in approximately 80% of cases. Optic atrophy may be caused by either the compressive effects of narrowed optic canals or by long-standing papilledema.473 Visual loss in osteopetrosis may also result from a primary retinal degeneration associated with diminished electroretinographic amplitudes. Some affected infants develop multiple lacunar areas of macular depigmentation.473 The recent association of infantile malignant osteopetrosis with neuronal storage disease suggests that the degenerative retinal changes in osteopetrosis may be secondary to neuronal storage disease. Lysosome dysfunction has been identified in both infantile malignant osteopetrosis and neuronal storage diseases.

Infantile malignant osteopetrosis is lethal if untreated within the first decade of life.473 Bone marrow transplantation is the only definitive therapy, with a success rate approaching 50%.583 Bone marrow transplantation has been reported to lead to reversal of optic canal stenosis and preservation of vision may be associated.297 In one child, the electroretinogram reportedly normalized following bone marrow transplantation, while the visual evoked response remained undetectable.4 Optic canal decompression may result in improved visual function when visual loss is associated with CT evidence of narrowing of the optic canals, a normal electroretinogram, and subjective or objective evidence of decreased optic nerve function (e.g., progressive abnormality on serial visual evoked potential [VEP] examinations).10,583 In rare cases, visual loss can result from obstruction of cerebral venous outflow at the jugular foramina, leading to elevated intracranial pressure.498

Malaria

Although rarely seen in western countries, malaria remains an important cause of papilledema worldwide. In children with papilledema, laser Doppler flowmetry shows an increase in the microvascular blood volume of the optic nerve head.35

Paraneoplastic

Cancer-associated retinopathy (CAR) is a well-recognized paraneoplastic syndrome that is mediated by antiretinal antibodies is adults. Inflammatory changes such as optic disc edema and retinal vasculitis have not been reported in CAR. However, several purported cases of paraneoplastic optic neuropathy have recently been reported in children. Scott et al491 ascribed bilateral papilledema in a child without elevated intracranial pressure or hypertension to the paraneoplastic effect of a pheochromocytoma. Paraneoplastic optic disc edema with retinal periphlebitis has been reported in two children with pineal germinoma.153 In both cases, the inflammatory fundus changes resolved after removal of the tumor.

Uveitis

Intraocular inflammation and hypotony are well-recognized causes of optic disc swelling. These two conditions often coexist in children with uveitis (juvenile rheumatoid arthritis, sarcoidosis, pars planitis) (Fig. 3.13). Postoperative hypotony, particularly following glaucoma surgery, is also a common cause of transient optic disc swelling in children. Visual acuity is thought to be unaffected by disc swelling alone in inflamed or hypotonous eyes.380 The finding of optic disc swelling and decreased acuity in an eye with uveitis should suggest the possibility of an associated anterior optic neuritis, whereas decreased acuity in a hypotonous eye is usually attributable to coexistent macular edema.380 Beardsley et al34 and Minckler and Bunt383 have demonstrated compromised axoplasmic transport anterior to the lamina cribrosa in ocular hypotony, just as in increased intracranial pressure. Interestingly, elevated intraocular pressure is also rarely associated with optic disc swelling.384 The biochemical mechanisms by which any of these conditions eventuate in optic disc swelling are speculative.228

Blau Syndrome

Blau syndrome is an autosomal dominant condition characterized by a triad of dermatitis, arthritis, and uveitis that mimics childhood sarcoidosis but is less responsive to immunosuppressive treatment. It is caused by a mutation in the

Fig. 3.13  Disc swelling and macular edema in 12-year-old girl with pars planitis and 20/25 vision

NOD2 gene, a regulatory molecule that acts as a receptor for microbes on monocytic cells.52,321,523

gammaglobulin and high doses of aspirin are administered within the first days following the onset of illness.29,404,471

CINCA

Chronic infantile neurological cutaneous articular (CINCA) syndrome, also known as neonatal-onset multisystem inflammatory disease (NOMID), is a rare congenital inflammatory disease characterized by cardinal signs that include a variable congenital maculopapular urticarial rash, chronic noninflammatory arthropathy with abnormal cartilage proliferation, and chronic meningitis with progressive neurological impairment associated with polymorphonuclear and, occasionally, eosinophilic infiltration.545

Neurologic abnormalities are characterized by chronic meningitis and secondary cerebral atrophy. Sensorineural hearing loss leading to deafness occurs in 22% of patients. Morphologic features include macrocephaly, saddle nose, and short, thick extremities, with clubbing of fingers.129 The CINCA syndrome is associated with childhood uveitis and papillitis with chronic disc swelling.477 The appearance of swollen optic discs, the presence of increased white blood cells without evidence of infection,129 and the absence of elevated intracranial pressure in most patients suggests an infiltrative etiology for the swollen optic discs,246 which may evolve into optic atrophy.129

CINCA syndrome results from mutations of the CIAS1 gene, which results in reduced apoptosis of the inflammatory cells with upregulation of interleukin 1 (IL1). Neutrophilic infiltration of multiple organs, including the skin, lymph nodes, spleen, and synovium, has been documented.339 Therapeutically, it responds poorly to immunosuppressives, including steroids, but seems to respond to recombinant human IL1 receptor antagonists (rHuI1, 1Ra), and anakinra (Kineret, Amgen).203 Matsubayashi et al370 noted resolution of papilledema with use of anakinra when treating a patient with intractable arthopathy.

Kawasaki Disease

Kawasaki disease is an acute multisystem vasculitis of infancy and early childhood.287 It is characterized by fever, bilateral conjunctival injection, mouth changes (dry, fissured lips; prominent tongue papillae (i.e., strawberry tongue); diffuse reddening of the oropharyngeal mucosa), extremity changes (reddening of the palms and soles, indurative edema of the hands and feet, desquamation of the hands and feet), polymorphous nonvesicular rash of the trunk or face, and cervical lymphadenopathy.51 In addition to conjunctival injection, iridocyclitis, vitritis and optic disc edema may complicate the clinical picture.15 Because of its strong association of lifethreatening coronary artery aneurysms, it is important to recognize and treat this condition early.260 The risk of complications can be decreased if a single, large dose of intravenous

Poststreptococal Uveitis

In addition to acute bilateral nongranulomatous uveitis, children with poststreptococcal syndrome uveitis may develop vitritis, focal retinitis, optic disc swelling, and multifocal choroiditis in up to one third of cases. An elevated antistreptococcal lysin O titer can be used to establish the diagnosis when a history of recent tonsillitis is obtained.449

Posttraumatic Optic Disc Swelling

In addition to its well-known association with posterior uveitis, optic disc edema can accompany anterior uveitis. It does not significantly affect visual function, and resolution of the optic disc edema can trail resolution of the anterior uveitis for up to 6 weeks.387 This section emphasizes systemic uveitis syndromes that produce optic disc edema in children.

Traumatic optic neuropathy typically involves the intracanalicular segment of the optic nerve and is not associated with optic disc swelling. We have examined three young patients (two children and one young adult) in whom blunt ocular trauma caused an unusual form of optic neuropathy, characterized by prolonged optic disc swelling, negative orbital imaging studies, and slow visual recovery over weeks to months (Fig. 3.14).66 The associated findings of choroidal ruptures and peripapillary subretinal hemorrhages suggest a

Fig. 3.14  Posttraumatic optic disc swelling. Note peripapillary hemorrhages, choroidal ruptures and segmental pallor of inferior disc