Optic nerve hypoplasia

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Optic nerve hypoplasia
Classification and external resources
ICD-10 H47.0
ICD-9 377.43

Disease Entity

Optic nerve hypoplasia is characterized by decreased number of optic nerve axons. It can present unilaterally or bilaterally[1]. It may present as an isolated anomaly or be associated with midline brain structural defect, such as septum pellucidum absence, agenesis of corpus callosum, cerebral hemisphere abnormalities, or pituitary gland abnormalities. Septo – Optic dysplasia (de Morsier syndrome) is used to describe the association between optic nerve hypoplasia and the absence of septum pellucidum and agenesis of corpus callosum.


Optic nerve hypoplasia ICD 9 code 377.43



First optic nerve hypoplasia case was described by Briere in 1877, and the first schematic drawing of optic disc appearance of optic nerve hypoplasia was done by Schwarz in 1915. In 1941, Dr. David Reeves at CHLA first described the association of optic nerve hypoplasia with agenesis of septum pellucidum. And subsequently the term of “la dysplasia septo –optique” was described by Georges de Morsier in 1956. In 1970 Dr. William Hoyt’s landmark paper recognized the association between optic nerve hypoplasia and growth hormone deficiency. And Dr. Hoyt attributed the discovery of the association of optic nerve hypoplasia with septum pellucidum agenesis to de Morsier, and resurrected the term of septo-optic dysplasia syndrome[2].


In 2007, ONH is considered as the 3rd most prevalent cause for any vision impairment in children < 3yo (Hatton, 2007)[3] after cortical vision impairment and retinopathy of prematurity. Optic nerve hypoplasia was identified in 12% of blind infants in Harris County in Texas in early 1980s. (Willamson 1987)[4] The incidences of optic nerve hypoplasia are 7.1 in 100,000 in Sweden and 10.9 per 100,000 in England. (Blohme 1997, Patel 2006)[5][6]


Vast majority of ONH cases cannot be attributed to specific gene mutations (Borchert 2012)[7]. There have been 2 genes reported for possible association with the development of optic nerve hypoplasia: HESX1 gene (associated with holoprosencephaly) (<1% cases in large series, 5 reported cases); SOX2 gene (associated with anterior pituitary hypoplasia and hypogonadism) (none in large series).

Risk Factors

Many prenatal risk factors have been reported: young maternal age, primiparity, maternal use of recreational drugs, anticonvulsants, or antidepressants; viral infections during pregnancy; fetal alcohol syndrome (25-48% of FAS patient presented with ONH) (Stomland 1987, Ribeiro 2007)[8][9]

General Pathology

In optic nerve hypoplasia, retinal nerve fiber layer and ganglion cell number are decreased, while the outer retinal layer is unaffected. (Zeki 1990)[10]



In optic nerve hypoplasia, optic disc is often pale or gray and smaller than normal. Optic discs often present with double ring sign – yellow to white ring around the disc. A ring of hypopigmentation or hyperpigmentation often, but not always surrounds the disc defining the area of the putative scleral canal. The outer ring represents the normal junction between sclera and the lamina cribrosa; the inner ring represents the abnormal extension of retina and pigment epithelium over the outer portion of the lamina cribrosa. Tortuous retinal arterioles, venules, or both may accompany ONH, but retinal vessels can also present with normal caliber. Assessment of area of disc relative to the distance between fovea to temporal edge of the disc often reveals the small disc diameters: DD/DM ratio < 0.35. (DD: disc diameter; DM: distance between fovea and temporal edge of the disc.) Some patients with the DD/DM ratio of 0.3-0.35 have normal VA, while the DD/DM ratio < 0.35 correlates with poor vision outcomes. (Patients’ age needs to be considered when evaluating the DD/DM ratio. In premature infants, the normal DD/DM ratio has been reported as DD/DM ≥ 0.26) (Rosenfeld 1995, Wang 2001).


In optic nerve hypoplasia patients’ visual acuity can range from normal to light perception. Visual acuity in optic nerve hypoplasia patients is related to the integrity of the macular fibers, and is often not correlated with overall size of the disc. Visual field often has localized defects combined with visual field constrictions, commonly in nasal or inferior fields. (Ouvrier 1986)[11] Eighty percent of optic nerve hypoplasia cases are bilateral and about 2/3 of the cases are symmetrically affected. Congenital sensory nystagmus often presents in bilateral ONH cases at 1-3 month of age, followed by strabismus development by 1 year of age, often esotropia. Primarily strabismus often develops in markedly asymmetric or unilateral cases. Hypothalamic dysfunction is the most common nonvisual problem in ONH cases. It has reported to be presented in 69% of unilateral cases vs 81% of bilateral cases (Garcia – Filion 2008)[12]. Absence of septum pellucidum was not associated with poor vision, pituitary dysfunction or development outcomes (Ahmad 2006)[13]. It has been reported that 13-34% of optic nerve hypoplasia cases have pituitary abnormalities: empty sella, ectopic posterior pituitary, nonvisualized infundibulum and posterior pituitary. Hypopituitarism occurs in 75% of optic nerve hypoplasia patients, although the majority of the patients have no pituitary abnormalities on neuroimaging. Hypopituitarism is believed to be due to hypothalamic dysfunction rather than pituitary dysgenesis (Ahmed 2006, Reidl 2002, Haddad 2005)[13][14] [15], and can present with different hormonal dysfunctions: moderated elevated serum prolactin (normally suppressed by hypothalamus); growth hormone deficiency (70%), hypothyroidism (43%); adrenocorticotropic hormone deficiency (27%); diabetes insipidus (5%). Normal pituitary function at initial evaluation does NOT preclude development of endocrinopathy in the future. Developmental delays occur in 75% of ONH cases (Margalith, 1984, Burke 1991, Garcia–Filion 2008)[16][17][12], with higher incidence in bilateral cases (78%) vs unilateral cases (39%). Patient can present with motor delays 75% cases, and communication delays 44% cases.

Differential diagnosis

Optic nerve atrophy, optic nerve coloboma, peripapillary staphyloma, morning glory disc anomaly, tilted disc syndrome, glaucoma.


All neonates with jaundice and recurrent hypoglycemia should have ophthalmic evaluation. All infants with poor visual behavior, strabismus, or nystagmus by 3 months of age should have an ophthalmic examination. MRI brain should be obtained for confirmed ONH cases to evaluate for hydrocephalus, corpus callosum hypoplasia, schizencephaly or polymicogyria. Positive MRI brain should prompt to neurologic exam. Endocrinologic and pituitary function evaluations should be done regardless of the status of septum pellucidum. Endocrine workups include: fasting morning cortisol and glucose, TSH, free4, growth hormone surrogates (IGF-1, IGFBP-3), LH, SFH, testosterone (if < 6mo age).

General treatment

All optic nerve hypoplasia patients with central nerve system abnormalities or endocrinolopathies should be managed by neurologist, neurosurgeons, endocrinologist or other specialists from respective fields. A team approach should be incorporated into management of those patients. Pediatric optic nerve hypoplasia patients should be monitor semiannually for growth pattern. Vision should be monitored at least annually, and all refractive errors should be corrected. Patching therapy is reserved for patients with good vision potential. Unilateral or markedly asymmetric optic nerve hypoplasia patients should not be treated with patching. Surgical correction for strabismus is reserved for patients with symmetrical functional vision in both eyes, and patients with some potential for binocularity. Otherwise, surgical strabismus can be deferred for psychosocial issues.


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