What are the treatment options for recurrent chronic posterior uveitis?

Treatment Options for Recurrent Chronic Posterior Uveitis

For patients with recurrent chronic posterior uveitis, systemic immunomodulatory therapy should be initiated with agents such as azathioprine, cyclosporine-A, interferon-alpha, or TNF inhibitors like adalimumab to control inflammation and prevent vision loss. 1

First-Line Treatment Options

• Systemic glucocorticoids should be used only in combination with immunosuppressive agents, not as monotherapy, for posterior uveitis to minimize corticosteroid-related adverse effects 1
• Azathioprine is a first-line immunosuppressive agent for posterior segment inflammation with level IB evidence 1
• Cyclosporine-A is another first-line option with level IB evidence for posterior uveitis 1
• Interferon-alpha has level IIA evidence for effectiveness in posterior uveitis 1
• Intravitreal glucocorticoid injection can be considered as an adjunct to systemic treatment in patients with unilateral exacerbation 1

Second-Line Treatment Options

• Monoclonal anti-TNF antibodies (like adalimumab) have level IIA evidence for posterior uveitis and should be considered for patients who fail first-line therapy 1, 2
• Adalimumab is FDA-approved for non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older 2
• For adults, the recommended dosage of adalimumab is 40 mg administered subcutaneously every other week 2
• Adalimumab has been shown to extend time to treatment failure to 24 weeks versus 13 weeks with placebo and reduced frequency of treatment failure from 78.5% to 54.5% in patients who don't respond to first-line therapy 3

Indications for Systemic Immunomodulatory Therapy

• Noncorticosteroid systemic immunomodulatory therapy (NCSIT) should be introduced when there is:

  • Persistent or severe inflammation 1
  • Risk of ocular structural complications that threaten visual function 1
  • Contraindications or intolerance to corticosteroids 1
  • Need for corticosteroid-sparing effect to maintain disease remission 1, 4

• Indicators of severe inflammation requiring systemic therapy include:

  • Impairment of visual function 1
  • Bilateral disease 1
  • Vitreous haze 1
  • Macular or optic nerve disease 1
  • Retinal vascular inflammation 1
  • Macular edema 1, 5
  • Exudative retinal detachment 1

Special Considerations for Specific Causes

Behçet's Syndrome

• Any patient with Behçet's syndrome and posterior segment eye involvement should be on a treatment regimen including azathioprine, cyclosporine-A, interferon-alpha, or monoclonal anti-TNF antibodies 1
• For acute sight-threatening uveitis in Behçet's, high-dose glucocorticoids, infliximab, or interferon-alpha should be used 1

Juvenile Idiopathic Arthritis (JIA)

• While primarily causing anterior uveitis, JIA-associated uveitis that extends to posterior segments requires systemic immunosuppression 1
• Methotrexate (0.5-1 mg/kg/week, maximum 30 mg) is the first-line systemic agent for JIA-associated uveitis 1
• If methotrexate fails or is not tolerated, TNF inhibitors (adalimumab or infliximab) should be used 1

Monitoring and Treatment Goals

• The goal of treatment is to promptly suppress inflammatory exacerbations and recurrences to prevent irreversible organ damage 1
• Treatment should aim to induce and maintain remission while minimizing corticosteroid use 3
• Regular monitoring by an ophthalmologist is essential during treatment and for at least 3 years after remission 1
• Success of therapy should be measured by:
  • Control of intraocular inflammation 4
  • Reduction in the number of disease relapses 4
  • Maintenance of vision 4
  • Reduction of corticosteroid dose to 10 mg/day or less 4

Emerging Therapies

• Sustained-release intravitreal corticosteroid implants (like fluocinolone acetonide 0.18 mg) can provide targeted therapy for chronic noninfectious posterior uveitis with reduced systemic side effects 6
• These implants deliver low-dose corticosteroids over an extended period, minimizing cumulative damage from recurrences and reducing injection frequency 6

Important Considerations and Pitfalls

• Before initiating systemic immunomodulatory therapy, patients should be screened for latent or active infections, particularly tuberculosis 1
• Baseline organ function tests should be performed before starting immunosuppressive agents 1
• Patients on TNF inhibitors should be monitored for potential adverse effects including infections and rarely, demyelinating disease 2
• Combination of TNF blockers with azathioprine or 6-mercaptopurine may increase the risk of hepatosplenic T-cell lymphoma, particularly in adolescent and young adult males 2
• Long-term management requires multidisciplinary coordination between ophthalmologists and other specialists (rheumatologists, internists) 1, 7