: 2%
• Acute iridocyclitis, chronic iridocyclitis, CME, retinal vasculitis, scleritis
• Uveitis may precede bowel disease

60. HLA-B27
• 6-14% Caucasian population
• 0-4% African American population
• 1-10% of the HLA-B27+ population will develop ankylosing spondylitis
• Testing for HLA B27 not helpful if history and exam not consistent with B27 disease

61. HLA B27 uveitis
• Typically sudden onset limited duration episodes, one eye at a time
• Treat aggressively with frequent topical steroids
• Prednisolone acetate
• Brand Pred Forte works better
• Need to shake well (suspension)
• Difluprednate – Durezol
• More effective than prednisolone
• Solution rather than suspension
• Caution re IOP, especially in children (Arch Ophthalmol 2011; 128(5): 667-668)
• Typically start drops hourly
• Dilator to break/prevent synechiae
• May need short course PO prednisone

62. Case 2
• 24 year old Caucasian female
• 3 week history redness, decreased vision OS
• Diagnosed with iritis
• Referred because non-responsive to hourly topical steroids and two sub-tenon
steroid injections
• VA 20/20 OU
• Slit lamp exam: normal OD
• IOP, Fundus normal OU

64. Case 2
• Past medical history
• ALL 3 years ago; chemotherapy and radiation
• Immediate anterior chamber tap
• Diagnosis: ALL recurrence

65. Case 2: take home message
• History often suggests diagnosis
• Review of systems, PMH, family history etc
• Patients will usually not volunteer history
• Remember the masquerade syndromes
• Even without history of cancer, an eye like this requires AC tap for diagnosis

66. Case 3
• 53 year old AA female
• 2 year history of anterior uveitis OS
• On PF QID OS, Combigan BID OS
• BCVA 20/20 OD. 20/50 OS
• SLE normal OD
• IOP 12, 25
• Fundus unremarkable OU, except C/D OS>OD

68. After therapy

69. Herpes simplex iritis
• Iris atrophy
• Patchy or diffuse
• Dilated pupil
• (CJO 2009;44: 314-316)
• Often becomes chronic

70. Treatment of HSV iritis
• Oral antivirals
• Acyclovir 400 mg PO 5/day
• Valacyclovir (Valtrex) 1 gram PO TID
• Famcyclovir (Famvir) 500 mg PO TID
• Dilators
• Treat IOP
• May be very difficult to taper topical corticosteroids
• HEDS regimen: prednisolone acetate 1% 6 x day x 1 wk, QID x 2 wks,
BID x 2wks, QD x 2 wks, QOD X2 wks

71. Case 3: take home points
• Suspect herpetic uveitis
• Subacute onset, often starts with foreign body sensation
• Corneal stromal or epithelial edema
• Descemet’s folds
• High IOP on presentation
• Posterior iris atrophy (transillumination defects)
• Dilated pupil

72. Case 4
• 5 year old Caucasian female
• Mom noticed something wrong with pupil OS
• PMH nil
• ROS: right knee red and painful at age two. Treated with oral NSAIDS.
Resolved by age 3
• VA 20/20 OD, 20/25 OS
• Slit lamp
• OD: no KP, 1+ AC cell
• OS: no KP, 2+ AC cell

73. Case 4
• DDx
• JIA uveitis
• Juvenile sarcoidosis
• Blau syndrome
• Work-up
• ANA 1:1280
• ACE minimally elevated
• CXR normal

74. JIA uveitis
• Chronic
• Bilateral
• Anterior
• Typically asymptomatic (white, quiet appearing eyes)
• Usually non granulomatous

75. JIA uveitis: risk factors
• ANA positive
• Female
• Younger age at onset of arthritis
• Oligoarticular disease at presentation
• Oligoarticular disease: 10-30%
• RF negative polyarthritis: 5-10%

76. JIA uveitis: complications
• Band keratopathy
• Posterior synechiae
• Anterior synechiae
• Cataract
• Glaucoma
• Hypotony
• Amblyopia

77. JIA uveitis
• Most develop after onset of arthritis
• Highest risk within 4 years of onset of arthritis, most within 7 years
• Uveitis activity and severity not related to activity of joint disease
• Uveitis risk not reduced if joint disease in remission
• Still require screening even if joints are asymptomatic

78. Screening for uveitis in JIA patients
• High risk group
• Oligo or monoarticular arthritis
• ANA positive
• Onset ≤ 7 years of age
• Disease duration < 4 years
• Screen every 3 – 4 months

79. Screening for uveitis in JIA patients
• Moderate risk
• Onset after age 7
• ANA negative
• ANA positive, disease duration > 4 years
• Screen Q 6 months
• Low risk
• systemic onset
• ANA negative, onset after age 7
• Joint disease (no eye disease) for more than 7 years
• Screen yearly

80. JIA uveitis screening examination
• Slit lamp exam at every visit
• Band keratopathy, KP, cell/flare, synechiae, lens status
• Once patient has uveitis
• Also need IOP, fundus exam (optic nerve)
• No longer follow screening schedule
• EUA not ideal
J AAPOS 2008;12:316

81. Worse prognosis
• More severe ocular involvement at
presentation
• Longer duration of uveitis
• Younger age at disease onset
• Uveitis diagnosis prior to arthritis
diagnosis
• Over reliance on topical steroids
• Late institution of IMT

82. JIA uveitis clinical points
• JIA uveitis is a chronic disease
• Aim for long term quiescence
• Intermittent treatment may result in repeated bouts of inflammation, with
worse anatomic and visual outcomes
• Limit topical steroids
• Cataract
• Glaucoma
• Better outcome with earlier IMT
• MTX
• TNFi
• Often higher dose/frequency than for joint disease

83. Case 5
• 32 year old neurosurgeon with decreased VA OS, floaters OS, worsening over
last year
• Born in Ukraine
• Healthy, no meds
• ROS: negative
• BCVA
• 20/15 OD
• 20/30 OS
• Slit lamp exam normal OD
• IOP 12, 19
• Fundus normal OU

84. Case 5
• SLE OS
• Fine stellate KP
• 1+ cell and flare
• No synechiae
• Early PSCC
• 2+ cells in anterior vitreous

85. Fuchs heterochromic iridocylitis
• Chronic disease
• Asymptomatic
• Decreased vision (cataract)
• Floaters
• 2-3% of patients with uveitis
• Often under-diagnosed and over-treated
• 3rd – 4th decade of life
• Unilateral in > 90%
• No gender predilection

86. FHI and Rubella
• Rubella Ab in 52/52 patients with FHI (modified Goldman-Witmer
coefficient)
• Many also had positive reverse transcription polymerase chain reaction
(RTPCR) for rubella virus, (i.e. active viral replication)
• Rubella Ab in aqueous in 13/14 FHI patients (Goldman-Witmer)
• Negative titers for HSV, VZV and T.Gondii
Am J Ophthalmol 2004;138:46-54
de Groot-Mijnes, de Visser, Rothova . Am J Ophthalmol 2006;141:212–214

87. FHI and rubella: epidemiologic evidence
• Decrease in incidence of FHI in US since Rubella vaccination in 1969
• 65% reduction in FHI in patients born 1959-1968 compared to earlier
• Further 40% drop in FHI in patients born 1969-78
• Foreign born FHI increased from 24% to 55%
• Epidemiologic support for Rubella as a cause of FHI
Am. J. Ophthalmol. 2007;144:424-428

88. FHI
• Glaucoma in 30%
• Often resistant to medical therapy
• Cataract in 70 – 100%
• PSCC
• Do well with standard phaco/PCIOL (increased risk hyphema)
• Inflammation doesn’t usually require treatment
• Require follow-up to monitor for elevated IOP, nerve damage

89. Case 6
• 38 year old AA female
• Decreased vision OU for three years
• Intermittent redness OU, treated in past with topical steroids, anti-histamines,
NSAIDs
• PMH: borderline diabetes, hypertension
• Meds: OCP
• ROS: asthma since age 20, occasional skin rashes

90. Case 6
• BCVA
• 20/30, 20/40

91. Case 6

92. Case 6
• QuantiFERON negative
• Elevated ACE
• CXR normal
• CT chest hilar adenopathy

93. Sarcoidosis
• Clinical syndrome, multi organ
• Multiple possible triggers in genetically predisposed host
• Airborne triggers
• New York City Firemen 9/11
• PCR of sarcoid granulomas may reveal bacterial DNA,RNA

94. Sarcoidosis Incidence (per 100,000)
• Northern Sweden 64
• US Caucasians 11
• US African Americans 36
• US AA females 107
Am J Epidemiol.1997;145:234

95. Sarcoid ocular disease
• Skin lesions
• Lupus pernio
• Lacrimal gland
• Dry eyes
• Conjunctival granulomas
• Anterior uveitis
• Posterior or pan uveitis
• Retinal vasculitis
• Optic nerve granulomas

98. Iris nodules

101. Sarcoidosis :work-up
• ACE, lysozyme (each elevated in approx. 40% pts with biopsy proven ocular
sarcoidosis, Arch Ophthalmol. 2011;129(4):409-413)
• CXR
• CT chest with infusion (adults)
• Upper body gallium scan
• PET scan
• BAL
• Rule out TB
• TST, IGRA (QuantiFERON gold)
• Definitive diagnosis requires biopsy

103. Diagnostic yield of >60% with
directed conjunctival biopsy with
multi-plane sectioning
Bui et al. Journal of Ophthalmic Inflammation
and Infection 2014, 4:8

104. Case 7
• 32 year old Caucasian female
• Decreased VA OS with floaters
• Began 4 weeks ago, after c-section
• PMH
• Genital herpes, poor response to acyclovir
• PSH
• C-section x 2 for genital herpes
• On exam
• BCVA 20/20, 20/40
• OS small hypopyon, 2+ AV cell

106. Case 7
• Further review of systems
• Painful oral ulcers every few months, last weeks
• Frequent painful bumps on skin “like hit with baseball bat”
• Small skin lesions on scalp

107. Behcet’s disease
• Diagnostic criteria
• Recurrent oral ulceration plus two other findings
• Recurrent genital ulceration
• Ocular inflammation
• Skin lesions
• Positive pathergy test
International Study Group for Behcet’s Disease - 1990
erythema nodosum

108. Behcet’s Disease: anterior segment
• Hypopyon
• Not common (<25%)
• Short-lived
• Less pain than with HLA B-27
Shifting
• No fibrin

109. Behçet Disease
• More common worldwide in patients from “Silk Route” countries
• However in US, majority of patients likely not from silk route countries
• Do not discount diagnosis in Caucasian patients
• Ocular Immunology and Inflammation. 2012; 20(1): 12–17
• HLA B51 present in 50%
• Anterior uveitis
• Intermediate uveitis
• Posterior uveitis
• Retinitis
• Retinal vasculitis: phlebitis or arteritis
• May mimic necrotizing herpetic retinitis
• Blinding disease

110. Behcet’s disease
• Posterior segment disease
• Occlusive vasculitis (arteritis or phlebitis)
• Retinitis

111. Work-up of anterior uveitis
Acute Chronic
• HLA B27
• FTA-ABS, RPR
• CXR +/- CT chest
• ACE/lysozyme
• Urine β-2 microglobulin,
esp if bilateral
simultaneous onset
• ? Lyme titers
• ANA in children
• FTA-ABS, RPR
• CXR
• Consider CT chest
• ACE/lysozyme
• PPD
• Urine β-2 microglobulin
• ? Lyme titers
Consider syphilis, sarcoid, TB in everyone

112. Treatment of acute anterior uveitis
• Topical corticosteroids
• Pred Forte (prednisolone acetate 1%), hourly (or more) if severe
• Durezol (difluprednate emulsion 0.05%)
• Cycloplegia
• Pain relief
• Break acute synechiae
• Prevent development of new synechiae
• Longer lasting agent if dark irides, shorter if light
• Avoid depot steroids if first attack (caution re endophthalmitis)
• May need oral steroids

113. Treatment of chronic iridocyclitis
• Topical steroids – less frequent than for acute
• May need chronic dilators
• Depot steroids
• e.g. subtenon triamcinolone acetonide
• Oral steroids
• Avoid long term use
• Immunosuppressive/immunomodulatory agents

114. Treatment of chronic iridocyclitis
• Use lowest dose of anti-inflammatory agents to prevent sequelae but
decrease risk of glaucoma
• Concept of chronicity
• “chronic disease is chronic”
• Treatment may be long term
• Patients often asymptomatic
• Compliance a major issue

115. Anterior uveitis
• Examine the fundus
• Posterior segment disease can present with pain, redness, AC reaction

116. Intermediate uveitis
AAO 2016
Debra Goldstein
Northwestern University

117. Disclosures
• I have served as a consultant for or received research support or honoraria from:
• Bausch and Lomb
• Allergan
• Abbott
• GSK
• Santen
• XOMA
• Clearside
• pSivida

118. Intermediate uveitis
• Inflammation in vitreous cavity and peripheral retina
• Pars planitis: idiopathic intermediate uveitis, with snowballs and snowbanks

119. Intermediate uveitis: differential diagnosis
• Par planitis
• Other idiopathic
• MS
• Sarcoidosis
• Syphilis
• Inflammatory bowel disease
• Intraocular lymphoma (older patient)
• Toxocariasis (young patient, unilateral)
• Whipple’s disease (older patient)
• Masquerade
• Malignant
• PVRL, metastatic disease
• Non-malignant
• Vitreous hemorrhage, chronic RD

120. Symptoms of intermediate uveitis
• Floaters
• Decreased vision
• Asymptomatic

121. Pars planitis
• Subtype of intermediate uveitis
• Pathology centered in pars plana, vitreous
• Snowballs, snowbank
• Idiopathic
• A disease of children and young adults
• 5-10% of all uveitis
• 15-30% of uveitis in children

122. Pars planitis
• Insidious onset, chronic course
• Typically bilateral at presentation
• CME most common cause of decreased vision

123. Evaluation: history
• Review of systems
• Neurologic (MS, intraocular lymphoma)
• Pulmonary (sarcoidosis)
• GI symptoms (IBD, Whipple’s)
• Joints (sarcoid)
• Skin rash (sarcoidosis, syphilis, Lyme disease)
• Tick bite? Endemic area for Lyme?

124. Exam
• Vitreous cells
• Always present in active disease
• Liquid vs formed vitreous
• Vitreous snowballs
• White or yellow aggregates of inflammatory cells
• Usually inferior
• Vitreous haze
• Snowbank

128. Exam
• Snowbanking
• Pars plana/ora serrata
• Usually inferior, but may extend 360o
• Coalesced exudates or fibroglial mass in active disease
• May be vascularized
• May sometimes be seen without condensing lens
Photo courtesy of Howard Tessler

129. Active snowbanks

130. Inactive snowbanks

131. Complications
• CME
• Cataract
• Secondary to inflammation and to corticosteroids
• Glaucoma
• Secondary to inflammation and to corticosteroids
• Retinal vasculitis
• Vitreous hemorrhage
• Retinoschisis
• Amblyopia

132. CME
• Most common cause of decreased acuity in pars planitis
• May be subtle or obvious

133. Fluorescein angiography
Image courtesy of Emilio Dodds

134. Complications: disc edema
• Optic disc edema
• Seen in 50% of children
• Not all disc edema is papilledema

135. Complications: vasculitis
• Periphlebitis frequent

136. Complications: macular dragging

137. Complications
• Vitreous hemorrhage
• Usually clear spontaneously
• May be presenting finding in children
• Retinal detachment
• Rhegmatogenous
• Tractional
• Exudative

138. Complications
• Neovascularization of the disc
• Rare
• Coat’s disease-like picture: rare

140. Complications: retinoschisis

142. Retinoschisis and retinal cysts

144. Retinoschisis and RD

145. Evaluation: work-up
• ACE, lysozyme, CXR for sarcoid, consider CT chest
• FTA-ABS, RPR
• Guided by history
• IBD: GI consult, IBD serology
• MS: neurologic examination, MRI
• Lyme disease: serology, western blot
• Toxocara: serology (not that helpful)
• TB: chest imaging, PPD, QuantiFERON
• Intraocular lymphoma: MRI brain, LP, diagnostic vitrectomy

146. When to treat
• Based on symptoms
• CME, even with good vision
• Decreased vision from vitritis
• Significant floaters
• Significant vasculitis

147. Treatment options
• Intermittent local therapy
• Intraocular triamcinolone
• Periocular triamcinolone
• Short acting dexamethasone implant
• Intravitreal VEGF inhibitors (for CME, not inflammation, off-label)
• Long acting local therapy
• Fluocinolone acetonide implant
• PPV with scatter laser photocoagulation
• Systemic therapy

148. Systemic therapy
• Antimetabolites are usual first line
• Methotrexate (off label)
• Mycophenolate (off-label)
• TNFi second line
• Adalimumab (FDA approved for adults with intermediate, posterior or
panuveitis)
• Infliximab (off-label)

149. Treatment considerations
• Pars planitis is usually bilateral
• Children may be more susceptible than adults to side effects of steroids
• Cataract
• Glaucoma
• Pars planitis is a chronic disease
• Intermittent treatment may result in repeated bouts of inflammation, with
cumulative damage

150. • 36-year old female
• Long history of bilateral intermediate uveitis with CME
• Well controlled on adalimumab q2weeks and methotrexate 15 mg/week
• VA 20/20 OU, no CME
• Decided to stop all systemic therapy
Cumulative damage

151. • Opted for local therapy only
• Treated with repeated local steroid injections

153. Cumulative damage

154. Treatment considerations
• Compliance
• Concept of chronicity
• Reminder of long term goals
• Aim is to maintain excellent visual acuity, while minimizing treatment side
effects

155. Infectious Posterior Uveitis
Sunil K. Srivastava, MD
A. Herpes Retinitis (Acute Retinal Necrosis and Progressive Outer Retinal Necrosis)
I. Etiology & Clinical Presentation
a. Most commonly caused by Varicella zoster (VZV ) and Herpes simplex (HSV)
b. Classic descriptions of ARN (immunocompetent patients) and PORN (HIV+,
CD4<50) represent ends of a continuous spectrum with clinical features such as
inflammation and rate of progression driven by the degree of
immunosuppression.
c. Range of clinical presentation (examples shown)
II. Current Treatment Options
a. Valacyclovir (Valtrex), famcyclovir (Famvir), Valganciclovir (Valcyte)
b. Intravenous Acyclovir
c. Intravitreal antivirals (foscarnet and ganciclovir)
d. Combination therapy – Intravitreal foscarnet + systemic
e. Prednisone
f. Duration of Therapy
g. Prophylactic Laser?
III. Treatment Recommendations for ARN/PORN
1) Intravitreal Foscarnet 2.4 mg every 3-4 days and/or intravitreal
ganciclovir 2 mg every 5 days until retinitis inactive
2) Valacyclovir (Valtrex) 1-2 gm TID for at least 1-3 months. Valganciclovir
900 mg BID in HIV positive patients. Treatment may be longer
3) Prednisone in patients with ARN until inflammation is clearly decreasing
then taper slowly. Prednisone not used in immunosuppressed
patients
4) Unclear if prophylactic laser is beneficial
5) Vitrectomy +/- silicone oil pros/cons of early vs late PPV.
B. Cytomegalovirus Retinitis (CMV Retinitis)

156. I. Etiology and Clinical Presentation
a. Caused by Cytomegalovirus
b. Typically seen in immunocompromised patients
c. Decreasing in incidence in HIV patients, but still seen
d. Seen in other immunocompromised patients especially organ
transplantation
e. Clinical presentation
II. Treatment Recommendations
a. Valcyte 900 mg BID loading dose for 3 weeks then QD dosing
maintenance
b. In those patients where immune recovery may not occur or those
intolerant to oral therapy – ganciclovir implant
c. Intravitreal anti-virals (ganciclovir and/or foscarnet) should be
considered in macular threatening disease.
d. Treatment tailored to chances of immune recovery
e. Watch for development of immune recovery uveitis after
improvement of CD4 count
f. Resistance
C. Syphilitic Chorioretinitis
I. Etiology and Clinical Presentation
a. Caused by Treponema pallidum
b. Diagnosis based on serologic testing. Treponemal antibody testing
with non-treponemal (FTA-Abs, Syphilis antibody, with RPR or VDRL)
c. Increasing incidence in younger men
d. Seen often in HIV patients
e. Clinical presentation
II. Treatment Recommendations
a. Treat as neurosyphilis
b. IV penicillin for 10-14 days or IM penicillin daily with probenecid po
c. Test for HIV
d. Usually good visual recovery if macula spared
D. Toxoplamosis Chorioretintis
I. Etiology and Clinical Presentation
a. Caused by Toxoplasma gondii parasite
b. More than 60 million people in US infected
c. Diagnosis made by clinical presentation with presence of toxoplasmosis
antibodies or PCR positive from ocular samples
d. clinical findings include chorioretinitis with adjacent scar and
associated vitritis

157. II. Treatment Recommendations
a. Treatment indicated for posterior lesions, immunocompromised
patients. Observation is an option for peripheral disease
b. Classic triple therapy: pyrimethamine 100 mg for 1 day as a loading
dose, then 25 to 50 mg per day, plus sulfadiazine 1 gram four times per
day, plus folinic acid (leucovorin) 5-25 mg with each dose of
pyrimethamine
c. Sulfa allergy - pyrimethamine plus clindamycin is an option
d. Monotherapy – Trimethoprim/sulfamethoxazole (double strength)
BID or clindamycin 300 mg qid
e. Treatment is for 2-6 weeks
f. Intravitreal clindamycin 1 mg every 1-2 weeks has also been described
g. Oral steroids to control inflammation
E. Bartonella Associated Retinal Infections
I. Etiology and Clinical Presentation
a. Caused by Bartonella Henselae
b. Diagnosis often difficult – based on serum titers which can vary based
on timing of infection
c. Range of clinical presentations (examples shown) – neuroretinitis,
optic nerve swelling, branch retinal artery occlusion, retinitis,
granuloma, angioma like lesion
II. Treatment Recommendations
a. Unclear if antibiotic therapy is useful in these patients
b. If treated choices include doxycycline or ciprofloxacin or azithromycin
c. Oral Prednisone used to treat the inflammatory lesions in the eye.
F. Ocular Lyme disease
I. Etiology and Clinical Presentation
a. Caused by spirochete – Borrelia borgdorferi
b. Transmitted via tick bite
c. Usually occurs in areas endemic to Lyme – Northeast, Midwest,
Northwest US
d. Can involve multiple organ systems
e. Ocular disease ranges from episcleritis, keratitis to intermediate
uveitis, retinal vasculitis
f. Diagnosis based on antibody testing and confirmatory Western Blot
II. Treatment Recommendations
a. If early in course can treat with oral doxycycline, erythromycin
b. Later in course – IV penicillin or ceftriaxone
c. Treatment effect can be slow

158. d. May require multiple courses of antibiotics
e. Systemic prednisone required to treat inflammation at times
G. Ocular Toxocarasis
I. Etiology and Clinical Presentation
a. Transmitted via eating contaminated foods, soil ingestion, oral-fecal
route.
b. Rarely get visceral larvae migrans at same time or ever.
c. Eosinophilia not always present
d. 3 syndromes typically seen:
i. Leukocoria (moderate-severe vitreous infl) 2-9 yrs old
ii. Localized macular granuloma 6-14 yrs old
iii. Peripheral granuloma 6-40 yrs old
II. Treatment Recommendations
a. Antibiotics typically not used
b. Diagnosis by serological testing or fluid analysis
c. Corticosteroids commonly used to treat inflammation
d. Vitreoretinal surgery may be needed to treat some tractional cases
H. DUSN Diffuse Unilateral Subacute Neuroretinitis
I. Etiology and Clinical Presentation
a. Unilateral wipe-out syndrome
b. Baylisascaris procyonis – nematode typically infects raccoons
(Midwest)
c. Ancylostoma caninium (Southeast, Latin America) dogs
d. Immunologic rxn to nematode
e. Biphasic response
f. First – multiple grayish white dots (400-1500 um) mild vitritis and
retinal vasculitis, can see nematode
g. Second phase – RPE, optic nerve, retina – atrophy, pigmentary
disruption.
II. Treatment Recommendations
a. Laser the worm
b. Systemic medications typically not indicated, but can be used in
children

159. White Dot Syndromes
Emilio M. Dodds, M.D.
Consultores Oftalmológicos
Hospital Juan A. Fernández
Buenos Aires, Argentina
Multiple Evanescent White Dot Syndrome
Acute Posterior Multifocal Placoid Pigment Epitheliopathy
Serpiginous Choroiditis
Birdshot Chorioretinopathy
Punctate Inner Choroidopathy
Multifocal Choroiditis and Panuveitis

160. Multiple Evanescent White Dot Syndrome
Acute symptoms: visual loss (20/70 or less), visual field loss, photopsias.
Gender: female 4:1 to 10:1 Age: 10-67, average 28
Etiology: unknown, less than 50% with a flu-like syndrome.
Presentation: usually unilateral. If bilateral, it is marked asymmetric.
White dots: small gray-white patches at the RPE level (100-200 µm)
localized around the perifoveal area, rarely beyond the arcades, on close
inspection they are made up of smaller white dots.
Macula: granular appearance with orange specks, almost always present.
Optic nerve: mild hyperemia to bilateral edema, +APD, dyschromatopsia,
visual field abnormalities.
Vitreous cells: none to +1
Fluorescein angiography: early hyperfluorescence with late staining of
the white dots, early leakage from disc capillaries with late optic disc
hyperfluorescence.
ICG: hypofluorescent spots that appear early and persist into late phases.
More spots are seen than in fluorescein angiography or on clinical
examination.
ERG: reduce amplitude of the a wave (RPE) that returns to normal.
Visual field: enlarged blind spot, centrocecal scotoma, arcuate defects.
OCT: disruptions of the IS/OS junction
Autofluorescence: typically hyperautofluorescent on FAF imaging
Progression: deep retinal-RPE lesions disappear first; average 7 weeks;
macular granularity and optic nerve lesions may persist longer.
Complications: recurrences and CNVM: rare

161. Acute Posterior Multifocal Placoid Pigment Epitheliopathy
Acute loss of central vision.
Gender: male-female 1:1 Age 29 (15-40) Etiology: unknown
Clinical findings: bilateral, asymmetric
Large, multifocal, yellow white placoid lesions at the level of RPE-inner
choroid, localized mainly in posterior pole
May be associated with anterior uveitis, mild vitritis (50%), scleritis,
retinal perivasculitis, and papillitis.
Fluorescein angiography: hypofluorescence initially with late
hyperfluorescence
ICG: hypofluorescence throughout the angiogram better visualized than
in FA and clinical examination, more spots are seen.
OCT: outer retinal and RPE disruption corresponding to the lesions, and
in some cases, outer retinal cysts have been described
Autofluorescence: a spectrum of abnormalities ranging from mostly
hypoautofluorescent lesions to a mottled signal of mixed hyper- and
hypo-autofluorescence
Progression: rapid resolution (10 days) with permanent alterations of
RPE. Visual improvement may continue for several weeks or months
(80% >20/30). Clearing of the lesions begins centrally, spreads
peripherally (pigment mottling)
Associated systemic inflammatory pictures:
erythema nodosum high incidence of + PPD
thyroiditis nephropathy
viral illness vaccines: flu, hepatitis
cerebral vasculitis meningo-encephalitis
Pathophysiology: primary RPE disease vs. choroidal arteriolar occlusion
with subsequent choriocapillary non-perfusion and secondary RPE
damage.
Complications: recurrences and associated exudative retinal detachment

162. Serpiginous Choroidits
Acute visual loss if fovea is involved, otherwise asymptomatic
Gender: more common in males, young adults
Etiology: unknown
Clinical findings: bilateral disease, asymmetric
Cream color infiltrates at the level of the RPE often adjacent to old scars,
beginning from the peripapillary area and extend centrifugally. May have
mild vitritis.
Histology: disappearance of RPE and choriocapillaris, signs of
inflammation in the choroid, normal large choroidal vessels, varying
degrees of hyper-pigmentation and fibrous proliferation.
Fluorescein angiography: If inactive: early hypofluorescence due to lack
of choriocapillaris, increase hyperfluorescence and late staining of the
sclera. If active: early hypofluorescence (due to either blockage or
choriocapillaris non-perfusion) surrounded by hyperfluorescence (active
border), late hyper-fluorescence.
OCT: shows disruption of the outer retinal structures and RPE
Autofluorescence: FAF imaging reveals hypoautofluorescence in areas of
atrophy, while more active areas are typically hyperautofluorescent
Progression: relapsing and remitting disease, multiple recurrences,
recurrences can be asymptomatic (photos, amsler grid). Centrifugal
progression heals in 4 weeks even without treatment.
Visual outcome: decrease vision only if fovea is involved, late recovery
may occur even with foveal involvement, more likely if edge of the lesion
involved the fovea.
Treatment: immunosuppression directed to prevent recurrences
Rule out Serpiginous-like choroiditis (serpiginoid) due to TB

163. Birdshot Chorioretinopathy
Chronic disease with exacerbations and remissions
Epidemiology: white and healthy young adults, male/female ratio 1:1
Etiology: unknown, HLA-A29+ in >90%
Clinical findings: bilateral and symmetric disease
Multiple, uniform, small (1/4 DD), cream colored lesions at the level of
the RPE, localized mainly nasally and radiating towards the equator.
Vitritis, papillitis, retinal vasculitis and CME. Anterior inflammation
<10%.
Fluorescein angiography: spots faintly apparent in venous phases, no late
staining, capillary leakage with CME (60%), venous leakage and disc
swelling 40%.
OCT: most useful in evaluating for macular edema
Autofluorescence: The presence of macular hypo autofluorescence was
correlated with a decreased visual acuity
Progression: stabilize over 3-4 years or can become a chronic disease.
Some patients retain good vision even without treatment
Treatment: corticosteroids (oral, periocular and intraocular) and
immunosuppressive agents
Complications: epiretinal membrane, CNVM, NVD-NVE, optic atrophy,
chronic CME.

164. Punctate Inner Choroidopathy
Acute symptoms: scotoma, blurred vision, photopsias
Epidemiology: young (16-40, 27), myopic (-3 to -10), women (>90%)
Etiology: no associated systemic illness
Clinical findings: bilateral in most of the cases, only one eye may be
symptomatic
Small, discrete yellow lesions at the level of the RPE and inner choroid
(100-300 µm), localized in the posterior pole randomly, in a linear pattern
or in clusters, can have serous detachment overlying the lesion initially.
No vitreous inflammation
Fluorescein angiography: early leakage with late staining, more leakage if
associated SRD. More lesions are seen than on clinical examination.
Visual field: may have enlarged blind spot.
Progression: healing into atrophic scars in one month, progressively
pigmenting and enlarging (500 µm, same as POHS). Retain good vision
unless they develop foveal lesions or CNVM.
Complications: CNVM: 30-60% normally within the first 6 months. Fifty
percent are subfoveal, 50% extrafoveal.
Progression: One time disease (no recurrences).
OCT: hyper-reflective outer retinal nodular lesions corresponding to
clinically apparent lesions with more widespread disruption in the
surrounding outer retinal architecture
Autofluorescence: lesions tend to show a hypoautofluorescent center with
surrounding hyperautofluorescence and become more uniformly
hypoautofluorescent once inactive.
Differentials: POHS: asymptomatic, not in clusters, peripapillary atrophy;
lacquer cracks: linear, hemorrhage, more myopic.

165. Multifocal Choroiditis and Panuveitis
Subacute onset of decrease in vision (20/20-LP)
Epidemiology: female 3:1; mean age 36 (9 to 69); whites 86%
Etiology: unknown
Clinical findings: bilateral (80%)
Anterior chamber inflammation: 50% (from KP to 4+ cells)
Vitreous inflammation: characteristic
Chorioretinal lesions: several to several hundreds at the level of RPE (50-
350µ), in clusters or in a linear pattern, usually in periphery, yellow when
acute and punched out when inactive.
40% had peripapillary atrophy
Not associated with periphlebitis
Fluorescein angiography: active chorioretinal lesions block fluorescence
early and stained late, punched-out lesions show early hyperfluorescence
that fades in the late phases (window defect).
OCT and Autofluorescence: same as PIC
Treatment: corticosteroids (oral, periocular and intraocular) and
immunomodulatory therapy
Complications: CNVM, peripapillary CNVM, CME
Differentials: POHS, sarcoidosis, TB

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syndrome that mimics ocular histoplasmosis. Arch Ophthalmol 1984;
102: 1776-1784.
Brown, J., Jr. and J.C. Folk, Current controversies in the white dot
syndromes. Multifocal choroiditis, punctate inner choroidopathy, and the
diffuse subretinal fibrosis syndrome. Ocul Immunol Inflamm 1998; 6:
125-127.
Brown J, Jr., et al. Visual prognosis of multifocal choroiditis, punctate
inner choroidopathy, and the diffuse subretinal fibrosis syndrome.
Ophthalmology 1996; 103: 1100-1105.
Michel SS, et al. Multifocal choroiditis and panuveitis:
immunomodulatory therapy. Ophthalmology 2002; 109: 378-383.
Spaide RF, et al. Redefining multifocal choroiditis and panuveitis and
punctate inner choroidopathy through multimodal imaging. Retina 2013;
33: 1315-1324.

169. 1
How to Diagnose Uveitis
Masquerade syndromes – Janet Davis
IUSG Classification of Uveitis
o Infectious
o Non-infectious
o Masquerades
Masquerade Syndromes in Uveitis
 Not hematopoietic or not human
o Neoplasia
o Parasitization
 Hematopoietic cells
o Hemorrhage
o Drug reactions
 Others: bestrophinopathy, central serous retinopathy
Neoplastic masquerades
 Retinoblastoma
 Primary intraocular lymphoma
 Metastasis
 Paraneoplasia
Retinoblastoma
 Pleomorphic appearance
 Age range critical: posterior uveitis less than 9 years is rare
 Critical importance for ophthalmologists: diagnostic taps may worsen
prognosis; fatal disease
Intraocular lymphoma
 Primary vitreoretinal lymphoma
 (Primary) choroidal lymphoma
 Metastatic (uveal) lymphoma
Primary Vitreo-Retinal Lymphoma (PVRL)
 Vitreous, retina, RPE
 Intravitreal growth
 Haze
 Good vision, no CME
 Cells appear homogeneous without vitreous stranding
RPE Lymphoma
 Sub-RPE growth
o Between Bruch’s and RPE
o Elevated or flat on OCT
o Characteristic yellow color
o Autofluorescence pattern
 Hyperautofluorescent if under the RPE
 Hypofluorescent (blocking) if in the retina
o Cells may die and lesions regress spontaneously
 Do not interpret resolution as the solution

170. 2
What to do if you suspect lymphoma
 Do
o Perform wide-angle autofluorescence and colors
o Wide-angle fluorescein also is useful
o Check basic labs to exclude true uveitis to the extent possible
o Refer promptly
o If there is delay in referral, order MRI of brain with and without
contrast, specifying DWI and FLAIR
 Don’t prescribe corticosteroids as a “trial”
How to diagnose lymphoma
 Screening IL-10 cytokines from aqueous
o Excellent definition of cut-off values
o Poor surrogate for confirmed diagnosis to enable treatment
 Biopsy the vitreous cells
o Assess quantity – are there at least 2+ cells?
o Cytology, flow cytometry, gene rearrangement
 Biopsy the sub-RPE and retinal tissues
o Aspiration only
o Incisional biopsy
Metastatic disease
o Focal masses
 Choroidal metastases mimicking scleritis
o Diffuse infiltrations
 Optic nerve
 Choroid
 Extraocular lymphoma
 Primary choroidal lymphoma
Paraneoplasia
o Masquerades as autoimmune retinopathy
o Paraneoplasia is rare, ocular paraneoplasia rarer
o What is an adequate work-up for cancer?
o Knowledge of likely tumors:
 Lung, breast, ovarian, prostate, melanoma
o History - directed
o Referral – preferred – get physical examination
o Testing: CT scan chest/abdomen, MRI brain/pelvis, cancer
biomarkers (PSA, CEA, C-125), mammogram, fecal occult blood, full
body skin examination, FDG PET.
o Test wisely! Shotgun testing is expensive, radiation laden, difficult to
justify in an exceedingly rare condition. Screening tests suffer from
false positive and negative results
Parasitosis
o Flat worms (trematodes)
o Cercaria are the infective form
o Anterior granulomas in India, Brazil

171. 3
o Contaminated water
o Roundwords (toxocara and others)
o Diffuse unilateral subacute neuroretinitis
o Small worms – unknown species
o Large worms – likely Baylisascaris
Blood and pigment
 Microhyphemas from IOL-iris trauma
o Severe cases can cause iritis and glaucoma (UGH) but mild cases may
just cause recurrent hemorrhage
o Typical history of sudden onset of blurred vision
o Cells may be present, clears in 24 hours
 Pigment dispersion with heavy angle pigment and K spindles
 Key to both diagnoses is gonioscopy and SLE
 UBM to check for IOL tilt and
Drug Reactions
 Rifabutin – used for mycobacterial infection
o Especially at high doses and when combined with medications that
retard metabolism such as clarithromycin and certain HIV
medications
 Moxifloxacin
o Iritis with pigment dispersion
o Irregular pupils
o Transillumination defects
 Sterile endophthalmitis after intravitreal triamcinolone injections
Conclusions
 Masquerades don’t need steroids
 They need proper diagnosis and treatment
 Don’t be misled by prior diagnoses, presence of cells, or HLA type
 Because masquerades by definition have a cause, the workup should be more
 directed and more successful than in endogenous non-infectious uveitis
References:
1. Casady M, Faia L, Nazemzadeh M, Nussenblatt R, Chan CC, Sen HN. Fundus
autofluorescence patterns in primary intraocular lymphoma. Retina. 2014
Feb;34(2):366-72.
2. Chan CC, Rubenstein JL, Coupland SE, Davis JL, Harbour JW, Johnston PB,
Cassoux N, Touitou V, Smith JR, Batchelor TT, Pulido JS. Primary vitreoretinal
lymphoma: a report from an International Primary Central Nervous System
Lymphoma Collaborative Group symposium. Oncologist. 2011;16(11):1589-99.
3. Saito T, Ohguro N, Iwahashi C, Hashida N. Optical coherence tomography
manifestations of primary vitreoretinal lymphoma. Graefes Arch Clin Exp
Ophthalmol. 2016 Jun 1.
4. Papadia M, Jeannin B, Herbort CP. Central Serous Chorioretinopathy
Misdiagnosed as Posterior Uveitis and the Vicious Circle of Corticosteroid
Therapy. J Ophthalmic Vis Res. 2015 Jul-Sep;10(3):303-8.

172. Panuveitis
Careen Y. Lowder, M.D., Ph.D.
Cleveland Clinic Cole Eye Institute
Panuveitis refers to intraocular inflammation involving all of the uvea with anterior
segment, vitreous, retinal and choroidal inflammation.
Infectious Etiologies
 Syphilis
 Lyme Disease
 Tuberculosis
 Toxoplasmosis
 Onchocerciasis
 Acute Retinal Necrosis Syndrome
o Herpes simplex virus
o Varicella zoster virus
 Fungal endophthalmitis
o Coccidiomycosis
o Cryptococcus neoformans
o Candida
o Arpegillus
o Blastomycosis
Non-Infectious Etiologies
 Sympathetic Ophthalmia
- Rare, bilateral, granulomatous panuveitis
- Occurs when injury to one eye, the exciting eye, is followed by the
development of uveitis in the other, uninjured, the sympathizing eye
- Inflammation develops 1 week to over 50 years, although 90% of cases
occur within the first year following injury
- Injuries are most often penetrating

173. - Cases have been reported as occurring following cyclocryotherapy and
non-contact Nd:YAG cyclotherapy
- Many of the clinical findings in SO are identical to those seen in Vogt-
Koyanagi-Harada (VKH) disease, therefore, the presence or absence of a
clear history of trauma is often the key differentiating factor in making the
appropriate diagnosis.
Clinical Signs and Symptoms
- Bilateral acute anterior uveitis with large mutton-fat keratic precipitates
- Moderate to severe vitritis may be present, choroiditis and papillitis
- Multiple yellow-white spots may be present in the periphery
- Choroidal nodules appear during active phase and later become
atrophic and depigmented in appearance
 Vogt-Koyanagi Harada Syndrome
- Granulomatous inflammatory disorder affecting the eyes, auditory system,
meninges and skin
- Asians, Native Americans, Hispanics, Asian Indians and those from the
Middle East, are most frequently affected
- Women> men in their 3rd
to 4th
decades
- Prodromal symptoms – headache, neck-stiffness or focal neurological
signs, temporary deafness or tinnitus
- Sensitivity of the hair and skin to touch appear early, and alopecia,
poliosis, whitening of the hair and vitiligo may appear later
- Bilateral, often asymmetric. Symptoms include severe pain, redness and
photophobia. Acute blurring of vision occurs in both eyes in the majority
of patients, however in some there is a delay of one to three days before
the second eye becomes involved, and in a few cases this interval may last
up to 10 days.
- Anterior uveitis
- Vitritis
- Diffuse choroiditis with overlying subretinal fluid or bullous serous retinal
detachment
- Optic disc hyperemia
- Chronic recurrent phase: smoldering panuveitis with exacerbations of
acute episodes of granulomatous anterior uveitis

174.  Multifocal Choroiditis and Panuveitis
- Bilateral (80%)
- Anterior chamber inflammation 50% (from KP to 4+ cells)
- Vitreous inflammation
- Chorioretinal lesions: several to several hundreds at the level of RPE (50-
350µ), in clusters or in a linear pattern, usually in periphery, yellow when
acute and punched out when inactive.
- 40% had peripapillary atrophy
- Subacute onset of decrease in vision (20/20-LP)
- Female 3:1; mean age 36 (9 to 69); whites 86%
- Complications: CNVM, CME
 Sarcoidosis
- The most common panuveitis syndrome is Ocular Sarcoidosis.
- Epidemiology
Caucasian: 8:100,000
African-American: 82:100,000
-Bimodal age distribution
20-30
50-60
-Geographically variable
Spain: 0.04:100,000
-Transmission Studies
Recipients of bone marrow, cardiac and lung transplants from
donors with sarcoidosis develop sarcoidosis.
-Clinical Presentation:
Scleritis
Lacrimal gland involvement
Conjunctival granulomas
Anterior granulomatous uveitis
Koeppe and Busacca nodules
Vitritis
Snowbanking
Retinal periphlebitis
Granulomas
Preretinal nodules
Serous retinal detachment
Secondary cystoid macular edema
Choroidal granulomas
Disc granuloma

175. -Diagnosis
Biopsy
Chest CT – More sensitive
Less sensitive: Chest X-ray and Gallium Scan
Angiotensin Converting Enzyme
Cutaneous Anergy
-Treatment
Systemic Corticosteroids or Steroid sparing agents
Topical Corticosteroids
Posterior Sub-Tenon’s or intravitreal kenalog injections