Uveitis

Essentials of Diagnosis

• Usually immunologic but possibly infective or neoplastic

• Inflammation may be confined to the eye or may be systemic

• Acute nongranulomatous anterior uveitis: pain, redness, photophobia, and visual loss

• Granulomatous anterior uveitis: blurred vision in a variably painful and inflamed eye

• Posterior uveitis: gradual loss of vision in a variably inflamed eye

General Considerations

• Intraocular inflammation (uveitis) is classified

  • By its clinical presentation: acute or chronic and nongranulomatous or granulomatous

  • By its distribution: anterior, intermediate, posterior, or panuveitis

• Most common types are

  • Acute nongranulomatous anterior uveitis

  • Granulomatous anterior uveitis

  • Posterior uveitis

Pathogenesis

• Systemic disorders associated with acute nongranulomatous anterior uveitis include

  • Ankylosing spondylitis

  • Reactive arthritis

  • Psoriasis

  • Ulcerative colitis

  • Crohn disease

• Chronic nongranulomatous anterior uveitis occurs in juvenile idiopathic arthritis

• Behçet syndrome produces

  • Anterior uveitis, with recurrent hypopyon but little discomfort

  • Posterior uveitis, characteristically with branch retinal vein occlusions

• Both herpes simplex and herpes zoster infections may cause nongranulomatous anterior uveitis as well as retinitis

• Diseases that produce granulomatous anterior uveitis also tend to be causes of posterior uveitis, including

  • Sarcoidosis

  • Toxoplasmosis

  • Tuberculosis

  • Syphilis

  • Vogt-Koyanagi-Harada disease

  • Sympathetic ophthalmia following penetrating ocular trauma

• In toxoplasmosis, there may be evidence of previous episodes of retinochoroiditis

• In HIV infection, other principal pathogens responsible for ocular inflammation are

  • Cytomegalovirus (CMV)

  • Herpes simplex and herpes zoster viruses

  • Mycobacteria

  • Cryptococcus

  • Toxoplasma

  • Candida

• Retinal vasculitis and intermediate uveitis

  • Predominantly manifest as posterior uveitis with central or peripheral retinal abnormalities in retinal vasculitis and far peripheral retinal abnormalities (pars planitis) in intermediate uveitis

  • Retinal vasculitis can be caused by a wide variety of infectious agents and noninfectious systemic conditions but also may be idiopathic

  • Intermediate uveitis is often idiopathic but can be due to multiple sclerosis or sarcoidosis

Symptoms and Signs

• Anterior uveitis

  • Characterized by inflammatory cells and flare within the aqueous humor

  • In severe cases, there may be hypopyon and fibrin within the anterior chamber

  • Cells may also be seen on the corneal endothelium as keratic precipitates (KPs)

• In granulomatous uveitis, the KPs are large, and iris nodules may be seen

• In nongranulomatous uveitis,

  • The KPs are smaller and iris nodules are not seen

  • The pupil is usually small, and with the development of posterior synechiae, it also becomes irregularly shaped and poorly reactive

• Nongranulomatous anterior uveitis tends to present acutely with unilateral pain, redness, photophobia, and visual loss

• However, the ocular inflammation associated with juvenile idiopathic arthritis is

  • Frequently indolent

  • Commonly asymptomatic initially

  • Carries a high risk of sight-threatening complications

• Granulomatous anterior uveitis is also frequently chronic, recurrent, and indolent, causing blurred vision in a variably inflamed eye

• Posterior uveitis

  • Tends to present with floaters and visual loss

  • Symptoms are commonly slower in onset, though acute presentations can occur

  • Bilateral involvement is common

  • Inflammatory lesions may be present in the retina or choroid

  • New retinal lesions are yellow, with indistinct margins, and with retinal hemorrhages

  • Older lesions have more defined margins and are commonly pigmented

  • Visual loss may be due to

    • Vitreous haze and opacities

    • Inflammatory lesions involving the macula

    • Macular edema

    • Retinal vein occlusion

    • Optic neuropathy (rarely)

Differential Diagnosis

• Retinal detachment

• Intraocular tumors

• Central nervous system lymphoma

• Primarily a clinical diagnosis, based on ophthalmologic examination

• However, various laboratory tests and imaging studies can help define the underlying diagnosis

  • Ankylosing spondylitis: Erythrocyte sedimentation rate (ESR), HLA-B27, sacroiliac joint radiographs

  • Behçet syndrome: Clinical diagnosis (though imaging of CNS lesions may be suggestive)

  • Candida infection: Dilated funduscopic examination, blood cultures

  • Crohn disease: Complete blood count (CBC), ESR, barium upper gastrointestinal series with small bowel follow-through or CT enterography or capsule (video) imaging of small intestine, colonoscopy with biopsy of intestine

  • Cryptococcus infection: Serum cryptococcal antigen; cerebrospinal fluid (CSF) for opening pressure, white blood count (WBC), glucose, protein, cryptococcal antigen, culture; blood culture; MRI or CT of head

  • CMV infection: CMV antibodies, polymerase chain reaction (PCR)

  • Herpes simplex virus infection: Viral culture and direct fluorescent antibody of vesicular skin lesions

  • Herpes zoster virus infection: Viral culture and direct fluorescent antibody of vesicular skin lesions

  • HIV infection: HIV-1 antibody ELISA, confirmed by Western blot, absolute CD4 lymphocyte count

  • Mycobacterium tuberculosis: Tuberculin skin test, cultures of sputum, pleural fluid, CSF

  • Psoriasis: Clinical diagnosis based on typical skin lesions, nail pitting or onycholysis

  • Reactive arthritis: Clinical diagnosis

  • Syphilis: Nontreponemal antigen tests (serum rapid plasma reagin [RPR] or Venereal Disease Research Laboratory [VDRL]), treponemal antibody tests (enzyme immunoassay [EIA] or chemiluminescence assay [CLIA]) and T pallidum hemagglutination ([TPHA], T pallidum particle agglutination [TPPA]), and treponemal antibody absorption [FTA-ABS] tests, PCR of genital ulcers, CSF for protein, WBC, VDRL

  • Toxoplasmosis: Isolation of T gondii or identification of tachyzoites in tissue or body fluids; PCR of aqueous humor, CSF, blood, other body fluids; serologic tests (including ELISA, indirect fluorescent test, agglutination test) for Toxoplasma antibodies; CT or MRI scan of head

  • Ulcerative colitis: CBC, ESR, serum albumin; sigmoidoscopy

Medications

• Anterior uveitis

  • Usually responds to topical corticosteroids

  • Periocular or intraocular corticosteroid injections or even systemic corticosteroids may be required

• Posterior uveitis

  • Requires systemic, periocular or intravitreal corticosteroids

  • In chronic cases, systemic corticosteroid-sparing immunomodulatory therapy with agents such as azathioprine, cyclosporine, mycophenolate, methotrexate, tacrolimus, or sirolimus is commonly required

  • Biologic therapies are often used

  • If an infectious cause is identified, specific antimicrobial therapy is often needed

Therapeutic Procedures

• Anterior uveitis

• Dilation of the pupil is important to relieve discomfort and prevent posterior synechiae

• Posterior uveitis

  • Pupillary dilation is not usually necessary

Prognosis

• In general, the prognosis of anterior uveitis, particularly the nongranulomatous type, is better than for posterior uveitis

When to Refer

• Any patient with suspected acute uveitis should be referred urgently to an ophthalmologist or emergently if visual loss or pain is severe

• Any patient with suspected chronic uveitis should be referred to an ophthalmologist, urgently if there is more than mild visual loss

When to Admit

• Patients with severe uveitis, particularly those requiring intravenous corticosteroid, immunosuppressive, or antimicrobial therapy, may require hospital admission