Optic Nerve

Published on 20/03/2015 by admin

Filed under Pathology

Last modified 22/04/2025

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 6078 times

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.

Optic Neuritis

In general, visual acuity is severely affected.

Causes

I. Secondary to ocular disease (e.g., acute corneal ulcer, anterior or posterior uveitis, endophthalmitis or panophthalmitis, and retinochoroiditis; see Fig. 4.26)

II. Secondary to orbital disease [Fig. 13.8; e.g., as bilateral idiopathic inflammation of the optic nerve sheaths, cellulitis (may be primary but more commonly secondary to sinusitis), thrombophlebitis, arteritis, and midline granuloma syndrome]

III. Secondary to intracranial disease (e.g., meningitis, encephalitis, and meningoencephalitis)

IV. Secondary to spread of distant infection (e.g., acquired immune deficiency syndrome, syphilis, tuberculosis, coccidioidomycosis, and bacterial endocarditis)

V. Secondary to vascular disease [Figs. 13.9 and 13.10; e.g., temporal arteritis, periarteritis nodosa, pulseless (Takayasu’s) disease, and arteriosclerosis]

A. Temporal (cranial, giant cell) arteritis (see Figs. 13.9 and 13.10)

1. Temporal arteritis (ischemic arteritic optic neuropathy) is most commonly found in middle-aged or elderly women. It is often associated with malaise, weight loss, fever, headaches, scalp pain, neck pain, intermittent jaw claudication, scalp necrosis, and visual loss.

Jaw claudication is the most reliable clinical sign, followed by neck pain.

2. The superficial temporal artery may be red, tender, firm, enlarged, and pulseless, or it may be normal.

3. The erythrocyte sedimentation rate (ESR) becomes elevated (usually above 44 mm/hour), often to a high degree.

The odds of a positive temporal artery biopsy are 5.3 times greater with a C-reactive protein above 2.45 mg/dl, 4.2 times greater with platelets above 400,000, and 1.5 times greater with an ESR of 47–107 mm/hour.

4. The aorta and its larger branches, including coronary arteries, may be involved in up to 10–15% of cases. Choroidal ischemia may be the first sign of temporal arteritis in elderly patients who have loss of vision.

5. Marked impairment of visual acuity, often with involvement of the second eye within days or weeks of involvement of the first eye, is the most frequent ocular problem, but ptosis and muscle palsies may also occur.

a. Approximately 14–27% of patients have permanent visual loss.

b. Regional choroidal nonperfusion, presumably secondary to arteritis of a ciliary artery, may cause a reversible (with steroid therapy) visual loss.

6. Although most teaching advises that a temporal artery biopsy should be performed before steroid therapy is instituted, some authorities suggest that it can be performed within 48 hours or even more, after treatment with steroid therapy has begun (in fact, temporal artery biopsy may be positive even after up to one month of steroid therapy for presumed temporal arteritis).

7. Histologically, a granulomatous reaction centering about a fragmented internal elastic lamina and spreading into the media and adventitia of the temporal artery is characteristic.

a. Giant cells are frequently present (see Fig. 13.10) but may be absent (see Fig. 13.9). Rarely, a chronic nongranulomatous reaction with lymphocytes and plasma cells without epithelioid or giant cells is seen (see Fig. 13.9).

b. The inflammatory reaction tends to be spotty so that microscopic sections cut at many levels may have to be done; thus, a positive finding is more significant than a negative one.

It is unclear whether the pathogenesis involves humoral immunity (direct immunofluorescence demonstrates immunoglobulin) or cell-mediated immunity (almost all lymphocytes in the inflammation are T lymphocytes, and often surrounding macrophages express human leukocyte antigen-DR). A significant association exists between varicella–zoster virus (VZV) DNA in temporal artery biopsies from patients who have temporal arteritis compared to patients who do not have the condition. VZV may play a role in the pathogenesis of some cases of temporal arteritis.

B. Anterior ischemic optic neuropathy (ANION; Fig. 13.11)

1. ANION (nonarteritic) occurs primarily in 55- to 70-year-old people who are usually otherwise well, except that approximately half have mild hypertension.

Cigarette smoking is an important risk factor in the development of ANION. Also, ANION has been reported as a complication secondary to treatment with interferon-α. Extracranial carotid occlusive disease is not significantly associated, and long-term follow-up shows no increased incidence of stroke. In the presence of Hollenhorst plaques, however, long-term follow-up shows increased incidence of stroke.

2. Clinically, a sudden or rapidly progressive monocular visual acuity loss is associated with pallid optic disc edema, followed by a stable visual field defect of variable degree.

The most common visual field defect is altitudinal, with a 3 : 1 preference for the inferior half of the field. The fixational area is spared at least as often as it is involved.

3. The other eye is involved in approximately 15% of patients over a five-year period.

Old optic atrophy coupled with fresh contralateral disc infarction may be confused with the Foster–Kennedy syndrome.

4. The ESR is usually less than 44 mm/hour, unlike the elevated ESR in temporal arteritis.

5. The pathophysiology and the anatomic background of ANION are not well understood. Histologic findings are consistent with optic disc edema of a noninflammatory type. In some cases, the optic nerve infarction is caused by embolic occlusion of small arteries supplying the anterior portion of the optic nerve.

6. A condition that has numerous similarities to ANION (abrupt onset, absence of ocular pain, altitudinal field loss, and lack of subsequent improvement) is called neuroretinitis (previously called Leber’s stellate maculopathy).

a. Neuroretinitis differs from ANION in involving a relatively young group (average age 27 years), the tendency to recur, and macular star formation (more common than in ANION).

b. Neuroretinitis differs from “garden-variety” optic neuritis in the absence of ocular pain, tendency to spare fixation, lack of visual recovery, macular star formation, and no increased risk for development of multiple sclerosis (MS).

VI. Secondary to demyelinating disease

A. Multiple sclerosis (Fig. 13.12; see Fig. 13.11)

1. Retrobulbar neuritis

a. Retrobulbar neuritis has an acute onset in one eye with sudden loss of vision, usually preceded by orbital pain (especially with ocular movement). Vision tends to recover in a few weeks to months.

With loss of vision, a central scotoma can be demonstrated on central visual field examination. Frequently, after the first eye has recovered, the second eye is involved. In MS, lesion progression is associated with large numbers of helper (inducer) T cells in the adjacent normal white matter, whereas suppressor–cytotoxic T cells are limited to the lesion margin. Demyelination seems to depend on the presence of macrophages. Evidence implicates cell-mediated immunity as the cause of MS.

b. The ophthalmoscopic appearance may be normal, or papillitis may simulate optic disc edema.

c. Associated sheathing of retinal veins is seen in 10–20% of patients.

d. The risk development of MS after an uncomplicated optic neuritis is 3.5 times greater in women than in men.

Approximately 13–15% of patients who had MS presented with optic neuritis, and 27–37% of patients who had MS show evidence of optic neuritis during the course of the disease. MS develops in approximately 17–38% of patients who have optic neuritis; younger patients have a higher incidence.

2. Ocular muscle palsies may occur (conjugate movements may be involved) along with nystagmus, frequently of the cerebellar type. Internuclear ophthalmoplegia may also occur. Variable, uncharacteristic pupillary changes may also be noted.

3. A link may exist between pars planitis and MS, especially when retinal periphlebitis is present at the time of diagnosis of pars planitis (MS develops in perhaps 15% of patients with pars planitis followed for at least eight years).

Other ocular inflammations associated with MS to a lesser extent include periphlebitis, granulomatous uveitis (especially anteriorly), and neuroretinitis.

B. Neuromyelitis optica (encephalomyelitis optica; Devic’s disease) consists of bilateral optic atrophy and paraplegia.

1. Bilateral optic atrophy

a. The loss of vision is acute in onset and rapid in progression, even to complete blindness.

Unlike in MS, pain precedes loss of vision in very few cases. The loss of vision precedes onset of paraplegia in approximately 80% of cases.

b. The ophthalmoscopic appearance may be normal, or a papillitis may simulate optic disc edema. Bilaterality of optic atrophy along with paraplegia is characteristic.

2. Extraocular muscle palsies and nystagmus may be seen infrequently.

3. Paraplegia usually follows loss of visual acuity in days to weeks, but it may follow in months or, rarely, in years.

C. Diffuse cerebral sclerosis primarily involves white matter of the CNS and includes Schilder’s disease (Fig. 13.13), Krabbe’s disease, Pelizaeus–Merzbacher syndrome, adrenoleukodystrophy, and metachromatic leukodystrophy.

A number of childhood diseases [e.g., neonatal and X-linked (childhood) adrenoleukodystrophy, infantile Refsum’s disease, and primary hyperoxaluria type 1] may be attributed to the malfunction of the subcellular organelle peroxisome.

VII. Secondary to nutritional or toxic or metabolic disease [e.g., starvation (nutritional), tobacco–alcohol toxicity, methyl alcohol, diabetes mellitus, hyperthyroidism, amiodarone, disulfiram, iodochlorohydroxyquinoline, ethambutol, and chloramphenicol]

VIII. Secondary to hereditary conditions (see later in this chapter)

IX. Secondary to idiopathic or unknown causes

X. Secondary to radiation (e.g., after radiation therapy for pituitary adenoma, a delayed necrosis of the perisellar optic nerves and chiasm may occur)

Histology of Optic Neuritis

I. General information

A. Optic neuritis, retrobulbar neuritis, papillitis, and neuroretinitis are clinical terms and do not connote specific causes. Actually, many causes exist (e.g., inflammatory, vascular, and degenerative).

The suffix –itis, therefore, as generally used here, is not necessarily synonymous with inflammation.

B. Topographic histologic classification of optic neuritis

1. Perineuritis: leptomeningeal involvement (e.g., extension of intracranial meningitis, of orbital inflammation, or from intraocular inflammations)

2. Periaxial neuritis: leptomeningeal involvement spreads to the optic nerve parenchyma, usually in its periphery.

3. Axial neuritis: inner or central portions of the optic nerve involved (e.g., MS, toxic factors, malnutrition, and vascular factors)

4. Transverse neuritis: total cross-sectional destruction of a variable length of optic nerve (e.g., Devic’s disease)

II. Specific types of tissue reaction

A. Inflammatory disease: the types of inflammatory disease of the optic nerve depend on the cause (see Figs. 13.8 and 13.13; see also Fig. 4.26; see section on Inflammation in Chapter 1 and see Chapters 3 and 4).

B. Vascular disease: the clinicopathologic picture depends on the type of vascular disease involving the optic nerve.

1. Temporal (cranial) arteritis: a granulomatous arteritis (see Figs. 13.9 and 13.10)

2. Nonarteritic (ischemic) optic neuropathy (see Fig. 13.11)

3. Periarteritis nodosa: a fibrinoid necrosis of muscular arteries and arterioles with acute and chronic nongranulomatous intra-arterial wall inflammatory reaction

4. Pulseless disease and arteriosclerosis: coagulative or ischemic type of necrosis

C. Demyelinating diseases

1. Demyelinating stage (see Figs. 13.11–13.13)

a. Early breakdown of myelin sheaths occurs. Macrophages phagocytose the disintegrated myelin.

b. The “fat-laden” phagocytes then move to perivascular locations. A perivascular “cuffing” or exudation of fluid, lymphocytes, and plasma cells around blood vessels frequently is seen in areas remote from the acute reaction.

2. Healing stage (see Fig. 13.13B)

a. Astrocytic response occurs in areas of demyelination.

b. Ultimately, the area of involvement shows gliosis.

D. Nutritional or toxic or metabolic diseases

1. Little is known of the acute reaction.

2. These conditions may cause considerable destruction of optic nerve parenchyma with resultant secondary optic atrophy.

Optic Atrophy*

Causes

I. Ascending optic atrophy

A. The primary lesion is in the neural retina or optic disc—for example, glaucoma* (see Figs. 16.32 and 16.33), retinochoroiditis,† retinitis pigmentosa,† traumatic or secondary retinitis pigmentosa,† central retinal artery occlusion* (see Fig. 11.10), chronic optic disc edema,† toxic or nutritional causes (e.g., chloroquine*), and Alzheimer’s disease (AD).*

1. AD

a. AD primarily causes more than 50% of all dementia in the United States, affecting approximately 8% of the population 65 years of age or older.

b. Patients may present with visual signs and symptoms—for example, difficulties with reading and writing, problems with navigation, and difficulty recognizing familiar objects.

c. The apolipoprotein E gene and a putative AD gene(s) on chromosome 10q are two known risk factors for late-onset AD.

The rare, early onset autosomal-dominant form of AD results from mutations in at least three different genes: amyloid precursor protein gene on chromosome 21, presenilin-1 gene on chromosome 14, and presenilin-2 gene on 14 chromosome 1.

d. The diagnosis of AD depends on antemortem evidence of dementia and postmortem findings of neuritic plaques, neurofibrillary tangles, and neuronal cell loss primarily in subcortical brain areas, such as hippocampus, amygdala, and locus ceruleus.

Although a few individual patients who have AD may exhibit a marked hypersensitivity in their pupillary response (i.e., rapid pupillary dilatation) to the topically administered cholinergic antagonist tropicamide, in most patients with AD the pupillary response is no different than in control subjects.

e. Histologically, the optic nerves seem to show preferential loss of the large-caliber fibers derived from the largest class of neural retinal ganglion cells (M cells). The M-cell system mediates specific visual functions, and selective involvement in AD leads to clinically measurable neuro-ophthalmic and psychophysical impairments.

B. The secondary effects are on the optic nerve and white tracts in the brain.

II. Descending optic atrophy

A. The primary lesion is in the brain or optic nerve [e.g., tabes dorsalis,* Creutzfeldt–Jakob disease,* hydrocephalus,* meningioma* (see Figs. 13.18 and 13.19), ONG,* and traumatic transection of the optic nerve*]; toxic or nutritional causes (e.g., methyl alcohol*); and genetically determined disorders* [e.g., Schilder’s disease (see Fig. 13.13), Pelizaeus–Merzbacher syndrome, adrenoleukodystrophy, and Krabbe’s disease].

B. The secondary effects are on the optic disc and neural retina.

III. Inherited optic atrophy

A. Familial optic atrophies (Table 13.2; see subsection Congenital (Familial) Optic Atrophies in this chapter)

TABLE 13.2

Optic Atrophies

Congenital Juvenile
Dominant Recessive Dominant Recessive Leber’s Behr’s
Inheritance Dominant Recessive Dominant locus on chromosome 2 Recessive X-linked Recessive
Systemic signs and symptoms — — — Diabetes, decreased hearing Headache, vertigo, nervousness, palpitations Increased tendon reflexes, + Babinski, ataxia, + Romberg, muscular rigidity, mental debility
Onset Birth or neonatal Birth or neonatal Slow onset, 2–6 years of age Slow onset, 6–12 years of age Acute onset, 16–30 years of age 1–9 years of age
Nystagmus Yes Yes No No No Possibly
Vision 20/100 to hand movements Poor 20/20 to 3/400 HM to LP ~10/200 ~10/200
Fields Constricted peripheral — Central scotoma; possibly bitemporal defect; blue inside red — Central scotoma Central scotoma
Fundi Marked narrow arteries Total atrophy Sector temporal atrophy Total atrophy Hyperemia/optic disc edema followed by white disc after neuritis Sector temporal atrophy
Color testing May be reduced — Possible blue-green defect — Red-green defect —
Electroretinogram — — Normal Normal Normal Normal
Visually evoked cortical potential — — Possibly diminished — — —
Dark adaptation — — Possibly diminished Normal Diminished Normal
Clinical course Slow progression — Atrophy usually is stationary — Acute course; outcome may be better (normal) or worse vision Evolution of neurologic symptoms for years; then stabilization
Pathology — — Optochiasmatic arachnoiditis seen at surgery — Atrophy of retinal ganglion cells, demyelination in optic nerve and temporal lobe Degeneration of second retinal neuron

image

(Modified from Caldwell JBH, Howard RO, Riggs LA: Dominant juvenile optic atrophy: A study of two families and review of the hereditary disease in childhood. Arch Ophthalmol 85:133–147, 1971. © American Medical Association. All rights reserved.)

B. Glucose-6-phosphate dehydrogenase (G-6-PD) Worcester

1. G-6-PD Worcester is a variant of G-6-PD deficiency with congenital, nonspherocytic hemolytic anemia, absent erythrocyte G-6-PD activity, and optic atrophy.

2. It is inherited as a sex-linked recessive trait.

C. Friedreich’s ataxia

Injuries

See Chapter 5.

Tumors

Primary

I. “Glioma” (more properly called juvenile pilocytic astrocytoma) of optic nerve (Figs. 13.16 and 13.17)

A. The prevalence is slightly greater in girls than in boys.

1. The median age at onset is approximately five years, with more than 80% of patients younger than 15 years of age; 71% of the tumors occur during the first decade of life.

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

2. Gliomas of the optic pathways account for 2–5% of intracranial tumors in children. Approximately two-thirds are diagnosed in the first five years of life, and it is quite rare after the second decade.

B. Proptosis, predominantly temporal, is the most common presenting sign; loss of vision is the next most common sign.

1. When intracranial involvement occurs, the presenting signs may be nystagmus, headache, vomiting, and convulsions.

2. Occasionally, the presenting sign clinically may be a central retinal vein occlusion; more commonly, however, it occurs as a late phenomenon.

C. Neurofibromatosis [NF: mainly NF type 1 (NF-1)] is present in approximately 25% of patients who have ONG; conversely, approximately 15% of patients who have NF have ONG.

D. Optic disc edema followed by optic atrophy is a frequent clinical finding.

E. The ONG is most often located in the orbital portion of the optic nerve alone, with combined involvement of both orbital and intracranial portions next most common (Table 13.3).

F. If the ONG is limited to the orbital or intracranial portion of the optic nerve, the optic foramen may still be enlarged.

Secondary meningeal hyperplasia may travel proximally (or distally) and is responsible for the enlargement of the optic foramen. An enlarged optic foramen, therefore, is not necessarily proof of intracranial extension of an orbital ONG. Conversely, the optic foramen may be normal in the face of intracranial or chiasmal ONG.

G. The mortality rate is significant.

1. If the astrocytoma is limited to the orbital portion of the optic nerve, the prognosis is excellent. Surgical removal, even when incomplete, usually cures.

2. With involvement of the intracranial optic nerve, the prognosis is guarded.

H. Histology

1. Three main patterns may all be present in different parts of the same tumor:

a. Transitional area: the tumor merges into the normal optic nerve and is difficult to differentiate from reactive gliosis: glial nuclei are more numerous and less orderly than in the normal nerve; increase in the number and size of glial cells results in enlarged nerve bundles; and the area has a finely reticulated appearance.

b. Coarsely reticulated and myxomatous area: microcystoid spaces in the tumor are probably secondary to tumor necrosis. The spaces contain acid mucopolysaccharides that are partially sensitive to hyaluronidase.

c. Astrocytic areas: the areas resemble juvenile astrocytomas of the cerebellum and are probably the same type of tumor.

1) The cellular areas show spindle cell formation.

2) Rosenthal fibers, which are cytoplasmic, eosinophilic structures in astrocytes, may be prominent.

Rosenthal fibers characteristically are found in ONG. The fibers also may be found in astrocytes in a number of inflammatory (e.g., Alexander’s disease) and other neoplastic processes involving the CNS. Rosenthal fibers are collections of ubiquitinated intermediate filaments (i.e., ubiquitinated glial fibrillary acidic protein).

2. Neoplastic astrocytes stain positively for glial fibrillary acidic protein, HNK-1 (type 1 astrocyte precursor marker), S-100, and vimentin, suggesting origin from type 1 astrocytes. Rarely, synaptophysin-positive neuronal cells may be present. The appropriate name then is ganglioglioma, which probably has the same prognosis as ONG.

3. Secondary effects

a. Infiltration by the ONG through the pia with resultant arachnoid hyperplasia is seen.

Secondary or reactive arachnoid (meningothelial) hyperplasia may extend well beyond the limits of the ONG. The hyperplasia may mimic a meningioma of the optic nerve sheath.

b. The tumor itself may enlarge the optic foramen (as may proliferating meningothelial cells).

c. The ONG may cause edema or atrophy of the optic nerve.

d. The ONG may infiltrate the optic nerve head or compress or occlude the central retinal vein.

II. Other astrocytic neoplasms

A. Oligodendrocytomas are rare.

More often, but still quite rarely, small collections of oligodendrocytes may be seen in ONGs that are made up predominantly of astrocytes.

B. Rarely, malignant astrocytic neoplasms may involve the optic nerve primarily, most commonly in adults. Histologically, the neoplasms are marked by areas of anaplasia and classed as low-grade astrocytomas, anaplastic astrocytomas, and glioblastoma multiforme.

1. Necrosis is the sine qua non of glioblastoma multiforme.

2. DNA analysis, combined with histologic grading, improves prognosis designation.

III. Meningioma (Figs. 13.18 and 13.19)

A. Primary meningioma of the intraorbital meninges of the optic nerve is more common in women than in men (5 : 1).

B. The average age at onset is 32 years (range, 3.5–73 years), with the median 38 years.

Approximately 40% of the tumors occur in patients younger than 20 years of age and 25% in patients younger than 10 years.

C. The main clinical presentations are loss of vision and progressive exophthalmos.

D. Optociliary (opticociliary) shunt vessels may be seen in approximately 25% of cases.

In addition, optociliary shunt vessels may be found in association with central retinal vein occlusion or as a congenital anomaly. The vessels have also been reported with optic nerve juvenile pilocytic astrocytomas (gliomas), arachnoid and optic nerve cysts, optic nerve colobomas and drusen, and chronic atrophic optic disc edema. Primary intracranial meningioma may extend into the orbit secondarily and even involve the optic nerve. Theoretically, a meningioma may arise primarily in the orbit from ectopic meningeal tissue.

E. There may be associated neurofibromatosis (mainly NF-2) in 16% of patients.

F. The prognosis for life depends somewhat on age at onset.

With onset in childhood, the meningiomas tend to be much more aggressive and to have a much worse prognosis than with onset at an older age. In one series, two of eight patients younger than 20 years of age were alive without recurrence (follow-up less than two years), four had recurrent tumor (one with intracranial extension and three without), and one died during an attempt to excise the recurrent tumor. In the same series, 10 of 13 patients older than 20 years of age were alive and well without recurrent tumor (follow-up, 3–21 years), and three patients had died (one an operative death). Adult patients who have primary optic nerve sheath meningiomas but do not have NF, followed over time after their diagnosis, tend to have a relatively stable course, and some may even show slight improvement.

G. Histologically, the tumors have a meningotheliomatous or a mixed-type pattern.

1. Fibroblastic and angiomatous types of meningiomas rarely occur primarily in the orbit.

“Angioblastic type” of meningioma, once thought to be of meningeal origin, is now generally accepted to be a hemangiopericytoma of the CNS. However, a case of primary orbital angiomatous meningioma, not arising from the optic nerve, has been reported.

2. Frequently, meningiomas extend extradurally to invade the orbital tissue.

3. Uncommonly, they invade the optic nerve and sclera and may even invade into the choroid and retina.

Malignant meningioma may be diagnosed if the tumor shows either, or both, unequivocal anaplasia or invasion of brain parenchyma (<10% of intracranial meningiomas are malignant).

image
Fig. 13.19 Meningioma of optic nerve. A, A meningioma of the orbital portion of the optic nerve has caused proptosis of the right eye. B, Fundus examination shows optic disc edema of long-term duration. C, A biopsy of another case (see Fig. 13.18) shows a proliferation of meningothelial cells. As is often the case, no psammoma bodies are present (b, blood vessels; n, nests of meningothelial cells). (A and B, Courtesy of Dr. WC Frayer.)

IV. Melanocytoma (see Chapter 17)

V. Hemangioma is usually associated with the phakomatoses (see Chapter 2).

Hemangiomas, usually cavernous, rarely capillary, infrequently may occur as a primary optic nerve tumor unassociated with the phakomatoses.

VI. Medulloepithelioma may rarely arise from the distal end of the optic nerve (see Chapter 17).

VII. Giant drusen of the anterior portion of the optic nerve are astrocytic hamartomas usually associated with tuberous sclerosis (see Chapter 2).

VIII. Ordinary drusen of the anterior portion of the optic nerve (Fig. 13.20)

A. Ordinary optic disc drusen occur in 3.4–24 per 1000 population and are bilateral in approximately 75%. They tend to increase in size with age because of increased calcium deposition.

B. These may present as pseudopapilledema. They also may occur in retinitis pigmentosa or pseudoxanthoma elasticum.

Drusen of the optic nerve occur 20–50 times more often in pseudoxanthoma elasticum than in the general, healthy population.

C. Although field defects are common (87% in one series), very rarely does a patient lose central vision.

D. Hemorrhage of the optic disc is a rare complication.

1. The hemorrhage may extend into the vitreous or under the surrounding retina.

2. Peripapillary subretinal neovascularization may occur.

E. Histologically, basophilic, calcareous, laminated acellular bodies of different sizes and shapes are located in the substance of the optic disc anterior to the scleral lamina cribrosa.

Drusen seem to start intracellularly but then enlarge and become extracellular. Alterations in axoplasmic transport (flow) may play a role in the formation of these drusen.

IX. Drusen of the adjacent RPE may protrude into the lateral aspect of the retinal layer of the optic nerve head.

Although drusen of the RPE and of the optic nerve have the same name, they are quite different. RPE drusen are basement membrane secretions of the RPE (Fig. 13.21), whereas optic nerve drusen are structurally as described previously and may be degenerative products of optic nerve glial cells, presumably astrocytes anterior to the scleral lamina cribrosa.

X. Corpora amylacea—these are intracellular, basophilic, periodic acid–Schiff-positive structures often observed in the white matter of the brain, including optic nerve and neural retina (mainly nerve fiber layer).

A. The structures are composed of a glycoprotein–acid mucopolysaccharide complex produced within neuronal axons, and probably represent products of axonal degeneration.

B. They have no clinical significance and are considered an aging phenomenon.

XI. Corpora arenacea (psammoma bodies)

A. These are laminated, basophilic bodies produced by the arachnoid meningothelial cells.

B. They are of no clinical significance and are an aging phenomenon.

Morphologically identical structures, psammoma bodies, may be found in meningiomas and in a variety of papillary carcinomas.

XII. Cysts of the optic nerve may be congenital, arise de novo, or occur secondary to conditions such as optic nerve juvenile pilocytic astrocytomas (gliomas), NF, empty sella syndrome, or hemangioma of leptomeningeal origin [optociliary veins (shunt vessels) may be found in the presence of optic nerve cysts].

XIII. Choristoma

XIV. Buscaiano bodies resemble corpora amylacea but are fixation artifacts.

Related posts:

Vitreous Nongranulomatous Inflammation Skin and Lacrimal Drainage System Ocular Melanocytic Tumors Lens Diabetes Mellitus