Uveitis is characterized by inflammation of one or all parts of the uveal tract (iris, ciliary body, choroids). The most common form is anterior uveitis (iritis, iridocyclitis); posterior uveitis (choroiditis, chorioretinitis) is uncommon and found mostly in persons with AIDS who have cytomegalovirus (CMV) infection. Uveitis occurs in acute (<6 weeks) and chronic forms. The cause is often unknown but may result from either ocular trauma (e.g., chemical exposure) or an underlying systemic disease; the latter accounts for 40% of all cases (see section entitled Etiology for more details). Rate of incidence in both the U.S. and worldwide is 8 to 15 cases per 100,000. Uveitis occurs in men and women of all ages, with most patients presenting between 20 and 50 years of age; peak incidence is during the third decade of life.

• Infection, including viral, bacterial, spirochetal, parasitic, and fungal infections (e.g., syphilis, tuberculosis, CMV, Lyme disease, histoplasmosis); toxoplasmosis is common cause of congenital posterior uveitis
• Masquerade syndromes (syndromes that simulate uveitis) include leukemia, lymphoma, retinitis pigmentosa, retinoblastoma, and malignant melanoma of the choroid
• Systemic disease, including suspected immune-mediated disorders (e.g., Behcet's and Crohn's disease, juvenile rheumatoid arthritis, multiple sclerosis, Reiter's syndrome, sarcoidosis); HLA-B27 genotype on chromosome 6 is present in some patients with acute anterior uveitis associated with ankylosing spondylitis, Reiter's syndrome, inflammatory bowel disease, psoriatic arthritis, and recurrent anterior uveitis
• Ocular trauma
• Idiopathic and/or confined to the eye, as in the case of acute retinal necrosis, birdshot choroidopathy, multifocal choroiditis, pars planitis, and Fuchs' heterochromic iridocyclitis
• Some drugs may cause uveitis; rifabutin, for example, has been identified in at least 113 cases by the FDA. Other drugs associated with uveitis include cidofovir, pamidronic acid, and sulfonamides.

Forms of uveitis are geographically endemic (e.g., histoplasmosis in Ohio and Mississippi Valleys and Lyme disease in the northeastern, north central, and western U.S.). Uveitis due to toxoplasmosis is sometimes associated with pets. General risk factors include the following:

• History of autoimmune disease
• Infections
• Other eye diseases

• Painful eye(s)
• Conjunctival redness
• Photophobia
• Blurred or decreased vision
• Tearing
• Redness
• Floaters (posterior)

• Corneal abrasion or ulceration
• Ulcerative or ultraviolet keratitis
• Glaucoma
• Scleritis
• Conjunctivitis

Complete history and physical exam are required to identify possible underlying systemic disease. Signs of systemic disease include joint deformities (arthritis), oral or genital lesions (Reiter's and Behcet's syndromes), low back pain (ankylosing spondylitis), breathing problems (sarcoidosis), rash, and nail pitting (psoriasis). An ophthalmologic examination may reveal the following:

Anterior:

• Pupil contraction
• Inflammatory cells visible via slit-lamp examination
• Keratic precipitates on posterior corneal surfaces

Posterior:

• Inflammatory cells
• Fuzzy white retinal lesions
• Retinal and/or choroid inflammation (may be localized, diffuse, or multifocal)

Laboratory tests should be tailored toward specific signs and symptoms when an underlying etiology is suspected.

• Angiotensin-converting enzyme (sarcoidosis)
• Antinuclear antibody testing (autoimmune diseases)
• Complete blood count (bacterial or viral etiology)
• Enzyme-linked immunosorbent assay (Lyme disease)
• Erythrocyte sedimentation rate (systemic disease)
• Human leukocyte antigen-B27 (HLA-B27)
• Syphilis serology; RPR and VDRL may also be associated with granulomatous uveitis; FTA-ABS and microhemagglutination assay for antibodies to Treponema pallidum are more specific for syphilis
• Purified-protein derivative skin test (tuberculosis)
• Skin test for anergy

Although specific pathophysiology is unknown, the most common cause is an immune reaction against foreign molecules or antigens, which may also cause direct injury to uveal vessels and cells. In the case of autoimmune disorders, immune complexes may deposit in the uveal tract. Findings may include the following:

• Inflammation of ocular structures
• Small, white (not mutton-fat) keratic precipitates without iris nodules (nongranulomatous anterior uveitis)
• Large mutton-fat keratic precipitates and iris nodules (granulomatous anterior uveitis)

• Chest X ray (tuberculosis and sarcoidosis)
• Joint X rays (juvenile rheumatoid arthritis and ankylosing spondylitis)
• Fluorescein angiography (may reveal late hyperfluorescence associated with cystoid macular edema)

• Slit-lamp examination helps confirm diagnosis by revealing leukocytes and increased protein (flare) in aqueous humor
• Gonioscopy determines the presence of progressive peripheral anterior synechia 
• Tonometry measured intraocular pressure

Prompt treatment is required to preserve vision. Conventional practitioners recommend warm compresses to help relieve symptoms; naturopathic doctors may recommend the addition of herbs, such as eyebright, goldenseal, or marigold (Calendula officinalis) to the water used to make the compress. Sunglasses can protect for light sensitivity. In posterior uveitis, the goals are to determine and treat the systemic cause of the inflammation.

• Corticosteroids (topical or systemic) (e.g., prednisone, 0.125% to 1%; fluorometholone; 0.1% to 0.25%) to reduce inflammation and pain, stabilize cell membranes, inhibit release of lysozyme by granulocytes, and suppress lymphocyte circulation; oral prednisone or intraocular injections may be used in recalcitrant cases; contraindicated in patients with viral, fungal, and tubercular infections; can lead to increased intraocular pressure; posterior subcapsular cataracts associated with chronic topical use
• Cyclopegics (e.g., cyclopentolate, 0.5% to 2%; homatropine, 2% to 5%) block neurotransmission to the ciliary muscle, reduce pain, prevent adhesion of the iris to anterior lens capsule, stabilize blood-aqueous barrier, and help prevent continued protein leakage (flare); contraindicated in patients with narrow-angle glaucoma; toxic anticholinergic side effects are rare and occur most often in children; side effects include loss of accommodation (difficulty reading closeup)
• Antimicrobials
• Anti-inflammatories
• Oral immunosuppressants require close monitoring of side effects
• Humanized anti-Tac monoclonal antibody (daclizumab; approved now for immunosuppression in the case of kidney transplantation)—phase I/II clinical trial conducted by the National Eye Institute (NEI) of the NIH suggests that this treatment, given IV one time per month, controlled uveitis as effectively as standard treatment with a marked decrease in side effects for the small group of patients studied; the next phase of research for daclizumab is to test the treatment on patients with Behcet's disease followed by a large, multicenter trial

Surgery is used to repair ocular damage, such as glaucoma, cataracts, or detached retina.

CAM therapies may be beneficial in reducing the severity of systemic diseases whose sequelae include uveitis. Reducing free radical damage with herbs and nutrients may prevent or slow the progression of uveitis.

Flavonoids are highly concentrated in the eye. They inhibit neutrophil respiratory burst and superoxide production, both of which can create free radical damage in ocular tissues. In one study, the flavonoid, quercetin, decreased intraocular inflammation, reduced hemorrhagic changes, and minimized choroidal thickening in rats with S-antigen-induced uveoretinitis (Romero et al. 1989). High concentrations of flavonoids are found in red grapes, blueberries, cherries, and onions. Quercetin, 200-400 mg tid with meals, may also be taken as a supplement, often with bromelain to enhance function. Carotenoids are also thought to have antioxidant activity, particularly in the eye. Orange, yellow, and dark green vegetables contain a lot of dietary carotenoids. Supplement forms include mixed natural carotenoids (50,000 IU/day) and the carotenoid lutein (5 mg/day); the latter is considered to have a particular affinity for the eyes. Food to avoid that may be pro-inflammatory include saturated fats, fried foods, dairy products, and refined foods; anti-inflammatory foods include flaxseed, fatty fish, and other forms of essential fatty acids.

A randomized, double-blind, placebo-controlled trial evaluated the effects of vitamins C (1,000 mg/day) and E (200 IU/day) in patients with a first or recurrent episode of acute anterior uveitis. A total of 130 patients completed the study. Patients were evaluated for changes in anterior segment inflammation, measured by a laser cell flare meter. Clinical assessments included best-corrected visual acuity (VA), scores on the Hogan-Kimura scale for uveitis, and the number of drops of prednisolone and mydriatic administered (van Rooij et al. 1999).

Upon completion of the study, no significant differences in laser flare and cell measurements were detected between the vitamin and placebo groups, possibly because all patients were also treated with steroids. However, average visual acuity was better on all points in the vitamin group as compared to the placebo group. The investigators suggest that oral vitamins C and E protect photoreceptors from free radical damage and, in this manner, help preserve visual acuity. In addition, vitamin E may play a role in protecting against cystoid macular edema. CME can lead to loss of visual acuity in uveitis patients (van Rooij et al. 1999).

Curcumin, the primary active substance in turmeric, has been reported to have anti-inflammatory effects including inhibition of prostaglandin synthesis and stabilization of lysosomal membranes. Specific application for uveitis is not definitive but results of a recent preliminary study are intriguing. In a three-year study following 32 patients with chronic anterior uveitis, researchers report that curcumin (Curcuma longa) showed effects comparable to those of corticosteroid therapy but had none of the adverse effects associated with steroid use. Patients received curcumin, along with topical mydriatics and warm compresses for spasm and pain relief. Antitubercular drugs were added to the regimen if the person had a strongly positive PPD (Purified Protein Derivative, a substance used to measure reactivity to tuberculosis). Curcumin 375 mg po tid was administered to patients for 12 weeks. Antitubercular therapy was continued for one year. Although patients in both groups had recurrences of anterior uveitis (55% in those receiving curcumin alone and 36% in those with the addition of anti-TB drugs), each group showed noticeable improvement. In addition, according to the authors, the rates of both recurrence and complications secondary to the uveitis for all 32 patients on curcumin, with or without anti-TB medications, were similar to these figures for patients taking corticosteroids to treat uveitis. Finally, none of the participants complained of side effects from the curcumin (i.e., any side effects experienced were in the anti-TB drug group and were attributable to those medications) (Lal et al. 1999).

Similar to particular foods (see Nutrition section), herbs with concentrated amounts of flavonoids, such as ginkgo (Ginkgo biloba) and bilberry (Vaccinium myrtillus), have a long tradition of use in treating diseases of the eye. However, their use in the treatment of uveitis specifically has not yet been validated by scientific studies (Blumenthal et al. 2000).

Homeopathic treatment can address both constitutional and acute aspects of disease in general. In homeopathic terminology, the constitutional state reflects a pattern of underlying vulnerability or weakness that is unique to the individual and persists throughout that person's life. Symptoms tend to alternate over time and treatment consists of selecting the appropriate remedy specific for the patient's constitutional type. By contrast, in acute conditions a remedy can be administered without reference to any particular constitutional state (Ullman 1995). Although there are no known scientific studies evaluating the utility of specific homeopathic remedies for treating uveitis, acute homeopathic remedies may be beneficial in providing symptomatic relief.

Acupuncture has been shown to be effective in the treatment of other ocular diseases (see Macular Degeneration monograph, for example) but has not been fully assessed in the treatment of uveitis.

N/A

Slit-lamp and intraocular pressure measurements every 1 to 7 days in acute phase, with follow up every 1 to 6 months.

There are no known preventive measures for uveitis. However, regular eye exams can screen for chronic asymptomatic uveitis. Treatment of causative disorders may help prevent onset.

• Glaucoma
• Cataracts due to neovascularization
• Permanent partial vision loss
• Retinal detachment
• Band keratopathy
• Cystoid macular edema
• Macula scarring impairs central vision

• Prognosis is good with early diagnosis and treatment; anterior uveitis tends to respond to treatment in days to weeks
• Outcome may be dependent on underlying condition
• Chronic uveitis (defined as presence of inflammation >6 weeks) may require long-term low-dose topical steroid use and can lead to ocular scarring and vision loss

Safety of topical steroid use in pregnant women has not been established.

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No author listed. Drug-induced uveitis can usually be easily managed. Drugs Ther Perspect. 1998;11(10):11-14.

Nussenblatt RB, Fortin E, Schiffman R, et al. Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: a phase I/II clinical trial. Proc Natl Acad Sci USA 1999;96(13):7462-7466.

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van Rooij J, Schwartzenberg SG, Mulder PG, Baarsma SG. Oral vitamins C and E as additional treatment in patients with acute anterior uveitis: a randomised double masked study in 145 patients. Br J Ophthalmol. 1999;83(11):1277-1282.