Medication Summary
The treatment of JIA-associated uveitis is a step-wise progression beginning with topical steroids and mydriatics, progressing to regional steroids, systemic NSAIDs, systemic steroids, immunosuppressive agents, and biologics.
Corticosteroids
Class Summary
These agents decrease inflammation. When considered, corticosteroid treatment often is initiated only after consultation with an ophthalmologist. However, long-term systemic therapy results in an unfavorable visual prognosis.
Prednisolone acetate (Pred Mild, Pred Forte, Econopred)
Strongest steroid of its group and best choice for uveitis. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Triamcinolone (Kenalog)
Periocular injections of corticosteroids reserved for patients with more severe disease, or those with posterior segment (eg, vitreous) inflammation. Also used in patients at high risk for CME.
Prednisone (Deltasone)
May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Dexamethasone intravitreal implant (OZURDEX)
Dexamethasone is a potent corticosteroid that suppresses inflammation by inhibiting multiple inflammatory cytokines. This inhibition results in decreased edema, fibrin deposition, capillary leakage, and migration of inflammatory cells. Its FDA-approved indications include treatment of macular edema following branch retinal vein occlusion or central retinal vein occlusion, and treatment of noninfectious uveitis affecting the posterior segment of the eye.
Cycloplegics
Class Summary
These agents block nerve impulses to the pupillary sphincter and ciliary muscles, easing pain and photophobia.
Cyclopentolate 0.5-2% (Cyclogyl)
Induces cycloplegia in 25-75 min and mydriasis in 30-60 min. These effects last up to 1 d; however, the duration may be less in the setting of a severe anterior chamber reaction. For this reason, cyclopentolate is less attractive for treating uveitis than homatropine.
Homatropine (Isopto)
Induces cycloplegia in 30-90 min and mydriasis in 10-30 min. Useful in treating pain from ciliary spasm and decreasing formation of synechiae. These effects last 10-48 h for cycloplegia and 6 h to 4 d for mydriasis, but the duration may be less in the setting of a severe anterior chamber reaction. Homatropine is the preferred agent of choice for uveitis.
Nonsteroidal anti-inflammatory drugs
Class Summary
NSAIDs reduce pain and inflammation and allow for improvements in mobility and function. Used to reduce effect of diffusing prostaglandins on retinal microvasculature and, hence, used in patients at high risk for the development of CME. There are several NSAIDs; however, no single agent exists that is superior to another. Naproxen is used commonly in children.
Indomethacin (Indocin)
For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.
Naproxen (Anaprox, Naprelan, Naprosyn)
For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.
Ibuprofen (Ibuprin, Advil, Motrin)
For relief of mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Ketorolac ophthalmic (Acular)
Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase, which results in decreased formation of prostaglandin precursors.
Diclofenac ophthalmic (Voltaren)
Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which, in turn, decreases formation of prostaglandin precursors. May facilitate outflow of aqueous humor and decreases vascular permeability.
Immunosuppressives (systemic)
Class Summary
These are second-line agents that ameliorate the disease process. Most frequently they are used in combination with first-line agents. They include methotrexate, cyclosporin A, cyclophosphamide, and chlorambucil.
Etanercept (Enbrel)
Binds specifically to tumor necrosis factor (TNF) and blocks its interaction with cell-surface TNF receptor. TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses.
Methotrexate (Folex PFS)
Folic acid analog, decreases inflammation, and has steroid-sparing effect. Useful in JIA-associated uveitis, where may reduce inflammation in patients who do not respond adequately to steroid treatment.
Cyclosporine (Sandimmune)
Potent immunosuppressive agent with narrow therapeutic range. Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft-vs-host disease) for a variety of organs.
Cyclophosphamide (Cytoxan, Neosar)
Chemically related to nitrogen mustards. As alkylating agent, mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Chlorambucil (Leukeran)
Aromatic nitrogen mustard derivative that acts as bifunctional alkylating agent. Alkylation takes place through formation of highly reactive ethylenimonium radical. Probable mode of action involves cross-linkage of the ethylenimonium derivative between 2 strands of helical DNA and subsequent interference with replication.
Tumor necrosis factor (TNF) inhibitors
Class Summary
TNF is a cytokine of which 2 forms have been identified with similar biological properties. TNF-alpha or cachectin is produced predominantly by macrophages, and TNF-beta or lymphotoxin is produced by lymphocytes. TNF is but one of many cytokines involved in the inflammatory cascade that may contribute to symptoms.
Adalimumab (Humira)
Recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF). Indicated to reduce inflammation and inhibit progression of structural damage in moderate-to-severe rheumatoid arthritis. Reserved for those who experience inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). Can be used alone or in combination with methotrexate (MTX) or other DMARDs. Binds specifically to TNF-alpha and blocks interaction with p55 and p75 cell-surface TNF receptors. In 2008, adalimumab was approved by the FDA for juvenile idiopathic arthritis.
Infliximab (Remicade)
Chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-alpha and inhibits its binding to TNF-alpha receptor. Reduces infiltration of inflammatory cells and TNF-alpha production in inflamed areas. Used with methotrexate in patients who have had inadequate response to methotrexate monotherapy.
Immunomodulator
Class Summary
Abatacept decreases inflammation by blocking T-cell activation.
Abatacept (Orencia)
Selective co-stimulation modulator that inhibits T-cell activation by binding to CD80 and CED86, thereby blocking CD28 interaction. CD28 interaction provides a signal needed for full T-cell activation that is implicated in RA pathogenesis. Indicated for reducing signs and symptoms of RA, slowing progression of structural damage and improving physical function in adults with moderate-to-severe RA who have inadequate response to DMARDs, methotrexate, or TNF antagonists. May be used as monotherapy or with DMARDs (other than TNF antagonists, because of increased risk of serious infections [4.4% vs 0.8%]). Not recommended for concomitant use with anakinra (insufficient experience).
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Acute anterior uveitis with hypopyon in a child. Courtesy of Manolette Roque, MD, Roque Eye Clinic.
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Juvenile idiopathic arthritis uveitis. Band keratopathy. Courtesy of Manolette Roque, MD, Roque Eye Clinic.
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Juvenile idiopathic arthritis uveitis. Pseudophakia with posterior chamber intraocular lens with anterior membrane and posterior capsular opacification with cyclitic membrane formation. Courtesy of Manolette Roque, MD, Roque Eye Clinic.
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Juvenile idiopathic arthritis uveitis. Use of Grieshaber iris hooks to create and maintain a large enough pupil for adequate visualization during membranectomy and pars plana vitrectomy in a pseudophakic child. The intraocular lens was clear after the anterior lenticular membrane was peeled off. Courtesy of Manolette Roque, MD, Roque Eye Clinic.
