Uveitis is a significant cause of vision loss.¹ Retina and uveitis specialists encounter ocular inflammatory disease either confined to the eye (in various anatomical locations) or as an element of a larger systemic process. The mainstay of uveitis management has been corticosteroids, assuming an infectious process has been either treated or ruled out. Steroid administration may be topical, periocular, intravitreal, or systemic.

Systemic corticosteroids have many potentially troublesome side effects. Use of systemic steroid-sparing agents has evolved as our knowledge of the uveitic process has advanced. In a “stepladder” approach, antimetabolites such as methotrexate, with folic acid on days the patient is not taking methotrexate, are often favored after steroid therapy. These are also occasionally used in preference to steroids.

Biologic response modifiers are often used next in this stepladder approach, most commonly the tumor necrosis factor alpha (TNF-alpha) inhibitors infliximab and adalimumab. These therapies inhibit the cell-signaling protein TNF-alpha, which modulates and amplifies the immune response.

Surgical options include therapeutic pars plana vitrectomy (considered previously in this column²) and sectoral or panretinal photocoagulation (if there is associated ischemia and neovascularization with the uveitis). This stepladder approach has been described by the Ocular Immunology and Uveitis Foundation as a “preferred practice pattern.”³ This month, we are fortunate to have the comments of uveitis and retina specialist Thomas Albini, MD, associate professor of Clinical Ophthalmology, University of Miami/Bascom Palmer Eye Institute, regarding this potential approach.

REFERENCES

1. Gritz D, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004;111(3):491-500.
2. Colucciello M, Vitale A, deSmet M. Controversies in care: pars plana vitrectomy for the induction of drug-free remission in uveitis? Retinal Physician. 2012;9(2):18-25. http://www.retinalphysician.com/articleviewer.aspx?articleID=106810
3. Foster CS, Kothari S, Anesi SD, et al. The Ocular Immunology and Uveitis Foundation preferred practice patterns of uveitis management. Surv Ophthalmol. 2016;61(1):1-17.

Steroid-Sparing Agents for Uveitis

THOMAS ALBINI, MD

The treatment approach to uveitis is complex and tailored to the patient’s ocular inflammatory disease and general health. Ruling out infectious causes of uveitis is paramount. Infectious uveitis, such as syphilis, herpetic disease, tuberculosis, Bartonella henselae, and endogenous fungal endophthalmitis, may precipitously deteriorate if treated with anti-inflammatory medications without appropriate antibiotic coverage.

First-line anti-inflammatory treatment is almost always a corticosteroid, delivered by one or a combination of topical, periocular, intravitreal, or systemic methods. Steroids are the most potent and fastest acting therapeutic strategy in the acute phase. Steroid use can cause complications such as cataract and glaucoma with local administration and hypertension, hyperglycemia, insomnia, osteoporosis, and many others with systemic administration. Many cases of uveitis, particularly those involving the posterior segment, tend to be recurring or chronic, requiring long-term treatment. Long-term systemic corticosteroids, specifically doses higher than 10 mg of prednisone daily for more than 2-3 months, is associated with increased rates of complications, including aseptic necrosis of the bone.¹

Traditional steroid-sparing agents are divided into antimetabolites such as methotrexate or mycophenolate mofetil, T-cell inhibitors such as cyclosporine and tacrolimus, and alkylating agents, such as cyclophosphamide and chlorambucil. These agents are not FDA approved for use in uveitis, and they have limited efficacy and possible side effects. All require careful monitoring of labs. Antimetabolites have the best side-effect profile and are typically the first-line steroid-sparing agent. When appropriately monitored, antimetabolites have a better safety profile than steroids in the long term.

The biologic adalimumab, a fully human monoclonal antibody to TNF-alpha, was recently approved by the FDA for the treatment of noninfectious uveitis and is already a commonly used second-line steroid-sparing agent.

Local therapies, especially the surgically inserted Retisert fluocinolone implant (Bausch & Lomb), have been shown to be viable, noninferior alternatives to systemic therapies and are particularly helpful in patients who cannot tolerate or decline systemic therapy. Injectable steroids, such as the Ozurdex dexamethasone implant (Allergan; FDA approved), the Durasert injectable fluocinolone implant (pSivida; not yet FDA approved), or Triescence triamcinolone depot injection (Alcon; FDA approved) have varying degrees of efficacy and may also be used in select cases. All local therapies are limited by the side effects of cataract formation, ocular hypertension, and glaucoma.

Several systemic biologics are in the pipeline, particularly those targeting interleukin-6 and interleukin-17. A few local therapies currently being studied include intravitreal sirolimus and suprachoroidal steroid delivery. Also, the injectable fluocinolone implant may achieve approval from the FDA for treatment of uveitis soon. The goal of these agents is to find effective long-term therapy for uveitis while minimizing side effects. RP

REFERENCES

1. Jabs DA, Rosenbaum JT, Foster CS, et al. Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol. 2000;130(4):492-513.
2. Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group, Kempen JH, Altaweel MM, et al. Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial. Ophthalmology. 2011;118(10):1916-1926. Erratum in: Ophthalmology. 2012;119(2):212.