The Basics of Uveitis

The fundamental management of this painful condition involves careful patient evaluation and
aggressive control of inflammation.
By Walt Whitley, O.D., M.B.A., and John Sheppard, M.D., M.Msc.
Release Date: AUGUST 2011
Expiration Date: AUGUST 1, 2014
Goal Statement:
Uveitis is one of the leading causes of preventable blindness in developed countries, which makes it
crucial for practicing optometrists to understand how best to diagnose, differentiate and treat it. This
course helps optometrists to distinguish the different forms of uveitis by outlining the appearance
and symptoms of this painful condition. In addition, this course enumerates specific laboratory tests
to pinpoint the underlying causes of uveitis. In addition, this course describes the appropriate
treatment regimens for the different forms of uveitis.
Faculty/Editorial Board:
Walt Whitley, O.D., M.B.A., and John Sheppard, M.D., M.Msc.
Credit Statement:
-COPE approval for 2 hours of CE credit is pending for this course. Check with your local state
licensing board to see if this counts toward your CE requirement for relicensure. This course is
COPE approved for 2 hours of CE credit. COPE ID 32130-AS. Check with your local state
licensing board to see if this counts toward your CE requirement for relicensure.
Joint-Sponsorship Statement:
This continuing education course is joint-sponsored by the Pennsylvania College of Optometry.
Disclosure Statement:
The authors have no relationships to disclose.

Uveitic conditions are much more common than you may think. The prevalence of uveitis in
the general U.S. population is 38 per 100,000 persons, with the mean onset at 30.7 years of age.1
Roughly 5% to 10% of these cases occur in children under age 16.1
Uveitis was once considered a single disease entity; however, we now know that uveitis can be
caused by autoimmune disorders, infections, malignancy, exposure to toxins or may be idiopathic in
nature. Uveitis has more than 85 different causes, with approximately 50% due to idiopathic
conditions and 20% due to trauma, which leaves about 20% due to a systemic underlying cause,
such as rheumatoid arthritis or sarcoidosis, and 10% due to a localized ocular condition, such as
herpes zoster or toxoplasmosis.1
Although the prevalence of uveitis cases seen by general primary eye care practices varies,
anterior uveitis makes up 60% to 90% of those cases reported.1 The percentage of idiopathic
anterior uveitis, among all etiologies of anterior uveitis, ranges from 38% to more than 70%; this is,
by far, the most common form of anterior uveitis.2 Often, the presentation of acute anterior uveitis
is urgent. It is typically a very painful condition for the patient, and has the potential to be sight
threatening if not managed properly or promptly.

The sight-threatening complications of uveitis include glaucoma, damage to the retina and
macular edema. Uveitis is currently the third leading cause of preventable blindness in developed
countries, which makes it crucial for the practicing optometrist to understand how best to diagnose,
differentiate and treat it.3

This patient demonstrates signs of severe anterior uveitis: 3+ cells in the anterior chamber
and fibrin on anterior lens capsule.
Patient Evaluation
As in any medical examination, the key to targeted and efficient patient evaluation is a
thorough history, physical examination and review of systems. When patients present with a nonresolving, painful, red eye, our goal is to determine: What is the extent of the current condition.
What ocular structures are affected? What is the underlying cause? And, how can the condition best
be treated and managed? The following steps will help answer those questions:
Acute or chronic? The first step in classifying uveitic patients is determining whether the clinical
course of the disease is acute or chronic. Acute conditions typically have an abrupt onset lasting
several weeks, whereas chronic conditions can wax and wane over months to years. If left
untreated, an acute condition can develop into a chronic cellular response.
What structures are affected? The next step is identifying the anatomical location of the
inflammation or infection. According to the International Uveitis Study Group, the anatomical
classification of uveitis is anterior uveitis (primary site of inflammation is the anterior chamber),
intermediate uveitis (primary site of inflammation is the ciliary body and the vitreous), posterior
uveitis (primary site of inflammation is the retina and choroid) and panuveitis (primary site of
inflammation involving all anterior and posterior structures), with each presenting with different
patient complaints.4,5 Common signs and symptoms of anterior uveitis include redness,
photophobia and pain, whereas posterior uveitis presents with complaints of floaters and visual
disturbances. (Later in this article, we further discuss uveitis by anatomical classifications
anterior, intermediate and posterior.)

 Granulomatous or nongranulomatous? Ocular histopathology is another classification used to

differentiate the condition as granulomatous or nongranulomatous. Granulomatous inflammation
may present acutely, but more often than not it presents as a chronic condition with large, muttonfat keratic precipitates (KPs) and inflammatory cells (epitheloid cells and macrophages) in the
anterior chamber. This presentation is often associated with systemic conditions and autoimmune
reaction, or from the hosts immune response to a systemic infectious process, such as syphilis,
Lyme disease, tuberculosis or a local reactivation of herpetic viral infection. Autoimmune diseases
are less common in the very young or very old, so consider masqueraders in these patients.
Nongranulomatous inflammation usually involves the anterior segment of the eye and has an acute
onset accompanied by a cellular reaction in the anterior chamber that represents smaller cell types
(lymphocytes) than those in granulomatous inflammation.6 Most commonly, nongranulomatous
presentations are idiopathic or due to HLA-B27 involvement. Nongranulomatous uveitis occurs
more frequently than does granulomatous uveitis, especially in patients with anterior uveitis.
Unilateral or bilateral? Laterality can help classify the type of uveitis. Unilateral conditions are
more commonly acute and can be infectious, while bilateral conditions are likely due to chronic,
systemic conditions.
What are the symptoms and signs? Patients with uveitis typically present with abrupt, dull pain
and photosensitivity that worsens the patients discomfort. Additional signs and symptoms include
pain that may be referred to the temple or periorbital region, redness denser toward the limbus with
no mucopurulent discharge and blurring of vision. Patients rarely have a watery discharge or
tearing, but may experience mild epiphora from the pain response.
There are multiple clinical signs that are important for practitioners to look for to help with the
differential diagnosis. Patients may present with a decrease in vision ranging from mild to severe.
Circumlimbal injection of the conjunctiva is commonly seen along with the classic presentation of
cells and flare on the cornea and in the anterior chamber. (See Standardized Grading Scales for
Uveitis, below.) In chronic uveitis, corneal edema may be present. Evaluate the anterior chamber
for the amount of white blood cells, red blood cells (may be seen in traumatic conditions) or flare
(proteins) and grade them by severity. With significant inflammation, a hypopyon may be present,
which is highly suggestive of diseases associated with HLA-B27, Behets disease or, less
commonly, infectious uveitis.
Standardized Grading Scales for Uveitis
One of the difficulties in uveitis management is the inconsistency of grading scales used by
practitioners. In an effort to better organize the classification and grading of various uveitic
entities, the Standardization of Uveitis Nomenclature (SUN) Working Group developed a process
to standardize the approach to reporting clinical data in research to help all clinicians
improve consistency in grading.5
SUN Grading Scheme for Anterior Chamber Cells
Grade

Cells in Field

<1

0.5+

15

1+

6 15

2+

16 25

3+

26 50

4+
50+
(using 1mm slit beam)
SUN Grading Scheme for Anterior Chamber Flare
Grade

Description

None

1+

Faint

2+

Moderate (iris/lens details clear)

3+

Marked (iris/lens details hazy)

4+

Intense (fibrin/plastic aqueous)

Intraocular pressure should also be taken into account in the diagnosis. Low IOP is due to
decreased aqueous production in acute phases, and high IOP is found in viral conditions such as
herpes simplex virus (HSV) keratouveitis.
The iris also plays a role in the differential of uveitic conditions. Peripheral anterior synechiae or
posterior synechiae have the potential to lead to secondary glaucomatous conditions. Viral
conditions can be differentiated by iris atrophy; herpes simplex conditions cause diffuse atrophy
while herpes zoster more commonly causes sectoral atrophy. Fuchs uveitis syndrome, with its
characteristic heterochromia, can cause iris atrophy due to chronic lowgrade inflammation and loss
of iris stromal architecture.
Posterior subcapsular cataracts may develop with recurrent episodes due to chronic steroid
use. Although less commonly seen, posterior involvement may occur, which is mostly due to
infectious causes such as toxoplasmosis and cytomegalovirus that may present with vitritis, optic
neuritis, choroiditis, retinitis and macular edema.
Is there a systemic cause? Patients may present with signs of a cellular response with minimal
symptoms, which may suggest a chronic condition related to a systemic cause. Additionally,
whenever patients present with a recurrent, bilateral, chronic uveitis, the optometrist must
remember the importance of the review of systems. As we know, uveitis is a disorder of diverse
etiologies, including a wide spectrum of infectious and noninfectious causes. Epidemiological
studies of uveitis reveal that approximately 25% are due to systemic causes.3 (See Causes of
Uveitis, below)
Causes of Uveitis
(in no particular order)
Idiopathic
Traumatic
Autoimmune

Juvenile idiopathic arthritis

Ankylosing spondylitis
Ulcerative colitis

Crohns disease

Reiters syndrome

Lens induced
Infections

Syphilis

Tuberculosis

Herpes zoster

Herpes simplex

Adenovirus
Malignancy

Retinoblastoma

Leukemia

Lymphoma

Malignant melanoma
Posterior

Cytomegalovirus

Toxoplasmosis

AIDS

Herpes simplex

Herpes zoster

Candida
Asking patients about their medical history and other associated symptoms of their condition
provides invaluable clues to possible diagnoses, such as sarcoid for pulmonary symptoms,
ulcerative colitis for patients with GI symptoms, and systemic lupus for patients with
musculoskeletal symptoms. Any time a patient presents with minimal signs and symptoms, bilateral
presentation, a granulomatous response and a posterior extension of uveitis in the eye, be sure to
consider systemic causes.

Anterior Uveitis
Anterior uveitis (AU) is the presence of cell and flare in the anterior chamber, and may also
be referred to as iritis, iridocyclitis and anterior cyclitis.7 AU can be associated with other ocular
inflammatory conditions, including scleritis, episcleritis, keratitis, posterior segment disease,
postsurgical inflammation or it may be lens-related.
The largest number of anterior uveitis cases is idiopathic (or HLAB27 negative).1 The next
most common etiology is HLA-B27 positive. Be sure to perform a thorough case history and a
complete review of systems before diagnosing a patient as idiopathic.

Granulomatous inflammation may present acutely, but more often than not it presents as a
chronic condition with large, mutton-fat keratic precipitates (shown here) and inflammatory
cells (epitheloid cells and macrophages) in the anterior chamber.
An appropriate referral may have a significant impact on the patients general health if the
correct diagnosis of any underlying condition is the cause. For instance, autoimmune disease is
often associated with uveitis, predominantly those with the HLA-B27 gene. According to one study
of 514 patients with anterior uveitis, 7% had some autoimmune condition, and more than half of
those patients were diagnosed after a single episode of uveitis.1 Of these cases, ankylosing
spondylitis had the highest frequency of incidence.1
Other associated conditions commonly seen with anterior uveitic patients include juvenile
idiopathic arthritis (JIA, formerly juvenile rheumatoid arthritis or JRA), ulcerative colitis, Crohns
disease, Reiters syndrome, herpes simplex/zoster virus, syphilis and tuberculosis. It is imperative to
rule out these potentially lethal conditions because both infectious and noninfectious causes of
uveitis are responsible for 30,000 cases of legal blindness in the U.S. every year.8

Intermediate Uveitis
Intermediate uveitis is defined as intraocular inflammation that predominantly involves the
peripheral retina, pars plana and vitreous. Other terms used in the literature include chronic cyclitis,
peripheral uveitis and pars planitis. The term pars planitis is reserved to describe a subgroup of
patients with carefully evaluated idiopathic intermediate uveitis with snowbanking and/or snowball
formation.9 Traditionally, the proportion of patients with intermediate uveitis is estimated to be 4%
to 8% of uveitis cases in referral centers.9
Causes of intermediate uveitis include 69% of unknown etiology, 22% due to sarcoid, 1%
due to multiple sclerosis and Lyme disease.10 Helpful questions include asking patients about
difficulty in breathing or symptoms of eye pain, neurological symptoms consistent with multiple
sclerosis and any history of tick bites.

Posterior Uveitis
Posterior uveitis, as defined by the Standardization of Uveitis Nomenclature (SUN) Working
Group, is inflammation that is limited to the posterior segment of the eye; it is associated with the
highest risk of severe vision loss.5 The condition may be further characterized based on whether the
retina or the choroid is the predominant site of inflammation.
There are many systemic causes for posterior uveitis, which are more commonly due to infectious
processes. Ocular toxoplasmosis, for example, is the most common cause of posterior uveitis and
accounts for up to 90% of patients presenting with focal necrotizing retinitis. Noninfectious causes
may include immunologic or allergic origins, unknown causes and masquerade conditions (such as
neoplasm).8
Ocular diseases associated with posterior uveitis include sarcoidosis, toxoplasmosis, Eales
disease, frosted branch angitis, acute retinal necrosis, retinal arteritis and aneurysms, birdshot
choroiditis and pars planitis.
Unlike anterior and intermediate uveitis, ancillary testing, such as fluorescein angiography, optical
coherence tomography, B-scan ultrasonography and visual field testing, are useful. If a clinical
diagnosis cannot be determined from these tests, additional laboratory testing may be required.
Choose Appropriate Tests
Obtaining lab tests to better differentiate these diseases is now considered standard of care
for uveitis patients with the clinical suspicion of systemic conditions. Lab testing should be ordered
if the uveitis is bilateral, affects an atypical age group, or is recurrent, recalcitrant or hyperacute.
Additionally, patients with uveitis that worsens with tapering, is causing decreased visual acuity or
is seen in an immunocompromised patient should always be given lab tests. Patients with
significant systemic complaints should also receive directed initial screening tests or referral to the
appropriate specialist, such as a gastroenterologist, dermatologist, rheumatologist or pulmonologist.
For the first occurrence of an isolated acute anterior uveitic episode, no lab testing typically
is warranted because it can be very expensive and may give nonspecific information. Thereafter, it
becomes important to understand the most appropriate disease-specific labs for suspicious
presentations in order to target the pertinent clinical features and arrive at a tentative diagnosis.
Avoid ordering a standardized battery of tests in every patient with uveitis because this practice is
often useless, costly and confusing.
Minimal laboratory testing should include:

Complete blood cell (CBC) count

Urinalysis (psoriatic arthritis, proteins)

Lyme titers

HLA-B27 (ankylosing spondylitis and other seronegative spondylarthropathies)

Antinuclear antibody (ANA) test (juvenile idiopathic arthritis)

Angiotensin converting enzyme (ACE) test (sarcoidosis)

Venereal disease research laboratory (VDRL) test (syphilis)

Fluorescent treponemal antibody absorption (FTA-ABS) test (syphilis)

Chest X-ray should also be performed when testing for tuberculosis and sarcoidosis.

Lab Tests When You Suspect Systemic Disease

This table shows some common conditions related to uveitis, clinical features of the associated
condition, and what tests to order.1
Condition
Clinical Features
Tests Indicated
Ankylosing spondylitis
Young male, low back pain, chest pain
HLA-B27, sacroiliac X-ray
Reiters syndrome
Young male, arthritis, urethritis, conjunctivitis
HLA-B27, ESR, CRP
Juvenile idiopathic arthritis
Slight male predilection, sacroiliitis common
ANA, RF, knee radiograph
Inflammatory bowel disease
Ulcerative colitis, diarrhea, abdominal cramps
HLA-B27, GI referral for endoscopy
Sarcoidosis
African Americans, females, posterior segment inflammation including vasculitis, vitritis
ACE, chest X-ray or CT scan
Tuberculosis
Prolonged cough, fever, chills, night sweats, weight loss
PPD, chest X-ray
Syphilis
History of sexual contact with infected person, rash, fever, malaise, headache, joint pain
FTA-ABS, VDRL, RPR
Toxoplasmosis
Immunocompromised status, exposure to cats, history of eating raw meat, punched-out retinal
lesions (which may be seen with vitreous haze or headlight in the fog sign)
Toxoplasma IgG or IgM for acute
acquired cases
Birdshot retinochoroidopathy
Diffuse atrophic choroidal granulomata, optic atrophy, maculopathy
HLA-A29
Lyme disease
Recent tick bite
Lyme Western Blot
Wegeners granulomatosis
Sinus, pulmonary, kidney disease, scleritis
ANCA, sinus films, chest X-ray, serum

creatinine
Current Treatments for Uveitis
The goal of uveitis treatment and management is to alleviate the patients symptoms and
control inflammation. Additionally, the accurate treatment of inflammatory reactions preserves
vision as well as prevents systemic morbidity and mortality. Prior to initiating treatment, you must
rule out any infectious condition.
Topical steroids are the mainstay of treatment for the majority of uveitis conditions, but steroid
injections and oral steroids are often needed in cases of intermediate and posterior conditions.
Steroids should always be used aggressively to treat and suppress the inflammatory response, with
the initial dose ranging from q1h to q.i.d. (See Use Steroids Aggressively, below.)
Use Steroids Aggressively
One of the most common pitfalls in the management of uveitis is not using steroids
aggressively
enough. In order to be effective, steroids should be pulse-dosed frequently upon initial
presentation, with a gradual taper over several weeks depending on the response to treatment.
Steroids should not be tapered until there is a two-grade improvement in clinical signs
(e.g., 4+ cells to 2+ cells), and should not be stopped until there a complete resolution of all
cells, flare and macular edema.
Compliance with these drops is crucial for the resolution of uveitis, so emphasize its
importance to the patient. Additional instructions may be useful for patients, including how to instill
drops, specific dosage schedules and the importance of shaking bottles with steroid suspensions.
Steroid treatment should be continued even after the resolution of all cell and ocular inflammation.
A cold turkey discontinuation of topical or systemic steroid therapy is ill advised. Instead, be sure
the patient follows a tapering regimen after resolution to decrease the risk of any rebound effect.
Pred Forte (prednisolone acetate 1%, Allergan) has been the gold standard in uveitis treatment and
continues to be a very effective treatment today. (Be attentive to the frequent pharmacy practice of
substituting the generic 1% prednisolone acetate for Pred Forte ask the patient to show you the
bottle.)
One of the newer topical treatment options, Durezol (difluprednate 0.05%, Alcon), has been
very effective in prospective randomized trials in addressing the inflammation and pain associated
with both ocular surgery and uveitis.11 Current uveitis trials may establish an FDA indication for
uveitis, but currently it is an off-label use. Durezol is at least two times more potent than proprietary
prednisolone acetate 1%, explaining its significant success in treating intraocular inflammatory
reactions.11
Uveitis Pearls

Sufficient steroid therapy may induce

a readily treatable cataract, but insufficient

steroid therapy may potentiate permanent

irreversible cicatricial anatomical alterations.

Topical steroids can be withdrawn

if necessary while awaiting diagnostic
laboratory testing, but injectable steroids
cannot and thus should only be administered
to patients who clearly do not have
an untreated infectious condition, such as
syphilis, Lyme disease, toxoplasmosis or
tuberculosis.
Uveitis often presents with decreased
IOP due to diminished ciliary body aqueous
production. The exceptions are those
conditions that produce stellate keratic

precipitates and trabeculitis: Fuchs uveitis

syndrome, toxoplasmosis and herpetic
conditions, including herpes simplex, varicella
zoster and cytomegalovirus.

Whenever you prescribe steroids, always monitor for increased intraocular pressure and
cataract formation. As long as the pressure is continuously monitored and treated when indicated,
the benefits of steroid treatment outweighs the risks involved. In addition, topical steroids may
delay wound healing or epithelialization, reactivate latent herpes simplex infections and potentiate
bacterial, fungal or acanthamoebal infections. When considering IOP lowering agents, use caution
with prostaglandin analogues because they may exacerbate the inflammatory response.
Treatment Considerations
A growing number of practitioners now use Durezol as a firstline, off-label treatment for uveitis,
because the primary goal in treating uveitis is to reduce or eliminate the inflammation as quickly as
possible to avoid the dangerous and sight-threatening sequelae of inflammation. To alleviate some
concerns of long-term use of such a powerful steroid, consider using an ester-based steroid, such as
Lotemax (loteprednol 0.5%, Bausch + Lomb), for a long-term taper once the inflammation is
brought under control.
If you have a patient with diagnosed systemic disease, chronic uveitis is often well controlled with
immunomodulatory or antimetabolite systemic therapy. Be sure to stay in constant contact with a
rheumatologist in these cases. In rare instances, when a patient does not have a diagnosed systemic
disease and the chronic uveitis is difficult to manage, the patient may still benefit from systemic
antimetabolite therapy.
Although cataracts are well known complications of topical, injectable, implantable and systemic
steroids, modern cataract surgery is extremely safe and effective. Thus, a fully treatable cataract is
far preferable to permanent corneal scarring, peripheral anterior synechiae, trabecular cicatrization
with attenuated aqueous outflow, posterior synechiae, ciliary process fibrosis, vitreous opacification

and traction, permanent macular architectural changes or papillary fibrosis resulting from
inadequate steroid therapy.
Pain and photophobia are common symptoms in uveitis that can be treated effectively with
cycloplegics. Cycloplegics improve comfort by immobilizing the inflamed iris and ciliary body,
stabilizing the blood aqueous barrier to prevent the leakage of proteins, and breaking synechiae
formation. (Posterior synechiae affect the movement of aqueous into the anterior chamber, and can
lead to an iris bomb and possible secondary angle closure glaucoma when allowed to fuse
circumferentially.)
The most popular cycloplegics used are homatropine 5% b.i.d. (with a duration of action of about
eight hours), scopolamine 0.25% t.i.d. (with a duration of up to several days) and atropine 1%
(which may act up to a week). Cyclopentolate is not as effective for maximal cycloplegia, and
phenylephrine is a mydriatic with no cycloplegic effect. Make sure to inform the patient that the
course of mydriasis does not equal the length of analgesia. Just because the patient stays dilated for
a day or two that does not mean the pain will subside for that long.
Additional treatments for uveitis include sunglasses, topical or oral NSAIDs (for analgesia),
immunosuppressants, periocular steroid injections, intravitreal steroid injections, longand shortacting intravitreal steroid implants, intravitreal VEGF inhibitor injections and specific surgical
procedures when indicated. Cataract with IOL implantation, selective laser trabeculoplasty and
glaucoma drainage procedures are very common in advanced chronic or recurrent uveitis cases.
The majority of acute, anterior uveitis cases respond favorably to topical treatment within a few
weeks. For a case that does not respond to topical treatment or worsens with tapering, the next steps
are injectable or oral steroids and the consideration of lab testing. In our experience, sub-tenon
triamcinolone injection has been effective as adjunct therapy in recalcitrant, non-infectious cases.
This is preferred due to the less risk of systemic side effects due to steroids.
If the inflammation still doesnt improve, oral steroids are warranted. Other systemic treatment
options include methotrexate, cyclosporine or tumor necrosis factor (TNF) inhibitors, such as
Humira (adalimumab, Abbott), which should be comanaged with a primary care physician, internist
or rheumatologist.

Posterior synechiae (shown here) affect the movement of aqueous into the anterior chamber,
and
can
lead
to
an iris bomb and possible secondary angle closure glaucoma when allowed to fuse
circumferentially.
Further Uveitis Treatment
Several other treatment options for uveitis are available and more are in the drug pipeline.
Currently, intravitreal implants of dexamethasone (Ozurdex, Allergan) or fluconisone (Retisert,
Bausch + Lomb) are being used. Meanwhile, clinical trials are now evaluating the efficacy and
safety of TNF inhibitors, calcineurin inhibitors and alternative steroid delivery systems, such as
iontophoresis.
It is important to critically evaluate patients with anterior uveitis based on their clinical
presentation, to understand the appropriate laboratory and radiologic testing pertinent to each
unique case, and to be aggressive in treatment with both topical steroids and cycloplegia when
indicated.
Anterior uveitis is a very manageable condition, and when treated promptly and effectively,
it can be satisfying for you as the managing clinician and, more importantly, bring great relief to the
patient.
Dr. Whitley is the director of optometric services, and Dr. Sheppard is the president, at Virginia Eye
Consultants in Norfolk, Va.

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