Uveitis is inflammation of the uveal tract—the iris, ciliary body, and choroid. Most cases are idiopathic, but identifiable causes include various infections and systemic diseases, many of which are autoimmune. Symptoms include decreased vision, ocular ache, redness, photophobia, and floaters. Although intraocular inflammation is identified clinically, identifying the cause of the inflammation typically requires testing. Treatment depends on cause but typically includes topical, locally injected, or systemic corticosteroids with a topical cycloplegic-mydriatic drug. Noncorticosteroid immunosuppressive drugs may be used in severe and refractory cases. Infectious causes require antimicrobial therapy.
Inflammation of the uvea (uveitis) may occur with or without vitreitis, retinitis, papillitis, or optic neuritis. Uveitis is classified anatomically as anterior, intermediate, or posterior uveitis or panuveitis.
Anterior uveitis is localized primarily to the anterior segment of the eye and includes iritis (inflammation in the anterior chamber alone) and iridocyclitis (inflammation in the anterior chamber and anterior vitreous).
Intermediate uveitis (peripheral uveitis or chronic cyclitis) occurs in the vitreous.
Posterior uveitis refers to any form of retinitis, choroiditis, or inflammation of the optic disk.
Panuveitis (also called diffuse uveitis) implies inflammation in both the anterior and posterior chambers.
Most cases are idiopathic and presumed to be autoimmune in origin. Identifiable causes include
The most common cause of anterior uveitis is trauma (traumatic iridocyclitis). Other causes are spondyloarthropathies (20 to 25%), juvenile idiopathic arthritis, and herpesvirus (herpes simplex and varicella-zoster) infection. Half of all cases of anterior uveitis are idiopathic.
Most intermediate uveitis is idiopathic. Uncommon identifiable causes include multiple sclerosis, sarcoidosis, TB, syphilis, and, in endemic regions, Lyme disease.
Most posterior uveitis (retinitis) is idiopathic. The most commonly recognized cause of posterior uveitis in immunocompetent patients is toxoplasmosis; the most commonly recognized cause in patients with HIV/AIDS is cytomegalovirus (CMV).
The most commonly identified cause of panuveitis is sarcoidosis, but most cases remain idiopathic despite appropriate testing.
Infrequently, systemic drugs cause uveitis (usually anterior). Examples are sulfonamides, pamidronate (an inhibitor of bone resorption), rifabutin, and cidofovir.
Systemic diseases causing uveitis and their treatment are discussed elsewhere in The Manual.
Symptoms and Signs
Symptoms and signs may be subtle and vary depending on the site and severity of inflammation.
Anterior uveitis tends to be the most symptomatic, usually manifesting with pain (ocular ache), redness, photophobia, and, to a variable degree, decreased vision. Signs include hyperemia of the conjunctiva adjacent to the cornea (ciliary flush or limbal injection). Slit-lamp findings include cells and flare (a haze) in the anterior chamber (aqueous humor), keratic precipitates (WBC clumps on the inner corneal surface), and posterior synechiae. With severe anterior uveitis, WBCs may layer in the anterior chamber (hypopyon).
Intermediate uveitis is typically painless and manifests with floaters and decreased vision. The primary sign is cells in the vitreous humor. Aggregates and condensations of inflammatory cells often occur over the pars plana (near the junction of the iris and sclera), forming snowballs. Vision may be decreased because of floaters or cystoid macular edema, which results from fluid leakage from blood vessels in the macula. Confluent and condensed vitreous cells and snowballs over the pars plana may cause a classic snowbank appearance, which can be associated with neovascularization of the retinal periphery.
Posterior uveitis may give rise to diverse symptoms but most commonly causes floaters and decreased vision as occurs in intermediate uveitis. Signs include cells in the vitreous humor; white or yellow-white lesions in the retina (retinitis), underlying choroid (choroiditis), or both; exudative retinal detachments; retinal vasculitis; and optic disk edema.
Panuveitis may cause any combination of the previously mentioned symptoms and signs.
Consequences: Consequences of uveitis include profound and irreversible vision loss, especially when uveitis is unrecognized, inadequately treated, or both. The most frequent complications include cataract; glaucoma; retinal detachment; neovascularization of the retina, optic nerve, or iris; and cystoid macular edema (the most common cause of decreased vision in patients with uveitis).
Uveitis should be suspected in any patient who has ocular ache, redness, photophobia, floaters, or decreased vision. Patients with anterior uveitis have ocular ache in the affected eye if light is shined in the unaffected eye (true photophobia), which is uncommon in conjunctivitis. Diagnosis of anterior uveitis is by recognizing cells and flare in the anterior chamber. Cells and flare are seen with a slit lamp and are most evident when using a narrow, intensely bright light focused on the anterior chamber in a dark room. Findings of intermediate and posterior uveitis are most easily seen after dilating the pupil (see Approach to the Ophthalmologic Patient: Ophthalmoscopy). Indirect ophthalmoscopy (usually done by an ophthalmologist) is more sensitive than direct ophthalmoscopy. (Note: If uveitis is suspected, patients should be referred immediately for complete ophthalmologic evaluation.)
Many conditions that cause intraocular inflammation can mimic uveitis and should be considered in the appropriate clinical settings. Such conditions include intraocular cancers in the very young (typically retinoblastoma and leukemia) and in the elderly (intraocular lymphoma). Less commonly, retinitis pigmentosa (see Retinal Disorders: Retinitis Pigmentosa) can manifest with mild inflammation, which may be confused with uveitis.
Treatment of active inflammation usually involves corticosteroids given topically or by periocular or intraocular injection along with a cycloplegic-mydriatic drug (eg, homatropine 2% or 5% drops bid to qid depending on severity). Antimicrobial drugs are used to treat infectious uveitis. Particularly severe or chronic cases may require systemic corticosteroids, systemic noncorticosteroid immunosuppressive drugs, laser phototherapy, cryotherapy applied transsclerally to the retinal periphery, or surgical removal of the vitreous (vitrectomy).
Uveitis Caused by Connective Tissue Disease
A number of connective tissue diseases cause inflammation of the uveal tract.
The seronegative spondyloarthropathies (see Joint Disorders: Seronegative Spondyloarthropathies) are a common cause of anterior uveitis. RA, in contrast, is not associated with uveitis. Ocular inflammation is most common with ankylosing spondylitis but also occurs with reactive arthritis, inflammatory bowel disease (ulcerative colitis and Crohn's disease), and psoriatic arthritis. Uveitis is classically unilateral, but recurrences are common and active inflammation may alternate between eyes. Men are affected more commonly than women. Most patients, regardless of sex, are HLA-B27 positive.
Treatment requires a topical corticosteroid and a cycloplegic-mydriatic drug. Occasionally, periocular corticosteroids are required.
Juvenile idiopathic arthritis (JIA, also known as juvenile RA)
JIA characteristically causes chronic bilateral iridocyclitis in children, particularly those with the pauciarticular variety (see Joint Disorders: Juvenile Idiopathic Arthritis (JIA)). Unlike most forms of anterior uveitis, however, JIA tends not to cause pain, photophobia, and conjunctival injection but only blurring and meiosis and is, therefore, often referred to as white iritis. JIA-associated uveitis is more common among girls.
Recurrent bouts of inflammation are best treated with a topical corticosteroid and a cycloplegic-mydriatic drug. Long-term control often requires use of a noncorticosteroid immunosuppressive drug (eg, methotrexate, mycophenolate mofetil).
Sarcoidosis (see also Sarcoidosis) accounts for 10 to 20% of cases of uveitis, and about 25% of patients with sarcoidosis develop uveitis. Sarcoid uveitis is more common among blacks and the elderly.
Virtually any symptoms and signs of anterior, intermediate, posterior, or panuveitis can occur. Suggestive findings include conjunctival granulomas, large keratic precipitates on the corneal endothelium (so-called granulomatous or mutton fat precipitates), iris granulomas, and retinal vasculitis. Biopsy of suggestive lesions, which provides the most secure diagnosis, is usually done on the conjunctiva; it is rarely done on intraocular tissues because of the risk associated with the procedure.
Treatment usually involves topical, periocular, intraocular, or systemic corticosteroids, or a combination, along with a topical cycloplegic-mydriatic drug. Patients with moderate to severe inflammation may require a noncorticosteroid immunosuppressive drug (eg, methotrexate, mycophenolate mofetil, azathioprine).
This condition is rare in North America but is a fairly common cause of uveitis in the Middle East and Far East (see also Vasculitis: Behçet's Syndrome).
Typical findings include severe anterior uveitis with hypopyon, retinal vasculitis, and optic disk inflammation. The clinical course is usually severe with multiple recurrences.
Diagnosis requires the presence of associated systemic manifestations, such as oral aphthous or genital ulcers; dermatitis, including erythema nodosum; thrombophlebitis; or epididymitis. Oral aphthae may be biopsied to show an occlusive vasculitis. There are no laboratory tests for Behçet's syndrome.
Treatment with local and systemic corticosteroids and a cycloplegic-mydriatic drug may alleviate acute exacerbations, but most patients eventually require systemic corticosteroids and a noncorticosteroid immunosuppressive drug (eg, cyclosporine, chlorambucil) to control the inflammation and avoid the serious complications of long-term corticosteroid treatment. Biologic agents such as interferons and tumor necrosis factor inhibitors have been effective in selected patients unresponsive to other therapies.
Vogt-Koyanagi-Harada (VKH) syndrome
VKH syndrome is an uncommon systemic disorder characterized by uveitis accompanied by cutaneous and neurologic abnormalities. VKH syndrome is particularly common among people of Asian, Asian Indian, and American Indian descent. Women in their 20s and 30s are affected more often than men. The etiology is unknown, although an autoimmune reaction directed against melanin-containing cells in the uveal tract, skin, inner ear, and meninges is strongly suspected.
Neurologic symptoms tend to occur early and include tinnitus, dysacusis (auditory agnosia), vertigo, headache, and meningismus. Cutaneous findings frequently occur later and include patchy vitiligo (especially common on the eyelids, low back, and buttocks), poliosis (a localized patch of white hair), and alopecia, often involving the head and neck. Common findings include serous retinal detachment, optic disk edema, and choroiditis. Long-term complications include cataracts, glaucoma, subretinal fibrosis, and choroidal neovascularization.
Early treatment includes local and systemic corticosteroids and a cycloplegic-mydriatic drug. Many patients also require a noncorticosteroid immunosuppressive drug (eg, methotrexate, azathioprine, mycophenolate mofetil).
Endophthalmitis is an acute panuveitis resulting most often from bacterial infection.
Most cases of endophthalmitis are caused by gram-positive bacteria, such as Staphylococcus epidermidis or S. aureus. Gram-negative organisms can also cause endophthalmitis, tend to be more virulent, and predict a poorer prognosis. Fungal and protozoan causes of endophthalmitis are rare. Most cases occur after penetrating ocular trauma or intraocular surgery (exogenous). Less commonly, infection reaches the eye via the bloodstream after systemic surgery or dental procedures or when IV lines or IV drugs are used (endogenous).
Endophthalmitis is a medical emergency because vision prognosis is directly related to the time from onset to treatment. Rarely, untreated intraocular infections extend beyond the confines of the eye to involve the orbit and CNS.
Exogenous endophthalmitis typically causes severe ocular ache and decreased vision. Signs include intense conjunctival hyperemia and intraocular inflammation within the anterior chamber and vitreous, occasionally with eyelid edema.
Diagnosis requires a high index of suspicion in at-risk patients, especially those with recent eye surgery or trauma. Gram stain and culture of aspirates from the anterior chamber and vitreous are standard. Patients with suspected endogenous endophthalmitis should also have blood and urine cultures.
Initial treatment includes broad-spectrum intravitreal antibiotics, most commonly vancomycin and ceftazidime. Patients with endogenous endophthalmitis should receive both intravitreal and IV antibiotics. Therapy is modified based on culture and sensitivity results.
Vision prognosis is often poor, even with early and appropriate treatment. Patients with count-fingers or worse vision at presentation should be considered for vitrectomy and use of intraocular corticosteroids. Corticosteroids are, however, contraindicated in fungal endophthalmitis.
A number of infectious diseases cause uveitis (see Table 1: Uveitis and Related Disorders: Infectious Causes of Uveitis). The most common are herpes simplex virus, varicella-zoster virus, and CMV infection and toxoplasmosis. Different organisms affect different parts of the uveal tract.
|Infectious Causes of Uveitis
Viruses or Infections
Herpes simplex virus
*Particularly in patients with AIDS.
Herpes simplex virus (see also Herpesviruses: Herpes Simplex Virus (HSV) Infections) causes anterior uveitis. Varicella-zoster virus does so less commonly, although the prevalence of zoster-associated anterior uveitis increases with age. Symptoms include ocular ache, photophobia, and decreased vision. Signs include redness; conjunctival injection and anterior chamber inflammation (cells and flare), often accompanied by corneal inflammation (keratitis); decreased corneal sensation; and patchy or sectorial iris atrophy. Intraocular pressure may be elevated as well; elevation can be detected by using applination tonometry with a Schiotz tonometer, a Goldmann tonometer, or a pneumotonometer.
Treatment should generally be initiated by an ophthalmologist and should include a topical corticosteroid and a cycloplegic-mydriatic drug. Acyclovir (400 mg po 5 times/day for herpes simplex virus and 800 mg po 5 times/day for herpes zoster virus) may also be given. Drops to lower intraocular pressure may be required in patients with ocular hypertension.
Much less commonly, varicella-zoster and herpes simplex viruses cause a rapidly progressing form of retinitis called acute retinal necrosis (ARN), which typically manifests as confluent retinitis, occlusive retinal vasculitis, and moderate to severe vitreous inflammation. One third of ARN cases become bilateral, and in three fourths of eyes, retinal detachment occurs. ARN may also occur in patients with HIV/AIDS, but severely immunocompromised patients can have less prominent vitreous inflammation. Vitreous biopsy for culture and PCR analysis may be useful in diagnosing ARN. Treatment options include IV acyclovir, IV ganciclovir or foscarnet, intravitreal ganciclovir or foscarnet, and oral valacyclovir or valganciclovir.
Toxoplasmosis (see also Extraintestinal Protozoa: Toxoplasmosis) is the most common cause of retinitis in immunocompetent patients. Most cases are transmitted congenitally, although acquired cases occur. Symptoms of floaters and decreased vision may be due to cells in the vitreous humor or to retinal lesions or scars. Concurrent anterior segment involvement can occur and may cause ocular ache, redness, and photophobia. Laboratory testing should include serum anti-Toxoplasma antibody titers.
Treatment is recommended for patients with posterior lesions that threaten vital visual structures, such as the optic disk or macula, and for immunocompromised patients. Multidrug therapy is commonly prescribed; it includes pyrimethamine, sulfonamides, clindamycin, and, in select cases, systemic corticosteroids. Corticosteroids should not, however, be used without concurrent antimicrobial coverage. Long-acting periocular and intraocular corticosteroids (eg, triamcinolone acetonide) should be avoided. Patients with small peripheral lesions that do not directly threaten vital visual structures may be observed without treatment and should begin to show slow improvement in 1 to 2 mo.
CMV (see also Herpesviruses: Cytomegalovirus (CMV) Infection) is the most common cause of retinitis in immunocompromised patients, affecting ≤ 5% of patients with HIV/AIDS receiving highly active antiretroviral therapy (HAART). Most affected patients have a CD4+ count < 100 cells/μL. CMV retinitis may also occur in neonates and in pharmacologically immunosuppressed patients but is uncommon.
The diagnosis is largely clinical based on direct or indirect ophthalmoscopic examination; serologic tests are of limited use. Treatment in patients with HIV/AIDS is with systemic or local (implant) ganciclovir, systemic foscarnet, or valganciclovir. Therapy is typically continued indefinitely, unless immune reconstitution is achieved with combination antiretroviral therapy (typically a CD4+ count > 100 cells/μL for at least 3 mo).
Last full review/revision July 2008 by Emmett T. Cunningham, Jr., MD, PhD, MPH