What is the recommended management for autoimmune uveitis?

Management of Autoimmune Uveitis

Autoimmune uveitis requires immediate treatment with topical corticosteroids for anterior disease, but posterior, intermediate, or panuveitis demands urgent systemic immunosuppression combined with corticosteroids—never topical therapy alone—to prevent irreversible vision loss. 1, 2

Immediate Assessment and Treatment Initiation

Anatomic Classification Determines Treatment Strategy

• Anterior uveitis only: Initiate topical corticosteroids (prednisolone acetate 1% or dexamethasone) immediately as first-line therapy 3, 1
• Posterior, intermediate, or panuveitis: Requires immediate systemic immunosuppression and should never be treated with topical corticosteroids alone 1, 2, 4

Urgent Referral Indicators

• Moderate to severe eye pain, photophobia, blurred vision, or decreased visual acuity requires urgent ophthalmology referral 1
• Vision worse than 20/40 requires same-day ophthalmology assessment 2
• Posterior or intermediate uveitis indicates higher risk of vision-threatening complications requiring urgent management 1

First-Line Treatment Algorithm

For Anterior Uveitis

• Start topical prednisolone acetate or dexamethasone every 1-2 hours while awake, then taper based on response 3, 2
• Low-dose topical corticosteroids (≤3 drops daily) can be used over moderate periods with low risk of cataract formation 3
• If inflammation persists beyond 3 months or structural damage develops, escalate to systemic immunosuppression 1

For Posterior/Intermediate/Panuveitis

• Methotrexate is the first-line systemic immunosuppressive agent with Grade B evidence for maintenance and improvement of visual acuity 3
• Systemic corticosteroids must always be combined with immunosuppressive agents, never used as monotherapy 1, 4
• High-dose systemic corticosteroids provide rapid suppression during acute attacks but require concurrent immunosuppression 4

Second-Line Biologic Therapy

When to Escalate

• Inadequate response to methotrexate or other conventional disease-modifying antirheumatic drugs 3
• Corticosteroid-dependent disease requiring steroid-sparing 3
• Intolerance or contraindications to first-line agents 3

Biologic Agent Selection

• Adalimumab has Grade A evidence (highest quality) for nonanterior noninfectious uveitis in adults, significantly reducing flares and vision loss 3, 5
• Adalimumab dosing: 80 mg initial dose, then 40 mg every other week starting one week after initial dose 5
• For JIA-associated anterior uveitis: Adalimumab plus methotrexate reduces treatment failure by 75% (HR 0.25) compared to methotrexate alone 3, 5
• Infliximab has Grade B/C evidence for noninfectious uveitis, particularly effective in Behçet's disease 3
• Etanercept is not supported—no evidence of efficacy 3

Alternative Immunosuppressive Options

• Mycophenolate mofetil: Grade C evidence, controlled inflammation in 70.9% of posterior uveitis cases, comparable efficacy to methotrexate 3, 6
• Azathioprine: Level IB evidence for posterior segment inflammation but higher rates of side effects and discontinuation compared to methotrexate and mycophenolate 3, 4
• Cyclosporine-A: Level IB evidence for preserving visual acuity and preventing relapses 4
• Interferon alfa-2a: Grade B evidence for non-anterior uveitis 3, 4

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, not immunosuppression 6

Monitoring Strategy During Treatment

• Frequency of ophthalmological follow-up should be based on ocular disease severity and decided with an expert ophthalmologist 3
• Anterior chamber cell grade increases correlate with elevated rates of vision loss in dose-dependent fashion 3
• Regular monitoring is mandatory to detect complications: glaucoma, macular edema, cataracts, hypotony, retinal detachment 3, 1, 6

Treatment Withdrawal Protocol

Before Stopping Immunosuppression

• Require >2 years of inactive uveitis before withdrawing methotrexate 3
• Require 2 years of inactive disease while not using topical steroids before reducing systemic immunosuppression 3, 4
• Majority of patients relapse within 24 months of stopping therapy 3

Post-Withdrawal Surveillance

• After stopping immunosuppression, screen by ophthalmologist at least every 3 months for minimum of 1 year 3, 1, 4
• Continue monitoring for at least 3 years off all forms of treatment to detect early recurrence 3, 1, 4
• Risk of relapse is highest in first year after stopping treatment 3

Special Population: JIA-Associated Uveitis

• Children with JIA typically have chronic anterior uveitis that is insidious and asymptomatic, requiring regular screening rather than symptom-based detection 3, 2
• All patients with JIA should be screened according to contemporary protocols regardless of symptoms 3
• Early intensive treatment with close monitoring reduces complications and prevents vision loss in most cases 3, 1
• For JIA-associated uveitis requiring systemic therapy, adalimumab plus methotrexate is superior to methotrexate alone 3, 5

Common Pitfalls to Avoid

• Never treat posterior, intermediate, or panuveitis with topical corticosteroids alone—this is inadequate and risks permanent vision loss 1, 2, 4
• Absence of symptoms does not exclude active uveitis, particularly in children with JIA and patients with posterior involvement 2
• Do not use systemic corticosteroids as monotherapy for posterior uveitis—always combine with immunosuppressive agents 1, 4
• High-dose topical corticosteroids (>3 drops daily) increase cataract risk independent of active inflammation 3
• Do not delay systemic immunosuppression when structural damage, macular edema, or optic disc edema is present at diagnosis 1