Juvenile Idiopathic Arthritis Uveitis

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Background

Approximately 6% of all cases of uveitis arise in children.[1] The most frequent cause of chronic intraocular inflammation among children is juvenile idiopathic arthritis (JIA)-associated uveitis.[2] A unifying classification, juvenile idiopathic arthritis (JIA), encompassing juvenile chronic arthritis and juvenile rheumatoid arthritis (JRA), has been developed by consensus.



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Acute anterior uveitis with hypopyon in a child. Courtesy of Manolette Roque, MD, Roque Eye Clinic.

Chronic iridocyclitis occurs in 10-20% of all patients with JIA.[3, 4, 5, 6] Chronic uveitis characteristically is asymptomatic in children with JIA, leading to insidious but progressive morbidity and possible blindness. The involved eyes often are white and quiet appearing, yet 30-40% of patients with JIA-associated uveitis experience severe loss of vision as a consequence of their condition.

JIA, as defined by the American Rheumatism Association (ARA), is the presence of arthritis (chronic, seronegative, and peripheral) before age 16 years, of at least 3 months duration, when other causes have been excluded. It is classified by 1 of 3 types of onset.[7]

Oligoarticular (pauciarticular) onset JIA (40-60%) is common in girls (5:1). Peak age of onset is at age 2 years. Four or fewer joints are involved during the first 6 months of the disease (often asymmetric). Oligoarticular onset commonly involves the knees and, less frequently, the ankles and wrists. The arthritis may be evanescent, rarely destructive, and radiologically insignificant. Approximately 75% of these patients test positive for antinuclear antibody (ANA). This mode of onset rarely is associated with systemic signs. A high risk for uveitis exists.[8]

Polyarticular onset JIA (20-40%) is common in girls (3:1). Peak age of onset is at age 3 years. It involves 5 or more joints during the first 6 months of the disease. Polyarticular onset JIA commonly involves the small joints of the hand and, less frequently, the larger joints of the knee, ankle, or wrist. Asymmetric arthritis may be acute or chronic and may be destructive in 15% of patients. Immunoglobulin M (IgM) rheumatoid factor (RF) is present in 10% of children with this JIA subgroup. It is associated with subcutaneous nodules, erosions, and a poor prognosis. Approximately 40% of these patients test positive for ANA. Systemic symptoms, including anorexia, anemia, and growth retardation, are moderate. An intermediate risk for uveitis exists.

Systemic onset JIA (10-20%) is equal frequency in boys and girls and can appear at any age. Symmetric polyarthritis is present and may be destructive in 25% of patients. Hands, wrists, feet, ankles, elbows, knees, hips, shoulders, cervical spine, and jaw may be involved. ANA is positive in only 10% of the patients. Systemic onset is associated with fever (high in evening and normal in morning), macular rash, leukocytosis, lymphadenopathy, and hepatomegaly. Pericarditis, pleuritis, splenomegaly, and abdominal pain less commonly are observed. A low risk for uveitis exists.

Pathophysiology

The cause of uveitis and arthritis in JIA remains unknown.[9] Akin to many other autoimmune diseases, the target antigen is unidentified. Immune reactions to ocular antigens (S antigen or iris antigen) have been studied; however, their actual role (active or passive) is unknown. The course of the disease may be short and limited or progressive and severe.

Epidemiology

United States

JIA has an estimated prevalence of about 113 cases per 100,000 children. It is estimated that JIA afflicts 60,000-70,000 children, but only a minority develop eye disease. Incidence of eye disease in the JIA population is uncertain, but it is believed to be around 10%.[7]

Mortality/Morbidity

Morbidity in JIA-associated uveitis may result either from lack of treatment or from overzealous treatment. Mortality may result from the latter.

Race

No known racial predilection exists.

Sex

A strong predilection exists for girls. The girl-to-boy ratio is 4:1.

Age

JIA is a childhood disease.

By definition, JIA occurs in children younger than age 16 years.

In view of the fact that the ocular disease can follow the systemic disease by numerous years, a lot of patients are well beyond their teens when they are examined and treated for uveitis.[10]

Prognosis

Most vision-threatening morbidities in JIA are secondary to intraocular inflammation (eg, severity, chronicity). The development of JIA-associated uveitis heralds a poor prognosis.

Of affected eyes, 30-40% maintain long-term acuity greater than 20/40. Conversely, approximately 30-40% develop severe visual disability with acuity less than 20/200.

Poor prognosticators (higher risk for chronic iridocyclitis) include the following[11, 12] :

Patient Education

Patients (and relatives) with JIA-associated uveitis require a significant amount of education regarding the signs and symptoms of disease exacerbation. Emphasize the need for lifestyle changes to prevent exacerbations, to preserve vision, and for appropriate pain control.

The need to maintain regular eye visits to check for ocular activity cannot be overemphasized, if one is to preserve the patients remaining useful vision.

For excellent patient education resources, see eMedicineHealth's patient education articles Juvenile Rheumatoid Arthritis and Rheumatoid Arthritis Medications.

History

Always complete a thorough history of new patients. The ocular immunology and uveitis survey form, developed by Dr. C Stephen Foster, provides a complete checklist (present illness, past medical history, family history, and review of systems) and may assist the physician in the history. The patient questionnaire may be downloaded from the Massachusetts Eye and Ear Infirmary Immunology and Uveitis Service.

Many patients are referred first by a pediatrician or rheumatologist and often are asymptomatic. Typically, patients have no pain or photophobia and the eye appears white.

Asymptomatic patients may recall previous insignificant symptoms that may be useful in determining the duration of the ocular disease. Therefore, ask specific questions regarding past ocular history, such as previous episodes of pink eye or conjunctivitis, blurry vision, ocular pain, or abnormal pupil size/shape.

Past medical history may include the following:

Past ocular history may include the following:

Review of systems may reveal the following:

Physical

Ocular manifestations

Perform a complete ophthalmic examination.

Articular manifestations

Assessment must consist of a quick evaluation of the skin and joints (warmth, redness, effusion, and deformity). Identify the particular joint and number involved.

The ophthalmologist evaluating the patient may perform this; however, the pediatrician or rheumatologist is expected to execute a complete musculoskeletal examination.

Causes

The cause of uveitis and arthritis in JIA remains unknown. Akin to many other autoimmune diseases, the target antigen is unidentified. Associated factors may include the possibility of infectious triggers, a genetic predisposition, an autoimmune response, psychological stress, female sex, and hormone interaction.[13, 9]

Complications

Ocular complications may be sight threatening and include glaucoma, cataract, cyclitic membrane and hypotony, and band keratopathy.[14, 15, 8, 5]

Although uveitis in JIA usually is anterior, vitritis, CME, and optic nerve edema may be present.

Complications from lack of treatment[16]  may include the following:

Complications from treatment[12, 16]  may include the following:

Approach Considerations

The different subtypes of JIA have individual serologic characteristics. Specific laboratory studies may be helpful to gauge the risk for developing uveitis and to rule out other possible diagnoses.[8, 3, 7, 19]

Antinuclear antibody

The term ANA encompasses all the antibodies that can be demonstrated to react with nuclei in tissue sections by the classic indirect immunofluorescence test (IFA).

ANA-positivity is present in most children with oligoarticular onset JIA and uveitis; however, it is present in up to 80% of those without uveitis. For that reason, ANA negativity may be some help in predicting that a child will not develop uveitis, but their positivity does not assist in the prediction of the development of uveitis.

ANA-positivity in young girls with pauciarticular JIA presents the highest risk of developing uveitis.

Rheumatoid factor

RF classically is defined as an IgM antibody to the Fc portion of human immunoglobulin G (IgG) antibody; it often is present in serum in a complex with IgG antibody.

Many patients with JIA who develop uveitis are RF negative. A few adolescent girls who are RF positive have juvenile variant idiopathic arthritis, and they are not at significant risk for developing ocular disease.

Human leukocyte antigen B27

The only HLA antigen with a disease association strong enough to be useful in differential diagnosis is human leukocyte antigen B27 (HLA-B27).

A subgroup of older boys having pauciarticular arthritis with high risk for developing uveitis often is positive for HLA-B27 and negative for both RF and ANA.

A significant percentage of patients with JIA with spinal involvement are HLA-B27 positive.

HLA-B27 determination also is useful in ruling out seronegative spondyloarthropathies.

Imaging Studies

Radiography of joints: Radiographic studies of affected joints typically reveal nondestructive but chronic articular changes.

Other Tests

Additional serologic tests

After undergoing a complete history, a detailed review of systems, and a comprehensive examination, additional serologic tests may be requested based on the findings (differentials). These tests may include the following:

Serologic prognosticators presently under study

Recent investigations are concentrated on determining which specific subsets of ANA and human leukocyte antigen D (human leukocyte antigen DR, human leukocyte antigen DP, and human leukocyte antigen DQ) have significant associations with early onset pauciarticular (EOPA) JIA uveitis.[20]

Human leukocyte antigen DR5 is associated with uveitis in children with oligoarticular JIA. On the other hand, human leukocyte antigen DR1 and human leukocyte antigen DR4 are associated negatively with uveitis.

Histologic Findings

Pathologic results demonstrate that the synovium becomes hyperplastic, with subsynovial lymphocytic infiltration, vascular endothelial hyperplasia, and edema. A comparable histologic picture is observed in the eyes of patients with JIA-associated uveitis where lymphocytes, plasma cells, and scattered giant cells infiltrate the iris and ciliary body.

Approach Considerations

The management of patients with JIA-associated uveitis is difficult primarily because children rarely complain about their vision and are generally difficult to examine. Therefore, the authors of this article advocate a top-down approach in treatment, contrary to the stepladder manner frequently reported.[21, 11, 22, 23] Based on the top-down approach, systemic management is started as soon as possible and at the highest systemically tolerated level to eliminate intraocular inflammation in order to preserve vision potential.

The authors of this article advocate zero tolerance to ocular inflammation. If slit-lamp biomicroscopy examination reveals cells and flare or keratic precipitates, medical management is necessary, regardless of the absence of ocular complaints by the child.

Biologics, anti–tumor necrosis factor (TNF)–alpha agents in particular, are now accepted as the mainstream therapy for JIA-associated uveitis.

Systemic immunomodulatory agents may be useful for patients with limited or no response to systemic corticosteroids or those who develop unacceptable adverse effects.[9, 24, 25, 26, 27, 28, 29, 30, 31, 32]

The decision to use regional corticosteroids depends on the patient's response to topical therapy and/or the presence of posterior segment involvement. Monocular involvement also weighs in more toward regional corticosteroid use. Bilaterality may favor the use of systemic corticosteroids.

The presence of vitreous cells, severe disease, or chronic inflammation increases the risk for CME. These patients may be given additional nonsteroidal anti-inflammatory drugs (NSAIDs).

During the period of quiescence, some cells and flare may be noted, despite previous control with systemic or regional management. Topical corticosteroid treatment may be sufficient in managing the residual or recurrent inflammation. Most patients respond to this initial treatment. Around 20% of patients with JIA-associated uveitis have little or no response and may need systemic or regional management.

Surgical Care

Ethylenediaminetetraacetic acid (EDTA) chelation for band keratopathy may be performed. The procedural technique for EDTA chelation is as follows:

Cataract surgery is reserved for those patients with poor visual acuity or in cases where the vitreous and retina cannot be visualized. The decision to perform cataract surgery should be weighed against the risks and benefits. Routine placement of an intraocular lens is contraindicated in most patients with JIA.[33, 34, 35]

Glaucoma surgery is reserved for patients in whom medical therapy has failed and evidence exists of progressive optic nerve damage.

If vitreous debris prevents optimal vision or examination of the fundus, core vitrectomy for clearing inflammatory debris is a good adjunct to cataract surgery.

Membranectomy/vitrectomy for cyclitic membranes may be performed to prevent phthisis resulting from prolonged hypotony (see the images below).



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Juvenile idiopathic arthritis uveitis. Pseudophakia with posterior chamber intraocular lens with anterior membrane and posterior capsular opacificatio....



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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 memb....

With proper selection of patients and appropriate surgical technique and follow-up, the implantation of an intraocular lens simultaneous with cataract extraction has been shown to yield better visual results than cataract extraction alone. The risk of ocular hypertension, cystoid macular edema, and optic disc swelling was not higher with lens implantation with control of perioperative inflammation.[36]

Whenever the implantation of an intraocular lens is performed simultaneously with cataract extraction, posterior capsulotomy, anterior vitrectomy, and posterior steroid injection (or implantation) appear to improve the prognosis after surgery.[37, 38]

Consultations

A team approach to management of patients with severe, chronic disease requiring systemic immunomodulatory treatment is recommended, as follows:

Prevention

The cause of JIA-associated uveitis is unknown. Therefore, the prevention of the disease has not been established.

Evaluate children who are at risk for JIA-related ocular complications on a frequent regular basis and monitor closely for the development of ocular inflammation.

Long-Term Monitoring

Patients with JIA-associated uveitis need to be seen by an ophthalmologist regularly, every 3 or 4 months (more often if with active uveitis). It is easy to miss flare-ups due to the white and quiet presentation of this type of uveitis. Moreover, children often do not complain of visual problems, precluding the possibility of early detection.

Children with JIA-associated uveitis on systemic medications require meticulous monitoring (CBC, LFTs, BUN, creatinine) for drug toxicity (bone marrow, liver, kidney), disease complications (eg, glaucoma, cataract, band keratopathy), disease exacerbations, or breakthrough inflammation.

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.

Prednisolone acetate (Pred Mild, Pred Forte, Econopred)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Dexamethasone intravitreal implant (OZURDEX)

Clinical Context:  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.

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.

Cyclopentolate 0.5-2% (Cyclogyl)

Clinical Context:  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)

Clinical Context:  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.

Class Summary

These agents block nerve impulses to the pupillary sphincter and ciliary muscles, easing pain and photophobia.

Indomethacin (Indocin)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  For relief of mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Ketorolac ophthalmic (Acular)

Clinical Context:  Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclooxygenase, which results in decreased formation of prostaglandin precursors.

Diclofenac ophthalmic (Voltaren)

Clinical Context:  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.

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.

Etanercept (Enbrel)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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.

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.

Adalimumab (Humira)

Clinical Context:  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)

Clinical Context:  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.

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.

Abatacept (Orencia)

Clinical Context:  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).

Class Summary

Abatacept decreases inflammation by blocking T-cell activation.

Author

Manolette R Roque, MD, MBA, FPAO, Section Chief, Ocular Immunology and Uveitis, Department of Ophthalmology, Asian Hospital and Medical Center; Section Chief, Ocular Immunology and Uveitis, International Eye Institute, St Luke's Medical Center Global City; Senior Eye Surgeon, The LASIK Surgery Clinic; Director, AMC Eye Center, Alabang Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Barbara L Roque, MD, DPBO, FPAO, Senior Partner, Roque Eye Clinic; Chief of Service, Pediatric Ophthalmology and Strabismus Section, Department of Ophthalmology, Asian Hospital and Medical Center; Active Consultant Staff, International Eye Institute, St Luke's Medical Center Global City

Disclosure: Nothing to disclose.

C Stephen Foster, MD, FACS, FACR, FAAO, FARVO, Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Founder and President, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Aldeyra Therapeutics (Lexington, MA); Bausch & Lomb Surgical, Inc (Rancho Cucamonga, CA); Eyegate Pharma (Waltham, MA); Novartis (Cambridge, MA); pSivida (Watertown, MA); Xoma (Berkeley, CA); Allakos (Redwood City, CA)<br/>Serve(d) as a speaker or a member of a speakers bureau for: Alcon (Geneva, Switzerland); Allergan (Dublin, Ireland); Mallinckrodt (Staines-upon-Thames, United Kingdom)<br/>Received research grant from: Alcon; Aldeyra Therapeutics; Allakos Pharmaceuticals; Allergan; Bausch & Lomb; Clearside Biomedical; Dompé pharmaceutical; Eyegate Pharma; Mallinckrodt pharmaceuticals; Novartis; pSivida; Santen; Aciont.

Elisabetta Miserocchi, MD,

Disclosure: Nothing to disclose.

Specialty Editors

Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

R Christopher Walton, MD, Adjunct Professor, Department of Ophthalmology, University of Texas Health Science Center at San Antonio

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Andrew A Dahl, MD, FACS, Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the assistance of Ryan I Huffman, MD, with the literature review and referencing for this article.

References

  1. Nguyen QD, Foster CS. Saving the vision of children with juvenile rheumatoid arthritis-associated uveitis. JAMA. 1998 Oct 7. 280(13):1133-4. [View Abstract]
  2. Päivönsalo-Hietanen T, Tuominen J, Saari KM. Uveitis in children: population-based study in Finland. Acta Ophthalmol Scand. 2000 Feb. 78(1):84-8. [View Abstract]
  3. Boone MI, Moore TL, Cruz OA. Screening for uveitis in juvenile rheumatoid arthritis. J Pediatr Ophthalmol Strabismus. 1998 Jan-Feb. 35(1):41-3. [View Abstract]
  4. Kotaniemi K, Kaipiainen-Seppanen O, Savolainen A, et al. A population-based study on uveitis in juvenile rheumatoid arthritis. Clin Exp Rheumatol. 1999 Jan-Feb. 17(1):119-22. [View Abstract]
  5. Malleson P. Prevalence and outcome of uveitis in a regional cohort of patients with juvenile rheumatoid arthritis. J Rheumatol. 1998 Jun. 25(6):1242. [View Abstract]
  6. Kesen MR, Setlur V, Goldstein DA. Juvenile idiopathic arthritis-related uveitis. Int Ophthalmol Clin. 2008 Summer. 48(3):21-38. [View Abstract]
  7. Wright T, Cron RQ. Pediatric rheumatology for the adult rheumatologist II: uveitis in juvenile idiopathic arthritis. J Clin Rheumatol. 2007 Aug. 13(4):205-10. [View Abstract]
  8. Kanski JJ. Anterior uveitis in juvenile rheumatoid arthritis. Arch Ophthalmol. 1977 Oct. 95(10):1794-7. [View Abstract]
  9. Gallagher KT, Bernstein B. Juvenile rheumatoid arthritis. Curr Opin Rheumatol. 1999 Sep. 11(5):372-6. [View Abstract]
  10. Kotaniemi K. Late onset uveitis in juvenile-type chronic polyarthritis controlled with prednisolone, cyclosporin A and methotrexate. Clin Exp Rheumatol. 1998 Jul-Aug. 16(4):469-71. [View Abstract]
  11. Ceisler EJ, Foster CS. Juvenile rheumatoid arthritis and uveitis: minimizing the blinding complications. Int Ophthalmol Clin. 1996 Winter. 36(1):91-107. [View Abstract]
  12. Wolf MD, Lichter PR, Ragsdale CG. Prognostic factors in the uveitis of juvenile rheumatoid arthritis. Ophthalmology. 1987 Oct. 94(10):1242-8. [View Abstract]
  13. Donn RP, Farhan AJ, Barrett JH, et al. Absence of association between interleukin 1 alpha and oligoarticular juvenile chronic arthritis in UK patients. Rheumatology (Oxford). 1999 Feb. 38(2):171-5. [View Abstract]
  14. Dana MR, Merayo-Lloves J, Schaumberg DA, et al. Visual outcomes prognosticators in juvenile rheumatoid arthritis-associated uveitis. Ophthalmology. 1997 Feb. 104(2):236-44. [View Abstract]
  15. Fox GM, Flynn HW Jr, Davis JL, et al. Causes of reduced visual acuity on long-term follow-up after cataract extraction in patients with uveitis and juvenile rheumatoid arthritis. Am J Ophthalmol. 1992 Dec 15. 114(6):708-14. [View Abstract]
  16. Ozdal PC, Vianna RN, Deschênes J. Visual outcome of juvenile rheumatoid arthritis-associated uveitis in adults. Ocul Immunol Inflamm. 2005 Feb. 13(1):33-8. [View Abstract]
  17. Gray T, Kanski J, Lightman S. Steroid responsive disc neovascularisation in uveitis associated with juvenile chronic arthritis. Br J Ophthalmol. 1998 Mar. 82(3):327-8. [View Abstract]
  18. Ducos de Lahitte G, Terrada C, Tran TH, et al. Maculopathy in uveitis of juvenile idiopathic arthritis: an optical coherence tomography study. Br J Ophthalmol. 2008 Jan. 92(1):64-9. [View Abstract]
  19. Reininga JK, Los LI, Wulffraat NM, et al. The evaluation of uveitis in juvenile idiopathic arthritis (JIA) patients: are current ophthalmologic screening guidelines adequate?. Clin Exp Rheumatol. 2008 Mar-Apr. 26(2):367-72. [View Abstract]
  20. Yen JH, Tsai WC, Tsai JJ, et al. HLA-DMA and HLA-DMB genotyping in patients with rheumatic diseases. Kaohsiung J Med Sci. 1999 May. 15(5):263-7. [View Abstract]
  21. Cassidy JT. Medical management of children with juvenile rheumatoid arthritis. Drugs. 1999 Nov. 58(5):831-50. [View Abstract]
  22. Hemady RK, Baer JC, Foster CS. Immunosuppressive drugs in the management of progressive, corticosteroid-resistant uveitis associated with juvenile rheumatoid arthritis. Int Ophthalmol Clin. 1992 Winter. 32(1):241-52. [View Abstract]
  23. Yu EN, Meniconi ME, Tufail F, et al. Outcomes of treatment with immunomodulatory therapy in patients with corticosteroid-resistant juvenile idiopathic arthritis-associated chronic iridocyclitis. Ocul Immunol Inflamm. 2005 Sep-Oct. 13(5):353-60. [View Abstract]
  24. Kilmartin DJ, Forrester JV, Dick AD. Cyclosporin A therapy in refractory non-infectious childhood uveitis. Br J Ophthalmol. 1998 Jul. 82(7):737-42. [View Abstract]
  25. Okada AA. Immunomodulatory therapy for ocular inflammatory disease: a basic manual and review of the literature. Ocul Immunol Inflamm. 2005 Sep-Oct. 13(5):335-51. [View Abstract]
  26. Shetty AK, Zganjar BE, Ellis GS Jr, et al. Low-dose methotrexate in the treatment of severe juvenile rheumatoid arthritis and sarcoid iritis. J Pediatr Ophthalmol Strabismus. 1999 May-Jun. 36(3):125-8. [View Abstract]
  27. Singer NG, McCune WJ. Update on immunosuppressive therapy. Curr Opin Rheumatol. 1998 May. 10(3):169-73. [View Abstract]
  28. Weiss AH, Wallace CA, Sherry DD. Methotrexate for resistant chronic uveitis in children with juvenile rheumatoid arthritis. J Pediatr. 1998 Aug. 133(2):266-8. [View Abstract]
  29. Imrie FR, Dick AD. Biologics in the treatment of uveitis. Curr Opin Ophthalmol. 2007 Nov. 18(6):481-6. [View Abstract]
  30. Tynjala P, Kotaniemi K, Lindahl P, et al. Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis. Rheumatology (Oxford). 2008 Mar. 47(3):339-44. [View Abstract]
  31. Heiligenhaus A, Mingels A, Heinz C, et al. Methotrexate for uveitis associated with juvenile idiopathic arthritis: value and requirement for additional anti-inflammatory medication. Eur J Ophthalmol. 2007 Sep-Oct. 17(5):743-8. [View Abstract]
  32. Ilowite NT. Update on biologics in juvenile idiopathic arthritis. Curr Opin Rheumatol. 2008 Sep. 20(5):613-8. [View Abstract]
  33. BenEzra D, Cohen E. Cataract surgery in children with chronic uveitis. Ophthalmology. 2000 Jul. 107(7):1255-60. [View Abstract]
  34. Holland GN. Intraocular lens implantation in patients with juvenile rheumatoid arthritis-associated uveitis: an unresolved management issue. Am J Ophthalmol. 1996 Aug. 122(2):255-7. [View Abstract]
  35. Acevedo S, Quinones K, Rao V, et al. Cataract surgery in children with juvenile idiopathic arthritis associated uveitis. Int Ophthalmol Clin. 2008 Spring. 48(2):1-7. [View Abstract]
  36. Sijssens KM, Los LI, Rothova A, Schellekens PA, van de Does P, Stilma JS. Long-term ocular complications in aphakic versus pseudophakic eyes of children with juvenile idiopathic arthritis-associated uveitis. Br J Ophthalmol. 2010 Sep. 94(9):1145-9. [View Abstract]
  37. Grajewski RS, Zurek-Imhoff B, Roesel M, Heinz C, Heiligenhaus A. Favourable outcome after cataract surgery with IOL implantation in uveitis associated with juvenile idiopathic arthritis. Acta Ophthalmol. 2012 Nov. 90(7):657-62. [View Abstract]
  38. Cordero-Coma M, Garzo I, Calleja S, Galán E, Franco M, Ruíz de Morales JG. Preoperative cataract surgery use of an intravitreal dexamethasone implant (Ozurdex) in a patient with juvenile idiopathic arthritis and chronic anterior uveitis. J AAPOS. 2013 Dec. 17(6):632-4. [View Abstract]
  39. Aggarwal A, Misra RN. Juvenile rheumatoid arthritis in India--rarity of antinuclear antibody and uveitis. Indian J Pediatr. 1996 May-Jun. 63(3):301-4. [View Abstract]
  40. Akinci A, Cakar N, Uncu N, et al. Keratoconjunctivitis sicca in juvenile rheumatoid arthritis. Cornea. 2007 Sep. 26(8):941-4. [View Abstract]
  41. Anesi SD, Foster CS. The importance of recognizing juvenile idiopathic arthritis-associated uveitis and preventing blindness from it. Arthritis Care Res (Hoboken). 2012 Jan 9. [View Abstract]
  42. Angeles-Han S, Yeh S. Prevention and management of cataracts in children with juvenile idiopathic arthritis-associated uveitis. Curr Rheumatol Rep. 2012 Apr. 14(2):142-9. [View Abstract]
  43. Angeles-Han ST, Griffin KW, Harrison MJ, Lehman TJ, Leong T, Robb RR, et al. Development of a vision-related quality of life instrument for children ages 8-18 years for use in juvenile idiopathic arthritis-associated uveitis. Arthritis Care Res (Hoboken). 2011 Sep. 63(9):1254-61. [View Abstract]
  44. Baldassano VF Jr. Ocular manifestations of rheumatic diseases. Curr Opin Ophthalmol. 1998 Dec. 9(6):85-8. [View Abstract]
  45. Dollfus H. Eye involvement in children's rheumatic diseases. Baillieres Clin Rheumatol. 1998 May. 12(2):309-28. [View Abstract]
  46. Grajewski RS, Zurek-Imhoff B, Roesel M, Heinz C, Heiligenhaus A. Favourable outcome after cataract surgery with IOL implantation in uveitis associated with juvenile idiopathic arthritis. Acta Ophthalmol. 2011 Feb 11. [View Abstract]
  47. Heiligenhaus A, Foeldvari I, Edelsten C, Smith JR, Saurenmann RK, Bodaghi B, et al. Proposed outcome measures for prospective clinical trials in juvenile idiopathic arthritis-associated uveitis: A consensus effort from the multinational interdisciplinary working group for uveitis in childhood (MIWGUC). Arthritis Care Res (Hoboken). 2012 Mar 21. [View Abstract]
  48. Heiligenhaus A, Michels H, Schumacher C, Kopp I, Neudorf U, Niehues T, et al. Evidence-based, interdisciplinary guidelines for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis. Rheumatol Int. 2011 Nov 15. [View Abstract]
  49. Heiligenhaus A, Miserocchi E, Heinz C, Gerloni V, Kotaniemi K. Treatment of severe uveitis associated with juvenile idiopathic arthritis with anti-CD20 monoclonal antibody (rituximab). Rheumatology (Oxford). 2011 Aug. 50(8):1390-4. [View Abstract]
  50. Heinz C, Schumacher C, Roesel M, Heiligenhaus A. Elevated intraocular pressure in uveitis associated with juvenile idiopathic arthritis-associated uveitis, often detected after achieving inactivity. Br J Ophthalmol. 2012 Jan. 96(1):140-1. [View Abstract]
  51. Hoeve M, Kalinina Ayuso V, Schalij-Delfos NE, Los LI, Rothova A, de Boer JH. The clinical course of juvenile idiopathic arthritis-associated uveitis in childhood and puberty. Br J Ophthalmol. 2012 Mar 7. [View Abstract]
  52. Kalinina Ayuso V, van de Winkel EL, Rothova A, de Boer JH. Relapse rate of uveitis post-methotrexate treatment in juvenile idiopathic arthritis. Am J Ophthalmol. 2011 Feb. 151(2):217-22. [View Abstract]
  53. Kenawy N, Cleary G, Mewar D, Beare N, Chandna A, Pearce I. Abatacept: a potential therapy in refractory cases of juvenile idiopathic arthritis-associated uveitis. Graefes Arch Clin Exp Ophthalmol. 2011 Feb. 249(2):297-300. [View Abstract]
  54. Kotaniemi K, Säilä H, Kautiainen H. Long-term efficacy of adalimumab in the treatment of uveitis associated with juvenile idiopathic arthritis. Clin Ophthalmol. 2011. 5:1425-9. [View Abstract]
  55. Qian Y, Acharya NR. Juvenile idiopathic arthritis-associated uveitis. Curr Opin Ophthalmol. 2010 Nov. 21(6):468-72. [View Abstract]
  56. Rabinovich CE. Treatment of juvenile idiopathic arthritis-associated uveitis: challenges and update. Curr Opin Rheumatol. 2011 Sep. 23(5):432-6. [View Abstract]
  57. Singh S, Salaria M, Kumar L, et al. Clinico-immunological profile of juvenile rheumatoid arthritis at Chandigarh. Indian Pediatr. 1999 May. 36(5):449-54. [View Abstract]
  58. Tappeiner C, Heinz C, Roesel M, Heiligenhaus A. Elevated laser flare values correlate with complicated course of anterior uveitis in patients with juvenile idiopathic arthritis. Acta Ophthalmol. 2011 Sep. 89(6):e521-7. [View Abstract]
  59. Heiligenhaus A, Minden K, Tappeiner C, et al. Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis. Semin Arthritis Rheum. 2018 Dec 4. [View Abstract]
  60. Jabs DA. Immunosuppression for the Uveitides. Ophthalmology. 2018 Feb. 125 (2):193-202. [View Abstract]

Acute anterior uveitis with hypopyon in a child. Courtesy of Manolette Roque, MD, Roque Eye Clinic.

Juvenile idiopathic arthritis uveitis. Band keratopathy. Courtesy of Manolette Roque, MD, Roque Eye Clinic.

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.

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.

Acute anterior uveitis with hypopyon in a child. Courtesy of Manolette Roque, MD, Roque Eye Clinic.

Juvenile idiopathic arthritis uveitis. Band keratopathy. Courtesy of Manolette Roque, MD, Roque Eye Clinic.

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.

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.