+++
Optic Nerve
Hypoplasia
++
Optic nerve aplasia is extremely rare, and most often the diagnosis
represents an extreme example of optic nerve hypoplasia. Optic nerve
hypoplasia is characterized by a reduction in the number of axons
within the optic nerve. The nerve head is small and often pale.
There may be a white or yellow peripapillary halo surrounded by
a ring of pigment (double ring sign) corresponding to the size of
a normal disc (Fig. 593-1). The normal distance
from the temporal disc edge to the macula is 3 to 3.4 disc diameters.
If the optic nerve is small, the number of disc diameters increases
to greater than 4 disc diameters. The retinal vasculature may be
tortuous, and the fovea pit may be underdeveloped. On radiographic
study, the optic canal is small. The diagnosis can be difficult
if optic nerve hypoplasia is mild. Disc photography and quantitative
assessment of optic nerve head features by a nerve head analyzer
may be helpful in establishing a diagnosis.
++
++
Visual acuity ranges from normal to no light perception but is
stable over time. It is difficult to predict vision outcome based
on the appearance of the optic nerve head or with neuroimaging.
Most cases are sporadic. Familial instances are rare. Optic nerve
hypoplasia has been associated with fetal alcohol syndrome; maternal
diabetes (usually a hemihypoplasia affecting the upper or lower
half of the disc); maternal use of quinine, anticonvulsants, or
aminopterin; maternal illicit drug use; in utero cytomegalic infection;
toxemia; and adolescent pregnancy. Accompanying ocular disorders
may include aniridia, albinism, coloboma, Duane retraction syndrome,
high myopia, and numerous neurological and pediatric conditions.
++
Up to 78% of affected patients have bilateral optic
nerve hypoplasia, and 75% have neurodevelopmental problems
that accompany bilateral involvement. In bilateral optic nerve hypoplasia,
particularly in severe forms, poor vision and nystagmus may be apparent
early in life, and there may be associated abnormalities such as
mental retardation, delayed development, seizures, deafness, cerebral
atrophy, hemiparesis, ventricular defects, porencephalic cyst, hypopituitarism,
hypothyroidism, and diabetes insipidus. Sudden death has been reported
in response to a viral illness likely due to unrecognized pituitary
insufficiency. Septo-optic dysplasia, also known as de Morsier syndrome,
is one of the more common bilateral optic nerve hypoplasia syndromes.
It is characterized by midline central nervous system abnormalities
such as hypothalamic dysfunction, pituitary dysfunction, and agenesis
of the septum pellucidum; malformation of the optic chiasm; and
agenesis of the corpus callosum. Patients have a characteristic
facies with a broad forehead and large anterior fontanelle. Mutations
in the autosomal dominant HESX1 gene at 3p21.2-p21.1 may be responsible
in many affected patients.1
++
Because of the high incidence of associated central nervous system
anomalies and endocrinologic problems, all patients with optic nerve
hypoplasia, particularly if bilateral, need a complete neurological
workup, including brain computerized tomography (CT) or magnetic
resonance imaging (MRI). An absent infundibulum of the pituitary
or an ectopic posterior pituitary bright spot are characteristic
MRI findings. Endocrinologic evaluation should include growth hormone,
adrenal, and thyroid function. Patients with partial absence of
the septum pellucidum have a threefold lower risk of pituitary hormone
deficiency than those with complete absence of the septum pellucidum.
Abnormalities of the hippocampus correlate with severe neurological
problems. Early recognition and treatment of the hormonal imbalance
permits prompt endocrinologic management and helps the child achieve
normal growth and development.2
++
In unilateral optic nerve hypoplasia, serious central nervous
system abnormalities are present in about 20% of affected
individuals. Patients are typically seen because of strabismus and
decreased vision. Amblyopia may develop in addition to the organic
visual loss and should be treated if the visual impairment directly
due to the optic nerve malformation is felt not to be profound.
Because it is difficult to predict visual potential based on the
appearance of the nerve, patching of the unaffected (or less affected)
eye is often indicated. If the hypoplasia is unilateral or asymmetric,
there may be an afferent pupillary defect (Marcus Gunn pupil).3
++
Optic nerve coloboma is due to incomplete closure of the posterior end
of the embryonic fissure of the optic cup in the seventh week of
gestation. This process is in part driven by the PAX2 transcription
gene at 10q25, mutation of which can result in the renal-coloboma
syndrome characterized by renal malformations and isolated optic
nerve coloboma. Most cases of coloboma are sporadic. Optic nerve
coloboma may also be part of an incomplete closure of the rest of
the fissure affecting the iris, or choroid (with dysplasia of the overlying
retina). Multiple other genes have been implicated in this process.
++
The colobomatous optic nerve appears as an enlarged, white, excavated
nerve head with or without coloboma of the surrounding choroid (Fig. 593-2). Microphthalmia may be present.
If large, it may include the macula. Visual acuity can be very good
if coloboma is isolated to the nerve. Subarachnoid cerebrospinal
fluid around the optic nerve may flow through the defect under the
retina, interfering with macular function.
++
++
Optic nerve pits are a mild form of nerve head coloboma characterized
by dark gray oval or slitlike holes in the disc, usually on the
inferotemporal side or centrally. They are usually unilateral and
most often have no hereditary pattern. A wide variation in visual
acuity can occur, and the vision is usually normal. Optic pits are
important clinically, because they may produce scotomas, at times
associated with serous (caused by fluid under the retina) retinal
detachments.4 Although retinal detachment has been seen
in children in the first decade, it occurs in up to 50% of
the patients at a mean age of 31 years. It is believed that cerebrospinal
fluid tracks under the retina, causing the detachment. Attempts
to repair the elevated retina with silicone oil injected into the
eye have resulted in the silicone oil migrating into the subarachnoid
space of the optic nerve.5 Systemic abnormalities are not
commonly associated with congenital optic nerve pits.
++
This optic disc anomaly can be considered a form of optic nerve
coloboma. Most instances are unilateral and nonfamilial. The disc
appearance resembles the morning glory flower. The optic nerve is
located in the center of an enlarged, excavated disc with central
fibroglial tissue (Fig. 593-3). It can be
orange or pink in color, with the retinal vessels splayed out at
the periphery of the disc. It is twice as common in females as in
males, and the right eye is more frequently involved. Visual acuity
is usually 20/100 or worse, although it is difficult to
predict the visual potential based on the appearance of the anomaly.
Patients with vision as good as 20/40 are known. Patching
the unaffected eye may be helpful in reversing amblyopia, which
complicates the vision loss. High myopia and visual field defects
are prominent. Serous retinal detachment is the most serious ocular
complication and may occur in up to 38% of the patients.
Although usually isolated, association with sphenoidal encephalocele
is known and may be suspected if the patient also has a notch in
the center of the lip. Morning glory optic nerve has also been reported
in trisomy 4q and the PHACE syndrome (posterior
fossa malformations; hemangiomas; arterial
abnormalities; cardiac defects, especially aortic
coarctation; and eye abnormalities).6
++
+++
Myelinated Nerve
Fibers
++
Myelination of the optic nerve usually ceases at the lamina cribrosa
just before birth. Occasionally, it proceeds distally, extending
intraocularly to produce a congenital, white, feathery opacification
of the neuroretinal
rim and peripapillary retina (Fig. 593-4).
Visual acuity is usually unaffected unless the myelination extends
into the fovea. The blind spot may be enlarged. This condition is
bilateral in 20% of patients. Extensive myelinated nerve
fibers have been associated with high myopia and amblyopia.7
++
+++
Persistent Fetal
Vasculature
++
A persistence of the primary vitreous, previously referred to
as persistent hyperplastic primary vitreous (PHPV),
has been renamed persistent fetal vasculature (PFV).
The hyaloid artery and vein normally course from the optic disc
to the back of the lens in utero and spontaneously resorb in the
late third trimester. At the back of the lens, the hyaloid system
is confluent with a dense array of vasculature that envelops the
lens, including the tunica vasculosa lentis on the lens surface,
and communicates with iris vessels. The manifestations of PFV include
abnormalities of pupil size and iris development, which are usually
visually insignificant but can appear as a dense cataract with extensive
retrolental fibrovascular tissue between the optic nerve and posterior
lens. The lens posterior capsule is abnormally vascularized and
fibrotic. This may cause the ciliary processes to be pulled in centrally
with anterior displacement of the iris-lens diaphragm. Angle-closure
glaucoma may result. Occasionally the retina may also be involved.
Microphthalmia is common. Visual prognosis is guarded, but satisfactory
results can be obtained if the macular retina is not involved and
cataract surgery is performed early in infancy followed by aggressive
patching of the unaffected eye. The disorder is almost always unilateral,
isolated, and sporadic.8
++
With partial resorption, a thin patent vessel containing blood
extends from the optic disc to the posterior lens capsule, usually
attaching inferonasally to the optical center. This is usually visually
insignificant. A small posterior capsule opacity, called the Mittendorf
dot, falls within the spectrum of PFV but is not of any
visual concern.
++
Intrapapillary drusen or hyaline bodies of the optic nerve head
are tiny white or yellow translucent masses of hyaline-like material
buried within the substance of the optic nerve head anterior to
the lamina cribrosa. They occur almost exclusively in Caucasians,
with an incidence of 0.3% to 1.0% clinically and
2% histopathologically. They are bilateral in 75% to
80% of cases. In young children, the masses are inconspicuous,
but within 1 to 2 decades, they become visible on the surface of
the disc as shiny, refractile bodies that glow with indirect light.
They may elevate the nerve head, thus simulating papilledema (pseudopapilledema).
Drusen of the optic disc can be identified in at least 75% of
the instances of pseudopapilledema. Pseudopapilledema and neurological
disorders that frequently coexist by coincidence (eg, headache)
may lead to unnecessary neuroradiologic and neurosurgical investigations
for exclusion of an intracranial process. Because drusen of the
optic nerve can be inherited as an autosomal dominant trait, ophthalmoscopic
examination of family members may disclose similar lesions and thus
help establish the correct diagnosis in a child with pseudopapilledema.
Ophthalmoscopy is diagnostic if the drusen are visible. Ultrasonography,
CT scan, and intravenous fluorescein angiography may be helpful
ancillary tests if the drusen are buried. Visual acuity is usually
unaffected, although progressive visual field defects have been
reported in adults. Rarely, subretinal neovascular membranes with
hemorrhage may compromise central acuity.9