Optic Nerve Malformations

Optic nerve hypoplasia is a morphological description of a small-appearing optic nerve due to a decreased number of axons traveling from the retinal ganglion cells through the optic nerve head to the optic chiasm and lateral geniculate nucleus (Fig. 5.1). This results from either a primary lack of retinal ganglion cell and axon development or a retrograde loss of axons from disturbances in the posterior visual pathways before birth. Optic nerve hypoplasia is often associated with a number of midline intracranial malformations (septo-optic dysplasia or de Morsier’s syndrome) as well as structural brain abnormalities (schizencephaly, proencephaly).

Optic nerve hypoplasia is a congenital condition and can be unilateral, bilateral, or asymmetric in appearance. The diagnosis is usually made because the optic nerve head appears small on examination and there is decreased visual acuity or a visual field defect. Visual acuity deficits can vary from mild (20/20) to severe (NLP). Children with intracranial involvement can have pituitary dysfunction resulting in neonatal jaundice or hypoglycemia, and growth velocity can be decreased after age 3 or 4 years from decreased levels of growth hormone [1]. Associated cerebral maldevelopment can also cause mental retardation.

E.G. Buckley (*), M. Gearinger, J. Jing, and T. Mahmoud Duke University Eye Center Wadsworth Building, Erwin Road, PO Box 3802, DUEC, Durham, NC, USA

e-mail: buckl002@mc.duke.edu

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Fig. 5.1  Optic nerve hypoplasia (a) Right Optic nerve. Note small appearance to nerve with tortuosity of the vessels. Very little nerve tissue is present. (b) Left Optic nerve. Moderate hypoplasia. Some nerve tissue present. Vision 20/70

5.1.2  Classification

Brodsky has developed a classification based on the presence or absence of central nervous system abnormalities as seen on MRI scan [2]. Table 5.1 optic nerve hypoplasia can occur as an isolated finding in a small percentage of patients. The remainder of the patients had significant CNS abnormalities such as absent septum­ pellucidum, posterior pituitary ectopia, hemispheric migration abnormalities (schizencephaly,

Table 5.1  MRI findings in optic nerve hypoplasia

 Periventricular leukomalacia

 Encephalmalacia

cortical heterotopia and arachnoid cyst), or perinatal hemispheric injury (periventricular leukomalacia or encephalomalacia). Because of the strong association of other CNS lesions consistent with perinatal anoxia, he postulated that anoxia maybe a cause for optic nerve hypoplasia. The anoxic form is not associated with pituitary abnormalities indicating that a second etiology, which seems to be more developmental in origin, can also occur. MRI scanning is useful in distinguishing the various types.

Two additional variants of optic nerve hypoplasia can occur. The first is segmental ONH, which appears to be related to maternal diabetes mellitus [3, 4]. The second is homonymous hemioptic hypoplasia due to congenital cerebral hemispheric lesions. In these cases, retrograde axonal degeneration occurs before birth resulting in segmental hypoplasia of the superior and inferior poles of the ipsilateral optic nerve and a band of pallor across the contralateral optic nerve [5]. Visual loss results from both the cortical and optic nerve abnormalities. These children are usually profoundly visually impaired.

5.1.3  Genetics

There is no known mendelian pattern of inheritance of optic nerve hypoplasia, but there has been a report of monozygotic twins with ONH [6].

5.1.4  Pathophysiology

There have been a number of hypotheses regarding the etiology of ONH, including: primary deficiency of retinal ganglion cells, gestational CNS insult, improper axonal migration, and retrograde transsynaptic axonal loss [7].

A primary deficiency of retinal ganglion cells before the 17 mm embryonic stage can cause optic nerve hypoplasia. Scheie and Adler reviewed cases of optic nerve aplasia and hypoplasia [8]. They described histologic findings of an anencephalic infant and a cat with ONH that showed absence of ganglion cells and the nerve fiber layer. They did not comment on horizontal or amacrine cells. Mosier et al. point out that the retinal ganglion cell and horizontal and amacrine cells arise from a common stem cell [9]. Histologically, they found normal numbers and appearance of amacrine and horizontal cells, arguing against a primary deficiency of ganglion cells. However, Novakovic et al. describe a case of a child with bilateral macular colobomas and ONH– presumably from a primary lack of retinal ganglion cells [7].

Gestational CNS insult has also been postulated to lead to optic nerve hypoplasia. Brodsky has pointed out the association with periventricular leukomalacia and encephalomalacia points toward perinatal cerebral anoxic injury as a potential etiology of ONH [2]. ONH has been described with congenital suprasellar tumors [7]. Theoretically, space-occupying lesions can cause improper axonal migration as they course towards the lateral geniculate nucleus, and without appropriate connections, the axons die off. Finally, large prenatal cerebral lesions that affect the optic radiations or occipital cortex can cause retrograde transsynaptic axonal death (Fig. 5.2). This is thought to be the mechanism behind homonymous hemioptic hypoplasia.

5.1.5  Natural History

Optic nerve hypoplasia is a stationary process. If the disease is unilateral or asymmetric, amblyopia may occur and be a cause for some of the visual loss.

Fig. 5.2 MRI scan illustrating a large defect in the occipital lobe. Such injuries occurring before birth can lead to segmental optic nerve hypoplasia

5.1.6 Diagnosis

The diagnosis of optic nerve hypoplasia is based on the observation of a smaller than normal optic nerve, either globally or segmentally. Classically, there can be a “double ring” sign, with centrally placed nerve tissue

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Fig. 5.3 (a, b) Double ring sign seen in optic nerve hypoplasia (a). The outer ring is the scleral canal with the inner ring representing the optic nerve (b)

surrounded by a pigmented halo of retina and RPE (Fig. 5.3). This halo is over the peripheral lamina cribrosa and lacks underlying choroid.

Many authors have attempted to create guidelines for the normal size of the optic nerve. Jonas et al. measured optic nerve dimensions of 88 normal subjects from fundus photographs [10]. They found a mean optic disc area of 2.89 mm2 (and a range of 0.86–5.39 mm2). A microdisc was then determined to be less than 1.4 mm2 (two standard deviations below the mean). Romano measured the horizontal disc diameter from 35 mm transparencies of normal and clinically hypoplastic optic nerves [11]. He found no overlap between the two groups. Zeki et al. evaluated the disc to macula/ disc diameter and found a ratio greater than 2.94 provided a one-tailed upper population limit of 95% [12].

The appearance of the optic discs can be very asymmetrical, and it is difficult to assess vision potential based only on appearance. Since a large portion of the optic nerve serves the macula, a small optic disc can have reasonably good function. When ONH is associated with a strabismus or anisometropia, amblyopia may occur and vision can be poor for that reason. In such cases, amblyopia therapy should be entertained. The presence of a significant afferent pupillary defect mitigates against amblyopia as a cause for the visual loss.

Most patients with significant ONH have nystagmus, which is present shortly after birth. The nystagmus can be jerk, pendular, or a combination. If the ONH is severe, then searching random eye movements will often occur.

All patients with hypoplastic optic nerves should have an MRI evaluation to determine the presence of

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