What is the treatment for uveitis?

Treatment of Uveitis

For noninfectious anterior uveitis, topical corticosteroids (prednisolone acetate 1% or dexamethasone) are first-line treatment, while moderate to severe intermediate, posterior, or panuveitis requires systemic immunosuppression with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, mycophenolate mofetil, azathioprine, cyclosporine, or tacrolimus, with biologic TNF inhibitors (adalimumab or infliximab) reserved for refractory cases. 1, 2

Initial Treatment Approach by Anatomical Location

Anterior Uveitis

• Topical corticosteroids are the mainstay of treatment, with prednisolone acetate 1% preferred over difluprednate 1
• For cases requiring >1-2 drops daily of prednisolone acetate 1% for ≥3 months, add systemic immunosuppression rather than continuing topical therapy alone 1
• Infectious causes (toxoplasmosis, herpes, tuberculosis, HIV) require systemic antimicrobial treatment with or without corticosteroids depending on severity 2

Intermediate, Posterior, and Panuveitis

• Mild intermediate uveitis may be monitored without initial treatment 2
• Moderate to severe disease requires systemic therapy due to high risk of sight-threatening complications including cystoid macular edema, glaucoma, and vision loss 2, 3
• Systemic corticosteroids are indicated when topical therapy fails or with bilateral posterior involvement, especially macular edema and occlusive vasculitis 3

Systemic Immunosuppression Algorithm

First-Line Non-Biologic DMARDs (Grade B Recommendation)

The following agents have equivalent evidence (EL 2B) for noninfectious uveitis 1:

• Methotrexate (subcutaneous preferred over oral for better efficacy) 1
• Mycophenolate mofetil - achieved inflammation control in 70.9% (95% CI, 57.1%-83.5%) and demonstrated steroid-sparing effect 1, 2
• Azathioprine 1
• Cyclosporine 1
• Tacrolimus 1

Key decision point: Choice among these agents should be based on patient history (e.g., hepatitis contraindication), underlying uveitis cause, cost, and convenience 1

When First-Line Therapy Fails

Before changing therapy, rule out: 1

• Treatment nonadherence
• Infectious causes
• Masquerade syndromes (lymphoma, retinal degeneration) - occurs in up to 2.5% of cases

If inadequate response after appropriate trial:

1. Dose escalation to maximum tolerated therapeutic dose may be considered first (Grade B) 1
2. Switch to alternative DMARD or add additional agent (Grade A) 1

Second-Line Biologic Therapy

Indications for biologics:

• Refractory to first-line DMARD therapy 1
• Severe active disease with sight-threatening complications at presentation 1

Biologic agent selection:

• Monoclonal antibody TNF inhibitors (adalimumab or infliximab) are preferred over etanercept (Grade A for avoiding etanercept) 1
• 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<.001) 2
• Etanercept should NOT be used for uveitis based on meta-analysis evidence 1

For severe active disease with sight-threatening complications: Start methotrexate AND monoclonal antibody TNF inhibitor immediately rather than methotrexate monotherapy 1

Third-Line Options for Refractory Disease

If inadequate response to first monoclonal antibody TNF inhibitor:

1. Escalate dose and/or frequency above standard before switching 1
2. If failed at above-standard dosing, switch to another monoclonal antibody TNF inhibitor 1

If failed methotrexate and 2 monoclonal antibody TNF inhibitors:

• Biologic options: Abatacept or tocilizumab 1
• Non-biologic alternatives: Mycophenolate, leflunomide, or cyclosporine 1

Monitoring and Adjustment Criteria

Parameters indicating need to adjust therapy (Grade B/C): 1

• Deterioration in visual acuity
• Increased anterior chamber cells or flare
• Worsening vitreous haze
• New or worsening chorioretinal lesions
• Retinal vascular lesions
• Macular or optic nerve involvement

Monitoring frequency:

• On stable therapy: every 3 months minimum 1
• When changing topical corticosteroids: within 1 month 1
• When tapering/changing systemic therapy: within 2 months 1

Special Considerations

Juvenile Idiopathic Arthritis-Associated Uveitis

• Systemic immunosuppression recommended if poor prognostic factors present at first visit or if remission not achieved within 3 months 1
• Methotrexate is first choice 1
• For severe active disease, combine methotrexate with monoclonal antibody TNF inhibitor immediately 1

Sarcoid Uveitis

• Local, intravitreal, or systemic steroids based on severity 4
• Methotrexate, azathioprine, and mycophenolate mofetil for steroid-refractory cases 3
• Infliximab and adalimumab for refractory or sight-threatening disease 3

Common Pitfalls to Avoid

• Do not use etanercept for uveitis treatment - it lacks efficacy compared to monoclonal antibody TNF inhibitors 1
• Do not continue topical corticosteroids alone if requiring >1-2 drops daily for >3 months - add systemic therapy to prevent complications like cataracts and glaucoma 1
• Do not switch systemic therapy without first ruling out nonadherence, infection, and masquerade syndromes 1
• Do not delay systemic therapy in moderate to severe posterior or panuveitis - these carry high risk of irreversible structural damage 1, 2