What are the treatment guidelines for non-infectious uveitis?

Treatment Guidelines for Non-Infectious Uveitis

Corticosteroids remain the first-line treatment for non-infectious uveitis, but noncorticosteroid systemic immunomodulatory therapy (NCSIT) should be initiated when corticosteroid therapy fails, causes intolerable side effects, or when disease requires prolonged control beyond 3 months. 1

Initial Treatment Approach

Corticosteroid Therapy (First-Line)

• Topical, periocular, or systemic corticosteroids are the gold standard initial treatment for controlling acute inflammation in non-infectious uveitis 2, 3
• Aggressive induction dosing is required to rapidly overcome inflammation and prevent permanent tissue damage 2
• Systemic corticosteroids should not be used as monotherapy for posterior uveitis—they must be combined with immunosuppressive agents to minimize adverse effects 4
• Topical prednisolone should be limited to ≤3 months due to significant risk of elevated intraocular pressure and cataract formation 5
• Maintenance corticosteroid treatment should not exceed 6-12 months due to severe adverse effects 2

Indications for Noncorticosteroid Systemic Immunomodulatory Therapy (NCSIT)

NCSIT should be initiated based on specific ocular and therapeutic criteria: 1

Ocular/Anatomic Indications:

• Sight-threatening acute disease (exudative retinal detachment, posterior/macular involvement, binocular disease) 1
• Chronic persistent inflammation 1
• Visual acuity worse than 20/100 1
• Vitreous haze increase of grade 2+ 1
• Relapse of cystoid macular edema 1
• Disease impacting quality of life 1

Therapeutic Failure Indications:

• Failure of regional corticosteroids (periocular injections or topical corticosteroids in JIA-associated uveitis) 1
• Active uveitis while taking ≥30 mg or ≥0.5 mg/kg prednisone daily 1
• Relapse when oral corticosteroid dose reduced to <7-10 mg/day prednisone 1
• Steroid intolerance or contraindications (history of tuberculosis, hepatitis, noncompliance, reproductive status) 1

Pre-Treatment Evaluation

Before initiating NCSIT, mandatory screening includes: 1

• Baseline vital organ function tests (liver, kidney, bone marrow) 1
• Screening for latent or active tuberculosis 1, 4, 6
• HIV testing 1
• Assessment for history of malignancy, age, and family history of malignancy 1
• Screening for hepatitis 1

First-Line NCSIT Options (Non-Biologic Immunomodulators)

The following agents have Grade B evidence for effectiveness in non-infectious uveitis: 1

Antimetabolites:

• Methotrexate (EL 2B) 1, 7, 3
  • First-line for JIA-associated uveitis: 0.5-1 mg/kg/week, maximum 30 mg 4
• Mycophenolate mofetil (EL 2B) 1, 7, 3
  • Grade B recommendation with evidence of inflammation control, steroid-sparing effect, and visual acuity improvement 1
• Azathioprine (EL 2B) 1, 7, 3
  • First-line for posterior segment inflammation with level IB evidence 4

Calcineurin Inhibitors:

• Cyclosporine (EL 2B) 1, 7, 3
  • Level IB evidence for posterior uveitis 4
• Tacrolimus (EL 2B) 1, 7, 3

The choice between these agents depends on anatomic location, severity, and patient-specific factors (contraindications, cost, convenience), though methotrexate and mycophenolate mofetil are generally preferred over azathioprine 8

Second-Line NCSIT: Biologic Therapy

TNF-α inhibitors should be considered when first-line immunomodulators fail or are not tolerated: 4, 9, 8

FDA-Approved Biologic:

• Adalimumab (HUMIRA) is FDA-approved for non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients ≥2 years of age 10
  • Dosing for adults and children ≥30 kg: 40 mg subcutaneous every other week 10
  • Dosing for children 15-30 kg: 20 mg every other week 10
  • Dosing for children 10-15 kg: 10 mg every other week 10
  • Level IIA evidence for posterior uveitis 4
  • If methotrexate fails in JIA-associated uveitis, TNF inhibitors (adalimumab or infliximab) should be used 4

Other TNF-α Inhibitors:

• Infliximab has shown strong results for NIU, particularly in Behçet's syndrome with posterior involvement 4, 9

Alternative Biologics:

• IL blockers and anti-CD20 therapy (rituximab) have emerged as alternatives 9
• Interferon-alpha has level IIA evidence for posterior uveitis 4

Treatment Adjustment Algorithm

When NCSIT is inadequate, follow this sequence: 1

1. First, rule out treatment nonadherence, infections, and masquerade syndromes (Grade B recommendation) 1
2. Consider dose escalation to maximum tolerated therapeutic dose before switching agents (Grade B recommendation) 1
3. Transition to alternative or additional agent if disease remains uncontrolled (Grade A recommendation) 1

Monitor disease activity using: 1

• Visual acuity (strongest evidence) 1
• Anterior chamber cells and flare 1
• Vitreous haze 1
• Chorioretinal lesions 1
• Retinal vascular lesions 1
• Macular or optic nerve involvement 1

Special Considerations by Etiology

Behçet's Syndrome:

• Any patient with Behçet's and posterior segment involvement requires azathioprine, cyclosporine-A, interferon-alpha, or monoclonal anti-TNF antibodies 4
• For acute sight-threatening disease: high-dose glucocorticoids, infliximab, or interferon-alpha 4

JIA-Associated Uveitis:

• Methotrexate is first-line systemic agent (0.5-1 mg/kg/week, maximum 30 mg) 4
• If methotrexate fails: use TNF inhibitors (adalimumab or infliximab) 4

Critical Safety Warnings

Absolute Contraindications:

• Never initiate immunosuppression before ruling out infectious causes—this can worsen infection and cause poor outcomes 6
• Never use corticosteroids in viral corneal diseases, mycobacterial eye infections, or fungal diseases 5

Monitoring Requirements:

• Regular ophthalmologic monitoring during treatment and for at least 3 years after remission 4, 6
• Monitor for elevated intraocular pressure and cataract formation with corticosteroid use 5
• Using ≥2 drops/day topical prednisolone is a strong risk factor for IOP elevation 5

Special Warnings for TNF Inhibitors:

• Risk of hepatosplenic T-cell lymphoma, particularly when combined with azathioprine or 6-mercaptopurine in adolescent/young adult males with Crohn's disease or ulcerative colitis 10
• Screen for tuberculosis and hepatitis before initiating biologic therapy 1

Treatment Goals

The primary goal is to promptly suppress inflammatory exacerbations and recurrences to prevent irreversible organ damage while minimizing medication adverse effects 4, 2