What is the treatment for uveitis?

Treatment of Uveitis

Begin with topical corticosteroids (prednisolone acetate 1% or dexamethasone) as first-line therapy for anterior uveitis, but immediately escalate to systemic immunosuppression with methotrexate for posterior/intermediate uveitis or if anterior inflammation persists beyond 3 months. 1, 2

Initial Treatment Strategy

Anterior Uveitis

• Start topical prednisolone acetate 1% or dexamethasone immediately as these have superior corneal penetration compared to other formulations 1, 3, 2
• Limit topical corticosteroids to ≤3 drops daily during maintenance phase to minimize cataract and glaucoma risk 1, 3
• Discontinue topical corticosteroids within 3 months due to significant risk of glaucoma and cataracts with prolonged use 1
• Topical NSAIDs have no effect as monotherapy but may reduce corticosteroid requirements when used adjunctively 3, 2

Acute Anterior Uveitis (HLA-B27 Associated)

• This episodic, unilateral presentation with sudden erythema, pain, and photophobia generally does not require systemic treatment 1
• Topical corticosteroids alone are typically sufficient as this subtype is self-limiting 4

Posterior, Intermediate, or Panuveitis

• Never treat with topical corticosteroids alone—these patients require immediate systemic immunosuppression 2, 5
• Systemic corticosteroids must always be combined with immunosuppressive agents, never used as monotherapy 3, 2

Indications for Systemic Immunosuppression

Escalate to systemic therapy immediately if any of the following are present:

• Posterior segment involvement (choroid, retina, optic nerve) 3, 2
• Bilateral sight-threatening disease 3
• Severe inflammation indicators: vitreous haze, macular edema, retinal vascular inflammation, or exudative detachment 3, 2
• Structural damage at diagnosis (posterior synechiae, band keratopathy, glaucoma, cataract) 1, 2
• Hypotony or rubeosis iridis 2
• Failure to achieve control within 3 months of topical therapy 1, 3
• Inflammation reactivates during corticosteroid taper 3
• Requirement for >1-2 drops/eye/day of topical corticosteroids to maintain control 1

Systemic Treatment Algorithm

First-Line Systemic Agent

• Methotrexate is the preferred initial systemic immunosuppressive agent with demonstrated inflammation control and steroid-sparing effect 1, 3
• Methotrexate achieved remission in 52.1% (95% CI, 38.6%-67.1%) of patients with posterior uveitis 5
• Alternative first-line options include mycophenolate mofetil (controlled inflammation in 70.9% of patients), azathioprine, and cyclosporine 1, 3, 5

Second-Line Biologic Therapy

If inadequate response to methotrexate or other conventional DMARDs:

• Adalimumab is the preferred biologic agent, extending time to treatment failure from 13 to 24 weeks and reducing treatment failure rate from 78.5% to 54.5% (P<0.001) 1, 3, 5
• Adalimumab demonstrated superiority over infliximab in maintaining remission over 3-year treatment periods in multiple studies 1
• Infliximab is the second-choice biologic, particularly effective in Behçet's disease-associated uveitis and significantly superior to etanercept 1, 3
• Golimumab may be considered after failure of other anti-TNF agents, with 14/17 patients achieving positive response in refractory cases 1
• Etanercept should never be used for uveitis—it is associated with high relapse rates and may paradoxically worsen uveitis 1, 3

Switching Between Biologics

• If one anti-TNF agent becomes ineffective, switching to a different anti-TNF agent is clinically beneficial in 65.4% of cases 1
• Consider checking drug trough levels and anti-drug antibodies if loss of efficacy occurs 1

Pre-Treatment Safety Requirements

Before initiating systemic immunosuppression, complete the following:

• Screen for latent/active tuberculosis 1, 2
• Test for hepatitis B and C 1, 3
• Obtain baseline complete blood count, liver function tests, and renal function tests 1, 3
• Pregnancy test in women of childbearing age 3
• Rule out infectious causes before starting immunosuppression to avoid worsening outcomes and permanent vision loss 2

Monitoring Protocol

During Active Treatment

• Ophthalmologic monitoring within 1 month after each change in topical glucocorticoids 1
• Ophthalmologic monitoring within 2 months of changing systemic therapy 1, 4
• On stable therapy, monitor no less frequently than every 3 months 1, 4

After Achieving Remission

• Require ≥2 years of inactive disease off topical steroids before reducing systemic therapy 3
• Continue monitoring for at least 3 years after remission to detect early recurrence 3, 2
• After discontinuing immunosuppression, evaluate every 3 months for minimum 1 year as majority of relapses occur within 24 months 1, 3, 2

Poor Prognostic Factors Requiring Aggressive Treatment

Institute immediate aggressive immunosuppression if any of these high-risk features are present:

• Uveitis antedating arthritis 1
• Male gender 1
• Posterior synechiae at presentation 1
• Band keratopathy, glaucoma, or cataract at diagnosis 1
• Poor initial vision, hypotony, macular edema, or dense vitreous opacification 1
• Non-Caucasian race 1

Critical Pitfalls to Avoid

• Never use systemic corticosteroids as monotherapy for posterior uveitis—always combine with immunosuppressive agents 3, 2
• Never delay systemic immunosuppression beyond 3 months in anterior uveitis requiring ongoing topical steroids 1
• Never use etanercept for uveitis treatment as it may worsen inflammation 1, 3
• Never treat posterior/intermediate/panuveitis with topical therapy alone 2, 5
• Periocular and intraocular corticosteroid injections are at ophthalmologist discretion but carry risks of elevated intraocular pressure and cataract 1

Special Considerations for JIA-Associated Uveitis

• Chronic anterior uveitis in JIA is usually asymptomatic with no external inflammation, affecting 10-20% of children 1
• Uncontrolled disease leads to sight-threatening complications in 25-50% and vision loss in 10-20% 1
• High-risk children (early-onset arthritis, ANA-positive, oligoarticular subtype) require ophthalmology screening every 3 months 1
• Treatment approach follows same algorithm as adult uveitis: topical corticosteroids first, then methotrexate, then monoclonal anti-TNF agents 1