BASICS

DESCRIPTION

• Abnormally small optic nerve; often appears pale or gray in color

– 80% are bilateral, but may be asymmetric

• Most common congenital optic disc anomaly encountered; it was not widely recognized until the late 1960s

EPIDEMIOLOGY

Incidence

10.9:100,000 (England 2006) (1)

Prevalence

6.3:100,000 (Sweden -1997)

RISK FACTORS

• Maternal use of alcohol, quinine, PCP, LSD, and Dilantin

• Maternal insulin dependent diabetes (associated with subtype – superior segmental optic hypoplasia [topless disc])

• Young maternal age

• Primiparity

• Preterm labor

• Low maternal weight gain

• Gestational vaginal bleeding

• Most factors occur without known predisposing factors

Genetics

• Reported cases of affected siblings are rare

• Subsequent siblings of children with optic nerve hypoplasia are at little additional risk

– Mutations in HESX1 have been identified in children with sporadic septo-optic dysplasia and pituitary disease

– Homozygous mutations in the HESX1 gene have been found in 2 siblings with optic nerve hypoplasia, absence of the corpus callosum, and pituitary hypoplasia

GENERAL PREVENTION

There are no known methods of general prevention except for avoidance of known teratogenic agents such as Dilantin, Quinine, PCP, LSD, and alcohol.

PATHOPHYSIOLOGY

• Possible relationship to axon guidance molecules, such as Netrin-1 at the optic nerve head. Similar mechanism may account for other associated CNS abnormalities

• There is also evidence that some cases of optic nerve hypoplasia may result from axonal degeneration (apoptosis)

ETIOLOGY

• Usually unknown

• Teratogenic agents listed under risk factors

COMMONLY ASSOCIATED CONDITIONS

• Septo-optic dysplasia – constellation of optic nerve hypoplasia, absence of the septum pellucidum, and thinning or agenesis of the corpus callosum

• Pituitary – endocrine dysfunction

– Clinical hypopituitarism in 15%

– Subclinical endocrinopathy in 72%

Growth hormone most common, followed by thyrotropin, corticotrophin, and antidiuretic hormone

• 45% patients have cerebral anomalies such as error in hemispheric migration (schizencephaly, cortical heterotopias) or hemispheric injury (periventricular leukomalacia, encephalomalacia)

• Developmental delay is present in 39% of unilateral optic nerve hypoplasia and 78% of bilateral patients

– Developmental delay is most highly correlated with corpus callosum hypoplasia and hypothyroidism (2)

DIAGNOSIS

HISTORY

Bilateral optic nerve hypoplasia often presents with poor vision and nystagmus (often develops at 1–3 months of age). Unilateral optic nerve hypoplasia may present later with strabismus.

PHYSICAL EXAM

• Careful attention to visual acuity, including difference in acuity between the two eyes.

• Range of visual acuity is 20/20 to NLP

• Nystagmus

• Strabismus

• Small optic discs, may be pale or gray in appearance.

• Superior segmental optic nerve hypoplasia (associated with insulin dependent diabetic mothers) may be referred to as topless disc syndrome.

• Double ring sign (larger ring representing sclera canal that surrounds small optic nerve)

• Major retinal vessels may be tortuous

DIAGNOSTIC TESTS & INTERPRETATION

Lab

Initial lab tests

• Endocrine evaluation

– Fasting morning cortisol and glucose

– TSH, free T4

– IGF-1, IGFBP-3

– Prolactin

– In children <6 months, luteinizing hormone, follicle stimulating hormone, and testosterone levels should also be checked.

Follow-Up & Special Considerations

• Neonatal jaundice suggests congenital hypothyroidism

• Neonatal seizures suggest congenital panhypopituitarism

• Irreversible adverse effects of hypothyroidism may occur by 15 months of age – Serum TSH levels are helpful for early detection

Imaging

Initial approach

MRI is indicated to evaluate for associated CNS malformations.

Follow-up & special considerations

Posterior pituitary ectopia on MRI is highly associated with anterior pituitary hormone deficiency.

Diagnostic Procedures/Other

Automated visual field testing may be useful, but children are often too young to do this test reliably.

Pathological Findings

Markedly reduced retinal ganglion cells and nerve fiber layer

DIFFERENTIAL DIAGNOSIS

• Optic atrophy

• Ocular albinism

• Optic nerve coloboma

TREATMENT

MEDICATION

No known medical therapy available.

ADDITIONAL TREATMENT

General Measures

• Eyeglasses for protection of the better-seeing eye when asymmetry is present

– Correction of refractive errors

– Treatment of possible concurrent amblyopia

– Surgery for concurrent strabismus or nystagmus may be considered

Issues for Referral

• Pediatric ophthalmology referral to treat any underlying amblyopia and possible surgery for strabismus/nystagmus

• Pediatric neurology referral if evidence of coexisting CNS abnormalities

• Pediatric endocrinology referral to evaluate frequent coexisting endocrinopathies

COMPLEMENTARY & ALTERNATIVE THERAPIES

Stem cell transplantation is not proven to affect visual function in optic nerve hypoplasia

SURGERY/OTHER PROCEDURES

• There is no known useful surgery for optic nerve hypoplasia at this time.

– Surgery may be considered for coexisting strabismus or nystagmus

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Yearly or more frequent examinations for evaluation and treatment of strabismus, amblyopia, and refractive errors

Patient Monitoring

Patients should be monitored for possible coexisting amblyopia. This may occur as a result of the optic nerve hypoplasia itself or associated refractive errors or strabismus.

PATIENT EDUCATION

Importance of treating any associated conditions, such as amblyopia and the need for low vision assessment and aids should be discussed.

PROGNOSIS

Visual acuity generally remains stable over time. There is some tendency for mild visual improvement with maturity.

COMPLICATIONS

Generally related to associated endocrinopathies and other CNS malformations

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