Ординатура / Офтальмология / Английские материалы / Handbook of Pediatric Neuro-Ophthalmology_Wright, Spiegel, Thompson_2006

sympathetic neuron in Horner’s syndrome. Paredrine has a sympathomimetic effect by releasing norepinephrine from vesicles at the end of an intact third-order neuron. Paredrine will dilate a normal pupil as well as the pupil of a firstor second-order Horner’s syndrome. Paredrine will not dilate the pupil of a thirdorder Horner’s syndrome because the neuron is not intact. Paredrine has been unavailable in the past, but now can be obtained by contacting Allergan Pharmaceuticals.

PARASYMPATHETIC LESIONS

Parasympathetic lesions are all characterized by loss of the pupillary constricting action of the oculomotor nerve. The pupillomotor fibers travel in the outer aspect of the third nerve and are therefore more sensitive to compression, but are less likely to be involved by microvascular disease. Depending on the site of the lesion, one may see a complete third nerve palsy or may only see a dilated, poorly reactive pupil. The anisocoria is largest under conditions requiring the parasympathetic pupillomotor fibers to be working, that is, in the light.

THIRD NERVE PALSY

The signs of a complete third nerve palsy—a fixed, dilated pupil, an incomitant exotropia, hypotropia, and ptosis—are easily recognized and do not cause diagnostic confusion. Expanding intracranial mass lesions result in uncal herniation with resultant compression of the third nerve. The pupillomotor fibers travel in the outer aspect of the nerve, and thus are sensitive to compression. Pupillary dilation (the Hutchinson pupil) is an early sign of an expanding, supratentorial mass lesion. Most patients with an expanding mass lesion show other signs of third nerve involvement or worsening mental status by the time the ophthalmologist arrives, making the pupillary examination moot. The Hutchinson pupil does not have denervation supersensitivity, and will not constrict to 0.1% pilocarpine solution, but will constrict to 1% pilocarpine.

ADIE’S TONIC PUPIL

This condition may occur in children37 but is more commonly seen in young women. Children present because of the anisocoria, photophobia, or difficulty reading at near. The Adie’s pupil is generally the result of a viral-mediated ciliary ganglionitis with disruption of the accommodative and the pupillomotor

fibers. The process is usually unilateral, but may be bilateral with an asymmetrical onset. Segmental iris involvement occurs, and may vary from a small sector to near total iris involvement. Initially, both accommodation and pupil constriction are lost, but accommodation generally recovers within 3 months due to the large proportion of parasympathetic fibers that innervate the ciliary body (97%) as compared to the iris sphincter (3%). The dilated pupil remains poorly reactive to light, but develops a tonic, slow constriction to a near stimulus as a result of aberrant regeneration. Because of the tonic nature of the accommodative response, the pupil dilates slowly once the accommodative stimulus is removed. The vermiform movements seen at the slit lamp represent “hippus” of the iris sectors still connected to the original pupillomotor fibers. The Adie’s pupil has denervation supersensitivity, and constricts to dilute 0.1% pilocarpine, whereas a normal pupil will not constrict.2 Patients with Adie’s syndrome have diminished deep tendon reflexes, reflecting a generalized ganglionitis affecting dorsal root ganglia.32 One other potential complication of Adie’s pupil in children is the development of amblyopia in the involved eye. The authors have also seen an intermittent exotropia made worse by an Adie’s pupil. This condition was treated successfully with dilute pilocarpine 0.125% three times a day.

ATROPINE MYDRIASIS

Dilated, nonreactive pupil(s) may result from ingestion or topical application of atropine or other parasympatholytic substances. Children may accidentally gain access to a parent’s or grandparent’s eyedrops, but environmental exposure to the seeds of jimson weed, or the berries of deadly nightshade and henbane, is also possible. A pupil dilated with atropine will not constrict to 0.1% or 1% pilocarpine solutions. Children with systemic atropine poisoning have bilateral dilated pupils that may constrict to 1% pilocarpine solution.

OTHER CAUSES

Pilocarpine, phospholine iodide, and other miotics may occasionally be instilled in one eye only and will give unilateral miosis. Phenylephrine or cocaine may get in one eye and cause unilateral mydriasis. Anisocoria may result from localized processes such as iris sphincter damage, iritis, or prior intraocular surgery.

genital Horner’s syndrome with a history of birth trauma or cardiothoracic surgery need no further workup.22 The iris heterochromia could be treated with a cosmetic contact lens when the child reaches adolescence. Patients with a congenital Horner’s syndrome with no obvious cause may need to be investigated with a chest radiograph, an MRI scan or CT scan of the head, neck, and upper thorax, as well as a 24-h urine catecholamine assay to rule out an occult neuroblastoma.42 Patients with an acquired Horner’s syndrome must be evaluated with chest radiograph, MRI or CT scan of the head, neck, and upper thorax, as well as a 24-h urine catecholamine assay. Sauer and Levinsohn have emphasized the seriousness of an acquired Horner’s syndrome in children.30

Patients with a Hutchinson’s pupil need urgent neurosurgical intervention to treat their brain herniation. The management of patients with a congenital or acquired third nerve palsy is beyond the scope of this chapter. Children with Adie’s tonic pupil do not require further evaluation, but the parents should be warned that the other eye may become affected in the future. The photophobia and accommodative paresis may be improved with pilocarpine 0.1% solution in the affected eye several times daily. Young children should be carefully observed for the development of amblyopia or strabismus in the affected eye. Patients with atropine mydriasis need to be evaluated for signs of atropine poisoning. The mnemonic “hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hen” provides a useful way of recalling the associated symptoms.36 If the child has no signs of atropine poisoning, the parents can be reassured that the pupils will return to normal within 2 weeks.

NEONATAL VISUAL IMPAIRMENT

The causes of neonatal visual impairment can be grouped into four major categories: (1) disorders of the media, (2) disorders of the retina, (3) disorders of the optic nerve, and (4) disorders of the visual pathways and cortex. Some causes in each category are easily diagnosed such as congenital cataracts, optic nerve colobomas, or macular toxoplasmosis. The disorders that present with an essentially “normal” ocular examination provide the real diagnostic confusion and are the topic of this section. One must take care to distinguish between poor vision from birth and acquired visual loss. Patients with near-normal

vision in infancy that develop progressive visual loss are beyond the scope of this section.

Causes of Visual Impairment with a “Normal” Ocular Examination

DELAYED VISUAL MATURATION

Delayed visual maturation (DVM) is characterized by visual inattention during infancy, which improves significantly by 3 to 9 months of age. Fielder et al. divided DVM into three groups: an isolated finding, in association with neurological abnormalities, and in association with ocular abnormalities.8 Patients with isolated DVM show a normal flash electroretinogram (ERG) and also an essentially normal flash and pattern visual evoked potential (VEP).18 These patients generally have normal visual attention by 6 months of age; their prognosis for normal intellectual development is good. Patients with DVM in association with neurologic defects often have mental retardation and seizures. These children appear to see better when their seizures are controlled; their vision is often variable and is better when sound or tactile means also stimulates them. These children have a slower and less complete recovery of vision. Patients with DVM in association with ocular disease will have acuity worse than expected for the ocular disease alone. Their acuity will likely recover to the expected level by 9 to 12 months of age.

SACCADE PALSY

Disorders such as oculomotor apraxia or bilateral type III Duane’s syndrome may mimic blindness because the child cannot fix or follow objects in the horizontal plane. Patients with type III Duane’s syndrome can follow objects moving vertically; patients with oculomotor apraxia can be diagnosed by the characteristic head thrusts.

HIGH AMETROPIA

Occasionally infants with very high refractive errors may present with visual inattention, which probably represents delayed visual maturation in association with ocular disease. A cycloplegic refraction should be performed on every infant with neonatal visual impairment. These children should be followed to assure normal visual development.

milestones, seizures, and visual failure. Death occurs by 4 years of age.29 The pathogenesis is neuronal storage of lipopigments of the ceroid-lipofuscin type with secondary neuronal destruction and phagocytosis. The fundus is similar to Leber’s amaurosis. The ERG and VEP are both markedly attenuated or absent. Inheritance is autosomal recessive. Diagnosis is by histopathological study of rectal neurons or conjunctiva.

PEROXISOMAL DISORDERS

The peroxisome is a subcellular, single membrane-bound organelle that harbors a large number of important biochemical reactions, including the catabolism of long chain fatty acids such as phytanic acid and pipecolic acid. Absence of peroxisomes gives rise to three important disorders: Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum’s disease. All three disorders are characterized by poor vision, a pigmentary retinopathy, retinal arteriolar attenuation, an extinguished ERG, optic atrophy, elevated serum long chain fatty acids, and autosomal recessive inheritance. Zellweger syndrome is further characterized by facial dysmorphism, hypotonia, seizures, psychomotor retardation, renal cysts, and hepatosplenomegaly. Most patients die within 1 year of age. Neonatal adrenoleukodystrophy is additionally characterized by adrenal cortical atrophy, patchy brain demyelination, and seizures. The disease is milder than Zellweger syndrome, and patients live an average of 4 years. Infantile Refsum’s disease is the least severe of these three disorders, and is further characterized by deafness. Further information can be obtained in the excellent review by Folz and Trobe (see also Chapter 54).10

ACHROMATOPSIA

Achromatopsia (rod monochromatism) is a stationary retinal dystrophy characterized by a lack of functioning cones in the retina. It can be divided into complete (no functioning cones), incomplete (some functioning cones), and blue cone (no functioning red or green cones). All three disorders are characterized by marked photophobia, nystagmus, paradoxical pupil responses (constriction in the dark), poor color vision, reduced central visual acuity, and a normal scotopic (rod) response with an absent photopic flicker response on electroretinography. Com-

plete rod monochromatism is the most severe, and adults have 20/200 acuity and no color vision. Incomplete rod monochromatism is less severe, and adults have 20/50 to 20/200 acuity with abnormal color vision.4 Patients with both forms have decreased photophobia and decreased nystagmus as adults. The fundus examination is usually normal, although complete rod monochromats may show a nonspecific or bull’s-eye maculopathy as adults. Complete and incomplete rod monochromatisms are inherited in an autosomal recessive manner; blue cone monochromatism differs with X-linked recessive inheritance. Specialized psychophysical tests can be used to diagnose blue cone monochromatism.1

ALBINISM

Patients with ocular albinism and oculocutaneous albinism have reduced vision, nystagmus, iris transillumination, foveal hypoplasia, and defective fundus pigmentation. Oculocutaneous albinism type 1 (OCA1) is due to a defect in the tyrosinase gene located on chromosome 11q. Oculocutaneous albinism type 2 (OCA2) results from a defect in a transmembrane protein necessary for melanogenesis. Patients with tyrosinase-negative oculocutaneous albinism (OCA1) are easy to diagnose, but those with tyrosinase-positive oculocutaneous albinism (OCA2) and ocular albinism (OA) may provide diagnostic confusion. The key to diagnosis is to suspect ocular albinism (OA) in any male child with congenital nystagmus, especially in darkly pigmented races. There are three types of ocular albinism, called OA1, OA2, and OA3. OA1 is the classic X-linked variety (Nettleship–Falls) mapped to chromosome Xp22.3. OA1 results from the formation of abnormal macromelanosomes. These abnormal macromelanosomes can be detected on skin biopsy. OA2 has been defined in a series of patients from the Aland Islands. OA3 is an autosomal recessive type that has an unknown genetic defect. Slit lamp examination in the classic type will show iris transillumination, and the fundus will be lightly pigmented with macular hypoplasia. Female carriers (the patient’s mother) have normal vision with iris transillumination (Fig. 12-7) and hypopigmented areas in the peripheral retina. The ERG is normal in all varieties of albinism, and may be supranormal due to light scatter in these lightly pigmented fundi.5 Tinted lenses and low-vision aids are recommended for these patients.

poor vision and nystagmus from birth. Lesser degrees of bilateral hypoplasia may result in milder visual defects. All patients with optic nerve hypoplasia should be referred for a pediatric endocrinology evaluation. Clinical diagnosis is based upon careful observation of the optic disc size in relation to the exiting vessels; accuracy is improved with the direct ophthalmoscope and the use of the slit lamp with a 90 diopter lens, but few children are cooperative for this unless under anesthesia.

CEREBRAL VISUAL IMPAIRMENT

Cerebral visual impairment describes poor vision resulting from injuries to either the optic radiations or to the visual cortex. These injuries are generally hypoxic and occur as a result of hypotension, birth asphyxia, or cardiac surgery; other causes include hydrocephalus, stroke, and direct trauma. Children with cortical visual impairment have bilateral poor visual acuity and loss of optokinetic nystagmus with brisk pupillary reactions, clear media, and normal fundi. Other associated neurological defects are common. Children with cortical visual impairment may have some gradual visual recovery over months to years. An MRI scan of the visual pathways and cortex may aid in providing an ultimate visual prognosis; changes in the visual cortex do not correlate well with the final visual acuity, but changes in the optic radiations do correlate well.16

Patient Evaluation

In evaluating the child with neonatal visual impairment, one should question the parents about the child’s visual behavior and if things seem to be stable or improving. Observations of photophobia (achromatopsia) or eye-poking (Leber’s) are quite useful. Determine if the pregnancy was complicated, or if perinatal asphyxia occurred. Assess the infant’s medical history for hydrocephalus, head trauma, meningitis, developmental delay, failure to thrive, and seizures. The family history is often negative, as most of these disorders are autosomal recessive.

Visual acuity assessment in young children is frequently difficult. Fixation on the examiner’s face is commonly used in children under 6 months of age. The optokinetic nystagmus drum is quite useful, and can be used in an attempt to superimpose a