What is the recommended treatment approach for a patient presenting with uveitis?

Treatment Approach for Uveitis

The treatment of uveitis depends critically on anatomical location and etiology: anterior uveitis requires topical corticosteroids as first-line therapy, while posterior or panuveitis requires systemic immunosuppression with disease-modifying antirheumatic drugs (DMARDs) or biologics to prevent vision-threatening complications. 1, 2

Initial Assessment and Classification

Before initiating treatment, determine:

• Anatomical location: Anterior (iris/ciliary body), intermediate (pars plana), posterior (choroid/retina), or panuveitis (all layers) 2
• Infectious vs. non-infectious etiology: Rule out toxoplasmosis, herpes, tuberculosis, HIV, and fungal infections before starting immunosuppression 1, 2
• Associated systemic disease: Screen for juvenile idiopathic arthritis (JIA), spondyloarthritis, Behçet's syndrome, sarcoidosis, or inflammatory bowel disease 1, 3
• Severity indicators: Visual acuity, anterior chamber cells/flare, vitreous haze, macular edema, retinal vasculitis, or optic nerve involvement 1

Treatment by Anatomical Location

Anterior Uveitis

Topical corticosteroids are the mandatory first-line treatment:

• Prednisolone acetate 1% or dexamethasone drops should be initiated immediately 1
• Add cycloplegic agents (e.g., cyclopentolate, atropine) to prevent synechiae formation 4, 5
• Limit topical prednisolone to ≤3 months due to significant risk of elevated intraocular pressure and cataract formation 5, 6
• Using ≥2 drops/day increases IOP elevation risk; ≥4 drops/day significantly increases cataract risk 5

Escalate to systemic therapy if:

• Still requiring 1-2 drops/day of prednisolone acetate 1% for ≥3 months 1
• Inflammation not controlled within 3 months 1
• Bilateral disease or posterior segment involvement develops 3, 2

Posterior Uveitis, Intermediate Uveitis, or Panuveitis

These require systemic immunosuppression from the outset due to high risk of vision-threatening complications:

First-line systemic therapy:

• Methotrexate (0.5-1 mg/kg/week, maximum 30 mg; subcutaneous preferred over oral) achieves remission in 52.1% of patients 1, 3, 2
• Azathioprine has level IB evidence for posterior segment inflammation 3
• Mycophenolate mofetil controls inflammation in 70.9% of patients with good tolerability 3, 2
• Cyclosporine-A is another first-line option with level IB evidence 3

Topical/local corticosteroids as adjunct:

• Continue topical prednisolone for anterior component 1, 4
• Consider intravitreal or periocular corticosteroid injection for unilateral exacerbation 3
• Systemic corticosteroids should only be used temporarily in combination with immunosuppressive agents, never as monotherapy 3

Biologic Therapy Indications

Initiate TNF inhibitor (monoclonal antibody) when:

• Inadequate response to first-line DMARD after appropriate trial 1, 3
• Severe active disease with sight-threatening complications at presentation 1, 3
• Behçet's syndrome with posterior segment involvement (requires azathioprine, cyclosporine-A, interferon-alpha, or anti-TNF from diagnosis) 3

Specific biologic recommendations:

• Adalimumab is the preferred TNF inhibitor with highest evidence (EL 1B) and extends time to treatment failure from 13 to 24 weeks 1, 3, 2
• Infliximab is the alternative monoclonal antibody TNF inhibitor 1, 3
• Never use etanercept - it is ineffective for uveitis and may worsen inflammation 1, 4
• For severe JIA-associated uveitis with sight-threatening complications, start methotrexate AND monoclonal antibody TNF inhibitor simultaneously 1

If first TNF inhibitor fails:

• Escalate dose and/or frequency above standard before switching 1
• If inadequate response at above-standard dosing, switch to another monoclonal antibody TNF inhibitor 1
• Check antidrug antibodies and trough levels; if no antibodies but low levels, increase dose or shorten interval 1

Third-line biologics after failing 2 TNF inhibitors:

• Tocilizumab, abatacept, or rituximab are options for refractory cases 1

Special Populations and Etiologies

JIA-Associated Uveitis

• Regular ophthalmology screening every 3 months for high-risk patients (oligoarthritis, ANA-positive, early onset) 1
• Methotrexate is first-line systemic agent 1
• Monoclonal antibody TNF inhibitors (adalimumab/infliximab) if methotrexate fails 1

Acute Anterior Uveitis in Spondyloarthritis

• Educate patients on warning signs (sudden pain, redness, photophobia) to decrease treatment delay 1, 7
• Treat with topical corticosteroids and cycloplegics 7
• If well-controlled on systemic therapy and develops isolated short-lived AAU episode, treat with topicals first rather than switching systemic therapy immediately 1

Crohn's Disease with Uveitis

• Adalimumab or infliximab are first-line as they treat both conditions 4
• Add azathioprine or methotrexate for synergistic effect 4
• Never use IL-17 inhibitors - they exacerbate Crohn's disease 4

Monitoring Requirements

During active treatment:

• Ophthalmologic monitoring every 3 months minimum for controlled uveitis on stable therapy 1
• Within 1 month after each change in topical corticosteroids 1
• Within 2 months after changing systemic therapy 1
• Monitor IOP and cataract formation with prolonged topical corticosteroid use 5, 6

After achieving remission:

• Continue monitoring for at least 3 years 3

Critical Pitfalls to Avoid

Before starting immunosuppression:

• Screen for latent tuberculosis - mandatory before biologics 1, 3, 4
• Perform baseline organ function tests 3, 4
• Rule out infectious causes and masquerade syndromes (lymphoma, retinal degeneration) 1

Never use corticosteroids in:

• Viral corneal diseases (especially herpetic keratitis) 5
• Mycobacterial or fungal eye infections 5, 6
• Starting steroids before ophthalmologic examination may mask diagnosis or worsen infection 5

If inflammation persists despite treatment:

• Rule out nonadherence, infection, and masquerade syndromes before escalating 1
• Consider fungal invasion in any persistent corneal ulceration where corticosteroids have been used 6
• Obtain fungal cultures when appropriate 6

Treatment goals:

• Achieve complete suppression of inflammation to prevent irreversible structural damage 1, 3
• Minimize corticosteroid exposure to reduce adverse effects 3, 2
• Aim for steroid-free remission with immunomodulatory therapy 4