Pod Uveitis DWNLD PDF

Academy
MOC Essentials®
Practicing
Ophthalmologists
Curriculum
2017–2019
Uveitis
***
Uveitis 2 © AAO 2017-2019

Practicing Ophthalmologists Curriculum
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diplomates, the American Academy of Ophthalmology has developed the Practicing
Ophthalmologists Curriculum (POC) as a tool for members to prepare for the
Maintenance of Certification (MOC) -related examinations. The Academy provides
this material for educational purposes only.
The POC should not be deemed inclusive of all proper methods of care or exclusive
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in compliance with applicable law.
The Practicing Ophthalmologists Curriculum is intended to be the basis for MOC

examinations in 2017, 2018 and 2019. However, the Academy specifically disclaims
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Practicing Ophthalmologists Curriculum
Authors and Financial Disclosures
The Practicing Ophthalmologists Curriculum was developed by a group of dedicated

ophthalmologists reflecting a diversity of background, training, practice type and
geographic distribution.
Jeffrey D. Henderer, M.D., American Academy of Ophthalmology Secretary for

Curriculum Development, serves as the overall project director for the acquisition
and review of the topic outlines.
The Academy gratefully acknowledges the contributions of the American Association

for Pediatric Ophthalmology and Strabismus.
Practicing Ophthalmologists Curriculum Panel 

Russell W. Read, M.D., Ph.D., Chair
Andrea D. Birnbaum, M.D., Vice Chair
Nicholas J. Butler, M.D.
Lisa J. Faia, M.D.
Grace A. Levy-Clarke, M.D.
P. Kumar Rao, M.D.
Wendy M. Smith, M.D.
Financial Disclosures
not restrict expert scientific clinical or non-clinical presentation or publication,

provided appropriate disclosure of such relationship is made. All contributors to
Academy educational activities must disclose significant financial relationships
(defined below) to the Academy annually.
Contributors who have disclosed financial relationships:

Nicholas J. Butler, M.D.
Aduro Biotech: O; Alimera Sciences, Inc.: O; Linde Healthcare: O; Stryker
Corp/Medical Division: O
Grace A Levy-Clarke, M.D.
Abbvie: C; Genzyme: L; Mallinckrodt Pharmaceuticals: C; XOMA (US) LLC: C
P. Kumar Rao, M.D.
National Eye Institute: S, Regeneron Pharmaceuticals, Inc.: S
Russell W. Read, M.D.
Abbvie: C
Contributors who state they have no significant financial relationships to

disclose:
Andrea D Birnbaum, M.D
Lisa J. Faia, M.D.
Jeffrey D. Henderer, M.D.
Wendy M. Smith, M.D.

Key:
Category Code Description
Consultant / C Consultant fee, paid advisory boards or fees for attending a meeting
Advisor (for the past 1 year)
Employee E Employed by a commercial entity
Lecture Fees L Lecture fees (honoraria), travel fees or reimbursements when
speaking at the invitation of a commercial entity (for the past 1 year)
Equity Owner O Equity ownership/stock options of publicly or privately traded firms
(excluding mutual funds) with manufacturers of commercial
ophthalmic products or commercial ophthalmic services
Patents / P Patents and/or royalties that might be viewed as creating a potential
Royalty conflict of interest
Grant S Grant support for the past 1 year (all sources) and all sources used for
Support this project if this form is an update for a specific talk or manuscript
with no time limitation
Background on Maintenance of Certification (MOC)
Developed according to standards established by the American Board of Medical

Specialties (ABMS), the umbrella organization of 24 medical specialty boards,
Maintenance of Certification (MOC) is designed as a series of requirements for
practicing ophthalmologists to complete over a 10-year period. MOC is currently
open to all Board Certified ophthalmologists on a voluntary basis; time-limited
certificate holders (ophthalmologists who were Board Certified after July 1, 1992) are
required to participate in this process. All medical specialties participate in a similar
process.
The roles of the American Board of Ophthalmology (ABO) and the American
Academy of Ophthalmology relative to MOC follow their respective missions.
 The mission of the American Board of Ophthalmology is to serve the public by

improving the quality of ophthalmic practice through a process of certification
and maintenance of certification that fosters excellence and encourages
continual learning.
 The mission of the American Academy of Ophthalmology is to protect sight

and empower lives by serving as an advocate for patients and the public,
leading ophthalmic education, and advancing the profession of
ophthalmology.
The role of the ABO in the MOC process is to evaluate and to certify. The role of the
Academy in this process is to provide resources and to educate.
Organization of the POC

The Practicing Ophthalmologists Curriculum comprises 10 practice emphasis areas
(PEA), plus Core Ophthalmic Knowledge.
• Core Ophthalmic Knowledge (a r
examinations.)
• Comprehensive Ophthalmology

• Cataract/Anterior Segment
• Cornea/External Disease
• Glaucoma
• Neuro-Ophthalmology and Orbit
• Oculoplastics and Orbit
• Pediatric Ophthalmology/Strabismus
• Refractive Management/Intervention
• Retina/Vitreous
• Uveitis
In addition to two practice emphasis areas of choice, every diplomate sitting for the
DOCK examination will be tested on Core Ophthalmic Knowledge. The ABO defines
Core Ophthalmic Knowledge as fundamental knowledge every practicing
ophthalmologist should have regardless their practice focus.
Each PEA is categorized into topics presented in an outline format for easier reading
and understanding. These outlines are based on a standard clinical diagnosis and
treatment approach
topic, there are Additional Resources that may contain journal citations and
reference to textbooks that may be helpful in preparing for MOC examinations.
Creation of the POC

The POC was developed by panels of Academy members who are practicing
ophthalmologists in each of the ten practice emphasis areas. The panels reflect a
diversity of background, training, practice type and geographic distribution.
Additionally, all panel members are time-limited certificate holders actively
participating in the MOC process.
The panels have reviewed the tlines for the MOC examinations and
developed and clinical review topics that they feel are most likely to appear on MOC
examinations. These clinical topics also were reviewed by representatives from each
subspecialty society.
Revision Process
The POC is revised every three years. The POC panels will consider new evidence in
the peer-reviewed literature, as well as input from the subspecialty societies, and the
-Assessment Committee, in revising and updating the POC.
Prior to a scheduled review the POC may be changed under the following
circumstances:
• A Level I (highest level of scientific evidence) randomized controlled trial
indicates a major new therapeutic strategy
• The FDA issues a drug/device warning
• Industry issues a warning

Uveitis
Basic concepts in immunology
1. Basic concepts in immunology: effector cells and the innate immune response
............................................................................................................................................................... 11
Diagnostic Tests/Procedures
2. Lab testing in uveitis ................................................................................................................ 14
3. Optical coherence tomography (OCT) - in uveitis ....................................................... 26
4. Posterior segment angiography: fluorescein angiography ...................................... 29
5. Posterior segment angiography: indocyanine green angiography (ICG) ........... 31
6. Conjunctival biopsy/pathology ........................................................................................... 33
7. Diagnostic vitreoretinal procedures in uveitis: vitreous biopsy .............................. 35
8. Diagnostic vitreoretinal procedures in uveitis: chorioretinal biopsy ..................... 37
Anterior Uveitis
9. Acute anterior uveitis .............................................................................................................. 40
10. Tubulointerstitial nephritis and uveitis (TINU) syndrome ........................................ 44
11. Lens-associated uveitis........................................................................................................... 47
12. Persistent (chronic) iridocyclitis ........................................................................................ 50
13. Juvenile idiopathic arthritis .................................................................................................. 54
14. Fuchs heterochromic iridocyclitis ..................................................................................... 59
Intermediate Uveitis
15. Intermediate uveitis ................................................................................................................ 62
Posterior Uveitis
16. Acute posterior multifocal placoid pigment epitheliopathy ................................... 67
17. Birdshot uveitis ......................................................................................................................... 69
18. Multiple evanescent white dot syndrome (MEWDS) ................................................. 72

19. Multifocal choroiditis with panuveitis .............................................................................. 74
20. Serpiginous choroidopathy ................................................................................................ 76
21. Systemic vasculitis - intraocular manifestations .......................................................... 80
Panuveitis
22. Sarcoidosis panuveitis........................................................................................................... 86
23. Sympathetic ophthalmia ...................................................................................................... 90
24. Vogt-Koyanagi-Harada disease ........................................................................................ 93
25. Behçet disease ......................................................................................................................... 97
Scleritis-Non infectious
26. Scleritis........................................................................................................................................ 100
Viral Uveitis
27. Herpetic anterior uveitis ....................................................................................................... 106
28. Necrotizing herpetic retinitis: acute retinal necrosis and progressive outer retinal
necrosis .............................................................................................................................................. 111
29. Cytomegalovirus retinitis ..................................................................................................... 114
30. Other rare infections: Human T-cell lymphotrophic virus ...................................... 119
Fungal uveitis
31. Ocular histoplasmosis syndrome ....................................................................................... 122
Protozoal Uveitis
32. Toxoplasmic retinochoroiditis ........................................................................................... 125
Helminthic Uveitis
33. Toxocariasis posterior uveitis ............................................................................................ 131
34. Other infectious uveitis: cysticercosis ............................................................................ 134
35. Diffuse unilateral subacute neuroretinitis (DUSN) ..................................................... 136
Bacterial Uveitis
36. Delayed-onset pseudophakic uveitis .............................................................................. 139

37. Syphilitic panuveitis ............................................................................................................... 142
38. Lyme disease ............................................................................................................................ 147
39. Leptospiral uveitis .................................................................................................................. 151
40. Tuberculous uveitis................................................................................................................ 155
41. Ocular bartonellosis ................................................................................................................ 162
42. Brucellar uveitis ....................................................................................................................... 165
Scleritis-Infectious
43. Post-surgical and traumatic infectious scleritis .......................................................... 169
Endophthalmitis
44. Candida and Aspergillus endophthalmitis .................................................................... 172
Masquerade Syndromes
45. Masquerade syndromes ....................................................................................................... 177
46. Autoimmune retinopathy (AIR) ........................................................................................ 186
Acquired Immune Deficiency Syndrome related disease
47. Ocular manifestations of acquired immunodeficiency syndrome ....................... 190
Medical Therapy
48. Treatment guidelines utilizing systemic therapy for non-infectious ocular

inflammatory disease.................................................................................................................... 202
49. Cycloplegics ............................................................................................................................. 205
50. Nonsteroidal anti-inflammatory drugs ........................................................................... 207
51. Corticosteroids ......................................................................................................................... 210
52. Methotrexate ............................................................................................................................ 214
53. Azathioprine ............................................................................................................................. 218
54. Mycophenolate ........................................................................................................................ 221
55. Alkylating agents: Cyclophosphamide and chlorambucil ....................................... 224
56. Cyclosporine ............................................................................................................................. 228

57. Biologic response modifiers ............................................................................................... 232
58. Antiviral therapy...................................................................................................................... 237
Complications of uveitis and their management
59. Cataract extraction for uveitis patients ......................................................................... 241
60. Glaucoma surgery for uveitis patients ........................................................................... 244
61. Complications of uveitis ........................................................................................................ 247
Uveitis 10 © AAO 2017-2019

I. Definitions
A. Immune response
1. Sequence of cellular and molecular events designed to rid the host of an offending pathogenic organism,
toxic substance, cellular debris, or neoplastic cell
a. Adaptive (or acquired) responses are directed against unique antigens with an immunologic
response specific for that antigen
b. Innate immune responses, or natural immunity, require no prior contact with the stimulus against
which they are directed
II. Cellular components of the immune system
A. Leukocytes
1. Nucleated cells that can be distinguished from one another by the shape of their nuclei and the presence or
absence of granules/ various histologic stains
a. Polymorphonuclear leukocytes
b. Eosinophils
c. Basophils
d. Mast cells
e. Monocytes and macrophages
f. Lymphocytes
III. Innate immunity triggers
A. Bacteria-derived molecules
1. Bacterial lipopolysaccharide
2. Other bacterial cell wall components
3. Exotoxins and other secretory products
B. Traumatic or toxic stimuli within ocular sites can trigger innate immunity
IV. Mediator systems that amplify immune responses
A. Plasma-derived enzyme systems
1. Complement factors
2. Fibrin and other plasma factors
3. Histamine
B. Lipid mediators
1. Eicosanoids
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a. Cyclooxygenase (COX) pathway
b. Produces prostaglandins, thromboxanes, and prostacyclins
c. COX-derived products can either up-regulate or down-regulate the production of cytokines, enzyme
systems, and oxygen metabolites
d. 5-lipoxygenase pathway
i. Produces hydroxyeicosatetraenoic acid, lipoxins, and leukotrienes
i) Contribute significantly to inflammatory infiltration.
ii) Leukotriene B4, a potent chemotactic factor that causes lysosomal enzyme release
and reactive oxygen radical production by granulocytes
iii) May have 1000 times the effect of histamine on vascular permeability
C. Platelet-activating factors
D. Cytokines
1. Soluble polypeptide mediators
2. Synthesized and released by cells for intercellular signaling and communication
3. Signal neighboring cells at the site (paracrine action)
4. Stimulate a receptor on its own surface (autocrine action)
5. Act on a distant site by release into the blood (endocrine action)
6. Growth factors, interleukins, lymphokines, interferons, monokines, and chemokine
E. Reactive oxygen intermediates
F. Reactive nitrogen products
G. Neutrophil-derived granule products
V. Adaptive immunity
A. Interaction between antigen and the adaptive immune system at a site such as the skin can be subdivided
into 3 phases
1. Afferent phase
a. Recognition, transport, and presentation of antigenic substances to the adaptive immune system
2. Processing phase
a. Conversion of the antigenic stimulus into an immunologic response
b. Priming of naive B and T lymphocytes
c. Within the lymph nodes and spleen
d. Also called activation, or sensitization, of lymphocytes
3. Effector phase
a. The elimination of offending foreign antigen physically carried out.
b. Antigen-specific effectors exist in 2 major subsets
i. T lymphocytes
ii. B lymphocytes plus their antibodies
i) Antibodies, or immunoglobulins, are soluble antigen-specific effector molecules
ii) After appropriate antigenic stimulation with T-lymphocyte help
iii) B lymphocytes secrete IgM antibodies
iv) Later, other isotypes, into the efferent lymph fluid draining into the venous
circulation
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v) Mediate a variety of immune effector activities by combining with antigen in the
blood or in tissues
B. Normal function of HLA molecules
1. All animals with white blood cells express major histocompatibility complex (MHC) proteins, in humans,
termed human leukocyte antigen (HLA) molecules
a. 3 MHC class I
i. HLA-A, -B, -C
b. 3 MHC class II
i. HLA-DR, -DP, -DQ
2. Allelic variation
a. Polymorphic variants of each of the 6 HLA types exist
b. 25 alleles for HLA-A
c. 50 for HLA-B
d. 10 for HLA-C
e. 100 for HLA-DR
3. Disease associations
a. Defined as the statistically increased frequency of an HLA haplotype in persons with that disease as
compared to the frequency in a disease-free population
i. The ratio of these 2 frequencies is called relative risk
b. The HLA association identifies individuals at risk, but it is not a diagnostic marker
c. The association is only as strong as the clinical diagnosis
d. Testing for HLA can provide supportive evidence for a particular diagnosis
e. Cannot make a definitive diagnosis
i. 8% of the white American population is HLA-A29 positive, but fewer than 1 in 10,000
Americans have birdshot uveitis
ii. The vast majority of individuals who are HLA-A29 positive will never have birdshot uveitis
C. Theories on the role of HLA in uveitis
1. HLA molecules act as peptide-binding molecules for etiologic antigens or infectious agents
2. Molecular mimicry between bacterial antigens and an epitope of an HLA molecule
3. T-lymphocyte antigen receptor (gene) is really the true susceptibility factor
4. Specific T-lymphocyte receptor uses a specific HLA haplotype
5. A strong correlation would exist between an HLA and the T-lymphocyte antigen receptor repertoire
Additional Resources
1. AAO, Basic and Clinical Science Course. Section 9: Intraocular Inflammation and Uveitis, 2015-2016.
Uveitis 13 © AAO 2017-2019

I. Indications and contraindications
A. Indications
1. Anterior uveitis
a. Chronic, persistent, or recurrent disease
b. Presence of hypopyon
c. Bilateral disease
d. Granulomatous disease
e. Positive review of systems
2. Intermediate uveitis
3. Posterior uveitis
4. Panuveitis
5. Scleritis
6. Retinal vasculitis
7. HIV screening required if AIDS defining ocular opportunistic infection is present
8. Suspicion of infectious uveitis
9. Suspicion of neoplastic masquerade syndrome
10. Suspicion of other masquerade syndrome (e.g. amyloidosis)
II. Describe the pre-procedure evaluation
A. History, physical examination, review of systems and formulation of a working differential diagnosis are
essential cornerstones of the work-up of a uveitis patient and should precede any laboratory testing
B. History
1. Ocular history
2. Medical history
a. All medications (especially new medications such as rifabutin, cidofovir, bisphosphonates,

sulfonamides, moxifloxacin)
b. Recent illness
c. Chronic conditions
3. Social History, especially sexual history, travel history, history of incarceration, drug use, smoking history,
and occupational history
4. Family History
5. Response to previous therapy
C. Review of systems
D. Thorough ophthalmologic examination
1. Must include every part of the exam - avoid commonly missed areas such as
a. Lids - e.g. cutaneous nodules
b. Conjunctiva - e.g. nodules/granuloma, symblepharon
c. Lacrimal gland - enlargement
Uveitis 14 © AAO 2017-2019

d. Cornea - diminished sensation or edema in suspected herpetic uveitis
e. Anterior segment slit lamp examination - including vitreous, iris
f. Gonioscopy
g. Dilated fundus examination
E. Thorough physical examination based upon pertinent positives in review of systems e.g.
1. Examine oral aphthae
2. Cutaneous rashes
3. Joint deformities and abnormalities in range of motion
4. Lymph nodes, glandular enlargement
5. Genital ulcers and rashes
F. Working differential diagnosis should include the following (based on complete history and physical)
1. Sarcoidosis
2. Syphilis
3. Tuberculosis
III. List the alternatives to the procedure
A. Radiologic procedures (chest X-ray, chest CT, MRI of head and orbits)
B. Tissue biopsy -
1. Ocular: skin, conjunctiva, aqueous/vitreous, retina/choroid,
2. Extraocular (e.g. lung/mediastinum) - gold standard for sarcoidosis
C. Ophthalmic imaging procedures
1. Fundus autofluorescence
2. Fluorescein angiography
3. ICG Angiography
4. OCT
IV. Describe instrumentations and technique
A. Venipuncture to obtain blood for serologic testing
B. CSF tap for VDRL, cytology
C. If the vitreous is involved, either
1. Vitreous tap
a. May not yield sufficient material for cytology but may be sufficient for culture or polymerase chain
reaction (PCR) examinations
2. Vitrectomy: Stop corticosteroids prior to procedure to improve sensitivity
a. Ideally, undiluted sample obtained prior to infusion
D. If aqueous is involved, then anterior chamber tap
1. Useful for PCR
a. Lower yield for viral infection with antiviral therapy
b. Consider stopping topical corticosteroids
2. Sterile technique is important.
3. Avoid contact with the crystalline lens in phakic individual
Uveitis 15 © AAO 2017-2019

V. List the complications of the procedure, their prevention and management
A. Vitrectomy
1. As for any vitrectomy, infection, bleeding, retinal detachment, cataract formation
2. Failure to obtain a diagnosis
B. Anterior chamber tap
1. Infection, bleeding, cataract formation, wound leak, pain
2. Failure to obtain a diagnosis
C. CSF Tap
1. CSF leak
2. Headache
3. Infection, bleeding
D. False positive results may cause unwarranted anxiety for patients
VI. Describe the considerations in interpretation - specific tests
A. List of all laboratory tests and indications
B. Flowchart for evaluation of uveitis Patients
C. Syphilis tests
1. Consider reverse sequence testing
a. Serologic tests are divided into treponemal and nontreponemal tests
b. Screen with treponemal enzyme immunoassays (EIA), chemiluminescence immunoassays (CIA) or

microbead immunoassays (MBIA) as initial screen
i. Qualitative
ii. Persistent over lifetime
c. Nontreponemal tests to detect active infection:
i. Rapid plasma reagin (RPR) detects antibodies against cardiolipin, released by cells
damaged by T. pallidum
ii. Venereal disease research laboratory test (VDRL) is a microflocculation assay using
nontreponemal antigen, cardiolipin
d. Serologic testing for syphilis has limitations
e. False-negative results in latent syphilis
i. VDRL testing is falsely negative in 30%
ii. FTA-ABS is falsely negative in 1-2% of the cases
2. HIV testing should be performed if treponemal tests are positive, as recommended by the CDC
D. TB testing Tuberculin skin test (TST, also known as purified protein derivative (PPD) test)
1. Background
a. Test for latent TB infection (LTBI)
b. Not a test for active infection
c. In ophthalmology, used as indirect evidence, along with clinical signs, of possible TB ocular
infection
d. A positive TST is indicative of prior exposure to TB but not necessarily of active systemic infection
2. Dosage
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a. Purified protein derivative (PPD) - simple protein precipitate of old tuberculin
b. 5-tuberculin unit (TU) dose of PPD
3. Technical aspects
a. Intracutaneous injection of 5 TU of PPD in 0.1 mL of solution, typically on the volar aspect of the
forearm
b. Use a short, beveled 26 - or 27- gauge needle
c. Injection should produce a raised, blanched wheal
d. Deeper injections may be washed out by vascular flow
e. Read reaction in 48 to 72 hours
f. Positive test defined by diameter of induration, not erythema
g. In the United States, PPD is considered positive requiring intervention if
i. Induration of >5 mm in
i) Patients with human immunodeficiency virus HIV
ii) Patients with contacts with active TB
iii) Radiographs consistent with healed TB lesions
ii. Induration of > 10 mm in
i) Patients with diabetes mellitus
ii) Patients with renal failure
iii) Patients using immunosuppressive agents
iv) Health care workers
v) Recent immigrants from high prevalence countries
iii. Induration is > 15 mm in patients with no known risk factors
h. False-negative skin testing occurs at a rate of 25%
i. Profound acute illness
ii. Immunosuppression
iii. Corticosteroid use
iv. Advanced age
v. Poor nutrition
vi. Sarcoidosis
i. False-positive skin testing
i. Individuals infected with atypical mycobacteria
ii. Prior immunization with bacillus Calmette-Guerin (BCG), especially children who develop
weak reactions
iii. Prior treatment with intra-luminal BCG injections for bladder carcinoma
iv. Booster effect - TST may become positive if two tests are repeated within a short interval,
such as a week. A negative test followed by a positive test in 1 week is considered
non-reactive
4. Indications for testing
a. Center for Disease Control and Prevention (CDC) & American Thoracic Society recommendations
for TST testing
i. No specific recommendations for testing in uveitis patients, but many recommend that all
uveitis patients undergo TB testing
b. Any patient who may require systemic immunosuppression for uveitis of other etiologies who has
not had testing for tuberculosis as part of their diagnostic evaluation.
Uveitis 17 © AAO 2017-2019

E. TB testing: Interferon-gamma (IFN-g) assays for latent TB infection
1. T-cell based in vitro assays that detect interferon-gamma (IFN-g) released by T cells after stimulation by
Mycobacterium tuberculosis antigens.
2. Two IFN-g assays are currently available
a. QuantiFERON-TB Gold (Cellestis Ltd., Carnegie, Australia) assay
i. Uses whole blood
ii. Enzyme-linked immunoabsorbent assay (ELISA)-based test
b. T SPOT-TB (Oxford Immunonotec, Oxford, UK)
i. Uses peripheral blood mononuclear cells
ii. ELISPOT technology
3. Current evidence suggests
a. IFN-g assays have higher specificity than TST (95-100% vs 70-95%)
b. IFN-g assays seem to be at least as sensitive as the PPD-based TST in active TB (80-95% vs
75-90%)
c. IFN-g assays have less cross-reactivity due to BCG vaccination than the TST
4. Recommendation
a. United States CDC recommended that the Quanti-FERON-TB Gold assay be used in all
circumstances in which the TST is currently used
F. Human leukocyte antigen (HLA) testing in uveitis
1. Use of HLA testing in uveitis
a. No HLA type is sufficiently sensitive or specific to make the diagnosis of any disease
b. The results must be considered in the context of the clinical picture
2. HLA-A29
a. HLA-29 is present in 95-97% of patients with birdshot chorioretinopathy (BCR)
i. The relative risk of the presence of HLA-A29 for BCR has been estimated to be over 200,
and the sensitivity and specificity over 90%
b. About 7-9% of Caucasians are HLA-A29+
i. Therefore, as many as 7-9% of Caucasians with other forms of uveitis that are not class I
HLA associated may be expected to be HLA-A29 +
ii. HLA-A29 + individuals with sarcoidosis with a picture mimicking BCR have been reported
3. HLA-B27
a. HLA-B27 is present in 50-75% of Caucasian individuals with unilateral acute anterior uveitis (See
Acute anterior uveitis)
i. Other clinical pictures, including chronic anterior uveitis, bilateral anterior uveitis and vitritis
may be seen in HLA-B27 + individuals, but less commonly
b. About 7-9% of the Caucasian population is HLA-B27+
i. Therefore, as many as 7-9% of Caucasians with other forms of uveitis that are not class I
HLA associated may be expected to be HLA-B27+.
c. The relative risk for AAU in HLA-B27 + individuals has been estimated to be 10
d. The association of AAU with ankylosing spondylitis and reactive arthropathies may be higher in
HLA-B27 + individuals with AAU than HLA-B27 - individuals with AAU
e. AAU may be more severe in HLA-B27+ individuals than in HLA-B27- individuals with AAU
4. Other HLA Associations
a. HLA-B51 in Behçet disease (See Behçet disease)
i. Relative risk only about 5; the diagnosis should be made on clinical grounds
Uveitis 18 © AAO 2017-2019

b. HLA-DRB1 for TINU
G. Urine β-2 microglobulin
1. Elevated in up to 60% of patients with tubulointerstitial nephritis and uveitis syndrome (TINU)
2. Used for screening patients with bilateral acute anterior uveitis
3. Confirmatory biopsy necessary to make diagnosis of TINU
H. Antistreptolysin O titers
1. Patients with recent infection (throat skin)
2. Used to diagnose post-infectious uveitis
I. Antinuclear antibodies (ANA) testing in uveitis
1. Definition
a. ANAs: antibodies detectable in blood that have the capability of binding to certain structures within
the nucleus of cells
b. ANAs are found in multiple autoimmune diseases and indicate possible presence of autoimmunity
2. Design of the ANA Test and its indications
a. ANAs can be found in patients with a number of different autoimmune diseases
i. Systemic lupus erythematosus
ii. Sjögren syndrome
iii. Rheumatoid arthritis
iv. Polymyositis
v. Scleroderma
vi. Hashimoto thyroiditis
b. ANAs can also be found in patients with conditions that are not considered "classic" autoimmune
diseases, such as chronic infections, cancer, and medications
c. The presence of ANA alone should not be used to establish a specific disease diagnosis
3. Implications of the presence of ANA
a. Patterns of ANA fluorescence: certain conditions can more frequently be associated with one
pattern or another
b. ANAs can be found in up to 25% of the normal population, usually in low titers. These persons
usually have no disease
i. Titers of lower than 1:80 are less likely to be significant
ii. ANA titers of less than or equal to 1:40 are considered negative
iii. Even higher titers are often insignificant in patients > 60 years of age
c. ANA result must be interpreted in the specific context of an individual patient's symptoms and other
test results. It may or may not be significant in a given individual
4. ANA testing in ocular inflammatory disease
a. Screening all patients with uveitis for ANA would result in approximately 100 false positive results
for every one positive test in an individual with SLE. Therefore, to increase pretest likelihood of
diagnosing a condition (e.g. SLE), disease-specific testing should be performed only in those in
whom the clinical suspicion is high
i. E.g., chronic iridocyclitis in a child with juvenile idiopathic arthritis (JIA) (See Juvenile
idiopathic arthritis)
ii. Retinal vasculitis (SLE) (See Systemic vasculitis - intraocular manifestations)
iii. Scleritis (See Scleritis)
J. Antineutrophil cytoplasmic autoantibody (ANCA)
1. Introduction
Uveitis 19 © AAO 2017-2019

a. ANCA tests are most valuable when selectively ordered in clinical situations where some form of
ANCA-associated vasculitis is a serious consideration
b. ANCA should not be used a screening test (i.e. if clinical suspicion is low)
c. Three patterns of neutrophil staining possible
i. c-ANCA: cytoplasmic staining
ii. p-ANCA: perinuclear staining
iii. Atypical patterns
2. Association with ANCA and active vasculitis
a. Granulomatosis with polyangiitis (formerly known as Wegener granulomatosis) - 70-80% have

positive c-ANCA, <10% have positive p-ANCA
b. Polyarteritis nodosa - 60% have positive p-ANCA, 30% have positive c-ANCA
c. Microscopic polyangiitis - c-ANCA or p-ANCA may be positive
d. Churg-Strauss syndrome - 50-80%have positive p-ANCA, c-ANCA rarely positive
e. Idiopathic pauci-immune necrotizing vasculitis - 50-80% have positive p-ANCA, c-ANCA rarely
positive
3. ANCA detection methods
a. ANCA reacts with neutrophil cytoplasmic antigens that were previously shielded
b. Detection methods
i. Indirect immunofluorescence microscopy (IFM) is the most sensitive widely used method
for ANCA detection
c. C-ANCA: characterized by finely granular staining of neutrophil cytoplasm with central accentuation
between the nuclear lobes
i. Antigenic specificity of c-ANCA has been identified as a 29 kDA neutral serine protease,
proteinase 3 (PR-3)
d. P-ANCA: characterized by staining of the perinuclear area
i. Autoantibodies against myeloperoxidase (MPO-ANCA)
4. Interpretation
a. ANCA tests should not be used as a screening test in non-selected patient groups (i.e. when no
scleritis or vasculitis)
b. ANCA tests are valuable when ordered in clinical situations when some form of ANCA-associated
vasculitis is a serious consideration
c. ANCA may be negative in patients with associated disease, particularly in patients on prednisone or
other systemic anti-inflammatory agents
5. Indications for ANCA testing in ocular inflammatory disease
a. Scleritis - especially necrotizing scleritis
b. Peripheral ulcerative keratitis
c. Retinal vasculitis
K. Serum angiotensin converting enzyme (ACE) level
1. Indications
a. Suspected underlying systemic sarcoidosis
b. Any anterior, intermediate, posterior or panuveitis that necessitates work-up
2. ACE detections methods
a. Serum ACE activity is measured by kinetic spectrophotometry of furylacryloyl-phenylalanyl-glycyl-

glycine hydrolysis
3. Interpretation
Uveitis 20 © AAO 2017-2019

a. Sensitivity 70%
b. Specificity 80%
i. Higher if
i) ACE levels are >2SD above mean
ii) Combined with chest radiograph or chest CT
c. Predictive value is less than 50% (even if values are high)
d. ACE should be ordered in combination with chest radiograph, chest CT, and positive gallium scan
4. False negatives - common
a. ACE activity inhibited by ACE inhibitors (antihypertensive medication)
b. Hyperthyroidism
c. Cystic fibrosis
d. COPD
e. Systemic corticosteroids
f. Lung cancer
g. Hyperlipidemia
5. False positives
a. Tuberculosis
b. Leprosy
c. Hyperthyroidism
d. Pulmonary histoplasmosis
e. Alcoholic cirrhosis
f. Diabetes mellitus
L. HIV testing
1. Serologic tests divided into screening assays and confirmatory tests
a. Screening assays
i. Enzyme-linked immunoabsorbent assay (ELISA) tests
ii. Results considered reactive or nonreactive
b. Confirmatory tests
i. Western blot or immunofluorescence assays
ii. Results are termed positive, negative or indeterminate
c. U.S. Preventive Services Task Force currently recommends screening the following patients:
i. One of more individual risk factors
i) Men having sex with men
ii) Men and women having unprotected sex with multiple partners
iii) Past or present injection drug users
iv) Men and women who exchange sex for money or drugs or have sex partners who
do
v) Persons whose past or present sex partners were human immunodeficiency virus
(HIV)-infected, bisexual, or injection drug users
vi) Persons with a history of blood transfusion between 1978 and 1985
vii) Persons who request an HIV test despite reporting no individual risk factors
viii) People who report no individual risk factors but are seen in high-risk or
Uveitis 21 © AAO 2017-2019

high-prevalence clinical settings
ii. Ophthalmologists should strongly consider testing patients if an HIV-associated diagnosis is

suspected -
i) CMV retinitis
ii) Atypical or extensive toxoplasma retinochoroiditis
iii) Some forms of necrotizing herpetic retinitis
iv) Infectious multifocal choroiditis
v) Syphilis
vi) (See Ocular manifestations of acquired immune deficiency syndrome)
iii. Pre and post-test counseling is mandatory
iv. Syphilis serology should be obtained if HIV suspected
v. Informed consent mandatory
vi. Occasionally T-cell subsets may be performed if a person presents with possible CMV
retinitis and HIV is suspected if social situation warrants
2. Screening test
a. ELISA test
i. Most sensitive test for HIV infection (> 99.5% sensitive)
ii. False positives may be significant (1-10%)
iii. Positive tests are confirmed with a more specific test (W) -ELISA captures HIV antibody
using immobilized HIV antigens
iv. Detecting HIV infection during the HIV-1 seroconversion period
i) During window period (period between exposure and seroconversion), the antibody
levels may be below the limit of detection
ii) Newer generation ELISA tests have combined the standard test with a p24 antigen
detection assay
iii) This improves detection of viral antigen (p24) during early virus infection
b. Western blot - confirmatory
i. Specific method to detect the presence of serologic reactivity to individual viral antigens
ii. Specificity > 99%
iii. Gold standard confirmatory test for HIV infection
M. Chest imaging in uveitis: chest radiograph
1. Indications
a. Tuberculosis suspect
b. Sarcoidosis suspect - 90% sensitivity in active sarcoidosis
2. List the alternatives to this procedure
a. Computed tomography (CT) scan - higher sensitivity in inactive sarcoidosis and in Caucasian
women over 50 years of age; increased exposure to radiation
3. Describe the considerations in interpretation of this diagnostic procedure
a. Tuberculosis
i. Multinodular infiltrates and cavitation in one or both upper lobes of the lungs
ii. Multiple infiltrates are suggestive of tuberculosis.
iii. Pleural effusion
b. Sarcoidosis
i. Bilateral hilar adenopathy
Uveitis 22 © AAO 2017-2019

ii. Right paratracheal adenopathy
iii. Symmetrical diffuse ground-glass appearance, fine reticular or miliary lesions, large nodular
lesions, or multiple large confluent infiltrates
iv. Pulmonary fibrosis may produce contraction and distortion
N. Chest imaging in uveitis: chest computed tomography (CT)
1. Indications
a. High resolution contrast CT scans provide improved anatomic lung detail and are more sensitive
than plain chest radiographs in delineating parenchymal, mediastinal, and hilar structures
b. Sarcoidosis. May be useful in making diagnosis of sarcoidosis in patient with normal or

non-diagnostic chest x-ray, especially if sarcoid pulmonary disease is inactive, and the clinical
suspicion, based on ocular findings, is high
c. Tuberculosis
2. Describe the pre-procedure evaluation
a. Check blood urea nitrogen level (BUN), creatinine prior to contrast
3. List the alternatives to this procedure
a. Chest x-ray (less sensitive)
b. Positive emission computed tomography with 18F labeled fluorodeoxyglucose (FDG-PET)
4. Describe the considerations in interpretation of this diagnostic procedure
a. Sarcoidosis
i. It can show parenchymal infiltrates, mediastinal or hilar adenopathy
ii. Enlarged lymph nodes are often observed in paratracheal, pretracheal, para-aortic, internal
mammary, subcarinal, or axillary regions, which are not appreciated on chest radiographs
b. Tuberculosis
i. Active pulmonary tuberculosis
i) Centrilobular nodules and branching linear structures (tree-in-bud appearance)
ii) Lobular consolidation
iii) Cavitation
iv) Bronchial wall thickening
ii. Inactive pulmonary tuberculosis
i) Calcified nodules or consolidation
ii) Irregular linear opacity
iii) Parenchymal bands
iv) Pericicatricial emphysema
O. Nuclear medicine and positron emission tomography
1. Nuclear medicine
a. Gallium scan for sarcoidosis may be considered - Low sensitivity and specificity
b. May demonstrate uptake in the lacrimal and salivary glands and variably in lungs if granulomatous
inflammation present
c. Rarely performed and expensive
2. Positron emission computed tomography - PET scan
a. PET scan using 18F labeled fluorodeoxyglucose for suspected sarcoidosis (FDG-PET)
i. Functional imaging modality
ii. Based on increased glucose metabolism in metabolically active sites of sarcoid

inflammation
Uveitis 23 © AAO 2017-2019

iii. Useful in the diagnosis of pulmonary and extrapulmonary sarcoidosis
i) Even when anatomic radiographic studies such as CT scans appear normal
b. Expensive and not widely available
i. Does not typically alter therapy
P. Examination of intraocular fluids
1. PCR
a. PCR can be done to identify the following
i. HSV I&II, VZV, CMV, EBV
ii. Toxoplasma gondii
iii. Mycobacterium tuberculosis (65 kDA sAg)
iv. Borrelia burgdorferi (41 kda flagellin gene)
v. Propionibacterium (Pa1, rPa2, rPa3 antigens)
vi. Fungi (28S rRNA gene)
vii. Tropheryma whipplei and other bacteria (16S rRNA gene)
viii. Intraocular lymphoma (IgH gene)
b. A false negative result may occur. Many commercial laboratories are not experienced in handling
specimens, and PCR primers are not available or standardized for all infectious agents
c. A false positive result may occur. PCR is very sensitive and if the sensitivity of the standards is too
low, any contamination or viral DNA from leukocytes may be recovered.
2. Cultures
a. Culture vitreous or anterior chamber fluid specimens to culture plates or culture tubes directly when
possible
b. Check with the laboratory that will do the cultures for their preferred media
c. Separate media may be required for aerobic, anaerobic and acid fast bacilli, as well as for fungal
and viral organisms
d. Prompt transport to the laboratory is critical
e. Give sufficient time for cultures of slow growing or fastidious organisms; these may take longer to
incubate
3. Cytology
a. It is very important to get a sufficient specimen
b. It is very important that the specimen is handled properly. Consult with the pathologist (who may
want to be there when the specimen is obtained)
c. False negatives can occur if insufficient material, material not handled properly or preparation
delayed, or if treatment has altered the cellular material
Q. Electrocardiogram (ECG)
1. Shortness of breath, palpitations, syncope, other cardiac symptoms
2. Cardiac sarcoidosis can lead to fatal arrhythmias - refer to cardiology for any positive ROS or ECG findings
1. AAO, Basic and Clinical Science Course. Section 9: Intraocular and Inflammation and Uveitis, 2015-2016.
2. Nahid P, Pai M, Hopewell P. Advances in the Diagnosis and Treatment of Tuberculosis. Proc Am Thorac
Soc 2006;3:103-110.
3. Guidelines for Using the QuantiFERON-TB Gold Test for Detecting Mycobacterium tuberculosis infection.
MMWR 2005 December 16. C
4. McPherson and Pincus. Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. W.B.
Uveitis 24 © AAO 2017-2019

Saunders Company; 2006.
5. Mandell, Bennett & Dolin. Principles and Practice of Infectious Diseases. 6th ed. Churchill Livingstone
(Elsevier); 2005.
6. U. S. Preventive Services Task Force. "Screening for HIV: Recommendation Statement." American
Academy of Family Physicians, 2005.
7. Branson BM, Handsfield HH, Lampe MA, et al; Centers for Disease Control and Prevention (CDC). Revised
recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings.
MMWR Recomm Rep 2006 Sep 22;55(RR-14):1-17.
8. Bénéteau-Burnat B, Baudin B. Angiotensin-converting enzyme: clinical applications and laboratory

investigations on serum and other biological fluids. Crit Rev Clin Lab Sci. 1991;28(5-6):337-56.Lynch DA,
Webb WR, Gamsu G, et al. Computed tomography in pulmonary sarcoidosis. J Comput Assist Tomogr
1989;13:405-410.
9. Lee, J. Y., K. S. Lee, et al. Pulmonary tuberculosis: CT and pathologic correlation. J Comput Assist Tomogr
2000;24:691-8.
10. Kaiser PK, Lowder CY, et al. (2002). Chest computerized tomography in the evaluation of uveitis in elderly
women. Am J Ophthalmol 2002;133:499.
11. Levinson RD, Park MS, et al. Strong Associations between Specific HLA-DQ and HLA-DR alleles and the
Tubulointersitial Nephritis and Uveitis Syndrome. Invest. Ophthalmol. Vis. Sci. February 2003 vol. 44 no. 2
653-657.
12. MMWR Discordant Results from Reverse Sequence Syphilis Screening ---Five Laboratories, United States,
2006-2010. February 11, 2011 / 60(05);133-137.
Uveitis 25 © AAO 2017-2019

I. Underlying physical principles
A. Interferometric technique- reflected light is analyzed to produce a cross section of tissue
B. Requires optically clear media (different from ultrasonography)
C. Provides real-time, in situ, "optical biopsy"
D. Resolution depends on equipment
1. Time-domain OCT ~ 18 µm
2. Spectral-domain OCT ~ 8 µm
3. Ultra high resolution OCT ~ 2 µm
II. List the indications/contraindications
A. Indications
1. Macular diseases - OCT may be of value in the evaluation of:
a. Macular edema
b. Macular hole
c. Epiretinal membrane
d. Vitreoretinal interface disorders such as
i. Vitreomacular traction syndrome
e. Posterior panuveitis
f. Macular atrophy
g. Atrophy of retinal pigment epithelium (RPE)
h. Evaluation of IS/OS junctions (e.g. AZOOR, AR)
i. Subretinal fluid
j. Choroidal/retinal folds
2. Optic nerve diseases - OCT may be of value in the evaluation of the nerve fiber layer in the following:
a. Glaucomatous optic neuropathy
b. Optic atrophy
c. Optic nerve pits
3. Choroidal disease - using "enhanced depth imaging" (EDI)
a. VKH and SO- loss of focal hyperreflectivity of inner choroid
b. Posterior scleritis - choroidal thickening
4. Anterior segment disease (e.g. cornea thinning or edema, UGH, IOL placement, scleral edema and
thinning)
B. Assessment of response to treatment
C. Contraindications
1. No absolute contraindications, but media opacity, poor pupil dilation and poor co-operation may limit
usefulness of test
Uveitis 26 © AAO 2017-2019

III. Describe the pre-procedure evaluation
A. Explain procedure
B. Pupillary dilation required for optimal imaging
C. Media clarity required for optimal imaging
D. Adequate patient fixation is required
IV. List the alternatives to this procedure
A. Macular contact lens examination at the slit-lamp
B. Fluorescein angiography
C. Indocyanine green angiography
D. Confocal scanning laser ophthalmoscopy
E. B-scan for choroidal thickening
V. Describe considerations in interpretation of this procedure
A. Acquisition of a good quality OCT scan
1. Adequate pupillary dilation - may be problematic if posterior synechiae present
2. Clear ocular media - problematic if corneal, lenticular, or vitreous opacities
3. Steady patient fixation - problematic if poor vision
4. Proper scanning module alignment
5. Appropriate scan image optimization
B. Accurate OCT scan interpretation - qualitative information
1. Identification of morphological changes in tissue layers - atrophy, thickening, distortion
2. Interpretation of changes in the relative reflectivity of tissue layers - hyporeflectivity, hyperreflectivity
3. Correct identification of common artifacts
C. Accurate OCT scan interpretation - quantitative information
1. Retinal thickness/volume measurement
2. Retinal thickness map
3. Retinal nerve fiber layer thickness/volume measurement
4. Retinal nerve fiber layer thickness map
5. Serial analysis
D. Disease specific findings
1. Uveitic macular edema
a. Focal
b. Diffuse
c. Cystoid
d. Serous retinal detachment
e. Used to quantitatively follow treatment efficacy
2. White dot syndromes - (Inflammatory chorioretinopathies of unknown etiology)
a. Loss of the Inner segment - outer segment band common to most inflammatory chorioretinopathies
Uveitis 27 © AAO 2017-2019

b. Multifocal choroiditis and panuveitis
i. Transretinal reflectivity of active lesions
c. Serpiginous choroiditis
i. Hyper-reflectivity of outer retina
ii. "Waterfall effect" - loss or thinning of the RPE and choriocapillaris
3. VKH syndrome and sympathetic ophthalmia
a. Acute phase
i. Hypo reflective collections of subretinal and occasionally intraretinal fluid
ii. Serous retinal detachments with fibrin bridges
i) Can be used to quantitatively follow treatment efficacy
iii. Disruption of photoreceptor outer segments
iv. Choroidal thickening with EDI (enhanced depth imaging)
b. Chronic phase
i. Retinal disorganization and thinning - atrophy
4. Vitreomacular traction (VMT) syndrome - usually found in idiopathic panuveitis
a. Focal versus broad based hyaloidal traction on fovea
b. Can result in tractional macular edema
1. AAO, Basic and Clinical Science Course. Section 12: Retina and Vitreous, 2015-2016.
2. Carl Zeiss Ophthalmic Systems, Inc. Optical Coherence Tomographer - Model 3000, User manual.
Germany, 2002.
3. Schuman JS, Puliafito CA, Fujimoto JG. Optical Coherence Tomography of Ocular Disease. 2nd ed. Slack
Incorporated; 2004.
4. Massin P, Girach A, Erginay A, et al. Optical coherence tomography: a key to the future management of
patients with diabetic macular oedema. Acta Ophthalmol Scand 2006;84:466-474.
5. AAO, Focal Points: Optical Coherence Tomography in the Management of Retinal Disorders. Module 11,
2006.
6. Gallagher MJ, Castaneda-Cervantes RA, Foster CS. The characteristic features of optical coherence
tomography in posterior uveitis. Br J Ophthalmol. 2007; 91:1680-1685.
7. Tran THC, deSmet MD, Bodaghi B, Fardeau C, Cassoux N, Lehoang P. Uveitic macular oedema:
correlation between optical coherence tomography patterns with visual acuity and fluorescein angiography.
Br J Ophthalmol. 2008;92(7):922-7.
Uveitis 28 © AAO 2017-2019

I. List indications and contraindications
A. Indications
1. Choroidal neovascularization
2. Retinal neovascularization
3. Chorioretinal inflammatory conditions
4. Subretinal fluid accumulation
5. Retinal perfusion abnormalities
6. Macular edema
7. Other retinal vascular leakage, such as retinal vasculitis
8. Optic disc leakage
B. Contraindications (relative)
1. Prior urticarial reaction (1%) increases the risk of a similar reaction
2. Pregnancy (although teratogenic effects have not been identified)
A. Funduscopic examination to establish a correct indication
III. List the alternatives to this procedure
A. Optical coherence tomography (OCT) in some diseases (cystoid macular edema, epiretinal membranes,
choroidal neovascularization, macular atrophy)
B. Indocyanine green angiography (ICG) in select conditions such as birdshot chorioretinopathy and
multifocal evanescent white dot syndrome as an adjunct procedure to view the choroid. (See Posterior
segment angiography: indocyanine green angiography (ICG))
C. Autofluorescence photography
IV. Describe the instrumentation and technique
A. Pupillary dilation
B. Intravenous dye injection (5 cc of a 10% solution in adults followed by a flush of saline)
C. Oral administration of fluorescein (mixed with orange juice or chocolate milk) for those without vein access
or children (oral quality as not as good as IV)
D. Start timer with dye injection and measure arm to eye time and monitor transit phase in eye of greater
clinical interest
E. Capture photographs at frequent intervals immediately following the injection of the dye until the dye
disappears from the blood vessels (late phases, typically > 10 minutes after injection)
F. Consider late photos of periphery to scan for peripheral choroiditis or wide field angiography to identify
peripheral choroiditis and vasculitis
Uveitis 29 © AAO 2017-2019

A. Nausea, vomiting or vasovagal reactions: 10% of injections
B. Severe vasovagal reactions: bradycardia, hypotension, shock, and syncope: rare
C. Extravasation of dye with subcutaneous granuloma, local tissue necrosis
D. Urticarial reactions (1%) - diphenhydramine can be used
E. Anaphylactic reactions (cardiovascular shock): less than 1 in 100,000 injections
F. Death - extremely rare - usually due to anaphylactic shock or MI
VI. Describe the considerations in interpretation of this diagnostic procedure
A. Capillary non-perfusion - must scan periphery - occlusive retinal vasculitis
B. Optic nerve head leakage
C. Petaloid pattern of leakage in macula - Cystoid macular edema
D. Retinal vascular staining - must scan periphery - retinal vasculitis, birdshot uveitis
E. Multiple pinpoint areas of leakage: marked increase in fluorescence through the study with greatest
intensity in the late phases - VKH, sympathetic ophthalmia, posterior scleritis
F. Early hypofluorescence and late hyperfluorescence of multiple lesions seen in APMPPE, active areas of
choroiditis
G. Early hyperfluorescence and diffuse leakage associated with retinal neovascularization (NVD, NVE) must
scan periphery with attention to junction of nonperfused retina
H. Early hyperfluorescence with late leakage associated with choroidal neovascularization (commonly seen in
POHS, MCP, PIC, SFU)
2. AAO, Ophthalmology Monograph 5. Fluorescein angiography: technique and interpretation. Berkow J, Orth
DH, Kelley JS.
Uveitis 30 © AAO 2017-2019

I. List indications and contraindications
A. Indications
1. Choroidal neovascularization blocked by pigment, blood, fluid or lipid
2. Choroidal inflammatory conditions
a. Serpiginous choroidopathy
b. Birdshot uveitis
c. Acute posterior multifocal placoid pigment epitheliopathy
d. Multiple evanescent white dot syndrome
e. Multifocal choroiditis
i. Multifocal choroiditis and panuveitis (MCP)
ii. Punctate inner choroidopathy (PIC)
f. Vogt Koyanagi Harada syndrome
g. Sympathetic ophthalmia
B. Contraindications (relative)
1. Allergies to iodides and shellfish (ICG contains 5% iodide)
A. Funduscopic examination to establish a correct indication
A. Biomicroscopic examination of fundus
B. Optic coherence tomography
C. Fluorescein angiography
A. Pupillary dilation
B. Intravenous dye injection (25 mg of ICG dissolved in 5 ml solvent)
C. ICG fluoresces in the near-infrared range. It can be detected with specialized infrared video angiography
(modified fundus cameras, digital imaging system, scanning laser ophthalmoscope)
A. Nausea and vomiting are rare (less than 1%)
B. Anaphylaxis (very rare)
Uveitis 31 © AAO 2017-2019

A. Choroidal neovascularization: is seen as a focal "hot spot", plaque, or combination of both
B. Serpiginous choroiditis
1. Hypofluorescence throughout the study
2. Better seen than clinically or on fluorescein angiography.
3. Due to
a. Choroidal perfusion abnormalities
b. Blockage by inflammatory exudative material
c. Edema of the retinal pigment epithelium (RPE) and outer retina
C. Acute posterior multifocal placoid pigment epitheliopathy (APMPPE):
1. Hypofluorescent in both early and late phase of the study
2. Due to a partial choroidal vascular occlusive vasculitis
D. Multiple evanescent white dot syndrome (MEWDS)
1. Hypofluorescent spots throughout the posterior pole and peripheral retina
a. Appear about 10 minutes after dye injection and persist throughout the remainder of the study
b. Abnormality in choroidal circulation
2. Larger and greater in number than the white dots seen clinically and by fluorescein angiography
E. Birdshot uveitis
1. Multiple hypofluorescent lesions
2. Correspond to the clinical creamy lesions
3. May help in diagnosis when spots not visible clinically
F. Multifocal choroiditis
1. Active and inactive atrophic lesions block fluorescence
G. Vogt Koyanagi Harada Syndrome
1. Delay in choroidal perfusion
2. Multiple hypofluorescent spots (foci of lymphocytic infiltration)
2. Hope-Ross M, Yannuzzi LA, et al. Adverse reactions due to indocyanine green. Ophthalmology
1994;101(3):529-33.
3. Ryan. Chorioretinal Inflammatory Diseases. Mosby (online book).
Uveitis 32 © AAO 2017-2019

I. List the indications/contraindications
A. Indications
1. Granulomatous disease - sarcoidosis
2. Mucosa-associated lymphatic tissue (MALT) tumor/Conjunctival tumor (masquerading as follicular

conjunctivitis or granulomatous disease)
3. Acquired immune deficiency syndrome (AIDS) related disease
a. Kaposi sarcoma
b. Molluscum contagiosum
4. Ocular mucous membrane pemphigoid
5. Exclude other infectious etiologies
B. Contraindications
1. Prior history of ligneous conjunctivitis
2. Evident, active conjunctival infection
A. In suspected sarcoidosis
1. Search for skin lesions consistent with sarcoidosis that might give a higher diagnostic yield
2. Purified protein derivative (PPD) or interferon gamma release assay (IGRA) for tuberculosis
3. Chest x-ray or chest computed tomography (CT) scan to evaluate for pulmonary involvement
4. Serum angiotensin converting enzyme (ACE) and lysozyme levels as well as gallium scan have low
sensitivity and specificity
5. Avoid topical corticosteroids prior to biopsy, as nodules will dissolve
B. Evaluation for systemic lymphoma in suspected conjunctival lymphoma
C. Bartonella henselae serum immunoglobulin (Ig)G and IgM in suspected cat scratch disease
D. Evaluation for additional sites of mucous membrane pemphigoid.
A. Suspected sarcoid
1. Biopsy of other involved tissue such as skin, lung, parotid or lacrimal or minor salivary gland
B. Mucous membrane pemphigoid
1. Consider oral biopsy or skin biopsy since conjunctival biopsy may cause exacerbation of disease
A. Identify an appropriate lesion potentially consistent with conjunctival sarcoid (blind biopsy of conjunctiva
has very low diagnostic yield and is not recommended as a screening tool in the absence of a nodule)
B. Excisional biopsy preferred (incisional biopsy reserved for large lesions)
C. Communication with examining pathologist essential to ensure thorough tissue evaluation and increase
yield)
Uveitis 33 © AAO 2017-2019

D. Gentle handling of tissue to prevent crush artifact
E. Place specimen flat (to avoid rolling of conjunctiva) on a substance like filter paper
F. Light microscopy pathology studies (formalin-fixed tissue)
1. Hematoxylin and eosin
2. Periodic Acid Schiff
3. Acid-fast bacillus & fungal staining
G. Examination of the section under polarized light microscope
1. To rule out other causes of granulomatous disease (eg foreign body, mycobacterium, fungal diseases) since
sarcoid is a diagnosis of exclusion
2. Warthin-Starry staining to diagnose cat-scratch (Bartonella henselae) disease
H. Immunohistochemistry, cytology and flow cytometry - in suspected lymphoma
1. Fresh tissue
2. Sufficient quantity to allow clonality testing (via flow cytometry) and cytogenetics
I. Immunofluorescence - need fresh tissue, NOT in formalin
1. Linear basement membrane staining in ocular cicatricial pemphigoid (linear IgA, IgG, and complement
staining along the basement membrane zone)
J. Cultures and polymerase chain reaction may be indicated
V. List the complications of the procedure, their prevention & management
A. Subconjunctival hemorrhage - prevention includes avoiding anti-platelet agents pre-operatively
B. Symblepharon
C. Ligneous reaction
D. Infection - prevention by utilizing sterile technique
VI. Describe the follow-up care
A. Usually heals without sequelae
B. If diagnostic, then appropriate therapy depending on etiology
2. Shields CL, Shields JA, Carvalho C, Rundle P, Smith AF. Conjunctival lymphoid tumors: clinical analysis of
117 cases and relationship to systemic lymphoma. Ophthalmology. 2001 May;108(5):979-84.
Uveitis 34 © AAO 2017-2019

A. Indications
1. Uveitis where neoplastic or infectious disease are suspected (either due to the clinical appearance or to
failure to respond to conventional therapy)
a. Primary vitreoretinal lymphoma (PVRL)
b. Viral infection (Herpes simplex, herpes zoster, cytomegalovirus, Epstein Barr, human herpesvirus-6)
c. Atypical toxoplasmosis
d. Mycobacterium tuberculosis
e. Whipple disease
2. Microbiologic evaluation of endophthalmitis
A. Magnetic resonance imaging (MRI) of the brain and lumbar puncture for cerebrospinal fluid cytology often
done if there is a strong suspicion of central nervous system lymphoma
B. Other diagnostic evaluations for uveitis if appropriate (e.g., blood cultures for bacteria and fungi, serology
for syphilis, chest X-ray)
C. Preparation for distribution of samples
1. Involve the pathologist before collecting the specimen to be sure of proper specimen handling and delivery
2. Contact laboratory if planning PCR - some laboratories will not accept small samples for quantitative PCR
3. IL-6 levels, IL-10 levels, IgH gene changes, immunohistochemistry for T and B cell populations
A. If lymphoma is suspected, lumbar puncture with cerebrospinal fluid cytology, MRI and brain biopsy may be
other options
B. Polymerase chain reaction (PCR) analysis of aqueous humor via paracentesis is a reasonable option in the
detection of herpetic eye disease
A. Standard 3-port pars plana vitrectomy to obtain 1.5 cc to 2.0 cc of undiluted vitreous
B. Once the pure vitreous aspirate has been obtained, syringe is capped and should be given immediately to
the pathologist (who should be informed of the procedure and the differential diagnosis being considered).
Undiluted vitreous specimen may be aliquoted for
1. Cytopathology to determine if malignant lymphoma cells are present.
a. The cells in these vitreous specimens are particularly susceptible to rapid degradation and death.
Thus, immediate processing by a cytopathologist is essential. Choice of tissue culture media
should be left to the cytopathologist
b. Clear communication must exist between the cytopathologist and ophthalmologist regarding the
differential diagnosis being considered
2. Immunohistochemistry and flow cytometry to determine monoclonality and diagnosis of primary intraocular
Uveitis 35 © AAO 2017-2019

lymphoma
3. Molecular studies for gene rearrangement for diagnosis of lymphoma (IgH gene rearrangement) (must
request in advance to be certain that laboratories can perform studies requested)
4. Culture and staining for bacteria and fungi
5. Polymerase chain reaction (PCR) for specific infections (especially HSV1, HSV2, VZV, CMV, and
Toxoplasmosis)
6. IL-6, IL-10, 16S and 18S ribosomal RNA, BCL-2 gene -PCR - (these tests may not be commercially
available)
C. Subsequently, pars plana vitrectomy is completed. At the end of the procedure, the vitreous cassette
containing diluted vitreous may be sent to be centrifuged for additional flow cytometry, cultures, and PCR
studies
A. Vitreous or suprachoroidal hemorrhage
B. Retinal tear or detachment
C. Cataract
D. Endophthalmitis
A. Recognition of limitations in cytology
B. Pre-procedure clinical suspicion impacts selection of tests and ultimate diagnostic yield
C. Decreased diagnostic yield with prior treatment
1. Corticosteroids may be lympholytic to lymphoma cells
2. Antimicrobial or antiviral therapy in infectious cases
D. Repeat biopsy may be performed if there is sufficient suspicion for particular processes such as primary
intraocular lymphoma, and initial biopsy is inconclusive
VII. Describe the follow-up care
A. If the biopsy reveals lymphoma, refer to oncologist for management
B. If the biopsy reveals infectious agent, the patient should be treated for the infection May require infectious
disease expert in cases of systemic infection (i.e. endogenous endophthalmitis).
VIII. Describe appropriate patient instructions
A. Emphasize follow-up examinations and care by oncologist for the lymphoma
B. Procedure may not yield diagnosis in some cases
C. Procedure may lead to complications and loss of vision
2. Han DP, Wisniewski SR, Kelsey SF, et al. Microbiologic yields and complication rates of vitreous needle
aspiration versus mechanized vitreous biopsy in the Endophthalmitis Vitrectomy Study. Retina
1999;19:98-102.
3. AAO, Focal Points: Intraocular Lymphoma, Module #12, 2005.
Uveitis 36 © AAO 2017-2019

A. Indications
1. Intraocular lymphoma mostly confined to the subretinal space
2. Sight-threatening chorioretinitis of unknown etiology involving one eye or both eyes
a. Biopsy is performed in eye with worse visual potential
b. Includes cases with an atypical presentation, inconclusive system work up, inadequate response to
conventional therapy
c. Useful to distinguish between cases of suspected infection or malignancy in which the biopsy has
the potential to alter management
3. Suspected intraocular malignancy mostly confined to the subretinal space
1. Disease in which there is a reasonable expectation that vitreous biopsy would provide sufficient material for
cytologic examination
2. Chorioretinitis in which there is reasonable expectation that culture, or polymerase chain reaction analysis or
antibody determinations of ocular fluid would be sufficient to make the diagnosis
3. Possible retinoblastoma in which intraocular biopsy may worsen the systemic prognosis
A. Usually, prior attempt at intraocular diagnosis with analysis of vitreous humor obtained by pars plana
vitrectomy (unless subretinal material can be easily obtained by aspiration) or aqueous humor obtained by
anterior chamber paracentesis
B. Systemic evaluations
1. Suspected lymphoma
a. Magnetic resonance imaging (MRI) of brain
b. Lumbar puncture
2. Suspected chorioretinitis
a. Chest x-ray or computed tomography (CT)
b. Blood and urine cultures
c. Skin test or tuberculin skin test (TST), interferon-gamma release assay (IGRA), such as
QuantiFERON-TB Gold
d. Syphilis testing with direct testing such as Syphilis IgG
e. Additional testing as appropriate for clinical presentation
C. Ocular evaluations
1. B-scan ultrasonography to evaluate extent of chorioretinal involvement prior to biopsy
2. Subretinal aspirations, retinal biopsy or retinal-choroidal biopsy, ab interno
a. Evaluate for surgical site that is easy to access and contains sufficient tissue
i. Ideal location
i) Outside the arcades, posterior to equator, superior hemisphere (for easier

tamponade)
Uveitis 37 © AAO 2017-2019

b. Create plan for repairing retinal defect (pars plana vitrectomy, endolaser, internal tamponade (long-
acting gas, silicone oil in cases of severe retinopathy, possible scleral buckle))
c. Preoperative laser to surround site may be useful
d. Plan for cautery to blood vessels contained within the biopsy site
e. VERY IMPORTANT: Pathologic consultation should be done prior to procedures to discuss biopsy
site, proper handling and fixation of tissue, and appropriate evaluation of specimens
3. Chorioretinal biopsies, ab externo
a. May be accomplished via fine needle aspiration techniques, but requires a fairly anterior lesion with
sufficient thickness for biopsy
A. Analysis of another involved tissue, such as skin, lung, cerebral spinal fluid, or brain if more appropriate in
cases where there are systemic involvements
B. Analysis of ocular fluid with vitreous biopsy or anterior chamber paracentesis
C. Analysis of other ocular tissue (e.g., conjunctiva)
A. Ab interno subretinal aspiration
B. Ab interno retinal-choroidal biopsy
C. Ab externo chorioretinal biopsy
D. Pathologic examination
1. Histopathology
a. Tissue is fixed
b. Light and electron microscopy
c. Stain for suspected organisms
2. Immunohistochemistry
a. Frozen tissue
b. Polymerase chain reaction (PCR)
c. Specific stains for lymphoma
3. Culture if infection suspected
V. List the complications of this procedure
A. Retinal detachment
B. Cataract
C. Vitreous hemorrhage
D. Decreased or lost vision from surgical complications
E. Choroidal hemorrhage
F. Subretinal hemorrhage
G. Infection
Uveitis 38 © AAO 2017-2019

A. Lymphoma cells may be sparse, necrotic and difficult to interpret
1. Patients should be off from therapy with corticosteroids or immunosuppressive medications prior to having
biopsy to maximize yield of pathologic cells
B. Retinal biopsies are often small, difficult to partition and may contain necrotic tissue only
C. Chorioretinal biopsy can separate during fixation making the relationship of the various layers difficult to
interpret
D. Proper orientation of biopsy specimen should be maintained when submitting to pathology
A. Usual postoperative care for vitreoretinal procedures
B. Head positioning to tamponade the site of biopsy
A. Procedure may not lead to diagnosis
B. Procedure may lead to sight-threatening complications
Uveitis 39 © AAO 2017-2019

I. Describe the approach to establishing the diagnosis
A. Describe the etiology of the disease
1. Etiology (see differential diagnosis)
a. Idiopathic (up to 50% of cases, depending on practice setting)
b. Autoimmune (commonly associated with seronegative - Rheumatoid factor-negative -

spondyloarthropathies)
c. Infectious
d. Other causes - see differential diagnosis
2. Genetic risk factor
a. Human leukocyte antigen (HLA)-B27 - approx. 8% population + for HLA-B27, only 1/4 will develop
arthritis/ systemic inflammatory disease
B. Describe the relevant aspects of the epidemiology of the disease
1. Peak incidence in young adults but wide age range
2. Worldwide
3. Male predominance
C. List the pertinent elements of the history
1. Sudden onset
2. Pain, redness, photophobia
3. May have decreased vision
4. Patterns
a. Most common: Acute, unilateral, recurrent in the same eye or contralateral eye. Periods of disease
quiescence off treatment are typically longer duration than episodes of acute disease
i. Consider herpes viruses as an etiology
ii. Inquire about cutaneous manifestations of Herpes infections
b. Rarely: Bilateral, simultaneous
i. Tubulointerstitial nephritis and uveitis (TINU) syndrome History of recent

infections/pharyngitis
D. Describe the pertinent clinical features
1. Mild ptosis
2. Tearing
3. Ciliary flush or bulbar conjunctival injection with quiet palpebral conjunctival surfaces
4. Anterior chamber flare and cells
5. Fibrinous anterior chamber exudates and hypopyon with severe episodes . HLA B-27 associated uveitis is
the most common cause of hypopyon with iridocyclitis
6. Posterior synechiae are common and often fully resolve with appropriate treatment
7. Anterior vitreous cells
8. Secondary CME and optic nerve hyperemia common with severe episodes of inflammation
9. Intraocular pressure commonly several mm Hg lower in the involved eye. (Suspect herpetic cause if
intraocular pressure is elevated)
E. Describe the appropriate testing and evaluation for establishing the diagnosis
Uveitis 40 © AAO 2017-2019

1. History and review of systems with particular attention to
a. Joint pain, redness or swelling - occurring at night or upon awakening. Particularly persistent low
back pain after awakening, hip, knee, heel pain
b. Swelling or deformity of distal digits of hands or feet
c. Skin rashes, particularly psoriasis, rash on palms or soles, nail bed abnormalities, genital skin
abnormalities
d. Mucus membrane lesions of mouth or genitalia
e. Episodes of abdominal pain, blood in stool, history of "colitis" or bowel inflammation
f. Urinary tract symptoms
g. Neurologic or pulmonary symptoms
h. General health problems, medications (particularly new ones), illicit drug use, pets, travel history,
occupational history
2. Physical examination - easily performed components
a. Inspection of hands
b. Inspection of skin for rashes, hair loss or abnormality
c. Spine flexibility
d. Inspection for oral lesions
3. Laboratory evaluation
a. HLA-B27, HLA-DRB1*0102 (TINU)
b. Syphilis IgG with reflex RPR
c. Urinalysis and serum creatinine in acute bilateral cases in young women
d. Urine for Beta 2 microglobulin
e. If granulomatous, ACE, lysozyme, PPD, chest radiograph
II. List the differential diagnosis
A. Systemic diseases associated with the HLA B-27 haplotype
1. Ankylosing spondylitis
2. Reactive arthritis (Reiter syndrome)
3. Inflammatory bowel disease
4. Psoriatic arthritis
B. Behçet disease (See Behçet disease)
C. Sarcoidosis (See Sarcoidosis panuveitis)
D. Infection
1. Viral
a. Herpesvirus family (See Herpetic anterior uveitis)
b. Numerous other viral agents
2. Syphilis (See Syphilitic panuveitis)
3. Leptospirosis
4. Endophthalmitis
E. Post-traumatic iritis
F. Intraocular lens-associated uveitis and UGH (Uveitis Glaucoma Uveitis) syndrome
G. Drug-related uveitis
Uveitis 41 © AAO 2017-2019

1. Rifabutin
2. Cidofovir
H. Tubulointerstitial nephritis uveitis (TINU)
III. Describe patient management in terms of treatment and follow-up
A. Describe medical therapy options for ocular disease
1. Topical corticosteroids
2. Cycloplegia
3. Adjunctive therapy for severe attacks
a. Periocular corticosteroid injections
b. Oral corticosteroids
c. Intravenous pulse corticosteroid
4. Immunomodulatory therapy, especially but by no means exclusively in patients with an underlying systemic
disease, including use of anti - tumor necrosis factor (TNF) alpha agents (See Biologic response modifiers)
5. Sulfasalazine prophylaxis for highly frequent recurrent bouts of HLA-B27 related disease
B. Describe surgical therapy options
1. Rare patients with 360 degree posterior synechiae and iris bombe may require laser iridotomy, and some,
with brown irides, may even require surgical iridectomy
2. Cataract surgery may be performed in selected patients as long as the eye has been inflammation-free for
at least 3 months (See Cataract extraction for uveitis patients)
3. Glaucoma surgery may be necessary. (See Glaucoma surgery for uveitis patients)
IV. List the complications of treatment, their prevention and management
A. Complications of topical corticosteroids
1. Elevated intraocular pressure
2. Cataracts
B. Complications of oral steroid
1. (See Corticosteroids)
C. Complications of immunomodulatory therapy
1. (See Biologic response modifiers)
V. Describe ocular disease-related complications
A. Posterior synechiae and pupillary seclusion
1. Prophylactic PIs not indicated in absence of bombe
B. Peripheral anterior synechiae
C. Glaucoma
D. Cataracts
E. Cystoid macular edema
F. Epiretinal membrane formation
VI. Describe appropriate patient instructions
Uveitis 42 © AAO 2017-2019

A. Medication instructions
1. Discuss side effects
B. Follow-up instructions
C. Discussion of natural history of the disease
D. Appropriate rheumatologic consultation
2. D'Alessandro LP, Forester DJ, Rao NA. Anterior uveitis and hypopyon. Am J Ophthalmology;
1991;112:317-321.
3. Rodriguez A, Akova YA, Pedroza-Seres M, et al. Posterior segment ocular manifestations in patients with
HLA-B27-associated uveitis. Ophthalmology. 1994;101:1267-1274.
4. Chang JH, McCluskey PJ, Wakefield D. Acute anterior uveitis and HLA-B27. Surv Ophthalmol 2005;
50:364-88.
5. Mackensen F, Billing H. Tubulointerstitial nephritis and uveitis syndrome. Curr Opin Ophthalmol. 2009
Nov;20(6):525-31.
Uveitis 43 © AAO 2017-2019

A. Describe the etiology of this disease
1. Unknown
2. Possible association with medications and infections not established
3. Diagnosis requires establishment of acute interstitial nephritis (AIN) and uveitis
4. Known causes of ocular and renal inflammation must be ruled out
a. Systemic lupus erythematosus (SLE)
b. Sarcoidosis
c. Granulomatosis with polyangiitis (GPA), formerly Wegener granulomatosis
d. Systemic infections
B. List the pertinent elements of the history
1. Little to no history of systemic symptoms
2. Self-limited febrile illness
a. Often flank or abdominal pain
b. Usually lasts 2 weeks or more
c. Often weight loss
3. Uveitis usually sudden onset with symptoms:
a. Pain
b. Redness
c. Photophobia
d. Bilateral in nature
C. Describe pertinent clinical features
1. Evidence of AIN (see laboratory findings below)
2. Bilateral non-granulomatous anterior uveitis
a. Granulomatous features (Koeppe nodules, mutton fat keratic precipitates (KP)) have been
described
b. Usually moderate uveitis, but hypopyon has been reported
c. Intermediate and posterior uveitis less common
d. Uveitis can either precede or follow the onset of AIN, occasionally separated in time by a significant
interval (months to years)
3. Recurrent or chronic uveitis in about half the patients
D. Describe appropriate testing and evaluation for establishing the diagnosis
1. Evidence of AIN
a. Non-nephrotic proteinuria (<3.5 g/day)
i. Urinary B2 microglobulin may remain elevated when all else returns to normal
b. Glucosuria
c. Sterile pyuria
Uveitis 44 © AAO 2017-2019

d. Interstitial nephritis on renal biopsy (not always required or performed)
e. Mildly elevated serum blood urea nitrogen level (BUN) and creatinine during AIN
f. Elevated erythrocyte sedimentation rate (ESR) (can be very high during period of febrile illness)
g. Anemia
h. Studies may be indicated to rule out systemic disease. Must be individualized.
II. Define the risk factors
A. Possibly related to drug exposures
B. HLA-DRB1
III. List the differential diagnosis
A. Systemic diseases that can affect the kidneys and eyes
1. SLE
2. Sarcoidosis
3. Polyarteritis nodosa
4. GPA
5. Metastatic/systemic infections
IV. Describe patient management in terms of treatment and follow-up
A. Describe medical therapy options
1. Often AIN treated with systemic corticosteroids
a. AIN usually self-limited
b. Nephrology consult recommended
2. Topical corticosteroids and cycloplegia usually sufficient for anterior uveitis
a. Use of anti-metabolites may be necessary
b. Treat cystoid macular edema (CME) as per other types of uveitis
V. List the complications of treatment, their prevention and management
A. Corticosteroids
1. Cataract and increased intraocular pressure (IOP) as per use of corticosteroids in any form of anterior
uveitis
2. Prevention: minimize dose of corticosteroids
3. Treat elevated IOP as usual
4. Treat cataracts as usual
VI. Describe disease-related complications
A. Prognosis of reported cases has generally been good
B. CME
1. Treat as in any form of uveitis
Uveitis 45 © AAO 2017-2019

VII. Describe appropriate patient instructions
A. Explain need for taking medications when active inflammation (even without symptoms)
B. Explain need for follow-up for possible chronic/recurrent uveitis, complications of disease or treatment
Uveitis 46 © AAO 2017-2019

1. Immune reaction to lens material
a. Phacoantigenic - rupture of the lens capsule
b. Phacolytic - leakage of lens protein through an intact capsule
i. Lens protein and swollen macrophages block the trabecular meshwork
B. Define the relevant aspects of epidemiology of this disease
1. Phacoantigenic
a. Rupture of the lens capsule following trauma or surgery
b. Retained lens fragments after cataract extraction
2. Phacolytic
a. Occurs in setting of mature or hypermature cataract
1. Phacoantigenic
a. History of trauma or intraocular surgery
b. Sudden or insidious onset of decreased vision, pain, redness, photophobia
2. Phacolytic
a. Progressive loss of vision due to gradually worsening cataract
b. Sudden or insidious onset of decreased vision, pain, redness, photophobia
D. Describe pertinent clinical features
1. Phacoantigenic
a. Anterior uveitis
i. Granulomatous or nongranulomatous
ii. Mild to severe
iii. Keratic precipitates; small, punctate, or mutton-fat
iv. Posterior synechiae
v. Hypopyon in some
b. Retained lens material in anterior chamber possible
c. Elevated intraocular pressure
d. Vitreous cells often present
2. Phacolytic
a. Large, refractile cells in the aqueous (lipid containing macrophages)
b. Elevated intraocular pressure
c. Corneal edema possible
d. Lens capsule may appear wrinkled
e. Keratic precipitates rare
f. Posterior synechiae rare
Uveitis 47 © AAO 2017-2019

E. Describe appropriate testing and evaluation for establishing the diagnosis
1. Phacoantigenic
a. History and clinical exam paramount
b. B-scan ultrasonography
i. Useful if lens material located in vitreous
c. Histopathology of lens material
i. Zonal granulomatous inflammation centered about the site of injury. Neutrophils with the
lens material surrounded by lymphocytes, plasma cells, epithelioid cells, macrophages
2. Phacolytic
a. Anterior chamber paracentesis may be considered
i. Aqueous cytology may reveal swollen macrophages
A. Trauma
B. Cataract or glaucoma surgery
C. Advancing age, dense cataract
A. Sympathetic ophthalmia
B. Postoperative endophthalmitis
C. Traumatic iritis
D. Anterior uveitis
E. Intermediate uveitis
F. Posner-Schlossman syndrome (phacolytic)
IV. Describe patient management in terms of treatment and follow up
1. Phacoantigenic
a. Corticosteroids
i. Topical or regional. Severe cases may require systemic therapy
b. Cycloplegics
c. Aqueous suppressants to control intraocular pressure
2. Phacolytic
a. Aqueous suppressants to control intraocular pressure
i. Additional topical and/or systemic therapy may be required to lower the intraocular pressure
b. Topical corticosteroids
1. Phacoantigenic
a. Cataract extraction is typically curative and should be performed as soon as possible
b. In cases with retained lens material
Uveitis 48 © AAO 2017-2019

i. Removal of all residual lens material in most cases, consider vitrectomy for cases of lens
material in posterior segment
ii. Patients with very small amounts of lens material may improve with corticosteroid therapy
alone
2. Phacolytic
a. Cataract extraction as soon as possible
V. Describe the complications of treatment, their prevention, and management
A. Medical (See Corticosteroids)
B. Surgical (See Cataract extraction for uveitis patients)
A. Pupillary membrane
B. Glaucoma
C. Corneal edema and decompensation
D. Cystoid macular edema
A. Use medications as prescribed
B. Adhere to postoperative instructions
C. Report changes in vision and/or pain immediately
2. Michel SS, Foster CS. Lens-Induced Uveitis. In: Foster CS, Vitale AT, eds. Diagnosis and Treatment of
Uveitis. Philadelphia: W.B. Saunders; 2002:817-21.
Uveitis 49 © AAO 2017-2019

1. See differential diagnosis below
2. Often idiopathic
1. Onset is usually insidious
2. Duration is at least 3 months
3. Blurred vision
4. Floaters
5. May be asymptomatic
6. Pain, redness and photophobia are rare, although may occur at onset or intermittently
1. Keratic precipitates (KP)
a. Often medium or large and "mutton fat"
b. May be inactive, crenellated "ghost" KP
c. Anterior chamber (AC) cell
d. AC flare, may be significant, even with few cells
e. Anterior vitreous cells
f. Iris nodules
g. Koeppe
i. At pupillary border
ii. Not pathognomonic of granulomatous disease
h. Busacca
i. In iris stroma, pathognomonic of granulomatous disease
1. Detailed history, review of systems is paramount
2. Chest x-ray (CXR). Alternatively, in adults, consider high resolution computed tomography of chest with and
without contrast or similar imaging, such as gallium scanning
3. Angiotensin converting enzyme, lysozyme - Not very sensitive or specific for sarcoid; may be suggestive of
granulomatous disease but should be used in conjunction with chest imaging
4. Purified protein derivative (PPD) if appropriate or QuantiFERON-TB testing
5. Specific treponemal test, such as syphilis IgG
6. Rest of work-up guided by history/age of patient e.g., antinuclear antibodies looking for juvenile idiopathic
arthritis (JIA) in pediatric age group
A. Systemic inflammatory disease such as sarcoidosis
B. Trauma or multiple intraocular eye surgeries
Uveitis 50 © AAO 2017-2019

A. Local eye disease - e.g.
1. Fuchs heterochromic iridocyclitis (See Fuchs heterochromic iridocyclitis)
2. Viruses such as herpes simplex, herpes zoster, cytomegalovirus, and rubella may cause recurrent or
chronic anterior uveitis in immunocompetent individuals
3. Intermediate or posterior uveitis with anterior segment inflammation
B. Associated with systemic disease, inflammatory or infectious - e.g.
1. Multiple sclerosis
2. Sarcoidosis
3. Tuberculosis
4. Syphilis
5. Inflammatory bowel disease
6. JIA
a. Less frequently than for acute disease
b. Prednisolone acetate 1% two to four times a day
c. Check intraocular pressure (IOP) at every visit, even patients with on topical corticosteroids for
years may develop corticosteroid-induced IOP elevations
2. Dilating drops
a. Homatropine 5%, atropine 1%, cyclopentolate 1-2%
b. May be required indefinitely, especially in patient with posterior synechiae and chronic flare
3. Local injection (off-label use) (See Corticosteroids)
a. Corticosteroids - watch IOP
i. Anterior Sub-Tenons for anterior chamber reaction
ii. Posterior Sub-Tenons for cystoid macular edema (CME)
iii. Orbital floor injection for CME
iv. Triamcinolone acetonide can be used
v. Intravitreal injection triamcinolone acetonide for CME (off-label use)
b. Intravitreal injection of anti-VEGF agents (off-label use) for CME
4. Systemic therapy
a. Oral prednisone (See Corticosteroids)
i. Avoid long term; remember that bone metabolism negative effects are seen as early as 3
months of therapy with prednisone as low as 5 mg a day. Baseline DEXA scan for anyone
in whom corticosteroid therapy beyond 3 months is anticipated
ii. If require more than 5 mg/day prednisone after 3 - 6 months, consider steroid-sparing
immunomodulatory treatment (IMT)
b. Corticosteroid-sparing agents (See Corticosteroids)
i. Methotrexate
ii. Azathioprine
Uveitis 51 © AAO 2017-2019

iii. Cyclosporine
iv. Tacrolimus
v. Mycophenolate mofetil
vi. TNF inhibitors (not etanercept)
5. Internal medicine consultation for systemic disease, if appropriate
B. Describe surgical therapy options (See Cataract extraction for uveitis patients) (See Glaucoma surgery for
uveitis patients)
A. Topical corticosteroids: cataract, glaucoma, ptosis
B. Depot corticosteroid injection: as above, plus inadvertent perforation of globe
C. Systemic therapy (See Corticosteroids)
VI. Describe disease related complications
A. Posterior synechiae are frequent
B. Anterior synechiae (peripheral anterior synechia (PAS))
C. Ocular hypertension/glaucoma
1. Frequent
2. Open angle
a. Cells and debris in meshwork
b. "Corticosteroid response"
3. Closed angle
a. Progressive PAS
b. Pupillary block secondary to posterior synechiae
D. Hypotony
1. More difficult to treat than glaucoma
2. Atrophy of ciliary processes
3. Inflammation of ciliary processes
a. Treat with anti-inflammatory drugs
4. Ciliary body detachment
a. Due to cyclitic membranes
b. Diagnose with ultrasound biomicroscopy
c. May be able to treat surgically
E. Iris atrophy
F. Epiretinal membrane
G. CME - frequent cause of decreased vision
H. Cataract, due to underlying inflammatory disease and corticosteroid use - very frequent
I. Band keratopathy (much more common in children)
Uveitis 52 © AAO 2017-2019

A. Nature of chronic disease, i.e., we may not be able to cure the disease, and the patient may require eye
drops indefinitely
B. Necessity of using eye drops even in absence of symptoms
C. Requirement for follow-up, even in absence of symptoms
1. For example, may develop asymptomatic glaucoma secondary to corticosteroid drops
Uveitis 53 © AAO 2017-2019

A. Describe the etiology of the uveitis
1. Usually associated with oligoarticular juvenile idiopathic arthritis (JIA) (previously known as juvenile
rheumatoid arthritis - JRA), but may also occur in those children with polyarticular onset form of the disease
B. Describe the relevant aspects of the epidemiology of juvenile arthritis
1. Oligoarticular onset JIA - most common chronic form of arthritis in children in North America/Europe
a. Four or fewer joints (within 6 months of presentation)
b. Female: male 5:1
c. Onset of age 2-8 years
d. 50 - 60 % of cases
e. ANA + in 85%, RF Negative
f. Uveitis frequent - up to 30% will develop AU in first 4 years of disease
2. Polyarticular, rheumatoid factor negative onset JIA
a. More than 4 joints
b. Female: male 3:1
c. Bimodal age of onset <5, teenager
d. ANA + in 40%
e. Intermediate risk of uveitis - up to 10% will develop AU
3. Polyarticular rheumatoid factor positive
a. Older onset than typical JIA patients
b. Female predominance
c. Behave like adult rheumatoid arthritis
d. Uveitis may occur
e. May develop scleritis
4. Systemic onset JIA
a. Any number of joints
b. Onset <5 years and no sex predilection
c. 10 - 20% cases
d. Antinuclear antibodies (ANA) usually negative (10% positive)
e. Uveitis is rare
5. Juvenile human leukocyte antigen (HLA) B27 associated enthesitis
a. Recurrent acute iritis, one eye at a time
b. More common in boys
6. Psoriatic arthritis
a. Resembles Oligoarthritis or RF negative Polyarthritis and 2 of the following
i. Nail pitting or onycholysis, dactylitis or history of psoriasis in a 1st degree relative
b. Up to 10% will develop AU
Uveitis 54 © AAO 2017-2019

1. Uveitis associated with oligoarticular JIA
a. Asymptomatic
b. Painless loss of vision
2. Uveitis associated with HLA-B27 (See Acute anterior uveitis)
D. Describe the pertinent clinical features of JIA uveitis
1. Bilateral
2. Non-granulomatous iridocyclitis
3. Quiet conjunctiva
E. Describe the diagnostic procedures
1. ANA
2. Rheumatology consult if necessary
A. Oligoarticular onset JIA
B. Female sex
C. ANA +
D. Arthritis onset between 2 and 5 years of age
1. Highest risk is within 2 years of onset of arthritis
2. 90% have arthritis first, although uveitis may precede arthritis diagnosis
E. Describe the factors associated with poorer visual outcome
1. More severe ocular involvement at presentation
2. Longer duration of uveitis
3. Longer delay from onset to employment of steroid-sparing immunomodulatory therapy
4. Female sex
5. Younger age at onset of uveitis
6. Uveitis diagnosis prior to arthritis diagnosis
7. Not associated with worse visual outcome:
a. Severity of arthritis
b. Titer of ANA
A. Sarcoidosis (juvenile onset)
B. Inflammatory bowel disease associated uveitis
C. Herpetic uveitis (unilateral)
D. Lyme disease
E. Tubulointerstitial nephritis and uveitis
A. Mild disease
Uveitis 55 © AAO 2017-2019

2. Mydriatics
B. Moderate disease
1. Consider adding periocular corticosteroids
2. Consider adding oral non-steroidal anti-inflammatory drugs (NSAIDs)
3. Consider corticosteroid-sparing immunomodulatory therapy (IMT) such as methotrexate, azathioprine,

cyclosporine
C. Severe disease
1. Short term oral corticosteroids
2. Immunomodulatory therapy (e.g., methotrexate, azathioprine or cyclosporine; in rare instances,

chlorambucil)
3. Biologic inhibitors
a. Anti-tumor necrosis factor agents
i. Etanercept has poor efficacy as treatment for uveitis although it does work for inflammatory
joint involvement
ii. Both infliximab and adalimumab appear efficacious for the uveitis
b. Other biologic inhibitors such as anti-CD20 (rituximab), T-cell activation inhibitors (abatacept,
daclizumab)
D. Ethylene diamine tetra acetate chelation of band keratopathy
E. Cataract surgery
1. Quiet/controlled inflammation for at least three months before surgery
2. Lensectomy, vitrectomy, and no intraocular lens (IOL) is a commonly utilized approach
3. Although controversial, may consider phacoemulsification/posterior chamber IOL in selected favorable

circumstances, with strict inflammatory control
4. Anti-inflammatory coverage
5. Since cataract surgery may create additional problems, it is strongly recommended to employ systemic
steroid-sparing agents to minimize steroid exposure BEFORE cataract formation begins
A. Topical and periocular corticosteroid therapy
1. Cataract
2. Glaucoma
3. Ptosis
4. Periocular corticosteroid therapy only - Inadvertent perforation of the globe
B. Systemic corticosteroids and immunosuppressive therapy (See Corticosteroids) (See Methotrexate) (See
Cyclosporine)
A. Posterior synechiae (very frequent)
B. Band keratopathy
C. Cataract
D. Glaucoma
E. Hypotony
F. Macular edema
Uveitis 56 © AAO 2017-2019

G. Amblyopia
A. JIA patients without uveitis require screening
1. Low risk - e.g., systemic onset, ANA negative oligo or polyarthritis with older age of onset: Annual exam
2. Moderate risk
a. ANA negative: Younger than 6 years of age at onset of arthritis and duration of arthritis less than 4
years: every 6 months
b. ANA positive: Older than 6 years of age at arthritis onset with duration less than 4 years or younger
than 6 years with duration more than 4 years: Every 6 months
3. High risk: ANA positive, age of arthritis onset less than 6 years, duration of arthritis less than 4 years: Every
3 months
B. Patients with uveitis
1. Follow-up based on severity of disease
2. Need for treatment even without symptoms
C. Summary of screening guidelines
VIII. Describe "chronic iridocyclitis of young girls"
A. Uveitis resembles that seen in JIA
B. No joint disease
C. ANA may be positive or negative
D. Some of these patients, particularly with positive ANA, may go on to develop bona fide JIA
2. Cunningham ET Jr. Uveitis in children. Ocul Immunol Inflamm. 2000;8:251-261.
3. Dana MR, Merayo-Lloves J, Shaumberg DA, et al. Visual outcomes prognosticators in juvenile rheumatoid
arthritis-associated uveitis. Ophthalmology. 1997;104:236-244.
4. Giannini EH, Brewer EJ, Kuzmina N, et al. Methotrexate in resistant juvenile rheumatoid arthritis. Results of
the U.S.A.-U.S.S.R. double-blind placebo-controlled trial. The Pediatric Rheumatology Collaborative Study
Group and the Co-operative Children's Study Group. N Engl J Med. 1992;326:1043-1049.
5. Kanski JJ. Juvenile arthritis and uveitis. Surv Ophthalmol. 1990;34:253-267.
6. Probst LE, Holland EJ. Intraocular lens implantation in patients with juvenile rheumatoid arthritis. Am J
Ophthalmol. 1996;122:161-170.
7. Weiss AH, Wallace CA, Sherry DD. Methotrexate for resistant chronic uveitis in children with juvenile
rheumatoid arthritis. J Pediatr. 1998;133:266-268.
8. Smith JA, Thompson DJ, Whitcup SM et al. A randomized, placebo-controlled, double-masked clinical trial
of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis. Arthritis Rheum 2005;
53:18-23.
9. Heiligenhaus A, Miserocchi E, Heinz C, Gerloni V, Kotaniemi K. Treatment of severe uveitis associated with
juvenile idiopathic arthritis with anti-CD20 monoclonal antibody (rituximab). Rheumatology (Oxford). 2011
Aug;50(8):1390-4. Epub 2011 Mar 4.
10. Kenawy N, Cleary G, Mewar D, Beare N, Chandna A, Pearce I. Abatacept: a potential therapy in refractory
cases of juvenile idiopathic arthritis-associated uveitis. Graefes Arch Clin Exp Ophthalmol. 2011
Feb;249(2):297-300. Epub 2010 Oct 5.
11. Sen HN, Levy-Clarke G, Faia LJ, Li Z, Yeh S, Barron KS, Ryan JG, Hammel K, Nussenblatt RB.High-dose
daclizumab for the treatment of juvenile idiopathic arthritis-associated active anterior uveitis. Am J
Uveitis 57 © AAO 2017-2019

Ophthalmol. 2009 Nov;148(5):696-703.e1. Epub 2009 Aug 6.
12. Cassidy J, Kivlin J, Lindsley C, Nocton J; Section on Rheumatology; Section on Ophthalmology.

Ophthalmologic examinations in children with juvenile rheumatoid arthritis. Pediatrics. 2006
May;117(5):1843-5.
13. Heiligenhaus A, Niewerth M, Ganser G, Heinz C, Minden K; German Uveitis in Childhood Study Group.
Prevalence and complications of uveitis in juvenile idiopathic arthritis in a population-based nation-wide
study in Germany: suggested modification of the current screening guidelines. Rheumatology (Oxford).
2007 Jun;46(6):1015-9.
Uveitis 58 © AAO 2017-2019

1. Evidence for an association with rubella, cytomegalovirus, Toxoplasmosis
2. Heterochromia, abnormal angle vessels, links to sympathetic disorders, and electron microscope studies
suggest theory of decreased adrenergic innervation
3. Immunoglobulin deposit in iris vessel walls may be related to formation of disease
1. No pain, redness or photophobia
2. Often found on routine exam
3. Decreased vision, usually caused by cataract
4. Floaters
1. Usually unilateral, but bilateral in 7 - 15%
2. Heterochromia
a. Not required for diagnosis
b. May be hard to discern in dark irides
c. Affected eye usually lighter
d. Affected eye may be darker late in disease in blue-eyed patient with extensive loss of stroma
(increased visibility of posterior iris pigment epithelium)
3. Keratic precipitates (KP)
a. Small
b. Stellate
c. Distributed throughout the whole cornea, rather than in Arlt triangle
4. Iris atrophy
a. Diffuse, involving anterior iris stroma and loss of crypts
b. Transillumination defects rare
5. Koeppe nodules may be present, but does not form posterior synechiae in absence of surgery
6. Anterior chamber cells and flare
7. Anterior vitreous cells
8. No posterior synechiae (rare exceptions)
9. Cataract
a. Usually posterior subcapsular cataract
b. In approximately 70%
10. Elevated intraocular pressure/glaucoma
a. Up to 50%
b. Open-angle
11. Abnormal angle vessels
a. Do not grow or fibrose like rubeotic vessels
Uveitis 59 © AAO 2017-2019

b. Do not cause angle closure
c. Amsler sign
i. Bleeding after anterior chamber paracentesis e.g. 180 degrees away from paracentesis site
A. Herpetic uveitis
B. Sarcoid uveitis or other chronic anterior uveitis
C. Other causes of heterochromia - e.g., congenital Horner syndrome, iridocorneal endothelial syndrome,
diffuse iris melanoma
D. Prostaglandin analogue therapy for glaucoma (especially if the eye drop is only used in one eye; no stellate
KP or vitreous cells)
E. Syphilis
1. Inflammation does not tend to require treatment unless the patient is symptomatic
2. Some patients see better if the keratic precipitates are cleared with topical corticosteroids
3. Treatment of glaucoma
a. May be resistant to medical therapy
b. May require trabeculectomy or shunt procedures
4. Treatment for confirmed infectious causes
a. Anti-viral
i. Ganciclovir
b. Antibiotic
i. Toxoplasmosis
1. Cataract
a. Do well with standard phacoemulsification surgery for cataract
b. Increased risk of intraoperative or postoperative hyphema (because of abnormal angle vessels)
2. Glaucoma may be resistant to medical therapy
3. Vitreous opacities, if visually significant, may consider pars plana vitrectomy
A. Rarely need corticosteroid therapy
B. Avoid over-treatment
C. Treat patient symptoms only, not the amount of cells in the eye
V. Describe disease related complications
A. Glaucoma
B. Cataract
C. Vitreous opacification
Uveitis 60 © AAO 2017-2019

A. Need follow-up because of risk for glaucoma
2. La Hey E, Mooy CM, Baarsma GS, de Vries J, de Jong PT, Kijlstra A. Immune deposits in iris biopsy
specimens from patients with Fuchs' heterochromic iridocyclitis. Am J Ophthalmol. 1992 Jan
15;113(1):75-80.
3. Chee SP, Bacsal K, Jap A, Se-Thoe SY, Cheng CL, Tan BH. Clinical features of cytomegalovirus anterior
uveitis in immunocompetent patients. Am J Ophthalmol. 2008 May;145(5):834-40. Epub 2008 Feb 6.
Uveitis 61 © AAO 2017-2019

1. Idiopathic
a. Pars planitis
b. Non pars planitis
2. Associated with systemic inflammatory or infectious disease
a. Multiple sclerosis (MS)
b. Sarcoidosis
c. Inflammatory bowel disease
d. Tubulointerstitial nephritis and uveitis
e. Masquerade [central nervous system (CNS) lymphoma]
f. Infections
i. Lyme disease
ii. Whipple disease (older patient)
iii. Toxocara
iv. Syphilis
v. HTLV
vi. If dense vitritis must consider other infections with focus of retinitis not seen (e.g. primary
acquired ocular toxoplasmosis)
B. Define the relevant aspects of epidemiology of the disease
1. Pars planitis
a. Disease of children and young adults
b. Bimodal age distribution
i. 5 - 15 years
ii. 25 - 35 years
1. Floaters
2. Decreased vision
3. Pain and photophobia are very rare (more common in young children)
4. Onset is usually insidious
5. Long duration (chronic)
1. Anterior chamber reaction
a. Absent or very mild in adults
b. May be more severe in children
2. Vitreous cell always present in active disease
Uveitis 62 © AAO 2017-2019

3. Snowballs
a. White or yellowish aggregates of inflammatory cells
i. More common inferiorly
4. Snowbanks
a. Coalesced exudates or in late stages fibroglial mass
b. May be vascularized, especially in pediatric age group (vitreous hemorrhage may be a presenting
sign of pars planitis in children)
c. Seen in pars planitis
d. Pars plana/ora serrata
e. Usually inferior, may extend 360 degrees
5. Periphlebitis is common
6. Periarteritis is not typical of pars planitis
7. Pars planitis is bilateral at presentation in 70-80%
1. MS (history suggestive of MS, e.g. limb paresthesias (face less commonly), weakness, gait disturbance,
balance problems and vertigo, bladder incontinence, tingling)
a. Neurologic exam
b. Magnetic resonance imaging (MRI)
c. CSF analysis for atypical cases
d. Human leukocyte antigen (HLA)-DR2
2. Sarcoid
a. LFTs
b. Urine and serum calcium
c. PFTs (pulmonary consult)
d. Angiotensin converting enzyme/lysozyme
i. Low sensitivity and specificity
e. Chest x ray (sensitivity ~60%); if chest x ray negative and suspicion remains high, consider chest
CT (>90% sensitive)
i. Radiation exposure of CT chest ~70x that of x ray
f. Gallium scan or PET in select cases
g. Definitive diagnosis requires biopsy with histology showing noncaseating granulomas without other
cause (negative stains for infectious agents such as fungi and TB; no evidence of foreign body by
polarized light)
3. Lyme disease
a. Serology (confirmation needed by western blot if ELISA positive or equivocal)
b. History suggestive of exposure or Lyme disease (erythema chronicum migrans rash)
4. Masquerade syndrome (e.g. Lymphoma)
a. Diagnostic vitrectomy with cytology and flow cytometry
b. MRI of the brain
c. Lumbar puncture
5. Other infections (e.g. Whipple disease, toxocariasis, syphilis)
a. Serologies
b. Cultures and PCR of vitreous
Uveitis 63 © AAO 2017-2019

c. Small bowel biopsy revealing PAS-positive macrophages (Whipple disease)
A. Pars planitis - idiopathic
B. Infections
1. Syphilis
2. Lyme disease - clinical history
3. Whipple disease - older patient
4. Toxocariasis - unilateral, look for granuloma
C. Sarcoidosis
D. Intraocular lymphoma - older patient
E. Inflammatory bowel disease
F. Intermediate uveitis associated with MS
1. May not need therapy, if vision is good and there is no cystoid macular edema, vitreous hemorrhage, or
other vitreous opacity
2. Offer treatment if there is cystoid macular edema (CME), even if good vision
3. Local corticosteroids
a. Sub-Tenon or periocular corticosteroid injection
b. Intravitreal triamcinolone acetonide
c. Fluocinolone implant (Retisert®)
d. Dexamethasone pellet (Ozurdex®)
4. Oral corticosteroids
a. Short-term only; avoid long-term high dose
5. Corticosteroid sparing agents
a. Methotrexate
b. Azathioprine
c. Cyclosporine
d. Mycophenolate mofetil
e. TNF inhibitors; contraindicated if any question of masquerade syndrome, infection or demyelinating

disease
1. As primary therapy to decrease the immunologic stimulus (debatable, not proven)
a. Cryotherapy to snowbank-rarely performed now in deference to laser treatment
b. Laser application posterior to the snowbank
c. Vitrectomy
2. For management of disease related complications (e.g. retinal neovascularization, epiretinal membrane,
retinal detachment)
a. Vitrectomy
b. Cryotherapy or laser of ischemic retina
Uveitis 64 © AAO 2017-2019

A. Cryotherapy
1. Increased inflammation
2. Increased risk of rhegmatogenous retinal detachments
B. Vitrectomy
1. Increased risk of cataract
2. Increased risk of proliferative vitreoretinopathy
3. Increased risk of retinal detachment
4. Potentially, increased risk for flare-up in the immediate postoperative period
C. Periocular/intraocular corticosteroid injection (off-label) or slow release device implantation
1. Cataract
2. Glaucoma
3. Ptosis with periocular injection
4. Perforation with periocular injection-very rare
5. Endophthalmitis with intravitreal injection
V. Describe disease related complications
A. Cystoid macular edema
1. Most frequent cause of decreased vision
B. Vitreous hemorrhage
1. More common in children
2. Usually clears spontaneously
C. Optic disc edema is frequent
D. Neovascularization of the disc or elsewhere
1. Rare
E. Band keratopathy
F. Cataract
G. Glaucoma or hypotony
H. Epiretinal membrane
I. Retinal detachment
1. Rhegmatogenous and tractional
2. Coats-like reaction
a. Rare
A. Chronic nature of the disease
B. In pars planitis, 2/3 of treated patients maintain visual acuity of 20/40 or better in at least one eye
Uveitis 65 © AAO 2017-2019

2. Park SE, Mieler WF, Pulido JS. 2 peripheral scatter photocoagulation for neovascularization associated with
pars planitis. Arch Ophthalmol. 1995 Oct;113(10):1277-80.
3. Böke WRF, Manthey KF, Nussenblatt RB. Intermediate Uveitis. Developments in Ophthalmology 23. Basel:
Karger; 1992.
4. Dugel PU, Rao NA, Ozler S, et al. Pars plana vitrectomy for intraocular inflammation-related cystoid macular
edema unresponsive to corticosteroids: a preliminary study. Ophthalmology. 1992;99:1525-1541.
5. Hikichi T, Trempe CL. Role of the vitreous in the prognosis of peripheral uveitis. Am J Ophthalmol.
1993;116:401-405.
6. Hooper PL. Pars planitis. In: Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American
Academy of Ophthalmology; 1993;9:11.
7. Malinowski SM, Pulido JS, Folk JC. Long-term visual outcome and complications associated with pars
planitis. Ophthalmology. 1993;100:818-824.
8. Michelson JB, Friedlaender MH, Nozik RA. Lens implant surgery in pars planitis. Ophthalmology.
1990;97:1023-1026.
9. Mochizuki M, Tajima K, Watanabe T, et al. Human T-lymphotropic virus type 1 uveitis. Br J Ophthalmol.
1994;78:149-154.
10. Park SE, Mieler WF, Pulido JS. Peripheral scatter photocoagulation for neovascularization associated with
pars planitis. Arch Ophthalmol. 1995;113:1277-1280.
11. Potter MJ, Myckatyn SO, Maberley AL, et al. Vitrectomy for pars planitis complicated by vitreous
hemorrhage: visual outcome and long-term follow-up. Am J Ophthalmol. 2001;131:514-515.
12. Pulido JS, Mieler WF, Walton D, et al. Results of peripheral laser photocoagulation in pars planitis. Trans
Am Ophthalmol Soc. 1998;96:127-141.
13. Raja SC, Jabs DA, Dunn JP, et al. Pars planitis: clinical features and class II HLA associations.
Ophthalmology. 1999;106:594-599.
Uveitis 66 © AAO 2017-2019

1. Etiology is unknown
2. Many cases have been reported following viral syndromes
3. Sporadic cases reported in association with other systemic illnesses, including cerebral vasculitis, which
may be fatal
1. Usually in young, healthy adults
2. Although it is a well-known type of posterior uveitis, it is infrequent
1. Sudden onset of bilateral disturbance in vision
2. No photopsias
3. May be asymmetric with complaints involving only one eye
4. Review of systems
a. Patient should be queried for
i. Recent viral illnesses
ii. Neurological (to uncover a systemic/central nervous system vasculitis) and other symptoms
iii. Review of system may be negative
1. Creamy yellow to gray white, flat, subretinal lesions at the level of the retinal pigment epithelium (RPE)
2. Central or paracentral scotomas
3. Rapid resolution of the lesions, with varying degree of residual RPE disturbance which may limit vision
4. OCT imaging may reveal disruption in the inner/outer photoreceptor junction (ellipsoid zone)
5. Good return of vision in most cases is expected (though potentially less in ampiginous version) (See
Serpiginous choroidopathy)
a. May be associated with episcleritis, vein occlusion, or optic nerve edema
b. Mild vitreous reaction may be present, but iritis would be very unusual
c. Subretinal fluid collections are sometimes seen
E. Describe appropriate testing and evaluation to establish the diagnosis
1. Fundus photography
2. Fluorescein angiography may be the most characteristic finding of the disease
a. In acute disease, the visible lesions block early and stain late with fluorescein
b. Window defects are present on angiography in later stages of disease, due to damage to the RPE
A. Serpiginous choroidopathy
Uveitis 67 © AAO 2017-2019

B. Syphilitic, Sarcoid, TB, Bartonella chorioretinitis
C. Punctate outer retinal toxoplasmosis if unilateral
D. Multifocal choroiditis
E. Punctate inner choroidopathy
F. Birdshot chorioretinopathy
G. Viral retinitis
H. Diffuse unilateral subacute neuroretinitis
I. Cerebral vasculitis with ocular manifestations
J. Primary CNS lymphoma/primary vitreoretinal lymphoma
1. Oral corticosteroids have been recommended to speed resolution, especially in cases with extensive
macular or foveal involvement
a. However, its efficacy has not been proven
b. High dose corticosteroid treatment suggested if cerebral vasculitis is present
IV. Describe disease-related complications
A. Choroidal neovascularization
B. Persistent scotomata/reduced vision, especially if foveal involvement
C. Permanent reduction in vision due to RPE scarring or choroidal neovascular membrane
V. Describe appropriate patient instructions
A. Reassurance that resolution of symptoms is likely to occur with return of normal or near normal vision
B. Improvement in vision occurs over a period of months
C. Periodic ophthalmologic examinations are needed to document changes as disease resolves and check for
complications
D. Corticosteroid treatment is optional and unproven, but some feel that it might shorten the time to resolution
or improve outcomes
E. Headache or neurologic symptoms should be reported promptly
2. AAO, Focal Points: White Dot Syndrome, Module #4, 2007.
Uveitis 68 © AAO 2017-2019

1. Etiology unknown
B. Define the relevant aspects of the epidemiology of this disease
1. People of Northern European extraction with HLA-A29 genetic background
2. Mean age at presentation 53 years
3. Slight female predominance
1. Visual loss
2. Floaters
3. Nyctalopia
4. Dyschromatopsia
1. Spots: cream to pale orange, 200-600 microns in diameter, indistinct borders, choroidal, most prominent
nasally>inferiorly>superiorly (temporal periphery spared); ovoid-shaped lesions with the long axis oriented
along radial lines centered on the disc
2. Minimal or no anterior chamber inflammation
3. Mild vitreous inflammation
4. Fluorescein Angiography (FA) is useful as it may show retinal venular leakage, disc leakage, and cystoid
macular edema. Birdshot lesions show up on FA depending on the stage of the disease.
5. Cystoid macular edema
6. Narrowed arterioles
7. Indocyanine green angiography will show the spots as hypocyanescent, and there may be more spots or
larger spots than are seen ophthalmoscopically or on FA
1. The diagnosis is clinical; not established unequivocally by any test
2. The presence of Human leukocyte antigen (HLA) -A29 is considered strong evidence in the appropriate
clinical setting, as this gene is strongly associated with Birdshot (up to 95%); however, HLA-29 is not
diagnostic (8% of Caucasians have the allele). Some practitioners consider the diagnosis problematic in the
absence of this cell surface marker
A. Northern European ancestry
B. Presence of HLA-A29
A. Sarcoidosis
B. Intraocular lymphoma
C. Syphilitic chorioretinitis
D. Multifocal choroiditis
Uveitis 69 © AAO 2017-2019

E. Punctate inner choroiditis
F. Multiple evanescent white dot syndrome (MEWDS)
G. Tuberculosis
1. Short-term and intermittent flare up control
a. Corticosteroids systemically, by intravitreal or periocular injection (not drops), or by intraocular

corticosteroid implant
b. Due to typical bilateral and chronic nature, intermittent local therapy is not a viable long term option,
though it may be useful for control of cystoid macular edema in the short term
2. Long-term control
a. Immunomodulatory medications
i. May be needed in most patients (some clinicians treat all patients regardless of visual
status due to generally poor long-term prognosis)
ii. May help slow down the rate of progression of disease, but whether induces durable,
drug-free remission is debated
iii. Mycophenolate commonly employed, some combine with cyclosporine
b. Long-acting steroid implant (i.e. fluocinolone intraocular implant for multi-year control)
B. Describe follow-up options
1. FA is useful to follow clinical activity by detecting vasculitis, disc leakage, and/or macular leakage
a. Retinal vascular leakage typically ceases in advanced disease yet vision loss may continue
b. FA in advanced disease may demonstrate poor perfusion with early loss of visible dye in vessels at
1 to 2 minutes post injection
2. OCT helpful in rapidly assessing for CME
3. Visual fields, either computerized or Goldmann, to measure retinal sensitivity and map blind spots
a. Pericentral scotomas and perineural scotomas common even in early disease
b. Peripheral vision loss common in advanced disease
4. ICG
a. May reveal many more choroidal lesions than exam or FA
b. Could be used to assess response to therapy
5. ERG to evaluate for photoreceptor dysfunction in advanced disease
a. Reduction of rod B wave amplitude correlates with nyctalopia
b. Prolongation of cone 30 Hz flicker B wave implicit time correlates with overall disease activity
6. Visual field and ERG abnormalities may improve in patients on IMT
A. Corticosteroid (See Corticosteroids)
B. Immunomodulatory therapy (IMT) should be considered at the outset for symptomatic disease and possibly
for all disease
C. Disease progression may ensue despite IMT
Uveitis 70 © AAO 2017-2019

A. Cystoid macular edema
B. Epiretinal membranes
C. Moderate to severe vision loss from retinal degeneration (over many years)
D. Optic atrophy
E. Subretinal neovascularization
F. Night blindness
G. Reduced contrast sensitivity, color perception
H. Visual field loss
I. Apparent increased risk of normal tension glaucoma related to choroidal thinning and ischemia
VII. Prognosis
A. Some studies have suggested that some patients with birdshot (15-20%) have a favorable prognosis,
however, the largest studies with long-term follow up suggest that the prognosis is poor without treatment
and that this is a function of disease duration and independent of systemic corticosteroid use
B. Two large cohorts show about a 20%, 5-year cumulative incidence of visual acuity of worse than 20/200
C. Systemic corticosteroids are ineffective as monotherapy
D. Preservation of visual function, with a reduction of inflammation, reduced risk of macular edema, and
preservation of global retinal integrity as measured by VF and ERG
E. Some believe that the induction of long-term remission is possible in patients with birdshot managed with
aggressive IMT
A. Medication should be taken as instructed
B. Disease may be chronic or spontaneously remit in 20%. Treatment for 2 to 4 years may increase the
chances of remission
C. Risk of long-term visual disability
D. Familial cases of birdshot retinochoroidopathy rare, despite HLA-A29 association
2. Monnet D, Brezin AP. Birdshot choroidopathy. Curr Opin Ophthalmol 2006;17:545-50.
3. Kiss S, Anzaar F, Foster SC. Birdshot retinochoroidopathy. Int Ophthlamol Clin 2006;46:39-55.
4. Levinson RD, Brezin A, Rothova A et al. Research criteria for the diagnosis of birdshot choroidretinopathy:
results of an international consensus conference. Am J Ophthalmol 2006;141:185-7.
5. Shah KH, Levinson RD, Yu F et al. Birdshot choroidretinopathy. Surv Ophthalmol 2005;50:519-41.
Uveitis 71 © AAO 2017-2019

1. Unknown
2. MEWDS may represent a spectrum of disease from an acute idiopathic blind spot to multi focal choroiditis
1. Most common in young, healthy women
2. May follow a viral syndrome
1. Sudden onset of blurred vision in one eye associated with photopsias and paracentral scotomata
2. May be aware of a shadow in the temporal field of vision (enlarged blind spot)
1. Ocular features depend on the time of examination following onset.
a. In early stages, gray-white, poorly demarcated, patchy outer retinal lesions are present along and
outside the arcades, usually 200 to 500 microns
i. They may not be visible in all quadrants
ii. They fade rapidly
iii. Acute lesions are hyperfluorescent
b. Orange, granular pigmentation of the fovea as the acute lesions resolve
c. Vitreous cellular reaction (mild, if present)
d. May have a prominent sectoral field defect in the area most involved with the white dots
e. May have an afferent pupillary defect
f. Subtle clinical signs may be present in absence of symptoms
2. Rapid resolution of retinal lesions and usually a return to normal vision
3. Slower resolution of granular macular pigmentation
4. Retinal pigment epithelium scarring infrequently occurs but when it does may be associated with permanent
field defects
1. Fluorescein angiography may demonstrate the typical "wreath-like" collections of punctate

hyperfluorescence at the site of the white lesions
2. Indocyanine green angiography (ICG) may show multiple hypocyanescent spots, more numerous than on
exam, in the posterior pole and typically clustered around the optic nerve
3. Although MEWDS is nominally unilateral, ICG angiography usually shows a few subtle lesions in the fellow,
asymptomatic eye
4. Visual fields may reveal enlarged blind spot (possibly explained by peripapillary location of lesions on ICG
described in I.D.7. above.
5. OCT imaging reveals transient disruption of the outer retina, IS/OS junction.
6. Fundus autofluorescence may reveal additional white punctate lesions
Uveitis 72 © AAO 2017-2019

A. Female sex
B. Young adult age
A. Acute idiopathic enlarged blind spot syndrome
B. Acute zonal occult outer retinopathy (AZOOR)
C. Multifocal choroiditis
D. Syphilitic retinitis
E. Acute macular neuroretinopathy
1. None recommended
2. Corticosteroids used in some cases with optic nerve edema and reduced vision
V. Describe disease-related complications
A. Permanent scotomata or sectoral field defects (rare)
B. Development of a more permanent posterior uveitis such as AZOOR
A. Disorder is usually self-resolving within several weeks
B. Return of vision is usually excellent
C. Follow-up is needed to document resolution
D. This can be the first sign of a very rare, permanent condition (AZOOR)
E. Very rarely, MEWDS has been reported to recur or to symptomatically affect the fellow eye
Uveitis 73 © AAO 2017-2019

1. Unknown
a. By definition, this condition is idiopathic. If a specific associated disease is diagnosed, then the
condition is named based on that disease, such as "sarcoid choroiditis"
1. Generally younger individuals, including children
1. Visual disturbance; vitreous floaters; scintillating scotomata, enlarged blind spot
2. Query regarding residence in regions where histoplasmosis is endemic
1. Small (200 to 1500 micron) lesions at the level of the inner choroid
a. Active lesions are creamy white with hazy, less distinct borders
b. Healed lesions appear punched out
2. Lesions usually in different stages of evolution with several lesions of the same "age" or pigmentation, often
clumped
3. Variable vitreous and anterior chamber reaction
4. Unilateral or bilateral
5. Variable subretinal fibrosis
II. Describe appropriate testing and evaluation for establishing the diagnosis
A. The diagnosis is clinical; no ancillary testing establishes the diagnosis, though a work up should be
performed to rule out other identifiable causes, especially infectious
B. Imaging
1. FA shows early blockage, late staining of active lesions. Choroidal neovascular membrane (CNVM), cystoid
macular edema (CME) show characteristic staining patterns
2. Indocyanine green angiography (ICG) shows mid-phase hypocyanescence, greater number of lesions than
evident on FA, frequently confluent around optic nerve
3. Optical coherence tomography (OCT) shows IS/OS junction disruption
A. Sarcoid choroiditis
B. Secondary underlying choroidal scarring from toxoplasmic retinitis (usually unifocal)
C. Vogt-Koyanagi-Harada disease
D. Serpiginous choroidopathy
E. Acute posterior multifocal placoid pigment epitheliopathy
F. Diffuse unilateral subacute neuroretinitis (unilateral cases)
G. Birdshot choroidopathy (this disease has much less vitreous cell and does not involve the inner choroid)
H. Multiple evanescent white dot syndrome (MEWDS, similar initially, with a different clinical course because
Uveitis 74 © AAO 2017-2019

MEWDS resolves)
I. Presumed Ocular Histoplasmosis Syndrome (POHS) (absolute absence of cell)
J. Punctate Inner Choroidopathy (PIC)
K. West Nile Virus chorioretinitis
L. Syphilis
M. Tuberculous uveitis
N. Primary intraocular/CNS lymphoma
O. Dengue fever
1. Systemic or periocular corticosteroids for acute disease
2. Corticosteroid sparing immunomodulatory therapy for chronic disease, especially with presence of
subretinal fibrosis
3. Anti-vascular endothelial growth factor (VEGF) agents should be considered for choroidal neovascular
membranes
1. Laser photocoagulation with thermal laser surgery or photodynamic therapy for extrafoveal lesions.
2. Corticosteroid implant for unilateral or asymmetrical disease or patients who cannot tolerate systemic
medication
A. Refer to topics on specific agents in Medical Therapy section e.g. Corticosteroids
A. Choroidal neovascularization
B. Scotomata, enlargement of the blind spot, visual impairment, or blindness
C. Progressive subretinal fibrosis
D. Cytoid macular edema
A. Report changes in vision
B. Follow Amsler grid if lesions present in posterior pole to detect signs of choroidal neovascularization
C. Regular eye examinations to detect progression of disease
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1. Unknown
2. Association with tuberculosis
a. Term "Tuberculous Serpiginous-like Choroiditis" is now proposed in reference to the form

associated with tuberculosis
i. This condition presents with significant vitreitis, multifocal lesions, and in individuals from
endemic TB areas (in contrast to classic serpiginous choroidopathy)
1. Rare - <5% of all posterior uveitis
2. Men > Women
3. Onset in 4th or 5th decades
4. Eventually bilateral (may be asymmetric at onset)
5. Usually no associated systemic diseases
a. Rarely can occur in Crohn disease, sarcoidosis, and periarteritis nodosa
b. Reports of an association with varicella zoster reactivation
c. Tuberculosis is the cause of tuberculous serpiginous-like choroiditis, as detailed above
1. Sudden onset of
a. Decreased vision
b. Scotoma
c. Metamorphopsia
2. Two-thirds of patients may present with scars in fellow eye with similar visual history
3. Relapsing and remitting disease
a. Intervals between activity variable (weeks to years)
1. Three distinct entities
a. Classic peripapillary geographic choroiditis (80%)
b. Macular serpiginous choroiditis (10%)
c. Ampiginous choroiditis (relentless placoid chorioretinitis) (<10%)
2. Classic peripapillary geographic choroiditis
a. Choroid
i. Grayish areas of active choroiditis that spread centrifugally from the optic disc with
pseudopodal extensions
ii. Serpentine like progression toward macula
iii. Symptomatic as the disease approaches macula
iv. Natural history
i) Lesions heal over 6-8 weeks
ii) Atrophic choriocapillaris and RPE
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iii) Recurrences develop at edges of old lesions
(i) Skip lesions may occur
(ii) Periphery may be involved
iv) Each recurrence increases area of atrophy in a serpentine or pseudopodal fashion
v) Choroidal neovascularization (CNV)
(i) Occurs in up to 35%
(ii) Peripapillary or at edge of atrophy
vi) Subretinal fibrosis in up to 25%
b. Retina
i. Thickened and opacified over areas of active choroiditis
ii. Subretinal fluid may be present
iii. Subretinal hemorrhage may be present
c. Vitreous - minimal cellular reaction
3. Macular serpiginous choroiditis
a. Less common (10%)
b. Typical serpentine, chorioretinal lesions involving macula without continuity with edge of the optic
disc
c. Poorer visual prognosis due to greater likelihood of foveal involvement
4. Ampiginous choroiditis (relentless placoid chorioretinitis)
a. Hybrid between APMPPE and serpiginous
b. Multifocal, grey white areas of RPE, choriocapillaris, choroidal, and outer retinal inflammation
c. Anterior chamber and vitreous cells - more prominent
d. Can be relentless and progressive involving the posterior pole and periphery, often randomly
e. Usually responds to corticosteroids and immunomodulatory therapy (IMT)
f. Visual prognosis better that classic or macular serpiginous choroidopathy
1. Clinical diagnosis based on characteristic peripapillary choroiditis with pseudopodal extensions
2. Laboratory testing
a. PPD or Gamma interferon release assay for TB
i. Tuberculous choroiditis (serpiginoid) can appear identical to classic serpiginous

choroidopathy
ii. Should be ruled out especially before IMT
b. Chest radiograph or CT
c. Serologic
i. RPR/FTA-ABS
a. Older lesions are hypofluorescent with edges that stain
b. Active lesions are hypofluorescent early and stain late
4. Indocyanine green angiography
a. Active lesions are hypocyanescent in early phases and remain unchanged with minimal
hypercyanescence even in the late phases of the angiogram
i. Even if minimal activity with a lesion
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ii. Extremely useful in advanced disease or equivocal cases, especially those close to fovea
5. Fundus Autofluorescence
a. Hypoautofluorescence of areas of chorioretinal atrophy in quiet disease
b. Hyperautofluorescent signal of active areas during flare
i. Hyperautofluorescence may also be seen in regions of choroidal neovascularization
A. Acute posterior multifocal placoid pigment epitheliopathy
B. Multifocal choroiditis
C. Sarcoid choroiditis
D. Presumed ocular histoplasmosis syndrome
E. Peripapillary choroidal neovascularization
F. Acute zonal occult outer retinopathy
G. Choroidal ischemia/infarct from systemic vasculitides and hypercoagulable states
H. Tuberculosis (Tuberculous serpiginous-like choroiditis)
I. Syphilis
J. Non-Hodgkin lymphoma - rare
1. Aggressive treatment needed - typically including immunosuppressive agents
2. Corticosteroids
a. Local or systemic treatment of vision threatening lesion
3. Immunomodulatory therapy
a. Refer to guidelines by Jabs et al. 2000 (referenced below)
1. Intravitreal fluocinolone implant
a. Provides up to 3 years of inflammatory control
b. Ocular complications
i. Cataract - inevitable
ii. Ocular hypertension - 74.8% overall (36.6% required glaucoma surgery)
2. CNV
a. Focal laser photocoagulation if extrafoveal
b. Intravitreal VEGF inhibitor
i. If juxtafoveal or subfoveal
A. Corticosteroids (See Corticosteroids)
B. Immunomodulatory therapy
1. See topics on specific immunomodulatory agents
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A. CNV - up to 35%
1. Peripapillary
2. Adjacent to areas of choriocapillaris and RPE atrophy
3. Important cause of visual loss even if inflammation is quiescent
4. Visual prognosis related to proximity to fovea
B. Chorioretinal atrophy
1. Natural progression of disease
2. Inactive lesions
3. Absolute scotoma
C. Subretinal fibrosis
1. Due to severe choroidal inflammation
2. Due to CNV
3. Poor prognosis if extends into fovea
4. Best treatment is prevention and aggressive treatment of acute choroidal inflammation
D. Retinal vasculitis and retinal neovascularization - rare
A. Course of disease is highly variable with long periods of remission possible
B. Severe loss of vision may occur if scarring involves both the macula and the peripheral retina
C. Report changes in vision promptly
D. Use Amsler grid to monitor central vision area
E. Treatment with immunosuppressive drugs may slow or arrest disease
2. Lim WK, Buggage RR, Nussenblatt RB. Serpiginous choroiditis. Surv Ophthalmol 2005;50:231-44.
3. AAO, Focal Points: Infectious Posterior Uveitis, Module #3, 2005.
5. Vasconcelos-Santos DV, Rao PK, Davies JB, Sohn EH, Rao NA. Clinical Features of Tuberculous
Serpiginouslike Choroiditis in Contrast to Classic Serpiginous Choroiditis. Arch Ophthalmol.
2010;128(7):853-8.
6. Yeh S, Forooghian F, Wong WT, Faia LJ, Cukras C, Lew JC, et al. Fundus Autofluorescence Imaging of the
White Dot Syndromes. Arch Ophthalmol. 2010;128(1):46-56.
7. Goldstein DA, Godfrey DG, Hall A, Callanan DG, Jaffe GJ, Pearson PA, Usner DW, Comstock TL.
Intraocular pressure in patients with uveitis treated with fluocinolone acetonide implants.Arch Ophthalmol.
2007 Nov;125(11):1478-85. Epub 2007 Oct 8.
8. Jabs DA, Rosenbaum JT, Foster CS, Holland GN, Jaffe GJ, Louie JS, Nussenblatt RB, Stiehm ER, Tessler
H, Van Gelder RN, Whitcup SM, Yocum D. Guidelines for the use of immunosuppressive drugs in patients
with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000
Oct;130(4):492-513.
Uveitis 79 © AAO 2017-2019

1. Retinal vasculitis associated with
a. Systemic Lupus Erythematosus (SLE)
i. Retinal or choroidal vasculitis or small vessel occlusive disease related to the vasculopathy
of systemic lupus erythematosus (SLE)
ii. Contributory factors
i) Antiphospholipid antibodies
ii) Lupus anticoagulant
iii) Immune complex deposition
iv) Complement activation
b. Giant cell arteritis (GCA)
i. Large vessel vasculitis
c. Granulomatosis with polyangiitis (GPA) (previously known as Wegener granulomatosis)
i. Small and medium vessel vasculitis
d. Polyarteritis nodosa
i. Medium vessel vasculitis
e. Rheumatoid arthritis associated vasculitis
1. SLE
a. More common in young African American women
b. Severe vaso-occlusive retinal disease more common in SLE patients with cerebral vasculitis
2. GCA
a. Adults > 50 years
b. Female > male
c. Northern European > Southern European > African or Hispanic
3. GPA
a. No age or racial restriction
a. Middle age
b. Men > women
5. Rheumatoid arthritis associated vasculitis (rheumatoid vasculitis)
a. Epidemiology
i. Late stages of disease
ii. Men (1/9)>women (1/38)
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1. Change in vision
2. Visual field defect, especially altitudinal
3. Vitreous floaters
4. SLE
a. Asymptomatic, or visual disturbance, or sudden, severe vision loss
b. Prior diagnosis of SLE or meets diagnostic criteria for SLE or antiphospholipid syndrome
c. History of vaso-occlusive events
d. History of miscarriage
5. GCA
a. Jaw claudication
b. Temporal head pain
c. Scalp tenderness
d. Fever
e. Weight loss
f. Malaise
g. Polymyalgia rheumatica
6. GPA
a. Upper airway disease
b. Pulmonary symptoms
c. Renal disease
d. Sinusitis
a. Malaise
b. Skin lesions
c. Neuropathy
d. Hypertension
e. Abdominal pain
8. Rheumatoid arthritis associated vasculitis
a. Leg Ulcers
b. Cerebral vasculitis
c. Mesenteric vasculitis
d. Nephropathy, renal failure
e. Pericarditis, ischemic heart disease
f. Ominous signs, high mortality
1. SLE
a. Spectrum of retinal vasculopathy
i. Background retinopathy, especially cotton wool patches. (25% of hospitalized patients with
active lupus)
ii. Small vessel occlusions, especially arteriolar capillaries
iii. Areas of capillary closure can be extensive.
iv. Large vessel occlusions, especially arterioles including central retinal artery, but also
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thrombotic venular occlusion
v. Rarely, mild to moderate vitreous cellular reaction
b. Spectrum of choroidal vasculopathy
i. Thickening of choroidal layers with leakage of fluid in the subretinal space
ii. Fibrinoid subretinal deposits
iii. Exudative retinal detachments
c. Scleritis
d. Lupus optic neuropathy in 1%
2. GCA
a. Central or branch artery occlusion
b. Anterior ischemic optic neuropathy (AION)
c. Ocular ischemic syndrome
d. Background retinopathy consisting of peripapillary cotton wool patches
3. GPA
a. Ocular disease may be a presenting sign
b. Scleritis (necrotizing)
c. Peripheral ulcerative keratitis
d. Orbital inflammatory disease
e. Retinal branch arteriolar or venular occlusions
f. Choroidal vascular occlusions
a. Small and large retinal and choroidal vascular occlusions
b. Scleritis (necrotizing)
c. Peripheral ulcerative keratitis
a. AION - rare
b. Retinal and choroidal vasculitis - rare
c. Scleritis / scleromalacia perforans
1. SLE
a. Clinical diagnosis based on criteria from the American College of Rheumatology (American College
of Rheumatology Criteria for Classification of Systemic Lupus Erythematosus
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0041704/)
b. Antinuclear antibodies screen and lupus antibody panel including antibodies to double-stranded
DNA
c. Antiphospholipid antibodies
d. Lupus anticoagulant
e. C3, C4, CH50
f. Fluorescein angiography
i. Delay in choroidal filling
ii. Capillary nonperfusion -
iii. Capillary leakage or large vessel staining
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iv. Isolated or grouped pinpoint leaks resembling central serous retinopathy with variable
degrees of pooling in the subretinal space
g. Indocyanine green angiography
i. Choroidal hypoperfusion if choroidal vasculopathy present
2. GCA
a. Erythrocyte sedimentation rate (ESR)
b. C-reactive protein (CRP)
c. Temporal artery biopsy
i. Should be performed within two weeks of beginning oral corticosteroids
ii. Biopsy segment should be at least 1 cm in length to avoid false negative biopsy of a "skip"
lesion
iii. Pathologic diagnosis is based on the presence of arterial inflammation with mononuclear
cells, giant cells, and fragmentation of the elastic lamina
d. Fluorescein angiography
i. Delay in both retinal and choroidal circulation
ii. Small and large vessel occlusions
e. Visual field
i. Altitudinal defects in arteritic anterior ischemic optic neuropathy
3. GPA
a. Anti-neutrophil cytoplasmic antibody (c-ANCA, an antibody to Proteinase-3) and

anti-myeloperoxidase antibody
b. Imaging studies upper airways (i.e., chest X-ray and sinus computed tomography (CT) scan)
c. Urinalysis with microscopy, renal function studies
d. Biopsy of non-ocular or orbital sites showing necrotizing granulomas
a. Biopsy of tissue such as nerve or muscle for diagnosis of microscopic disease of small and medium
sized arteries
i. Inflammation may be acute or chronic
ii. Lesions in all stages of evolution in the same specimen
iii. Thrombosis and fibrosis may be present
b. Anti-neutrophil cytoplasmic antibody (p-ANCA)
c. Hepatitis B surface antigen
d. Abdominal angiogram
a. High Rheumatoid factor titers
b. Anti-cyclic citrullinated peptide antibodies
c. Low C3, C4
A. GCA (older age, Caucasian and female)
B. Lupus retinal and choroidal vasculitis - SLE and antiphospholipid antibody syndrome
C. Rheumatoid vasculitis - advanced rheumatoid arthritis with high titers of rheumatoid factor and presence of
anti-cyclic citrullinated peptide antibodies
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A. Other systemic vasculitides have been associated with ocular inflammation of various types
1. Churg-Strauss vasculitis
a. Eosinophilia
b. Pulmonary symptoms, including asthma
2. Leukocytoclastic angiitis
a. Common
b. Involves mainly the skin with palpable lesions as well as other organs
c. May be self-limited
B. Behçet retinal vasculitis
C. Diabetic retinopathy
D. Hypertensive retinopathy
E. Embolic vascular occlusions
F. Non-arteritic anterior ischemic optic neuropathy
G. Necrotizing herpetic retinitis - occlusive retinal vasculitis
1. SLE (In conjunction with rheumatologist)
a. Oral corticosteroids
b. Corticosteroid-sparing agents
i. Methotrexate
ii. Azathioprine
iii. Mycophenolate mofetil
iv. Alkylating agents may be necessary in cases of lupus nephritis
c. Anti-platelet agents
d. Anti-thrombotic agents
2. GCA
a. Oral corticosteroids
b. Follow-up with ESR and CRP monitoring
3. GPA
a. Cyclophosphamide and oral corticosteroids
b. Rituximab more commonly utilized
c. Methotrexate, mycophenolate, azathioprine, cyclosporine as an alternative for chronic maintenance
a. Cyclophosphamide and oral corticosteroids
5. Rheumatoid arthritis
a. Antimetabolites (methotrexate, azathioprine, mycophenolate)
b. TNF inhibitors
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c. Rituximab
1. Panretinal photocoagulation for neovascular complications of vaso-occlusive disease
2. Intravitreal anti-VEGF for neovascular complications
3. Otherwise - none
A. Scotomata, visual impairment or blindness
B. Secondary neovascularization of retina, optic nerve, or anterior segment
C. Cystoid macular edema
D. Ocular ischemic syndrome (GCA)
E. Retinal capillary nonperfusion
G. Cataract
H. Glaucoma
I. Retinal detachment
A. Follow physician instructions regarding medication
B. Report changes in vision
C. Examine eyes when systemic vasculitis flares up
D. Regular eye examinations necessary
2. Aristodemou P, Stanford M. Therapy insight: The recognition and treatment of retinal manifestations of
systemic vasculitis. Nat Clin Pract Rheumatol. 2006 Aug;2(8):443-51.
3. AAO, Focal Points: Scleritis and Episcleritis: Diagnosis and Management, Module #9, 1995, p. 6-7.
4. American College of Rheumatology. The 1997 Update of the 1982 American College of Rheumatology
Revised Criteria for Classification of Systemic Lupus Erythematosus. http://www.rheumatology.org/practice
/clinical/classification/SLE/1997_update_of_the_1982_acr_revised_criteria_for_classification_of_sle.pdf
5. Dunn JP, Norily SW, Petri M, et al. Antiphospholipid antibodies and retinal vascular disease. Lupus 1996;
5:313-322.
6. Edworthy SM. Clinical manifestations of systemic lupus erythematosus. In: Ruddy S, Harris ED, Sledge CB
et al., eds. Kelly's textbook of rheumatology, 6th ed. Philadelphia: Saunders; 2001:1105-1123.
7. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of
systemic lupus erythematosus [letter]. Arthritis Rheum 1997;40:1725.
8. Jabs DA, Fine SL, Hochberg MC, et al. Severe retinal vaso-occlusive disease in systemic lupus
erythematosus. Arch Ophthalmol 1986; 104:558-563.
9. Nguyen QD, Uy HS, Akpek EK, et al. Choroidopathy of systemic lupus erythematosus. Lupus 2000;
9:288-298.
10. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, et al. The 1982 revised criteria for the
classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271-7.
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1. Unknown
2. Environmental agents (infections or other exposures) thought to play a role
1. More common between ages 20 - 50
a. Women often diagnosed after age 50 years
2. Familial clustering
3. More prevalent among African-Americans in the United States and Scandinavians but has been reported in
all racial groups
4. 15%-50% of patients with systemic sarcoid have ocular manifestations
5. 3%-10% of all cases of uveitis
6. Uncommon in children
a. Early onset (≤ 5 years of age less likely to manifest pulmonary disease, more likely to have
cutaneous and articular involvement than adults)
b. Suspect Blau syndrome if onset in early childhood or family history of granulomatous disease
(familial juvenile systemic granulomatosis)
C. Pathology
1. Multisystem disease characterized by granulomatous inflammation
2. Hallmark is a noncaseating granuloma containing epithelioid cells, multinucleated giant cells (Langhans
giant cell with nuclei at the periphery of the cell) and a thin rim of lymphocytes . Must exclude other causes
of granulomatous inflammation
D. List the pertinent elements of the ocular history
1. Symptoms are variable from mild to severe
2. Pain, redness and photophobia in acute disease
3. Blurred vision and floaters in chronic disease
E. Describe pertinent clinical features
1. Systemic
a. Pulmonary symptoms (shortness of breath, cough, asthma)
b. Lymphadenopathy
c. Cutaneous (lupus pernio, perioral granulomatous plaques, erythema nodosum.) Lupus pernio and
perioral plaques are more suggestive clinically of sarcoidosis. Erythema nodosum, while classically
associated with the disease is uncommon and non-specific
d. Central nervous system granulomatous disease
e. Arthritis
f. Cardiac involvement (rare)
2. Ocular
a. Acute or chronic anterior uveitis
b. Orbital and lacrimal gland involvement
c. Conjunctival granulomas
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d. Nummular corneal infiltrates
e. Band keratopathy
f. Mutton fat keratic precipitates especially involving the anterior chamber angle
g. Koeppe and Busacca iris nodules
h. Posterior synechiae, peripheral anterior synechiae
i. Snowballs, "string of pearls"
j. Vitritis
k. Perivenous sheathing (classic candle-wax dripping, or "taches de bougie")
l. Retinal and choroidal granulomas
m. Occlusive retinal vascular disease
i. Branch retinal vein occlusion (BRVO), central retinal vein occlusion (CRVO)
ii. Retinal neovascularization
iii. Vitreous hemorrhage
iv. Peripheral microaneurysms
n. Cystoid macular edema
o. Optic nerve edema may be secondary to uveitis or central nervous system disease
p. Optic nerve granulomatous invasion is direct involvement of the optic nerve by sarcoidosis
3. Syndromes
a. Löfgren syndrome
i. Erythema nodosum, febrile adenopathy, hilar adenopathy, acute iridocyclitis
b. Heerfordt syndrome (uveoparotid fever)
i. Parotitis, fever, facial nerve palsy, uveitis
F. Describe appropriate testing and evaluation for establishing the diagnosis
1. Chest X-ray (should be used in conjunction with serum ACE and lysozyme)
2. Chest computed tomography (CT) of thorax with contrast
3. Fluorodeoxyglucose positron emission tomography (FDG-PET) scan
4. Laboratory testing
a. Serum angiotensin converting enzyme (in patients not using an ACE inhibitor) and lysozyme in
conjunction with an imaging modality
b. Liver Function
c. Serum calcium
5. Biopsy
a. Conjunctiva (directed)
b. Lacrimal gland
c. Lymph node
d. Pulmonary
i. Bronchoalveolar lavage
ii. Transbronchial lung biopsy
e. Skin rash
i. Biopsy of erythema nodosum is non-specific
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II. List the complications of treatment
A. Cataract
B. Glaucoma
C. Macular edema
D. Occlusive retinal vascular disease
1. BRVO, CRVO
2. Retinal neovascularization
3. Vitreous hemorrhage
A. Idiopathic
B. Syphilis tuberculosis
C. Familial juvenile systemic granulomatosis (Blau syndrome) (children)
D. Vogt-Koyanagi-Harada syndrome
E. Behçet disease
F. Sympathetic ophthalmia
G. Multifocal choroiditis with panuveitis
H. Juvenile idiopathic arthritis (children)
I. Pars planitis
J. Masquerade syndromes (intraocular lymphoma) (older patients)
K. Coccidioidomycosis (endemic in certain areas of California). May present with an intraocular granuloma or
granulomas that can mimic sarcoidosis. This is a rare and usually rapidly progressive endogenous
endophthalmitis
L. Lyme disease
A. Topical, periocular and systemic corticosteroids are tailored to the location and severity of inflammation
1. Intravitreal corticosteroids, including long lasting fluocinolone implants, may be useful, but keep in mind the
patient may need systemic treatment for systemic disease
B. Cycloplegia
C. Immunomodulatory agents
D. Work with internist regarding systemic disease and potentially fatal systemic complications (in particular,
CNS and cardiac involvement)
V. List the complications of treatment, their prevention and management (Refer to topics on
specific agents in Medical Therapy section e.g. Corticosteroids)
A. Dry eyes
B. Cataract
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C. Band keratopathy
D. Glaucoma
E. Iris bombé
F. Macular edema and epiretinal membrane formation
G. Neovascularization of the retina, optic nerve
H. Vascular occlusions
I. Vitreous hemorrhage
J. Optic atrophy
A. Report redness, pain, photophobia, blurred vision or decreased vision (report systemic symptoms)
B. Follow the doctor's instructions regarding medication
C. Course of disease is variable
D. Side effects of medications must be understood
2. Dana MR, Merayo-Lloves J, Schaumberg DA, et al. Prognosticators for visual outcome in sarcoid uveitis.
Ophthalmology. 1996;103:1846-1853.
3. Bonfioli AA, Orefice F. Sarcoidosis. Semin Ophthalmol. 2005; 20: 177-82.
4. Power WJ, Neves RA, Rodriguez A, et al. The value of combined serum angiotensin-converting enzyme
and gallium scan in diagnosing ocular sarcoidosis. Ophthalmology. 1995;102:2015-2016.
5. Jabs DA, Johns CJ. Ocular involvement in chronic sarcoidosis. Am J Ophthalmol,1986; 102: 297-301.
Uveitis 89 © AAO 2017-2019

1. Autoimmune response to previously sequestered intraocular antigens
1. Bilateral, non-necrotizing, diffuse, granulomatous panuveitis
2. Occurs after injury to one eye (the exciting eye), including intraocular surgery, trauma, laser procedures
(less common)
3. Latent period followed by development of uveitis in the uninjured globe (sympathizing eye)
4. Incidence has decreased with improved wound closure and early removal of severely damaged eyes
5. Shift in prevalence from penetrating ocular injury to surgical trauma is secondary to improved management
of ocular trauma and increase in number of intraocular surgeries.
C. Define the relevant pathological features
1. Diffuse granulomatous uveal involvement with lymphocytes, epithelioid cells, giant cells, and occasional
eosinophils
2. Relative lack of retinal inflammation
3. Inflammation in choriocapillaris in 25-40% of patients
4. Classic teaching is that sympathetic ophthalmia spares the choriocapillaris (versus VKH). This was likely
due to early enucleation in sympathic ophthalmia and not an accurate pathologic description
5. Phagocytosis of pigment by epithelioid cells
6. Dalen-Fuchs nodules (collections of epithelioid histiocytes between the RPE and Bruch membrane)
7. Granulomatous process may extend to scleral canals and optic disc
D. List the pertinent elements of the history
1. Insidious onset with mild photophobia, redness and blurring of vision
a. These findings in the early post injury period must be differentiated from expected post-injury
inflammation
2. Onset of inflammation
a. Within 3 months of trauma in 80%
b. Within 1 year of trauma in 90%
c. May develop years after trauma
E. Describe pertinent clinical features
1. Ocular
a. Panuveitis in the injured or operated eye
b. Sympathizing eye
i. Thickening of the uveal tract
ii. Mutton fat keratic precipitates
iii. Infiltration of the iris, iris nodules
iv. Extensive peripheral anterior synechiae
v. Loss of accommodation
vi. Vitritis
vii. Multifocal, yellow-white, mid-equatorial choroidal lesions
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viii. Peripapillary choroidal lesions
ix. Exudative retinal detachment
x. Papillitis
xi. Multiple foci of subretinal fluid (pooling on fluorescein angiogram)
xii. Choroidal thickening (B-scan ultrasonography)
2. Extraocular findings may overlap with those seen in Vogt-Koyanagi-Harada (VKH) syndrome
a. Cerebral spinal fluid pleocytosis
b. Sensory neural hearing disturbance
c. Alopecia, poliosis, vitiligo
A. Should suspect SO in patients with following risk factors
1. Perforation or penetration of the globe with or without uveal prolapse
a. Perforating ulcers
b. Scleral rupture
c. Following ocular surgery
i. Cataract surgery, especially with iris prolapse
ii. Trabeculectomy
iii. Iridencleisis
iv. Vitrectomy, especially when performed in the context of other penetrating ocular injuries or
with multiple surgeries
2. Has been reported in non-penetrating situations as well
a. Severe contusion
b. Contact and noncontact YAG laser cyclodestruction
c. Cyclocryotherapy
d. Proton beam or helium ion irradiation for melanoma
A. Bilateral uveitis following any ocular trauma or surgery should suggest SO
B. Vogt-Koyanagi-Harada disease. Prior penetrating trauma or surgery excludes VKH
C. Phacoanaphylactic endophthalmitis
D. Ocular sarcoidosis
E. Tuberculosis
F. Syphilis
G. Traumatic, postoperative, fungal endophthalmitis
A. Early enucleation within first week of trauma may prevent SO
B. The course is characterized by chronic inflammation with frequent exacerbations
C. Treatment
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1. Topical corticosteroids and cycloplegic agents as adjuncts for anterior chamber inflammation (insufficient for
posterior involvement)
2. Systemic corticosteroids
3. Immunomodulatory therapy as extended therapy is anticipated in most patients
D. Once SO is established, enucleation has no effect on inflammation, but may be useful in establishing the
diagnosis in a blind eye
E. With advances in treatment, an exciting eye may turn out to be the eye with the better visual acuity
V. Complications of treatment (Refer to topics on specific agents in Medical Therapy section

e.g. Corticosteroids)
VI. Disease related complications
A. Peripheral anterior and posterior synechiae
B. Glaucoma
C. Cataracts
D. Rubeosis iridis
E. Pupillary membrane
F. Cystoid macular edema
G. Exudative retinal detachment
H. Choroidal neovascularization
I. Optic atrophy
J. Vision loss
VII. Prognosis
A. Visual prognosis is good if the condition is recognized early and prompt aggressive treatment initiated, with
75% achieving 20/40 or better at 1 year
A. Report changes in vision promptly
B. Medication instructions
C. Follow-up instructions
2. AAO, Focal Points: Sympathetic Ophthalmia, Module #5, 2004.
3. Gass JD. sympathetic ophthalmia following vitrectomy. Am J Ophthalmol 1982; 93:552-558.
4. Kilmartin DJ, Dick AD, Forrester JV. Prospective surveillance of sympathetic ophthalmia in the UK and
Republic of Ireland. Br J Ophthalmol 2000; 84:259-263.
5. Kilmartin DJ, Dick AD, Forrester JV. Sympathetic ophthalmia following vitrectomy: should we counsel
patients? Br J Ophthalmol 2000; 84:448-449.
6. Kilmartin DJ, Wilson D, Liversidge J, et al. Immunogenetics and clinical phenotype of sympathetic
ophthalmia in British and Irish patients. Br J Ophthalmol 2001; 85:281-286.
7. Damico FM, Kiss S, Young LH. Sympathetic ophthalmia. Semin Ophthalmol 2005; 20:191-7.
Uveitis 92 © AAO 2017-2019

1. Unknown
2. Presumptive, cell-mediated autoimmune process against self-antigens associated with melanocytes
3. Immunogenetics of VKH disease and sympathetic ophthalmia (SO) similar in association with human
leukocyte antigen (HLA)-DR4
1. More common among ethnic groups originating in the original peoples of Asia (Asian, Native American
Indian, Middle Eastern, Hispanic)
2. Patients are typically 20 and 50 years of age
3. 1%-4% of uveitis cases in US, 8% in Japan
4. Association with HLA-DR4/DRB1*04
1. Headache
2. Stiff neck
3. Rarely, loss of consciousness, paralysis and seizures
4. Skin and hair signs
a. Alopecia, vitiligo, poliosis in 30% - usually weeks to months later (or years) but may be
simultaneous
5. Temporary hearing loss or tinnitus
6. Ocular history
a. Decreased vision
b. Pain
c. Redness
d. Photophobia
1. Prodromal stage
a. Headache
b. Meningismus
c. Cerebrospinal fluid (CSF) pleocytosis (80%)
d. Focal neurologic signs (rare)
i. Hemiparesis, cranial neuropathies, aphasia, transverse myelitis
e. Nausea
f. Vertigo
g. Dysacusia, tinnitus
h. Fever
i. Hypersensitivity of skin or hair to touch
j. Photophobia
k. Orbital pain
Uveitis 93 © AAO 2017-2019

2. Acute uveitic stage
a. Acute onset bilateral, sequential decreased vision (1-3 days following central nervous system (CNS)
signs
b. Mild to extremely severe bilateral anterior uveitis
i. Iris nodules, mutton-fat KPs
c. Variable degrees of vitritis
d. Choroidal thickening and elevation of peripapillary retinal-choroidal layer
e. Optic disc hyperemia and edema
f. Multiple serous neurosensory detachments
3. Convalescent stage
a. Weeks following acute uveitic stage
b. Resolution of neurosensory detachments
c. Depigmentation of the choroid resulting in orange-red discoloration known as the "Sunset glow
fundus" with retinal pigment epithelial hypo and hyperpigmentation
d. Small, discrete, round depigmented lesions in the inferior peripheral fundus representing focal
chorioretinal atrophy from old granulomas . These do not represent old Dalen Fuchs nodules
e. Perilimbal vitiligo (Sugiura sign) 85% Japanese patients
f. Integumentary changes 30%, may correspond to fundus depigmentation
i. Alopecia
ii. Vitiligo
iii. Poliosis
4. Chronic recurrent stage
a. Usually recurrent bouts of granulomatous anterior uveitis only
b. Recurrent posterior uveitis with exudative retinal detachments are uncommon
c. Granulomatous keratic precipitates ranging from small to large
1. Diagnosis is clinical based on characteristic clinical findings
2. Revised comprehensive diagnostic criteria include complete, incomplete and probable forms of VKH
3. Essential diagnostic features, irrespective of disease form include:
a. Bilateral involvement
b. Absence of a history of penetrating ocular trauma
c. No evidence of other ocular or systemic disease
a. Multiple focal areas of subretinal leakage in the early phase with late pooling of dye in the subretinal
space in areas of neurosensory detachment
5. ICG angiography
a. Shows choroidal involvement
b. Delay in choroidal perfusion
c. Multiple hypofluorescent spots
6. Ultrasound
a. Diffuse choroidal thickening
7. OCT
a. Subretinal fluid
Uveitis 94 © AAO 2017-2019

b. Enhanced depth imaging shows choroidal thickening
8. If a cerebrospinal fluid (CSF) tap is obtained
a. Lymphocytosis
b. Melanin laden macrophages
A. Sympathetic ophthalmia
B. Primary intraocular lymphoma
C. Posterior scleritis
D. Sarcoidosis
E. Acute posterior multifocal placoid pigment epitheliopathy
F. Uveal effusion syndrome
G. Syphilis
A. Systemic, periocular and local corticosteroids for at least 6 months
1. Early and aggressive use of high dose oral or IV corticosteroids
2. Early initiation of Immunomodulatory therapy may improve visual outcomes
a. Methotrexate, mycophenolate mofetil
b. Biologics
3. Visual prognosis of patients managed in this fashion is fair
a. 60%-70% retaining vision of 20/40 or better
IV. Describe disease related complications
A. Peripheral anterior synechiae
B. Posterior synechiae
C. Cataract
D. Hypotony
E. Secondary glaucoma
F. Choroidal neovascularization (CNV)
G. Subretinal fibrosis
H. Phthisis bulbi
A. Report changes in vision promptly
B. Medication instructions
C. Follow-up instructions
Uveitis 95 © AAO 2017-2019

2. Davis JL, Mittal KK, Friedlin V, et al. HLA associations and ancestry in Vogt-Koyanagi-Harada disease and
sympathetic ophthalmia. Ophthalmology. 1990;97:1137-1142.
3. Moorthy RS, Inomata H, Rao NA. Vogt-Koyanagi-Harada syndrome. Surv Ophthalmol. 1995;39:265-292.
4. Bykhovskaya I, Thorne JE, Kempen JH, et al. Vogt-Koyanagi-Harada disease: clinical outcomes. Am J
Ophthalmol 2005; 140:674-678.
5. Read RW, Holland GN, Rao NA et al. Revised diagnostic criteria for Vogt-Koyanagi-Harada disease: report
of an international committee on nomenclature. Am J Ophthalmol 2001; 131:647-652.
6. Read RW, Rechodouni A, Butani N et al. Complications and prognostic factors in Vogt-Koyanagi-Harada
disease. Am J. Ophthalmol 2001; 131:599-606.
7. Shindo Y, Ohno S, Yamamoto T et al. Complete association of the HLA-DRB1*04 and DZ1*04 alleles with
Vogt-Koyanagi-Harada disease. Hum Immunol 1994; 39:169-176.
8. Weisz JM, Holland GN, Roer LN et al. Association between Vogt-Koyanagi-Harada syndrome and HLA-DR1
and -DR4 in Hispanic patients living in Southern California. Ophthalmology 1995; 102:1012-1015.
9. Andreoli CM, Foster CS. Vogt-Koyanagi-Harada disease. Int Ophthalmol Clin 2006; 46:11-122.
10. Damico FM, Kiss S, Young LH. Vogt-Koyanagi-Harada Disease. Semin Ophthalmol. 2005; 20:183-90.
11. Rajendram R, Evans M, Rao NA. Vogt-Koyanagi-Harada disease. Int Ophthalmol Clin 2005; 45:115-34.
12. Rao NA. Pathology of Vogt-Koyanagi-Harada disease. Int Ophthalmol 2007;27:81-5.
13. Abu El-Asrar AM, Al Tamimi M, Hemachandran S, Al-Mezaine HS, Al-Muammar A, Kangave D. Prognostic
factors for clinical outcomes in patients with Vogt-Koyanagi-Harada disease treated with high-dose
corticosteroids. Acta Ophthalmol. 2013 Sep;91(6):e486-93.
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1. A multisystem disorder of unknown etiology
2. A chronic relapsing vasculitis
1. Countries that line the ancient Silk Road, particularly East Asia, Middle East, and the Mediterranean
2. Usual age of onset is third to fourth decades of life
3. Men more commonly affected than women
1. Recurrent painful oral ulcers
2. Visual symptoms including pain, photophobia, floaters, or visual loss
3. Genital ulcers
4. Skin lesions
5. Other systemic manifestations such as arthritis, vasculitis, CNS manifestations
1. The most widely used diagnostic criteria are those of the International Study Group (1990). The five major
features are:
a. Recurrent oral aphthous ulcers (recurring at least 3 times in a 12-month period)
b. Recurrent genital ulcers (or scarring)
c. Eye lesions - anterior, posterior or pan uveitis with or without hypopyon, retinal vasculitis and
retinitis
d. Skin lesions: Specifically, erythema nodosum, pseudofolliculitis, or papulopustular lesions or

acneiform papules in post adolescent patients without steroid treatment
e. Positive pathergy (skin hyper reactivity) testing: an intracutaneous needle stick with a 21G on the
inside forearm results in a pustular reaction, read by a physician after 24-48 hours
2. Several other diagnostic schemes include other clinical features, known as "minor criteria"
a. Arthritis
b. Gastrointestinal symptoms
c. Epididymitis
d. Thrombophlebitis, arterial occlusions and aneurysms
e. Central nervous system or neuropsychiatric symptoms
1. Definitive diagnosis of Behçet disease, based on the International Study Group criteria, requires oral
ulceration plus any two of the other five major criteria
2. Exclusion of other possible causes
3. Fluorescein angiography is highly useful to detect subtle retinal vasculitis, retinal vascular leakage,
ischemia, retinal neovascularization, and extent of vasculitis
4. Presence of the HLA-B51 genetic marker is not a requirement for diagnosis
Uveitis 97 © AAO 2017-2019

A. Asian, Mediterranean or middle Eastern ancestry
B. HLA-B51
C. Male sex
A. Sarcoidosis
B. HLA-B27 related uveitis
C. Syphilis
D. Necrotizing viral retinitis (HSV, VZV, CMV)
E. Tuberculosis
F. Vasculitis related to collagen vascular diseases (i.e., lupus)
G. Idiopathic retinal vasculitis and uveitis
H. Vein occlusion
A. Patient management includes consultation with a rheumatologist
1. Life-threatening involvement of the gastrointestinal system, vascular system, and central nervous system
may occur
B. Systemic medical therapy with high dose corticosteroids is most useful in patients with acute disease (refer
to specific outline)
C. Immunomodulatory agents are required in patients with vision-threatening posterior segment disease. The
long term goal is to prevent (or decrease) relapses
1. Tumor necrosis factor (TNF) - alpha antagonists and interferon alpha demonstrate high rates of complete
response
2. Other medications may include methotrexate, mycophenolate, azathioprine, cyclosporine, and tacrolimus
D. Describe surgical therapy options
1. Primarily for management of complications
a. Scatter laser photocoagulation to treat retinal non-perfusion after the development of optic nerve or
retinal neovascularization
b. Cataract extraction
c. Vitrectomy
2. Certain cases may benefit from intraocular corticosteroid implant
V. List the complications of treatment, their prevention and management (See Corticosteroids)
(See Azathioprine) (See Cyclosporine) (See Methotrexate) (See Alkylating agents:
Cyclophosphamide and chlorambucil) (See Biologic response modifiers)
VI. Describe disease-related ocular complications
A. Retinal ischemia
B. Retinal neovascularization
D. Retinal detachment
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E. Moderate to profound vision loss
F. Optic atrophy
G. Cataract
H. Glaucoma
I. Prognosis: guarded with approximately 25% of patients worldwide with legal blindness
A. Take medication as instructed
B. Discussion of the chronic, relapsing nature of the disease and the long-term risk of blindness
C. Discussion of possible life-threatening systemic complications and other systemic manifestations of

Behçet disease, and the importance of consultation and life-time follow-up by a rheumatologist
2. AAO, Focal Points: Diagnosis and Management of Anterior Uveitis, Module #1, 2002, p.8.
3. Yazici H, Pazarli H, Barnes CG, et al. A controlled trial of azathioprine in Behçet's syndrome. N Engl J Med.
1990 Feb 1;322(5):281-5.
4. Okada AA. Behcets disease: general concepts and recent advances. Curr Opin Ophthlamol 2006;
17:551-6.
5. Yates PA, Michelson JB. Behcet disease. Int Ophthalmol Clin 2006; 46:209-33.
6. Bonfioli AA, Orefice F. Behcets disease. Semin Ophthlmol 2005; 20:199-206.
7. Evereklioglu C. Current concepts in the etiology and treatment of Behcet disease. Surv Ophthalmol 2005;
50:297-350.
8. Criteria for diagnosis of Behcet's disease. International Study Group for Behcet's Disease. Lancet. 1990
May 5;335(8697):1078-80.
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1. 50% not associated with systemic disease
a. About 5% per year will develop a systemic rheumatic disease
2. 40% associated with a systemic disease
a. Majority will have a systemic diagnosis at presentation in a tertiary center
b. Rheumatoid arthritis- most common
i. 1.3 million individuals in US, 75% females
ii. Age of onset usually between 4th and 6th decades of life
iii. Symptoms
i) Morning stiffness
ii) Pain, swelling, limitation of movement in joints
(i) Any joint possible, but small joints in hands and feet most common
c. Seronegative spondyloarthropathy
i. Ankylosing spondylitis
ii. Reactive arthritis (Reiter syndrome)
iii. Psoriatic arthritis
iv. Inflammatory bowel disease
d. Relapsing polychondritis
e. Systemic vasculitis syndromes
i. Systemic lupus erythematosus (SLE)
ii. Granulomatosis with polyangiitis (GPA) (previously known as Wegener granulomatosis)
iii. Polyarteritis nodosa
iv. Microscopic polyangiitis
v. Behçet disease
vi. Giant cell arteritis
vii. Takayasu arteritis
f. Granulomatous disease
i. Sarcoidosis
g. Congenital erythropoietic porphyria
3. 10% Infectious
a. Treatment requires corticosteroids because of significant immunologic component, in addition to

anti-microbials
i. Varicella zoster virus
ii. Herpes simplex virus
iii. Syphilis
iv. Lyme disease
v. Tuberculosis
Uveitis 100 © AAO 2017-2019

vi. Leprosy
4. Surgery related
a. Surgically induced necrotizing scleritis (SINS)
b. Infectious; pseudomonas, mycobacteria, fungi, et al.
c. Surgical implant
1. Most commonly present in fourth to sixth decade
2. Women more commonly affected than men
3. Occurs bilaterally in 50% of cases
4. Necrotizing scleritis has a 50% 5-year mortality rate without systemic treatment
1. Pain that can radiate to jaw or forehead
a. Typically, severe, "boring" pain
b. Awakens from sleep
c. Worsened with eye movement
2. Redness: focal or diffuse
3. Photophobia
1. Eye pain and tenderness to palpation
a. Pain is absent in cases of scleromalacia perforans in advanced rheumatoid arthritis; pain is variable
with posterior scleritis
2. Scleral edema
3. Violaceous appearance to sclera (bluish-red color) best seen in natural light (less visible at slit lamp)
a. Blanches incompletely with topical phenylephrine 10%
4. Chalky white, avascularized patch of sclera in necrotizing scleritis; with progressive thinning/damage,
underlying uvea may be visible
5. Classification
a. Diffuse anterior scleritis
i. Most common clinical presentation affecting 25-50% of scleritis patients
ii. Least severe
iii. Recurrent attacks
iv. Inflammation of deep as well as superficial episcleral vascular network
v. Violet, blue, salmon color
vi. After resolution involved areas may have bluish gray appearance secondary to scleral
thinning
b. Nodular anterior scleritis
i. Second most common presentation of scleritis
ii. Recurrent attacks
iii. Firm, tender, immobile nodule
iv. Color of nodule is yellow to deep red
v. Systemic disease association in almost 50%
vi. Permanent visual loss and progression to necrotizing scleritis uncommon
Uveitis 101 © AAO 2017-2019

c. Necrotizing anterior scleritis with inflammation
i. Most severe
ii. Associated with greatest potential for visual loss
iii. Extreme discomfort and severe distress
iv. White avascular areas of sclera with surrounding scleral edema and congestion
i) Areas of capillary closure in episcleral vasculature
ii) Uveal tissues apparent as sclera thins
iii) Ciliary body and choroid may only be covered by conjunctiva
iv) Spontaneous perforation rare
v) Healing is remarkably good if inflammation controlled
d. Necrotizing scleritis without clinically apparent inflammation - scleromalacia perforans
i. Severe, bilateral
ii. No redness, pain, or edema
iii. Patients typically have long standing rheumatoid arthritis
iv. Thinning and atrophy of the sclera and episclera with loss of episcleral vasculature
v. Concomitant uveitis in active disease
vi. Spontaneous perforation rare despite marked uveal visualization (often underlying uvea is
bulging anteriorly)
vii. Fairly treatment refractory, though disease progression may be halted with cytotoxic
therapy or rituximab
e. Posterior scleritis
i. 33% bilateral
ii. Symptoms
i) Usually painful, especially with eye movement
ii) Decreased vision - often profound
iii. Clinical presentation
i) Exudative retinal detachment (often in posterior pole) - most common
ii) Annular choroidal detachment
iii) Optic nerve edema
iv) Choroidal and/or retinal folds
v) Subretinal mass effect
vi) Uveitis
vii) Retinal vasculitis
1. Complete blood count (CBC) and complete metabolic panel (CMP)
a. Assessing for evidence of systemic disease or infection
b. Baseline prior to starting immunosuppressive therapy
2. Anti-neutrophil cytoplasmic antibodies (ANCA)
a. cANCA- GPA
b. pANCA- Microscopic polyangiitis and polyarteritis nodosa
c. All positive ANCA tests should be confirmed by testing for antibodies to proteinase-3 and
myeloperoxidase (confirmatory- increased specificity)
Uveitis 102 © AAO 2017-2019

3. Rheumatoid factor and/or anti-cyclic citrullinated peptide- if polyarthritis or suspicion for rheumatoid arthritis
4. Urinalysis with microscopy
5. Syphilis IgG or other anti-treponemal serology with reflex non-treponemal (RPR or VDRL) titer if positive
6. Chest X-ray
7. B-Scan/high frequency ultrasound, in posterior scleritis, looking for evidence of posterior scleral thickening
and fluid accumulation beneath Tenon's capsule extending into the sub-optic nerve sheath space (so called
"T sign")
8. Other test to obtain in selected cases, based on history and clinical suspicion
a. Antinuclear antibodies
b. Lyme serology
c. HLA-B27
d. Purified protein derivative (PPD) skin test or QuantiFERON-TB gold
e. Erythrocyte sedimentation rate (ESR) and/or CRP (If giant cell arteritis suspected, would want to
obtain temporal artery biopsy)
f. Serum uric acid and inflamed joint tap (urate crystals) for gout
g. Scleral biopsy for PCR and culture (suspected infectious etiologies)
A. History of rheumatoid arthritis or other connective tissue disease or systemic vasculitis
B. Exacerbation after recent unrelated intraocular surgery (such as cataract extraction)
C. Scleral trauma
A. Episcleritis
B. Conjunctival lymphoma
C. Conjunctival intraepithelial neoplasia /squamous cell carcinoma
D. Orbital myositis
E. Orbital inflammatory syndrome (orbital pseudotumor)
F. Infectious causes of scleritis- viral, bacterial (syphilis, Lyme, TB, pseudomonas, nocardia, etc.), fungal (See
Post-surgical and traumatic infectious scleritis)
G. For posterior scleritis: Vogt-Koyanagi-Harada disease, choroidal metastases, choroidal melanoma, retinal
vasoproliferative tumor, chronic rhegmatogenous retinal detachment
IV. Management of non-infectious scleritis
A. Nonsteroidal anti-inflammatory drugs (NSAIDs)
1. Non-necrotizing scleritis
2. Relieve pain and reduce inflammation
3. No one drug is proven to be better than another
a. Indomethacin, flurbiprofen, naproxen preferred
b. In the case of failure to one of the above, a second one can be tried before switching to
corticosteroids
B. Corticosteroids
1. Topical
Uveitis 103 © AAO 2017-2019

a. Potentially useful only in very mild cases or as adjunctive therapy
b. Difluprednate stronger, and hence more effective, than prednisolone
2. Regional
a. Anterior non-necrotizing scleritis
b. Subconjunctival depot injection adjacent to active scleritis
c. Controversial, as historically steroids were felt to potentiate scleral thinning; however, more recent
literature suggests high efficacy without significant risk
i. Counselling of risk required
3. Systemic
a. Non-necrotizing scleritis not responsive to NSAIDs and necrotizing scleritis (initial agent)
b. Oral or high dose intravenous pulsed
C. Immunomodulatory therapy
1. Refer to treatment paradigm monograph
2. Cyclophosphamide or rituximab are the drugs of choice for GPA , polyarteritis nodosa, and microscopic
polyangiitis
D. Pain management
1. Oral NSAIDs
2. Judicious use of oral narcotics
3. Topical atropine once or twice daily for ciliary spasm
E. Surgery
1. Surgery in scleritis patients should be approached cautiously, as these patients may be prone to worsening
of scleral melting/thinning from the trauma of surgery
2. Nonetheless, scleral surgery may be needed to stop or repair scleral perforation and/or to harvest tissue for
diagnostic studies, especially if infection has not been excluded as a possible cause
a. Complete control of the scleritis is mandatory, if at all possible, prior to surgery
b. Materials used for grafting include sclera, but the scleral graft may melt and some have
recommended autogenous periosteum
V. List the complications of treatment, their prevention and management (See Nonsteroidal
anti-inflammatory drugs) (See Corticosteroids) (See Alkylating agents: Cyclophosphamide
and chlorambucil) (See Methotrexate) (See Azathioprine) (See Cyclosporine) (See
Mycophenolate)
A. Occur late in the course of the disease
B. Worst complications encounter in necrotizing scleritis followed by posterior scleritis
C. Scleral thinning common in all forms
D. Visual loss - necrotizing scleritis and posterior scleritis most commonly, due to:
1. Uveitis
a. Poor prognostic sign
2. Keratitis
a. Peripheral ulcerative keratitis is particularly difficult to treat and carries a poor visual prognosis.
b. Interstitial keratitis - in rheumatoid arthritis, Cogan's, infectious etiologies (herpetic, syphilis, Lyme,
TB, leprosy)
Uveitis 104 © AAO 2017-2019

3. Glaucoma
a. Increased episcleral venous pressure
b. Uveitis with secondary posterior and peripheral anterior synechiae
4. Cataract
a. Remove using a clear corneal incision
5. Fundus abnormalities
a. Serous retinal detachments
b. Cystoid macular edema
c. Epiretinal membrane
A. Contact ophthalmologist for worsening pain or vision loss
B. Life threatening disease association especially with
1. GPA
3. Microscopic polyangiitis
4. Relapsing polychondritis (laryngeal inflammation)
2. AAO, Focal Points: Scleritis and Episcleritis: Diagnosis and Management, Module #9, 1995.
3. Akpek EK, et al. Evaluation of patients with scleritis for systemic disease. Ophthalmology 2004;111:501-506.
4. Okhravi N, Odufuwa B, McClusky P, et al. Scleritis. Surv Ophthalmol 2005;50:351-63.
5. AAO, Focal Points: Steroid Therapy for Ocular Inflammatory Disease, Module #7, 2006.
6. Sainz de la Maza M, Molina N, Gonzalez-Gonzalez LA, Doctor PP, Tauber J, Foster CS. Clinical
characteristics of a large cohort of patients with scleritis and episcleritis. Ophthalmology. 2012
Jan;119(1):43-50. Epub 2011 Oct 2.
7. Yamazoe K, Shimazaki-Den S, Otaka I, Hotta K, Shimazaki J. Surgically induced necrotizing scleritis after
primary pterygium surgery with conjunctival autograft. Clin Ophthalmol. 2011;5:1609-11. Epub 2011 Nov 10.
Br J Ophthalmol. 1992 January; 76(1): 17-21.
8. Lin HC, Ma DH, Chen YF, Yeh LK, Hsiao CH. Late-onset intrascleral dissemination of Stenotrophomonas
maltophilia scleritis after pterygium excision. Cornea. 2011 Jun;30(6):712-5.
9. Tittler EH, Nguyen P, Rue KS, Vasconcelos-Santos DV, Song JC, Irvine JA, Smith RE, Rao NA, Yiu
SC.Early surgical debridement in the management of infectious scleritis after pterygium excision. J
Ophthalmic Inflamm Infect. 2012 Feb 22. [Epub ahead of print]
10. Rich RM, Smiddy WE, Davis JL.Infectious scleritis after retinal surgery. Am J Ophthalmol. 2008
Apr;145(4):695-9. Epub 2008 Feb 1.
11. Gonzalez-Gonzalez LA, Molina-Prat N, Doctor P, Tauber J, Sainz de la Maza MT, Foster CS. Clinical
Features and Presentation of Infectious Scleritis from Herpes Viruses: A Report of 35 Cases.
Ophthalmology, 2012 Mar 28 [Epub ahead of print].
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A. Describe the etiology of this disease - may be confirmed by aqueous PCR
1. Herpes simplex
a. In most cases herpes simplex virus (HSV)-1, with or without herpetic corneal infection
b. Rarely, HSV-2 may be associated with anterior segment Herpetic infection
2. Varicella-zoster virus (VZV)
3. Cytomegalovirus (CMV) in immunocompetent patients
B. List the pertinent elements of the history that suggest HSV or VZV as a cause of uveitis
1. HSV
a. Recurrent or chronic unilateral acute anterior uveitis (rarely bilateral)
b. History of herpetic corneal disease (not necessary for diagnosis)
c. History of oral or genital cold sores (not necessary for diagnosis)
2. VZV
a. Usually have a history of ipsilateral herpes zoster skin lesions
i. Note: Rarely skin lesions are not present (zoster sine herpeticum)
1. HSV
a. Foreign body sensation, pain and redness
i. Pain may be out of proportion to the amount of cellular inflammation
b. May be associated with herpes simplex corneal epithelial disease which is usually mild and
transient
c. May be associated with herpes simplex corneal stromal disease
i. May be severe
ii. Severity of uveitis not correlated with severity of corneal disease
iii. May be associated with corneal edema ("endotheliitis")
d. Associated with disciform keratitis
i. May see keratic precipitates in a linear distribution resembling a rejection line, or clustered
under area of corneal stromal thickening
e. Isolated anterior chamber inflammation with no corneal signs, or only corneal edema
("endotheliitis")
f. Keratic precipitates (KP) - highly variable, may be absent
i. Small and stellate, distributed throughout the entire corneal endothelial surface
i) The KP may also be large and mutton fat underlying an area of corneal haze, often
in the central cornea
ii. Pigment may be present
g. Corneal scarring or haze
i. May be subtle
ii. May be best seen with sclerotic scatter
h. Herpetic iritis can occur in the absence of corneal disease
Uveitis 106 © AAO 2017-2019

i. Elevated intraocular pressure (IOP) with signs of acute iritis whereas most acute iritis is associated
with low IOP
j. Variable corneal anesthesia
k. Pupillary dilation and irregular pupil (even in absence of synechiae)
l. Iris atrophy; transillumination defects
i. Diffuse or sectoral with loss of iris pigment epithelium and iris stroma
m. Intra-iris hemorrhage rarely occurs
n. Hypopyon can occur but it is not common
o. The presence of blood admixed with the white blood cells should suggest the diagnosis of herpes
2. VZV
a. Pain, redness, photophobia is common
b. May occur in absence of corneal disease
c. Intraocular pressure is often high
d. Keratic precipitates are small or large
e. May have severe anterior chamber reaction with fibrin
f. Iris atrophy with transillumination defects
g. May be associated with scleritis
3. CMV
a. May present with redness, pain, and photophobia similar to Posner-Schlossman syndrome
b. Asymptomatic presentation similar to Fuchs heterochromic uveitis may also occur
c. Intraocular pressure may be very high (>40mm Hg)
d. Mild intraocular inflammation (<2+ cells)
e. Small, diffuse keratic precipitates
f. Iris atrophy without heterochromia
g. No iris nodules
h. No posterior synechiae
1. Primarily a clinical diagnosis
2. May (rarely) do anterior chamber paracentesis for polymerase chain reaction (PCR) on aqueous
3. Serology rarely helpful
a. Absence of antibody probably excludes disease
A. HSV anterior uveitis
1. Herpetic corneal disease
2. Prior HSV infection
3. Atopy (asthma, eczema/atopic dermatitis, seasonal allergies: 2-9x higher risk compared to those without
atopy)
B. VZV anterior uveitis
1. Increased risk with immunosuppression
a. Advanced age
b. Secondary to immunosuppressive agents
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c. Leukemia, lymphoma and human immunodeficiency virus (HIV) infection
2. Atopy (asthma, eczema/atopic dermatitis, seasonal allergies: 2-3x higher risk)
A. Glaucomatocyclitic crisis
B. Fuchs heterochromic iridocyclitis
C. Idiopathic acute or chronic anterior uveitis
D. Uveitis associated with sarcoidosis
E. Anterior uveitis associated with toxoplasmosis and high intraocular pressure
F. Anterior uveitis associated with CMV retinitis in an immunocompetent patient
A. HSV anterior uveitis
1. In presence of epithelial keratitis
a. Treat epithelial keratitis with topical antivirals
b. May add cycloplegic agent
c. May benefit from oral antivirals in standard doses for herpes simplex infection
i. Acyclovir
ii. Famciclovir
iii. Valacyclovir
iv. Long-term, low dose systemic maintenance antiviral therapy may be necessary in severe,
recalcitrant cases
d. Topical corticosteroids: Avoid unless given with oral antiviral
2. No active corneal disease
a. Topical corticosteroids
b. Topical cycloplegia
c. May benefit from oral antivirals
i. Acyclovir
ii. Famciclovir
iii. Valacyclovir
B. VZV anterior uveitis
1. Systemic antiviral therapy
a. Ideally started within 72 hours of skin lesions
i. Acyclovir
ii. Valacyclovir
iii. Famciclovir
b. May reduce incidence of anterior uveitis
c. Long-term, low-dose systemic antiviral therapy may be necessary for severe, recalcitrant cases
2. Topical corticosteroids and cycloplegics
3. Pain control: Consider referral to pain clinic for post-herpetic neuralgia
4. Disease may persist for years and requires regular follow up
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C. CMV anterior uveitis
1. Oral valganciclovir in conjunction with topical corticosteroids
a. Used for several months or years
b. Recurrence may occur if therapy stopped
2. Topical corticosteroids and cycloplegics
3. Glaucoma control may be difficult
4. Disease may persist for years
A. Elevated IOP from topical corticosteroids; use judiciously
B. Epithelial keratitis from toxicity of prolonged topical antivirals
C. Acyclovir is well tolerated in patients with normal renal function; however, Renal function should be
monitored yearly or more often if there are other renal risk factors
A. Iris atrophy
B. Dilated pupil
C. Post-herpetic neuralgia
D. Cataract
E. Glaucoma
F. Hypotony
A. May require long-term use of antiviral agents
B. May also require chronic low dose topical corticosteroids
C. Necessity of follow-up, medication compliance
2. Barron BA, Gee L, Hauck WW, et al. Herpetic Eye Disease Study: a controlled trial of oral acyclovir for
herpes simplex stromal keratitis. Ophthalmology. 1994;101:1871-1882.
3. Cunningham ET Jr. Diagnosis and management of herpetic anterior uveitis. Ophthalmology.

2001;107:2129-2130.
4. Parrish CM. Herpes simplex virus eye disease. In: Focal Points: Clinical Modules for Ophthalmologists. San
Francisco: American Academy of Ophthalmology; 1997;15:2.
5. Van der Lelij A, Ooijman FM, Lijlstra A, et al. Anterior uveitis with sectoral iris atrophy in the absence of
keratitis: a distinct clinical entity among herpetic eye disease. Ophthalmology. 2000;107:1164-1170.
6. Wilhelmus KR, Gee L, Hauck WW, et al. Herpetic Eye Disease Study: a controlled trial of topical
corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994;101:1883-1895.
7. AAO, HIV: HIV/AIDS and the Eye: A Global Perspective, 2002, p.46.
8. AAO, Focal Points: Diagnosis and Management of Anterior Uveitis, Module #1, 2002, p.2.
9. Tyring S, Engst R, Corriveau C, et al. Famciclovir for ophthalmic zoster: a randomized acyclovir controlled
study. Br. J Ophthalmol. 2001;85:576-81.
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10. Chee SP, Bacsal K, Jap A, Se-Thoe SY, Cheng CL, Tan BH. Clinical features of cytomegalovirus anterior
uveitis in immunocompetent patients. Am J Ophthalmol. 2008; 145:834-40.
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1. Varicella zoster virus (VZV)
a. Most common agent
2. Herpes simplex virus (HSV), usually HSV II
a. Most common etiologic virus in patients < 25 years old
b. Has occurred years after prior herpetic encephalitis
3. Cytomegalovirus - least common in the immunocompetent patient
1. Acute retinal necrosis
a. Relatively immunocompetent patient
b. Diagnosis of ARN syndrome implies prominent intraocular inflammation
2. Progressive outer retinal necrosis
a. Immunosuppressed patients. e.g., acquired immune deficiency syndrome (AIDS) with low CD4
count
b. Absence of prominent intraocular inflammation
1. Decreased vision
2. Floaters
3. May have pain in patients with acute retinal necrosis, rare in progressive outer retinal necrosis
1. Acute retinal necrosis
a. Peripheral retinal necrosis with discrete borders
b. Rapid progression in the absence of antiviral therapy
c. Circumferential spread
d. Occlusive vasculopathy involving retinal arterioles
e. Prominent inflammation in anterior chamber and vitreous, with or without optic nerve inflammation
f. May have associated scleritis
2. Progressive outer retinal necrosis
a. Relatively clear vitreous
b. Clinical features suggestive of outer retinal or full thickness retinal necrosis involving peripheral
retina with or without macular involvement and relative sparing of retinal arterioles
c. Lesions rapidly coalesce
d. Extremely rapid progression to total retinal detachment and optic atrophy
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1. Polymerase chain reaction (PCR) of aqueous or vitreous fluids
A. Prior herpetic infection, especially, herpetic encephalitis
B. Immunosuppression in cases of progressive outer retinal necrosis
C. Herpes zoster ophthalmicus in patients with immunocompromise
A. Other infections
1. Toxoplasmosis
2. Fungal
B. Behçet disease with retinal vasculitis
C. Primary CNS lymphoma (primary intraocular or primary vitreoretinal lymphoma) with ocular involvement
D. Systemic leukemias and primary intraocular lymphomas
A. Describe medical therapy options for acute retinal necrosis
1. Initial IV acyclovir followed by oral acyclovir
2. Initial oral valacyclovir (1-2 grams three times daily), usually combined with intravitreal antiviral injections,
followed by oral valacyclovir or acyclovir
3. Initial oral famciclovir, usually combined with intravitreal antiviral injections, followed by oral famciclovir or
acyclovir
4. Duration of maintenance therapy with oral anti-viral agents to prevent involvement of second eye: 6 weeks
to 3 months if normal immunity
a. Most involvement of second eye occurs within first 3 months
b. Late disease after 3 months can occur in contralateral eye
c. Recurrences in same eye are rare
d. Prolonged oral therapy often given even if both eyes involved initially
e. The duration of treatment with oral anti-viral agents to protect the second eye is not well
established. Some have suggested indefinite prophylaxis especially if the agent is herpes simplex,
if tolerated as second eye involvement (or retinitis after herpes encephalitis) can be delayed by
many years - if prolonged therapy used, monitor for bone marrow suppression and renal
complications
5. Oral prednisone usually prescribed in early stages of ARN, usually within 24 hours of systemic and/or
intravitreal therapy to treat the significant inflammatory component of this disease and tapered over weeks.
Supplementary periocular corticosteroid injections may be useful to reduce inflammation after the infection
is controlled
B. Describe medical therapy options for progressive outer retinal necrosis
1. IV acyclovir
2. Combination IV therapy with 2 agents (e.g., acyclovir or ganciclovir plus foscarnet) - improved efficacy
compared to monotherapy with acyclovir
3. Combination systemic antiviral therapy plus intravitreal therapy with ganciclovir and/or foscarnet at
induction, then maintenance doses
4. May consider addition of aspirin to protect from vascular occlusion
C. Describe surgical therapy options
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1. Consider laser photocoagulation surgery for prophylaxis of retinal detachment
2. Consider vitrectomy with demarcated laser photocoagulation in eyes with dense vitritis or media opacity
preventing laser photocoagulation
3. Vitrectomy with silicone oil for retinal detachment
A. Risk of renal failure with high dose IV acyclovir
B. Crystalluria with high doses
C. Patients with baseline impairment in creatinine clearance require reduction in dose frequency or amount
D. Monitor creatinine, encourage high oral intake, measure input and output
A. Retinal detachment
1. Often occurs at time of vitreous detachment 8 to 12 weeks after onset
2. Laser prophylaxis to demarcate necrotic retina may reduce risk of detachment
B. Optic atrophy
1. May be secondary to overall loss of retinal substance
2. May be primary and related to direct optic nerve involvement, especially in post-encephalitic cases
C. Capillary non-perfusion
1. Related to retinal vascular inflammation
2. Can involve macular region
D. Epiretinal membranes
E. Vitreous membranes
F. Cataract
G. Hypotony
A. Risk of developing the retinitis in the contralateral eye (if disease unilateral)
B. Risk of retinal detachment
C. Potentially blinding disease
D. Need for adequate hydration with high dose acyclovir
E. Follow-up is every one to four weeks during the first 3 months after infection and periodically thereafter
2. AAO, HIV/AIDS and the Eye: A Global Perspective, 2002.
3. AAO Focal Points: Clinical Modules for Ophthalmologists, Infectious posterior uveitis, Module #3, 2005.
4. Bonfioli AA, Eller AW. Acute retinal necrosis. Semin Ophthalmol 205;20:155-60.
6. Huynh TH, Johnson MW, Comer GM, Fish DN. Vitreous penetration of orally administered valacyclovir. Am
J Ophthalmol 2008;145(4):682-6.
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1. Cytomegalovirus (CMV) is in the herpesvirus family
2. Transmission
a. Congenital infection with vertical transmission from a mother infected during pregnancy
b. Acquired infection from sexual contact, contact with other body fluids, including urine
c. Transfusion of infected blood
d. Transplantation of an organ from a CMV+ donor to a CMV- recipient
3. Latency
a. CMV is a deoxyribonucleic acid virus that can establish latency in a variety of human cell types
b. Recurrence from latency can occur when the immune system becomes impaired
4. Clinical manifestations of CMV infection
a. Congenital infection can have devastating neurologic and ocular effects, including blindness
b. Acquired infection in children or adults may cause signs and symptoms similar to the infectious
mononucleosis syndrome
c. Recurrent infection - depends on body tissue affected
i. In HIV/AIDS, retinitis is the most common, clinically important disease associated with
CMV
ii. Retinal involvement occasionally occurs with other forms of immunosuppression such as
patients undergoing solid organ transplantation
iii. CMV retinitis patients with HIV/AIDS may have symptomatic CMV infection in other organs,
particularly the GI tract (esophagitis, colitis), and the central nervous system
1. Certain populations are more likely to have serologic evidence of prior infection with CMV
a. Men who have sex with men
b. Childcare workers or women with more pregnancies
c. Hemophiliacs have a low rate of prior exposure
d. Persons from developing countries
2. CMV retinitis from recurrent disease occurs in patients who are immunocompromised
a. Patients with HIV/AIDS
b. Organ-transplant patients and other patients with iatrogenic systemic immunosuppression
c. Rarely, after local immunosuppression with intravitreal injection of triamcinolone or placement of

fluocinolone acetonide implant
3. CMV retinitis is still one of the major opportunistic infections (OIs) in patients with AIDS
a. Approximately 30% of AIDS patients developed CMV retinitis in the pre-highly actively anti-retroviral
therapy (HAART) era in western countries
b. Number of new cases in developed countries was reduced by 80% with the advent of HAART and
has stabilized at this level in the post-HAART era
c. In developing countries, particularly in resource-poor settings, CMV retinitis remains an unmet

clinical challenge and a substantial cause of blindness
4. In AIDS, CMV retinitis usually occurs in patients with CD4+ T-lymphocyte counts < 50 cells/mm (rate
Uveitis 114 © AAO 2017-2019

~20%/person-year) and rarely occurs at CD4 counts > 200 (rate < 5%/person-year)
1. Ocular symptoms
a. The eye is virtually always pain-free, and the patient may be entirely asymptomatic
b. Blurred vision is the most common ocular symptom followed by vitreous floaters. Some patients
have photopsia
c. Peripheral disease may not produce perceived scotomata and most patients with central disease
will complain of blurred vision rather than field loss
d. Presentation with moderate to severe permanent vision loss in one eye is not uncommon
2. CMV retinitis, as the first manifestation of AIDS leading to diagnosis, is uncommon (less than 1%) in
western countries
a. History of human immunodeficiency virus (HIV) infection with recent CD4 counts < 50 is helpful
b. History of other opportunistic infections
c. History of prior infection with CMV in another organ
3. Newly diagnosed CMV retinitis usually occurs in the setting of active viral shedding in blood and urine
a. Other body tissues commonly involved
b. Constitutional symptoms such as fever, malaise and weight loss are common and may be related to
disseminated infection in the blood
c. Symptoms related to specific organ systems may occur
i. Diarrhea from gastrointestinal involvement
ii. Pain on swallowing from esophageal involvement
iii. CMV radiculopathy
4. Inquire about risk factors for HIV infection
5. If an organ transplant patient, inquire about CMV status of donor and recipient at time of transplantation, any
CMV prophylaxis treatment, and immunosuppressive drugs
6. In patients with HIV/AIDS and at high risk of CMV retinitis (CD4 count below 50), routine screening with the
pupil fully dilated and using an indirect ophthalmoscope can be carried out every 3 months, because
examination based only on history and symptoms is unreliable
1. CMV causes a necrotizing retinitis with the following basic characteristics
a. Dense retinal whitening
b. An irregular active or advancing border with satellite lesions is highly characteristic
c. Intraretinal hemorrhage is common but not invariable, and not essential to diagnosis
d. Centrifugal spread with central clearing
e. Tendency to follow vessels
2. The patient with CMV retinitis may predominantly show one of several different typical clinical presentations
a. Thick or fluffy, edematous retinal necrosis with hemorrhage along one of the major vascular arcades
("cottage cheese and ketchup")
b. Dry granular appearing retinal whitening of the peripheral retina
c. Isolated involvement of the optic nerve, having the same appearance as necrotizing retinitis, occurs
is a small percentage of cases. The optic nerve is more commonly involved from spread from
adjacent retinitis
d. Frosted branch angiitis occurs in small percentage of patients
3. Unilateral disease is more common, but one-third to one-half of cases are bilateral. Most eyes contain only
one focus of retinitis
4. Intraocular inflammation is generally "low-grade" with a clear media
Uveitis 115 © AAO 2017-2019

a. A few anterior chamber cells, and some keratic precipitates (KP) and fibrin strands on the corneal
endothelium are common
b. The eye is white and there are usually not posterior synechiae, except with immune recovery
1. An eye examination by an experienced ophthalmologist is the clinical standard for diagnosing CMV retinitis
in patients with a high risk of disease
2. HIV antibody status and CD4 count are the essential tests to establish the level of risk for most patients
suspected of having CMV retinitis
3. Differentiating CMV retinitis from other types of necrotizing retinitis in equivocal cases is best done by
polymerase chain reaction (PCR) for herpes class viruses and toxoplasmosis on aqueous humor collected
by anterior chamber paracentesis
4. Differentiating CMV retinitis from HIV retinopathy is accomplished by serial examination after several
weeks. CWS condense and fade, while CMV retinitis advances
A. HIV infection with CD4+ T-lymphocyte count <200 cells/ìl, with much higher risk if CD4+ count < 50
B. Organ transplant recipient on immunosuppressive medication, especially those who were negative for CMV
antibodies pre-transplant and received a transplant from a seropositive donor
C. Other patients on high-dose immunosuppressive medication
A. HIV retinopathy with hemorrhages and cotton wool spots
B. Necrotizing herpetic retinitis due to varicella zoster or herpes simplex virus
C. Toxoplasmic chorioretinitis
D. Syphilitic chorioretinitis
E. Intraocular lymphoma
F. Other bacterial and fungal infection of the retina
1. Induction therapy with high doses of anti-viral medication for 2 to 3 weeks
a. Oral valganciclovir
b. Intravenous ganciclovir
c. Intravenous foscarnet
2. Maintenance therapy with lower doses of anti-viral medication until there is improvement in the immune
system
a. Oral valganciclovir
b. Intravenous ganciclovir
c. Intravenous foscarnet
3. Withdrawal of specific anti-CMV therapy is generally possible under the following conditions
a. HAART therapy and reconstitution of the immune system with the CD4 count above 100 for at least
3 months if the retinitis is completely inactive
1. Intravitreal injection of ganciclovir or foscarnet (off-label) for induction therapy for patients with immediately
Uveitis 116 © AAO 2017-2019

sight-threatening lesions, therapy for relapsed or resistant disease, or for patients intolerant to systemic
medication
2. Laser barrier for retinal detachment prophylaxis may be considered for patients with inactive retinitis and
large (>25% retinal surface) areas of chorioretinal atrophy.
A. Hematologic toxicity
1. Neutropenia, anemia, and thrombocytopenia common with ganciclovir
2. Anemia may occur with foscarnet
3. Treatment
a. Bone marrow stimulants
b. Withdrawal of other bone-marrow suppressive drugs
B. Renal toxicity
1. Common with foscarnet
a. Incidence reduced with careful dose calculation based on creatinine clearance
b. Adequate hydration may also help prevent toxicity
C. Other: nausea, penile ulceration and pancreatitis from foscarnet
A. Blindness from retinitis involving either the macula or optic nerve
B. Retinal detachment
C. Immune Recovery Uveitis (IRU) with reconstitution of the immune system (CD4 counts greater than 100 or
any rise CD4 counts after the initiation of HAART) in HIV-positive patients with CMV retinitis, with vision
loss from
1. Vitritis
3. Epiretinal membrane
4. Cataract
5. Consider treatment with local or systemic steroid
D. CMV strains resistant to anti-viral therapies exist and may need to be explored in non-responding patients
E. Death from coincident extra-ocular CMV disease
A. Take all prescribed CMV medications without skipping doses
B. Report changes in vision promptly
2. AAO, HIV: HIV/AIDS and the Eye: A Global Perspective, 2002, p. 56-62.
3. Holbrook JT, Jabs DA, Weinberg DV, et al. Visual loss in patients with cytomegalovirus retinitis and acquired
immunodeficiency syndrome before widespread availability of highly active antiretroviral therapy. Arch
Ophthalmol 2003;121:99-107.
4. Yust I, Fox Z, Burk M, Johnson A, Yurner D, et al (2004) Retinal and extra-ocular cytomegalovirus
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end-organ disease in HIV-infected patients in Europe: a EuroSIDA study, 1994-2001. Eur J Clin Microbiolo
Infect Dis 23:550-559.
5. Martin DF, Sierra-Madero J, Walmsley S, et al. A controlled trial of valganciclovir as induction therapy for
cytomegalovirus retinitis. N Engl J Med 2002;346:1119-26. Erratum in: N Engl J Med 2002;347:862.
6. Thorne JE, Jabs DA, Kempen JH, et al. Causes of visual acuity loss among patients with AIDS and
cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Ophthalmology. 2006
Aug;113(8):1441-5.
7. Kempen JH, Min Y, Freeman WR, Holland GN, Friedberg DN, et al (2006) Risk of immune recovery uveitis
in patients with AIDS and cytomegalovirus retinitis. Ophthalmology 113(4):684-94.
8. Pathanapitoon K, Ausayakhum S, Kunavisarut P, Wattanakikorn S, et al (2007) Blindness and low vision in a

tertiary ophthalmologis center in Thailand: the importance of cytomegalovirus retinitis. Retina 27:635-640.
9. Jabs DA, Ahuja A, van Natta M, Lyon A, Srivastava S, Gangaputra S, for the SOCA Research Group.
Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: Five-year Outcomes.
Ophthalmology 2010 Nov;117(11):2152-61.
10. Sugar EA, Jabs DA, Ahuja A, Thorne JE, Danis RP, Meinert CL for the Studies of the Ocular Complications
of AIDS (SOCA) Research Group. Incidence of cytomegalovirus retinitis in the era of highly active
antiretroviral therapy. Am J Ophthalmol 2012 Epub ahead of press.
Uveitis 118 © AAO 2017-2019

1. Infection with human T-cell lymphotrophic virus (HTLV-1), a single stranded RNA retrovirus
2. HTLV-1 is the cause of a number of diseases
a. Adult T-cell leukemia (ATL)
b. HTLV-1-associated myelopathy (HAM)/tropical spastic paresis (TSP)
c. HTLV-1 uveitis
d. Other inflammatory diseases
1. Worldwide, 10-20 million people are infected but most are asymptomatic
2. Transmitted by sexual contact, sharing of contaminated needles and syringes, blood transfusion, as well as
vertical transmission from mother to child including breast-feeding
3. Endemic areas include:
a. Southern Japan: highest prevalence
b. Parts of Central Africa
c. Parts of Central and South America
d. Caribbean islands
e. Southeastern United States
4. Rare in North America- except S.E. United States
1. Most infected patients remain asymptomatic
2. Patents with HTLV-1 uveitis frequently report blurred vision and floaters
1. Manifestations differ by presence or absence of major systemic disease
a. Asymptomatic, infected patients without systemic disease
i. Keratoconjunctivitis sicca
ii. Scleritis
iii. Interstitial keratitis
iv. Uveitis (anterior and intermediate uveitis most common)
i) Probably due to inflammatory cytokines released by HTLV-1-infected CD4+ T cells
ii) Anterior uveitis (granulomatous/nongranulomatous)
iii) Intermediate uveitis
iv) Retinal vasculitis
v) Retinochoroidal lesions
vi) Papilledema
vii) Cystoid macular edema (CME)
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viii) Optic atrophy
b. Patients with Adult T-Cell Leukemia/Lymphoma
i. Opportunistic infection of the eye
i) Cytomegalovirus retinitis (similar to AIDS)
ii) Associated with poor prognosis
ii. Malignant infiltration of the eye by HTLV-1-infected lymphocytes: almost all tissues affected
c. Patients with HTLV-1-associated myelopathy (HAM)/tropical spastic paresis (TSP)
i. Chronic interstitial keratitis is more common in patients with HAM/TSP
ii. May not respond to topical corticosteroids
1. Screening tests
a. Enzyme immunoassay (EIA)
b. Particle agglutination test
2. Confirmatory tests
a. Western blot: indeterminate results may occur
b. Polymerase chain reaction (PCR)
A. Unprotected sexual intercourse
B. Children with an infected mother (intrauterine/ peripartum transmission, breast feeding)
C. Sex workers
D. Sharing needles or syringes
E. Transfusion of infected blood products
A. HIV
B. Syphilis
C. Cytomegalovirus
D. Epstein-Barr virus
E. Multiple sclerosis
F. Lyme disease
G. Sarcoidosis
A. Describe the natural history, outcome and prognosis
1. Most patients with anterior uveitis or intermediate uveitis respond to therapy with corticosteroids
a. 60% are unilateral
b. Recurrent disease in up to 50% of patients
2. Patients with retinal vasculitis typically respond to therapy with periocular or systemic corticosteroids
3. Chronic interstitial keratitis (white anterior stromal opacities) may not respond to topical corticosteroid
Uveitis 120 © AAO 2017-2019

therapy
B. Describe medical therapy options
1. Corticosteroids for HTLV-1 uveitis
a. Topical
b. Periocular
c. Systemic
2. Adult T-cell leukemia/lymphoma with opportunistic eye infections or malignant cell infiltration
a. Poor prognosis
b. Allogeneic hematopoietic stem cell transplantation is probably the best curative therapy;
improvement in eye complications has been observed in accordance with a decrease in HTLV-1
proviral load
3. Keratoconjunctivitis sicca
a. Lubricating eye drops as for any type of dry eye syndrome
A. Cataract
B. Glaucoma
A. Cataract
B. Glaucoma
C. Epiretinal membrane
D. Retinal vascular occlusion
E. Retinal degeneration
F. Optic atrophy
G. CME
A. Patients should be counseled about the risks of transmission and urged to practice safe sex (including the
use of condoms). Additionally, infected women should be counseled about pregnancy and the avoidance of
breastfeeding
2. Buggage RR. Ocular manifestations of human T-cell lymphotropic virus type 1 infection. Curr Opin
Ophthalmol 2003;14:420-425.
3. Verdonck K, González E, Van Dooren S, et al. Human T-lymphotropic virus 1: recent knowledge about an
ancient infection. Lancet Infect Dis 2007;7:266-281.
4. Kamoi K, Mochizuki M. HTLV infection and the eye. Curr Opin Ophthalmol. 2012 Nov;23(6):557-61.
Uveitis 121 © AAO 2017-2019

I. Approach to establishing the diagnosis
1. Ocular histoplasmosis syndrome is believed to be due to exposure to Histoplasma capsulatum via the
respiratory tract
a. Respiratory flu-like illness as child or young adult
b. The organism may then spread through the bloodstream from the lungs to the choroid
2. Definitive histopathological evidence of Histoplasma capsulatum in chorioretinal scars and PCR evidence as
well
1. This condition occurs most frequently in patients who live near the Ohio River and Mississippi River valley
areas and watershed areas
2. Mid-Atlantic region
3. Similar syndrome seen in Northern Europe, in areas not endemic for Histoplasma
1. Asymptomatic if no choroidal neovascularization (CNV)
2. Central scotoma, visual loss and metamorphopsia if CNV develops
1. Atrophic "punched-out" round or streak-shaped scars often prominent in retinal periphery
2. Peripapillary atrophy
3. CNV (arising from macular scars or peripapillary scars)
4. Absence of vitreous cells - although choroidal inflammation without vitreous cells or choroidal
neovascularization may occur (in primarily acquired disease) and cause vision loss in immunocompetent
patients
5. In rare cases immunocompromised patients exposed to the fungal pathogen may develop
a. Endophthalmitis from Histoplasma capsulatum
b. Solitary histoplasmic granuloma
c. Systemic antifungal therapy is required in these cases
A. Exposure to Histoplasma as a child or young adult
B. Residing in endemic areas (Mississippi and Ohio River Valleys)
A. Multifocal choroiditis and panuveitis
B. Age-related macular degeneration (AMD)
C. Multifocal toxoplasmosis
D. Idiopathic CNV
E. Punctate inner choroidopathy (PIC)
F. Myopic degeneration and CNV
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A. If no CNV is present
1. Observation
2. Amsler grid
3. If no CNV is present and vision loss occurs from parafoveal active choroiditis
4. Oral, periocular, or intravitreal corticosteroids
5. +/-Oral antifungals - Itraconazole
6. Close follow-up for development of choroidal neovascularization
B. If CNV develops
1. Anti-vascular endothelial growth factor (VEGF) therapy
a. Bevacizumab (Avastin), pegaptanib sodium (Macugen), ranibizumab (Lucentis) intravitreal injection
b. Not currently FDA-approved for CNV in histoplasmosis
2. Periocular or intravitreal triamcinolone
3. Laser therapy options
a. Photodynamic therapy (Verteporfin in Ocular Histoplasmosis, VOH, study)
b. Thermal laser photocoagulation for extrafoveal and juxtafoveal CNV if classic CNV or well-defined
CNV
4. Rarely large lesions with poor vision and extrafoveal vascular ingrowth sites may be amenable to subfoveal
surgery
V. List the complications of treatment
A. Intravitreal anti VEGF therapy: rare cardiovascular complications (myocardial infarction (MI), stroke),
endophthalmitis
B. Intravitreal triamcinolone: glaucoma, cataract, endophthalmitis (infectious, sterile)
C. Laser: extension of laser burns or scar into fovea
D. Recurrence of CNV despite treatment
A. Loss of central vision due to subfoveal CNV
A. Amsler grid for both eyes
B. Prognosis depends on location of atrophic scars, although CNV can develop in eye with previously normal
macula
2. AAO, Laser Photocoagulation of the Retina and Choroid, 1997, p.150, 152-153,162,171-173,190-191.
3. Busquets MA, Shah GK, Wickens J, et al. Ocular photodynamic therapy with verteporfin for choroidal
neovascularization secondary to ocular histoplasmosis syndrome. Retina 2003;23:299-306.
4. Saperstein DA, Rosenfeld PJ, Bressler NM, et al. Photodynamic therapy of subfoveal choroidal
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neovascularization with verteporfin in the ocular histoplasmosis syndrome: one-year results of an
uncontrolled, prospective case series. Ophthalmology 2002;109:1499-505.
5. Ciulla TA, Piper HC, Xiao M, et al. Presumed ocular histoplasmosis syndrome: update on epidemiology,
pathogenesis, and photodynamic antiangiogenic, and surgical therapies. Curr Opin Ophthalmol
2001;12:442-9.
6. Parnell JR, Jampol LM, Yannuzzi LA, et al. Differentiation between presumed ocular histoplasmosis
syndrome and multifocal choroiditis with panuveitis based on morphology of photographed fundus lesions
and fluorescein angiography. Arch Ophthalmol 2001;119:208-12.
7. Berger AS, Conway M, Del Priore LV, et al. Submacular surgery for subfoveal choroidal neovascular
membranes in patients with presumed ocular histoplasmosis. Arch Ophthalmol 1997;115:991-6.
8. Melberg NS, Thomas MA, Dickinson JD, et al. Managing recurrent neovascularization after subfoveal
surgery in presumed ocular histoplasmosis syndrome. Ophthalmology 1996;103:1064-7; discussion 1067-8.
9. Cummings HL, Rehmar AJ, Wood WJ, et al. Long-term results of laser treatment in the ocular
histoplasmosis syndrome. Arch Ophthalmol 1995;113:465-8.
10. Weingeist TA, Watzke RC. Ocular involvement by Histoplasma capsulatum. Int Ophthalmol Clin.
1983;23:33-47.
11. Callanan D, Fish GE, Anand R. Reactivation of inflammatory lesions in ocular histoplasmosis. Arch
Ophthalmol. 1998;116:470-474.
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A. Describe the etiology of the disease - Toxoplasmosis gondii
1. Protozoal infection of the retina
a. The choroid may also be infected in immunocompromised hosts
2. Exists as inactive scars, latent infection encysted in host cells at borders of scars, or active replicating
infection
3. Active infection produces inflammatory reaction
4. Infection is tissue destructive
1. Regional differences in prevalence of toxoplasmosis infection
2. Definitive host is the cat
3. Infective forms are oocysts (soil forms which are ingested) and tachyzoites (metabolically active and
antigenic organism)
a. Usually ingested in contaminated food or water or in undercooked meat
4. Vertical transmission (intrauterine infection) possible
a. Formerly thought to be the most common type of transmission
b. Acquired disease in postnatal period is more common than previously appreciated
c. Thought to occur only if mother acquires infection for the first time while pregnant
5. Most toxoplasma retinochoroiditis is acquired after birth (>50%)
C. List the pertinent elements in the history
1. Exposure to materials fecally contaminated by cats
a. Litter boxes
b. Garden soil
c. Improperly stored water (unsecured reservoirs)
d. Food
2. Exposure to undercooked meats from infected animals, which in turn were exposed to material fecally
contaminated by cats
3. Exposure to uncooked vegetables grown in fecally contaminated soil
4. Maternal prenatal infection
5. Recent febrile illness or lymphadenopathy (acquired toxoplasmosis)
1. Unilateral focal chorioretinitis adjacent to healed chorioretinal scar
a. Healed scars may be multiple, but usually only one reactivates at a time
b. Atypical forms of extensive chorioretinitis can occur in immunocompromised individuals e.g.,

patients with acquired immunodeficiency syndrome (AIDS) or those over age 70
i. Up to 25% of AIDS patients with ocular toxoplasmosis may have concomitant CNS
toxoplasmosis
c. In acquired disease, the typical chorioretinal scar may not be present
d. Active chorioretinitis is yellow-white, slightly elevated, with a relatively well-defined border
2. Intraocular inflammation
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a. Anterior uveitis
i. Often granulomatous
b. Intermediate uveitis
i. Often intensified over the lesion
c. Vasculitis
i. Variably present
i) Often arteritis, but also periphlebitis
ii) May be remote from the chorioretinitis
d. Optic neuropathy
i. Secondary inflammation in nerve or infective neuroretinitis
e. Ocular hypertension
i. Resolves with treatment of the anterior uveitis
3. Pathologic findings
a. Intracellular cysts containing bradyzoites are found at the border of healed lesions
b. Active lesions are characterized by the presence of tachyzoites
c. Both cysts and tachyzoites are found in retina and not in choroid
d. Retinal necrosis ensues from active disease with granulomatous inflammation in the choroid
e. Healed lesions show destruction of retina, retinal pigment epithelium, and choroid with variable
hyperpigmentation
1. Diagnosis is clinical, but the following may be utilized as well
2. Confirmation of exposure to toxoplasmosis by serum antibody titers
a. High sensitivity and low specificity because of high prevalence of positive antibody titers in general
population (a positive serology does not make the diagnosis but only confirms exposure)
b. Immunoglobulin (Ig) M antibody determinations helpful in the diagnosis of acquired toxoplasmosis
3. Determination of toxoplasmosis IgG or IgA antibody titers in aqueous humor useful in cases with atypical
features
4. Polymerase chain reaction (PCR) of aqueous humor/vitreous for toxoplasmosis DNA useful in older patients
with large lesions or in patients who are immunocompromised
5. CT or MRI of the brain in patients with AIDS and toxoplasmosis since up to 25% may have CNS
toxoplasmosis
A. Risk of congenital infection
1. Acquired toxoplasmosis infection in a pregnant woman
a. Most severe effects on fetus if acquired during first trimester
b. Risk of transmission greatest if acquired during third trimester
2. Screening programs for non-immune mothers are in place in Europe
a. Seroconversion treated with antibiotic therapy
b. Prenatal treatment reduces fetal effects
B. Risk of acquired infection
1. Residence in endemic area
2. Contact with cat litter or soil contaminated by cats
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3. Consumption of undercooked meat
4. Consumption of uncooked vegetables from soil contaminated by cats
5. Consumption of contaminated water
C. Risk of recurrent infection
1. Intraocular surgery such as cataract surgery or instrumentation of glaucoma filtering blebs
2. Impairment of immune system (esp. AIDS) or advanced age
A. Infections
1. Toxocariasis
2. Cytomegalovirus retinitis
3. Necrotizing herpetic retinitis
4. Syphilis
5. Focal fungal or bacterial infections
B. Posterior uveitis
C. Masquerade syndromes
1. Intraocular tumors
2. Intraocular lymphoma
A. Decision to treat based on proximity to macula and optic nerve, amount of inflammation, and vision
1. Sight-threatening infections always treated
2. Small, peripheral lesions often observed
3. Infection is self-limited in most cases in healthy patients
B. Antibiotic treatment - there are no studies to suggest that one therapy is more effective than another
1. Combined therapy
a. Pyrimethamine has been classically employed
i. Can be combined with sulfadiazine or triple-sulfa, azithromycin, or clindamycin
ii. Usually given with leucovorin to mitigate hematologic toxicity
iii. "Classic" or "triple therapy" refers to Pyrimethamine, sulfadiazine and prednisone.
b. Trimethoprim-sulfamethoxazole increasing in use
i. Can be combined with clindamycin for increased efficacy
ii. Economical
2. Monotherapy - generally reserved for non-sight-threatening disease
a. Doxycycline or minocycline
b. Azithromycin
c. Atovaquone
d. Clindamycin. Pregnancy Category B
3. Other agents
a. Clarithromycin
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b. Intravitreal clindamycin
4. Maintenance therapy
a. Usually used and may be required in
i. Patients with AIDS who do not demonstrate immune reconstitution
ii. Patients with multiple sight threatening recurrences
b. Reduced drug dosage and frequency compared to induction levels
c. A common regimen is sulfamethoxazole/trimethoprim three times weekly
5. Congenital toxoplasmosis
a. Antibiotic therapy may be required for up to 1 year in newborns
6. Duration of Therapy - There are no specific guidelines on duration of antibiotic therapy but duration is
tailored to response and requires a minimum of 4-6 weeks of systemic antibiotics
C. Anti-inflammatory treatment
1. Topical corticosteroids - in patients with significant anterior chamber reaction
2. Oral corticosteroids
a. Indicated for vision threatening inflammation
b. Low to moderate doses for 2 to 3 weeks
c. Not given alone because of risk of worsened infection without antibiotic coverage
d. Periocular corticosteroids felt to be contraindicated by many experts because of reports of

uncontrolled infection after injection
e. Generally, not used in immunocompromised patients with toxoplasmosis
A. Pyrimethamine
1. Hematologic toxicity
a. Prevention
i. Leucovorin use
b. Periodic blood counts if high doses given
B. Clindamycin
1. Pseudomembranous colitis
a. Management
i. Culture of diarrhea stool
ii. Oral vancomycin
C. Sulfa drugs
1. Rash
2. Nausea
3. Stevens-Johnson syndrome
4. Aplastic anemia
a. Management
i. Discontinuation of medication
ii. Supportive care
D. Tetracyclines
1. Photosensitivity
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2. Discoloration of tooth enamel in children < 11 years or in babies of treated mothers
E. Corticosteroids
1. Possible increase in risk of recurrence
2. Risk of impairment of immune responses with spread of infection
a. Prevention
i. Limit quantity and duration of use
ii. Always give with antibiotic coverage
A. Loss of vision related to chorioretinal scars
B. Chronic vitreous opacification
C. Epiretinal membrane formation
D. Choroidal neovascularization
E. Retinal hole formation and retinal detachment, including giant retinal tears
F. Secondary cataract
A. Report redness, pain, blurred vision, or sensitivity to light immediately
B. If infection was acquired, try to prevent infection in family and neighbors by finding the source
C. If pregnant and the infection is newly acquired, take antibiotic treatment to reduce risk of severe fetal
effects
D. If pregnant and chorioretinitis is recurrent from prior disease, treatment is for maternal indications only
E. Take all medications as instructed for the length of time indicated
2. AAO, HIV: HIV/AIDS and the Eye: A Global Perspective, 2002.
3. Lam S, Tessler HH. Quadruple therapy for ocular toxoplasmosis. Can J Ophthalmol 1993;28:58-61.
4. Rutzen AR, Smith RE, Rao NA. Recent advances in the understanding of ocular toxoplasmosis. Curr Opin
Ophthalmol 1994;5:3-9.
5. Holland GH, Lewis KG: Perspective: An update on current practices in the management of ocular
toxoplasmosis. Am J Ophthlamol 2002;134:102-114.
6. Silveira C, Belfort R Jr, Muccioli C, et al. The effect of long-term intermittent trimethoprim/sulfamethoxazole
treatment on recurrences of toxoplasmic retinochoroiditis. Am J Ophthalmol 2002;134:41-6.
7. Holland GN. Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and
management. Am J Ophthalmol. 2004 Jan;137(1):1-17.
8. Holland GN. Ocular toxoplasmosis: a global reassessment. Part I: epidemiology and course of disease.
Am J Ophthalmol. 2003 Dec;136(6):973-88.
9. Rothova A, Meenken C, Buitenhuis HJ, et al. Therapy for ocular toxoplasmosis. Am J Ophthalmol
1993;115:517-23.
10. Koo L, Young LH. Management of ocular toxoplasmosis. Int Ophthalmol Clin 2006;46:183-93.
11. Bonfioli AA, Orefice F. Toxoplasmosis. Semin Ophthalmol 2005; 20:129-41.
12. Scheilian M, Sadoughi MM, Ghajarnia M et al. Prospective randomized trial of

trimethoprim/sulfamethoxazole versus pyrimethamine and sulfadiazine in the treatment of ocular
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toxoplasmosis. Ophthalmology 2005;112:1876-82.
Uveitis 130 © AAO 2017-2019

1. Infestation of the retina/choroid/vitreous with a second stage larva of Toxocara canis or Toxocara catis
2. Infestation is presumed to occur after ingestion or cutaneous infection with hematogenous spread to the eye
1. Most cases occur in children because of their more frequent contact with soil
2. Age range of 3 to 4 years is typical
3. 30% of dogs under 6 months and 25% of cats are infected
4. More common in lower socioeconomic settings
5. More common in subtropical or tropical climates where the ground does not freeze
6. More common where domestic animals are not routinely "wormed"
1. Severe loss of vision in one eye in a child
2. Loss of red reflex in one eye of a child
3. Strabismus with vision loss in one eye in a child
4. History of a red eye
5. Play in soil contaminated by pets
6. Pica
7. Unilateral floaters and blurred vision
1. Three forms
a. Peripheral granuloma
i. Focal, elevated, white, peripheral nodule with variable degrees of surrounding peripheral
membranes and pigmentary scarring
ii. Falciform fold in retina from lesion to optic nerve
iii. Possible retinal detachment
iv. Vitreous opacities
v. Usually diagnosed in cicatricial phase when the inflammation is quiescent
b. Posterior granuloma
i. Focal, elevated, white nodule, usually < 1-disc diameter, with variable pigmentation
ii. Vitreous opacities and membranes
iii. Secondary inflammatory changes more mild than with peripheral granuloma
iv. Prognosis depends on location
c. Endophthalmitis
i. Panuveitis with red, painful eye
ii. Often no view of fundus
iii. Ascribed to death of the parasite with a secondary exuberant inflammatory reaction
Uveitis 131 © AAO 2017-2019

1. Toxocara serology (enzyme-linked immunosorbent assay (ELISA)) with compatible clinical picture is usually
considered diagnostic, although the level of antibody positivity in the community should be taken into
account as toxocariasis is endemic in some populations (14% in the U.S. and up to 40% in other parts of the
world)
2. Antibody to toxocara may not be lifelong
3. Intraocular fluid can be assayed for specific anti-Toxocara antibodies, cytology for eosinophilic leukocytes
A. Low socioeconomic status
B. Hot, humid environment
C. Exposure to puppies and/or cats
D. Contact with soil or food contaminated with feces from infected animals (dogs and cats)
E. Cutaneous larva migrans
F. Visceral larva migrans
A. Toxoplasmosis
B. Retinoblastoma
C. Pars planitis (peripheral granuloma or endophthalmitic forms of ocular toxocariasis)
D. Coats disease
E. Other forms of uveitis
F. Congenital falciform fold of the retina (peripheral granuloma)
G. Retinopathy of prematurity
H. Cysticercosis
1. Parasite is assumed to be dead when the patient presents with either cicatricial or acute inflammatory
changes.
2. Treatment with albendazole or thiabendazole is of unclear benefit for eye disease
a. Treatment not ordinarily given unless active infection suspected
3. Corticosteroid therapy
a. Mainstay of inflammatory control
b. Can reduce secondary damage from intraocular inflammation
c. Systemic, periocular, and topical corticosteroids may be used
1. Diagnostic biopsy of vitreous (cytology for eosinophils, anti-Toxocara antibodies)
2. Repair of retinal detachment
3. Excision of granuloma may be necessary (if small and posteriorly located)
4. Possibility of severe amblyopia limiting response to treatment especially in children less than 11 years of
age
Uveitis 132 © AAO 2017-2019

A. Phthisis or atrophia bulbi
1. Diffuse endophthalmitic form - uncontrolled inflammation
2. Irreparable retinal detachment
B. Retinal folds and retinal detachment
1. Anti-inflammatory treatment
2. Pars plana vitrectomy, possible scleral buckle
C. Macular scar from macular granuloma
D. Amblyopia
1. May occur ex anopsia from vitreous opacification during acute inflammation
2. Treat by controlling inflammation and following patching schedule appropriate for age
E. Cataract
G. Choroidal neovascular membrane
A. Assess home environment for risks to other children
B. Report changes in vision that may indicate retinal detachment
3. Woodhall D, Starr MC, Montgomery SP, Jones JL, Lum F, Read RW, Moorthy RS. Ocular toxocariasis:
Epidemiologic, anatomic, and therapeutic variations based on a survey of ophthalmic subspecialists.
Ophthalmology 2012 Feb 14.
4. www.cdc.gov/parasites/toxocariasis/
Uveitis 133 © AAO 2017-2019

I. Establishing the diagnosis
1. The pork tapeworm is Taenia Solium
a. Ocular disease is caused by the tapeworm's larva Cysticercus cellulosae
1. Endemic to Mexico, Africa, Southeast Asia, eastern Europe, Central and South America and India
2. Especially in areas of poor hygiene
3. Often occurs between ages 10 and 30 years
1. Ingestion of potentially contaminated food (pork), vegetables, fruit or water in endemic areas
1. Hematogenous spread to eye
2. Larvae can be found in any ocular or adnexal tissue
a. Most often subretinal, causing exudative detachment
b. May then break through retina to vitreous
i. Cyst is 1.5-6 disc diameters
i) Round, translucent or white
3. May present with other organ involvement
a. Seizures with CNS involvement
1. Cyst may be seen in intraocular tissue including vitreous
2. Enzyme-linked immunoabsorbent assay (ELISA)
a. Not sensitive (only in 50% of patients with ocular involvement)
3. Anterior chamber paracentesis
a. May show eosinophils
4. B-scan
a. May reveal cysts
5. Computed tomography (CT) for CNS involvement
a. Calcification or hydrocephalus
6. Stool may be positive for eggs of T. solium
A. Ingestion of contaminated food or water in endemic area
A. Causes of leukocoria
Uveitis 134 © AAO 2017-2019

1. Blindness with posterior segment involvement over 3-5 years
1. Anti-helminthic therapy not effective for ocular disease
2. Useful for systemic and CNS disease with corticosteroids
1. Laser
a. May result in poor outcome as dead larvae remains in the eye
2. Surgical removal of larvae - offers best chance of visual recovery
Uveitis 135 © AAO 2017-2019

1. Solitary nematode; two different sizes
a. Smaller worm probably Ancylostoma caninum (dog roundworm) or Toxocara canis or Toxocara catis
b. Larger worm probably Baylisascaris procyonis (raccoon roundworm)
1. Rare disorder affecting healthy young patients (mean age 14 years; range 11-65 years)
a. T. canis endemic to the southeastern U.S., Caribbean islands, and Brazil
b. B. procyonis found in the northern midwestern U.S. and Canada. Associated with raccoon
infestations
1. Gradual, unilateral visual loss; rarely bilateral
1. Recurrent, focal, multifocal, and diffuse inflammation of the retina, retinal pigment epithelium (RPE), and
optic nerve. Most cases are unilateral
2. Early stage
a. Mild to moderate visual acuity loss
b. Mild to moderate vitritis
c. Optic disc edema
d. Crops of multiple, gray-white or yellow-white evanescent lesions; 300-500 µm in diameter located in

the post equatorial retina. Overlying serous retinal detachment may be present
e. Subretinal nematode or subretinal tracks may be visible
f. Abnormal electroretinogram (ERG)
3. Late stage
a. Retinal arteriolar narrowing
b. Optic atrophy
c. Diffuse RPE degeneration
d. Abnormal ERG
e. Choroidal neovascularization rare
1. Systemic and laboratory testing usually negative
2. ERG may be abnormal; even during early stages of the disease
3. Fundus examination is most important to determine the presence of a motile worm in the subretinal space
A. Exposure to raccoons or canines
B. B. procyonis can be found in many other animals in addition to raccoons, but exposure to raccoon activity
Uveitis 136 © AAO 2017-2019

is most common zoologic historical feature
A. Early stage
1. Multifocal choroiditis with panuveitis (See Multifocal choroiditis with panuveitis)
2. Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (See Acute posterior multifocal placoid
pigment epitheliopathy)
3. Multiple evanescent white dot syndrome (MEWDS) (See Multiple evanescent white dot syndrome
(MEWDS))
4. Sarcoidosis-associated Uveitis (See Sarcoidosis panuveitis)
5. Serpiginous choroidopathy (See Serpiginous choroidopathy)
6. Behçet disease (See Behçet disease)
7. Toxoplasmosis (See Toxoplasmic retinochoroiditis)
8. Ocular histoplasmosis syndrome (See Ocular histoplasmosis syndrome)
9. Optic neuritis
10. Papillitis
11. Cysticercosis
B. Late stage
1. Post-traumatic chorioretinopathy
2. Occlusive vascular disease
3. Toxic retinopathy
4. Retinitis pigmentosa
5. Autoimmune retinopathy
1. Without treatment, the nematode may migrate within the subretinal space for several years
2. Progressive ocular damage and visual loss occurs due to optic atrophy and widespread RPE degeneration
3. The prognosis in untreated patients is poor although spontaneous death of the nematode and stabilization
undoubtedly occurs in some cases
4. Frequent examinations are indicated both before and after effective treatment has been applied
a. Resolution of vitritis is presumptive evidence that the nematode has died
b. Formation of a dominant white lesion after treatment with anti-helminthic drugs may indicate death
of the nematode
5. Fundus photography useful to detect changes in spots that may indicate movement of the nematode and
need for focused examination
1. Antihelminthic therapy should be considered in two situations
a. If the nematode cannot be initially located; may immobilize the worm
b. In patients who continue to have signs of inflammation following laser photocoagulation
2. Two agents are used
a. Albendazole for up to 30 days. Well tolerated
b. Thiabendazole for 2 to 4 days. Poorly tolerated
Uveitis 137 © AAO 2017-2019

3. Corticosteroids alone may produce transient improvement, but recurrence of symptoms occurs followed by
progression
1. Direct laser photocoagulation of the subretinal nematode during the early stage. Typically results in
stabilization of visual acuity. Does not cause a severe inflammatory reaction
A. Medical therapy
1. Albendazole
a. Hepatoxicity may occur; liver function tests should be obtained prior to initiating therapy and every 2
weeks thereafter
b. Pancytopenia rarely occurs; a complete blood count should be obtained prior to initiating treatment
and every 2 weeks while on therapy
c. Should not be used in women who are pregnant except in those situations where no alternative
exists
2. Thiabendazole
a. Most side effects are transient and mild including nausea, vomiting, anorexia, and dizziness
b. Transient increases in liver function tests have been reported
3. Corticosteroids (See Corticosteroids)
A. Optic atrophy
B. Diffuse retinal pigment epithelium (RPE) degeneration
C. Severe to profound vision loss
A. Use medications as prescribed
B. Report any changes in vision
3. Gass JD. Stereoscopic Atlas of Macular Diseases. Diagnosis and Treatment. 4th ed. St. Louis: Mosby;
1997:622-628.
4. McEvoy GK, ed. AHFS: Drug Information. Bethesda, MD: American Society of Health-System Pharmacists;
2007.
5. de Amorim Garcia Filho CA, Gomes AH, de A Garcia Soares AC, de Amorim Garcia CA. Clinical features
of 121 patients with diffuse unilateral subacute neuroretinitis. Am J Ophthalmol 2012;153(4):743-9.
Uveitis 138 © AAO 2017-2019

1. Propionibacterium acnes (P. acnes) - most common (40% of cases)
2. Other slow-growing bacteria and fungi (Candida, aspergillus species)
3. IOL associated inflammation
4. Retained lens fragments
1. Late onset (6 weeks to years) after cataract surgery
2. Blurred vision
3. Recent neodymium yttrium-aluminum-garnet (Nd: YAG) laser capsulotomy
1. Indolent late postoperative anterior chamber inflammation that may initially respond to topical corticosteroid
treatment
2. Anterior chamber cells and flare
3. Iris transillumination defects
4. Hypopyon is less common than acute bacterial endophthalmitis
5. Granulomatous or fine keratic precipitates
6. Deposits on the intraocular lens,
7. Capsular plaque is characteristic
1. Careful gonioscopy
a. With the pupil maximally dilated
b. Look for capsular plaque behind the iris
2. Look carefully for retained lens fragments
a. In the chamber angle - gonioscopy
b. On the pars plana - indirect ophthalmoscopy with scleral depression
c. Ultrasound biomicroscopy (UBM) or anterior segment OCT to evaluation lens position
3. Vitreous and anterior chamber "taps" (aspirations)
a. Culture and cytology
b. PCR for P. acnes, consider pan bacterial or pan fungal PCR if available
4. Incisional posterior capsulectomy for culture
A. Posterior YAG laser capsulotomy and release of organisms
B. Complicated surgery
Uveitis 139 © AAO 2017-2019

A. Inflammation due to retained lens fragments
B. Rule out other infectious or non-infectious causes of uveitis - masquerade syndrome (lymphoma)
A. Definitive treatment involves a step-wise approach
1. Combine medical (intraocular antibiotics) and surgical (pars plana vitrectomy) therapy
2. Partial or total capsulectomy,
3. intraocular lens explantation (with or without vitrectomy)
4. intraocular lens exchange (delayed or simultaneous)
B. Describe management - medical and surgical therapeutic options
1. Pars Plana Vitrectomy (PPV), posterior capsulectomy, intravitreal and endocapsular antibiotics
a. Intraocular antibiotics - may occasionally be given alone without PPV
b. Consider combination therapy
i. Vancomycin
ii. Clindamycin
iii. Voriconazole or Amphotericin
c. Adjust therapy based on culture
d. Should be given both in the vitreous and within capsule
2. If recurrent inflammation, consider capsulectomy and removal of intraocular lens (IOL)
a. Primary IOL lens exchange - sutured in sulcus
b. Delayed IOL placement - sutured in sulcus
A. Complications of intraocular antibiotics
B. Complications of vitreous tap/vitrectomy surgery
C. Complications of capsulectomy and/or IOL removal
A. Posterior synechiae and peripheral anterior synechiae
B. Glaucoma
B. Follow-up instructions (importance of follow-up and risk of vision loss)
2. Meisler DM, Palestine AG, Vastine DW, DeMartini DR. Chronic Propionibacterium endophthalmitis after
extracapsular catarract extraction and intraocular lens implantataion. Am J Ophthalmol 1986;102:733-739.
Uveitis 140 © AAO 2017-2019

3. Winward KE, Pflugfelder SC, Flynn HW Jr., Foussel TJ, David JL. Postoperative Propionibacterium
endophthalmitis. Treatment strategies and long-term results. Ophthalmology. 1993 Apr;100(4):447-51.
4. Shirodkar AR, Pathengay A, Flynn HW Jr, Albini TA, Berrocal AM, Davis JL, Lalwani GA, Murray TG,
Smiddy WE, Miller D. Delayed- versus acute-onset endophthalmitis after cataract surgery. Am J
Ophthalmol. 2012 Mar;153(3):391-398.e2. Epub 2011 Oct 25.
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1. Multi-systemic disease caused by the spirochete Treponema pallidum
2. Acquired (sexual transmission) and congenital forms
1. Incidence
a. Marked reduction in primary and secondary syphilis in the United States and other industrialized
nations with introduction of penicillin and effective screening programs
2. Can affect individuals of any socioeconomic group
a. Recent increased incidence among men and African Americans (5.2 times greater than among
non-Hispanic whites)
3. Increased risk among homosexual and heterosexual patients engaging in high risk sexual behavior and
those with acquired immune deficiency syndrome (AIDS)
4. 1%-2% of all uveitis cases in tertiary referral clinics
C. Describe pertinent stages and features of systemic disease
1. Acquired disease
a. Primary syphilis
i. Incubation 3 weeks
ii. Painless chancre
b. Secondary syphilis
i. 6-8 weeks later
ii. Lymphadenopathy
iii. Contagious macular-papular rash prominent on palms and soles
iv. Uveitis in less than 10% of secondary syphilis cases
c. Latency: one year (early latency) to decades (late latency)
d. Tertiary syphilis
i. Benign (gumma: skin, mucus membranes)
ii. Cardiovascular syphilis
iii. Neuro-syphilis
iv. Uveitis in 2.5-5% tertiary cases
e. Disease course may be atypical or more fulminant in patients with AIDS
2. Congenital disease
a. Early (≤2 years of age)
i. Hepatosplenomegaly
ii. Characteristic long-bone changes
iii. Abdominal distension
iv. Pneumonia
v. Desquamative skin rash, low birth weight, anemia
b. Late congenital disease (≥ 3 years of age)
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i. Hutchinson teeth, Mulberry molars
ii. Abnormal facies
iii. Cranial Nerve (CN) VIII deafness
iv. Saber shins
v. Perforations of hard palate
vi. Rhagades (cutaneous lesions)
vii. Neurosyphilis
D. Ocular manifestations
1. Protean: may affect all ocular structures
2. Conjunctiva, sclera, cornea, lens, uveal tract, retina, retinal vasculature, optic nerve, cranial nerves and
pupillomotor pathways
3. Uveitis most common, and may occur at any stage of infection although most often is secondary stage
E. List the pertinent elements of the ocular history
1. Onset 6 weeks to years after primary systemic disease
2. Sudden or insidious
3. Variable severity
4. Variable pain, redness and photophobia
5. Blurred vision or floaters
6. May be bilateral in one-half of the patients
F. Describe pertinent ocular features
1. Secondary syphilis
a. Interstitial keratitis
i. Unilateral
ii. Deep stromal vascularization
iii. Necrotizing stromal keratitis- rare
b. Nodular or diffuse anterior scleritis
c. Iridocyclitis
i. Acute or chronic
ii. Granulomatous or non-granulomatous
iii. Unilateral or bilateral
iv. Granulomatous iris nodules, Iris roseola (dilated iris vessels), vascularized papules (iris
papulosa)
d. Cystoid macular edema
e. Vitritis with superficial retinal precipitates
f. Diffuse or localized choroiditis or chorioretinitis
g. Acute posterior placoid chorioretinitis
i. Infection of retinal pigment epithelium
ii. lesions in macula or peripapillary region
iii. ± serous retinal detachment with macular pseudohypopyon
iv. Leopard pattern of retinal pigment epithelium with resolution
h. Retinitis (focal or necrotizing)
i. Retinal vasculitis
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j. Exudative retinal detachment
k. Isolated papillitis
l. Neuroretinitis
2. Tertiary syphilis
a. Interstitial keratitis (unilateral)- deep stromal ghost vessels
b. Anterior or posterior uveitis
c. Mild to severe iridocyclitis
d. 1/4 have central nervous system involvement
e. Gummas of the uveal tract or miliary granulomas
f. Chorioretinitis may be focal or multifocal
g. Lens dislocation
3. Congenital syphilis
a. Early congenital syphilis
i. Acute iritis at 6 months of age in untreated infants
ii. Necrotizing stromal keratitis (rare), bilateral
iii. Posterior uveitis with multifocal inflammation of the choriocapillaris
iv. Postinflammatory changes
i) Diffusely scattered foci of chorioretinal atrophy
ii) Proliferation of retinal pigment epithelium
iii) Narrowed retinal vessels
iv) Salt and pepper spots can be diffuse or in the periphery
b. Late congenital syphilis (5-20 years of age)
i. Interstitial keratitis (bilateral) accompanied by anterior uveitis
ii. Nodular or diffuse anterior scleritis
iii. Recurrent iridocyclitis in adults is uncommon
iv. Residual signs: multifocal, hypopigmented chorioretinal scars
c. Other
i. Optic neuritis, glaucoma, cataract
G. Describe appropriate testing and evaluation for establishing the diagnosis
1. OCT may show small areas of subretinal fluid and disruption of ellipsoid zones syphilitic posterior placoid
chorioretinitis
2. It is important to obtain both a treponemal and non-treponemal test for diagnosis
3. Serodiagnosis: treponemal tests - Most important tests to obtain to confirm etiology
a. Anti-treponemal IgG
b. Fluorescent treponemal antibody absorption (FTA-Abs)
c. Microhemagglutination assay - Treponema pallidum (MHA-TP)
d. False positive results may occur due to antigenic cross-reactivity in individuals who may be positive
for other spirochetal infections (Lyme disease, leptospirosis) and autoimmune disease (systemic
lupus erythematosus)
4. Serodiagnosis: nontreponemal tests
a. Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR)
i. Positive VDRL or RPR indicates active disease and exposure to the bacteria
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i) Titers return to normal with effective therapy
ii) Titers may also return to normal without treatment in patients with late latent and
tertiary syphilis
ii. Biological false positive results may result from cross reactive lipoidal antibodies and it
occurs more commonly in human immunodeficiency virus-infected patients and in the
geriatric population
i) Other causes for false positive tests include
(i) Recent viral infection
(ii) Immunization
(iii) Pregnancy
(iv) Lupus anticoagulant
(v) Antiphospholipid antibodies
iii. False negatives can occur due to the prozone effect (Antibody excess), if the undiluted
RPR is extremely high. If syphilis is strongly suspected, request repeat testing with at least
a 1:2 dilution of serum
5. Cerebrospinal fluid (CSF) analysis
a. In patients with uveitis and positive serology, asymptomatic neurosyphilis must be ruled out
b. In latent syphilis, serum VDRL may be positive or negative but the fluorescent treponemal antibody
absorption (FTA-Abs) is positive, and CSF is negative
c. In tertiary syphilis or in neurosyphilis, serum and CSF FTA-Abs are both positive but the VDRL may
be negative
i. CSF VDRL may be insensitive but its presence is highly specific for neurosyphilis
d. CSF VDRL may be negative in CNS syphilis. Elevated protein and leukocytes in CSF are
presumptive evidence of syphilis even if the VDRL is negative
6. Darkfield microscopy
a. Direct visualization of spirochetes
7. Direct fluorescent antibody test of lesion exudates or tissue
8. PCR (not commonly used)
9. Human immunodeficiency virus (HIV) testing on all patients with syphilis given high rate co-infection
10. Congenital syphilis
a. Darkfield microscopy or fluorescent antibody test of cutaneous lesions, placenta, umbilical cord
b. Immunoglobulin M (IgM) FTA-Abs in infant
i. IgG crosses placenta
A. Syphilis is the "great masquerader"
1. Retinitis pigmentosa
2. Necrotizing herpetic retinopathies (acute retinal necrosis, progressive outer retinal necrosis)
3. Cytomegalovirus retinitis
4. Tuberculosis
5. Lyme disease
6. Sarcoidosis
a. Consider the possibility of syphilis in any case of diffuse uveitis unresponsive to conventional
anti-inflammatory therapy
7. Toxoplasmosis (especially in AIDS patients)
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8. Neuroretinitis
A. Ocular inflammation secondary to syphilis should be treated as neurosyphilis
1. Aqueous, crystalline penicillin G, 18-24 million units (MU), administered as 3-4 MU every 4 hours or as a
continuous infusion for 10 - 14 days
2. May be supplemented with intramuscular benzathine penicillin G at dose of 2.4 MU weekly for 3 weeks
3. Alternative regimen for neurosyphilis is Procaine Penicillin G delivered as 1.2 million unit intramuscular
injections twice daily for 10 to 14 days combined with probenecid 500 mg four times daily for 10 to 14 days
and followed by the 3 benzathine penicillin G injections as above for 3 weeks
4. Topical, regional or oral corticosteroids may be used to quiet anterior or posterior segment inflammation
B. In patients allergic to penicillin
1. Strongly consider desensitization therapy to penicillin by allergist
2. Doxycycline 100 mg by mouth twice a day or tetracycline 500 mg by mouth 4 times a day for 28 days
3. Intravenous ceftriaxone has not been fully validated as a treatment for neurosyphilis
C. For patients with positive CSF serology, repeat CSF exam every 6 months until cell count, protein and VDRL
return to normal
D. Congenital syphilis
1. Aqueous penicillin G 100,000/150,000 units/kg per day administered as 50,000units/kd per day IV every 12
hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days
IV. Describe appropriate patient instructions
A. Importance of long term serologic monitoring
B. Monitor patient for development of Jarisch-Herxheimer reaction during first 24 hours of treatment
C. Report to health department / discuss notification and treatment of partners
2. Aldave AJ, King JA, Cunningham ET, Jr. Ocular syphilis. Curr Opin Ophthalmol 2001;12:433-441.
3. Browning DJ. Posterior segment manifestations of active ocular syphilis, their response to a neurosyphilis
regiment of penicillin therapy, and the influence of human immunodeficiency virus status on response.
Ophthalmology 2000;107:2015-2023.
4. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002.
MMWR 2002;51 (No. RR-6).
5. Gass JD, Braunstein RA, Chenoweth RG. Acute syphilitic posterior placoid chorioretinits. Ophthalmology
1990;97:1288-97.
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1. Tick-borne spirochetal disease caused by Borrelia burgdorferi
1. Most prevalent vector-borne illness in the United States (US)
a. Northeastern U.S.
b. Western Wisconsin/Upper Midwest
2. Men and women nearly equally affected
3. Bimodal distribution - Children (5-14) and Adults (50-59)
4. Seasonal outbreaks
a. Early summer and mid-autumn
5. Animal reservoirs
a. Rodents
i. White footed mouse may be obligate carrier
b. Deer
c. Birds
d. Cats
e. Dogs
6. Transmitted to humans through the bite of a tick that was previously infected by feeding on an infected
carrier
a. Ixodes dammini (eastern US)
b. Ixodes pacificus (western US)
1. Stage 1
a. Erythema chronicum migrans
i. Elevated annular erythematous skin lesion with central clearing at the site of the tick bite
ii. Most characteristic feature of Stage 1 - 60-80%
iii. Develops within 4 weeks after tick bite
b. Headache
c. Stiff neck
d. Malaise
e. Myalgias
f. Arthralgias
g. Fever
2. Stage 2
a. 1-4 months after infection
b. Neurologic (cranial nerve palsies, especially cranial nerve VII), musculoskeletal, cardiac
involvement
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c. Encephalitis or meningitis
d. Arthritis
e. Tendonitis
f. Joint effusions
g. Myocarditis
h. Heart block
i. Erythema chronicum - remote sites from bite via hematogenous spread
3. Stage 3
a. 5 months or more after infection
b. Chronic arthritis - most common manifestations
c. Chronic atrophic skin changes
d. Chronic meningitis
e. Adult respiratory distress syndrome
D. Describe pertinent clinical features (ophthalmic)
1. Stage 1
a. Follicular conjunctivitis
b. Interstitial Keratitis
c. Episcleritis
2. Stage 2 (Uveitis most common in Stage 2)
a. Anterior uveitis - granulomatous
b. Intermediate uveitis (one of the most common presentations)
c. Panophthalmitis
d. Multifocal choroiditis
e. Optic neuritis, papillitis, neuroretinitis
f. Neuro-ophthalmic manifestations (CN VII palsy most common but diplopia from other involved
cranial nerves can be seen)
g. Interstitial keratitis
3. Stage 3
a. Keratitis
i. Most common manifestations
ii. Bilateral, patchy, focal, and stromal infiltrates
b. Chronic iridocyclitis and vitreitis - less common than in stage 2
1. Diagnosis is based on history (though only 25-30% recall tick bite), clinical presentation, and serology
2. High rate of false positive and poor predictive value for serology
3. Borrelia burgdorferi expresses common bacterial antigens that are cross reactive with antigens on other
bacteria
4. 2- Step serological diagnosis is commonly used:
a. Indirect immunofluorescence assay or enzyme-linked immunosorbent assay for immunoglobulin M

and immunoglobulin G use whole Borrelia burgdorferi as antigen source
b. If enzyme immunoassay is positive, Western blot testing indicated to confirm serologic screening -
CDC Guidelines
i. IgG - a positive Western blot - at least 5 of 10 bands present
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ii. IgM - at least 2 of 3 bands present
c. No standardization of assays
d. Wide differences between laboratories
5. PCR testing of ocular fluids, skin, and synovial fluids may be useful
A. Tick bites
B. Endemic areas (e.g. Northeastern U.S.)
A. Syphilis
B. Pars planitis or intermediate uveitis
C. Sarcoidosis
D. Multiple sclerosis
E. JIA in children
F. Large cell lymphoma
A. Antibiotic treatment of suspected ocular Lyme should be treated as central nervous system (CNS)
involvement
B. Easier to eradicate in earlier stages
C. Regimens
1. Tetracycline
2. Doxycycline
3. Penicillin
4. Azithromycin
5. Duration of treatment determined by clinical response (2-4 weeks)
6. Newer ketolide antibiotics may be of value (telithromycin or cethromycin)
D. CNS and/or ocular (i.e. uveitis) involvement requires intravenous antibiotic
1. IV ceftriaxone or penicillin x 10-14 days is advised for neurologic or neuroophthalmologic disease
2. Topical corticosteroids along with antibiotic treatment
3. Systemic corticosteroids - controversial
a. Increased incidence of antibiotic treatment failures
b. But Jarisch-Herxheimer reaction with antibiotics alone may require some systemic corticosteroids
V. List the complication of treatment, their prevention and management
A. Penicillin allergy, anaphylactic shock
B. Tetracyclines
1. Photosensitivity
2. Discoloration of tooth enamel in children <11 years
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C. Corticosteroids
1. Local
a. Cataract
b. Glaucoma
2. Systemic (See Corticosteroids)
D. Describe disease-related complications
1. Exposure keratopathy or corneal ulceration from facial paralysis
2. Macular edema
3. Exudative retinal detachment
4. Optic atrophy
5. Pupillary abnormalities
6. Cranial nerve palsies
A. Report recurrent symptoms of redness, pain, floaters, diplopia, or blurred vision
B. Try to prevent infection in family members by avoiding tick bites, cover extremities when in endemic areas
3. Centers for Disease Control and Prevention, Lyme Disease-United States 2015-2016, MMWR 2004;
53:365- 369.
4. Hilton E, Smith C, Sood F. Ocular Lyme borreliosis diagnosed by polymerase chain reaction in vitreous fluid.
Ann Intern Med 1996; 125:424-425.
5. Karma A, Seppälä I, Mikkilä. Diagnosis and clinical characteristics of ocular Lyme borreliosis. Am J
Ophthalmol 1995; 119:127-135.
6. Mikkilä HO, Seppälä I, Viljanen MK. The expanding clinical spectrum of ocular Lyme borreliosis.
Ophthalmology 2000; 107:581-587.
7. Winterkorn JNS. Lyme disease: Neurologic and ophthalmic manifestations. Surv Ophthalmol 1990;
35:191-304.
8. Wormser GP, Nadelman RB, Dattwyler RJ, et al. Practice guidelines for the treatment of Lyme disease. The
Infectious Disease Society of America. Clin Infect Dis 2000; 31:1-14.
9. Kuschak T. The laboratory diagnosis of Lyme borreliosis: Guidelines from the Canadian Public Health
Laboratory Network. Can J Infect Dis Med Microbiol. 2007 March; 18(2): 145-148. PMCID: PMC2533539
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I. Describe the approach to establishing diagnosis
1. Leptospira interrogans
a. 200 strains
b. Pathogenic to humans
c. Very thin, spiral-shaped, tightly coiled gram negative aerobic spirochete that is motile and flexible
B. Define the relevant aspects of the epidemiology of the disease
1. Zoonotic infection common in
a. Endemic areas - tropical and subtropical regions
i. Any area where wild animals may contaminate water sources with infected urine
ii. In U.S. - Hawaii accounts for 50% of cases
iii. South East Asia - India
b. High-risk occupations
i. Sewer workers, farmers, dairy farmers, fishery workers, water sports (e.g. whitewater
rafting)
2. Infected rodents and other animals pass the bacteria in their urine, contaminating soil and water reservoirs
3. Humans acquire disease by bacteria invading intact mucosa or abraded skin and hematogenously
disseminating the organism into various organ systems including kidneys, liver, lungs, heart, central nervous
system, and eyes
4. Age 3rd through 5th decades
5. Men more commonly affected than women
6. Bilateral 50% of the time
1. Biphasic disease
2. Acute leptospiremic phase - 2-4 weeks after exposure
a. Patients usually have a febrile illness, headache, fatigue and myalgias with variable severity of fever
i. In four to seven days the Leptospira organisms are eliminated from the body except in
immunologically privileged sites such as the eyes and brain
ii. 80-90% have self-limited anicteric disease
iii. 10-15% - Weil Disease - hepatitis, nephritis
i) 3-6 days after infection
ii) Mortality - 15-30%
b. Yellow sclera and circumlimbal conjunctival injection and chemosis is regarded as pathognomonic
sign for acute phase of Leptospirosis
3. Immune phase
a. May start weeks or years after initial exposure
b. Organisms that are not cleared by the immune system remain in immunologically privileged sites
like the brain and eye
c. Meningitis and leptospiruria-most important features
d. Uveitis may start two days to four years after systemic infection but typically three to six months
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after initial illness
i. Anterior uveitis - 10%
i) Conjunctival Injection
ii) Nongranulomatous keratic precipitates
iii) Fine and diffusely distributed
iv) Anterior chamber cells and flare
(i) 12% - Hypopyon (in tropical countries one of the most common causes is
leptospiral uveitis)
(ii) Young males develop leptospirosis as well and this must be differentiated
from HLA-B27 associated disease and Behçet disease
ii. Interstitial keratitis - 18%
iii. Panuveitis - 44%
i) May be characteristic
ii) Significant vitritis
(i) May be difficult to differentiate from endogenous endophthalmitis
(ii) Significant vitreous debris and precipitates along with vitreous "snowball"
like opacities and vitreous veils
iii) Retinal Vasculitis /periphlebitis
(i) mainly involving the retinal venules but occasionally the arteries
(ii) perivascular sheathing and inflammation
(a) Nonischemic
iv) Disc hyperemia and edema
iv. Neuro-ophthalmic manifestations
i) Neuroretinitis
ii) Optic neuritis (retrobulbar as well)
iii) Other neuro-ophthalmic manifestations compatible with central nervous system

disease and encephalitis include cranial nerve palsies, chronic headaches
D. Describe appropriate testing and evaluation for establishing diagnosis
1. Microscopic agglutination test (MAT) is gold standard
a. Difficult to perform and not widely available
2. Anti-leptospiral IgG and IgM antibody testing-highly sensitive and specific
a. ELISA
b. Complement fixation
3. PCR - under development
4. Leptospirosis causes false positive RPR or FTA-ABS
A. HLA-B27 associated anterior uveitis
B. Behçet disease
C. Syphilis
D. Sarcoidosis
E. Pars planitis
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F. Tuberculosis
G. Eales Disease
III. Describe medical treatment options
A. Acute phase illness
1. IV penicillin G 1.5MU Q6 hours for 1 week
a. Ideal if begun in the first 4 days of acute phase
2. Doxycycline - 100mg po BID
a. Useful for mild cases
3. Whether systemic antibiotics given in acute phase prevent uveitis is unknown
B. Immune phase - uveitis
1. Systemic antibiotic treatment should be given as part of uveitis treatment
2. Corticosteroids
a. Mainstay of treatment of uveitis
b. Systemic, periocular, and topical corticosteroids
3. Mydriatics/cycloplegics
IV. List complications of treatment and prevention management
A. Antibiotic
1. Drug allergies to specific agents
2. Corticosteroids (See Corticosteroids)
V. List disease-related complications
A. Cataracts
B. Glaucoma
VI. Patient instructions
A. The course of Leptospiral uveitis can be highly variable but the visual prognosis is quite good with
treatment
B. Report exposure to contaminated water related to outdoor activities to your physician
C. Report any severe fevers to your physician
D. Report any severe increase in pain or loss of vision to your physician.
E. Leptospirosis can become a chronic relapsing and recurrent illness if not treated aggressively with
systemic antibiotics at the onset of acute phase illness
1. Basic and Clinical Science Course. Section 9. Intraocular Inflammation and Uveitis. Chapter 8: Infectious
Uveitis: Leptospirosis. 2015-2016.
2. Martins MG, Matos KT, da Silva MV, DeAbreu M. Ocular manifestations in the acute phase of leptospirosis.
Ocul Immunol Inflamm. 1998;6:75-79.
3. Rathinam SR, Rathinam S, Selvaraj S, et al. Uveitis associated with an epidemic outbreak of leptospirosis.
Am J Ophthalmol. 1997;124:71-79.
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4. Shukla D, Rathinam SR, Cunningham ET Jr. Leptospiral uveitis in the developing world. Int Ophthalmol Clin.
2010 Spring;50(2):113-24.
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1. Intraocular inflammation resulting from Mycobacterium tuberculosis infection
2. Transmitted by aerosolized respiratory droplets when the primary site of infection is the lung
3. High affinity for highly oxygenated tissues
a. Apex of lung
b. Choroid
4. 90% of individuals infected with the organism remain asymptomatic
5. 5% of infected patients develop disease within 1-2 years
6. 5% of infected persons develop disease several to many years later
7. Ocular involvement indicates extra-pulmonary dissemination of the organisms
8. Hematogenous dissemination of tuberculosis (TB), in the form of miliary disease, is seen with
immunosuppression
1. United States
a. 1-2% of uveitis is related to TB
b. Increased incidence with acquired immunodeficiency syndrome (AIDS) epidemic
c. Increased incidence among foreign-born patients
2. Worldwide distribution
a. Most important systemic disease worldwide
b. Accounts for up to 10% of uveitis cases
c. 8 million new systemic TB cases and 3 million deaths annually
d. 95% of new cases occur in developing countries
C. List the pertinent elements in the history
1. History of previous exposure to TB
2. Immigrant from an area with endemic TB
3. Immunosuppression especially with human immunodeficiency virus (HIV)
4. History of Bacille Calmette Guerin (BCG) vaccination (important for interpretation of PPD skin test)
5. Previous treatment for TB
1. Systemic infection
a. Pulmonary TB is common (~80%)
b. Extra-pulmonary disease is seen in about 20%
c. 50% of patients with extra-pulmonary disease have a normal chest radiograph
d. Up to 20% of patients with extra-pulmonary disease can have a negative purified protein derivative
(PPD) skin test
e. Extra-pulmonary disease is common in HIV infected and other immunocompromised hosts
2. Symptoms of systemic TB
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a. Systemic disease manifests with
i. Fever
ii. Night sweats
iii. Weight loss
iv. Extra-pulmonary disease may be asymptomatic without these constitutional symptoms
b. Tuberculous uveitis patients may or may not present with systemic disease and its symptoms
3. Ocular manifestations of TB are due to
a. Active infection involving ocular tissue
b. Paucibacillary disease: May represent immunologic reaction to the organism that may be present in
small numbers in the eye or in systemic organs
4. External eye and adnexal TB
a. Primary inoculation of the eye or contiguous spread from the sinuses or face
i. Very rare
ii. May present as an eyelid tubercle, conjunctivitis, dacryoadenitis, dacryocystitis
5. Intraocular TB - tuberculous uveitis
a. Hematogenous dissemination of the organism, usually from lung, or immune response to

extraocular TB
b. Ocular symptoms
i. Waxing and waning course
ii. Progressive increase in floaters
iii. Worsening of vision due to progressive intraocular inflammation, choroidal and retinal
involvement or cystoid macular edema
c. Chronic granulomatous anterior or posterior or intermediate or panuveitis or sclerouveitis
d. Scleritis
i. Nodular anterior scleritis
ii. Posterior scleritis with acute angle closure glaucoma
i) Rare - TB should be considered in such cases
e. Anterior uveitis
i. Mutton-fat keratic precipitates (KP)
ii. Iris nodules
iii. Posterior synechiae
iv. Secondary glaucoma
v. Nongranulomatous uveitis may also occur
f. Intermediate uveitis
i. Waxing and waning course
ii. Disseminated choroiditis-most common presentation
i) choroidal tubercles
ii) Deep, multiple, discrete, yellowish lesion
iii. Vitreous cells and haze with accumulation of vitreous opacities
iv. Cystoid macular edema
v. Retinal periphlebitis
vi. Posterior uveitis or panuveitis
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vii. Single, large elevated choroidal mass (tuberculoma)
viii. Serpiginous-like choroiditis
ix. Retinal periphlebitis-Eales disease
x. Subretinal abscess in immunocompromised host
xi. Optic neuritis
xii. Acute panophthalmitis
1. Definitive diagnosis requires demonstration of mycobacteria from bodily fluids or affected tissues; however,
this is not accomplished in most cases of ocular TB. Nonetheless, acid fast staining should be performed
on all chorioretinal biopsies from uveitis cases unresponsive to therapy
2. Diagnosis is presumptive in the majority of cases and based on indirect evidence such as positive PPD or
Gamma interferon release assay response tests and therapeutic response to anti-TB agents
3. A positive PPD is indicative of prior exposure to TB but not necessarily of active systemic infection
a. In the United States, PPD is considered positive requiring intervention if
i. Induration of >5 mm in
i) Patients with HIV
ii) Patients with contact with active TB
iii) Radiographs consistent with healed TB lesions
ii. Induration of > 10 mm in
i) Patients with diabetes mellitus
ii) Patients with renal failure
iii) Patients using immunosuppressive agents
iv) Health care workers
v) Recent immigrants from high prevalence countries
iii. Induration is > 15 mm in patients with no known risk factors
b. False-negative skin testing occurs at a rate of 25%
i. Profound acute illness
ii. Immunosuppression
iii. Corticosteroid use
iv. Advanced age
v. Poor nutrition
vi. Sarcoidosis
c. False-positive skin testing
i. Individuals infected with atypical mycobacteria
ii. Immunized with BCG
iii. Treated with intra-luminal BCG injections for bladder carcinoma
4. Definitive diagnosis may require intraocular fluid analysis or tissue biopsy
a. Nucleic acid amplification techniques
i. Polymerase chain reaction (PCR)
b. Biopsy of affected ocular tissue
5. Interferon Gamma Release Assays (IGRAs) Quanti-Feron-TB™ or Gold Assay, or T-spot TB™ assay
a. Measure interferon gamma release from subjects' lymphocytes after exposure to selected
tubercular antigens - notably not the BCG antigen
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b. Good sensitivity in detecting latent disease
II. Define risk factors - CDC-defined high risk groups
A. Groups at higher risk of exposure to or infection with M. Tuberculosis
1. Close contacts of persons known or suspected to have TB
2. Foreign-born persons, including children from areas that have a high TB incidence or prevalence (e.g., Asia,
Africa, Latin America, Eastern Europe, Russia)
3. Residents and employees of high-risk congregate settings (e.g., correctional institutions, nursing homes,
mental institutions, other long-term residential facilities and shelters for the homeless)
4. Health care workers who serve high-risk clients
5. Some medically underserved, low-income populations as defined locally
6. High-risk racial or ethnic minority populations, defined locally as having an increased prevalence of TB
7. Infants, children and adolescents exposed to adults in high-risk categories
8. Persons who inject illicit drugs, any other locally identified high-risk substance users (e.g., crack cocaine
users)
B. Persons who are at higher risk of developing TB disease once infected with M. tuberculosis include
1. Persons with HIV infection
2. Persons who were recently infected with M. tuberculosis (within the past 2 years), particularly infants and
very young children
3. Persons who have medical conditions which result in immune suppression (e.g., diabetes mellitus,
end-stage renal disease) or who are iatrogenically immunosuppressed
4. Persons who inject illicit drugs, other groups of high-risk substance users (e.g., crack cocaine users)
5. Persons with a history of inadequately treated TB
A. Sarcoidosis
B. Toxoplasmosis
C. Syphilis
D. Masquerade syndrome
E. Multifocal choroiditis
F. Serpiginous choroiditis
G. Pars planitis
H. Retinal vasculitis
I. Chronic fungal endophthalmitis
IV. Describe patient management in terms of treatment and follow up
A. Systemic antibiotic therapy
1. Note that this is typically coordinated through an infectious disease specialist or state health department
2. Indications
a. Patients with uveitis with positive bacterial cultures or PCR results or presumed TB
b. Recently converted TB skin test
c. Positive QuantiFERON-TB Gold or similar Gamma interferon release assay test
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d. Abnormal chest radiograph
B. Multiple-agent therapy, usually isoniazid (INH), rifampin, ethambutol, and pyrazinamide for 6 to 9 months
1. Increasing incidence of resistance to isoniazid
2. Multi-drug-resistant TB (MDRTB)
a. Risk factors for MDRTB development
i. Noncompliant patients on single-agent therapy
ii. Migrant or indigent populations
iii. Immunocompromised patients, e.g., HIV patients
iv. Recent immigrants from countries where INH and rifampin are available over the counter
b. If drug-resistant
i. Add ethambutol or streptomycin
c. Direct observed therapy (DOT) ideal
C. Corticosteroids
1. Topical and systemic corticosteroids
a. Should only be used with appropriate anti-TB coverage
b. Intensive corticosteroid treatment administered without appropriate anti-TB coverage leads to

progressive worsening of ocular disease
D. Prophylactic treatment: single agent
1. Positive PPD or abnormal chest film
a. If systemic treatment of corticosteroids is being considered
b. If patient received corticosteroids for longer than 2 weeks at doses greater than 15mg per day
i. Prophylactic treatment with INH for 6 months to a year
2. If anti-TNF therapy is being considered in patients with latent TB (positive PPD or IGRA)
a. INH prophylaxis beginning at least 3 weeks prior to the first infusion
V. List complications of treatment, their prevention and management
A. Side effects of therapeutic agents
1. INH
a. Hepatotoxicity
b. Neurotoxicity - due to pyridoxine deficiency
i. Peripheral neuropathies
ii. Seizures
iii. Agitation
iv. Insomnia
v. Treated with pyridoxine
2. Pyrazinamide
a. Hepatotoxicity
3. Rifampin
a. Thrombocytopenia
b. Nephritis
c. Hepatotoxicity
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4. Ethambutol
a. Optic neuritis
i. Can improve with drug cessation
B. Non-compliance
1. Leads to MDRTB
2. Recurrence of disease
3. Reduced by DOT
A. Cataract
B. Glaucoma
D. Choroidal neovascularization
E. Subretinal abscesses
F. Spontaneous scleral rupture
G. Retinal neovascularization
H. Retinal detachment
I. Neovascular, or angle closure (with posterior scleritis) glaucoma
J. Fulminant panophthalmitis
A. Importance of compliance with medical therapy
B. Report any dramatic weight loss, new fevers and chills to physician
C. Report any significant visual loss while on therapy to physician
D. Importance of regular laboratory evaluation while on long-term anti-tuberculosis therapy
E. Need for screening of patient's close contacts
1. AAO, Basic Clinical and Science Course Section 9. Intraocular inflammation and uveitis, 2015-2016.
2. Gupta A, Gupta V. Tubercular posterior uveitis. Int Ophthalmol Clin 2005;45:71-88.
3. Mehta S, Gilada IS. Ocular tuberculosis in acquired immunodeficiency syndrome (AIDS). Ocul Immunol
Inflamm 2005;13:87-89.
4. Morimura Y, Okada AA, Kawahara S, et al. Tuberculin skin testing in uveitis patients and treatment of
presumed intraocular tuberculosis in Japan. Ophthalmology 2002;109:851-857.
5. Rosenbaum JT, Wernick R. The utility of routine screening of patients with uveitis for systemic lupus
erythematosus or tuberculosis. A Bayesian analysis. Arch Ophthalmol 1990;108:1291-1293.
6. Sheu SJ, Shyu JS, Chen LN, et al. Ocular manifestations of tuberculosis. Ophthalmology
2000;108:1580-1585.
7. Thompson NJ, Albert DM. Ocular tuberculosis. Arch Ophthalmol 2005;123:844-847.
8. Varma D, Anand S, Reddy AR, et al. tuberculosis: an underdiagnosed aetiological agent in uveitis with an
effective treatment. Eye 2005; Advanced online publication October 2005.
9. Gupta A, Gupta V. Tubercular posterior uveitis. Int Ophthalmol Clin 2005;45:71-88.
10. Demirci H, Shields CL, Shields JA, et al. Ocular tuberculosis masquerading as ocular tumors. Surv
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Ophthalmol 2004;49:78-89.
11. Bodaghi B; LeHoang P. Ocular tuberculosis. Curr Opin Ophthalmol 2000;11:443-8.
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1. Several species of Bartonella
a. In particular B. henselae and quintana
b. Identified in intraocular fluid of patients with intraocular inflammation
2. Bartonella
a. Small, rod-shaped, gram negative, bacteria
b. Hemotropic
3. The bacteria chronically infect
a. Erythrocytes
b. Macrophages
c. Vascular endothelial cells
4. Pathogenesis of ocular involvement is still unknown.
a. Direct infection
b. Secondary immune reaction
1. Cat-scratch disease (CSD) is seasonal
a. Occurs predominantly in the fall and winter
b. Most prevalent in southern states, California and Hawaii
2. Ocular involvement in 5-10% of CSD
a. Uncommon compared to non-ocular disease.
b. CSD: annual occurrence of 9.3 per 100,000 in the US
c. Highest incidence is among children younger than ten years, but has been reported in all ages
1. Exposure to pet cats
a. Asymptomatic cats serve as a major persistent reservoir for years
b. Harboring Bartonella in or on the surface of erythrocytes
2. Flea and tick bites
a. Cat and dog fleas and, less often, deer and dog ticks carry the bacteria and serve as the main
vector of transmission
i. Cat to cat
ii. Cats to humans
3. Clinical History
a. Skin entry site
i. Papule, vesicle or pustule
ii. Forms 3-10 days later
b. One week later regional lymphadenopathy
c. Mild to moderate flu-like symptoms
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d. Then ocular findings develop
4. Systemic dissemination of the bacteria can cause
a. Encephalopathy
b. Aseptic meningitis
c. Osteomyelitis
d. Hepatosplenic disease
e. Pneumonia, and pleural effusions
f. Pericardial effusions
1. Usually unilateral
2. Focal Chorioretinitis is most common manifestation. May resemble Toxoplasma retinochoroiditis
3. Neuroretinitis (most well recognized finding-only in 1-2% of CSD) with macular star formation
4. Papillitis
5. Multifocal chorioretinitis
6. Isolated anterior uveitis
7. Parinaud oculoglandular syndrome (granulomatous conjunctivitis and ipsilateral preauricular and/or

submandibular lymphadenopathy)
E. Describe the appropriate laboratory testing for establishing the diagnosis
1. Serologic testing
a. Indirect fluorescent antibody testing (>1:64 considered positive)
b. Enzyme immunoassay
c. Western blot analysis
2. Standard bacterial culture (highly sensitive and specific, takes longer)
a. Low sensitivity
b. Requires one to four weeks of incubation
c. Special techniques to increase sensitivity of cultures
3. Polymerase chain reaction (PCR) analysis of DNA for 16S rRNA gene or B. henselae DNA
A. Syphilis
B. Sarcoidosis
C. Lyme disease
D. Toxoplasmosis
E. Herpes viral infection
F. Mumps
G. Acute chlamydia infection
H. Toxocariasis
I. Leptospirosis
J. Tuberculosis
K. Histoplasmosis
L. Rocky Mountain Spotted Fever
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M. Ehrlichiosis
N. Tularemia
1. Ocular manifestations: conjunctivitis and glandular swelling - like Parinaud syndrome - rarely if ever causes
uveitis
2. Diagnostic studies: culture, immunofluorescent antibody analysis (IFA), serology or by a polymerase chain
reaction (PCR) assay from affected tissues
A. Effectiveness of antibiotics for this self-limited disease have not been established, nor have optimum
durations of treatment
B. Antibiotics administered orally or intravenously include
1. Doxycycline
a. Typical therapy (>8 years old): 100mg twice daily for 2-4 weeks
2. Azithromycin (alternative to doxycycline in children)
3. Rifampin (should be used in combination with other therapy to avoid resistance)
4. Ciprofloxacin
5. Trimethoprim
C. Systemic corticosteroid use has not been established but may be needed. Topical corticosteroid treatment
is warranted to reduce inflammatory damage to ocular structures
A. Complications of systemic antibiotics
A. Permanent macular dysfunction and scarring may occur in severe cases
B. Optic neuropathy or atrophy
1. Take oral antibiotics with six ounces of water
B. Follow-up instructions
1. Frequency of followup visit tailored to the severity of the disease
C. Natural history of the disease
1. Self-limited course with good visual outcomes
D. Appropriate infectious disease consultation
1. Referral to infectious disease specialist for evaluation of systemic manifestation of disease and selection of
antibiotics
2. AAO, Focal Points: Infectious Posterior Uveitis, Module #3, 2005, p.3.
Uveitis 164 © AAO 2017-2019

I. Describe approach in establishing diagnosis
A. Describe the etiology of disease
1. Caused by Brucella melitensis, B. abortus, B. canis, and B. suis
2. Most cases of human disease are caused by B. melitensis, the most virulent species
3. B. abortus most prevalent Brucella species in North America
4. Humans acquire disease by
a. Consuming unpasteurized milk or milk products from infected animals
b. Eating meat products from infected animals
c. Occupational contact of infected animals and products
d. Organisms enter body through abraded skin or mucous membranes or by aerosolization
B. Define relevant aspects of epidemiology of the disease
1. Worldwide distribution, more common in Latin America
2. Endemic areas such as Peru, Kuwait, Saudi Arabia
3. Important health problem in Middle East, Mediterranean, Mexico, Central and South America
4. Less common now with quality control of animal products, adequate livestock vaccination
5. Age 16 to 35 years
6. High-risk groups
a. Dairy farmers
b. Meat inspectors
c. Animal handlers
d. Veterinarians
e. Travelers to endemic areas
C. Describe pertinent elements in the history
1. Ocular involvement variably seen with acute phase or chronic phase of systemic illness (up to 25%)
2. Acute phase of systemic Brucellosis
a. Fever, drenching sweats, chills, and weakness
i. Reticuloendothelial system - preferentially involved
i) Bone, CNS, heart, lungs, liver, testes, and skin
b. Patient may have unilateral or bilateral sudden onset of
i. Pain
ii. Decreased vision
iii. Floaters
iv. Scotoma
v. Metamorphopsia
3. Relapsing and chronic phases of the illness
a. Blurred vision
b. Central scotoma
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c. Metamorphopsia
1. Acute phase of illness
a. Nummular keratitis
b. Scleritis
i. Diffuse
ii. Nodular
c. Anterior Uveitis
i. Granulomatous or non-granulomatous
ii. May be more common in acute phase
d. Vitritis
e. Peripapillary, nodular or multifocal choroiditis
f. Panuveitis
g. Endophthalmitis
h. Retinitis
i. Retinal vasculitis
j. Neuro-ophthalmic manifestations can include
i. Papilledema
ii. Retrobulbar optic neuritis
iii. Optic atrophy
2. Chronic phase of illness
a. Anterior uveitis - chronic smoldering
b. Posterior, panuveitis, optic nerve edema
E. Describe appropriate testing and evaluation in establishing the diagnosis
1. Clinical diagnosis based on febrile illness in endemic areas or after exposure to unpasteurized dairy
products and presence of anterior uveitis, nodular choroiditis, retinal edema and hemorrhages
a. History of recent exposure to infected animals and animal products, presence of systemic features
of disease is also helpful
b. Brucella agglutination test
c. Blood cultures, specifically using tryptic soy broth
i. Will be positive in the acute phase
ii. May take 6 weeks to grow
d. PCR of ocular fluids
e. ELISA based serologic testing for anti-Brucella IgM for acute disease and IgG for chronic and
recurrent phases of disease
A. Tuberculosis
B. Sarcoidosis
C. Syphilis
D. HLA-B27 positive anterior uveitis
E. Outer retinal toxoplasmosis
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F. Multifocal choroiditis and panuveitis
G. Lyme disease
H. Behçet disease (in endemic areas)
III. Describe medical therapy
A. Systemic antibiotics
1. Doxycycline must be used in combination with one of the following
a. Rifampin - drug of choice and recommended by WHO
b. Streptomycin IV
c. Gentamicin IV
2. Trimethoprim/sulfamethoxazole - in children under 6 when tetracyclines contraindicated
3. Given for 6 weeks in the acute phase and up to 3 months for chronic disease
B. Corticosteroids
1. Systemic, periocular, and topical given concomitantly with systemic antibiotics
IV. Describe disease-related complications
A. Chronic smoldering uveitis may cause
1. Cataracts
2. Glaucoma
4. Macular scars secondary to choroiditis
B. Visual prognosis
1. Most cases of acute Brucellosis curable with prompt antibiotic therapy
2. Uveitis prognosis is good if diagnosis is made and treatment instituted early
3. Worse in patients with
a. Posterior and panuveitis particularly if there is macular scar present
b. Optic neuritis
V. Patient instructions
A. Prevention of infection best
1. Avoid exposure in endemic areas
a. Pasteurize all milk
b. Heating milk to 60ºC for 10 minutes kills Brucella sp.
B. Report high fevers with exposure to unpasteurized milk, infected meat products, or infected animals
2. Ronaldo I. Olarte L. Vilchez G., et al. Ocular Manifestations Associated with Brucellosis: A 26 Year
Experience in Peru. Clin Infect Dis. 2008; 46: 1338-45.
3. Rolando I. Vilchez G., Olarte L., et al. Brucellar Uveitis: Intraocular Fluids and Biopsy Studies. Int J Infect
Dis. 2009; 13: e206-211.
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4. Sungur G. K., Hazirolan D Gurbuz Y, et al. Ocular Involvement in Brucellosis, Can J Ophthalmol. 2009; 44:
598-601.
5. Vitale AT. Brucellosis. In Diagnosis and Treatment of Uveitis. Eds. Foster CS and Vitale AT. WB
Saunders. Philadelphia. 2002. pp.278-285.
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1. Pseudomonas species
a. Most common after pterygium excision
2. Actinomyces species and Nocardia
3. Mycobacteria
4. Fungal
a. Fusarium
b. Aspergillus
5. Gram positive cocci
a. Staphylococcus pneumococcus and Streptococcus species
6. Surgically induced
a. Reaction from Vicryl suture
b. Exposure to mitomycin C
1. Men and women equally affected
2. Previous ocular surgery
a. Pterygium surgery
i. Beta irradiation utilized
ii. Mitomycin C utilized
b. Scleral buckle
c. Cataract surgery
d. Pars plana vitrectomy
3. Trauma
a. Penetrating injury contaminated by soil or vegetable matter
1. Pain
2. Redness
3. Decreased vision
4. Recent anterior segment surgery
a. Can be delayed presentation (rarely many years)
1. Necrotic, thin, avascular sclera with inflammation at edges
2. Usually at site of a surgical or traumatic wound
3. May have mucopurulent discharge
4. Worsening with local corticosteroids or systemic immunosuppressive therapy
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1. Cultures - superficial at base of scleral necrosis
a. Bacterial and fungal
b. Causative organisms can be difficult to grow
2. Gram stain
3. Consider scleral biopsy if history of trauma or surgery
a. 5-8 mm square block of sclera at the margins of necrotic base including some healthy sclera
b. Pathological evaluation for presence of bacteria and fungi
c. PCR studies after homogenization and extractions
d. Immunohistochemistry (e.g., labeled anti-herpes antibody probes)
4. Testing for infectious and non-infectious scleritis
a. Anti-neutrophil cytoplasmic antibodies (ANCA)
i. cANCA- Granulomatosis with polyangiitis (GPA) (previously known as Wegener

granulomatosis)
ii. If positive, test for antibodies to myeloperoxidase and proteinase-3-confirmatory, increased

specificity
iii. pANCA- Microscopic polyangiitis (MPA)
b. Urinalysis
c. Fluorescent treponema antibody absorption/MHA-TP
d. Tuberculosis testing (PPD skin test or interferon-gamma release assays)
e. Rheumatoid factor, anti-cyclic citrullinated peptide antibodies
f. Lyme serology
g. Chest X-ray
h. SSA and SSB
i. Antinuclear antibodies
j. Erythrocyte sedimentation rate (ESR)
i. If giant cell arteritis suspected, would want temporal artery biopsy
A. Previous ocular surgery - especially anterior segment
1. Pterygium with mitomycin C or beta irradiation
2. Cataract or glaucoma surgery (especially if mitomycin C used)
3. Scleral buckle
B. Trauma
1. Penetrating ocular injury
2. Contaminated with soil or vegetable matter
A. Non-infectious necrotizing scleritis
1. Granulomatosis with polyangiitis (GPA) (previously known as Wegener granulomatosis)
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3. Relapsing polychondritis
4. Rheumatoid arthritis
5. Other collagen vascular disorders
A. Best outcomes when medical and surgical treatment combined
1. Surgical debridement of infected tissues, often combined with cryotherapy
2. Multiple surgeries may be required
3. Systemic antibiotics
4. Topical antibiotics and subconjunctival antibiotics
5. Systemic analgesics
a. Nonsteroidal anti-inflammatory drugs
b. Judicious use of mild oral narcotics
B. Avoid corticosteroids
C. Systemic and topical antibiotic treatment may be needed for six or more weeks
D. Scleral patch grafting may be needed in cases with severe thinning
A. Globe perforation during surgery; be prepared with scleral graft tissue
B. Inadequate excision of infected tissues can result in recurrence of disease
C. Toxicity of topical and systemic antibiotics
A. Corneal extension
B. Globe perforation - spontaneous
C. Endophthalmitis
D. Serous retinal detachments
E. Blind and painful eye
A. Long term treatment may be needed
B. Severe visual loss or loss of eye possible
C. Contact ophthalmologist for severe pain or vision loss
1. These two symptoms may indicate increased activity of the scleritis or persistence of the infectious process
requiring changes to the therapeutic regimen
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A. Describe the etiology of this disease - Candida albicans and Aspergillus spp
1. Hematogenous dissemination - Multiple sources of infection:
a. Systemic infections
i. Endocarditis
ii. Gastrointestinal and hepatic infections
iii. Urinary tract infections
iv. Cutaneous infections
v. Pulmonary infections - Aspergillus
b. Intravenous drug use
c. Iatrogenic
i. Indwelling intravenous catheters
ii. Contaminated intravenous fluids
iii. Contaminated injectable medications (Propofol - Candida)
iv. Parenteral nutrition
v. Invasive surgical/diagnostic procedures
vi. Hemodialysis
1. Uncommon
2. Can affect all ages; from neonates to the elderly
3. Bilateral in up to 25%
4. Patients typically present with systemic infection but others may appear healthy (rare)
a. Fungal: over 50% of all cases of endogenous endophthalmitis
i. Candida albicans
i) Candida endophthalmitis occurs in 37% of patients with candidemia
(i) C. glabrata - becoming important pathogen in post-penetrating keratoplasty

exogenous endophthalmitis. Voriconazole resistance
ii. Aspergillus spp.
1. Many patients have an underlying systemic infection or potential source of infection (Refer to section 1A
Describe the etiology of this disease - Candida albicans and Aspergillus spp.)
1. Symptoms
a. Decreased vision
b. Floaters or scotoma
c. Ocular pain (not always present)
d. Constitutional symptoms (not always present)
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2. Signs
a. Eyelid swelling possible
b. Conjunctival injection in some patients
c. Anterior chamber inflammation with or without hypopyon
d. Vitritis; may be severe; "string of pearls" or "fungus ball"
e. Vitreous abscess
f. Retinal hemorrhages
g. Vascular sheathing
h. Chorioretinitis - multiple, white, bilateral, well circumscribed lesions <1mm in diameter in posterior
pole - Candida endophthalmitis
i. Diffuse macular chorioretinitis - characteristic of Aspergillus endophthalmitis
1. Cultures
a. Blood
b. Other suspected sites of infection based upon clinical suspicion; urine, sputum, cerebrospinal fluid,
etc.
c. Indwelling catheters and/or intravenous lines
2. Intraocular fluid analysis - useful in absence of positive cultures from elsewhere
a. Vitreous biopsy
i. Giemsa stain, culture, sensitivities
ii. Polymerase chain reaction (PCR); may be useful with unusual organisms or culture-
negative samples.
3. Screening recommendations in patients with confirmed candidemia
a. All patients should have a baseline eye exam
b. Only patients with visual symptoms or those unable to verbalize symptoms should have dilated
fundus exam within 72 hours and followed closely for 2 weeks for ocular involvement (see reference
#9 below)
A. Known/confirmed candidemia or systemic aspergillosis
B. Recent major gastrointestinal surgery
C. Bacterial sepsis
D. Systemic antibiotic use
E. Indwelling catheters
F. Hyperalimentation
G. Immunocompromised and chronically ill patients
H. Immunomodulatory therapy
I. Intravenous drug use
1. Most common risk factor for Candida or Aspergillus endophthalmitis
A. Adults
1. Exogenous endophthalmitis
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2. Infectious retinitis or retinochoroiditis
a. Toxoplasmosis or toxocariasis
b. Viral retinitis
i. Acute retinal necrosis
ii. Cytomegalovirus retinitis
c. Fungal chorioretinitis -other sp.
3. Non-infectious intermediate uveitis
4. Masquerade syndromes
a. Ocular ischemic syndrome
b. Primary vitreoretinal lymphoma
c. Leukemia
d. Necrotic uveal melanoma
B. Children
1. Exogenous endophthalmitis
2. Infectious and non-infectious uveitis (Refer to section IIIA2 Infectious retinitis or retinochoroiditis and section
IIIA3 Non-infectious uveitis)
3. Masquerade syndromes
a. Retinoblastoma
b. Leukemia
c. Occult intraocular foreign body
A. Describe the natural history, outcome, and prognosis
1. Candida - Variable prognosis
2. Aspergillus - Poor prognosis
a. Secondary macular involvement
b. Vascular involvement
1. Consultation with an infectious disease specialist highly desirable
2. Topical therapy
a. Cycloplegics
b. Topical corticosteroid
3. Intravitreal therapy
a. Amphotericin B
b. Voriconazole
4. Systemic antifungals
a. Voriconazole (best ocular penetration of systemically administered drug)
b. Caspofungin
c. Fluconazole
d. Amphotericin in resistant cases
i. Liposomal lipid complex formulations to reduce renal toxicity
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1. Vitrectomy - therapeutic and diagnostic
a. Vitreous culture and sensitivities
b. PCR analysis of Intraocular fluids
c. Debulk organisms and microtoxins, as well as vitreous opacities or membranes
d. Required in fungal endophthalmitis if vitreous involvement
e. May not be necessary if only choroiditis (in candidiasis) is present without vitreous involvement
f. Cases of pseudophakic Aspergillus endophthalmitis may require IOL removal
V. List the complications of treatment, their prevention and management.
A. Side effects and risks of systemic medications, surgery, anesthesia
A. Ocular
1. Cataract
2. Glaucoma
3. Hypotony
4. Retinal detachment
5. Chorioretinal scar
6. Choroidal neovascularization
7. Phthisis
8. Enucleation
B. Systemic
1. Mortality: 5% or greater (especially with disseminated aspergillosis) associated with extraocular infection
A. Compliance with ocular and systemic therapy
B. Report any changes in visual acuity, redness, or pain
3. Smith SR, Kroll AJ, Lou PL, Ryan EA. Endogenous bacterial and fungal endophthalmitis. Int Ophthalmol
Clin 2007;47(2):173-83.
4. Chee SP, Jap A. Endogenous endophthalmitis. Curr Opin Ophthalmol 2001;12:464-70.
5. Samiy N, D'Amico DJ. Endogenous fungal endophthalmitis. Int Ophthalmol Clin 1996;36:147-62.
6. Breit SM, Hariprasad SM, Mieler WF, et al. Management of endogenous fungal endophthalmitis with
voriconazole and capsofungin. Am J Ophthalmol. 2005;139:135-140.
7. Essman TF, Flynn HW, Smiddy WE, et al. Treatment outcomes in a 10-year study of endogenous fungal
endophthalmitis. Ophthalmic Surg Lasers. 1997;28:185-194.
8. Weishaar PD, Flynn HW Jr., Murray TG, et al. Endogenous Aspergillus endophthalmitis: clinical features
and treatment outcomes. Ophthalmology. 1998;105: 57-65.
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9. Dozier CC, Tarantola RM, Jiramongkolchai K, Donahue SP. Fungal Eye Disease at a tertiary care center :
The utility of routine inpatient consultation. Ophthalmology. 2011; 118:1671-1676.
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Primary central nervous system intraocular lymphoma
A. Define the relevant aspects of epidemiology of the disease
1. Lymphoma arising in the eye or associated with the primary central nervous system lymphoma (PCNSL)
a. Also known as primary vitreoretinal lymphoma (PVRL) or primary intraocular lymphoma (PIOL)
b. 15% of patients with PVRL develop PCNSL and 65-90% of patients with PCNSL develop PVRL
c. Usually a diffuse large B cell lymphoma
d. Previously it was known as reticulum cell sarcoma
e. T-cell lymphomas involving the eye are rare
2. Typical age of onset: > 50 years, mainly affects patients in the 6th and 7th decade
3. Incidence increased until last decade:
a. Approximately 1900 cases of PCNSL per year in USA, approximately 380 cases of PIOL/PVRL
b. >30-fold increase in cases in 3 decades
c. 0.3 % per 100,000 persons-years among immunocompetent patients
d. 4-5 per 1,000 person-years patients with Acquired Immunodeficiency Syndrome (AIDS)
1. Central nervous system (CNS) signs and symptoms
2. Confusion, weakness, deterioration in mental functions
C. Ocular history
1. Bilateral, but may start in an asymmetrical fashion
2. Decreased vision and floaters
3. Rarely, pain and redness
4. 25% PCNSL present in the eye at diagnosis
1. Mild or no anterior segment inflammation, synechiae are uncommon
2. Clumps and sheets of white cells in the vitreous
3. Multifocal subretinal and sub-pigment epithelial infiltrates
4. Atypical presentations: hemorrhagic retinitis resembling viral retinitis, exudative retinal detachment
5. Preservation of visual acuity disproportionate to amount of cells
1. Must suspect the lymphoma in a patient who has chronic, medically unresponsive uveitis characterized by
vitreous cells and subretinal or subretinal pigment epithelium (RPE) infiltrates
2. Vitreous biopsy, sub-RPE aspirate and/or retinal biopsy
a. Cytology
b. Immuno cytopathology
c. Flow cytometry
d. Cytokine analysis
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e. Gene rearrangement
f. Handling of vitreous specimens (See Diagnostic vitreoretinal procedures in uveitis: vitreous biopsy)
i. Multiple vitreous specimens may be needed
3. Magnetic resonance imaging of the brain
4. Cerebrospinal fluid for cytology
F. Pathology
1. Cytology: gold standard
a. Lymphoma cells are large, pleomorphic with scanty cytoplasm, pleomorphic nuclei and prominent
nucleoli
b. Low sensitivity as samples are paucicellular, interpretation dependent on expertise of

cytopathologist
c. Coordination between surgeon and cytopathologist is necessary for proper handling of specimens
2. Immunophenotyping
a. Immunohistochemistry or flow cytometry
i. Used to establish clonality of B lymphocytes
ii. Immunoglobulin kappa or lambda light chains restriction and the presence of monoclonal
B-lymphocytes
iii. Predominant T-cell population with aberrant markers inverted CD4:CD8 ratio may indicate
T-cell lymphoma
3. Cytokine analysis
a. High IL-10/IL-6 ratio suggestive of PCNSL (PIOL/PVRL)
4. Gene rearrangement
a. Heavy chain gene rearrangements (IgH) for B-cell lymphoma or T-cell receptor gamma gene
rearrangements for T-cell lymphoma
A. Age
B. Immunosuppression
C. AIDS
A. Sarcoidosis
B. Syphilis
C. Tuberculosis
D. Acute retinal necrosis
E. Behçet disease
F. Cytomegalovirus retinitis
G. Toxoplasmosis
H. Birdshot chorioretinopathy
I. Acute posterior multifocal placoid pigment epitheliopathy
J. Multifocal choroiditis
K. Vogt Koyanagi Harada disease
L. Amyloid
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M. Metastatic Intraocular lymphoma
A. Corticosteroids are cytolytic to lymphoma cells leading to an apparent response to treatment initially.
Corticosteroids also decrease the yield of biopsy
B. Immediate referral to an oncologist for treatment and staging
C. Chemotherapy alone
D. Combination chemotherapy radiation
E. Consider local therapy/control with
1. Intravitreal methotrexate/rituximab in conjunction with systemic treatment
F. Median survival rate is 2-3 months with supportive care alone
1. Intrathecal chemotherapy may increase survival rate
2. With treatment, longest median survival approaches 40 months
V. List ocular complications of treatment
A. Cataract
B. Radiation retinopathy
C. Retinal detachment
A. Visual impairment or blindness
B. Serous retinal detachments
C. Optic atrophy
A. Importance of oncology referral
B. Follow instructions regarding medications
Leukemia (as masquerade syndrome)
I. Describe approach to establishing diagnosis
A. Epidemiology
1. Up to 75% of patients with acute leukemias may have intraocular findings
B. Ocular manifestations
1. Anterior uveal infiltration
a. Hypopyon (pseudohypopyon)
b. Hyphema
c. Both
2. Posterior segment
a. Intraretinal hemorrhages
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b. Cotton wool spots,
c. White-centered retinal hemorrhages (Roth spots)
d. Microaneurysms
e. Occasionally peripheral retinal neovascularization.
f. Vitritis - rare - leukemic cells can break through the internal limiting membrane
g. Exudative retinal detachment - choroidal involvement
C. Testing
a. Choroidal involvement
i. Similar to the pattern of Vogt-Koyanagi-Harada syndrome or posterior scleritis
ii. Multiple pinpoint areas of retinal pigment epithelial leakage in the early and mid-phases
iii. Pooling of fluorescein in the subretinal space in the late phases
2. Cytologic evaluation of aqueous specimen if hyphema or hypopyon
a. Obtained through a clear corneal anterior chamber paracentesis
b. Can be diagnostic
II. Therapy
A. Oncology referral
B. Systemic chemotherapy
III. Disease-related complications
A. Acute leukemic infiltration of the optic nerve
1. Sudden onset of no light perception vision
2. More common in children
3. Radiation-oncologic emergency
Uveal melanoma (as a masquerade syndrome)
I. Describe approach to establishing diagnosis
A. Epidemiology
1. Most common primary intraocular malignancy
B. Clinical manifestations
1. 5-20% percent of patients may present with intraocular inflammation
a. Episcleritis, scleritis
b. Anterior and posterior uveitis
c. Sectoral cataract
d. Endophthalmitis
2. Most that present with uveitis are epithelioid cell or mixed cell, necrotic tumors
C. Diagnostic testing
1. Ultrasonography
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a. Characteristic low to medium reflectivity of lesions
II. Therapy
A. Enucleation
B. Local therapy for smaller lesions
1. Surgical excision - smaller iris and ciliary body lesions
2. Plaque radiotherapy
III. Disease related complications
A. Metastasis - especially with ciliary body tumors and large choroidal tumors
1. All patients require metastatic evaluation
Retinoblastoma (as masquerade syndrome)
1. Intraocular tumor arising from photoreceptor precursor cells
1. Most common malignant ocular tumor of childhood
2. Diagnosed between 1 and 3 years of age
1. Most common initial sign is leukocoria, first noticed by the family
2. Strabismus
3. Suspected intraocular inflammation
1. Strabismus
2. Glaucoma
3. Proptosis
4. White retinal lesions
6. Calcification on B-scan or CT
7. Uveitis masquerade—aqueous or vitreous cellular infiltration mimicking uveitis
a. Vitreous seeding in endophytic retinoblastoma may be so extensive as to mimic endophthalmitis
b. Tumor cells may float in the anterior chamber (pseudo-iritis) and form a pseudohypopyon
c. No posterior synechiae
1. Retinoblastoma must be excluded in any young child with leukocoria, strabismus or an undiagnosed uveitis
2. Pars plana vitrectomy or paracentesis for diagnosis is contraindicated in suspected retinoblastoma because
it increases the possibility of metastasis
3. Computed tomography (CT) scan of the head and orbits
a. Intralesional calcification (less common with diffuse tumor)
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4. B-scan
a. Intralesional calcification (less common with diffuse tumor)
II. Describe patient management in terms of treatment and follow-up
A. Urgent ocular oncology and pediatric oncology referral
B. Enucleation still used in patients with large unilateral retinoblastoma
1. Invasion of optic nerve and extraocular extension are associated with a relatively poor prognosis
C. Neoadjuvant chemotherapy ("chemo reduction") is now used as primary treatment to reduce the size of the
lesion
D. Consolidation therapy is then performed with radiotherapy, cryotherapy or laser photocoagulation or

transpupillary thermotherapy (TTT)
E. External-beam radiotherapy for advanced retinoblastoma (tumor may recur and there is risk of secondary
tumors)
F. Local therapy for smaller tumors
1. Cryotherapy and laser photoablation
III. List the differential diagnosis of retinoblastoma/masquerade syndrome
A. Coats disease
B. Persistent hyperplastic primary vitreous
C. Ocular toxocariasis
D. Advanced retinopathy of prematurity
E. Retinal dysplasia
F. Retinal detachment
G. If Pseudohypopyon - consider leukemia, endogenous endophthalmitis, HLAB27 associated iridocyclitis, and

Behçet disease (unlikely in the retinoblastoma age group)
A. Chemotherapy
1. Neutropenia
2. Opportunistic infection
B. Radiation therapy
1. Radiation retinopathy
2. Cataract
3. Increased rate of orbital sarcoma development
A. Secondary tumors in patients with heritable disease
B. Midline brain tumors (trilateral retinoblastoma) in patients with heritable disease
A. Offspring are at risk for disease and should be examined shortly after birth
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B. Follow-up examination under anesthesia schedule is individualized based on patient's stage of disease
Bilateral diffuse uveal melanocytic proliferation
1. Unknown - circulating anti-retinal antibodies reported in some cases
2. Associated with systemic malignancy - paraneoplastic syndrome
a. Bronchogenic carcinoma
b. Ovarian Carcinoma
c. Squamous carcinoma of the lung
d. Uterine leiomyoma
e. Others
a. Rapid visual loss
1. Ocular manifestations
a. Cataracts
b. Multiple pigmented and non-pigmented iris nodules
c. Multiple pigmented and non-pigmented choroidal nodules
d. Serous retinal detachments
D. Histology
1. Diffuse uveal infiltration by benign nevoid and spindle shaped cells
2. Necrosis within tumors
3. Scleral involvement is common
II. Describe patient management in terms of treatment and follow-up
A. Find primary malignancy
B. Treat primary malignancy
C. Plasmapheresis - can be tried
D. Corticosteroids and immunomodulatory therapy - not very successful
Other masquerade syndromes
I. Juvenile xanthogranuloma
II. Metastatic cancer, melanoma or lymphoma
III. paraneoplastic retinopathy
Non-neoplastic masquerade syndromes
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I. Retinitis pigmentosa (RP)
II. Chronic retinal detachment
III. Retained intraocular foreign body
IV. Pigment Dispersion Syndrome
V. Ocular Ischemic Syndrome
2. AAO, Focal Points: Intraocular Lymphoma, Vol XXIII, Number 12, 2005.
3. Choi JY, Kafkala C, Foster CS. Primary intraocular lymphoma: A review. Semin Ophthalmol
2006;21:125-33.
4. Nussenblatt RB, Chan CC, Wilson WH and the CNS and Ocular Lymphoma Workshop Group. International
Central Nervous System and Ocular Lymphoma Workshop; recommendations for the future. Ocul Immunol
Inflamm 2006;14:139-44.
5. Chan CC, Rubenstein JL, Coupland SE, Davis JL, Harbour JW, Johnston PB,Cassoux N, Touitou V, Smith
JR, Batchelor TT, Pulido JS. Primary vitreoretinallymphoma: a report from an International Primary Central
Nervous System Lymphoma Collaborative Group symposium. Oncologist. 2011;16(11):1589-99. Epub 2011
Nov 1. Review. PubMed PMID: 22045784; PubMed Central PMCID: PMC3233294
6. Sen HN, Chan CC. Masquarade syndromes: Neoplasms. In Ophthalmology, 4th Edition. Yanoff M, Duker
JS. Elsevier, London, United Kingdom.
8. Kincaid MC, Green WR. (1983) Ocular and orbital involvement in leukemia. Surv Ophthalmol 27: 211-232.
9. Ayliffe W, Foster CS, Marcoux P, Upton M, Finkelstein M, Kuperwaser M, Legmann A. (1995) Relapsing
acute myeloid leukemia manifesting as hypopyon uveitis. Am J Ophthalmol 119: 361-364.
10. Lipton JH, McGowan HD, Payne DG. (1995) Ocular masquerade syndrome in lymphoid blast crisis of
chronic myeloid leukemia. Leuk Lymphoma 20: 161-163.
11. Fraser DJ, Jr., Font RL. (1979) Ocular inflammation and hemorrhage as initial manifestations of uveal
malignant melanoma. Incidence and prognosis. Arch Ophthalmol 97: 1311-1314.
12. Mathew B, Brownstein S, Kertes PJ, Gilberg S, Damji KF, Chialant D. (2004) Clinically unsuspected diffuse
uveal melanoma presenting as recurrent iritis. Can J Ophthalmol 39: 464-467.
13. Demirci H, Shields CL, Shields JA, Honavar SG, Eagle RC, Jr. (2002) Ring melanoma of the ciliary body:
report on twenty-three patients. Retina 22: 698-706; quiz 852-693.
14. All-Ericsson C, Economou MA, Landau I, Traisk F, Seregard S. (2007) Uveitis masquerade syndromes:
diffuse retinoblastoma in an older child. Acta Ophthalmol Scand 85: 569-570.
15. Shields CL, Ghassemi F, Tuncer S, Thangappan A, Shields JA. (2008) Clinical spectrum of diffuse
infiltrating retinoblastoma in 34 consecutive eyes. Ophthalmology 115: 2253-2258.
16. Balasubramanya R, Pushker N, Bajaj MS, Ghose S, Kashyap S, Rani A. (2004) Atypical presentations of
retinoblastoma. J Pediatr Ophthalmol Strabismus 41: 18-24.
17. Grossniklaus HE, Dhaliwal RS, Martin DF. (1998) Diffuse anterior retinoblastoma. Retina 18: 238-241.
18. Chowers I, Zamir E, et al. Retinitis pigmentosa associated with Fuchs' heterochromic uveitis. Arch
Ophthalmol 2000;118(6):800-2.
19. Grover S, Apushkin MA, Fishman GA. Topical dorzolamide for the treatment of cystoid macular edema in
patients with retinitis pigmentosa. Am J Ophthalmol 2006;141:850-858.
20. Berson EL, Rosner B, Sandberg MA, et al. A randomized trial of supplemental vitamin A and vitamin E
supplementation for retinitis pigmentosa. Arch Ophthalmol 1993;111:761-772.
21. In: Ryan SJ. Retina. Complicated retinitis pigmentosa. Chapter 17, p.432.
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23. Rothova A, Ooijman F, Kerkhoff F, Van Der Lelij A, Lokhorst HM. (2001) Uveitis masquerade syndromes.
Ophthalmology 108: 386-399.
24. Berson EL. (2000) Retinitis pigmentosa and allied diseases. In DM Albert, FA Jacobiec (eds.), Principles
and Practice of Ophthalmology, pp. 2262. W.B. Saunders, Philadelphia,
25. Ffytche TJ. (1972) Cystoid maculopathy in retinitis pigmentosa. Trans Ophthalmol Soc U K 92: 265-283.
26. Hendricks RL, Fishman GA. (1985) Lymphocyte subpopulations and S-antigen reactivity in retinitis
pigmentosa. Arch Ophthalmol 103: 61-65.
27. Marmor MF. (1999) The electroretinogram in retinitis pigmentosa. Arch Ophthalmol 97: 1300-1304.
28. Brown GC, Magargal LE. (1988) The ocular ischemic syndrome. Clinical fluorescein angiographic and
carotid angiographic features. Int Ophthalmol Clin 11: 239-251.
29. Sivalingam A, Brown GC, Magargal LE. (1991) The ocular ischemic syndrome. III. Visual prognosis and
the effect of treatment. Int Ophthalmol 15: 15-20.
30. Sivalingam A, Brown GC, Magargal LE, Menduke H. (1989) The ocular ischemic syndrome. II. Mortality
and systemic morbidity. Int Ophthalmol 13: 187-191.
31. Boke W, Hubner H. (1972) Acute retinal detachment with severe uveitis and hypotony of the eyeball. Mod
Prob Ophthalmol 10: 245-249.
32. Jarrett WH. (1981) Rhegmatogenous retinal detachment complicate by severe intraocular inflammation,
hypotony, and choroidal detachment. Trans Am Ophthalmol Soc 79: 664-683.
33. Schwartz A. (1973) Chronic open-angle glaucoma secondary to rhegmatogenous retinal detachment. Am J
Ophthalmol 75: 205-211.
34. Matsuo N, Takabatake M, Ueno H, Nakayama T, Matsuo T. (1986) Photoreceptor outer segments in the
aqueous humor in rhegmatogenous retinal detachment. Am J Ophthalmol 101: 673-679.
35. Kamath MG, Nayak IV, Satish KR. (1991) Case Report: Intraocular foreign body in the angle masquerading
as uveitis. Indian J Ophthalmol 39: 138-139.
36. Alexandrakis G, Balachander R, Chaudhry NA, Filatov V. (1998) An intraocular foreign body masquerading
as idiopathic chronic iridocyclitis. Ophthalmic Surg Lasers 29: 366-367.
37. Coleman DJ, Kucas BC. (1987) Management of intraocular foreign bodies. Ophthalmology 94: 1647-1673.
38. Behrens-Baumann W, Praetorius G. (1989) Intraocualr foreign bodies: 297 consecutive cases.
Ophthalmologica 198: 84-88.
39. Mieler WF, Ellis MK, Williams DF, Han DP. (1990) Retained intraocular foreign bodies and endophthalmitis.
Ophthalmology 97: 1532-1538.
40. Niyadurupola N, Broadway DC. (2008) Pigment dispersion syndrome and pigmentary glaucoma--a major
review. Clin Experiment Ophthalmol 36: 868-882.
41. Ritch R. (1996) A unification hypothesis of pigment dispersion syndrome. Trans Am Ophthalmol Soc 94:
381-405.
42. Zimmerman LE. Ocular lesions of juvenile xanthogranuloma. Nevoxanthoedothelioma. Am J Ophthalmol

1965;60:1011-35.
43. Zamir E, Wang RC, et al. Juvenile xanthogranuloma masquerading as pediatric chronic uveitis: a
clinicopathologic study. Surv Ophthalmol 2001;46:164-71.
44. Parmley VC, George DP, et al. Juvenile xanthogranuloma of the iris in an adult. Arch Ophthalmol
1998;116:377-9.
45. DeBarge LR, Chan CC, et al. Chorioretinal, iris, and ciliary body infiltration by juvenile xanthogranuloma
masquerading as uveitis. Surv Ophthalmol 1994;39:65-71.
46. Mochizuki M, Singh AD. Epidemiology and clinical features of intraocular lymphoma.Ocul Immunol Inflamm.
2009 Mar-Apr;17(2):69-72.
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1. Paraneoplastic vs. non-paraneoplastic AIR
a. Non-paraneoplastic AIR
i. Circulating anti-retinal antibodies - responsible for photoreceptor damage
ii. antibodies against recoverin, enolase
b. Paraneoplastic AIR - cancer-associated retinopathy (CAR) and melanoma-associated retinopathy

(MAR)
2. Retinal degeneration presumably immunologically based
a. Autoantibodies directed against retinal antigens
i. 23kD protein recoverin—most common autoantibody isolated in CAR
ii. Bound to outer retinal segments (e.g., photoreceptors in CAR) or to inner retinal segments
(e.g., bipolar cells in MAR) causing irreversible retinal dysfunction
b. Other protein targets have been identified
3. Associated with carcinomas
a. CAR most commonly associated with small-cell (oat cell) lung carcinoma
i. Diagnosis of CAR frequently precedes diagnosis of underlying malignancy
ii. Non-small cell lung, endometrial, breast, small cell cervical, and ovarian carcinoma also
reported
b. MAR associated with malignant melanoma often with metastases
i. Diagnosis of melanoma typically predates visual symptoms in MAR
1. Most common among patients > 50 years of age
2. No sex predilection
3. Rare, prevalence not well-described
1. Bilateral progressive visual loss
2. Nyctalopia (night blindness) or photo aversion
3. Photopsias that may be pulsating, shimmering
4. Glare, photosensitivity
5. Ring scotomas in CAR; central visual field defects with peripheral field sparing in MAR
1. Arteriolar narrowing
Uveitis 186 © AAO 2017-2019

2. Mild vitreous inflammation
3. Rarely retinal periphlebitis
4. Often no pigmentary changes in retina especially early in disease course; end stage disease may resemble
RP with optic nerve pallor and retinal atrophy/pigmentary changes
5. At the onset of the disease clinical signs are often minimal compared to the degree of visual loss
1. ERG: Either severe reduction of both a-wave (photoreceptors) and b-wave (bipolar cells) responses OR
negative pattern ERG (diminished scotopic b-wave but preserved a-wave responses). Delay in implicit times
a. MAR: negative pattern ERG is most typical
b. CAR: both rods and cones can be affected, cone ERG most often affected
2. Visual field testing may show rapid worsening in scotomas
3. Testing for antiretinal antibodies
a. Most often performed in research laboratories
b. CLIA certified testing available in some labs
c. Antiretinal antibodies are tested by
i. Western blot: serum electrophoresis displays antibodies present in high titers and defines
the molecular weight of the antigenic target
ii. Immunohistochemical staining of human retinal tissue: Patient serum applied to retinal
slices and bound immunoglobulin detected with secondary antibody tagged with fluorescent
marker. Localizes the immunoglobulin binding to certain retinal cell layers
iii. ELISA: only for known antigens (i.e., recoverin)
A. Not well defined
B. Positive prior history of or family history of cancer
C. History of heavy smoking possibly a risk factor as well
A. Retinitis pigmentosa
B. Cone-rod dystrophy
C. Intermediate uveitis
D. Syphilis
E. Retinal drug toxicity
F. Retinal degenerations associated with systemic disease
G. Acute zonal occult outer retinopathy (AZOOR)
1. Progressive, asymmetric visual acuity and visual field loss due to irreversible retinal degeneration
a. Rapid progression often seen with CAR is less common with MAR
2. Prognosis is generally poor even with treatment
B. Describe therapy options
Uveitis 187 © AAO 2017-2019

1. Prednisone
a. May consider intravitreal steroids in refractory cases
2. Plasmapheresis
3. Intravenous immunoglobulin (IV Ig)
4. Immunosuppressive drugs
a. DMARDs such as azathioprine, methotrexate, cyclosporine and biologic agents such as

alemtuzumab (pan-lymphocytic, anti-CD-52) and rituximab (B-cell, anti-CD 20)
5. Treatment for MAR similar to CAR with exception that typically diagnosis of the melanoma predates the
ocular findings
6. Treatment needs to be coordinated with the oncologist to avoid adverse effect on the underlying malignancy
A. Related to prednisone: Side effects are related to dose of prednisone and may include weight gain, moon
facies, elevated blood sugar or blood pressure, mood alterations, and bone loss. Rarely aseptic necrosis of
bone may occur
B. Related to immunosuppressive drug therapy: increased risk of infection, hepatotoxicity, cytopenias, and
increased risk of cancers. Risks are dependent on drug selected and dose
A. Systemic associations: Dependent upon the type of cancer associated with the retinopathy
B. Ocular associations: loss of visual acuity and visual field related to the retinal degeneration, secondary
optic atrophy/pallor
A. Referral to primary care doctor for malignancy work up if not already diagnosed with a malignancy
B. Refer to services for visually impaired as needed
2. Chowers I, Zamir E, et al. Retinitis pigmentosa associated with Fuchs' heterochromic uveitis. Arch
Ophthalmol 2000;118(6):800-2.
3. Grover S, Apushkin MA, Fishman GA. Topical dorzolamide for the treatment of cystoid macular edema in
patients with retinitis pigmentosa. Am J Ophthalmol 2006;141:850-858.
4. Berson EL, Rosner B, Sandberg MA, et al. A randomized trial of supplemental vitamin A and vitamin E
supplementation for retinitis pigmentosa. Arch Ophthalmol 1993;111:761-772.
5. In: Ryan SJ. Retina. Complicated retinitis pigmentosa. Chapter 17, p.432.
7. Zimmerman LE. Ocular lesions of juvenile xanthogranuloma. Nevoxanthoedothelioma. Am J Ophthalmol

1965;60:1011-35.
8. Zamir E, Wang RC, et al. Juvenile xanthogranuloma masquerading as pediatric chronic uveitis: a
clinicopathologic study. Surv Ophthalmol 2001;46:164-71.
9. Parmley VC, George DP, et al. Juvenile xanthogranuloma of the iris in an adult. Arch Ophthalmol
1998;116:377-9.
10. DeBarge LR, Chan CC, et al. Chorioretinal, iris, and ciliary body infiltration by juvenile xanthogranuloma
masquerading as uveitis. Surv Ophthalmol 1994;39:65-71.
11. Chan JW. Paraneoplastic retinopathies and optic neuropathies. Surv Ophthalmol. 2003;48(1):12-38.
Uveitis 188 © AAO 2017-2019

12. Ohnishi Y, Ohara S, Sakamoto T, Kohno T, Nakao F. Cancer-associated retinopathy with retinal phlebitis. Br
J Ophthalmol. 1993;77(12):795.
13. Goetgebuer G, Kestelyn-Stevens AM, De Laey JJ, et al. Cancer-associated retinopathy (CAR) with
negative-type ERG: a case report. Doc Ophthalmol. 2008;116(1):49-55.
14. Audo I, Robson AG, Holder GE, et al. The negative ERG: clinical phenotypes and disease mechanisms of
inner retinal dysfunction. Surv Ophthalmol. 2008;53(1):16-40.
15. Huynh N, Shildkrot Y, Lobo AM, Sobrin L. Intravitreal triamcinolone for cancer-associated retinopathy
refractory to systemic therapy. J Ophthalmic Inflamm Infect. 2012 Mar 14. [Epub ahead of print]
16. Shildkrot Y, Sobrin L, and Gragoudas E. Cancer-Associated Retinopathy: Update on Pathogenesis and
Therapy. Seminars in Ophthalmology, 26(4-5), 321-328, 2011.
17. Mahdi N, Faia LJ, Goodwin J, Nussenblatt RB, Sen HN. A case of autoimmuneretinopathy associated with
thyroid carcinoma. Ocul Immunol Inflamm. 2010Aug;18(4):322-3. PubMed PMID: 20662664.
Uveitis 189 © AAO 2017-2019

Immune recovery uveitis
1. Presumed immunologic activity against CMV antigen
1. HIV infected patients on HAART
a. Definition of HAART
i. Multidrug therapy directed against HIV
ii. Three or more anti-retroviral agents from 2 or more of the known classes used
simultaneously
iii. All initiated simultaneously to prevent early drug resistance
b. Treatment effects and treatment goals of HAART
i. Dramatic reduction in viral load
ii. Increase in CD4+ T-lymphocyte counts
iii. Delay in disease progression
iv. Reduction in opportunistic infections- by up to 82%
v. Fewer hospitalizations
vi. Improved survival
c. List the indications/contraindications for use of HAART
i. Indications
i) HIV+
ii) CD4 <350 cells/mm3 - treat
iii) HIV-1 RNA > 30,000 copies/ml - treat
iv) Symptomatic - AIDS - treat
ii. Contraindications
i) Asymptomatic patients with CD4>500 cells/mm3 and HIV -1 RNA <5000 copies /ml-
defer treatment
d. List the complications of HAART, their prevention and management
i. Emergence of drug resistant HIV strains
i) Alternative aggressive salvage therapy - 5 agents
ii) HIV drug sensitivity testing for most anti-retroviral agents available
ii. Drug toxicity
i) Can cause interruption in HAART therapy
ii) Close follow-up and periodic laboratory investigations looking for drug-specific
complications
iii) Switching to other agents in the three antiretroviral drug groups may result in
Uveitis 190 © AAO 2017-2019

reduction of side effects
2. CD4+ T-lymphocyte counts (increase by at least 50 cells/mm3 after HAART) >100 cells/mm3, usually >250
cells/mm3
3. Pre-existing intraocular opportunistic infection (especially CMV retinitis)
1. Slow decline in vision with increasing CD4 counts
2. Blurred vision
3. Metamorphopsia
4. CMV retinitis (active or inactive)
1. Cornea - dendritic keratic precipitates
2. Anterior chamber with variable cells and flare - can be severe
3. Iris
a. Rarely iris bombe and angle closure can occur
4. Lens
a. Intraocular lens may have cellular deposits
b. Posterior subcapsular (PSC) cataract
5. Vitreous
a. Trace cells to 2+ cells - vitreous haze
6. Macula
a. CME
b. Epiretinal membrane
c. Inactive CMV retinitis with retinal scarring and sclerotic vessels
7. Optic disc edema
1. HIV serology- assumed to be positive
2. CD4+ lymphocyte count
3. Viral load - usually undetectable-probably not predictive of uveitis
A. Rising CD4+ T-lymphocyte count with HAART
B. CMV retinitis (risk proportional to surface area of retina involved)
C. HAART therapy
D. History of Cidofovir therapy
A. Active CMV retinitis
B. Toxoplasmosis
C. Drug-induced uveitis
1. Rifabutin
2. Cidofovir
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D. Disseminated mycobacterial infections - worsened immune response after HAART
E. Other causes of iridocyclitis
1. Human leukocyte antigen (HLA) - B27 + (both HLA-B27 anterior uveitis and rifabutin-associated uveitis can
present with a hypopyon, creating potential confusion in etiology)
2. Idiopathic
A. Topical corticosteroids
1. Can control anterior chamber cells
2. May help CME especially in pseudophakic eyes
B. Regional corticosteroids
V. List the complications of treatment, their prevention and management (See Corticosteroids)
A. CME
1. Can be refractory to treatment
2. Occasionally visual loss can be profound
B. Epiretinal membrane
1. Can be removed surgically
2. Vision may still be limited by underlying CME
C. Posterior subcapsular cataract
D. Iris - posterior synechiae and iris bombe leading to angle closure - rare
A. Decreasing vision and metamorphopsia should be reported
B. Continued follow-up necessary even if CD4 counts are >300 and even if CMV retinitis is inactive off all
anti-CMV medications
Human immunodeficiency virus (HIV) retinopathy
A. Describe the etiology of this disease- controversial
1. HIV retinal vascular endothelial infection
2. Hematologic abnormalities
a. Increased leukocyte activation
b. Increased leukocyte rigidity
c. Increased red cell aggregation
3. Immune complex deposition in retinal capillaries
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1. Occurs at CD4+ counts < 50 cells/μl (50-70% of patients at this level of immune suppression will develop
HIV retinopathy)
1. Usually no symptoms
2. Rarely painless visual loss of sudden onset (3%)
a. Scotoma or blurred vision
b. Visual field defect in cases of vascular occlusion
1. Cotton wool spots
2. Retinal hemorrhages
3. Microaneurysms
E. Describe pertinent pathologic features
1. May resemble diabetic retinopathy and early CMV retinitis
2. Pericyte necrosis
3. Endothelial cell swelling
4. Thickened basement membranes
F. Describe appropriate testing and evaluation for establishing the diagnosis
1. HIV status - positive
2. CD4+ counts - often less than 50 cell/ μl
3. Rule out other common causes of retinal microvasculopathy
a. Check blood pressure
b. Fasting blood sugar
A. HIV positive
B. CD4+ counts <50 cells/μl
A. Diabetic retinopathy
B. Radiation retinopathy
C. Hypertensive retinopathy
D. Cytomegalovirus (CMV) retinitis
1. Large cotton wool spots in HIV retinopathy may be confused for CMV retinitis
2. In HIV retinopathy
a. Cotton wool spots
i. Do not enlarge and usually resolve in 4-6 weeks
ii. Are smaller than 750 microns
iii. Are not associated with contiguous areas of hemorrhage and intralesional hemorrhage
iv. No iridocyclitis or vitritis (which, though mild, often occurs in CMV retinitis)
E. Varicella zoster virus (VZV) retinitis
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A. None specific, focus on restoration of immune function with HAART therapy
A. Have dilated examinations every 3 months performed if CD4+<50 cells/μl
B. Should not typically have visual loss from these changes
HIV-related neuroretinal disorder (NRD)
A. Define the relevant aspects of epidemiology of this disease
1. Occurs in patients with AIDS with a history of low CD4+ count
1. Usually no symptoms
2. Rarely painless, insidious blurring of vision
1. Decreased contrast sensitivity, visual field and color vision
2. Often visual acuity is normal or near normal
3. Retinal vessels may be narrowed
4. Thinning of retinal nerve fiber layer on OCT testing.
1. HIV status - positive
2. CD4+ count and viral load
A. HIV positive
B. CD4+ counts <50 cells/μl
C. Unclear if this is a result of neuroretinal damage secondary to HIV retinopathy
Cytomegalovirus (CMV) retinitis (See Cytomegalovirus retinitis)
A. Describe the relevant aspects of epidemiology of this disease
1. Incidence of new CMV has fallen 60-80% since introduction of highly active anti-retroviral therapy (HAART)
2. It is still the most common opportunistic ocular infection in AIDS
3. Can resolve on HAART alone, provided patient responds to HAART
4. Has become self-limited disease that does not require lifetime maintenance therapy after immune
reconstitution with HAART
5. CMV retinitis is still associated with a substantial risk of vision loss despite HAART
a. Those receiving HAART have reduced risk of vision loss
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i. Some of that reduction of risk is lost if immune recovery uveitis is present
b. Causes of visual loss in the HAART era
i. Zone 1 involvement and retinal detachment - most common - overall
ii. Cataract, cystoid macular edema (CME), and epiretinal membrane in patients with HAART-
induced immune recovery
Herpes zoster ophthalmicus (HZO) in patients with human immunodeficiency virus (HIV) infection
1. Varicella zoster (VZV) virus
1. HIV+ individuals are six times more likely to develop HZO
2. Not AIDS defining illness but suggests immune compromise
3. Greater rates of recurrence than in non-AIDS patients
4. Can occur at any CD4 count level
5. Can be initial manifestation of AIDS
1. Painful rash with paresthesias on face
2. Dermatomal pain without antecedent rash (zoster sine herpete)
3. Foreign body sensation
4. Redness
5. Decreased vision
1. Cutaneous vesicular eruption along cranial nerve V1 (ophthalmic division)
a. Can be bilateral (multidermatomal) in HIV
2. Cornea-epithelial changes seen best with rose bengal
a. Small micro dendrites-multiple
b. Peripheral lesions
c. Geographic epithelial defect
3. Anterior chamber
a. Variable cells and flare
4. Iris
a. Chronic cases may show sectoral or diffuse stromal atrophy and transillumination defects
5. Vitreous
a. Presence of variable cells
6. Retinitis, progressive outer retinal necrosis (PORN)
7. Optic neuritis
1. Clinical diagnosis- rarely are labs needed - mainly to look for VZV (if obtained, negative results are helpful to
rule out prior exposure while positive results only indicate prior exposure but are not proof that the current
disease is secondary to the virus)
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a. Cutaneous vesicles, cornea epithelial scraping and culture in Hank's medium
b. Aqueous paracentesis with polymerase chain reaction (PCR)
A. Exposure to another patient with active zoster infection
B. Prior varicella infection (most common)
C. CD4 counts <100 may be associated with more severe disease in HIV infected individual
A. Herpes simplex virus keratitis/keratouveitis
B. Immune recovery uveitis
A. Depends on location of involvement
1. If retinitis is present, then high levels of intravitreal antivirals are needed
a. IV acyclovir 10-14 days
i. Alternative: Foscarnet
b. Intravitreal foscarnet or ganciclovir
2. If anterior uveitis
a. Oral acyclovir 800mg 5 times daily for 14 days
b. Maintenance therapy with oral acyclovir may be needed if frequent recurrences of keratitis or
iridocyclitis
c. Alternatives
i. Famciclovir 500 mg TID
ii. Valacyclovir 1-2 grams TID
d. Complications of treatment listed below
B. Varicella vaccine - live attenuated viral vaccine
1. Should not be given in cases of AIDS
2. Consider in asymptomatic children with early HIV infection with near normal CD4 counts
C. Varicella zoster virus immunoglobulin
1. Consider for postexposure prophylaxis in immunocompromised patients within 72 hours
2. May modify disease course for the exposed patient
A. Granulocytopenia - acyclovir, famciclovir, valacyclovir
B. Nephrotoxicity from foscarnet
A. Post-herpetic neuralgia
B. Keratitis
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1. Disciform keratitis
2. Chronic epithelial keratitis
C. Chronic iridocyclitis
1. Glaucoma
2. Cataract
D. Optic atrophy (in cases of optic neuritis)
E. Ipsilateral necrotizing scleritis
F. Dilated pupil
G. Increased risk of development of necrotizing herpetic retinitis (See Necrotizing herpetic retinitis: acute
retinal necrosis and progressive outer retinal necrosis)
A. Report pain, redness, vision loss
B. Recurrences are more common in HIV infection
C. Importance of medication compliance
Rapidly progressive necrotizing herpetic retinitis in immunocompromised patients (See Necrotizing herpetic retinitis: acute retinal
necrosis and progressive outer retinal necrosis)
I. Describe patient management in terms of treatment and follow-up
A. Often requires more than one antiviral agent given via multiple routes (IV and intravitreal injections)
II. Describe disease related complications
A. High rate of retinal detachment (>70%)
Toxoplasma retinochoroiditis in acquired immune deficiency syndrome (AIDS)
1. Toxoplasma gondii - obligate intracellular protozoan acquired infections or from pre-existing retinal focus
1. Human immunodeficiency virus (HIV)+ with or without previous toxoplasma scars
2. Patients with extraocular toxoplasma infections
3. Some population groups have higher prevalence - e.g. Brazilians, Central Americans
1. Floaters
2. Painless vision loss
3. Rarely - severe pain with extrascleral/orbital involvement
1. Full thickness retinal necrosis with overlying vitreous inflammation, with or without adjacent chorioretinal
scar (usually not seen)
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2. Larger lesions (areas of retinitis) and multiple lesions more prevalent in AIDS than immunocompetent
patients
3. Bilateral disease more likely, present in 1/3 of patients with ocular toxoplasmosis in AIDS patients
4. Inflammation less and variable in HIV+ patients (based on CD4 +lymphocyte count) compared to
immunocompetent patients
5. Invariably progressive without treatment in HIV/AIDS
6. 25%-50% of HIV+/AIDS patients will have central nervous system toxoplasmosis
1. In cases of diagnostic difficulty - consider aqueous paracentesis, vitreous tap, or pars plana vitrectomy to
obtain fluid for PCR (yield depends on lesion size and aqueous has less yield than vitreous)
2. Toxoplasma serology (anti-toxoplasma immunoglobulin G and immunoglobulin M) may not be reliable but
should be obtained
3. Computed tomography or magnetic resonance imaging with contrast to rule out co-existing central nervous
system (CNS) disease
A. HIV +
B. Pre-existing toxoplasma retinochoroiditis scar
C. Concomitant extraocular (especially CNS) toxoplasmosis
A. Acute retinal necrosis (more intraocular inflammation, early retinal vascular involvement)
B. Cytomegalovirus retinitis (slower rate of progression, early retinal vascular involvement)
C. Progressive outer retinal necrosis (PORN)
D. Syphilitic chorioretinitis
A. Combination therapy with all 3 agents - is effective in >75% of cases
1. Pyrimethamine
2. Sulfadiazine
3. Clindamycin
B. Alternative treatments
1. Atovaquone + clarithromycin
2. Trimethoprim-sulfamethoxazole double strength (160mg/800mg) plus clindamycin
3. Intravitreal clindamycin (1mg) plus intravitreal dexamethasone (400 micrograms)
C. Avoid systemic and periocular corticosteroids in the immunocompromised patient
D. Lifetime maintenance therapy is usually required even after the retinitis has become inactive
1. Trimethoprim-sulfamethoxazole double strength (160mg/800mg) - 1 tablet daily or three times per week can
aid in prophylaxis against toxoplasmosis
E. If immune recovery occurs and CD4 increases to >500 cells/mm3, can consider stopping maintenance
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A. Pyrimethamine and sulfadiazine
1. Sulfa drug allergies - Stevens-Johnson syndrome
2. Bone marrow suppression (add folinic acid to offset)
3. Zidovudine antagonizes anti-toxoplasma effects of pyrimethamine in vitro and in vivo
A. Macular and retinal scarring
B. Optic atrophy especially if optic nerve or peripapillary involvement
C. Retinal arteriolar or venular occlusions
D. Tractional and rhegmatogenous retinal detachments
E. Progressive extrascleral and orbital involvement
A. Watch for severe loss of vision
B. Watch for focal neurologic symptoms which suggest concomitant CNS disease
C. Continue maintenance medication even if vision is stable
Syphilitic chorioretinitis in acquired immune deficiency syndrome (AIDS) (See Syphilitic panuveitis)
Infectious multifocal choroiditis in acquired immune deficiency syndrome (AIDS)
1. Pneumocystis carinii
2. Cryptococcus neoformans
3. Atypical mycobacteria (mycobacterium avium-intracellulare (MAI), others)
4. Histoplasma capsulatum
5. Candida albicans
6. Aspergillus fumigatus
7. Mycobacterium tuberculosis
8. Multiple organisms may be involved
1. Less than 5% of patients with AIDS
1. Often systemically very ill with sepsis and disseminated infection from one or more causative organisms
2. Usually no visual symptoms
3. Rarely visual loss may occur if lesions involve the macula and posterior pole
1. Variable sized multifocal choroidal lesions
2. Slightly elevated, plaque-like, yellow-white lesions in choroid
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a. ¼ to 2-disc diameter sized lesions
b. Scattered throughout choroid
c. Minimal but variable vitritis
3. Cryptococcal meningitis can result in obstructive hydrocephalus and severe papilledema and subsequent
optic atrophy
a. Choroidal lesions are hypofluorescent early and hyperfluorescent in late phases of angiogram
1. Necessary if disseminated infection is suspected
a. Chest radiography
b. Arterial blood gas
c. Liver function tests
d. Abdominal computed tomography
e. Blood cultures
A. Human immunodeficiency virus (HIV) +
B. CD4+ <50 cells/μl
C. Patients with disseminated infections or sepsis
1. Disseminated extrapulmonary Mycobacterium tuberculosis
2. Cryptococcal meningitis
3. Pneumocystis sepsis or pneumonitis
4. Disseminated MAI infection
A. Toxoplasma retinochoroiditis
B. Primary central nervous system lymphoma with intraocular involvement
C. Presumed ocular histoplasmosis syndrome (POHS) - healed cases of multifocal choroiditis in AIDS may
resemble POHS
D. Idiopathic multifocal choroiditis
A. Organism dependent
B. Pneumocystis choroiditis
1. 3 weeks IV trimethoprim and sulfamethoxazole or
2. 3 weeks IV pentamidine (4mg/kg/day)
3. Maintenance with systemic pentamidine, trimethoprim/sulfamethoxazole, or dapsone
C. Cryptococcus choroiditis
1. IV amphotericin B plus flucytosine for 2 weeks
2. Followed by oral fluconazole for 10 weeks and maintenance oral fluconazole
3. Maintenance probably indicated even with successful immune reconstitution with highly active anti-retroviral
Uveitis 200 © AAO 2017-2019

therapy
D. Atypical mycobacterial choroiditis may be more stubborn and take longer to respond
1. Clarithromycin+ Rifabutin+ Ethambutol induction and maintenance appears the most effective in the
treatment of MAI and disseminated atypical mycobacterial infections in AIDS
a. Rifabutin induced uveitis can occur as a complication, especially when rifabutin given concurrently
with macrolide antibiotic
i. Classically unilateral hypopyon iridocyclitis
i) Acute onset with redness, pain, photophobia, and decreased vision
ii) Work-up is usually negative - human leukocyte antigen B27 is not present
ii. Treated with topical corticosteroids and cycloplegics
iii. Drug dosage may be reduced but rifabutin does not need to be discontinued unless iritis
recurs or does not respond completely
E. With treatment, lesions disappear in 3-12 weeks and leave behind retinal pigment epithelium mottling
A. If CD4+<100 cells/μl, importance of routine every 6-month follow-up even if no visual symptoms
B. Sepsis or systemic dissemination of pneumocystis, cryptococcus, and MAI requires more frequent and
detailed ophthalmologic evaluation
2. AAO, HIV/AIDS and the Eye: A Global Perspective, 2002.
3. Thorne JE, Jabs DA, Kempen JH, et al. Causes of visual acuity loss among patients with AIDS and
cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Ophthalmology 2006;113:1441-5.
4. Thorne JE, Jabs DA, Kempen JH, et al. Incidence of and risk factors for visual acuity loss among patients
with AIDS and cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Ophthalmology
2006;113:1432-1440.
5. Goldberg DE, Smithen LM, Angelilli A, Freeman WR. HIV-associated retinopathy in the HAART era. Retina
2005;25:633-49.
7. Jabs DA, Ahuja A, van Natta M, Lyon A, Srivastava S, Gangaputra S, for the SOCA Research Group.
Course of cytomegalovirus retinitis in the era of highly active antiretroviral therapy: Five-year Outcomes.
Ophthalmology 2010 Nov;117(11):2152-61.
8. Sugar EA, Jabs DA, Ahuja A, Thorne JE, Danis RP, Meinert CL for the Studies of the Ocular Complications
of AIDS (SOCA) Research Group. Incidence of cytomegalovirus retinitis in the era of highly active
antiretroviral therapy. Am J Ophthalmol 2012 Epub ahead of press.
9. Shah KH, Holland GN, Yu F, et al; Studies of Ocular Complications of AIDS (SOCA) Research Group.
Contrast sensitivity and color vision in HIV-infected individuals without infectious retinopathy. Am J
Ophthalmol. 2006 Aug;142(2):284-92.
10. Freeman WR, Van Natta ML, Jabs D, et al; SOCA Research Group. Vision function in HIV-infected
individuals without retinitis: report of the Studies of Ocular Complications of AIDS Research Group. Am J
Ophthalmol. 2008 Mar;145(3):453-462.
11. Soheilian M, Ramezani A, Azimzadeh A, Sadoughi MM, Dehghan MH, Shahghadami R, Yaseri M, Peyman
GA. Randomized trial of intravitreal clindamycin and dexamethasone versus pyrimethamine, sulfadiazine,
and prednisolone in treatment of ocular toxoplasmosis. Ophthalmology. 2011 Jan;118(1):134-41.
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A. Indications
1. Noninfectious ocular inflammatory disease
2. Other diseases in which an inflammatory component exists, if therapy is directed against the primary
etiology concurrently used (e.g., infectious disease)
II. Paradigm
A. Goal of therapy
1. Control of the inflammation so as to eliminate (or reduce as much as possible if other considerations limit
therapeutic options) the risk to vision that may occur from the structural and functional complications
resulting from unchecked inflammation
B. Choice of agent
1. The agent(s) and route(s) of administration chosen should be based on a careful consideration of all factors
of pertinence, including the specific diagnosis; concurrent ocular or systemic disease (both those related to
the ocular inflammatory disease and those that affect the choice of therapeutic agent); existing level of
ocular function compromise already present, monocular vs binocular disease and patient desires
C. Initial therapy
1. The initial goal of therapy should be to achieve control of inflammation as rapidly as possible
2. Corticosteroids are generally the most effective agent at achieving this goal and may be administered
topically, regionally, and systemically (See Corticosteroids)
a. The Multicenter Uveitis Steroid Treatment Trial (MUST), a randomized, controlled, superiority trial,
comparing systemic anti-inflammatory therapy, versus fluocinolone acetonide implant for
intermediate, posterior and panuveitis was conducted and published (2011) the following results:
i. In each treatment group, mean visual acuity improved over 24 months, with neither
approach superior, to a degree detectable with the study's power
ii. The specific advantages and disadvantages identified based on individual patients'
particular circumstances, should dictate selection between these two alternatives.
iii. Systemic therapy with aggressive use of corticosteroid-sparing immunosuppression, was

well tolerated
b. For certain conditions such as mild scleritis, non-steroidal anti-inflammatory agents may be used
instead of corticosteroids (See Nonsteroidal anti-inflammatory drugs)
3. The indications for the addition of immunomodulatory, IMT (immunosuppressive) therapy may include the
following settings:
a. Sight-threatening uveitis
b. Patients who are intolerant or resistant to corticosteroids
c. Patients who require long-term corticosteroid therapy (longer than 3 months) at doses greater than
5-10 mg/day
d. It should be noted that currently, the use of IMT for treating uveitis in the United States, is
considered off-label
4. Specific diseases entities that may warrant early use of IMT
a. Behçet with posterior segment, vision threatening involvement (See Behçet disease)
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b. Sympathetic ophthalmia (See Sympathetic ophthalmia)
c. Necrotizing scleritis with systemic association (See Scleritis)
d. Serpiginous choroidopathy with vision threatening involvement (See Serpiginous choroidopathy)
e. Vogt-Koyanagi-Harada Syndrome
f. Mucous membranous pemphigoid with ocular involvement
g. Birdshot uveitis (See Birdshot uveitis)
5. Tapering of initial therapy
a. If control of inflammation is achieved with initial therapy and disease is considered to be of acute or
limited duration, then an appropriate taper of the initial agent(s) is warranted
b. If disease activity recurs with taper, then the dose of corticosteroid at which the flare occurred
determines whether long-term corticosteroid therapy (baseline DEXA scan and bone preservation
measures implemented) or second line therapy is used (See Corticosteroids).
6. If control is not achieved with initial therapy, then transition to second line therapy
D. Second line therapy
1. In chronic disease not controlled at 5-10 mg/day of corticosteroid (There are FDA approved drugs for
prevention and treatment of corticosteroid-induced osteoporosis in patients. These medications are
indicated for at-risk patients receiving the equivalent of 7.5 mg or more of daily prednisone); acute or limited
duration disease in which initial corticosteroid therapy failed to achieve control; or in individuals unable to
tolerate doses of initial therapy needed to achieve control, transition to second line therapy
2. Multiple drug classes and agents within each drug class are available. Quality data from randomized
controlled trials of specific agents in specific ocular inflammatory diseases is generally lacking to guide the
choice of agent; the published results of the Systemic Immunosuppressive Therapy for Eye Diseases
Cohort (SITE) Study, with a secondary outcome measure delineating the beneficial effects of IMT, is an
added resource for ophthalmologists (see individual agents for specific references):
a. Selection of agent is thus based on a consideration of an individual patient's comorbidities
3. Drug Classes (as new agents are continually being developed and released, this list may be incomplete)
a. Antimetabolites
i. Methotrexate (See Methotrexate)
ii. Azathioprine (See Azathioprine)
iii. Mycophenolate mofetil or mycophenolic acid (See Mycophenolate)
b. Inhibitors of T-Cell signaling
i. Cyclosporine (See Cyclosporine)
ii. Tacrolimus
iii. Sirolimus
c. Alkylating agents (See Alkylating agents: Cyclophosphamide and chlorambucil)
i. Cyclophosphamide
ii. Chlorambucil
d. Biological response modifiers (See Biologic response modifiers)
E. Beyond second line therapy
1. If use of initial and second line therapy are ineffective in controlling inflammation, the literature becomes
very sparse regarding efficacy data on combinations or newer agents. Considerations of the individual
needs for each patient should guide choices
2. Options may include
a. Medical
i. Combination IMT - multiple drugs from more than one class of drugs
b. Surgical therapy in specific uveitic entities (i.e. therapeutic PPV in pars planitis) (See Intermediate
uveitis, including pars planitis)
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III. Special considerations
A. Pregnancy testing: As part of the systemic work-up, prior to initiating systemic immunosuppressive
therapy, a pregnancy test should be done
B. Vaccine recommendations
1. Patients receiving anti-TNF therapy should not have live vaccines, including, but not limited to varicella
zoster, oral polio, or rabies vaccination, and the influenza vaccine made with a live virus
2. Kempen, JH et al: Randomized Comparison of Systemic Anti-inflammatory Therapy Versus Fluocinolone

Acetonide Implant for Intermediate, Posterior, and Panuveitis Steroid Treatment Trial. Ophthalmology 2011;
118:1916-1926.
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A. Indications
1. Anterior chamber involvement in uveitis
a. To prevent formation of new posterior synechiae with either continual or intermittent dilation
b. To decrease photophobia and pain due to ciliary and sphincter muscle spasm
c. To break recently formed posterior synechiae
1. Allergy or sensitivity to agent or to others in its class
II. Describe the pre-procedure/therapy evaluation
A. Comprehensive eye examination
B. Question for history of allergy or adverse reaction
C. Check angle depth because of possibility of inducing narrow-angle glaucoma
III. List the alternatives to this procedure/therapy
A. To not use the therapy (mainly in cases of allergy or exceptionally mild anterior segment inflammation)
IV. Describe the dosage (agents listed in decreasing order of duration of effect)
A. The dosages are adjusted according to desired duration
1. Atropine 1% one to 4 times daily. The higher dose should be used with caution in young children
2. Scopolamine 0.25% one to four times daily
3. Homatropine 2% or 5% one to four times daily
4. Cyclopentolate 1% one to four times daily
5. Tropicamide 0.5% to 1% for prophylactic nightly dilation when the other agents produce prolonged daytime
dilation
B. Alpha-adrenergic agents provide greater dilation but are not ordinarily used
C. Most effective use to prevent new synechiae requires monitoring of pupil size and shape by the patient.
V. List the complications of the procedure/therapy, their prevention and management
A. Psychosis, acute psychotic reaction
1. Limit dosage to no more than recommended frequency
2. Most case reports in pediatric age group, but has been reported with adults
3. Treat with supportive care
B. Tachycardia
C. Fever
D. Urinary retention
Uveitis 205 © AAO 2017-2019

E. Cycloplegia/blurred vision
1. Can be minimized by use of a short acting cycloplegic with bedtime regimen (not indicated if patient is at
highest risk for synechiae)
2. Temporary use of reading eyeglasses (or temporary use of stronger reading eyeglasses)
F. Posterior synechiae formation in the dilated position can be minimized by prescribing strong cycloplegics
only with adequate anti-inflammatory treatment
A. Routine monitoring of the extent of posterior synechiae and anterior inflammation
B. Drawings or photos of pupil shape helpful
A. Inform the physician of any new symptoms while on the medication
B. Use only as prescribed, not more frequently
C. Explain to patient rationale for use, including need to keep pupil moving to prevent synechiae
D. Recommend protection from bright light
E. Counsel use of reading eyeglasses for near work (with bilateral use)
F. Patient should be instructed to wash hands after use, to prevent inadvertent application in the contralateral
eye (with monocular use)
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I. Pharmacology
A. Mechanism of action
1. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX), the enzyme which converts
arachidonic acid to prostaglandin derivatives which mediate inflammation
2. There are two isoforms of cyclooxygenase, COX-1 and COX-2, both of which may be inhibited or selectively
targeted (COX-2) by NSAIDs
a. COX-1 is responsible for maintenance of normal renal function, gastric mucosal integrity, and
hemostasis. This isoform is constitutively expressed, and appears to be critical for housekeeping
actions in the GI mucosa
b. COX-2 appears to be expressed in most tissues in response to growth factors and cytokines, under
pathological conditions such as inflammation. Specific inhibitors should therefore have less risk of
adverse events such as gastric ulceration and renal toxicity
c. However, all NSAIDS are now known to be associated with an increased risk of cardiovascular
adverse events related to selective effects on the clotting system
i. Therefore, use of these agents for ophthalmic indications should be carefully considered in
the context of a patient‘s comorbidities
A. Indications
1. Noninfectious ocular inflammatory disease, especially scleritis/episcleritis
a. Topical NSAIDs may be of benefit in episcleritis only
2. Maybe useful as a steroid -sparing adjunct during tapering of topical corticosteroids in selected cases of
JIA/JRA and HLA-B27-associated iridocyclitis
3. Cystoid macular edema (CME)
a. Topical NSAIDs
4. Analgesia
1. Renal insufficiency or other kidney disease
2. Allergy or sensitivity to agent or others in its class
3. Peptic ulcer disease
4. Bleeding diathesis
5. Use of COX- inhibitors with an established history or risk factors for cardiovascular or thrombotic disease
III. Describe the pre-procedure/therapy evaluation
A. Renal function panel
B. Complete blood count
C. Blood pressure
D. Liver enzymes
IV. List the alternative to this procedure/therapy
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A. For anti-inflammatory effect
1. Corticosteroids
2. Other immunosuppressive agents
B. For analgesic effect
1. Opioid analgesics
2. Acetaminophen
V. Describe the routes of administration
A. Oral
B. Topical
VI. Agents available for use in USA
A. Oral
1. Non-selective COX inhibitors
a. Fenamate derivatives: Meclofenamate (Meclomen®), mefenamic acid (Ponstel®)
b. Indoleacetic acid derivative: Indomethacin (Indocin®)
c. Naphthylalkanone derivative: Nabumetone(Relafen®)
d. Oxicam derivative: Meloxicam (Mobic®), piroxicam (Feldene®), tenoxicam (Tilcotil®)
e. Phenylacetic acid derivative: Diclofenac (Voltaren®, Cataflam®)
f. Propionic acid derivatives: Fenoprofen (Nalfon®), flurbiprofen (Ocufen®), ibuprofen, ketoprofen,

naproxen (Aleve®, Naprosyn®, Anaprox®), oxaprozin (Daypro®), tiaprofenic acid
g. Pyranoindoleacetic acid: Etodolac (Lodine®)
h. Pyrazole derivative: Phenylbutazone (Butazolidine®)
i. Pyrroleacetic acid derivatives: Sulindac, (Clinoril®) tolmetin (Tolectin®)
j. Salicylic acid derivative: Diflunisal (Dolobid®)
2. COX-2 selective inhibitors
a. Celecoxib (Celebrex®)
B. Topical (topical NSAIDs are of no value in uveitis or scleritis, but may be useful in episcleritis and CME)
1. Ketorolac tromethamine (Acular®; Acuvail))
2. Diclofenac sodium (Voltaren®)
3. Flurbiprofen sodium (Ocufen®)
4. Nepafenac (Nevanac®, Levro®)
5. Bromfenac (Xibrom®; Prolensa, Bromday))
VII. List the complications of the procedure/therapy, their prevention and management
A. Oral
1. Renal insufficiency
a. Management: dosage reduction or discontinuation
2. Gastritis/peptic ulcer
a. Management: concurrent H2 blocker or proton pump inhibitor or misoprostol use
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3. Nausea
a. Management: take with food
4. Decreased clotting ability (for non-specific COX inhibitors)
5. Abnormal liver enzymes
B. Topical
1. Corneal epithelial breakdown, thinning, erosion, ulceration, perforation
a. Do not exceed recommended frequency of use
2. Ocular wound healing delay
3. Ocular bleeding
4. Conjunctival hyperemia
VIII. Describe the follow-up care
A. Routine monitoring or blood work, response to therapy
1. Hematocrit, creatinine, liver enzymes: periodic testing is recommended, based on the patient's clinical
profile
IX. Describe appropriate patient instructions
A. Inform the physician of any new symptoms while on the medication
1. Bleeding
2. Increased bruising
3. Changes in stool
4. Changes in urination
B. Take with food
C. Do not use aspirin containing products or potentially nephrotoxic medications (Cyclosporine) concurrently
D. Concomitant use of systemic corticosteroids and NSAIDs significantly increases risk of peptic ulceration
2. AAO, Focal Points: Scleritis and Episcleritis: Diagnosis and Management, Module 4, 2009.
3. Conaghan PG. A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology,
comparative efficacy, and toxicity. Rheumatol Int. 2012 June; 32(6): 1491-1502.
4. Lindstrom R. The pharmacologic and pathophysiologic rationale for using NSAIDs in ocular inflammatory
disease and ocular surgery. Int Ophthalmol Clin 2006; 46:7-11.
5. Hemady RK, Chan AS, Nguyen AT. Immunosuppressive agents and nonsteroidal anti-inflammatory drugs
for ocular immune and inflammatory disorders. Ophthalmol Clin North Am 2005; 18:511-28.
6. Warren KA, Fox JE. Topical nepafenac as an alternative treatment for cystoid macular edema in steroid
responsive patients. Retina 2008; 28:1427-34.
7. Imrie FR, Dick AD. Nonsteroidal drugs for the treatment of noninfectious posterior and intermediate uveitis.
Curr Opin Ophthalmol 2007; 18:212-9.
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A. Indications
2. Acute endophthalmitis (as an adjunctive therapy)
3. Acute retinal necrosis (as an adjunctive therapy)
4. Other diseases in which an inflammatory component exists, if therapy directed against the primary etiology
is also used (e.g., infectious disease)
1. Infectious etiology, unless covered by appropriate antibiotics
2. Poorly controlled or difficult to control diabetes
3. Peptic ulcer or erosive gastritis
4. Concomitant oral NSAIDS
C. Relative Contraindications
1. A history of corticosteroid-induced intraocular pressure (IOP) elevation
2. An immunocompromised state
3. An existing psychiatric disorder
II. List the alternatives to this procedure/therapy for systemic use
A. The initial goal of therapy should be to achieve control of inflammation as rapidly as possible.
Corticosteroids are generally the most effective agent at achieving this goal and may be administered
topically, regionally, or systemically. (See Treatment guidelines utilizing systemic therapy for non-infectious
ocular inflammatory disease)
III. Describe the instrumentation and technique
A. Describe the routes of administration
1. Local
a. Topical
b. Regional
2. Systemic
a. Oral
b. Intravenous
B. Agents commonly used in the United States
1. Topical
a. Difluprednate 0.05%
b. Prednisolone acetate 1%, 1/8%
c. Loteprednol etabonate 0.5% (suspension, gel and ointment)
d. Prednisolone sodium phosphate 1%
e. Dexamethasone sodium phosphate 0.1%
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f. Rimexolone 1%
2. Regional
a. Triamcinolone acetonide (Triesence) 1-4mg (25-100µl of 40mg/ml)
b. Fluocinolone acetonide 0.59 mg (Retisert) intravitreal implant (elutes corticosteroid medication into
the eye for up to 3 years). It requires a surgery for implantation, and is secured with partial
thickness scleral sutures
c. Dexamethasone 0.7 mg(Ozurdex) injectable corticosteroid implant with extended drug release, it is
a continuous release for 35 days, then it biodegrades
d. Fluocinolone acetonide 0.19 mg(Iluvien) an injectable corticosteroid implant
3. Oral
a. Prednisone 1 mg/kg
b. Prednisolone 1 mg/k/g
c. Dexamethasone 0.2 mg/kg
4. Intravenous
a. Methylprednisolone 1 gm/day, typically for 3 days total
b. Dexamethasone 200 mg/day x 3 days
IV. List the complications of the therapy, their prevention and management
A. For all forms
1. Posterior subcapsular cataracts (not reversible)
2. Increased intraocular pressure (IOP) (often reversible)
B. Systemic use
1. Note that there is some overlap between short and long term side effects
2. Short term
a. Weight gain
b. Mood effects, sleep disturbance and psychosis
c. Acute hyperglycemia
d. Manifestations of latent diabetes mellitus, increased requirements for insulin or oral hypoglycemic
agents in persons with diabetes
e. Exacerbation of hypertension, fluid retention, congestive heart failure in susceptible patients,

potassium loss, hypokalemic alkalosis, and hypertension
f. Aseptic necrosis of femoral and humeral heads (Dosages over 60mg/day associated with greater
risk of aseptic necrosis of the femoral head)
g. Menstrual irregularities
h. Urticaria and other allergic, anaphylactic or hypersensitivity reactions
i. Infection, reduced symptoms from infection
j. Increased intracranial pressure with papilledema (pseudo-tumor cerebri), convulsions, vertigo,

headache, insomnia, emotional disturbances
3. Long term
a. Osteoporosis, osteopenia (this begins by 3 months of steroid therapy)
b. Impaired wound healing, thin fragile skin, petechiae and ecchymoses, facial erythema, increased
sweating, striae and may suppress reactions to intradermal skin tests (e.g., purified protein
derivative test for tuberculosis infection)
c. Pancreatitis; abdominal distention; ulcerative esophagitis; increases in alanine transaminase,
Uveitis 211 © AAO 2017-2019

aspartate transaminase and alkaline phosphatase have been observed following corticosteroid
treatment ("fatty liver")
i. In most cases, side effects are minor, not associated with any clinical syndrome and are
reversible upon discontinuation
ii. Peptic ulcer with possible perforation and hemorrhage (risk appears to be associated
primarily with concurrent use of non-steroidal anti-inflammatory drugs)
d. Reactivation of latent tuberculosis
e. Pathologic fracture of long bones, muscle weakness, steroid myopathy, loss of muscle mass,
osteoporosis, tendon rupture, particularly of the Achilles tendon, vertebral compression fractures
f. Fat redistribution, adrenal suppression, accelerated atherosclerosis, development of Cushingoid

state; secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in
trauma, surgery or illness; suppression of growth of children; decreased carbohydrate tolerance
C. Intravitreal use
1. Endophthalmitis
2. Sterile, toxic-type reaction
3. Infectious
4. Vitreous hemorrhage
D. Topical use
1. Worsening of external infectious disease
2. Increased incidence and frequency of spontaneous subconjunctival hemorrhages
E. Regional use
1. Unintended injection into the choroidal or retinal circulation or emboli
2. Perforation of the globe with permanent loss of vision
3. Ptosis (more common with superior injections)
4. Proptosis
5. Orbital fat atrophy, fibrosis
6. Orbital fat prolapse (with inferior retroseptal injections)
7. Delayed hypersensitivity reactions
8. Subconjunctival hemorrhage
9. Chemosis
10. Infection
11. Pain from injection, syncope, scarring, Cushing Syndrome, pupillary dilatation
F. Intravitreal corticosteroid implants
1. Surgical complications
a. Approximately 100% of phakic patients will need cataract surgery at 2 years (sustained release
implants)
b. Approximately 40% will need surgical intervention for glaucoma at 2 years, approximately 50% will
need topical medication for glaucoma at 3 years (sustained release implants)
c. Vitreous opacities
d. Vitreous hemorrhage
e. Macular edema
f. Retinal hemorrhage
g. Hypotony
h. Choroidal detachment
Uveitis 212 © AAO 2017-2019

i. Retinal detachment
j. Sterile endophthalmitis
k. Lens penetration
2. Rare complications
a. Late spontaneous dissociation of the implant from the anchoring strut
b. Conjunctival erosion of anchor suture with a high risk for endophthalmitis
3. Perioperative management
a. Maintenance of optimal immunomodulatory therapies preoperatively
b. Begin tapering concomitant immunomodulatory therapy when clinically optimal post-operatively
c. Monitor carefully for intraocular pressure rise and treat aggressively with MMT; engage glaucoma
specialist early to manage and intervene surgically when appropriate to prevent irreversible optic
nerve damage
d. Monitor cataract progression and intervene surgically when inflammatory status is stable and
cataract is visually significant
V. Describe the follow-up care
A. Systemic use
1. Routine monitoring of blood pressure, weight, and response to therapy may vary, but generally every 4 to 6
weeks; blood glucose level will need to be individualized
2. Long-term use should be avoided
3. If long term therapy cannot be avoided, monitor bone mineral density initially, then approximately yearly, as
well as cholesterol and lipids, and embark upon bone preservation strategies
4. Monitor for gastric ulcers, especially in patients on concomitant oral NSAIDS
B. Topical, regional, intravitreal use
1. Monitor IOP and cataract status
A. All patients should have blood sugar and blood pressure monitored, in conjunction with their primary care
physician
B. Use supplemental calcium and vitamin D to decrease the risk of osteopenia
C. Maintain physical activity and optimal body weight
D. If on oral corticosteroids for longer than 2-3 weeks, therapy should not be abruptly discontinued
2. Jabs DA, Rosenbaum JT, Foster CF, et al. Guidelines for the Use of Immunosuppressive Drugs in Patients
With Ocular Inflammatory Disorders: Recommendations of an Expert Panel. Am J Ophthalmol 2000;
130:492-513.
Uveitis 213 © AAO 2017-2019

I. Pharmacology
1. Methotrexate is an inhibitor of dihydrofolate reductase, an enzyme necessary in the metabolism of folic acid
to folate cofactors, which are required in reactions including DNA replication and RNA transcription
2. Methotrexate thus reduces the growth of rapidly dividing cells
3. Increasing the rate of T-cell apoptosis
4. Increasing endogenous adenosine concentration
5. Altering cytokine production and humoral response
B. Pharmacokinetics
1. Methotrexate absorption following oral administration varies greatly
2. In addition, methotrexate undergoes first pass metabolism in the liver, reducing bioavailability
3. Parenteral administration, particularly subcutaneous injection, is associated with greater bioavailability and
reduced gastrointestinal side effects
4. The onset of action is slow, usually requiring 6 to 8 weeks to become effective and up to 3 to 4 months for
full effect
A. Some uveitis specialists do not manage the administration of these agents themselves, but coordinate care
of the patient with an internist/rheumatologist
B. Indications
1. Noninfectious intraocular and scleral inflammatory disease
a. Nonresponsive or incompletely responsive to corticosteroids, or recurrence with tapering of

corticosteroids
b. Incomplete response to other corticosteroid-sparing agents
2. Primary central nervous system- intraocular lymphoma
a. Treatment paradigm is complex but main point are:
i. High dose systemic therapy
ii. Intrathecal therapy
iii. Intravitreal therapy (especially in primary intraocular lymphoma)
1. Infectious etiology
2. Liver disease
3. Renal insufficiency or other kidney disease (dosage adjustment required)
5. Pregnancy (includes males impregnating others)
6. Breast feeding
7. Pulmonary disease
8. Hematologic abnormalities (relative contraindication)
Uveitis 214 © AAO 2017-2019

B. Complete blood count (CBC)
C. Liver function tests
D. Some clinicians perform hepatitis panel
E. Chest x-ray
IV. List the alternatives to this procedure/therapy
A. Corticosteroids
B. T-Cell signaling inhibitors
1. Cyclosporine
2. Tacrolimus
3. Sirolimus
C. Other antimetabolites
1. Azathioprine
2. Mycophenolate mofetil
D. Alkylating agents
1. Cyclophosphamide
2. Chlorambucil
E. Biologic Response Modifiers (see section)
V. Describe the dosage
A. For noninfectious intraocular inflammatory disease and scleritis
1. A typical initial dose is 7.5-15 mg/week
2. Maximum dosage varies per clinician and clinical response, but is typically in the range of 15 mg to 25
mg/week. (higher doses may be used cautiously)
3. Pediatric dosing 5-15 mg/m2
4. May be administered orally, intramuscularly or subcutaneously. Because of variable intestinal absorption

mucosal irritation related side effects, parenteral administration may increase bioavailability and reduce
gastro-intestinal side effects
B. For primary central nervous system- intraocular lymphoma
1. High-dose systemic methotrexate alone or in combination with other chemotherapeutic agents
2. Intrathecal methotrexate via Omaya reservoir
3. Intravitreal methotrexate (400µg/0.1ml) with or without systemic treatment
VI. List the complications of the procedure/therapy, their prevention and management
A. Complications
1. Leukopenia
2. Elevation of liver enzymes
3. Pulmonary fibrosis
4. Headache
Uveitis 215 © AAO 2017-2019

5. Nausea
6. Oral ulcers/stomatitis
7. Alopecia
8. Fatigue
9. Hyper eosinophilia
10. Teratogenicity
B. Prevention
1. Use of folic acid 1 mg/day usually decreases severity of side effects. May use higher doses (e.g., 2 mg/day)
2. Alcohol abstinence to obviate additive hepatotoxicity
3. Avoidance of other medications which affect liver
4. Appropriate contraception for women of childbearing age for at least 3 months after discontinuing the
medication
5. Potential for sperm mutation: 4 months off drug for males prior to attempting conception
A. Routine monitoring of
1. CBC
2. Liver function tests (LFT's: aspartate transaminase, alanine transaminase, total bilirubin)
3. Renal function
4. Dose adjustments should be made based on therapeutic response and the results of routine monitoring.
A. Inform the ophthalmologist of any new symptoms while on the medication
B. Appropriate contraception should be stressed for both male and female patients, during therapy and for
some time after the medication is stopped
2. AAO, Focal Points: Management of Chronic Uveitis, Module #11, 2007
3. Samson CM, Waheed N, Baltztzis S, et al. Methotrexate therapy for chronic noninfectious uveitis: analysis
of a case series of 160 patients. Ophthalmology. 2001 Jun; 108(6):1134-9.
4. Dev S, McCallum RM, Jaffe GJ. Methotrexate treatment for sarcoid-associated panuveitis. Ophthalmology.
1999 Jan; 106(1):111-8.
With Ocular Inflammatory Disorders: Recommendations of an Expert Panel Am J Ophthalmol 2000;
130:492-513.
6. Galor A, Jabs DA, Leder HA, et al. Comparison of antimetabolite drugs as corticosteroid-sparing therapy for
noninfectious ocular inflammation. Ophthalmology 2008; 115: 1826-32.
7. Kempen JH, Gangaputra S, Daniel E, et al. Long-term risk of malignancy among patients treated with
immunosuppressive agents for ocular inflammation: a critical assessment of the evidence. Am J Ophthalmol
2008; 146: 802-12.
8. Gangaputra S et al. Methotrexate for Ocular Inflammatory Diseases. Ophthalmology 2009; 116:2188-2198.
9. Wessels JA, Huizinga TW, Guchelaar HJ. Recent insights in the pharmacological actions of methotrexate in
the treatment of rheumatoid arthritis. Rheumatology (Oxford) 2008; 47: 249-55.
Uveitis 216 © AAO 2017-2019

10. Chan ES, Cronstein BN. Methotrexate-how does it really work. Nat Rev Rheumatol. 2010 Mar; 6(3):175-8.
Uveitis 217 © AAO 2017-2019

I. Pharmacology
1. Azathioprine is a purine analog and prodrug, which is converted to 6-mercaptopurine, a competitive inhibitor
of purine synthesis, that produces an immunosuppressive effect by inhibiting DNA and RNA synthesis in
actively dividing cells, including lymphocytes
B. Pharmacokinetics
1. Well absorbed orally
2. Crosses the placenta
3. Hepatically metabolized; then renally excreted
4. It may take several months to become maximally active
A. Some uveitis specialists do not manage the administration of these agents themselves, but coordinate care
of the patient with an internist/rheumatologist
B. Indications
1. Noninfectious intraocular inflammatory and scleral disease

corticosteroids
c. May be useful in intermediate uveitis; the Systemic Immunosuppressive Therapy for Eye Disease
Cohort Study, indicated comparatively good results, for patients with mucous membrane
pemphigoid
2. Hematologic disorders
3. Liver disease
7. Breast feeding
8. Homozygous thiopurine methyltransferase (TPMT) deficiency
E. Chest x-ray
F. Pretreatment testing for inherited thiopurine methyltransferase (TPMT) deficiency
Uveitis 218 © AAO 2017-2019

1. 89% wild type
2. 11% heterozygous
3. 0.3% homozygous
A. Corticosteroids
1. Systemic administration
2. Local administration to the eye
B. T-cell signaling inhibitors
1. Cyclosporine
2. Tacrolimus
3. Sirolimus
C. Other antimetabolites
1. Methotrexate
1. Cyclophosphamide
2. Chlorambucil
E. (See Biologic response modifiers)
A. 1 - 3.0 mg/kg/day (100-200 mg/day typical dose)
B. Reduced dose
1. Heterozygous TPMT deficiency
2. Concomitant allopurinol
A. Leukopenia
1. Potentially rapid/life threatening bone marrow suppression if homozygous TPMT mutation
B. Elevation of liver enzymes
C. Possible increased long-term risk of malignancy (lymphoma, leukemia)
D. Nausea
E. Fatigue
F. Teratogenicity: appropriate contraception for women of childbearing age
A. Routine monitoring of CBC, liver function tests, renal function, response to therapy may vary, but generally
every 4 to 6 weeks
B. Decrease dose
1. LFT's ≥ 3x upper limit of normal
Uveitis 219 © AAO 2017-2019

C. Interrupt therapy
1. WBC ≤ 2,500 cells/mm3
2. Platelet ≤ 75,000 cells/mm3
3. LFT's ≥ 5x upper limit of normal
A. Inform the ophthalmologist of any new symptoms while on the medication, including, but not limited to, the
following
1. Fever, chills, sore throat
2. Dark urine
3. Black tarry stools
4. Unusual bleeding
5. Unusual tiredness or weakness
6. Yellowing of the skin or eyes
7. Stomach or abdominal pain
8. Muscle or joint pain
130:492-513.
2008; 146: 802-12.
5. Fargher EA, Tricker K, Newman W, et al. Current use of pharmacogenetic testing: a national survey of
thiopurine methyltransferase testing prior to azathioprine prescription. J Clin Pharm Ther 2007; 32:187-95.
6. Pasadhika S et al. Azathioprine for Ocular Inflammatory Diseases. Am J Ophthalmol 2009; 148:500-509.
Uveitis 220 © AAO 2017-2019

I. Pharmacology
1. Mycophenolate mofetil, a prodrug of mycophenolic acid, is a selective inhibitor of de novo lymphocyte purine
synthesis by reversibly and noncompetitively binding the enzyme inosine monophosphate dehydrogenase
2. The enzyme is predominantly active in T and B lymphocytes which are dependent on de novo purine
synthesis accounting for the selectivity of the drug compared to azathioprine, which also inhibits purine
synthesis
3. In addition, mycophenolate suppresses antibody synthesis, interferes with cellular adhesion to vascular
endothelium, and decreases recruitment of leukocytes
B. Pharmacokinetics
A. Some uveitis specialists would not manage the administration of these agents themselves but would
coordinate care of the patient with an internist/rheumatologist
B. Indications

corticosteroids
2. Hematologic disorders
3. Liver disease
6. Pregnancy: females of child-bearing potential and potential fathers (teratogenic effects may occur in children
whose fathers are receiving the medication, at the time of conception)
7. Breast feeding
E. Chest x-ray
A. Corticosteroids
Uveitis 221 © AAO 2017-2019

B. Mycophenolic acid (Myfortis®) can be used in place of mycophenolate mofetil with a different dosing but a
similar pharmacologic effect
C. T-cell signaling inhibitors
1. Cyclosporine
2. Tacrolimus
3. Sirolimus
D. Other antimetabolites
1. Methotrexate
2. Azathioprine
E. Alkylating agents
1. Cyclophosphamide
2. Chlorambucil
F. (See Biologic response modifiers)
A. Initially 1 g twice a day (some clinicians begin with 500 mg twice daily and if tolerated, increase to 1 g twice
daily)
B. With failure to control disease and if medication well tolerated, may increase dose to 1500 mg twice daily (3
g daily total dose)
A. Gastrointestinal (GI) disturbance
B. Leukopenia, pure red cell aplasia (PRCA)
C. Possible increased long-term risk of malignancy (lymphoma, leukemia)
D. Progressive multifocal leukoencephalopathy
E. Nausea
F. Fatigue
G. Miscarriage
H. Teratogenicity: appropriate contraception for women of childbearing age
A. CBC assessment monthly to every two months
B. Many clinicians perform liver function tests every three months during therapy as well
C. Women should be advised to use two methods of birth control -- or total abstinence -- for four weeks prior
to starting therapy and should continue contraception or abstinence during treatment and for six weeks
after stopping therapy
A. Inform the physician of any new symptoms while on the medication,
B. Appropriate contraception should be discussed as indicated in section VII
Uveitis 222 © AAO 2017-2019

2. AAO, Focal Points: Management of Chronic Uveitis, Module#11, 2007.
3. Thorne JE, Jabs DA, Qazi FA. Mycophenolate Mofetil Therapy for Inflammatory Eye Disease.
Ophthalmology 2005; 112:1472-1477.
With Ocular Inflammatory Disorders: Recommendations of an Expert Panel. Am J Ophthalmol 2000;
130:492-513.
5. Teoh SC, Hogan AC, Dick AD, et al. Mycophenolate mofetil for the treatment of uveitis. Am J Ophthalmol
2008; 146; 752-60.
immunosupressive agents for ocular inflammtion: a critical assessment of the evidence. Am J Ophthalmol
2008; 146: 802-12.
8. Daniel E et al. Mycophenolate Mofetil for Ocular Inflammation. Am J Ophthalmol. 2010; 149(#): 423-432.
Uveitis 223 © AAO 2017-2019

I. Pharmacology
A. Mechanism of action: alkylating agents
1. Cyclophosphamide
a. Following oral administration, it is metabolized in the liver to phosphoramide mustard and acrolein
b. Phosphoramide mustard inhibit T and B-cell proliferation by producing cross-linkage in DNA

between guanine and thymidine with aberrant base pairing, DNA strand breakage and interruption
of transcription
c. This results in cytotoxicity to both resting and dividing lymphocytes with suppression of both cellular
and humoral immune responses
d. Acrolein is responsible for bladder toxicity
2. Chlorambucil
a. Nitrogen mustard derivative
b. Similar mechanism as cyclophosphamide with slower time of onset
B. Pharmacokinetics
2. Metabolized in liver
3. Renally excreted, but most is reabsorbed
A. Most uveitis specialists do not manage the administration of these agents themselves but coordinate care
of the patient with an internist, rheumatologist or oncologist
B. Indications
a. In certain conditions such as necrotizing scleritis or granulomatosis with polyangiitis (GPA)

(previously known as Wegener granulomatosis), cyclophosphamide is indicated as first line therapy
where it is particularly efficacious for the eye and for saving the patient's life. Similarly, chlorambucil
has been shown to induce long- term remission (cure) in patients with otherwise intractable sight-
threatening noninfectious uveitis such as Behcet disease, sympathetic ophthalmia and serpiginous
choroidopathy
b. Nonresponsive or incompletely responsive to corticosteroids, or recurrence with tapering of

corticosteroids
c. Incomplete response to other corticosteroid-sparing agents
4. Breast feeding
5. Hematologic disorders (relative contraindication)
6. History of prior cancer
Uveitis 224 © AAO 2017-2019

C. Urinalysis
D. Liver enzymes
A. Corticosteroids
B. T-cell signaling inhibitors
1. Cyclosporine
2. Tacrolimus
3. Sirolimus
C. Antimetabolites
1. Methotrexate
2. Azathioprine
D. Other alkylating agents
1. Chlorambucil
2. (See Biologic response modifiers)
V. Describe the dosage and follow-up care
A. Cyclophosphamide
1. May be used orally or intravenously. Most uveitis specialist will treat in conjunction with an
oncologist/rheumatologist or another subspecialist
2. Routine monitoring of CBC weekly, renal function, urinalysis with microscopic examination generally every 4
weeks once on stable regimen
3. Dose titrated to leukocyte count of 3000-4000 cells/µl
4. Discontinue therapy
a. WBC ≤ 2,500 cells/ µl
b. Hematuria
B. Chlorambucil
1. Long-term, low-dose therapy, 12 months
a. 0.1-0.2 mg/kg/day orally, single undivided dose
b. Dosage adjusted based on tolerance and laboratory values
i. Target leukocyte count 3,000-4,000 cells/µl off steroids
2. Short-term, high-dose therapy, 3-6 months
a. Initial daily dose 2 mg/day for 1 week
b. Increase dose by 2 mg/day each week until
i. Inflammation suppressed
ii. Leukocyte count reaches 2500 cells/ µl
iii. Platelets drop below 125,000 cells/ µl
Uveitis 225 © AAO 2017-2019

A. Leukopenia or bone marrow suppression
B. Infection
1. Pneumocystis carinii prophylaxis
a. Trimethoprim-sulfamethoxazole, one tablet, single strength, daily
C. Hemorrhagic cystitis (increases risk of subsequent bladder cancer)
D. Gonadal suppression and permanent infertility
1. Banking of sperm, eggs, embryos before treatment
E. Pulmonary fibrosis
F. Rash
G. Long-term risk of secondary malignancy (bladder, lymphoma, leukemia, skin cancer)
H. Nausea
I. Fatigue
J. Hair loss does occur with both but may more pronounced with Cyclophosphamide
K. Teratogenicity: appropriate contraception for women of childbearing age
A. Inform the ophthalmologist of any new symptoms while on the medication. , including, but not limited to,
the following
1. Fever, chills, sore throat
2. Dark urine
3. Blood in urine (hematuria)
4. Black tarry stools
5. Unusual bleeding
6. Unusual tiredness or weakness
7. Yellowing of the skin or eyes
8. Stomach or abdominal pain
9. Muscle or joint pain
B. Take dose of cyclophosphamide in early morning with at least 2 L fluid per day, maintain good urine flow
1. This reduces contact time of acrolein metabolite with bladder wall
C. Avoid live virus vaccines
D. Appropriate follow up with rheumatologist or oncologist
2. AAO, Focal Points: Management of Chronic Uveitis, Module#11, 2007.
3. AAO, Focal Points: Scleritis and Episcleritis: Diagnosis and Management, Module 4, 2009.
130:492-513.
Uveitis 226 © AAO 2017-2019

2008; 146: 802-12.
6. Goldstein DA, Fontanilla FA, Kaul S, et al: Long-term follow-up of patients treated with short-term high-dose
chlorambucil for sight-threatening ocular inflammation. Ophthalmology 109:370, 2002.
7. Pujari SS, et al. Cyclophosphamide for Ocular Inflammatory diseases. Ophthalmol, 2010; 117(2): 356.
8. Hemady R, Tauber J, Foster CS. Immunosuppressive drugs in immune and inflammatory ocular disease.
Surv Ophthalmol 1991; 35;:369-8
Uveitis 227 © AAO 2017-2019

I. Pharmacology
1. Cyclosporine is a non-cytotoxic immunomodulatory agent which selectively and reversibly inhibits

helper/inducer CD4+ T- lymphocyte mediated immune responses
a. Cyclosporine binds to cyclophilin
b. The cyclosporine-cyclophilin complex then binds to and inhibits calcineurin
c. Calcineurin catalyzes reactions necessary for early activation of T-cells particularly the expression
and production of cytokines such as interleukin-2 (IL-2)
2. Cyclosporine does not affect suppressor T-cells or T-cell independent, antibody-mediated immunity
B. Pharmacokinetics
1. Different formulations have different bioavailabilities, therefore consistency in the formulation used is
needed (see dosages)
a. The USP modified microemulsion formulation (Neoral, Gengraf) has greater oral bioavailability than
unmodified cyclosporine A (Sandimmune)
b. Unmodified cyclosporine A is the only liquid formulation. (There are 2 oral solution formulations, and
2 soft gelatin capsule formulations: the Sandimune oral solution and soft gel capsules both have
decreased bioavailability compared to the Neoral formulations)
2. When converting from one formulation to another, a dosage adjustment is needed
3. Cyclosporine crosses the placenta and is found in breast milk
4. Food consumed with cyclosporine affects absorption
a. The liquid formulation can be diluted with orange or grape juice, or chocolate milk
b. Taking cyclosporine with meals of a relatively uniform composition from day to day may result in
more even drug levels
c. Food generally enhances absorption
A. Some uveitis specialists do not manage the administration of these agents themselves, but coordinate
care of the patient with an internist/rheumatologist
B. Indications

corticosteroids
c. Cyclosporine is frequently used in combination with systemic steroids in patients who need a rapid
control of inflammation
2. Poorly controlled or difficult to control hypertension
3. Renal insufficiency or other kidney disease
D. Relative contraindications
Uveitis 228 © AAO 2017-2019

1. Pregnancy
2. Breast feeding
3. Advanced age (increased risk of renal dysfunction)
A. Renal function panel and estimated creatinine clearance.
B. Liver function panel
C. Serum cholesterol and triglycerides
D. Complete blood count (CBC)
E. Blood pressure (BP).
A. Other calcineurin inhibitors (tacrolimus) and agents that interfere with signals leading to IL-2 production
(sirolimus)
1. Competes with tacrolimus
2. Synergistic with sirolimus
B. Antimetabolites
1. Methotrexate
2. Azathioprine
C. Alkylating agents
1. Cyclophosphamide
2. Chlorambucil
D. (See Biologic response modifiers)
A. 2 to 5 mg/kg/day, typically in two divided doses with adjustment depending on clinical response and toxicity
1. USP modified cyclosporine is typically 4 mg/kg/day
2. Unmodified cyclosporine A is typically 5 mg/kg/day
3. Maintenance doses are usually one half the typical dose
4. Doses more than 200 mg/day in adults have a higher incidence of side effects
5. Decrease dose 20% when moving from unmodified to modified cyclosporine, and increase dose 20% when
moving from modified to unmodified cyclosporine
6. Taper dose by 20% every 2 to 3 weeks when decreasing therapy to prevent rebound of inflammation
7. Caution with doses in patients who are markedly underweight or overweight
A. Hypertension
1. Antihypertensive medication may be necessary
2. Angiotensin converting enzyme inhibitors preferred
3. Calcium channel blockers may increase blood cyclosporine levels
Uveitis 229 © AAO 2017-2019

4. Avoid diuretics as dehydration may affect kidney function
B. Reduction in estimated creatinine clearance
1. Dosage reduction required if declines by more than 20%
C. Hirsutism
D. Gingival hyperplasia
1. Prophylactic dental cleaning and daily gum massage and flossing
E. Trembling and shaking of hands/paresthesia
F. Acne or oily skin
G. Headache
H. Leg cramps
I. Nausea
J. Infection
K. Malignancy
L. Central nervous system dysfunction or peripheral neuropathies
M. Osteoporosis
A. Routine monitoring of BP, renal function generally every 4 to 6 weeks initially, then at least every 3 months
B. Magnesium levels if patient having cramps or neurological symptoms
C. Uric acid may rise during early treatment
D. Liver enzymes may rise during early treatment
E. Cholesterol may rise during prolonged treatment
F. Whole blood drug levels may be checked as an indicator of compliance, bioavailability, or in suspected
toxicity, however most clinicians do not routinely check levels and do not use them for treating to a target
level.
G. Reduce dose
1. Systemic BP>140/90 Hg or clinically significant increase in blood pressure above baseline if not controlled
by antihypertensive medication
2. Decrease in renal function as measured by estimated creatinine clearance by >20% from baseline
H. Taper and discontinue drug
1. BP not controlled despite antihypertensive therapy
2. Estimated creatinine clearance decreased by 30% since baseline
I. Reliance on normal BP ranges and normal creatinine ranges without considering age, sex, body weight, and
baseline values may lead to underestimation of toxicity
A. Certain foods and medications can result in an increase in blood levels
1. Macrolide antibiotics erythromycin and clarithromycin (not azithromycin)
2. Cholesterol drugs atorvastatin, lovastatin, simvastatin (not pravastatin or rosuvastatin)
3. Grapefruit juice (if taken at the same time as the medication)
4. Drug interactions summarized at http://medicine.iupui.edu/clinpharm/ddis/
B. Inform the ophthalmologist of any new symptoms while on the medication
Uveitis 230 © AAO 2017-2019

1. Especially
a. Fever, chills, sore throat
b. Headache
c. Confusion, depression
d. Muscle and joint aches
e. Changes in urine production or color
f. Changes in gums
g. Numbness or tingling in hands or feet
C. Inform ophthalmologist of any new medications added to regimen
D. Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) due to increase in risk of renal toxicity
2. AAO, Focal Points: Management of Chronic Uveitis, Module #11, 2007
3. Ramadan AM, Nussenblatt RB, de Smet MD. Long-term follow-up of patients with chronic uveitis affecting
the posterior pole treated with combination cyclosporine and ketoconazole. Ophthalmology.1997;
104:706-11.
4. Nussenblatt RB, de Smet MD, Rubin B, et al. A masked, randomized, dose-response study between
cyclosporine A and G in the treatment of sight-threatening uveitis of noninfectious origin. Am J Ophthalmol.
1993; 15:115-91.
130:492-513.
6. Murphy CC, Greiner K, Plskova J et al. Cyclosporine vs tacrolimus therapy for posterior and intermediate
uveitis. Arch Ophthalmol 2005; 123: 634-41.
7. Hesselink DA, Baarsma GS, Kuijpers RW, et al. Experience with cyclosporine in endogenous uveitis
posterior. Transplant Proc 2004; 36 (2 Suppl.): 372-377S
2008; 146: 802-12.
9. Kaçmaz, RO et al. Cyclosporine for Ocular Inflammatory Diseases. Ophthalmol, 2010; 117(#): 576-584.
Uveitis 231 © AAO 2017-2019

I. Pharmacology
A. Biologics Response Modifiers (BRM's) are immune-modulatory agents that result in targeted therapy by
inhibiting specific cytokines. They include:
1. Recombinant cytokines and monoclonal antibodies directed against specific cell-surface markers on
lymphocytes
2. Cytokines or their receptors which selectively suppress the inflammatory cascade
a. The major classes of BRM's relevant to ocular inflammatory disease include
i. Tumor necrosis factor (TNF) inhibitors
ii. Interleukin inhibitors
iii. B-cell inhibitors
iv. Recombinant human cytokines/cytokine analogues
v. Costimulation modulators
B. Mechanisms of action and rationale for use
1. TNF-alpha inhibitors
2. Inhibition of tumor necrosis factor (TNF)-alpha has been shown in several studies in the rheumatology and
dermatology literature to favorably impact diseases such as rheumatoid arthritis (RA), ankylosing
spondylosis, psoriasis, and inflammatory bowel disease, among others
a. Anti-TNF antibodies
i. Infliximab is a chimeric IgG monoclonal antibody containing human and murine portions,
directed against TNF-alpha, it competitively and irreversibly inhibits both soluble and
transmembrane forms of TNF-α.
ii. Adalimumab is a recombinant IgG containing 100% human peptide sequences, and is
directed against TNF-alpha, targets and neutralizes membrane bound TNF-α.
iii. Golimumab is a monoclonal antibody directed against TNF-α receptor; prevents the binding
and inhibits biological activity
b. TNF receptor blocker
i. Etanercept is a fusion protein consisting of two human extracellular TNF binding domains
complexed to the Fc portion of human immunoglobulin G (IgG), it can bind well to soluble
TNF-α but not as effectively to trans-membrane TNF-α.
3. Interleukin Inhibitors
a. Anakinra: IL-1 Receptor Antagonist (Kinaret®); it blocks the biologic activity of IL-1 by competitively
inhibiting IL-1binding to the interleukin-1 type I receptor (IL-1RI)
b. Tocilizumab: IL-6 Receptor Antagonist (Actemra®); it is a humanized monoclonal antibody that

binds specifically to IL-6 receptors
c. Ustekinumab: a monoclonal antibody which binds with specificity to the shared p40 protein subunit
used by both IL-12 and IL-23 cytokines
4. Anti- CD20 monoclonal antibody
a. Anti-CD20 monoclonal antibodies, widely expressed on B-cells, have been used to treat B-cell
malignancies as well as systemic autoimmune diseases such as RA. They mediate B-cell lysis,
possibly by complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity
b. Rituximab is a chimeric monoclonal antibody directed against CD20-positive cells, largely

expressed on B-lymphocytes
5. Recombinant human cytokine/cytokine analogues
a. Recombinant human cytokines and their analogues such as the interferons (INFs) have been used
in the treatment of hepatitis C, neoplastic diseases and autoimmune diseases such as MS
Uveitis 232 © AAO 2017-2019

b. The mechanism of action of interferons is poorly understood but these agents are known to have
antiviral, antineoplastic, and antiangiogenic effects
6. Costimulation modulators
a. Orencia®(abatacept) is a fusion protein of immunoglobulin bound to the extracellular domain of

CTLA-4, a molecule which binds B7 on antigen presenting cells, effectively preventing binding of
the APC to T-lymphocytes and preventing T cell activation
A. Most uveitis specialists do not manage the administration of these agents, but refer the patient to an
internist/rheumatologist/oncologists
B. Note that the employment of these medications is off label for ocular disease
C. Indications

corticosteroids
c. Infliximab and adalimumab may be considered as first-line immunomodulatory agents for the
treatment of ocular manifestations of Behçet disease; as second-line immunomodulatory agents for
the treatment of uveitis associated with juvenile arthritis; as potential second-line
immunomodulatory agents for the treatment of severe ocular inflammatory conditions including
posterior uveitis, panuveitis, severe uveitis associated with seronegative spondyloarthropathy, and
scleritis in patients requiring immunomodulation; in patients who have failed or who are not
candidates for antimetabolite or calcineurin inhibitor immunomodulation.
d. Etanercept is not considered a preferred agent for uveitis treatment. There are some reports of
paradoxical inflammation with etanercept
e. Currently there is some published data available supporting the use of Rituxan for the following
ocular inflammatory diseases: orbital inflammation associated with rheumatoid arthritis (RA) and
(granulomatous polyangiitis (GPA); GPA associated peripheral ulcerative keratitis; scleritis
associated with RA, GPA; mucous membranous pemphigoid with ocular involvement; chronic
uveitis associated with juvenile idiopathic arthritis and BD
f. Published case series from Europe, suggests efficacy of interferon α-2a in the treatment of uveitic
CME and ocular manifestations of Behçet disease (BD)
g. Preliminary data on the interleukin inhibitors, suggests possible utility in JIA-associated uveitis and
uveitic macular edema
D. Contraindications
1. Infectious etiology of intraocular inflammatory diseases
2. Infection elsewhere (e.g., active tuberculosis, untreated latent tuberculosis)
3. Allergy or insensitivity to agent or others in its class
4. Pregnancy (Category B)
5. Breast feeding
6. Moderate to severe congestive heart failure
7. Multiple sclerosis or other demyelinating diseases
8. Moderate or severe heart failure
A. Chest X-ray
B. Purified protein derivative/QuantiFERON-TB Gold test (Special recommendations for TNF agents: if latent
tuberculosis is detected, appropriate anti-tubercular therapy should be initiated. Anti-TNF treatment may be
started one month after initiation of TB therapy
Uveitis 233 © AAO 2017-2019

C. Rule out possibility of demyelinating diseases such as multiple sclerosis (MRI)
D. Metabolic panel
E. Complete blood count (CBC)
F. Query on history or risks for heart failure
G. Antinuclear antibodies
A. Corticosteroids
B. Inhibitors of T-Cell Signaling
1. Cyclosporine
2. Tacrolimus
3. Sirolimus
C. Antimetabolites
1. Methotrexate
2. Azathioprine
1. Cyclophosphamide
2. Chlorambucil
V. Agents
A. TNF-alpha inhibitors
1. Infliximab (Remicade®)
a. 3-10 mg/kg intravenous (IV) infusion
i. Anecdotal reports have used higher doses in nonresponsive cases.
b. Timing between infusions varies but generally at weeks 0, 2, 6, and every 8 weeks thereafter. For
uveitis, every 4 weeks is preferred, with a beginning dose of 5 mg/kg
2. Adalimumab (Humira®)
a. 40mg SC every other week or weekly as clinically indicated
3. Etanercept (Enbrel®)
a. 25 mg subcutaneously (SC), once or twice weekly
B. Anti- CD20 monoclonal antibody
1. Rituximab (Rituxan®)
a. 1g administered by IV infusion, as two consecutive doses, 2 weeks apart; subsequent doses may
be administered 16-24 weeks later, but no sooner, based on clinical response.
C. Recombinant human cytokine/cytokine analogues
1. IFN alpha 2a (Roferon-A®)
a. 3-9 million international units/day, 3 times weekly, subcutaneous injections
A. TNF alpha inhibitors
Uveitis 234 © AAO 2017-2019

1. Infusion reactions other than hypersensitivity reactions
2. Hypersensitivity reactions
3. Exacerbation of demyelinating disease
4. Exacerbation of tuberculosis and other latent infections (e.g., histoplasmosis)
5. Heart failure
6. Production of neutralizing antibodies
7. Drug induced lupus
8. Neoplasia (acute leukemia, infliximab)
9. De novo uveitis (etanercept)
B. Anti-CD20 monoclonal antibody
1. Hypersensitivity reactions
2. Infusion reactions other than hypersensitivity reactions
C. Interleukin-2 receptor blockade
1. Psoriasiform skin rashes
2. Lymphadenopathy
3. Peripheral edema (mild)
4. Infections (usually mild, may be severe with concomitant cytolytic therapy)
5. Neoplasia (one case, possibly related to treatment)
D. Recombinant human cytokine/cytokine analogues (IFNs)
1. Arthralgia, fever, first week of therapy very common
2. Erythema, discomfort at injection site
3. Leukopenia
4. Alopecia
5. Depression
6. Cotton wool spot retinal, venous occlusion, retinal hemorrhage
A. Patients treated with biologic response modifiers generally have blood work at time of each infusion, or as
clinically appropriate for the specific agent
B. Vaccination Recommendations for TNF agents: Pneumococcal, Influenza (non-live virus), Completion of
Hepatitis B vaccinations, Patients receiving anti-TNF therapy should not have live virus vaccine including
varicella zoster, oral polio, or rabies vaccination.
A. Inform the physician of any new symptoms while on the medication, including but not limited to:
1. Fever, cough, sore throat
2. Allergic reactions
3. Numbness, weakness
4. Shortness of breath
5. Swelling, fluid retention
6. Rash
Uveitis 235 © AAO 2017-2019

2. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with
ocular inflammatory disorders. Levy-Clarke G, Jabs DA, Read RW, Rosenbaum JT, Vitale A, Van Gelder
RN. Ophthalmology. 2014 Mar; 121(3):785-96.
3. Pharmacotherapy for uveitis: current management and emerging therapy.Barry RJ, Nguyen QD, Lee RW,
Murray PI, Denniston AK.Clin Ophthalmol. 2014 Sep 22; 8:1891-911.
Uveitis 236 © AAO 2017-2019

A. Treatment of uveitis secondary to a viral agent
1. Cytomegalovirus (CMV) retinitis
2. Acute retinal necrosis (ARN) syndrome
a. Herpes simplex retinitis
b. Varicella zoster retinitis
3. Progressive outer retinal necrosis syndrome
a. Herpes simplex retinitis
b. Varicella zoster retinitis
A. Comprehensive eye examination
B. Obtain ocular sample (optional)
1. Aqueous or vitreous sampling for PCR to identify viral agent prior to treatment (whether systemic,
intravitreal, or both)
a. Ocular sampling can be done at the time of intravitreal injection
III. List the alternative routes
A. Intravenous (IV) therapy
B. Oral therapy
C. Intravitreal therapy
1. May be in conjunction with IV or Oral antiviral therapy when clinically appropriate
IV. Dosage of agents commonly used in USA
A. Intravenous (IV)
1. Dose of IV antivirals may need to be adjusted in patients with kidney problems
a. Ganciclovir
i. CMV retinitis
i) Induction
(i) 5mg/kg IV BID for 14-21 days
ii) Maintenance
(i) 5mg/kg IV q day
b. Acyclovir
i. Necrotizing retinitis due to simplex or zoster in immunocompetent patients
i) 5-10mg/kg IV TID
Uveitis 237 © AAO 2017-2019

ii. Progressive outer retinal necrosis
i) 5-10mg/kg IV TID
c. Foscarnet
i. CMV retinitis
i) Induction
(i) 90 mg/kg IV BID or 60 mg/kg IV TID over 2 to 3 weeks depending on

clinical response
(ii) If acyclovir resistant, 40 mg/kg IV either every 8 or 12 hours for 2 to 3

weeks or until healed
ii) Maintenance
(i) 90 mg/kg/day IV
d. Cidofovir
i. CMV retinitis
i) 5 mg/kg, once a week for 2 weeks and then once every other week
B. Oral
1. Not all clinicians admit patients for IV therapy but rather cover with high dose oral antivirals
2. Dose of oral antivirals may need to be adjusted in patients with kidney problems
a. Valganciclovir
i. CMV retinitis
i) 900mg PO BID
ii) May use 900mg PO qday for maintenance
(i) Risk of mutations conferring resistance to antiviral medication with

long-term maintenance therapy
b. Valacyclovir
i. Necrotizing retinitis due to simplex or zoster in immunocompetent patients
i) 1-2 grams PO TID
ii. Progressive outer retinal necrosis
i) 1-2 grams PO TID
C. Intravitreal
1. Ganciclovir
a. CMV retinitis
i. 0.2 to 5 mg in 0.05-0.1ml 1-2 times weekly for 2-3 weeks followed by weekly injections
i) 5 mg is the highest dose reported in the literature
ii) 2 mg is the conventional dose and has pharmacokinetic data regarding vitreous
levels
iii) Vitreous levels will rise if 2 mg dose given 3 times weekly for more than 2 weeks
iv) 0.2 mg is the originally dose described as effective when given weekly
v) Dose should be titrated to location and extent of retinitis
ii. Alternative, 2.5 mg in 0.05ml once weekly
b. Necrotizing retinitis due to simplex or zoster in immunocompetent patients
i. Single dose (0.2 to 2 mg) followed by IV or oral therapy may be adequate for ARN
ii. Injections may be repeated depending on the clinical response
Uveitis 238 © AAO 2017-2019

c. Progressive outer retinal necrosis and necrotizing herpetic retinitis in immunosuppressed
i. See dosing for ARN
ii. Individuals may require combinations of antiviral agents and routes of administration
(including intravenous/oral and intravitreal therapy)
2. Foscarnet
a. CMV retinitis
i. 1.2 to 2.4 mg in 0.05-0.1ml every 2-3 days for up to 2 to 3 weeks followed by weekly
injections as needed
i) This is the highest reported dose in the literature
ii) Originally described as effective when given in doses of 1.2 to 2.4 mg weekly
b. Necrotizing retinitis due to simplex or zoster
i. Single dose followed by IV or oral therapy may be adequate for ARN
ii. Repeat injections may be done depending on the clinical response
c. Progressive outer retinal necrosis and necrotizing herpetic retinitis in immunocompromised

individuals
i. See dosing for ARN
ii. May require combinations of antiviral agents and routes of administration (including
intravenous/oral and intravitreal therapy)
V. Describe the technique
A. Intravenous therapy
1. Hospital admission
2. Consult infectious disease
B. Oral therapy
1. Check creatinine clearance
C. Intravitreal injection
1. Guidelines according to American Academy of Ophthalmology 2015 Committee (see reference below)
2. Some clinicians will perform AC tap initially with the first injection to use fluid for diagnostic testing
(polymerase chain reaction (PCR) and/or local antibody production)
VI. List the potential complications of the procedure/therapy, their prevention and management
A. IV therapy
1. Monitor renal function
2. Monitor blood counts
a. Ganciclovir
i. Neutropenia
ii. Anemia
iii. Thrombocytopenia
B. Oral therapy
1. Monitor renal function
2. Monitor blood counts
a. Valganciclovir
i. Neutropenia
Uveitis 239 © AAO 2017-2019

ii. Anemia
iii. Thrombocytopenia
b. Valacyclovir
C. Intravitreal therapy
2. Endophthalmitis
3. Cataract
4. Increased IOP
A. Frequent serial eye examinations to confirm response
A. Inform the ophthalmologist of any new symptoms following the treatment
1. Especially decreased vision, pain, increasing redness (other than subconjunctival hemorrhage)
B. Do not rub the eye or get water in it for 24 hours
2. AAO, Focal Points: Necrotizing Herpetic Retinopathies, Module 10, 2008.
3. Kirsch LS, Arevalo JF, Chavez de la Paz E, et al. Intravitreal cidofovir (HPMPC) treatment of
cytomegalovirus retinitis in patients with acquired immune deficiency syndrome. Ophthalmology. 1995
Apr;102(4):533-42.
4. Arevalo JF, Garcia RA, Mendoza AF. European Journal of Ophthalmology. Sept/Oct; 15(5):610-618.
5. Tibbetts MD et al. Treatment of Acute Retinal Necrosis. Ophthalmology 2010; 117: 818-824.
6. Gore DM et al. Progressive Outer Retinal Necrosis: Outcomes in the Intravitreal Era. Arch Ophthalmol.
2012; 130(6): 700-706.
7. American Academy of Ophthalmology Injection Guideline February 2015. Clinical Statements.
8. Avery RL, Bakri SJ, Blumenkranz MS, Brucker AJ, Cunningham ET Jr, DʼAmico DJ, Dugel PU, Flynn HW Jr,
Freund KB, Haller JA, Jumper JM, Liebmann JM, McCannel CA, Mieler WF, Ta CN, Williams GA.
Intravitreal injection technique and monitoring: updated guidelines of an expert panel. RETINA 2014 Dec;
34 Suppl 12:S1-S18.
9. Lalezari JP, Stagg RJ, Kuppermann BD, Holland GN, Kramer F, Ives DV, Youle M, Robinson MR, Drew WL,
Jaffe HS. Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS. A randomized,
controlled trial. Ann Intern Med. 1997 Feb 15;126(4):257-63.
10. Taylor SRJ, Hamilton R, Hooper CY, Joshi L, Moraji J, Gupta N, and Lightman S. Valacyclovir in the
treatment of acute retinal necrosis. BMC Ophthalmology. 2012 12:48.
Uveitis 240 © AAO 2017-2019

A. Indications
1. Decreased visual acuity explained by cataract
2. Inability to examine posterior segment in potentially progressive posterior segment disease
3. Lens-induced inflammation
4. Consider age of patient
a. Urgent if in amblyogenic age group
b. Can often be deferred in middle childhood and teen years until more mature
1. Active anterior segment inflammation (other than that associated with lens induced inflammation, in which
cataract extraction is therapeutic)
2. Active surface infection
3. Concurrent ocular pathology that is likely to prevent functional vision improvement for the patient even with
successful cataract surgery; surgery should be done only if necessary to allow visualization of the patient's
fundus for treatment purposes
A. History
1. Course of visual loss (rapid, gradual)
2. Previous best corrected acuity
3. Previous eye surgery/trauma
B. Medical history
1. Type of uveitis
2. Previous work-up
3. Response to treatment, including elevation in intraocular pressure with corticosteroids
C. Medications (ocular and systemic)
D. Comprehensive eye examination including refraction and dilated fundus examination
1. Special attention should be paid to
a. Concurrent corneal disease that might require combined penetrating keratoplasty with cataract
extraction
b. Elevated intraocular pressure (IOP)/glaucoma requiring surgery
c. Posterior synechiae requiring attention during surgery
d. Presence of phacodonesis
e. Zonular integrity
f. Presence of cystoid macular edema, which should be treated prior to surgery
2. If no view of posterior segment, B-scan is required to rule out retinal detachment, intraocular mass
E. Decision regarding whether to implant intraocular lens (IOL)
1. Degree of flare chronically present in the anterior chamber is associated with the presence of posterior
synechiae
Uveitis 241 © AAO 2017-2019

a. Whether this is a risk factor for subsequent posterior synechiae formation after cataract surgery is
unknown
2. The ability of the ophthalmologist to prevent active inflammation is most likely the key factor in successful
IOL implantation in uveitis patients
3. Uveitic diagnosis such as juvenile idiopathic arthritis (JIA) and chance of recurrent disease
a. Many uveitis specialists consider a diagnosis of JIA a relative contraindication to IOL implantation
b. As adults, former JIA uveitis patients can be considered for an implant, depending on uveitis status
4. Patient compliance
5. Patient age
F. Managing expectations - the following should be discussed PRIOR to surgery
1. The reason for surgery (i.e. visual rehabilitation versus improved visualization of posterior pole) and
expected outcome
2. Prolonged follow-up and increased need for medications in perioperative period
3. Increased likelihood of additional procedures (i.e. injections, imaging, lasers)
A. Refraction
B. Observation
C. Dilation may help with small central posterior subcapsular cataracts
IV. Describe the technique
A. Pre-procedure
1. Commonly followed rule-of-thumb is no active anterior segment inflammation for 3 or more months.
Disease control during this period is maintained with any means required, including chronic topical or
periocular corticosteroids, or immunomodulatory therapy
2. Days to 1 week prior to surgery, patient should have an examination to confirm the eye is quiet. At this time,
periocular, systemic or intraocular corticosteroids may be administered
3. Topics NSAID therapy may be use adjunctively as prophylaxis against macular edema
4. Prior to surgery, it may be helpful to prescribe a pulse of oral and/or topical corticosteroids or give a
periocular or intraocular corticosteroid injection
B. Special considerations during procedure
1. Intraoperatively, methylprednisolone may be given intravenously to minimize the likelihood of a

postoperative flare
2. Consider clear corneal incision for preservation of conjunctiva for future glaucoma procedures, which are
more common in uveitis patients
3. Consider placing suture, as these patients will be on frequent topical steroids and may have delayed wound
healing.
C. Postoperative management
1. Oral corticosteroids may be tapered and discontinued based on the degree of intraocular inflammation
2. Topical corticosteroids are generally given frequently while awake for several days postoperatively, and then
tapered according to disease activity
3. Postoperative cycloplegia is generally helpful to minimize the likelihood of iridocapsular synechiae (iris will
stick to the lens capsule) and provide comfort
V. List the postoperative complications of the procedure/therapy and their management
Uveitis 242 © AAO 2017-2019

A. Uveitis flare up
1. Prevention
a. Increase anti-inflammatory drug agents preoperatively
b. Remove all nuclear and cortical material
2. Management
a. Aggressively reduce the inflammation and quickly taper as tolerated
b. Identify any retained nuclear or cortical particles; may need to have nuclear pieces removed
surgically
B. Retinal detachment
C. Endophthalmitis
D. Increased IOP
E. Corneal decompensation
F. Ptosis
G. Cystoid macular edema
H. Wound leak
I. Posterior capsular opacification
J. Iridocapsular synechiae
K. IOL capture
L. Capsular distension syndrome
A. Postoperative examination within 1 day and then as dictated by the examination findings depending on
presence of uveitis and other complications
B. Topical ± systemic corticosteroids as needed for disease control
C. Topical antibiotics
D. Protect eye (shield, eyeglasses)
E. Limit strenuous activity for initial postoperative period
A. Inform the ophthalmologist of any worsening in visual acuity, pain, redness of eye
B. Stress compliance with medications, limitations, and follow up visits
C. Provide instructions for contacting office in emergency, including after hours
2. Alio JL, Chipont E, BenEzra D, et al. Comparative performance of intraocular lenses in eyes with cataract
and uveitis. J Cataract Refract Surg. 2002;28:2096-108.
Uveitis 243 © AAO 2017-2019

A. Indications
1. Increased intraocular pressure (IOP) unable to be controlled medically that is high enough to cause optic
nerve damage
2. Need for local corticosteroid treatment in known steroid responder
1. Active anterior segment inflammation or active scleritis (relative contraindications that require assessment of
relative risks and benefits)
2. Active surface infection
3. Poor visual potential (relative contraindication)
A. History
1. Course of pressure rise (rapid, gradual) and maximum pressure
B. Previous eye surgery/trauma - medical history
C. Medications (ocular and systemic)
D. Comprehensive eye examination including refraction and dilated fundus examination
1. Special attention should be paid to
a. Concurrent conjunctival disease
b. Cataract that would require concurrent extraction
c. Depth of anterior chamber
d. Presence and degree of posterior synechiae
2. Extra special attention should be paid to the status of the conjunctiva
3. If no view of posterior segment, B-scan is required to rule out retinal detachment and intraocular mass
E. Decision regarding type of surgery
1. Filtering procedure (trabeculectomy)
2. Seton (tube shunts)
a. Lower failure rate than trabeculectomy in uveitis patient, in which scarring is more common.
b. Other, less commonly used procedures
i. Goniotomy in children
ii. Laser cyclodestruction; caution in patients with iridocyclitis at risk for later hypotony, e.g.,
juvenile idiopathic arthritis (JIA)
iii. Gonioscopic stripping of angle membranes if present
F. Preoperative management
1. Whenever possible, uveitis should be inactive for 3 months preoperatively
a. This may require repeat corticosteroid injections, long term topical corticosteroid use, often with
immunosuppressive medication as well
b. A vigorous inflammatory response should be anticipated postoperatively
i. Discuss realistic outcome expectation with patient and family, including need for addition
Uveitis 244 © AAO 2017-2019

surgery.
2. Combined glaucoma and elective cataract surgery may exacerbate the amount of postoperative
inflammation
A. Oral or topical medications
B. Laser trabeculoplasty is relatively contraindicated
IV. Describe the technique
A. Anesthesia
1. Topical
2. Peribulbar
3. Retrobulbar
4. General
B. Pathologic examination should be carried out on removed tissue including iris and/or trabecular meshwork
V. List the postoperative complications of the procedure/therapy, their prevention and

management
A. Uveitis flare up
1. Control inflammation preoperatively, whenever if possible
2. Oral, periocular, intravenous, and/or topical corticosteroids are used for preoperative, intraoperative and
postoperative disease control
3. Treat as appropriate, often requires intraocular corticosteroid postoperatively or prolonged use of systemic
corticosteroids
B. Acute endophthalmitis
C. Delayed endophthalmitis
D. Retinal detachment
E. Hypotony
F. Choroidal effusion and choroidal hemorrhage
G. Increased IOP
H. Corneal decompensation
I. Ptosis
J. Cystoid macular edema
K. Epiretinal membrane development
L. Wound leak
M. Peripheral anterior synechiae around tube with pupil distortion
N. Overfiltration with low intraocular pressure
A. Postoperative examinations frequently during first 90 days, based on condition afterwards
B. Topical corticosteroids frequently
Uveitis 245 © AAO 2017-2019

C. Oral corticosteroids as needed for disease control
D. Topical antibiotics
E. Protect eye (shield, eyeglasses)
F. Limit strenuous activity for initial postoperative period
A. Inform the ophthalmologist of any worsening in visual acuity (VA), pain, redness of eye
B. Stress compliance with medications, limitations, and follow up visits
C. Provide instructions for contacting office in emergency, including after hours
Uveitis 246 © AAO 2017-2019

I. Calcific band-shaped keratopathy
A. Calcium deposits along the epithelial basement membrane and Bowman layer
1. Common in the interpalpebral zone, often extending into the visual axis
2. Removal with epithelial debridement and chelation with sodium ethylenediaminetetraacetic acid (EDTA)
II. Cataract
A. More common in chronic or recurrent uveitis
B. Etiology of cataract progression
1. Intraocular inflammation
2. Corticosteroid use
C. Surgical management when visually significant or precluding view of posterior segment needed for proper
monitoring of disease status (for guidelines and technique see section on Cataract extraction in uveitis
patient)
III. Glaucoma
A. Uveitic ocular hypertension - intraocular pressure (IOP) 10 mm Hg or greater above baseline or any
pressure greater than 21 mm Hg without evidence of glaucomatous optic nerve damage
1. Treat inflammation
2. Consider steroid response if IOP increase occurs after 3 weeks of corticosteroid treatment
3. Consider alternative cause, such as viral or toxoplasma
B. Uveitic glaucoma - progressive neuroretinal rim loss and/or development of typical, perimetric,
glaucomatous field defects secondary to high eye pressure in the setting of intraocular inflammation.
C. Secondary angle-closure glaucoma
1. Acute
a. Choroidal inflammation with anterior rotation of ciliary body and lens iris diaphragm
i. Vogt-Koyanagi-Harada disease (VKH)
ii. Sympathetic ophthalmia
iii. Posterior scleritis
iv. Idiopathic orbital inflammation
b. Clinical findings
i. Complaint of pain
ii. Elevated IOP
iii. No posterior synechiae
iv. Severe inflammation
c. Ultrasound biomicroscopy (UBM) to detect choroidal thickening and anterior rotation of the ciliary
body
d. Treatment
i. Aggressive corticosteroid therapy
ii. Aqueous suppressants
Uveitis 247 © AAO 2017-2019

iii. Peripheral iridotomy or iridectomy is NOT effective
2. Subacute angle closure
a. Significant posterior synechiae, pupillary block, and iris bombé
i. Lead up may be subacute, but rise in IOP may be acute or hyperacute
b. Management
i. Peripheral iridotomy (PI) with the Nd: YAG or argon laser
i) Multiple and large
(i) High rate of spontaneous closure
ii) Intense topical corticosteroid following procedure
iii) Consider argon laser pre-treatment to shrink iris tissue and coagulate vessels
before YAG
ii. Surgical iridectomy
i) Failure of laser PI
ii) Darker irides
iii) Consider histology of iris specimen
3. Chronic angle closure
a. Chronic peripheral anterior synechiae (PAS) and secondary angle-closure glaucoma
i. Topical aqueous suppressants may be inadequate
ii. May temporize with oral carbonic anhydrase inhibitors
iii. May require surgical intervention
i) Goniosynechialysis
ii) Trabeculectomy
iii) Tube shunt placement
D. Secondary open-angle glaucoma
1. Acute, typically attributed to trabeculitis
a. Associated with infectious uveitis
i. Herpes simplex and zoster iridocyclitis
ii. Cytomegalovirus Iridocyclitis
iii. Fuchs heterochromic iridocyclitis
iv. Toxoplasma retinochoroiditis
v. Necrotizing herpetic retinitis
b. Responds to topical cycloplegics, corticosteroids, and treatment of infection
2. Chronic - inflammatory debris clogging the angle or direct damage to the trabecular meshwork
E. Corticosteroid-induced ocular hypertension and glaucoma
1. Common with more potent topical corticosteroids
a. Difluprednate > prednisolone acetate
2. Periocular, intravitreal steroids, and steroid implants
3. Less common with oral and nasal corticosteroids, but still needs monitoring
F. Combined-mechanism uveitic glaucoma
G. Management
1. Control intraocular inflammation
2. Treat trabeculitis (e.g. antiviral in the setting of viral anterior uveitis)
Uveitis 248 © AAO 2017-2019

3. Control IOP with topical and additional systemic therapy, if required
4. Prevent glaucomatous optic nerve damage
a. Gonioscopy to assess angle (should be repeated at least annually and whenever IOP elevates)
b. Optic nerve evaluation (disc photos and OCT nerve fiber layer)
c. Automated visual fields
5. Prostaglandin analogs do not generally exacerbate intraocular inflammation, especially when used
concomitantly with IMT and corticosteroids
6. May require surgical intervention to prevent vision loss and allow for treatment of uveitis, if unable to control
pressure medically
7. ALT and SLT generally contraindicated in the setting of uveitis (concern for exacerbating inflammation)
though they may be useful in situation of well controlled inflammation with steroid response OcHTN
IV. Hypotony
A. Decreased aqueous production
1. Acute inflammation of the ciliary body - resolves with treatment
a. Intensive corticosteroids
b. Cycloplegia
2. Chronic ciliary body damage with atrophic or absent ciliary processes
a. PPV in patients with ciliary processes on UBM or traction from cyclitic membranes
b. PPV with silicone oil requires reinjection in ~50% 1 year
3. Often associated with serous choroidal detachment
V. Cystoid macular edema
A. Common cause of visual loss in uveitis
B. Quantified by spectral-domain OCT
C. Fluorescein angiography identifies petaloid leakage in the macula
D. Severity of CME does not necessarily correspond to the level of inflammation; in fact, may persist despite
control of inflammation
E. Increased incidence in smokers, especially in intermediate and panuveitis
F. Treatment
1. Control of inflammation with corticosteroids and IMT
a. Periocular therapy
i. Superotemporal posterior sub-Tenon injection of 20-40 mg of triamcinolone acetonide

delivers corticosteroid closest to the macula
ii. Injections may be repeated
b. Intravitreal therapy
i. Preservative-free triamcinolone acetate or triamcinolone acetonide (Triesence)
ii. Preserved triamcinolone acetate (Kenalog) NOT approved for intravitreal injection
iii. Drug is eliminated more quickly from the vitreous cavity of vitrectomized eyes
iv. Maximum visual improvement and reduction of CME after intravitreal triamcinolone
injection occurs within 4 weeks
v. Intravitreal dexamethasone implant (Ozurdex)
i) Comparable to intravitreal triamcinolone in effect but
Uveitis 249 © AAO 2017-2019

(i) May last longer (3-6 months)
(ii) Less risk of IOP rise (better pharmacokinetics)
vi. The fluocinolone acetonide implant dramatically reduces uveitic CME but with high rate of
cataract formation and glaucoma
vii. Intravitreal bevacizumab effective in short term but repeat injections typically required
viii. Intravitreal methotrexate effective in short term
c. Topical ketorolac and nepafenac can be beneficial especially in pseudophakic CME
d. Oral acetazolamide variably effective in reducing uveitic CME; may have additional benefit with
concomitant ocular hypertension
e. Topical difluprednate for CME in phakic and pseudophakic patients
i. High intraocular penetrance
ii. Risk of IOP elevation
2. Surgical therapy for uveitic CME is still controversial, likely helpful where traction is a component of
condition (e.g. epiretinal membrane, vitreomacular traction)
VI. Vitreous opacification and vitritis
A. Common in Toxoplasma retinitis and pars planitis.
B. Visual acuity improved in majority of patients undergoing PPV
VII. Rhegmatogenous retinal detachment
A. 3% of patients with uveitis
1. Panuveitis and infectious uveitis are the entities most frequently associated with RRD (especially acute
retinal necrosis)
2. Pars planitis and posterior uveitis can also be associated with rhegmatogenous or tractional retinal
detachments
3. Worse prognosis than in non-uveitic eyes
VIII. Retinal neovascularization
A. Associated with chronic inflammation or capillary nonperfusion
1. Pars planitis
2. Sarcoid panuveitis
3. Behcet
4. Retinal vasculitis
B. Treatment is directed toward the underlying etiology.
1. Control inflammation
2. Scatter laser photocoagulation of areas with documented ischemia by fluorescein angiography
3. Intravitreal VEGF inhibitor in conjunction with control of inflammation
IX. Choroidal neovascularization (CNV)
A. More common in posterior uveitis, especially the white dot syndromes, and panuveitis
1. Ocular histoplasmosis syndrome
2. Punctate inner choroidopathy (PIC)
Uveitis 250 © AAO 2017-2019

3. Multifocal choroiditis
4. Serpiginous choroiditis
5. VKH syndrome
6. Birdshot uveitis
B. Treat inflammation and CNV
1. Ensure complete control of underlying inflammation (may reduce the incidence of new CNV lesions)
2. Focal laser photocoagulation of peripapillary, extrafoveal, and juxtafoveal CNV
3. Intravitreal bevacizumab or other anti-VEGF injections
4. Pars plana vitrectomy and subfoveal CNV extraction in selected cases
Uveitis 251 © AAO 2017-2019

PRACTICING OPHTHALMOLOGIST CURRICULUM , 2017-2019
UVEITIS
COPYRIGHT © 2017
AMERICAN ACADEMY OF OPHTHALMOLOGY
ALL RIGHTS RESERVED
Item No. 022036PD ISBN 978-1-61525-991-5

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Academy

Uveitis 2 © AAO 2017-2019

As a service to its members and American Board of Ophthalmology (ABO)

The Practicing Ophthalmologists Curriculum is intended to be the basis for MOC

THE AMERICAN ACADEMY OF OPHTHALMOLOGY DOES NOT WARRANT OR

Any questions or concerns related to the relevance and validity of questions on

Uveitis 3 © AAO 2017-2019

The Practicing Ophthalmologists Curriculum was developed by a group of dedicated

Jeffrey D. Henderer, M.D., American Academy of Ophthalmology Secretary for

The Academy gratefully acknowledges the contributions of the American Association

Practicing Ophthalmologists Curriculum Panel

not restrict expert scientific clinical or non-clinical presentation or publication,

Contributors who have disclosed financial relationships:

Contributors who state they have no significant financial relationships to

Uveitis 4 © AAO 2017-2019

Background on Maintenance of Certification (MOC)

Developed according to standards established by the American Board of Medical

 The mission of the American Board of Ophthalmology is to serve the public by

 The mission of the American Academy of Ophthalmology is to protect sight

Organization of the POC

Uveitis 5 © AAO 2017-2019

Creation of the POC

Uveitis 6 © AAO 2017-2019

2. Lab testing in uveitis ................................................................................................................ 14

3. Optical coherence tomography (OCT) - in uveitis ....................................................... 26

4. Posterior segment angiography: fluorescein angiography ...................................... 29

5. Posterior segment angiography: indocyanine green angiography (ICG) ........... 31

6. Conjunctival biopsy/pathology ........................................................................................... 33

7. Diagnostic vitreoretinal procedures in uveitis: vitreous biopsy .............................. 35

8. Diagnostic vitreoretinal procedures in uveitis: chorioretinal biopsy ..................... 37

9. Acute anterior uveitis .............................................................................................................. 40

10. Tubulointerstitial nephritis and uveitis (TINU) syndrome ........................................ 44

11. Lens-associated uveitis........................................................................................................... 47

12. Persistent (chronic) iridocyclitis ........................................................................................ 50

13. Juvenile idiopathic arthritis .................................................................................................. 54

14. Fuchs heterochromic iridocyclitis ..................................................................................... 59

15. Intermediate uveitis ................................................................................................................ 62

16. Acute posterior multifocal placoid pigment epitheliopathy ................................... 67

17. Birdshot uveitis ......................................................................................................................... 69

18. Multiple evanescent white dot syndrome (MEWDS) ................................................. 72

Uveitis 7 © AAO 2017-2019

20. Serpiginous choroidopathy ................................................................................................ 76

21. Systemic vasculitis - intraocular manifestations .......................................................... 80

22. Sarcoidosis panuveitis........................................................................................................... 86

23. Sympathetic ophthalmia ...................................................................................................... 90

24. Vogt-Koyanagi-Harada disease ........................................................................................ 93

25. Behçet disease ......................................................................................................................... 97

26. Scleritis........................................................................................................................................ 100

27. Herpetic anterior uveitis ....................................................................................................... 106

29. Cytomegalovirus retinitis ..................................................................................................... 114

31. Ocular histoplasmosis syndrome ....................................................................................... 122

32. Toxoplasmic retinochoroiditis ........................................................................................... 125

33. Toxocariasis posterior uveitis ............................................................................................ 131

34. Other infectious uveitis: cysticercosis ............................................................................ 134

35. Diffuse unilateral subacute neuroretinitis (DUSN) ..................................................... 136

36. Delayed-onset pseudophakic uveitis .............................................................................. 139

Uveitis 8 © AAO 2017-2019

38. Lyme disease ............................................................................................................................ 147

39. Leptospiral uveitis .................................................................................................................. 151

Practicing Ophthalmologists Curriculum Panel 