What is the treatment for anterior uveitis?

Anterior Uveitis: Causes and Treatment

Causes of Anterior Uveitis

Anterior uveitis is most commonly idiopathic (27-51% of cases) or associated with systemic autoimmune diseases (37-49% of cases), with infectious causes accounting for 11-21% in high-income countries. 1

• Autoimmune/inflammatory causes include juvenile idiopathic arthritis (JIA), axial spondyloarthritis, and other HLA-B27-associated conditions 2, 1
• Infectious causes include toxoplasmosis, herpes viruses, tuberculosis, and HIV, though these more commonly cause posterior or panuveitis 1
• Genetic factors such as HLA-B27 positivity significantly increase risk 1
• A substantial proportion remains idiopathic despite thorough evaluation 2, 1

Treatment Algorithm

First-Line Treatment: Topical Corticosteroids

Prednisolone acetate 1% is the first-line treatment for anterior uveitis, requiring frequent initial dosing (more than 1-2 drops/eye/day based on inflammation severity) with the goal of discontinuation within 3 months. 3, 4

• Prednisolone acetate 1% is preferred over other topical corticosteroids due to superior corneal penetration and intraocular efficacy 3, 5
• Initial dosing must be aggressive based on severity, often requiring hourly administration in severe cases 2, 3
• Taper gradually as anterior chamber cellular reaction comes under control 3, 6
• Monitor within 1 month of any change in topical therapy 2, 3

Critical Timeframe: The 3-Month Rule

If uveitis cannot be controlled within 3 months or requires more than 1-2 drops/day of prednisolone acetate to maintain control, systemic immunosuppression must be added. 2, 3

• The 3-month threshold exists because prolonged topical corticosteroid use significantly increases risk of glaucoma and cataracts 2, 3
• Recurrent uncontrolled disease (≥1+ anterior chamber cells) during steroid taper to twice daily or less mandates systemic therapy 2
• Development of new ocular complications (posterior synechiae, band keratopathy, cystoid macular edema, elevated intraocular pressure, hypotony) during topical steroid therapy requires escalation 2

Second-Line Treatment: Methotrexate

Methotrexate is the first-choice systemic immunosuppressive agent for anterior uveitis requiring steroid-sparing therapy. 3, 7

• Subcutaneous administration is preferred over oral due to higher bioavailability, though both routes are acceptable 2
• Methotrexate achieved remission in 52.1% (95% CI, 38.6%-67.1%) of patients with uveitis 1
• Can be used in children naive to steroid-sparing therapy or adults requiring systemic immunosuppression 2
• Methotrexate intolerance can often be managed with anti-emetics, folic acid/leucovorin, and dose adjustment 2

Third-Line Treatment: TNF Inhibitors

For uveitis refractory to methotrexate, adalimumab or infliximab are the recommended biologic agents. 3, 7

• Adalimumab extended time to treatment failure to 24 weeks versus 13 weeks with placebo and reduced treatment failure from 78.5% to 54.5% (P < .001) 1
• Adalimumab dosing options include weekly or every-other-week administration 2
• Infliximab dosing starts at 6-10 mg/kg with loading at 0 and 2 weeks, then every 4 weeks, with dose escalation permitted up to 20 mg/kg 2
• Etanercept should be avoided as it may worsen or trigger uveitis 7

Alternative Systemic Agents

For patients failing both methotrexate and TNF inhibitors, mycophenolate mofetil is the most supported alternative, controlling inflammation in 70.9% (95% CI, 57.1%-83.5%) of patients. 1

• Other options include abatacept, tocilizumab, cyclosporine, though consensus on these is limited 2
• Switching between different anti-TNF agents may be valuable if refractory to the first 7

Special Treatment Considerations

Periocular and Intravitreal Injections

Periocular and intravitreal glucocorticoid injections may be considered at the discretion of the treating ophthalmologist for refractory cases. 2, 3

• These are typically reserved for cases not responding adequately to topical therapy 2
• Useful as bridging therapy while awaiting efficacy of systemic agents 6

Systemic Corticosteroids

Systemic corticosteroids should be avoided in chronic anterior uveitis management and used only as short-term bridging therapy (≤2 weeks) while awaiting efficacy of steroid-sparing agents. 2, 6

• Reserved for vision-threatening uveitis, bilateral severe inflammation, or uveitis with systemic involvement 6
• Taper should begin no longer than 2 weeks after initiation of steroid-sparing therapy 2

NSAIDs

Topical and systemic NSAIDs have no demonstrable effect as monotherapy for anterior uveitis but may be used as adjunctive therapy. 3, 5

Monitoring Requirements

Ophthalmologic Monitoring

Patients with uncontrolled uveitis should be monitored every 2-6 weeks, while those on stable therapy require monitoring at least every 3 months. 2

• When tapering or discontinuing topical corticosteroids, monitor within 1 month after each change 2, 3
• Eye exams should occur within 6 weeks after starting systemic therapy 2
• All eye exam records between study visits should be reviewed 2

Treatment Goals

The goal is to achieve <1+ anterior chamber cells (fewer than 6 cells per high-power field) without topical corticosteroids. 2

• Although 0.5+ cells is technically "active" by SUN criteria, therapy escalation is not necessarily warranted at this level 2
• Adequately controlled disease requires: no systemic steroids, ≤0.5+ AC cells, ≤2 drops/day topical steroids, and no new complications for ≥3 months 2

Common Pitfalls and Caveats

Corticosteroid Complications

The most common complications of topical corticosteroid therapy are corticosteroid-induced glaucoma and cataracts, requiring vigilant monitoring. 2, 5, 8

• Risk increases significantly with doses >1-2 drops/day and duration >3 months 2
• Loteprednol and fluorometholone have weaker anti-inflammatory effects but induce less IOP elevation 5
• These complications are not reversible and should not trigger treatment changes in the absence of active inflammation 2

Infectious Uveitis

Always rule out infectious causes before initiating immunosuppression, as infectious uveitis requires antimicrobial treatment, not immunosuppression alone. 1

• Infectious causes are more common in low- and middle-income countries (50% vs 11-21%) 1
• Systemic antimicrobials are required for infectious uveitis, with local/systemic steroids added depending on severity 1

JIA-Associated Uveitis

Children with JIA at high risk for uveitis require ophthalmology screening every 3 months, as this population has unique treatment considerations. 2

• JIA-associated uveitis is typically chronic and asymptomatic, requiring proactive screening 2
• Treatment algorithms for JIA-associated uveitis follow the same general principles but with specific pediatric dosing considerations 2