Ординатура / Офтальмология / Английские материалы / Ocular Pathology_6th edition_Yanoff, Sassani_2009

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-alfa.

2.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, longterm follow-up shows increased incidence of stroke.

3.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.

4.The second eye is involved in about 15% of patients over a 5-year period.

No form of therapy has proved efficacious. Old optic atrophy coupled with fresh contralateral disc infarction may be confused with the Foster–Kennedy syndrome.

5.The ESR is usually below 44 mm/hour, unlike the elevated ESR in temporal arteritis.

6.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.

7.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 di ers 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 di ers 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.MS (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).

b.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-cyto- toxic 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.

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

d.Associated sheathing of retinal veins is seen in 10% to 20% of patients.

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

In one study, 13% to 15% of patients who had MS presented with optic neuritis, and 27% to 37% of patients who had MS showed evidence of optic neuritis during the course of the disease. MS develops in approximately 17% to 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 8 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.

c.Bilaterality of optic atrophy along with paraplegia is characteristic.

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

Pupillary changes are not characteristic.

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

C.Di use cerebral sclerosis primarily involves white matter of the CNS and includes Schilder’s disease (Fig. 13.13), Krabbe’s disease, Pelizaeus–Merzbacher syn-

drome, 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 p. 514 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 in-

flammation, 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 destruc-

tion 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; section on Inflammation in Chapter 1; and 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 (usually has giant cells) with necrosis of the arterial wall and a splitting and destruction of the inner elastic lamina (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 to 13.13)

a.Early breakdown of myelin sheaths occurs.

b.Macrophages phagocytose the disintegrated myelin.

c.The “fat-laden” phagocytes then move to perivascular locations.

d.A perivascular “cu ng” 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, e.g., 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 over 50% of all dementia in the United States, a ecting approximately 8% of the population 65 years of age or older.

b.Patients may present with visual signs and symptoms, e.g., di culties with reading and writing, problems with navigation, and di culty 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

*Usually very little, if any, gliotic reaction on surface of optic disc, hence “white” or primary optic atrophy.

†Usually gliotic reaction on surface of optic disc, hence “dirty” or secondary optic atrophy.

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 e ects 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*; 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 e ects are on the optic disc and neural retina.

III.Inherited optic atrophy

A.Familial optic atrophies (Table 13.1; and see subsection

Congenital (Familial) Optic Atrophies on p. 501 in this chapter)

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

Histology of Optic Atrophy

I.Shrinkage or loss of parenchyma and loss of both myelin and axis cylinders are seen (Figs 13.14 and 13.15; see Fig. 13.13).

A.Shrinkage results in widening of the subarachnoid and subdural spaces and redundancy of the dura.

B.Pial septa widen to occupy the space made by the loss of parenchyma.

C.The normal spongy texture of the optic nerve is lost.

II.Optic nerve gliosis and proliferation of astrocytes are prominent.

III.The physiologic cup widens or deepens and results in a baring of the lamina cribrosa.

IV. Secondary changes

A.Glial proliferation on the surface of the disc results in a “secondary” optic atrophy.

*see footnote on p. 513.

B.Hyaluronic acid accumulates in the anterior portion of the optic nerve [i.e., cavernous (Schnabel’s) optic atrophy; see Fig. 16.33] after long-standing glaucoma (see p. 659 in Chapter 16).

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 5 years, with over 80% of patients younger than 15 years of age; 71% of the tumors occur during the first decade of life.

2.Gliomas of the optic pathways account for 2% to

5% of intracranial tumors in children.

3.The tumor is quite rare after the second decade of life (approximately two-thirds are diagnosed in the

first 5 years of life).

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.

Although a rare case of ONG may occur in NF-2, most occur in NF-1. Gliomas in patients who have NF-1 appear to be more indolent than in patients who do not have NF-1, and tend to occur at a later age (average 7.1 years) than in patients without NF-1.

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 13.2).

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.

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

Although Rosenthal fibers are characteristically found in ONG, they are not pathognomonic. The fibers 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 pre-

cursor marker), S-100, and vimentin, suggesting origin from type 1 astrocytes.

3.Secondary e ects

Rarely, synaptophysin-positive neuronal cells may be present. The appropriate name then is ganglioglioma, which probably has the same prognosis as ONG.

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.

TABLE 13.2 Juvenile Pilocytic Astrocytoma of the Optic Nerve: Location of Astrocytoma

(Adapted from Yanoff M et al.: Juvenile pilocytic astrocytoma [“glioma”]. In Jakobiec FA, ed: Ocular and Adnexal Tumors. Birmingham, Aesculapius, 1978:685.)

d.The ONG may infiltrate the optic nerve head.

e.The tumor may 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 to 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.

Optociliary shunt vessels may also 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 with chronic atrophic optic disc edema. Primary intracranial meningioma may extend into the orbit secondarily and even involve the optic nerve. Also, 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, 2 of 8 patients younger than 20 years of age were alive without recurrence (follow-up less than 2 years), 4 had recurrent tumor (1 with intracranial extension and 3 without), and 1 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 to 21 years), and 3 patients had died (1 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.