What is the recommended evaluation and management for uveitis?

Evaluation and Management of Uveitis

Immediate Triage and Referral

Any patient presenting with moderate to severe eye pain, photophobia, blurred vision, or decreased visual acuity requires urgent same-day referral to an ophthalmologist experienced in inflammatory eye disease. 1

• Posterior or intermediate uveitis carries higher risk of vision-threatening complications and demands urgent subspecialty management 1
• Episcleritis (painless, hyperemic sclera with itching/burning, no visual changes) can be managed less urgently, but scleritis requires urgent referral similar to uveitis 2
• Symptoms are often nonspecific, making early ophthalmologic evaluation critical to prevent permanent vision loss 2

Initial Diagnostic Evaluation

History and Physical Examination Focus

Serological screening for syphilis is the only test appropriate for all forms of uveitis. 3

Beyond syphilis testing, investigations should be guided by:

• Anatomic location of inflammation (anterior vs. intermediate vs. posterior vs. panuveitis) 3
• Laterality (unilateral vs. bilateral) and onset pattern (acute vs. insidious) 2
• Associated systemic symptoms: chronic diarrhea, abdominal pain, weight loss (inflammatory bowel disease); morning stiffness >30 minutes, improvement with exercise, nocturnal back pain (spondyloarthritis); peripheral arthritis or enthesitis 4

Anatomically-Guided Testing

For unilateral acute anterior non-granulomatous uveitis:

• HLA-B27 testing 3
• Note: 10% of ankylosing spondylitis cases are HLA-B27 negative, so absence does not exclude spondyloarthritis 4
• Genetic testing beyond HLA-B27 is not indicated for routine practice 4

For chronic uveitis:

• Serum angiotensin converting enzyme 3
• Interferon-gamma release assay (tuberculosis screening) 3
• Chest CT 3

For intermediate or posterior uveitis in patients over 40 years:

• Cerebral MRI 3
• Anterior chamber tap with IL-10 analysis 3

Critical principle: Investigations ordered without clinical orientation are almost always unhelpful 3

Treatment Algorithm

Anterior Uveitis

Topical corticosteroids (prednisolone acetate or dexamethasone) are first-line treatment and should be initiated immediately. 5, 1, 6

• Active uveitis requires immediate treatment to prevent complications 5
• Early intensive treatment with close monitoring reduces complications and prevents vision loss in most cases 1
• Topical or systemic NSAIDs have no demonstrated effect as monotherapy but may be used as adjunctive therapy 5

Escalation criteria for systemic therapy:

• Inability to achieve inactivity within 3 months 5
• Inflammation reactivates during steroid dose reduction 5
• Poor prognostic factors present at first visit (structural damage, macular edema, optic disc edema, hypotony, rubeosis iridis) 5, 1

Intermediate, Posterior, and Panuveitis

These patients require immediate systemic immunosuppression and should never be treated with topical corticosteroids alone. 1

• Systemic corticosteroids must always be combined with immunosuppressive agents, never used as monotherapy 1
• First-line disease-modifying antirheumatic drugs (methotrexate) achieved remission in 52.1% (95% CI, 38.6%-67.1%) of patients 6
• Mycophenolate mofetil controlled inflammation in 70.9% (95% CI, 57.1%-83.5%) 6

Systemic Immunosuppression Protocol

Step 1: Methotrexate

• Methotrexate is the first choice for systemic immunosuppression 5

Step 2: Anti-TNF Biologics (if methotrexate fails or is not tolerated)

• Adalimumab is preferred over infliximab, which is preferred over golimumab 5
• Adalimumab extended time to treatment failure to 24 weeks vs. 13 weeks with placebo and reduced treatment failure from 78.5% to 54.5% (P<0.001) 6
• Etanercept should not be used for uveitis (level 1B evidence) 5

Step 3: Alternative biologics (if anti-TNF fails)

• Switching between different anti-TNF agents may be valuable even after first anti-TNF failure 5
• Before switching, test for antidrug antibodies and drug trough levels; if no antibodies but low trough levels, increase dose or shorten interval 5
• Tocilizumab, rituximab, or abatacept are potential options for cases refractory to anti-TNF therapy 5

Critical Safety Considerations

Rule out infectious causes before initiating immunosuppression to avoid worsening outcomes and permanent vision loss. 1

• Screen for latent or active tuberculosis before starting systemic immunomodulatory therapy 1
• Infectious uveitis (toxoplasmosis, herpes, tuberculosis, HIV) requires systemic antimicrobial treatment 6

Treatment Goals and Monitoring

The goal is no cells in the anterior chamber; macular/disc edema, ocular hypotony, or rubeosis iridis may require anti-inflammatory treatment even without anterior chamber cells. 5

Duration of Treatment

Require 2 years of inactive disease off topical steroids before reducing systemic immunosuppression (DMARDs or biologics). 5

Post-Treatment Monitoring

After stopping immunosuppression, patients must be evaluated by an ophthalmologist at least every 3 months for minimum 1 year. 5, 1

• Regular ophthalmological surveillance is mandatory for at least 3 years after achieving remission to detect early recurrence 1
• Majority of patients relapse within 24 months of stopping therapy 5

Multidisciplinary Coordination

Good communication between ophthalmologist and rheumatologist is essential concerning disease activity changes, treatment modifications, and monitoring responsibility. 5

• Active inflammatory disorders associated with uveitis should be treated by the appropriate specialist (e.g., rheumatologist for JIA, spondyloarthritis) 6
• Ophthalmologists assess uveitis activity and provide topical therapy; rheumatologists manage systemic treatment 5

Common Pitfalls

• Do not delay systemic therapy in posterior/intermediate uveitis or when poor prognostic factors are present 1
• Do not use etanercept for uveitis treatment 5
• Do not order unfocused laboratory investigations without clinical orientation 3
• Do not assume absence of symptoms means inactive disease in chronic anterior uveitis, which is frequently asymptomatic until complications develop 5
• Do not stop monitoring too early after treatment cessation—continue for at least 3 years 1