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Intermediate uveitis was first described by Ernst Fuchs in 1908 as chronic cyclitis. Other terms used over the years include vitritis, peripheral exudative retinitis, cyclochorioretinitis, chronic posterior cyclitis and peripheral uveoretinitis. Today, intermediate uveitis (IU) is the preferred term.
According to the Standardization of Uveitis Nomenclature Working Group,1 the classification of uveitis is made on the basis of the site of inflammation and not on the presence of structural complications. In IU, the primary anatomic location of inflammation is the vitreous and includes the pars plana and ciliary body.
The term pars planitis is used to describe a subset of IU in which exudates, commonly referred to as snowbanks, form over the pars plana (Fig. 1). Even though pars planitis is not a separate clinical entity, it is associated with worse vitritis, more severe macular edema and worse visual prognosis than are other types of IU.
Intermediate uveitis most commonly presents in young adults. Although it is relatively uncommon in children, it may account for up to 25 percent of all childhood uveitis cases.2
In a retrospective study conducted at a tertiary referral center, the mean age at onset of pediatric IU was 9 years old. With regard to gender, males predominated; with regard to ethnicity, the majority were Caucasian.3
Signs and symptoms. Most cases of pediatric IU are bilateral, nongranulomatous, noninfectious and recurrent.3 Patients typically present with blurred vision and floaters, but they may be asymptomatic. The most characteristic finding is vitritis. As noted above, snowbank formation is the hallmark of pars planitis; the mass most often is located along the inferior ora serrata and can best be seen with scleral depression while the patient is looking down. It is important to examine the area for neovascularization, which can be a source of vitreous hemorrhage.2
Etiology. Although most pediatric IU cases are idiopathic, a systemic workup is recommended to evaluate for underlying disorders (see “Possible Etiologies”). Some of the disease entities associated with adult IU, such as multiple sclerosis (MS) and intraocular lymphoma, are rare in children. Others, such as toxocariasis, present more commonly in childhood. It should be noted that some specialists use the term intermediate uveitis only when an underlying systemic cause is not found.
With regard to MS, a diagnosis of IU is associated with an increased chance of developing the disease. In one study, 43.5 percent of patients with IU demonstrated demyelinating lesions on MRI.4 Overall, MS rarely occurs in children; in that same study, only 13 percent of the IU patients with demyelinating lesions were younger than 25 years of age.4 Nonetheless, based on some studies and case reports, it appears that IU presenting in childhood may occasionally precede the development of MS.
Pediatric IU has several features generally not seen in adult-onset cases.
Poor visual acuity. Children presenting with IU have worse visual acuity at both initial diagnosis and follow-up than do adult patients. The reasons for this are not clear. Childhood IU may be a more aggressive disease process resulting in a worse prognosis. Alternatively, the relative inability of children to effectively communicate their symptoms may lead to a delay in diagnosis and, therefore, more advanced disease at presentation.
Risk of vitreous hemorrhage. Children with IU experience a higher rate of vitreous hemorrhage. In one study, 28 percent of children with pars planitis had vitreous hemorrhage, compared with 6 percent of adult patients.5 Moreover, vitreous hemorrhage was the presenting symptom in 20 percent of children, versus 1 percent of adults. The median age at diagnosis of uveitis was 14.5 years for patients with pars planitis complicated by vitreous hemorrhage, compared with 26 years for those without vitreous hemorrhage.
Anterior segment. Children with IU are more likely to experience anterior segment inflammation; some may present only with anterior uveitis and develop features of IU later in the course of disease. In contrast, most adults with IU have minimal anterior segment inflammation.
Amblyopia. It is important to keep the potential for amblyopia in mind when IU or its complications occur during childhood. As treatment of IU alone may not be sufficient to restore vision, amblyopia therapy should be begun in a timely manner.
Other complications. Cystoid macular edema, diffuse retinal vascular leakage, periphlebitis and optic disc edema may occur in active disease. Interestingly, 50 percent of children with IU have optic disc edema.2
Like adults with IU, pediatric patients are at risk of developing glaucoma, cataracts, band keratopathy, posterior synechiae, hypotony, rubeosis, retinal detachment and/or neovascularization of the disc and retina.
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Overall, adults are treated for IU more often than are children. This could be attributed to reluctance of both parents and doctors to start corticosteroids or other immunosuppressants.
Medication. In general, after infectious and malignant etiologies are ruled out, the first-line treatment is systemic corticosteroids. Topical steroids are ineffective for most phakic patients.
For unilateral IU, periocular or intravitreal injections often are given. However, children require general anesthesia or monitored sedation for these procedures, which limits their use. In addition, steroid-induced IOP elevation occurs more rapidly in children than in adults, and the rate of steroid-induced cataracts also is higher in children. If periocular steroid injections are selected as the treatment modality, they should be administered two to four times over a four- to 12-week period before the IU is considered resistant to periocular corticosteroid. 2 Sustained-release intravitreal steroid implants, such as Ozurdex, have become an option for noninfectious uveitis. Although these implants have not been tested extensively in children (and are not approved for use in this population), they may present a better vehicle for local steroid delivery.
For bilateral IU, systemic cortico-steroids are the preferred initial treatment. Steroid-related growth retardation is of particular concern. If corticosteroid treatment fails or patients develop side effects or require prolonged high-dose treatment (unable to taper below 10 to 15 mg/day for longer than three months), then steroid-sparing agents—such as azathioprine, cyclosporine, methotrexate or mycophenolate mofetil—can be added. Biologic immunomodulating agents are the next line of treatment and include adalimumab and infliximab, which inhibit tumor necrosis factor-alpha, and other immunomodulators, such as rituximab. It should be noted that some immunomodulators have been linked with central nervous system demyelinating disease and MS.
Surgery. Surgical intervention may be appropriate in selected cases. Cryotherapy can be used to destroy the neovascular component of a snowbank and eliminate a potential site for inflammatory mediators. Another option is pars plana vitrectomy, which removes inflammatory mediators from the eye and may facilitate resolution of the disease or minimize the need for long-term immunosuppressive therapy. (One caution: The usual surgery-safe zones must be free of inflammatory exudates.) Of course, complications such as cataracts, glaucoma and retinal detachment require surgical treatment.
Intermediate uveitis accounts for up to a quarter of all childhood uveitis cases. It is most often noninfectious and idiopathic. Compared with adult-onset IU, it carries a worse visual prognosis, an increased risk of vitreous hemorrhage and a higher frequency of anterior segment involvement. Notable challenges in treating children include their decreased ability to describe symptoms, resulting in delayed diagnosis; difficulties with examination and treatment; the potential for amblyopia; and the risk of growth retardation with steroid use. Early recognition and treatment are essential for preserving vision, and a multidisciplinary approach may be required.
1 Jabs DA et al. Am J Ophthalmol. 2005;140(3):509-516.
2 Whitcup SM. “Intermediate Uveitis,” in Uveitis: Fundamentals and Clinical Practice
(Philadelphia: Mosby; 2004).
3 Kump LI et al. Ophthalmology. 2005;112(7):1287-1292.
4 Prieto JF et al. Ocular Immunol Inflam. 2001;9(2):93-102.
5 Lauer AK et al. Ophthalmology. 2002;109(1):95-98.
Mr. Prinzi is a medical student, Dr. Fasiuddin is an assistant clinical professor in the pediatric ophthalmology service and Dr. Selvadurai is an assistant clinical professor in the retina and uveitis service; all are at the University at Buffalo, N.Y.