Optic Nerve

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13

Optic Nerve

Normal Anatomy

I. The optic nerve is made up of a number of components (Figs. 13.1 and 13.2).

A. The major component is myelinated nerve fibers or axons (white matter).

1. The axons of the optic nerve are extensions of the retinal ganglion cells whose unmyelinated axons form much of the nerve fiber layer of the neural retina.

2. The axons or “nerve fibers” then enter the optic disc by making a sharp turn, where they continue as a series of fascicles or bundles, separated from one another by helical columns of glial cells (astrocytes) and vascular connective tissue septa, to form the optic nerve.

3. The optic nerve becomes myelinated as it traverses the lamina cribrosa scleralis, doubling its diameter from approximately 1.5 mm at the optic disc to 3 mm as it leaves the scleral canal posteriorly.

The lamina cribrosa is a series of trabeculae, contiguous with the choroidal (lamina cribrosa choroidalis—glial) and scleral (lamina cribrosa scleralis—vascularized collagen) coats of the eye. The trabeculae form a crisscross pattern outlining “pores” through which the nerve fiber bundles pass. The myelinated orbital portion of the optic nerve can be considered more a tract of the brain than a true cranial nerve. The optic nerve is continuous at one end with the retina and at the other end with the brain, making it vulnerable to a variety of both ocular and central nervous system (CNS) diseases.

B. All the CNS meningeal sheaths (dura, arachnoid, and pia) are present and surround the orbital portion of the optic nerve. The subarachnoid space of the optic nerve is continuous with that of the intracranial contents.

An elevation of intracranial pressure, therefore, is directly transmitted to the subarachnoid space surrounding the optic nerve and contained within its dural sheath.

C. The capillary blood supply to the anterior 2 to 3 mm of the optic nerve (intrachorioscleral portion) is derived exclusively from the ophthalmic artery through two sources; the major supply consists of peripapillary choroidal branches, which are fed through the choroidal circulation by the short posterior ciliary arteries; the other minor source is the perineural plexus in the most anterior portions of the subarachnoid space surrounding the optic nerve.

D. The capillary blood supply of the remaining ophthalmic artery vessels enters the nerve from the pial surface in a symmetric, radially distributed pattern.

E. The central retinal artery first enters the optic nerve approximately 0.8–1.5 cm behind the globe.

II. The optic nerve is approximately 30 mm long, longer than the distance from the back of the eye to the optic canal, and so takes a somewhat sinuous course through the posterior orbit.

Congenital Defects and Anatomic Variations

Aplasia

I. Aplasia of the optic nerve (Fig. 13.3) is rare, especially in eyes without multiple congenital anomalies.

II. Most cases occur as unilateral disorders in otherwise healthy persons, although bilateral cases have been reported.

III. Most probably, the retinal ganglion cells fail to develop properly. Alternatively, the optic nerve aplasia may result from abnormal invagination of the ventral fissure.

IV. Histology

A. The optic nerve, optic nerve head, nerve fibers (axons) in the retinal nerve fiber layer, and retinal vessels are absent.

B. The retinal ganglion cell layer is diminished or absent. When present, the retinal ganglion cells appear undifferentiated, lacking axons or dendrites.

Hypoplasia

I. Although rare, hypoplasia (underdevelopment of the optic nerve) is more common than aplasia (congenital absence of the optic nerve).

A. Hypoplasia of the optic nerve is a major cause of blindness in children.

B. In optic nerve hypoplasia, a small optic disc with central vessels is present.

The term optic nerve hypoplasia should be reserved for cases that show hypoplasia as the main or sole anomaly of the nerve (e.g., colobomas of the optic nerve usually show hypoplastic nerves, but the main event is the coloboma, not the hypoplasia). Also, in situations in which multiple anomalies of the eye or brain or both are present, it is difficult to determine whether the optic nerve is hypoplastic (primary failure of development) or atrophic (secondary degeneration). A hypoplastic or atrophic optic nerve may be found in association with grossly malformed eyes (e.g., microphthalmos) or with deformities of the CNS (e.g., hydrocephalus). Hypoplasia of the optic nerve is also a prominent feature of septo-optic dysplasia (de Morsier syndrome), which consists of optic nerve hypoplasia, absence of the septum pellucidum, and pituitary insufficiency.

II. Optic nerve hypoplasia may be unilateral or bilateral, with or without optic foramina radiographic abnormalities, causes subnormal vision, and shows a decreased number of optic nerve axons.

III. Visual acuity is generally markedly decreased.

IV. The cause is failure of the retinal ganglion cells to develop normally.

A. Because the optic stalk is invaginated by mesoderm, the central retinal artery and vein are present on the disc.

B. Histologically, the nerve shows partial or complete absence of neurites.

Congenital (Familial) Optic Atrophies

I. Simple recessive congenital optic atrophy

A. It has an autosomal-recessive inheritance pattern and significant visual disability.

B. Clinically, its onset is in infancy, is accompanied by a pendular nystagmus, and shows total optic atrophy.

C. Histology—see Optic Atrophy later in this chapter.

II. Behr’s syndrome

A. Behr’s syndrome, a heterogeneous group, tends to have an autosomal-recessive inheritance pattern. Its onset is between one and nine years of age.

B. One form of Behr’s syndrome has been reported in Iraqi Jews who have 3-methylglutaconic aciduria.

1. The main neurologic signs in these patients, as well as other patients who have Behr’s syndrome but presumably no 3-methylglutaconic aciduria, consist of increased tendon reflexes, a positive Babinski sign, progressive spastic paraplegia, dysarthria, head nodding, and horizontal nystagmus.

2. The optic atrophy tends to be severe, but occasionally only or mostly involving the temporal optic disc.

C. Histology—see Optic Atrophy later in this chapter.

III. Dominant optic atrophy (Kjer)

A. Dominant optic atrophy is the most common of the inherited optic atrophies; the gene abnormality is in OPA1 (3q28–3q29), OPA2 (9X-linked;X; Xp11.4–11.212), OPA3 (autosomal recessive; 19q13.2–13.3), and OPA4 (autosomal dominant; 18q12.2–12.3).

B. The visual loss in dominant optic atrophy (Kjer type) has an insidious onset in approximately the first five years of life, with considerable variation in families. Approximately 58% of affected patients have onset of symptoms before the age of 10 years.

1. Long-term visual prognosis is relatively good, with stable or slow progression of visual loss.

2. Most patients have blue-yellow dyschromatopsia; the Farnsworth–Munsell test shows the characteristic tritanopia defect.

3. The optic nerve varies from mild pallor to complete atrophy. Some nerves are said to have a characteristic focal temporal excavation.

C. Histology—see Optic Atrophy later in this chapter.

IV. Leber’s hereditary optic neuropathy (LHON)

A. LHON, one of the mitochondrial myopathies (see Chapter 14), is inherited through the maternal transmission of one or more mitochondrial DNA (mtDNA) mutations.

The inheritance of these point mutations of mitochondrial DNA is from mothers alone because the mitochondrial contribution to the embryo comes only from the maternal ovum.

B. Molecular genetic studies have shown that the condition results from a point mutation in the extranuclear mtDNA.

For example, in the 11778 point mutation, a guanine-to-adenine substitution at nucleotide 11778 of the nicotinamide adenine dinucleotide dehydrogenase subunit 4 gene in mtDNA results in the disease.

1. At least 11 pathogenetic point mutations of mtDNA have been described.

2. Class I consists of four mutations that are capable of directly causing LHON: In order of decreasing frequency, the point mutations of mtDNA occur at nucleotide positions 11778G–A, 3460G–A, 15257G–G–A, and 14484T–C (previously reported 4160T–C was probably 14484T–C).

Diabetes mellitus, Crohn’s disease, and vitamin B12 deficiency have also been reported with the 14484 mitochondrial mutation. Secondary mutations such as 13708, 15257, and 15812 may also occur.

3. Class II contains five mutations and carries a much lower risk of blindness, but the mutations have an enhancing or predisposing effect when present with each other or with class I mutations.

4. Class I/II contains two mutations that have an intermediate effect between classes I and II.

5. LHON mainly affects men in European families, but only slightly more men than women in Japanese families. Presumably a gene (or genes) on the X chromosome (tentatively localized to the subregion p11.3) influences the expression of LHON mutations, and an ethnic variant exists in Europeans that predisposes to disease.

An unusual type of epidemic neuropathy in Cuba that resembles LHON, but is not associated with the primary and most common DNA mutations associated with LHON, has been described.

C. LHON is characterized by a subacute, sequential, bilateral, central loss of vision mainly in young men (usually between the ages of 18 and 30 years). Color vision is affected early.

1. The acute neuropathy is characterized by circumpapillary, telangiectatic neuropathy; swelling of the nerve fiber layer around the optic disc (pseudopapilledema); and absence of disc leakage on fluorescein angiography.

2. The acute neuropathy is followed by nerve fiber loss mainly in the papillomacular bundle, optic atrophy, and mostly irreversible visual loss. A transient worsening of visual function with exercise or warming (Uhthoff’s symptom) is not unusual.

3. The optic nerve and inner retinal atrophy in LHON may be a result of metabolic mitochondrial dysfunction that leads to intramitochondrial calcification.

D. Histology—see Optic Atrophy later in this chapter.

Coloboma (Table 13.1)

I. A coloboma (Figs. 13.4 and 13.5) may involve the optic disc alone or may be part of a complete coloboma involving the entire embryonic fissure.

A. Its clinical appearance may vary from a deep physiologic cup to a large hole associated with a retro­bulbar cyst.

B. The surrounding retina may be involved.

II. It is usually unilateral, and the cause is either a failure in fusion of the proximal end of the embryonic fissure or aplasia of the primitive Bergmeister’s papilla.

III. A coloboma of the optic disc may be associated with other ocular anomalies, such as congenital nonattachment of the retina, coloboma of the neural retina and choroid, and persistent hyaloid artery.

A coloboma of the optic nerve (cavitary optic disc anomaly) may be inherited as an autosomal-dominant trait. It is then usually bilateral and shows evidence of a serous detachment of the macular or extramacular neural retina. The types of anomalies in an individual family range to all possible combinations of coloboma of the optic disc, including optic nerve pit. Some family members show progressive optic nerve cupping with increasing age. Mutations in the PAX2 gene may occur in patients who have optic nerve colobomas and renal abnormalities.

IV. Vision may be normal but is usually defective.

V. Histologically, the coloboma appears as a large defect at the side of the nerve usually involving the neural retina, choroid, and sclera.

A. Fibrous tissue lines the defect, which often contains hypoplastic or gliotic retina. The gliosis may be so massive as to simulate a neoplasm.

B. The wall of the defect may contain adipose tissue and even smooth muscle cells.

A contractile peripapillary staphyloma may result from the presence of smooth muscle cells.

C. The coloboma may protrude into the retrobulbar tissue and cause microphthalmos with cyst (see Figs. 13.4B and 13.4C and Chapter 14).

VI. An optic nerve pit (see Fig. 13.5) is a form of coloboma of the optic nerve that shows a small, circular or triangular depression approximately one-eighth to one-half the diameter of the optic disc, usually located in the inferotemporal quadrant of the disc.

A. It tends to be unilateral, and more than one may be present. Bilateral optic pits have been reported in monozygotic siblings.

B. The optic disc is usually of greater size than the one in the uninvolved fellow eye.

Less frequently, a centrally placed pit of the optic disc may occur. The presenting symptom may be decreased vision or a defect in the visual field that usually remains unchanged. Central serous choroidopathy does not occur with a central pit. Rarely, an autosomal-dominant inheritance pattern is present.

C. In approximately one-third to one-half of cases, the optic pit may be associated with macular changes such as serous detachment of the macula (which probably is the basic lesion that causes the other macular changes), hemorrhages, pigmentary changes, cysts, and holes.

An alternative theory is that a macular detachment develops secondarily to a pre-existing schisis-like lesion consisting of severe outer neural retinal edema. Fluid may enter the retina directly from the optic pit rather than entering the neural retina from the subneural retinal space.

a. The condition usually occurs in people between 20 and 40 years of age and carries a poor visual prognosis.

b. There is no angiographic evidence of leakage of fluorescein dye into the area of the detached retina.

c. Subretinal fluid probably consists of vitreous fluid leaked into the area through the pit or, less likely, cerebrospinal fluid leaked around the pit into the subneural retinal space.

One reported attempt at intrathecal injection of fluorescein failed to show fluorescein leakage into the subretinal space in a case of optic nerve pit with a serous detachment of the macula. Only a minute amount of fluorescein, however, was injected. A second attempt used radioisotope cisternography in a patient who had serous detachment of the macula associated with a coloboma of the optic nerve; radioactivity of the subretinal fluid was not demonstrated. Rarely, peripapillary subretinal neovascularization may occur.

D. The optic pit is probably caused by an anomalous development of the primordial optic nerve papilla and failure of complete resolution of peripapillary neuroectodermal folds, which are part of the normal development of the optic nerve head.

Pit-like localized cupping of the optic nerve (acquired pit of the optic nerve) can occur in glaucoma, especially in normotensive (“low-tension”) glaucoma.

E. Histologically, the pit is an outpouching of neurectodermal tissue surrounded by a connective tissue capsule. The pit passes posteriorly through a defect in the lamina cribrosa and protrudes into the subarachnoid space.

VII. Morning glory syndrome (see Fig. 13.4A) is a form of coloboma of the optic nerve that shows an enlarged, deeply excavated optic disc, resembling the morning glory flower.

A. Although the condition is usually unilateral, rare bilateral cases have been reported.

Morning glory disc anomaly has been reported in association with ipsilateral optic nerve glioma.

B. Girls are affected twice as often as boys, and visual acuity is usually poor.

C. The tissue that surrounds the funnel-shaped staphylomatous excavation involving the nerve proper and peripapillary retina often appears elevated.

D. The demarcation of the elevated peripapillary tissue and normal surrounding retina is indistinct.

E. The retinal vessels seem to originate from deep within the excavation, travel along the peripheral optic disc and peripapillary neural retinal tissue, and exit radially.

F. Glial tissue may obscure the anomalous cup, and surrounding retinal pigment epithelial alterations may occur.

G. Neural retinal detachment, retinal vascular anomalies, and displacement (ectopia) of the macula may be seen along with systemic abnormalities such as transsphenoidal encephalocele, agenesis of the corpus callosum, midline CNS anomalies, endocrine dysfunction, cleft lip and palate, and renal anomalies.

H. Histologically, the optic disc is displaced deeply in the posterior, staphylomatous, colobomatous defect.

VIII. Choristoma

A. Rarely, choristomatous elements can be found in the optic nerve in the absence of a coloboma.

B. Because of the absence of a coloboma, these cases are usually mistaken for an optic nerve glioma (ONG).

C. Histologically, choristomatous elements such as adi­pose tissue and smooth muscle replace most of the parenchyma of the optic nerve.

image

(From Brodsky MC: Congenital optic disk anomalies. Surv Ophthalmol 39:89, 1994.)

Myopia

I. Even before the onset of juvenile myopia, children of myopic parents have longer-than-normal eyes (Fig. 13.6; see Chapter 11).

II. The optic disc in myopia is oblique, with exaggeration of the normally raised nasal and flattened temporal edges. A surrounding white scleral crescent is usually present temporally.

III. The optic nerve head is ovoid, with a long vertical axis. Pit-like structures can develop around the optic disc and myopic conus.

IV. Histologically, the optic nerve passes obliquely through the scleral canal.

A. Temporal side of optic disc

1. The RPE and Bruch’s membrane do not extend to the temporal margin of the optic disc.

2. The choroid extends farther toward the temporal margin of the disc than do the RPE and Bruch’s membrane.

3. The sclera exposed just temporal to the optic disc margin is seen through the transparent neural retina as a white crescent.

B. Nasal side of disc

Overlapping tissue (i.e., neural retina, RPE, Bruch’s membrane, and choroid) may extend as far as halfway over the nasal half of the scleral opening.

Optic Disc Edema

General Information (Fig. 13.7; see Fig. 13.22)

Pseudopapilledema

Optic disc edema may be simulated by hypermetropic optic disc, drusen of optic nerve head, congenital developmental abnormalities, optic neuritis and perineuritis, and myelinated (medullated) nerve fibers.

Histology of Optic Disc Edema

I. Acute (see Fig. 13.7)

A. Edema and vascular congestion of the nerve head result in increased tissue volume.

1. Hemorrhages may be seen in the optic nerve or in the retinal nerve fiber layer.

2. The increased tissue mass causes the physiologic cup to narrow.

Axonal swelling, caused by blockage of axoplasmic flow, rather than vascular alterations, appears to be the major factor in overall increase in tissue volume of the optic nerve head.

B. The aforementioned changes result in a displacement of the neural retina away from the edge of the optic disc.

1. The outer layers of the neural retina may buckle (retinal and choroidal folds are seen clinically).

2. The rods and cones are displaced away from the end of Bruch’s membrane.

The lateral displacement of the rods and cones results in enlargement of the blind spot. Sometimes the pigment epithelial cells are also pushed laterally so that the peripapillary RPE is flattened and cells farther away are “squeezed” together.

3. There may be a peripapillary neural retinal detachment, and this can add to the density of the peripapillary scotoma.

II. Chronic

A. Degeneration of nerve fibers may occur.

B. Gliosis and optic atrophy are most likely to occur with long-standing or chronic optic disc edema rather than with short-term or acute optic disc edema.

Optic disc edema secondary to increased intraocular pressure (e.g., acute closed-angle glaucoma) may cause necrosis of optic nerve fibers. Optic atrophy and even cavernous optic atrophy may result. The fibers in the optic nerve are more susceptible to injury by high intraocular pressure than are the retinal ganglion cells and nerve fiber layer.