• Optic nerve hypoplasia (ONH) is a congenital optic nerve disorder in which the optic nerve is smaller than normal, typically with decreased function.
– May be unilateral or bilateral
– Often associated with other CNS, in particular, midline defects (septo-optic dysplasia [SOD], de Morsier’s syndrome)
ONH: 6.3 per 100,000 children (3)
• Fetal alcohol syndrome (4)
– Maternal drug use (psychopharmaceutical drugs, some anticonvulsants, quinine LSD, and phencyclidine reported)
– Possibly younger maternal age (5)
– Premature/postmature birth
– Infants of diabetic mothers may have hemihypoplasia of the optic nerve.
• Most cases sporadic
– Mutation in HESX1 (3p21.1) identified in SOD, autosomal dominant
– Duplications of SOX3 identified in SOD
– There are numerous ocular (e.g., aniridia) and systemic genetic syndromes (e.g., oculocutaneous albinism) as well as intrauterine infections, which may have ONH as a feature.
• Maternal prenatal care
• Genetic counseling
• Reduced optic nerve fibers
• Poorly understood; possibly related to failed differentiation of retinal ganglion cells or excessive axonal regression during normal optic nerve development
• Decreased visual acuity (ranging to light perception)
• SOD (de Morsier syndrome) (MIM #182230): ONH associated with midline brain defects including absent septum pellucidum, agenesis of corpus callosum, and hypothalamic and pituitary dysfunction. May also have cortical migration defects (e.g., cortical ectopia, pachygyria). Classic de Morsier’s syndrome associated with abnormal facies, macrocrania, and large open anterior fontanelle
• Endocrinopathies including hyperprolactinemia, hypothyroidism, adrenal insufficiency, diabetes insipidus, growth hormone deficiency
• History of poor visual behavior in one or both eyes since birth with/without nystagmus
– Prenatal history of maternal alcohol/drug use
– Poor infant growth, neonatal jaundice, hypoglycemia, or seizures suggesting pituitary axis dysfunction
• Complete eye exam with indirect ophthalmoscopy to evaluate optic nerve appearance. May have the appearance of the “double ring sign”: a yellow–white ring around the small disc representing the scleral canal that is unfilled due to reduction in optic nerve size
• Increased distance between fovea and temporal optic nerve edge
• May have immature vascular pattern of arcades
• May have foveal hypoplasia
• Nystagmus or strabismus in affected eye(s) may be present.
• May have associated microphthalmia
• Loss of percentiles on growth chart
• May have microcephaly, large anterior fontanel (de Morsier), seizures, developmental delay
• Majority of children, especially with unilateral ONH, will be systemically well, developmentally normal, and with no brain or pituitary involvement.
DIAGNOSTIC TESTS & INTERPRETATION
Initial lab tests
If abnormal neuroimaging of pituitary or evidence of hormonal signs: thyroid functions (TSH, T3, T4), even if neonatal screen was normal, other serum hormonal screening per endocrinology
Follow-up & special considerations
• Endocrinology evaluation as indicated
• Follow growth charts
• MRI of brain and orbits to evaluate intracranial optic nerves and for midline CNS defects (5)[C], cortical migration defects, and pituitary abnormalities including absent pituitary stalk, or ectopic bright spot (displacement of the posterior pituitary up into area of pituitary stalk
• Neuroimaging is an imprecise way of determining optic nerve size or function.
Follow-up & special considerations
Follow development and neurologic signs
Referral to endocrinology and neurology as indicated
Reduced optic nerve fibers, reduced retinal ganglion cell count, normal outer retinal layers (2)
• Optic atrophy
– High hypermetropia
– Tilted optic nerve
– Optic nerve coloboma
– Peripapillary staphyloma/atrophy
Hormonal replacement therapy if needed
• Amblyopia treatment especially if asymmetric bilateral or unilateral
• Low vision aids and support
– Strabismus correction
– Refractive correction if indicated
– Protective eyewear if unilateral poor vision
Issues for Referral
• Endocrinology referral for pituitary dysfunction
• Neurology referral if neurologic signs
• Developmental assessment
• Genetics consultation
COMPLEMENTARY & ALTERNATIVE THERAPIES
• NOTE: there is currently no scientific evidence to support the use of stem cell treatment for this disorder.
Strabismus or nystagmus surgery as indicated
Admission rarely indicated but sudden death and severe pituitary dysfunction may occur.
• Ongoing ophthalmologic follow-up for visual evaluation, refractive correction, amblyopia therapy
– Low vision evaluation as indicated
– Endocrinology, neurology, and developmental follow-up
• Focus Families: ONH/SOD Information, Education and Support: www.focusfamilies.org/
• Visual prognosis variable depending on optic nerve function.
– Prognosis poorly correlated with optic nerve appearance on physical exam or neuroimaging
• Potentially significantly decreased visual acuity in affected eye(s)
– Pituitary axis dysfunction
– Neurologic sequelae including seizures and developmental delay
1. Kelberman D, Dattani MT. Genetics of septo-optic dysplasia. Pituitary 2007;10:393–407.
2. Patel L, McNally R, Harrison E, et al. Geographical distribution of optic nerve hypoplasia and septo-optic dysplasia in Northwest England. J Pediatrics 2006;148:85–88.
3. Ahmad T, Garcia-Filion P, Borchert M, et al. Endocrinological and auxological abnormalities in young children with optic nerve hypoplasia: a prospective study. J Pediatr 2006;148:78–84.
4. Zeki S, Dutton G. Optic nerve hypoplasia in children. Br J Ophthalmol 1990;74:300–304.
5. Hellstrom A, Wiklund L, Svensson E. The clinical and morphologic spectrum of optic nerve hypoplasia. J AAPOS 1999;3:212–220.
6. Brodsky M, Glasier C. Optic nerve hypoplasia: clinical significance of associated central nervous system abnormalities on magnetic resonance imaging. Arch Ophthalmol 1993;111:66–74.