Juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA; formerly referred to as juvenile chronic arthritis and juvenile rheumatoid arthritis), is the most common systemic disorder associated with anterior uveitis in the pediatric age group. It is characterized by arthritis beginning before age 16 years and lasting for at least 6 weeks.

Ocular involvement JIA can be classified into 5 types according to medical history and other presenting factors according to International League of Associations of Rheumatology (ILAR) guidelines:

• Systemic onset (Still disease). This type, usually observed in children under age 5 years, accounts for approximately 10%–15% of all cases of JIA. It is characterized by fever, rash, lymphadenopathy, and hepatosplenomegaly. Joint involvement may be minimal or absent initially. Ocular involvement is rare.

• Polyarticular onset. Patients with this type show involvement of more than 4 joints in the first 6 months of the disease; it represents 40% of JIA cases overall but only about 10% of cases of JIA-associated anterior uveitis. Patients who are positive for rheumatoid factor may not develop uveitis.

• Oligoarticular onset. This type, previously also known as pauciarticular onset, constitutes 40%–50% of all cases of JIA and includes 80%–90% of patients with JIA-associated uveitis. Four or fewer joints may be involved during the first 6 months of disease, and patients may have no joint symptoms. Girls under age 5 years and positive for antinuclear antibody (ANA) are at increased risk of developing chronic anterior uveitis; 25%–35% of these patients will develop uveitis, most in the first 4 years.

Other subgroups of JIA include enthesitis-related arthritis (ERA) and psoriatic arthritis (or psoriatic JIA). ERA accounts for 10%–20% of cases of JIA. Enthesitis, axial disease, and HLA-B27 positivity are common. The uveitis in these patients is more likely to be acute and recurrent, with pain, redness, and photophobia.

The average age of onset of uveitis in patients with JIA is 6 years. Uveitis generally develops within 5–7 years of the onset of joint disease but may occur as long as 28 years after the development of arthritis. There is usually little or no correlation between severity or timing of ocular and joint inflammation. Risk factors for the development of chronic uveitis in patients with JIA include female sex, oligoarticular onset, and the presence of circulating ANA. Most patients test negative for rheumatoid factor. HLA-DRB1*11 and *13 may be associated with increased risk of uveitis among JIA patients.

The eye is frequently white. Symptoms may include mild to moderate pain, photophobia, and blurring, although some patients are asymptomatic. Often, the eye disease is found incidentally during a routine screening or physical examination. The signs of inflammation include fine KPs, band keratopathy, flare and cells, posterior synechiae, and cataract (Fig 8-14). Patients in whom JIA is suspected should undergo ANA testing and be evaluated by a pediatric rheumatologist because the joint disease may be minimal or absent at the time the uveitis is diagnosed. The differential diagnosis includes TINU, Fuchs uveitis syndrome, sarcoidosis, Blau disease, Behçet disease, the seronegative spondyloarthropathies, herpetic uveitis, and Lyme disease.

Prognosis Because of the frequently asymptomatic nature of the uveitis, profound silent ocular damage can occur, and long-term prognosis often depends on the extent of structural complications at the time of first diagnosis. Complications are frequent and often severe; they include band keratopathy, cataract, glaucoma, macular edema, chronic hypotony, and phthisis. Children with JIA, especially those who are ANA positive or have oligoarticular disease, should undergo regular slit-lamp examinations. Table 8-1 outlines the recommended schedule for screening patients with JIA for development of uveitis, as developed by the American Academy of Pediatrics.

Treatment The initial treatment for patients with JIA who have uveitis consists of topical corticosteroids. More severe cases may require use of systemic corticosteroids or IMT. The goal of treatment is to eliminate active inflammation (anterior chamber cells) and prevent new complications. Short-acting mydriatic drugs may be useful in patients with chronic flare to keep the pupil mobile and to prevent posterior synechiae formation. Use of systemic NSAIDs may permit a lower dose of corticosteroids.

Figure 8-14 Juvenile idiopathic arthritis with complicated chronic calcific band keratopathy, cataract, and glaucoma in a patient with peripheral iridectomy superonasally.

(Courtesy of H. Nida Sen, MD/National Eye Institute.)

Table 8-1 Frequency of Ophthalmologic Examination in Patients With Juvenile Idiopathic Arthritis

Because of the chronic nature of the inflammation, corticosteroid-induced complications are common. The long-term use of systemic corticosteroids in children may lead to growth retardation from premature closure of the epiphyses. Also, prolonged use of topical corticosteroids leads to cataracts and glaucoma. Because long-term use of topical corticosteroids at doses ≥3 times daily can increase the risk of cataract formation, systemic IMT should be considered for such cases. In addition, there is evidence that even low-grade inflammation, if present for a prolonged period, can result in unacceptable ocular morbidity and loss of vision. For these reasons, many of these children are treated with methotrexate. Numerous studies have shown that this treatment regimen can effectively control the uveitis, is generally well tolerated, and can spare patients the complications of longterm corticosteroid use. In addition, several studies have demonstrated a benefit from TNF inhibitors and other biologic agents.

Treatment of cataracts in patients with JIA remains a challenge, and the use of IOLs remains controversial. Children who are left aphakic may develop amblyopia. Cataract surgery in patients with JIA-associated anterior uveitis has a high complication rate due to the difficulty in controlling the more aggressive inflammatory response present in these children. Lensectomy and vitrectomy via the pars plana have been advocated.

There have been reports, however, of more successful cataract surgery with IOL implants in patients with JIA. These reports highlight the importance of well-controlled uveitis through systemic IMT and the use of perioperative corticosteroids.

The following considerations are useful when selecting patients with JIA for cataract surgery with IOL implants:

• Patients’ intraocular inflammation must be well controlled with systemic IMT for at least 3 months before surgery and must not require frequent instillation of topical corticosteroids.

• Only acrylic lenses should be implanted.

• Patients must be monitored frequently after cataract surgery to watch for any inflammation, and inflammation that occurs must be aggressively treated.

• IMT must be used preoperatively and postoperatively, not just perioperatively.

• Because long-term results are not available, patients must be strongly advised about the need for careful, regular, lifelong follow-up to detect late complications that may lead to loss of the eye.

• The ophthalmologist must have a low threshold for IOL explantation in patients who have persistent postoperative inflammation and recurrent cyclitic membranes.

Patients with band keratopathy should be treated (eg, using chelation with sodium ethylenediaminetetraacetic acid [EDTA]) and allowed to heal well before cataract surgery is attempted. See also Chapter 14 and BCSC Section 6, Pediatric Ophthalmology and Strabismus, Chapter 24.

Glaucoma should be treated with medical therapy initially, although surgical intervention is often necessary in severe cases. Standard filtering procedures are usually unsuccessful, and the use of antifibrotic drugs or aqueous drainage devices is usually required for successful control of the glaucoma.

• Angeles-Han S, Yeh S. Prevention and management of cataracts in children with juvenile idiopathic arthritis–associated uveitis. Curr Rheumatol Rep. 2012;14(2):142–149.

• Clarke SL, Sen ES, Ramanan AV. Juvenile idiopathic arthritis-associated uveitis. Pediatr Rheumatol Online J. 2016;14(1):27.

• 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;90(7):657–662.

• Gregory AC 2nd, Kempen JH, Daniel E, Kaçmaz RO, et al; Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study Research Group. Risk factors for loss of visual acuity among patients with uveitis associated with juvenile idiopathic arthritis: the Systemic Immunosuppressive Therapy for Eye Diseases Study. Ophthalmology. 2013;120(1):186–192.

• Mehta PJ, Alexander JL, Sen HN. Pediatric uveitis: new and future treatments. Curr Opin Ophthalmol. 2013;24(5):453–462.

• Simonini G, Taddio A, Cattalini M, et al. Superior efficacy of adalimumab in treating childhood refractory chronic uveitis when used as first biologic modifier drug: adalimumab as starting anti-TNF-α therapy in childhood chronic uveitis. Pediatr Rheumatol Online J. 2013;11(1):16.

• Thorne JE, Woreta FA, Dunn JP, Jabs DA. Risk of cataract development among children with juvenile idiopathic arthritis–related uveitis treated with topical corticosteroids. Ophthalmology. 2010;117(7):1436–1441.

• Zannin ME, Birolo C, Gerloni VM, et al. Safety and efficacy of infliximab and adalimumab for refractory uveitis in juvenile idiopathic arthritis: 1-year followup data from the Italian Registry. J Rheumatol. 2013;40(1):74–79.

Fuchs uveitis syndrome

Fuchs uveitis syndrome (sometimes called Fuchs heterochromic iridocyclitis or Fuchs heterochromic uveitis) constitutes 2%–3% of patients referred to uveitis clinics. This condition is usually unilateral, and symptoms vary from none to mild blurring and discomfort. Signs include

• diffuse iris stromal atrophy with variable pigment epithelial layer atrophy (Fig 8-15)

• small, white, stellate KPs scattered diffusely over the entire endothelium (Fig 8-16)

• iris nodules

• cells in the anterior chamber as well as in the anterior vitreous

• late staining of the optic nerve on fluorescein angiography

• glaucoma and cataracts, which occur frequently

In addition, synechiae, chorioretinal scars, and retinal periphlebitis are rare or absent and macular edema is seldom present.

The diagnosis is made according to the distribution of KPs, presence of heterochromia, lack of synechiae, and lack of symptoms. Heterochromia may be subtle in a browneyed patient, and the clinician must look carefully for signs of iris stromal atrophy. Often, the inflammation is discovered during a routine examination, such as when a unilateral cataract develops. Usually, but not invariably, a lighter-colored iris indicates the involved eye. In blue-eyed persons, however, the affected eye may become darker as the stromal atrophy progresses and the darker iris pigment epithelium shows through.

Fuchs uveitis syndrome is now known to be associated with viral infections such as rubella and CMV. Association with ocular toxoplasmosis has also been reported.

Patients generally do well with cataract surgery, and IOLs can usually be implanted successfully. However, some patients experience substantial visual disability because of extensive vitreous opacification. Pars plana vitrectomy should be carefully considered in such instances. Glaucoma control can be difficult. Abnormal vessels bridging the angle can be seen on gonioscopy. These vessels may bleed during surgery, resulting in postoperative hyphema.

Figure 8-15 Heterochromia in Fuchs uveitis syndrome. A, Right (unaffected) eye. B, Left (affected) eye in the same patient. Note the lighter iris color and stromal atrophy (“moth-eaten appearance”) in the affected eye, which underwent surgical iridectomy at the same time as cataract surgery.

(Courtesy of H. Nida Sen, MD/National Eye Institute.)

Figure 8-16 Diffusely distributed stellate keratic precipitates in a patient with Fuchs uveitis syndrome.

(Courtesy of H. Nida Sen, MD/National Eye Institute.)

Few cases require therapy for inflammation. The prognosis is good in most cases, even when the inflammation persists for decades. Because topical corticosteroids can lessen the inflammation but typically do not resolve it, aggressive treatment to eradicate the cellular reaction is not indicated. Cycloplegia is seldom necessary. See BCSC Section 10, Glaucoma, for further discussion of Fuchs heterochromic uveitis (Fuchs uveitis syndrome).

• Accorinti M, Spinucci G, Pirraglia MP, Bruschi S, Pesci FR, Iannetti L. Fuchs’ heterochromic iridocyclitis in an Italian tertiary referral centre: epidemiology, clinical features, and prognosis. J Ophthalmol. 2016;2016:1458624.

• Birnbaum AD, Tessler HH, Schultz KL, et al. Epidemiologic relationship between Fuchs heterochromic iridocyclitis and the United States rubella vaccination program. Am J Ophthalmol. 2007;144(3):424–428.

• de Groot-Mijnes JD, de Visser L, Rothova A, Schuller M, van Loon AM, Weersink AJ. Rubella virus is associated with Fuchs heterochromic iridocyclitis. Am J Ophthalmol. 2006;141(1):212–214.

Undifferentiated anterior uveitis

Inability to positively identify a diagnosis, as is the case in many patients with chronic anterior uveitis, does not preclude treatment with topical steroids and/or cycloplegics, other steroids, or systemic steroid-sparing agents, assuming infectious causes have been ruled out. In some cases initially labeled idiopathic, repeat diagnostic testing at a later date as the clinical picture evolves may reveal an underlying systemic condition.

Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.