or a coexistent encephalitis. Riikonen and von Willebrandt459 found normal peripheral blood lymphocyte counts and function in most children with optic neuritis and MS. A thorough history of recent infection or systemic disease, illness, recent immunizations, bee stings,45 tick bites,582 or neurological symptoms suggestive of MS should be obtained. Symptoms of headache, malaise, lethargy, seizures, or fever should suggest the possibility of a coexistent encephalomyelitis. The findings of lymphadenopathy, hepatomegaly, or splenomegaly should suggest the possibility of infectious mononucleosis or cat scratch disease.154 A chest X-ray (to rule out sarcoidosis and tuberculosis) and a tuberculin skin test can be predicated on the index of suspicion. Systemic signs of vasculitis should be sought because systemic lupus erythematosis can occasionally cause a bilateral simultaneous optic neuritis in children that is usually associated with a poor visual outcome.3 In children with a discrete white inflammatory mass on the disc or prominent vitreous inflammation, serological testing for toxoplasmosis and toxocariasis should be obtained.109,164 Bilateral, multifocal chorioretinitis with circular “target-like” lesions scattered in the mid-periphery and often arranged in a radial, linear pattern has been a consistent feature. Other intraocular findings include mild iridocyclitis, vitritis, occlusive vasculities, and optic disc edema.17,26,401 The increasing use of etanercept and infliximab for juvenile rheumatoid arthritis and other autoimmune diseases is now a recognized cause of pediatric optic neuritis.600 Table 3.9 summarizes the recognized infectious and noninfectious causes of childhood optic neuritis.

Treatment

There has been no controlled study to determine the efficacy of oral or intravenous corticosteroids in the treatment of childhood optic neuritis.234 Recommendations in the literature are largely anecdotal.154 In typical demyelinating optic neuritis in adults, the Optic Neuritis Treatment Trial38 has found that neither oral nor intravenous steroids change the final visual outcome as measured 1 year after onset of symptoms. However, adults who received intravenous steroids in high doses had more rapid recovery of vision. Adult patients who received oral corticosteroids alone for acute optic neuritis had twice the number of recurrent attacks of optic neuritis over the following 2 years.39 In contrast, patients who were treated with intravenous corticosteroids had only half the number of systemic demyelinative episodes as the placebo or oral corticosteroid treated groups over the same 2-year period.39 The protective effect of intravenous corticosteroids was seen only in the subgroups with abnormal MR scans.60 On the basis of these results, some adults with optic neuritis and/or MS are now treated at 2-year intervals with intravenous

high-dose corticosteroids. These results may also be applicable to children with optic neuritis and signal abnormalities on MR imaging suggestive of MS or to children with MS. MR imaging is also crucial to define the multiple bilateral large signal abnormalities of ADE, which responds to corticosteroids.225

Leber Idiopathic Stellate Neuroretinitis

In 1916, Theodor Leber described the clinical syndrome of unilateral visual loss, optic disc swelling, macular star, and spontaneous resolution in otherwise healthy patients.190,332 He referred to this condition as an idiopathic stellate neuroretinopathy, emphasizing the star figure that surrounded the fovea (Fig. 3.17).

The onset of visual loss usually follows a viral prodrome by 2–4 weeks.424 Visual loss may be accompanied by symptoms of floaters and ocular pain. Ophthalmoscopic examination at onset shows a swollen optic disc with peripapillary retinal striae extending from the disc toward the macula or extending radially from the fovea, frequent serous detachment of the peripapillary retina, and cells in the anterior vitreous. An associated iridocyclitis is seen in some cases. Within weeks, the disc swelling and peripapillary edema begin to subside, and a yellowish star-shaped pattern of macular exudate appears and becomes more prominent190,475 (Fig. 3.19).

In most cases, visual acuity ranges from 20/50 to 20/200, and an afferent pupillary defect is present.190 Visual field testing shows a central or centrocecal scotoma.133 Fluorescein angiography shows evidence of abnormal capillary permeability, particularly from the capillaries deep within the optic disc.190

The disc swelling clears over 2 or 3 months, but the macular exudate may persist and be associated with retinopathic deficits for a longer period. A minority of patients with Leber stellate neuroretinitis have either focal neurological symptoms or elevated intracranial pressure at presentation; fulminant encephalitis or meningitis is not seen.424,569 The ultimate level of visual recovery seems to be the same in Leber idiopathic stellate neuroretinitis as in optic neuritis, but the course of visual recovery is prolonged in neuroretinitis. During the months between the resolution of disc edema and the resolution of macular exudates, a dissociation between color vision and visual acuity may be apparent, with the former normalizing first. Following resolution, patients are left with varying degrees of optic atrophy and mild macular pigmentary changes and, sometimes, macular hole formation.6 As with optic neuritis, most patients recover near-normal vision but, occasionally, patients fail to recover or recover only minimally.555

The distinction between Leber stellate neuroretinitis and anterior optic neuritis bears tremendous prognostic significance,

Fig. 3.19  Leber stellate neuroretinitis. (a) Scratches from a kitten on a girl with unilateral visual loss. (b) Vitritis, optic disc swelling, and a macular star in the same patient. Note the characteristic yellowish, white

nodular lesion which occupies the inferonasal portion of the optic disc. (c) Swelling of optic disc and macular star-shaped exudates in another patient

because the diagnosis of Leber stellate neuroretinitis virtually rules out the possibility of MS.424 This fundamental difference can be predicted from the known pathophysiology of the disease. Gass originally suggested that Leber stellate neuroretinitis is due to a prelaminar disc vasculitis that results in a leakage of lipid and protein-rich exudate from the disc capillaries into the outer plexiform layer.133,188,424 As the serous component is resorbed over days to weeks, lipid precipitates within Henle’s fiber layer, forming a star figure.133

Leber stellate neuroretinitis is thought to be fundamentally different from optic neuritis in that Leber stellate neuroretinitis presumably represents an autoimmune vasculitis confined to the nonmyelinated prelaminar optic disc.569 In anterior optic neuritis, the target tissue is primarily retrolaminar myelin.133 Although anterior optic neuritis can indirectly produce disc swelling, it does not cause the profuse leakage from the prelaminar disc capillaries necessary to produce a macular star.

Cat scratch disease has emerged as the most common infectious cause of neuroretinitis.525 Cat scratch disease is a self-limited illness caused by a gram-negative bacillus,

Bartonella henselae (now synonymous with Rochaliaea hensalae). The disease is transmitted by the bite or scratch of an infected animal, often a young cat or kitten.599 However, dogs, monkeys, and porcupines can also harbor the agent,206 and recent evidence suggests that cat fleas may also play a role as an arthropod vector.313 The infected individual often develops an erythematous pustule at the site of inoculation, followed by a systemic reaction in days to weeks. Typical symptoms include regional lymphadenopathy, fever, malaise, and fatigue. More severe systemic complications may develop, including splenomegaly or splenic abscesses, encephalopathy, granulomatous hepatitis, pneumonia, or osteomyelitis.525

The finding of angiomatous skin lesions (bacillary angiomatosis) resembling Kaposi’s sarcoma in the child with neuroretinitis or hepatosplenomegaly should also suggest the

possibility of cat scratch disease.207,448,571 Weiss and Beck569 noted that the swollen optic disc usually had a yellowishwhite nodular region located at the temporal aspect of the swollen disc (Fig. 3.19). Fish et al158 documented peripapillary angiomatosis on the surface of a swollen disc of a child with cat scratch disease. Papillary angiomatosis may turn out to be a unique ocular manifestation of cat scratch disease that is analogous to the skin lesions of bacillary angiomatosis. In the past, a cat scratch skin test and/or a lymph node biopsy were the methods most commonly employed to establish the diagnosis. Previously reported cases of cat scratch–associated neuroretinitis must be considered at least somewhat presumptive, because a positive skin test only demonstrates acquired immunity to the infection, which could have occurred months to years before.29

In patients with lymphadenopathy from cat scratch disease, a lymph node biopsy typically shows noncaseating necrosis and gram-negative coccobacilli with Warthin-Starry silver stain.87,158 The cat scratch skin test was never approved by the U.S. Food and Drug Administration and has now been replaced by serological testing of acute and chronic IgG and IgM. Rochalimaea can also be cultured from blood or skin lesions.207 Although some authors have recommended oral antibiotics207,247,347,446 or oral corticosteroids for the treatment of cat scratch disease, most patients recover fully without treatment.525 Despite a lack of proven benefit, systemic corticosteroids are often empirically added in patients with optic neuritis or neuroretinitis.158,554

Lyme disease is another recognized cause of Leber stellate neuroretinitis.345 Lyme disease is caused by the spirochete

Borrelia burgdorferi, which is transmitted by Ixodidae ticks.1

Serological testing is therefore particularly important in children who have recently been camping or have a history of a tick bite. Clinical signs of erythema migrans, carditis, arthritis, or facial palsy should raise suspicion for this diagnosis.1 Unfortunately, currently available serology for Lyme disease has problems with both false–positive and false–negative results, causing overdiagnosis and underdiagnosis, respectively.529,580 Patients with syphilis can have positive Lyme serology.580 Patients with Lyme disease who have early skin, joint, or

cardiac involvement are often treated with oral antibiotic therapy, while those with neuroborreliosis (encephalitis, neuroretinitis, facial palsy) or chronic arthritis require longer-term intravenous third-generation cephalosporins.

Other infectious and parainfectious causes of Leber stellate neuroretinitis in childhood include mumps,167 leptospirosis,133 infectious mononucleosis,53,172 exudative tuberculous retinitis,135 a toxocaral granuloma within the nerve head,48,109 toxoplasmic neuroretinitis,159 syphilis,156,165 and influenza.369 It also is important to remember that macular stars rarely accompany disc swelling due to elevated intracranial pressure.200 Tables 3.10 and 3.11 summarize the recognized infectious causes of Leber stellate neuroretinitis, along with suggested medical evaluations.

Other forms of childhood neuroretinitis include posterior scleritis and diffuse unilateral subacute neuroretinitis (DUSN). Posterior scleritis is an autoimmune disorder that is often associated with ocular pain, conjunctival injection, and ocular motility disturbances. Ophthalmoscopic abnormalities include optic disc edema, retinal and choroidal striae, exudative retinal detachment, annular choroidal detachment, and cystoid macular edema.43 The disc swelling in posterior scleritis may be caused by narrowing of the scleral canal due to contiguous scleral inflammation and edema. The diagnosis can be confirmed by ultrasonography, which demonstrates a fluid-filled space in Tenon’s tissue behind the globe or by CT scanning, which demonstrates enhancement and thickening of the posterior sclera. Diffuse unilateral subacute neuroretinitis occurs in healthy patients and, in its acute stage, is characterized by mild to moderate swelling of the optic disc, vitreous cells, and transient crops of focal, gray-white or yellow-white lesions that involve the deep or external layers of the retina and retinal pigment epithelium (RPE).190,192 DUSN can rarely be associated with a macular star.188 Over weeks to months, depigmentation of the overlying RPE occurs, along with severe optic atrophy and marked retinal arteriolar attenuation.188 DUSN is now considered a multietiologic syndrome caused by different species of nematodes.204 It is believed that larval excretory–secretory products, including various enzymes and metabolic wastes produced by nematode larvae, cause localized toxic effects

and/or stimulate an inflammatory response, especially one mediated by eosinophils.204 Direct photocoagulation has proven successful in eradicating the nematode and halting the progression of visual loss.192 Oral treatment with the antihelminthic agent thiabendazole has met with success in some patients and has been recommended for use in cases in which the worm cannot be located.192 In many Latin American countries, such as Venezuela, DUSN is seen primarily in young patients without a significant gender predilection.107,527 Occasionally, ocular involvement may be bilateral.123 In the United States, DUSN secondary to Baylisascaris procyonis (raccoon roundworm) should also be considered.

West Nile virus is a newly recognized cause of optic neuritis and optic atrophy that should be considered when accompanied by multifocal choroiditis and occlusive vasculitis.82,400 Ocular symptoms such as photophobia, retrobulbar pain, and diplopia have also been reported.570

Noninfectious disorders can mimic neuroretinitis. These etiologies should be suspected when atypical features such as bilaterality, lack of vitreous cells, lack of infectious risk factors, or no significant visual recovery are noted.559 It is important to check the blood pressure and rule out hypertensive retinopathy, particularly in bilateral cases.334,353 Bilateral neuroretinitis can also result from unruptured intracranial arteriovenous malformations (AVMs).559 The most common infectious etiology, by far, is cat scratch disease, but numerous other infectious and noninfectious disorders have been described. Both neuroretinitis and acute retinal necrosis occasionally follow chickenpox in children.340 Shoari and Katz509 described recurrent neuroretinitis in an adolescent with ulcerative colitis. Gass190 described acute visual loss with optic disc swelling, peripapillary exudate, and a macular star in two children with progressive facial hemiatrophy (Parry–Romberg syndrome). One of these children had angiographic evidence of increased peripheral retinal vascular permeability. Both patients developed optic atrophy as the peripapillary and macular exudation cleared, but neither demonstrated progressive loss of visual field. Similar cases have since been reported.474 The pathogenesis of this acute neuroretinopathy is not known.190 Lecleire-Collet et al333 described a stellate neuroretinitis in an 11-year-old girl with tubulointerstitial nephritis and uveitis (TINU) syndrome.

It is important to bear in mind that children with hypertensive retinopathy can present with bilateral disc edema with a macular star, which may thereby simulate neuroretinitis.334 Bartonella can induce sudden bilateral blindness without systemic signs of cat scratch disease.124

In 1983, Kincaid and Schatz307 formally described the idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome. The most common ocular findings are the characteristic aneurysmal dilatations of the retinal and optic nerve head arterioles. This condition typically occurs in young patients.226 These aneurysmal dilatations generally

leak on fluorescein angiography but tend not to cause subretinal, retinal, or vitreous hemorrhages.226 Peripapilary subretinal fluid and lipid deposition, along with peripheral capillary nonperfusion are common findings and can lead to retinal neovascularization. Vitritis may also be present. The pathophysiology is unclear, although an autoimmune mechanism has been suggested.592

The IRVAN syndrome can be associated with optic disc swelling in children.83,226,307 In 1973, Karel et al278 reported a series of children with uveitis. Among these children, a 15-year- old girl had fluorescein angiographic evidence of vasculitis and numerous aneurysmal changes on the optic nerve head and along the firstand second-order arteriolar bifurcations.

Visual loss is due to a combination of exudative maculopathy and sequelae of retinal ischemia. Capillary nonperfusion is often present, necessitating panretinal photocoagulation. One of the most characteristic features is the presence of numerous aneurysmal dilatations of the retinal and optic nerve head arterioles. These vascular abnormalities are present on the optic nerve head as well as on the retinal arterioles, either at or near the major branching sites. They typically have a triangular or “Y”-shaped morphology, but also are seen in a coiled configuration, resembling knots in the arteriolar tree. This process starts around the optic disc and marches out toward the periphery, eventually causing peripheral retinal ischemia. Poor vision results in about 50% of cases.83 Papilledema from elevated intracranial pressure rarely coexist.226 Systemic corticosteroids have little effect on the progression of the disease, and associated systemic disease is not found.83

Ischemic Optic Neuropathy

Classic spontaneous anterior ischemic optic neuropathy (AION) is rare in children. There is new evidence that the spontaneous optic nerve infarction of adulthood may actually be precipitated by venous insufficiency in adults, with venous congestion causing initial disc edema with creation of a compartment syndrome.346 Anterior ischemic optic neuropathy in children usually occurs under pathologic circumstances, as in diabetic papillopathy.90 Secondary nonarteritic ischemic optic neuropathy is a rare event in childhood, occurring mostly in the setting of spinal surgery or peritoneal dialysis, and hypovolemia was postulated to be the major etiology.67,330,519 Children subjected to vigorous treatment of accelerated hypertension and children with migraines and prothrombotic disorders have also developed AION.90 Those children capable of cooperating for visual field examination typically show an altitudinal defect in the affected eye. Treatment of pulmonary hypertension with sildenafil may have led to the development of ischemic optic neuropathy in one 5-year-old child.519