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

Often, the diameter of the choroidal portion of the optic nerve is smaller than normal and the optic nerve tissue is heaped up on the surface of the optic disc.

Congenital Crescent or Conus

I.A white, semilunar area lies at the margin of the optic disc, usually involving the inferior or inferotemporal margin of the disc. The conus often occurs with an oval disc whose long axis is parallel to the crescent.

II. Vision is usually defective.

III.An associated hypermetropia, often with an associated pit of the optic disc, is frequently seen.

IV. A congenital crescent should not be confused with a myopic crescent. Unlike the former, a myopic crescent is not present at birth, is progressive, has a temporal or annular location about the optic disc, and is associated with other retinal degenerative changes and with myopia.

V.Histologically, retinal pigment epithelium (RPE) and choroid are missing in the area of the conus.

A lack of embryonic development of RPE may be the primary defect.

Congenital (Familial) Optic Atrophies

I.Simple recessive congenital optic atrophy

A.Simple congenital optic atrophy has an autosomalrecessive 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.The histology is as described in the section Optic Atrophy

on p. 514 in this chapter.

II.Behr’s syndrome

A.Behr’s syndrome, a heterogeneous group, tends to have an autosomal-recessive inheritance pattern, and its onset is between 1 and 9 years of age.

B.One form of Behr’s syndrome has been reported in Iraqi Jews.

1.The patients have 3-methylglutaconic aciduria.

2.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.

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

C.The histology is as described in the section Optic Atrophy

on p. 514 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 the

OPA1 (3q28–3q29), OPA2 9X-linked;X; Xp11.4 to 11.212), OPA3 (autosomal recessive; 19q13.2 to13.3), and OPA4 autosomal dominant; 18q12.2–121.3).

B.The visual loss in dominant optic atrophy (Kjer type) has an insidious onset in the first 5 or so 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.The histology is as described in the section Optic Atrophy

on p. 514 in this chapter.

IV. Leber’s hereditary optic neuropathy (LHON)

A.LHON, one of the mitochondrial myopathies (see p. 538 in 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 e ect when present with each other or with class I mutations.

A

C

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

5.LHON mainly a ects men in European families, but only slightly more men than women in Japanese families.

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.

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.

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).

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.

B

Fig. 13.4 Coloboma of optic nerve. A, The enlarged, deeply excavated optic disc resembles a morning-glory flower, hence the name morningglory syndrome, another form of optic nerve coloboma. B, Another patient had bilateral microphthalmos with cyst secondary to 18 chromosome deletion defect. C, Histologic section shows smooth muscle, like that found in contractile peripapillary staphyloma, near a coloboma of optic nerve (see also Fig. 2.10). (B and C, From Yanoff M et al.: Am J Ophthalmol 70:391. © Elsevier 1970.)

2.Color vision is a ected early.

3.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.

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

D.The histology is as described in the section Optic Atrophy on p. 514 in this chapter.

Coloboma

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.

A

B

Fig. 13.5 Optic pit. Right (A) and left (B) eyes from same patient. Left eye shows large pit (another form of optic nerve coloboma) in the inferior temporal optic nerve head. C, Histologic section of another case shows herniation of retinal tissue through an enlarged scleral opening along one side of the optic nerve (o, area of optic pit; pe, pigment epithelium; r, primitive retinal tissue). (C, Courtesy of Dr. JB Crawford, from Irvine AR et al.: Retina 6:146, 1986, with permission.)

C

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 then is 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 Fig. 13.4B and C and p. 531 in 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 (retinopathy) 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, hemorrhages, pigmentary changes, cysts, and holes.

Serous detachment of the macula is probably the basic lesion that causes the other macular changes.

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.

Pitlike 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. The 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.

B.Girls are a ected twice as often as boys.

C.The visual acuity is usually poor.

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

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

F.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.

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

H.Neural retinal detachment, retinal vascular anomalies, and displacement (ectopia) of the macula may be seen.

Systemic abnormalities such as transsphenoidal encephalocele, agenesis of the corpus callosum, midline

CNS anomalies, endocrine dysfunction, cleft lip and palate, and renal anomalies have been reported.

I.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.

Myopia

I.Even before the onset of juvenile myopia, children of myopic parents have longer-than-normal eyes (Fig. 13.6; see p. 423 in 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.

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.

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)

I. Usually, visual acuity is not a ected.

II.Because the term papilledema is widely interpreted as a swollen optic nerve head secondary to raised intracranial pressure, the term optic disc edema, which is the generic term, is preferred for all noninflammatory causes of a swollen optic nerve head.

Fluorescein studies of optic disc edema show late

fluorescence.

III.The term papillitis is used for a swollen optic nerve head secondary to inflammation.

Causes

I. Relative or absolute increase in venous pressure at the lamina cribrosa or posterior to it, such as occurs in acute glaucoma, optic nerve tumors, orbital tumors, brain tumors, subarachnoid hemorrhage, meningitis, encephalitis, malignant hypertension, and from drugs (e.g., tetracycline)

II.Relative increase in venous pressure at the lamina cribrosa or anterior to it, such as occurs in accidental penetrating wounds, intraocular surgery, uveitis, central retinal vein thrombosis, and ocular hypotony from any cause (acute or chronic)

III.Local phenomena (e.g., the Irvine–Gass syndrome, irondeficiency anemia, gastrointestinal hemorrhage, papillitis,

juxtapapillary choroiditis, mucopolysaccharidoses, and perhaps from oral contraceptives)

IV. Axoplasmic transport (flow)

A.Orthograde axoplasmic transport occurs at various rates, including a rapid component (200 to 1000 mm/ day) and a slow component (0.5 to 3 mm/day). Retrograde axoplasmic transport also occurs.

B.Blockage of optic nerve axoplasmic flow at the level of the lamina choroidalis and lamina scleralis occurs through increased intracranial pressure, ocular hypotony, or increased intraocular pressure and results in increased mass or bulk of the optic nerve head.

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.

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.

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 NEURITIS

In general, visual acuity is severely a ected.

Causes

I.Secondary to ocular disease (e.g., acute corneal ulcer; anterior or posterior uveitis; endophthalmitis or panophthal-

mitis; 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.

2.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.

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

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

C-reactive protein above 2.45 mg/dl and an ESR of 47 mm/ hour or more is highly specific (97%) for temporal arteritis.

4.The aorta and its larger branches, including coronary arteries, may be involved in up to 10% to 15% of cases.

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% to 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.

Choroidal ischemia may be the first sign of temporal arteritis in elderly patients who have loss of vision.

6.Although most teaching is 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.

Temporal artery biopsy may be positive even after up to 1 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).

b.Rarely, a chronic nongranulomatous reaction with lymphocytes and plasma cells without epithelioid or giant cells is seen (see Fig. 13.9).

c.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 as 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 55to

70-year-old people who are usually otherwise well, except that approximately half have mild hypertension.