necessitate their use. In patients that fail systemic and periocular corticosteroids, systemic immunomodulatory therapy with methotrexate, azathioprine, mycophenolate mofetil, or cyclosporine may become necessary.

Complications of ocular sarcoidosis in children can result from untreated or inadequately treated disease, or as a side-effect of corticosteroid therapy. Chronic uveitis can result in band keratopathy. Anterior segment inflammation can lead to anterior and posterior synechiae. Posterior synechiae and iris granulomas can lead to iris bombe and angle-closure glaucoma. Secondary open-angle glaucoma can also develop. Cataracts commonly occur.

Untreated or inadequately treated posterior uveitis can lead to macular edema and optic disc edema with subsequent atrophy. Neovascularization of the retina and optic disc can result from large areas of capillary nonperfusion. In some cases, phthisis bulbi can result.

19.4.5  Pars Planitis

19.4.5.1  Historical Context

Intermediate uveitis, as defined by the SUN Working Group, is the subset of uveitis where the major site of inflammation is in the vitreous [2]. It was originally described by Fuchs in 1908 as “chronic cyclitis.” The term pars planitis, first used by Welch et al. in 1960 [61] today refers to the subset of intermediate uveitis where there is snow-bank or snowball formation (see below) in the absence of an associated infection or systemic disease.

19.4.5.2  Clinical Findings/Natural History

Intermediate uveitis is more common in children than adults, comprising 25% of all cases of uveitis in children versus 15% in adults [16]. Pars planitis is the most common form of intermediate uveitis, encompassing 85–95% of cases. It has a bimodal distribution, affecting children (age 5–15 years old) and young adults (20–40 years old); it has an approximately equal sex distribution. Approximately 80% of cases of pars planitis are bilateral, but can be asymmetric in severity [62].

The onset of disease in children may consist of a significant anterior chamber reaction with redness,

photophobia, and discomfort of the eye. In teenagers and young adults, the onset of pars planitis can be more insidious, often with the presenting complaint of floaters [63]. Since the major site of inflammation is in the vitreous (by definition), vitritis is the most consistent sign of intermediate uveitis, and it may become so dense as to obscure the retina entirely. Anterior chamber cells are more commonly found in children than adults. Inflammatory aggregates in the vitreous (snowballs) appear as mobile, globular, yellow-white opacities (Fig. 19.4). They are characteristic, but not specific, of pars planitis. The hallmark of pars planitis is a yel- low-white fibroglial exudative accumulation on the inferior pars plana (snow-bank). Inferior peripheral retinal phlebitis with retinal venous sheathing is common, although this finding can be subtle ophthalmoscopically and is best appreciated by fluorescein angiography. Optic nerve edema occurs approximately half the time in children. In 5–10% of cases, ischemia from retinal phlebitis, combined with angiogenic stimuli from long-standing intraocular inflammation, can lead to neovascularization along the inferior snowbank [14]. Vitreous hemorrhage can occasionally be the presenting sign in children secondary to bleeding from neovascularization.

Pars planitis, notorious for its long clinical duration, follows one of three clinical courses. Only 10% of patients have a self-limiting, benign course; 30% of cases are characterized as smoldering with remission and exacerbations, and the majority of cases (60%) have a prolonged course without exacerbations. Pars planitis may remain active for many years and has been documented at more than 30 years. However, the disease “burns out” in most cases after 5–15 years [64].

CME commonly develops in pars planitis, and is the major causes of visual loss. It can become chronic and refractory to treatment in 10% of cases. The amount of macular edema may not correlate with the degree of vitreous inflammation.

Pathophysiology/Genetics

The response of pars planitis to immunosuppressive therapy, the presence of familial clustering, and its occasional association with other presumed autoimmune diseases all suggest that autoimmunity plays a role in the pathogenesis of intermediate uveitis. The etiology of the antigenic stimulus is not clear, but there

Fig. 19.4  Photographs of a patient with pars planitis shows vitreous snowballs in

the right eye (a, b) and in the left eye (c, d)

a

b

c

d

may be an autoimmune reaction against the vitreous, peripheral retina, or ciliary body [65].

Familial clustering has led to an association between pars planitis and the HLA-DR15, -DR51, and -DR2 alleles [66–69].

Histopathologic examination of eyes with pars planitis demonstrates vitreous condensation and cellular infiltration of the vitreous base, with cells consisting of macrophages, lymphocytes, and a few plasma cells [70, 71]. Lymphocytic cuffing of venules is also present. The characteristic pars plana exudate has been identified as a loose fibrovascular membrane consisting of organized collagen, fibroblasts, and fibrous astrocytes, with scattered plasma cells, macrophages, and lymphocytes [72].

Diagnosis

The diagnosis of pars planitis is based on the clinical findings, and the exclusion of other causes of intermediate uveitis. In children, toxocariasis, sarcoidosis, and syphilis specifically need to be ruled-out. A peripheral

toxocara granuloma can mimic a unilateral pars plana snowbank in children. A history of infected puppies or pica and serologic testing (ELISA) for Toxocara antigen can help make the diagnosis. A B-scan ultrasound demonstrating a solid, highly reflective peripheral mass and a retinal fold between the mass and the optic nerve are useful in confirming the diagnosis of toxocariasis. There is no single diagnostic test to exclude the diagnosis of sarcoidosis in children, in which the presentation is different from that found in adults. Careful rheumatologic evaluation for systemic disease in children can be helpful in establishing the diagnosis. Serodiagnosis of syphilis can be made using the nontreponemal antigen tests, such as the Venereal Disease Research Laboratory (VDRL) and rapid plasma antigen (RPR), and treponemal antigen tests such as the fluorescent treponemal antibody absorption (FTAABS) assay.

The possibility of an occult intraocular foreign body must always be kept in mind when dealing with unilateral intermediate uveitis. A fibroglial membrane can form over a foreign body resting on the pars plana, obscuring it from view and simulating pars planitis.