Uveitis is defined as inflammation of the uveal tract, which is further subdivided into anterior and posterior components. The anterior tract is composed of the iris and ciliary body, while the posterior tract includes choroid. Hence, uveitis is inflammation of any of these components and may also include other surrounding tissues such as sclera, retina, and optic nerve.[1] Uveitis is often idiopathic but may be triggered by genetic, traumatic, immune, or infectious mechanisms.
View Image
Anatomy of the eye.
Signs and symptoms
Symptoms of uveitis depend on several variables, the most important of which are type (ie, anterior, posterior, intermediate) and duration of symptoms (ie, acute chronic).
Acute anterior uveitis presents as follows:[2]
Pain, generally developing over a few hours or days except in cases of trauma
Redness
Photophobia
Blurred vision
Increased lacrimation
Chronic anterior uveitis presents primarily as blurred vision and mild redness. Patients have little pain or photophobia except when having an acute episode.
Posterior uveitis presents as follows:[2]
Blurred vision and floaters
Absence of symptoms of anterior uveitis (ie, pain, redness, and photophobia)
The presence of symptoms of posterior uveitis and pain suggests one of the following:
Anterior chamber involvement
Bacterial endophthalmitis
Posterior scleritis
Intermediate uveitis presents as follows:[2]
Painless floaters and decreased vision (similar to posterior uveitis)
Minimal photophobia or external inflammation
Patients with panuveitis may present with any or all of the above symptoms.
Physical examination findings are as follows:
Lids, lashes, and lacrimal ducts are normal.
Conjunctival examination reveals 360° perilimbal injection, which increases in intensity as it approaches the limbus; this is the reverse of the pattern seen in conjunctivitis, in which the most severe inflammation occurs at a distance from the limbus.
Visual acuity may be decreased in the affected eye.
Extraocular movement is generally normal.
Pupillary examination may reveal direct photophobia when the light is directed into the affected eye, as well as consensual photophobia when light is directed into the uninvolved eye; consensual photophobia is typical of iritis, whereas photophobia due to more superficial causes, such as conjunctivitis, is direct but not consensual.
Pupillary miosis is common.
Slit-lamp examination
This is the most important aspect of the examination.
Examine the cornea via direct illumination with a broad beam at a 30°-40° angle between the viewing microscope and the light source.
Examine the epithelium for abrasions, edema, ulcers, or foreign bodies.
Inspect the stroma for deep ulcers and edema.
Keratitic precipitates (white blood cells) on the endothelium are a hallmark of iritis.
Ciliary flush, a violaceous ring around the cornea, is highly indicative of intraocular inflammation.[1]
Corneal edema and vitreous haze (large collection of inflammatory cells in the vitreous) may be observed.
Intraocular pressure may be normal or slightly decreased in the acute phase owing to decreased aqueous humor production; however, pressure may become elevated as the inflammation subsides.
Opacities of the lens (cataracts) may be present but are not specific for uveitis.
The most important structure to examine is the anterior chamber, as follows:
Examine the anterior chamber using a vertically and horizontally short beam.
Normally, the aqueous humor in the anterior chamber is optically clear.
In uveitis, an increase in the protein content of the aqueous causes an effect upon examination known as flare, which is similar to that produced by a moving projector beam in a dark smoky room.
White or red blood cells may be observed; layering of white blood cells in the anterior chamber is called hypopyon.
Grading of blood cells in the anterior chamber is as follows:
Laboratory studies are unlikely to be helpful in cases of mild, unilateral nongranulomatous uveitis in the following settings:
Trauma
Known systemic disease
History and physical not suggestive of systemic disease
A nonspecific workup is indicated if the history and the physical examination findings are unremarkable in the presence of uveitis that is bilateral, granulomatous, or recurrent.[2, 1] The following tests may be ordered by the consulting ophthalmologist, to be followed and further coordinated by the primary care physician:
Complete blood cell (CBC) count
Erythrocyte sedimentation rate (ESR)
Antinuclear antibody (ANA)
Rapid plasma reagin (RPR)
Venereal disease research laboratory (VDRL)
Purified protein derivative (PPD)
Lyme titer
HLA testing for ankylosing spondylarthroses
Chest radiography (to assess for sarcoidosis or tuberculosis)
Urinalysis (for red blood cells or casts)
Infectious workup (eg, HIV, toxoplasmosis), depending on the presentation
See Workup for more detail.
Management
Uveitis has no standard treatment regimen. Usually, the initial course of management is a stepwise approach starting with cycloplegics and corticosteroid drops to control pain and reduce inflammation. Progression to immunosuppressive agents may be necessary after consideration of the baseline etiology; however, this progression would be initiated by a primary care physician in consultation with an ophthalmologist after including physician and patient factors, which are beyond the scope of this review. Topical steroid eye drops and sustained-release steroid implants are the only FDA-approved medications; all other medications used are off-label use, with sparse and mostly equivocal supporting evidence for all treatment modalities.[3, 4, 5]
Considerations prior to initiating treatment include the following:
Supporting evidence is sparse
Check intraocular pressure and rule out herpes simplex virus (HSV) keratitis before starting topical corticosteroids
Initiate steroid treatment only in consultation with an ophthalmologist
Uveitis is defined as inflammation of the uveal tract, the anatomy of which includes the iris, ciliary body, and choroid. See the image below.
View Image
Anatomy of the eye.
The iris regulates the amount of light that enters the eye, the ciliary body produces aqueous humor and supports the lens, and the choroid provides oxygen and nourishment for the retina.
A classification scheme for uveitis exists based upon anatomic location.[6]
Table 1. Classification of Uveitis
View Table
See Table
Uveitis, particularly posterior uveitis, is a common cause of preventable blindness, so it is deemed a sight-threatening condition. Anterior uveitis is the form most likely to present to the emergency department. When the inflammation is limited to the iris, it is termed iritis. If the ciliary body is also involved, it is called iridocyclitis.
After anatomical classification, uveitis is further described by the following:[7]
Onset (sudden vs insidious)
Duration (limited, < 3 months in duration; persistent, >3 months in duration)
Course (acute, recurrent, or chronic)
Laterality (unilateral vs bilateral)
The distribution of general uveitis cases by anatomic site of disease has been found to differ significantly between community-based practice (anterior, 90.6%; intermediate, 1.4%; posterior 4.7%; panuveitis, 1.4%) and university referral practice (anterior, 60.6%; intermediate, 12.2%; posterior, 14.6%; panuveitis, 9.4%; P< 0.00005).[8]
The etiology of uveitis is often idiopathic,[7] However, genetic, traumatic, or infectious mechanisms are known to promote or trigger uveitis. Diseases that predispose a patient to uveitis and are likely to present to the emergency department include inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), sarcoidosis, tuberculosis, syphilis, and AIDS.
The mechanism for trauma is believed to be a combination of microbial contamination and accumulation of necrotic products at the site of injury, stimulating the body to mount an inflammatory response in the anterior segment of the eye.[7, 9]
For infectious etiologies of uveitis, it is postulated that the immune reaction directed against foreign molecules or antigens may injure the uveal tract vessels and cells.
When uveitis is found in association with autoimmune disorders, the mechanism may be a hypersensitivity reaction involving immune complex deposition within the uveal tract.
In one study at a tertiary referral center by Rodriguez et al,[10] the distribution in etiology among all anatomic forms of uveitis, anterior, intermediate, and posterior, were as follows:
Idiopathic (34%)
Seronegative spondyloarthropathies (10.4%)
Sarcoidosis (9.6%)
Juvenile rheumatoid arthritis (JRA) (5.6%)
SLE (4.8%)
Behçet disease (2.5%)
AIDS (2.4%)
Seronegative arthropathies include nonspecific, ankylosing spondylitis, Reiter syndrome, psoriatic arthropathy, and inflammatory bowel disease.
In the same Rodriguez et al study,[10] anterior uveitis was the most common form at 51.6%, and the etiologic distribution was as follows:
Idiopathic (37.8%)
Seronegative arthropathies (21.6%)
JRA (10.8%)
Herpes virus (9.7%)
Sarcoidosis (5.8%)
SLE (3.3%)
Rheumatoid arthritis (0.9%)
Posterior uveitis was next most common, with 19.4% of cases, the most common etiologies being Toxoplasma (24.6%), idiopathic (13.3%), cytomegalovirus (CMV) (11.6%), SLE (7.9%), and sarcoidosis (7.5%).
The approximate estimated annual incidence of uveitis in the United States ranges from 25-52 cases per 100,000 persons per year[3, 11, 12]
International
Finland has one of the highest annual incidences of uveitis, probably because of the high frequency of HLA-B27 spondyloarthropathy among the population.[3]
Race
Racial predisposition to uveitis is related to the patient's underlying systemic disease, as follows:[2]
No deaths due to iritis or uveitis have been reported.
Morbidity results from posterior synechiae formation (adhesions between the iris and the lens) that may lead to high intraocular pressure and subsequent optic nerve loss. Blindness may result from inadequate treatment. Complications of medications, specifically topical steroids, may include glaucoma, cataracts, and potential vision deterioration.[1, 13]
While most cases of uveitis are idiopathic, a history focused on identifying a potential underlying systemic cause (eg, in young adult men, conjunctivitis, urethritis, and polyarthritis suggest reactive arthritis) is necessary in order to determine if workup is needed.
Important elements of the medical history that should suggest uveitis as the cause of ocular pain include the following:
History of autoimmune disease such as inflammatory bowel disease, SLE, and sarcoidosis
Sexually transmitted diseases, particularly syphilis and chlamydia
Tuberculosis
AIDS
Anterior uveitis may have the following history findings:[2]
Acute - Pain, redness, photophobia, excessive tearing, and decreased vision; pain generally develops over a few hours or days except in cases of trauma
Chronic - Primarily blurred vision, mild redness; little pain or photophobia except during an acute episode
Posterior uveitis may have the following history findings:[2]
Blurred vision, floaters
Absence of symptoms of anterior uveitis (pain, redness, and photophobia)
Symptoms of posterior uveitis and pain suggest anterior chamber involvement, bacterial endophthalmitis, or posterior scleritis
Intermediate uveitis may have the following history findings:[2]
Similar to posterior uveitis; painless floaters and decreased vision
Minimal photophobia or external inflammation
Panuveitis may present with any or all these symptoms.
Evaluate vital signs and check visual acuity and extraocular movement. Perform a funduscopic examination and measure intraocular pressure. Most importantly, perform a slit-lamp examination.
Findings of the examination of the lids, lashes, and lacrimal ducts are normal.
The conjunctival examination reveals 360° perilimbal injection, which increases in intensity as it approaches the limbus. Differentiate this condition from conjunctivitis, in which the pattern is reversed, with the most severe inflammation at a distance from the limbus.
Visual acuity may be decreased in the affected eye.
Extraocular movement is generally normal.
On the pupillary examination, the patient may experience direct photophobia when the light is directed into the affected eye, as well as consensual photophobia when light is directed into the uninvolved eye. Consensual photophobia is helpful in distinguishing between iritis and more superficial causes of photophobia, such as conjunctivitis. In the latter, direct, but not consensual, photophobia is noted. Pupillary miosis is common.
Slit-lamp examination is performed as follows:
Examine the cornea by direct illumination with a broad beam at a 30°-40° angle between the viewing microscope and the light source.
Examine the epithelium for abrasions, edema, ulcers, or foreign bodies.
Inspect the stroma for deep ulcers and edema.
Scan the endothelium for keratitic precipitates (white blood cells on the endothelium), a hallmark of iritis (see the image below). Small to medium keratitic precipitates are classified as nongranulomatous, whereas granulomatous keratitic precipitates are large and have a greasy or "mutton-fat" granular appearance.
The most important structure to examine is the anterior chamber, which is bound by the cornea and the iris and is filled with aqueous humor. Examine the anterior chamber using a vertically and horizontally short beam. Normally, the aqueous humor is optically clear. In uveitis, however, an increase in the protein content of the aqueous causes an effect upon examination known as flare, which is similar to that produced by a moving projector beam in a dark smoky room.
White blood cells that layer in the anterior chamber are called hypopyon.
Opacities of the lens (cataracts) may be present but are not specific for uveitis.
Intraocular pressure may be normal or slightly decreased in the acute phase owing to decreased aqueous humor production; however, pressure may become elevated as the inflammation subsides. See the image below.
View Image
Small stellate keratic precipitates with fine filaments in a patient with Fuchs heterochromic iridocyclitis.
Although uveitis is often associated with an underlying systemic disease, approximately 50% of patients have idiopathic uveitis that is not associated with any other clinical syndrome.
Acute nongranulomatous uveitis is associated with diseases related to human leukocyte antigen B27 (HLA B27), including ankylosing spondylitis, inflammatory bowel disease, reactive arthritis, psoriatic arthritis, and Behçet disease. Herpes simplex, herpes zoster,[14] Lyme disease, and trauma also are associated with acute nongranulomatous uveitis.
Chronic nongranulomatous uveitis is associated with juvenile rheumatoid arthritis, chronic iridocyclitis of children, and Fuchs heterochromic iridocyclitis.
Chronic granulomatous uveitis is observed with sarcoidosis, syphilis, and tuberculosis.
Posterior uveitis is found in such diseases as toxoplasmosis, ocular histoplasmosis, syphilis, sarcoidosis, and in immunocompromised hosts with CMV or candidal or herpetic infection. Embolic retinitis also may cause posterior uveitis.
An acute rise in intraocular pressure secondary to pupillary block (posterior synechiae), inflammation or topical corticosteroid use is the single most important complication.
Examine all patients presenting with a red eye with a slit lamp to detect the presence of cells or flare.
Consider all other causes of a red eye[22] before uveitis is diagnosed.
An acute rise in intraocular pressure can lead to optic nerve atrophy and permanent vision loss.
The workup should be tailored to the patient according to the history or to the signs and symptoms that point to a certain etiology.
Laboratory workup may not be necessary in certain situations.[2] In cases of mild, unilateral nongranulomatous uveitis in the setting of trauma, known systemic disease, or a history and physical not suggestive of systemic disease, laboratory studies are unlikely to be helpful.
If the history and the physical examination findings are unremarkable in the presence of bilateral uveitis, granulomatous uveitis, or recurrent uveitis, a nonspecific workup is indicated.
The following tests do not need to be conducted in the emergency department and may be ordered by the consulting ophthalmologist[2] as outpatient workup.
The main goals in the emergency department are to correctly diagnose uveitis, to provide analgesia, and to refer the patient to an ophthalmologist[15] for possible initiation of topical steroids.
Although the patient's eye is erythematous and cells are present in the anterior chamber, antibiotics are not indicated.
Follow-up care with an ophthalmologist within 24 hours is imperative.
In the acute phase, cases of uveitis are monitored every 1-7 days with slit-lamp examination and intraocular pressure measurements.
The ophthalmologist tapers steroids and cycloplegics.[19]
When the condition is stable, patients are monitored every 1-6 months.
Two sustained-release corticosteroid vitreous implants, (fluocinolone acetonide [Retisert, Yutiq] and dexamethasone [Ozurdex]), have been approved by the FDA for the treatment of inflammation-induced cases of panuveitis, intermediate uveitis, and posterior uveitis.[1] These implants preclude risks associated with systemic steroids and reduce the need for immunosuppressive agents while providing continuous therapy (approximately 30-36 months).[20, 21] The installation and monitoring of these treatment modalities should be managed by an ophthalmologist.
The goals of pharmacotherapy are to reduce pain and inflammation with cycloplegics and corticosteroids. Corticosteroid eye drops have been the standard of care for uveitis since the early 1950s. Although evidence to support their use is somewhat sparse,[3, 4] they are the only medications approved by the FDA to treat uveitis. Corticosteroids should be initiated only in conjunction with an ophthalmologist because uveitis is a diagnosis of exclusion, and adverse effects of steroids include increased intraocular pressure, cataract formation, steroid-induced glaucoma,[1] and an increased risk of herpes keratitis, which should be managed by a specialist.
Studies comparing nonsteroidal anti-inflammatory drug (NSAID) eye drops to placebo and corticosteroids have not demonstrated benefit; their use as an alternative to corticosteroids is not supported by evidence.[3]
Potassium-sparing drugs are indicated when chronic steroid use is required to control inflammation.[1] Approximately half of patients with uveitis need more than corticosteroid treatment to prevent vision loss.[16]
Clinical Context:
Induces cycloplegia in 25-75 min and mydriasis in 30-60 min. Effects last as long as 1 d; however, duration may be less in setting of severe anterior chamber reaction. For this reason, Cyclogyl less attractive for treating uveitis than homatropine.
Clinical Context:
Induces cycloplegia in 30-90 min and mydriasis in 10-30 min. Effects last 10-48 h for cycloplegia and 6 h to 4 d for mydriasis, but duration may be less in setting of severe anterior chamber reaction. Homatropine is agent of choice for uveitis.
Clinical Context:
Strongest steroid of its group and best choice for uveitis. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Clinical Context:
The implants are surgically inserted by the ophthalmologist and indicated for chronic, noninfectious uveitis of posterior segment of eye. Retisert releases 0.6 mcg/day initially; amount released decreases after the first month to 0.3-0.4 mcg/day over ~30 months. Yutiq releases at a rate of 0.25 mcg/day over ~36 months.
Clinical Context:
The implant is surgically inserted by the ophthalmologist and indicated for chronic, noninfectious uveitis of posterior segment of eye.
Clinical Context:
Infliximab is a chimeric IgG1κ monoclonal antibody that binds specifically to the soluble and transmembrane forms of TNF-α and inhibits the binding of TNF-α to its receptors.
Clinical Context:
Adalimumab is a recombinant human IgG1 monoclonal antibody that is specific for human TNF. It reduces inflammation and inhibits progression of structural damage.
The American Uveitis Society has released expert panel recommendations on the use of tumor necrosis factor alpha (TNF-α) inhibitors in ocular inflammatory disorders, which is a widely studied but off-label application for these biologic agents.[17, 18]
These recommendations include the following considerations:
Use of infliximab or adalimumab early in the treatment of patients with vision-threatening ocular manifestations of Behçet disease.
Use of infliximab or adalimumab as second-line therapy in children with vision-threatening uveitis secondary to juvenile idiopathic arthritis for whom methotrexate therapy is ineffective or not tolerated. Methotrexate, if tolerated, can be combined with infliximab.
Use of infliximab and possibly adalimumab can be used as second-line treatment for patients with vision-threatening chronic uveitis caused by seronegative spondyloarthropathy.
Use of infliximab or adalimumab for vision-threatening corticosteroid-dependent disease in patients for whom first-line therapy has failed.
Use of infliximab or adalimumab before etanercept in treatment of ocular inflammatory disease, or switching of patients using etanercept to either infliximab or adalimumab.
What is uveitis?Which factors determine the symptoms of uveitis?What are the signs and symptoms of acute anterior uveitis?What are the signs and symptoms of chronic anterior uveitis?What are the signs and symptoms of posterior uveitis?What are the signs and symptoms of intermediate uveitis?Which physical exam findings are characteristic of uveitis?How is a slit-lamp exam for uveitis performed and what are the characteristic results?Which findings on exam of the anterior chamber are characteristic of uveitis?How are blood cells in the anterior chamber graded in uveitis?When are lab studies unhelpful in the diagnosis of uveitis?Which lab studies may be performed in the diagnosis of uveitis?What is the approach to treatment for uveitis?What are considerations prior to initiating steroid treatment for uveitis?What is the definition of uveitis?What is the severity of uveitis?How is uveitis described following anatomical classification?What is the distribution of general uveitis by anatomic site?What causes uveitis?What is the role of trauma in the pathophysiology of uveitis?What is the role of infection in the pathophysiology of uveitis?What is the role of autoimmune mechanisms in the pathophysiology of uveitis?What is the distribution in etiology for uveitis?What is the etiologic distribution of anterior uveitis?What is the etiologic distribution of posterior uveitis?What is the incidence of uveitis in the US?What is the global incidence of uveitis?What is the racial predilection of uveitis?How does the prevalence of uveitis vary by sex?What are the age-related predilections of uveitis?What is the morbidity associated with uveitis?What is the prognosis of iritis and uveitis?Where can patient education resources for uveitis be found?What is the focus of history in uveitis?Which elements of the medical history suggest uveitis as the cause of ocular pain?What are the signs and symptoms of anterior uveitis?What are the signs and symptoms of posterior uveitis?What are the signs and symptoms of intermediate uveitis and panuveitis?Which physical findings suggest uveitis?How is a slit-lamp exam performed for uveitis?What are the findings of intraocular pressure characteristic of uveitis?What causes uveitis?What is the cause of acute nongranulomatous uveitis?What causes chronic nongranulomatous uveitis?What causes chronic granulomatous uveitis?What causes posterior uveitis?What are potential complications of uveitis?What are the differential diagnoses for Iritis and Uveitis?How should the workup for uveitis be approached?What is the role of lab studies in the workup of uveitis?Which lab studies may be indicated for the workup for uveitis?What is the role of chest radiography in the evaluation of uveitis?What is included in emergency department (ED) care of uveitis?Which specialist consultations are recommended for the treatment of uveitis?What is included in follow-up care for uveitis?What is the role of drug treatment for uveitis?Which medications in the drug class Corticosteroid Ophthalmic Implants are used in the treatment of Iritis and Uveitis?Which medications in the drug class Corticosteroids, Ophthalmic are used in the treatment of Iritis and Uveitis?Which medications in the drug class Anticholinergic Agents, Ophthalmic are used in the treatment of Iritis and Uveitis?Which medications in the drug class Tumor Necrosis Factor Blockers are used in the treatment of Iritis and Uveitis?
Monalisa N Muchatuta , MD, MS, Resident Physician, Clinical Assistant Instructor, Department of Emergency Medicine, Kings County Hospital, State University of New York Downstate Medical Center
Disclosure: Nothing to disclose.
Coauthor(s)
Richard H Sinert, DO, Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Vice-Chair in Charge of Research, Department of Emergency Medicine, Kings County Hospital Center
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Pfizer Pharmaceutical<br/>Received research grant from: National Institutes Health.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Chief Editor
Gil Z Shlamovitz, MD, FACEP, Associate Professor of Clinical Emergency Medicine, Keck School of Medicine of the University of Southern California; Chief Medical Information Officer, Keck Medicine of USC
Disclosure: Nothing to disclose.
Additional Contributors
Eric M Kardon, MD, FACEP, Attending Emergency Physician, Georgia Emergency Medicine Specialists; Physician, Division of Emergency Medicine, Athens Regional Medical Center
Disclosure: Nothing to disclose.
Keith Tsang, MD, Resident Physician, Clinical Assistant Instructor, Department of Emergency Medicine, State University of New York Downstate, Kings County Hospital
Disclosure: Nothing to disclose.
Robert E O'Connor, MD, MPH, Professor and Chair, Department of Emergency Medicine, University of Virginia Health System
Disclosure: Nothing to disclose.
Acknowledgements
The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Kilbourn Gordon III, MD, to the development and writing of this article.
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