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Symptoms ⬇

Signs ⬆ ⬇

Critical

Keratic Precipitates (KP)

Hypopyon

Other

Low intraocular pressure (IOP) (more common, secondary to ciliary body hyposecretion), elevated IOP (e.g., herpetic, lens induced, FHIC, Posner–Schlossman syndrome), fibrin (e.g., HLA-B27, endophthalmitis), iris nodules (e.g., sarcoidosis, syphilis, TB), iris atrophy (e.g., herpetic, fourth-generation fluoroquinolones), iris heterochromia (e.g., FHIC), iris synechiae (especially HLA-B27, sarcoidosis), band keratopathy (especially JIA in younger patients, any chronic uveitis in older patients), uveitis in a “quiet eye” (consider JIA, FHIC, and masquerade syndromes), and CME (see Figure 12.1.1).

Figure 12.1.1: Anterior uveitis with posterior synechiae.

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Diagnostic Categories

Etiology ⬆ ⬇

NOTE

Patients with Behçet disease have a primarily cellular AC reaction and rarely have fibrin, thus the hypopyon may appear mobile (“shifting”) in contrast to other more fibrin forward inflammatory syndromes like HLA-B27–associated uveitis.

NOTE

Bilateral acute recurrent alternating anterior uveitis is very characteristic of HLA-B27 uveitis.

Workup ⬆ ⬇

  1. Obtain a thorough history and review of systems.

  2. Complete ocular examination, including an IOP check, gonioscopy, and a dilated fundus examination. The vitreous and fundus should be evaluated for signs of intermediate and posterior uveitis.

    NOTE

    Patients with anterior uveitis should ALWAYS have an initial complete dilated fundus examination to assess for vitreous and posterior segment involvement.

  3. A diagnostic workup may be unnecessary in the setting of a first episode of a mild, unilateral, nongranulomatous uveitis with a history and examination that are not suggestive of associated systemic disease.

  4. In most other situations, a targeted workup is recommended. If too many tests are ordered unnecessarily, a portion of them may come back falsely positive and shroud the diagnosis. See Table 12.1.3. However, if a patient presents with bilateral, granulomatous, or recurrent anterior uveitis the patient should be evaluated for sarcoidosis, syphilis, TB (in at-risk patients), and additional workup should be focused based on history and examination.

    • Treponemal test (syphilis enzyme immunoassay [EIA], fluorescent treponemal antibody absorption [FTA-ABS], Treponema pallidum particle agglutination [TP-PA]), followed by confirmatory nontreponemal test (rapid plasma reagin [RPR], venereal disease research laboratory [VDRL]). See 12.10, Syphilis.

    • Interferon gamma releasing assay (IGRA, QuantiFERON Gold) and/or purified protein derivative (PPD). Consider chest imaging (e.g., chest x-ray [CXR] or computed tomography [CT] chest) to assess for signs of active or prior pulmonary disease.

      • Isolated anterior uveitis is an uncommon manifestation of tubercular uveitis. Limit use of testing to patients: 

        • At risk of TB (e.g., immigrants from high-risk areas such as India, human immunodeficiency virus [HIV]-positive patients), homeless patients, or prisoners.

        • If considering immunosuppressive therapy (especially biologics).

    • Serologic testing for antibodies against HSV, VZV, CMV, and toxoplasmosis can be useful in ruling out a disease as the causative etiology (IgG and/or IgM negative). The presence of positive IgG titer is not necessarily indicative of active disease, but rather prior exposure. Very elevated IgG titers may make you more suspicious for active disease, and a positive IgM indicates recent infection, but again are not fully diagnostic. Negative testing helps to rule out the disease.

    • AC paracentesis for polymerase chain reaction (PCR) testing for suspected herpes virus–associated anterior uveitis (HSV, VZV, and CMV).

    • Angiotensin-converting enzyme (ACE), lysozyme, and chest imaging (CXR or CT chest).

    • HLA-B27 antigen typing (in acute unilateral or bilateral alternating anterior uveitis; especially if hypopyon is present; ask about symptoms of spondyloarthropathy, psoriasis, and reactive arthritis).

    • HLA-B51 testing is neither sensitive nor specific and has minimal clinical utility. Behçet disease is a clinical diagnosis.

    • Urinary beta-2 microglobulin, urinalysis, and renal function testing are useful in making a diagnosis of TINU.

    TABLE 12.1.3: Suggested Diagnostic Workup for Anterior Uveitis

    Suspected EtiologySuggested Workup
    Ankylosing spondylitisHLA-B27, SI joint films, rheumatology consult
    HSV/VZV/CMVAC tap to detect HSV/VZV/CMV DNA via PCR; consider HSV serologies, VZV serologies, and CMV serum PCR testing.
    Juvenile idiopathic arthritisRheumatoid factor, antinuclear antibodies, HLA-B27, radiographs of affected joints, urinalysis, and renal function testing; pediatric rheumatology consult
    Ocular ischemic syndromeIntravenous fluorescein angiography, carotid Doppler studies
    Psoriatic arthritisHLA-B27; rheumatology and/or dermatology consult
    Reactive arthritisHLA-B27, SI joint films (if symptomatic); referral for gastrointestinal or genitourinary inciting infection (campylobacter, chlamydia, salmonella, shigella).
    SarcoidosisCXR and/or CT chest, PPD or IGRA, ACE, lysozyme
    SyphilisRPR or VDRL, treponemal test (FTA-ABS, TPPA, EIA) followed by nontreponemal test (RPR, VDRL); FTA-ABS or treponemal-specific assay; HIV testing if positive
    TINUUrine beta-2 microglobulin, urinalysis, renal function testing; nephrology consultation
NOTE

Autoimmune diseases are less common in the elderly—consider masquerades.

Treatment ⬆ ⬇

  1. Cycloplegic (e.g., cyclopentolate 1% b.i.d. to help prevent posterior synechiae formation; cyclopentolate 1% t.i.d. or atropine 1% b.i.d. to help break early formed posterior synechiae).

  2. Topical steroid (e.g., prednisolone acetate 1%) q1–6h, depending on the severity of inflammation. Most cases of moderate to severe acute uveitis require q1–2h dosing initially. Difluprednate 0.05% may allow less frequent dosing than prednisolone acetate. Consider a loading dose (prednisolone acetate 1% one  drop every minute for 5 minutes at bedtime and awakening) or fluorometholone 0.1% ophthalmic ointment at night.

  3. If the uveitis is severe and is incompletely responsive to topical steroids, consider a course of oral steroids (after ruling out infectious etiologies).

  4. If the disease becomes persistent (lasting >3 months) or is frequently recurrent (≥3 episodes per year) consider consultation with a rheumatologist or uveitis specialist for possible steroid-sparing immunosuppressive therapy.

  5. Treat secondary glaucoma with aqueous suppressants. Avoid pilocarpine. Glaucoma may result from:

    • Cellular blockage of the trabecular meshwork. See 9.7, Uveitic Glaucoma.

    • Secondary angle closure from synechiae formation. See 9.4, Acute Angle Closure Attack and 9.5, Chronic Angle Closure Glaucoma.

    • Neovascularization of the iris and angle. See 9.13, Neovascular Glaucoma.

    • Steroid response. See 9.8, Steroid-Response Glaucoma.

    • Although topical prostaglandins may rarely cause uveitis and CME, they can be tried if other medical management is ineffective before considering glaucoma surgery.

  6. If an exact etiology for the anterior uveitis is determined, then additional ocular and/or systemic management may be indicated.

    • Behçet disease: Typically requires systemic immunosuppression. Antitumor necrosis factor (TNF) medications and azathioprine are considered first-line agents.

    • HLA-B27–associated uveitis.

      • Ankylosing spondylitis: Often requires systemic anti-inflammatory agents (e.g., NSAIDs such as naproxen). Consider consulting rheumatology, physical therapy, and cardiology (increased incidence of cardiomegaly, conduction defects, and aortic insufficiency).

      • IBD: Often benefits from systemic steroids, sulfadiazine, or other immunosuppressive agents. Obtain a medical or gastrointestinal consult.

      • Psoriatic arthritis: Consider a rheumatology and/or dermatology consult.

    • Reactive arthritis: If urethritis is present, then the patient and sexual partners are treated for chlamydia (e.g., doxycycline 100 mg b.i.d. for 7 days or alternatively a single-dose azithromycin 1 g p.o.). Obtain medical and/or rheumatology or urology consult.

    • FHIC: Usually does not respond to nor require steroids (a trial of steroids may be attempted, but they should be tapered quickly if there is no response); cycloplegics are not necessary.

    • Posner–Schlossman syndrome: See 9.7, Uveitic Glaucoma.

    • Herpetic uveitis: Herpetic iridocyclitis benefits from topical steroids and systemic antiviral medications; topical antivirals are usually ineffective for uveitis due to poor intraocular penetration. See 4.15, Herpes Simplex Virus and 4.16, Herpes Zoster Ophthalmicus/Varicella Zoster Virus.

    • JIA-associated uveitis: Topical steroids can be useful acutely for reducing cells and flare, but should be minimized for long-term therapy to reduce the risk of cataract and glaucoma, both of which are more common in children. Systemic steroid therapy in children may cause growth suppression and should be avoided if possible. Prolonged cycloplegic therapy may be required and necessitate appropriate refractive correction. Consultation with rheumatology, pediatrics, and/or a uveitis specialist is useful as immunomodulatory therapy (e.g., methotrexate, adalimumab) is often needed. Regular follow-up is essential, as flares may be asymptomatic; recurrent or chronic disease can lead to irreversible damage and various sequelae including synechiae, glaucoma (or hypotony), CME, ERM, and cataract formation.

    • Phacoantigenic glaucoma: Usually requires removal of the lens material. See 9.11, Lens-Related Glaucoma.

    • Sarcoidosis: Refer patients to an internist or pulmonologist for systemic evaluation and medical management which may include systemic steroids and immunosuppressives. Consider early referral to a uveitis specialist in complicated cases. A poor visual outcome has been reported with posterior uveitis, glaucoma, delay in definitive treatment, or presence of macula-threatening conditions such as CME. 

    • Syphilis: See 12.10, Syphilis.

    • Traumatic iritis: See 3.6, Traumatic Iritis.

    • TINU: Low-dose topical steroids are often enough to suppress mild, chronic anterior segment inflammation. If there is renal involvement, consultation with a nephrologist is necessary to consider systemic immunosuppression to prevent kidney damage.

    • TB: Refer the patient to an internist, infectious disease specialist, or public health officer for consideration of systemic treatment. Patients with ocular TB frequently have no pulmonary disease but still require systemic four-drug antituberculous therapy. Concomitant oral steroids or steroid-sparing immunosuppression may be necessary.

    • UGH syndrome: See 9.15, Postoperative Glaucoma.

Follow-Up ⬆

  1. Every 1 to 7 days in the acute phase, depending on the severity; every 1 to 3 months when stable.

  2. At each visit, the AC reaction and IOP should be evaluated.

  3. A vitreous and fundus examination should be performed with all flare-ups, decreased vision, or every 3 to 6 months. Macular edema is a frequent cause of decreased vision even after the uveitis is controlled; OCT of the macula can be very useful.

  4. If the AC reaction has resolved, then the steroid drops can be slowly tapered with intermittent examinations to ensure that the inflammation does not recur during the taper (usually by one drop per day every 7 to 14 days [e.g., q.i.d. for 1 week, then t.i.d. for 1 week, then b.i.d. for 1 week, etc.]). Steroids are usually discontinued following the taper when the AC is quiet. Occasionally, long-term, low-dose steroids (q.o.d. to b.i.d.) are required to keep the inflammation from recurring. Punctal occlusion techniques may increase the potency of the drug and decrease systemic absorption. The cycloplegic agents can be discontinued after the AC reaction has resolved.

NOTE

Topical steroids should be tapered slowly to prevent severe rebound inflammation. If oral steroids are used, consider concurrent calcium 600 mg with vitamin D 400 units twice a day to reduce the risk of osteoporosis. In patients with very severe disease, note that doses of prednisone >60 mg/d increase the risk of ischemic necrosis of bone, and a 3-day course of intravenous methylprednisolone 1 g/d for 3 days should be considered instead. Regular monitoring of glucose, blood pressure, lipids, and bone density should be done by a primary care doctor or rheumatologist if long-term oral steroid therapy is necessary.