normally early in the disease and become only mildly abnormal in advanced disease. Fluorescein angiography shows the characteristic absence of choroidal fluorescence (termed a silent choroid), in 65–85% of cases.109,338a,392 This angiographic finding correlates with the histopathological finding of increased retinal pigment epithelial lipofuscin content.35 Autofluorescence is also decreased in areas of lipofuscin deposition.136a Mutations in the ABCA4 gene, which encodes a photoreceptor-specific binding protein, are responsible for almost all cases of Stargardt disease.136a,338a,372,417,418,437a,442

Other retinal disorders can also manifest as unexplained visual loss in children. In the child with bilateral central visual loss, a normal retinal appearance, and a normal fluorescein angiogram, ERG may be useful to rule out a progressive cone dystrophy.236 In this condition, the attenuated photopic ERG may provide the only clue to the diagnosis. Other congenital retinal dystrophies, such as blue-cone monochromatism, can also present as acquired visual loss in the absence of visible retinal abnormalities. The diagnosis of blue-cone monochromatism must be established by ERG. Teenagers and adults may develop acute idiopathic blind spot enlargement (AIBSE) without optic disc edema or retinal abnormalities.110 In some cases, this disorder appears to be a variant of several inflammatory retinal disorders, including multiple evanescent white dot syndrome (MEWDS), multifocal choroiditis, and acute macular neuroretinopathy.48,156 In other cases, however, the retina appears normal.

AIBSE is usually unilateral and characterized symptomatically by a paracentral dark spot near fixation that may enlarge to eclipse fixation. The patient may report swirling photopsias within the confines of the spot. Although MEWDS may produce the same constellation of symptoms, a subgroup of patients has no visible retinal abnormalities, and it is unclear whether these patients had retinal lesions early in their course of disease. The diagnosis of AIBSE relies upon the ability to use kinetic perimetry to demonstrate a discoriented, steep enlargement of the blind spot with geographic borders but no other visual field abnormalities.

The young child’s inability to maintain fixation and to provide accurate and consistent responses may make it impossible to establish the diagnosis. These perimetric findings establish that the blind spot enlargement is due to a circumscribed dysfunction of the peripapillary retina rather than an optic neuropathy (which would have smooth borders and a sloping margin). AIBSE is now believed to be a postviral retinopathy. In some cases, the scotoma resolves, while in others, it persists or improves only minimally.

Oligocone trichromacy is a rare cone dysfunction syndrome characterized by reduced visual acuity, mild photophobia, normal fundi, and reduced amplitude of the cone ERG, but with color vision within normal limits.270,400 It has been proposed that affected patients might have a reduced number of normal functioning cones (oligocone syndrome),

with preservation of the three cone types in normal proportions, thereby permitting trichromacy. These patients generally have a history of reduced visual acuity from infancy (20/40–20/80), mild photophobia, good color vision, no nystagmus, and normal fundi. Cone ERG findings are absent or markedly reduced (in some cases, predominantly affecting the B waves). This disorder is likely inherited as an autosomal recessive trait.270

Other retinal disorders are increasingly recognized as causes of unexplained visual loss. Isolated foveal hypoplasia does rarely produce mildly decreased acuity in children with no visible nystagmus. In this setting, the diagnosis can be confirmed by optical coherence tomography (OCT) and multifocal ERG.193 Occult macular dystrophy can produce bilaterally visual central acuity without visible fundus abnormalities. Fluorescein angiograms and full-field ERGs are normal, but the amplitudes of the focal macular ERGs and multifocal ERGs are significantly abnormal.

Rare visual disorders such as bradyopsia (slow vision), are increasingly recognized and characterized. Affected children have subnormal visual acuity and complain of photophobia, difficulties adjusting to changes in illumination, and problems seeing objects at ball games. Pinhole vision (which omits surrounding light) is often better than the best corrected vision with glasses. It is caused by a mutation in the RGS9 (regulator of G-protein signaling 9) gene, which is involved in the deactivation of photoreceptor responses. Color and dark adaptation tests are normal, and visual field testing shows no defects, except for a generally reduced central sensitivity. The diagnosis of bradyopsia can usually be made on the basis of ERG measurements and confirmed by the detection of a mutation in either the RGS9 or R9AP gene.161 Averaged single-flash scotopic ERG measurements typically show reduced amplitudes with higher flash intensities, whereas single-flash responses to dim light (rod response) are normal in amplitude. The time to generate a fully recovered response to the second strong flash after a normal response to the first strong flash is severely prolonged when paired flash tests are used.161

Finally, a rare syndrome of acquired visual loss in adults with old retinopathy of prematurity can cause unexplained visual loss.379 OCT should be performed, as previous reports suggest that this form of visual loss may be attributable to subclinical tractional retinal detachment.360 Plasmin-assisted vitrectomy successfully restored baseline visual acuity in one patient.

Optic Nerve

Optic neuritis in children is usually associated with acute bilateral visual loss and bilateral optic disc swelling. In some

children, however, the visual loss may precede the development of optic disc swelling by several days. We have examined children who were initially thought to be feigning blindness, only to develop bilateral optic disc edema over several days. In this context, the dilated, poorly reactive pupils may be falsely attributed to the effects of recent mydriatic administration.

Dominant optic atrophy may also present with unexplained visual loss in the pediatric population. Dominant optic atrophy is a disorder in which segmental optic disc pallor is associated with decreased visual acuity in both eyes. Many children are unaware of any visual disability until they undergo routine visual screening. They typically complain of difficulty seeing the blackboard, but do well when placed at the front of the class. They are often mildly photophobic but do not have nystagmus. Visual acuity is usually in the 20/70–20/80 range but may vary from 20/25 to 20/400.199 Asymmetry in vision between the two eyes is not unusual. The temporal optic discs show marked focal pallor that may appear triangular, wedge-shaped, or excavated, with absence of the corresponding nerve fiber layer.199 The severity of visual loss can vary considerably between family members, and it is common to find affected siblings who are visually asymptomatic. Affected patients are systemically normal, although sensorineural hearing loss may occasionally coexist.174

Patients with dominant optic atrophy display a psychophysical profile that differs from other forms of optic atrophy. Goldmann or tangent screen perimetry demonstrates a central or centrocecal scotoma that may require considerable effort to identify. Patients with dominant optic atrophy are usually tritanopic when tested with Farnsworth-Munsell hue 100 but show diffuse dyschromatopsia when tested with color plates. This finding distinguishes them from patients with compressive, inflammatory, ischemic, or other forms of acquired optic atrophy, which are preferentially associated with red-green or global color deficits. Color perimetry in dominant optic atrophy demonstrates a characteristic inversion of color isopters, with the yellow or blue isopters smaller than the red and green isopters.

The major differential diagnostic consideration in dominant optic atrophy is a cone dystrophy, which may also be associated with temporal pallor of the disc and which may show minimal macular changes. Although most children with congenital cone dystrophies have nystagmus and photophobia, exceptions exist. In some cases, ERG may be necessary to distinguish these two conditions. Bilateral temporal disc pallor may also be seen as a familial condition in Leber optic neuropathy. These patients initially have normal acuity, but experience severe consecutive visual loss over weeks to months. In contrast, visual acuity in dominant optic atrophy remains stable or gradually diminishes by only a few lines over years of observation.99

Mild optic atrophy or hypoplasia of any cause can elude detection when close examination of the peripapillary nerve fiber layer is not possible. Segmental optic nerve hypoplasia involving the papillomacular bundle may cause sensory esotropia in the preschool population and present as strabismic amblyopia that is refractory to treatment. Leber optic atrophy can also cause unexplained visual loss before optic disc pallor becomes evident.

Central Nervous System

A child who seems to have psychogenic visual loss rarely has a suprasellar tumor infiltrating or compressing the visual pathways. The early diagnosis of functional visual loss is common in children who harbor a craniopharyngioma.274 Compressive or infiltrative suprasellar lesions often produce bitemporal hemianopia; however, reliable visual fields may be unobtainable in young children, and early visual symptoms may precede optic atrophy or other objective signs of anterior visual pathway dysfunction. It is inevitable that the diagnosis of craniopharyngioma or other suprasellar tumors are delayed in children who present with early isolated visual symptoms with no objective neuro-ophthalmologic findings to support an organic basis for their complaints. Close followup, neurologic consultation, and neuroimaging are all viable options in suspicious cases.

Neuroimaging is obtained when (1) the pupils are abnormally large or poorly reactive with light-near dissociation,

(2) confrontation visual fields show a bitemporal or homonymous hemianopia, (3) examination of the peripapillary nerve fiber layer shows dropout of the nasal nerve fiber layer consistent with band atrophy, and (4) neurologic or systemic signs are found (severe headaches, macrocephaly, café au lait spots, diabetes insipidus, short stature), which suggest that the child may harbor a suprasellar tumor. These cases remind us of the need for caution and humility when diagnosing psychogenic visual loss in a child.

Cortical visual loss is rarely present in children who have no overt neurological problems.246 A history of seizures, developmental delay, or perinatal hypoxia suggests that the child may have unrecognized cortical visual loss. Neuroimaging should therefore be obtained in the child with bilaterally symmetrical visual field defects. Rarely, occipital dysfunction that is long-standing or recently acquired can present as unexplained visual loss when a child confronts the increased visual demands of the school setting. Finally, children with selective dorsal stream injury involving the visual association areas can present with unexplained visual loss, because they can still navigate and pick up things without being able to consciously identify their features or orientation.138 A history of antecedent trauma to the occiput suggests the possibility of transient posttraumatic cerebral