How should uveitis be evaluated and treated?

Evaluation and Treatment of Uveitis

Initial Evaluation

All patients with suspected uveitis require urgent ophthalmologic referral for slit-lamp biomicroscopy to confirm the diagnosis, characterize anatomic location, grade inflammation severity, and identify sight-threatening complications. 1

Critical Warning Signs Requiring Immediate Referral

• Visual disturbance, photophobia, or moderate to severe pain indicate urgent need for ophthalmologic evaluation to prevent permanent vision loss 1
• True ocular pain with visual symptoms distinguishes uveitis from benign conditions like episcleritis (which presents with painless hyperemia, itching, and no visual changes) 1

Essential History Elements

Document the following to guide workup and treatment decisions 1:

• Onset characteristics: acute versus insidious
• Laterality: unilateral versus bilateral
• Recurrence pattern: first episode versus recurrent
• Age: children require JIA screening; adults over 40 with intermediate/posterior uveitis need lymphoma evaluation 1
• Systemic symptoms: joint pain, rash, respiratory symptoms, neurologic symptoms

Ophthalmologic Examination Requirements

Slit-lamp biomicroscopy must characterize 1, 2:

• Anatomic location (anterior, intermediate, posterior, or panuveitis)
• Inflammation type and anterior chamber cell grade
• Complications: synechiae, keratic precipitates, cataract, glaucoma, macular edema

Laboratory Testing Algorithm

Universal Testing

All patients with uveitis require syphilis serologic screening regardless of presentation, due to severe consequences of missing ocular syphilis. 1

Anatomically-Guided Testing

Further investigations should be directed by anatomic classification 1:

• Unilateral acute anterior non-granulomatous uveitis: HLA-B27 testing
• Chronic uveitis: serum angiotensin-converting enzyme and interferon-gamma release assay (for sarcoidosis and tuberculosis)
• Severe, bilateral, recurrent, or chronic anterior uveitis: chest radiography, HLA-B27, ACE level 3

Critical Pitfall

Avoid extensive autoimmune panels without clinical guidance—investigations ordered without anatomic or clinical orientation are almost always unhelpful and lead to false-positive results requiring unnecessary follow-up. 1 Do not delay ophthalmologic referral while awaiting laboratory results, as permanent vision loss can occur rapidly 1

Special Population: Juvenile Idiopathic Arthritis

Screening Protocol

Children with JIA require ophthalmologic screening every 3 months if at high risk for uveitis 4, 2, even before arthritis diagnosis is confirmed 1. JIA-associated uveitis is typically asymptomatic and chronic with insidious onset, making scheduled screening essential rather than symptom-based evaluation 1

Monitoring for Established JIA-Associated Uveitis

• Tapering/discontinuing topical glucocorticoids: monitor within 1 month after each change 4, 2
• Stable therapy: monitor no less frequently than every 3 months 4, 2
• Tapering/discontinuing systemic therapy: monitor within 2 months of changing systemic therapy 4, 2

Treatment Approach

Anterior Uveitis

Topical corticosteroids (prednisolone acetate 1%) are first-line therapy for anterior uveitis. 4, 2, 5

Initial Management

• Prednisolone acetate 1% is preferred over difluprednate due to better corneal penetration 4, 6
• Initial dosing may require more than 1-2 drops/eye/day for severe inflammation 6
• Topical corticosteroids should be used as short-term therapy (≤3 months) due to risks of glaucoma and cataract formation 6, 2

Indications for Systemic Therapy

Add systemic immunosuppression if 4, 2:

• Topical corticosteroids cannot be tapered to ≤2 drops/day within 3 months
• Patient still requires 1-2 drops/day of prednisolone acetate 1% for at least 3 months
• Poor prognostic factors present at first visit 6

Intermediate, Posterior, and Panuveitis

Patients with moderate to severe intermediate uveitis, posterior uveitis, and panuveitis are at high risk of sight-threatening complications and require systemic and/or intravitreal corticosteroids and immunosuppressive agents. 5

Mild intermediate uveitis may be monitored without initial treatment 5

Systemic Immunosuppressive Therapy

First-Line Systemic Therapy

Subcutaneous methotrexate is the first-choice systemic immunosuppressant, preferred over oral administration. 4, 6, 2

For posterior uveitis, methotrexate achieved remission in 52.1% (95% CI, 38.6%-67.1%) of patients 5. Mycophenolate mofetil controlled inflammation in 70.9% (95% CI, 57.1%-83.5%) of posterior uveitis cases 5

Second-Line Biologic Therapy

For methotrexate inefficacy or intolerance, monoclonal antibody TNF inhibitors (adalimumab or infliximab) are recommended over etanercept. 4, 6, 2

Adalimumab extended time to treatment failure to 24 weeks versus 13 weeks with placebo and reduced frequency of treatment failure from 78.5% to 54.5% (P < .001) 5

Severe Sight-Threatening Disease

For severe active uveitis with sight-threatening complications, start methotrexate and a monoclonal antibody TNF inhibitor immediately rather than methotrexate monotherapy. 4, 2

Escalation Strategy for Refractory Disease

• Inadequate response to standard-dose monoclonal TNFi: escalate dose and/or frequency above standard before switching 4, 2
• Failure of first monoclonal TNFi at above-standard dose: change to another monoclonal antibody TNFi 2
• Failure of methotrexate and 2 monoclonal TNFi at above-standard doses: consider abatacept or tocilizumab as biologic options, or mycophenolate, leflunomide, or cyclosporine as non-biologic alternatives 2

Infectious Uveitis

Screen for infectious causes before initiating immunosuppressive therapy to prevent catastrophic worsening. 1 Infectious uveitis requires systemic antimicrobial treatment 5. Toxoplasmosis, herpes, tuberculosis, and HIV comprise 11-21% of infectious cases in high-income countries and 50% in low- and middle-income countries 5

Tapering Strategy

Taper topical glucocorticoids first before tapering systemic therapy. 2 For patients well-controlled on systemic immunosuppressive therapy who develop isolated short-lived acute anterior uveitis, treat with topical glucocorticoids first before changing systemic therapy 2

Monitoring for Complications

Regular monitoring is required for 2:

• Ocular glucocorticoid complications: cataracts, glaucoma, increased intraocular pressure, infection
• Inflammation-related complications: peripheral anterior synechiae, posterior synechiae, cystoid macular edema

Patient education regarding warning signs of acute anterior uveitis is essential to decrease delay in treatment and complications. 6, 2