What is the diagnostic approach for a patient with suspected uveitis?

Diagnostic Approach to Uveitis

The diagnosis of uveitis requires slit-lamp biomicroscopy by an ophthalmologist to identify anterior chamber inflammation, combined with targeted laboratory testing guided by clinical presentation rather than indiscriminate screening. 1, 2

Initial Clinical Assessment

Key Presenting Features to Identify

The classical presentation includes eye pain, blurred vision, photophobia, and eye redness, though chronic forms may be insidious with minimal symptoms. 1 Critical warning signs requiring urgent ophthalmologic referral include visual disturbance, photophobia, or moderate to severe pain, as delays can lead to permanent vision loss. 1

Distinguish uveitis from less serious conditions immediately: Episcleritis presents with relatively painless hyperemic sclera and conjunctiva, itching and burning, and no visual changes—unlike uveitis which causes true pain and visual symptoms. 1

Essential History Elements

Document the following specific details rather than performing a generic review:

• Onset characteristics: Acute versus insidious onset (acute suggests HLA-B27-associated disease; insidious suggests chronic conditions like JIA or sarcoidosis) 1, 2
• Laterality: Unilateral versus bilateral (bilateral suggests systemic inflammatory disease like Crohn's disease or Behçet's disease) 1, 3
• Recurrence pattern: First episode versus recurrent (recurrent anterior uveitis strongly suggests HLA-B27-associated spondyloarthropathy) 3, 4
• Age: Children require JIA screening; adults over 40 with intermediate/posterior uveitis need primary ocular lymphoma evaluation 5, 4, 6
• Systemic symptoms: Skin lesions, joint pain, respiratory symptoms, neurologic symptoms 2, 6

Ophthalmologic Examination Requirements

Slit-lamp biomicroscopy is mandatory and must be performed by an ophthalmologist—this is not optional. 1, 2 The examination must characterize:

• Anatomic location: Anterior, intermediate, posterior, or panuveitis 2, 7
• Inflammation type: Granulomatous (suggests sarcoidosis, tuberculosis, syphilis) versus non-granulomatous 2, 7, 6
• Anterior chamber cell grade: Using standardized grading (Grade 1+ = 6-15 cells per 1mm × 1mm slit beam) 5
• Presence of complications: Synechiae, keratic precipitates, cataract, glaucoma, macular edema 5

Laboratory Testing Algorithm

Universal Testing (All Patients)

Syphilis serologic screening is the only test appropriate for all forms of uveitis regardless of presentation. 2, 6 This is non-negotiable given the severe consequences of missing ocular syphilis.

Anatomically-Guided Testing

After syphilis screening, further testing must be guided by anatomic classification—not ordered indiscriminately:

For Unilateral Acute Anterior Non-Granulomatous Uveitis

• HLA-B27 testing (strongly associated with ankylosing spondylitis and reactive arthritis) 2, 6

For Chronic Uveitis (Any Location)

• Serum angiotensin-converting enzyme (sarcoidosis screening) 2, 6
• Interferon-gamma release assay (tuberculosis screening—superior to tuberculin skin test which has high false-positive rates) 2, 4, 6
• Chest CT (identifies sarcoidosis and tuberculosis better than plain radiography) 2, 6

For Intermediate or Posterior Uveitis in Patients >40 Years

• Cerebral MRI (evaluates for multiple sclerosis and primary CNS lymphoma) 2, 6
• Anterior chamber tap with IL-10 analysis (distinguishes primary ocular lymphoma from uveitis) 2, 6

Tests NOT Routinely Recommended

Avoid these tests unless specifically indicated by history or examination findings, as they produce false-positives due to low disease prevalence: 4

• Lyme serology (unless endemic area with compatible history)
• Antinuclear antibody testing (except in children being screened for JIA-associated uveitis)
• Serum lysozyme
• Tuberculin skin testing (replaced by interferon-gamma release assay)

Special Population Considerations

Children with Suspected JIA-Associated Uveitis

All children with JIA require ophthalmologic screening even before arthritis diagnosis is confirmed. 5 The screening protocol is:

• High-risk patients (oligoarticular/polyarticular JIA, ANA-positive, age ≤6 years, disease duration ≤4 years): Screen every 3 months 5
• Moderate-risk patients: Screen every 6 months 5
• Low-risk patients: Screen every 12 months 5

JIA-associated uveitis is typically asymptomatic and chronic with insidious onset, making scheduled screening essential rather than symptom-based evaluation. 5

Drug-Induced Uveitis

Consider medication history carefully, as drug-induced uveitis can occur days to months after initial exposure and is often overlooked. 4

Critical Pitfalls to Avoid

Never order extensive autoimmune panels without clinical guidance—investigations ordered without anatomic or clinical orientation are almost always unhelpful and lead to false-positive results requiring unnecessary follow-up. 2, 6

Do not delay ophthalmologic referral for laboratory results—permanent vision loss can occur rapidly, particularly with infectious causes or highly inflammatory disease. 1

Screen for infectious causes before initiating immunosuppressive therapy—failure to identify tuberculosis or other infections before starting immunomodulatory treatment can cause catastrophic worsening. 8

In patients over 50 years with persistent intermediate or posterior uveitis not responding to anti-inflammatory therapy, always consider primary ocular lymphoma. 4