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

site eye; asymmetry of the bony orbits; and shallow orbits

III.The most common causes of exophthalmos are: thyroid disease (most common for both unilateral and bilateral exophthalmos); hemangioma; inflammatory pseudotumors; and benign and malignant lymphoid tumors (all others are relatively rare)

Although dermoids are one of the most common orbital tumors, if not the most common, they rarely cause exophthalmos because of their position, which is usually anterior to the septum orbitale.

DEVELOPMENTAL ABNORMALITIES

Developmental Abnormalities of Bony Orbit

Developmental abnormalities are usually associated with abnormalities of the cranial and facial bones such as tower skull or hypertelorism.

Microphthalmos with Cyst

I.Microphthalmos with cyst (see Fig. 2.10) is usually a unilateral condition, but may be bilateral.

II. The cyst may be so large as to obscure the microphthalmic eye.

III.Proliferated neuroectodermal tissue (i.e., pseudogliomatous hyperplasia) may simulate an orbital neoplasm.

The ophthalmic artery and nasociliary nerve enter the orbit intraconally and, wrapping around the lateral aspect of the optic nerve, travel to the medial wall where they both give off their ethmoidal branches

Optic nerve

Fig. 14.4 Normal orbit— side view. Retrobulbar contents of orbit. (From Levine MR, Larson DW: In Podos SM, Yanoff M, eds:

Textbook of Ophthalmology, vol. 4. New York, Gower Medical Publishing, 1993:10.4–10.13. © Elsevier

1993.)

Fig. 14.5 Normal orbit—front view. Lacrimal gland and surrounding structures. (From Buffam FV: In Podos SM, Yanoff M, eds: Textbook of Ophthalmology, vol. 4. New York, Gower Medical Publishing, 1993:7.1– 7.6. © Elsevier 1993.)

IV. The condition is caused by incomplete closure of the fetal cleft.

Although microphthalmos with cyst usually has no known cause, it may be associated with the 13q deletion or chromosome 18 deletion defect (partial 18 monosomy). A congenital cystic eye may also be associated with contralateral persistent hyperplastic vitreous and cerebrocutaneous abnormalities, called cranial ectodermopathy.

V.Histologically, the eye may range from relative normality to complete disorder, and may contain structures such as ectopic smooth muscle and cartilage.

The cyst may be lined by gliotic retina or it may be filled with proliferated glial tissue that can reach massive amounts

(massive gliosis) and simulate a glial neoplasm.

III.Histologically, most cephaloceles show a structure similar to that of the optic nerve (i.e., white matter separated by pial septa).

Congenital Alacrima

I.Hereditary congenital alacrima is part of a systemic disturbance such as the Riley–Day syndrome or anhidrotic

ectodermal dysplasia.

II.An isolated case of congenital alacrima, presumably caused by hypoplasia of the lacrimal gland, has been reported.

ORBITAL INFLAMMATION

Acute

I.Nonsuppurative (see section Nonsuppurative, Chronic Nongranulomatous Uveitis and Endophthalmitis in Chapter 3)

—orbital cellulitis is most commonly caused by extension

of an inflammation from the paranasal sinuses (Fig.

14.6).

II.Suppurative (see section Suppurative Endophthalmitis and

Panophthalmitis in Chapter 3)

A.Purulent infection (e.g., with Staphylococcus) occurs commonly after trauma.

A rare causative agent of posttraumatic acute orbital inflammation is atypical mycobacteria.

B.Phycomycosis (mucormycosis) is a devastating cause of suppurative orbital inflammation (Fig. 14.7; see p. 86 in

Chapter 4.)

1.It is usually associated with other disease, especially when acidosis is present (e.g., diabetes mellitus, renal disease, and malignancies).

2.Thrombotic complications may dominate the clinical picture.

Cephaloceles

I.Cephaloceles are caused by a developmental malformation in which brain tissue or meninges, or both, are present in the orbit.

A.Meningocele—only meninges are present

B.Encephalocele—only brain tissue is present; hydroen- cephalocele—considerable fluid is present in the cyst

C.Meningoencephalocele—meninges and brain tissue are present

D.All of the preceding may communicate with the brain.

Although the initial communication usually closes, it may rarely remain open.

II.Most cephaloceles are developmental displacements of brain tissue, and are generally referred to as ectopic brain tissue.

Chronic

I.Nongranulomatous

A.Chronic nongranulomatous inflammation is the most common inflammatory lesion of the orbit and is of unknown cause (see pp. 571–573 in this chapter).

B.A rare cause is the benign lymphoepithelial lesion of Godwin*; Fig. 14.8.

*Mikulicz’s disease is the old name for benign lymphoepithelial lesion.

Mikulicz’s syndrome is a confusing term that has been used to describe secondary diseases of the lacrimal or salivary glands, as may occur in tuber-

culosis, metastatic cancer, malignant lymphomas, and leukemia. Because what Mikulicz originally described is uncertain, the terms Mikulicz’s disease and Mikulicz’s syndrome should be completely avoided. This will eliminate

much confusion that now exists in the literature and in clinical terminology.

A

C

1.It is characterized by painless unilateral or bilateral enlargement of the salivary or, rarely, the lacrimal glands.

2.It may be part of Sjögren’s syndrome (see later).

3.Rarely, it may become malignant.

4.Histologically, two features characterize benign lymphoepithelial lesion: (a) replacement of the glandular parenchyma by a benign lymphoid infiltrate and general preservation of the lobular architecture of the lacrimal gland; and (b) epimyoepithelial islands of proliferation in the glandular ducts.

C.Sjögren’s syndrome (see Fig. 14.8)

1.Sjögren’s syndrome is defined as a chronic autoimmune disorder characterized by lymphoid inflammatory infiltration of the lacrimal and salivary glands, destroying acinar tissue.

Autoantibodies to the ribonucleoprotein (RNP) particles SS-A (also called Ro RNA particle) and SS-B (also called La

snRNA) are produced systemically. The immune response to 120-kD α-fodrin may be important in the initial development of Sjögren’s syndrome.

2.The tissue destruction results in the symptoms of keratoconjunctivitis sicca and xerostomia.

B

Fig. 14.6 Orbital cellulitis secondary to acute ethmoiditis. A, Acute purulent inflammatory infiltrate present around right eye in child.

B, Similar purulent reaction, consisting mainly of neutrophils, is seen in tissue removed from another child. C, Special stain shows many Grampositive cocci.

The tissue destruction in the lacrimal gland may be related to elaboration of granzyme A and perforin. Rarely, the infiltrate can extend outside the lacrimal gland into the orbit.

3.Indirect support exists for a putative role of the

Epstein–Barr virus (see p. 63 in Chapter 3) in the pathogenesis of the disease.

D.Inflammatory pseudotumor (see pp. 571–573 in this chapter)

II.Granulomatous

A.Granulomatous inflammations rarely involve the orbit.

B.Causes include tuberculosis, sarcoidosis, syphilis, fungi, parasites (trichinosis, schistosomiasis, and so forth), Crohn’s disease, cat-scratch disease, midline lethal granuloma syndrome (polymorphic reticulosis), and giant cell polymyositis (giant cell granulomatous necrotizing myositis).

Tolosa–Hunt syndrome is a benign granulomatous orbital inflammation of unknown cause that presents as a painful ophthalmoplegia. Symptoms usually disappear after steroid therapy.

C.Cholesterol granuloma

1.Cholesterol granuloma has also been called cholesteatoma, lipid granuloma of the frontal bone, xanthomatosis of the orbit, hematoma, and chronic hematic cyst.

Some authors incorrectly use the term cholesteatoma interchangeably with epidermoid cyst. The term epidermoid cyst should not be used, or should be restricted to postinflammatory tumors that contain squamous epithelium and keratin debris; cholesterol granuloma is never associated with any epithelial elements.

2.Cholesterol granuloma of the orbital bones is a rare extraperiosteal condition that usually involves the frontal bone above the lacrimal fossa.

3.The cause seems to be a hemorrhage into the diploë of the bone, probably secondary to trauma, but perhaps, secondary to an anomaly in the diploë that could initiate a hemorrhage.

4.Histologically, a granulomatous reaction surrounds cholesterol crystals and altered blood.

D.Inflammatory pseudotumor (see pp. 571–573 in this chapter)

INJURIES

Penetrating Wounds

I.Direct e ect on whatever tissue may be wounded by the injury

II.Complications (indirect e ect)

A.Infection

1.Organisms may be introduced at the time of injury.

a.Bacteria cause an acute purulent inflammation.

b.Fungi cause a delayed, chronic, granulomatous inflammation.

B.Inflammation

1.The inflammation may be secondary to toxic products of tissue destruction.

2.Orbital thrombophlebitis may result.

3.A retained intraorbital foreign body may induce inflammation.

a.Frequently, cilia and pieces of skin, bone, wood, and so forth may be introduced into the orbit at the time of injury and cause a

foreign-body granulomatous inflammatory reaction.

b.Fungi may enter as a coincidental saprophyte along with the penetrating foreign body, which usually causes a granulomatous inflammatory reaction or even superimposed infection if the organism proliferates.

C.Orbital inflammation may lead to other complications such as cavernous sinus thrombosis, central retinal vein thrombosis, glaucoma, and proptosis.

Nonpenetrating Wounds

The e ects of nonpenetrating wounds are those secondary to contusion and concussion, mainly hemorrhage, secondary muscle palsies, and infraorbital nerve involvement.

VASCULAR DISEASE

Primary

I. Primary orbital vascular disease is rare

II.Causes include varices, arteriovenular aneurysm, thrombophlebitis, and cavernous sinus thrombosis

Orbital varix, also called distensible venous malformation (Fig. 14.9), may occur anterior to the septum orbitale and not cause exophthalmos, or it may occur posterior to the septum orbitale, causing exophthalmos. The exophthalmos may be acute if the varix undergoes thrombosis.

Part of Systemic Disease

I. Collagen diseases (see pp. 182–184 in Chapter 6, and p.

540 in this chapter)

II.Midline lethal granuloma syndrome (natural killer (NK)/

T-cell lymphoma, polymorphic or malignant reticulosis; see section later this chapter and p. 184 in Chapter 6)

III. Allergic granulomatosis (vasculitis; see p. 184 in Chapter 6)

IV. Temporal (cranial) arteritis (see p. 507 in Chapter 13)

OCULAR MUSCLE INVOLVEMENT IN SYSTEMIC DISEASE

Graves’ Disease (Fig. 14.10)

I.Classification of eye changes of Graves’ disease (Table

14.1)

II.Mild form (“thyrotoxic” exophthalmos)

A.The mild form of Graves’ ophthalmopathy has its onset in early adult life, with women predominantly a ected (approximately 2 :1).

Smokers have an increased risk for development of both Graves’ disease and thyroid ophthalmopathy. Temporally, the diagnosis of Graves’ ophthalmopathy tends to follow the diagnosis of hyperthyroidism. Treatment of hyperthyroidism with iodine-131 does not seem to alter the course of Graves’ ophthalmopathy.

B.It may present initially with unilateral involvement, but usually becomes bilateral.

C.Clinically and chemically, the patient is hyperthyroid.

D.Lid retraction may simulate exophthalmos.

A

C

TABLE 14.1 Eye Changes in Graves’ Disease

(Modified from Werner SC: Am J Ophthalmol 68:646, 1969.)

Lid retraction is the most common clinical sign of Graves’ ophthalmopathy.

E.Occasionally exophthalmos is present.

F.Prognosis for vision is good.

III.Severe form (“thyrotropic” or “malignant” exophthalmos; thyroid ophthalmopathy; thyroid orbitopathy)

B

Fig. 14.10 Graves’ disease. A, In Graves’ disease, exophthalmos often looks more pronounced than it actually is because of the extreme lid retraction that may occur. This patient, for instance, had minimal proptosis of the left eye but marked lid retraction. B, The orbital contents obtained postmortem from a patient with Graves’ disease. Note the enormously thickened extraocular muscle. C, A histologic section shows both fluid and inflammatory cells separating the muscle bundles. The inflammatory cells are predominantly lymphocytes, plus plasma cells.

(A, Courtesy of Dr. HG Scheie; B and C, courtesy of Dr. RC Eagle, Jr., case in B and C reported in Hufnagel TJ et al.: Ophthalmology 91:1411. © Elsevier 1984.)

A.The severe form is an autoimmune disease that a ects people in middle age (average age, 50 years).

1.The disease is characterized by an increased percentage of suppressor/cytotoxic T lymphocytes.

2.Circulating T cells are directed against thyroid follicular cell antigens.

B.The severe form is most common in men, especially those older than 50 years of age. The disease is usually bilateral and asymmetric.

C.Clinically and chemically, the patient may be hyperthyroid, hypothyroid, or euthyroid.

The term euthyroid Graves’ disease describes ocular manifestations of Graves’ disease in patients who are “euthyroid,” and have no past history suggesting hyperthyroidism. The eye signs are frequently asymmetric. The patients may have a family history of thyroid disease or pernicious anemia. All of the euthyroid patients, however, do show some mild thyroid abnormality (e.g., thyroid autoantibodies, negative thyrotro- pin-releasing hormone test, negative triiodothyronine suppression test, goiter).

D.Exophthalmos is severe, and frequently associated with pretibial myxedema. Chemosis, dilated vessels (especially over the rectus muscles), and limitation of ocular motility often accompany the exophthalmos.

Orbital accumulation of glycosaminoglycans and increased adipogenesis may play an important role in the development of Graves’ ophthalmopathy.

E.Prognosis for vision is poor.

F.Histologically, the orbital tissue is characterized predominantly by extraocular and periorbital muscle

involvement by edema, lymphocytic infiltration (mainly CD4+ and CD8+ T cells along with some focal aggregates of B cells, plasma cells, and mast cells), endomysial fibrosis, and mucopolysaccharide deposition.

1.Positive staining occurs in extraocular and periorbital muscle for immunoglobulin A1 (IgA1) and

IgE antibodies, and C3bi (the terminal attack complex) complement component.

The inferior rectus muscle is most prone to fibrosis. If the patient is looking up during tonometry, abnormally high readings may be obtained. It is important, therefore, that the patient be looking straight ahead during applanation tonometry.

Myasthenia Gravis

I.Myasthenia gravis is an autoimmune disorder (defect on chromosome 19q13.3) that involves the extraocular muscles, especially the levator palpebrae superioris. A reduction in available acetylcholine receptors occurs at the

neuromuscular junctions of skeletal muscles.

II.The most common clinical manifestation is ptosis of the eyelid.

As a rough test, the ptosis can often be aggravated by having the patient raise and lower the eyes 10 to 30 times in rapid succession. The normal patient can do this easily with no ptosis afterward.

III.Histologically, the ocular muscles are edematous and infiltrated by lymphocytes.

Myotonic Dystrophy (Myotonia Dystrophica;

Steinert’s Disease)

I.Myotonic dystrophy, an autosomal-dominant condition, is characterized by myotonia (i.e., failure to relax a contracted muscle voluntarily).

Myotonic dystrophy, like Huntington’s disease, is caused by an expansion of a repeated sequence of three nucleotides. In myotonic dystrophy the expansion occurs in the 3’ untranslated region of the DM gene. Perhaps disrupted activity of a CUG-binding protein induced by repeats in RNA prevents the protein from doing its normal job of splicing a certain family of genes.

A.Its onset is between 20 and 30 years of age, with patients rarely living beyond 40 or 50 years.

B.Frontal baldness and endocrinopathy, especially testicular atrophy, are common.

II.Ocular findings

A.Cataracts showing iridescent dots in the anterior and posterior cortex, and a stellate grouping of opacities at the posterior pole of the lens along the posterior suture lines

B.Foveal dystrophy that hardly a ects vision

C.Pigmentary retinopathy

D.Ocular hypotension

III. Histologically, selective atrophy of muscle fibers is seen.

Myotonia Congenita (Thomsen’s Disease)

I.Myotonia congenita, an autosomal-dominant or recessive condition, is characterized by myotonia

A.Its onset is early in life and may involve muscles of the face and eyelids.

B.It does not cause death and rarely causes severe

disability.

II.Histologically, the muscles are not atrophic; individual muscle fibers may be larger than normal with an increase in sarcolemmal nuclei

Mitochondrial Myopathies

I.Mitochondrial myopathies (cytopathies) are rare multisystem diseases that mainly a ect the central nervous and musculoskeletal systems.

Abnormal mitochondria are found in the periphery of skeletal muscle fibers, which have a characteristic “ragged-

red” appearance when stained with the modified trichrome stain.

II.Four of these entities are of major ophthalmic importance:

Leber’s hereditary optic atrophy, chronic progressive external ophthalmoplegia (CPEO), Kearns–Sayre syndrome, and the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS).

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.

A.Leber’s hereditary optic atrophy (see p. 501 in Chapter 13)

B.CPEO

1.CPEO, one of the mitochondrial myopathies, is a slowly progressive, bilaterally symmetric, ocular muscle dystrophy that starts in late childhood or adulthood.

2.CPEO is inherited through the maternal transmission of one or more mitochondrial large-deletion

DNA mutations.

3.Ptosis, external ophthalmoplegia, and often a pigmentary retinopathy can be seen.

4.Histology of muscle fibers

a.Atrophy, large variation in diameter, and granular and vacuolar degeneration

b.Absence of glycogen, cross-striations, myofibrillar structure, and succinic dehydrogenase

c.Fibrous and fatty replacement of tissue

d.Preservation of myelinated nerve fibers and myoneural junctions

Mitochondria of selective muscle fibers appear abnormal in size, shape, number, and internal structure, whereas others seem normal, resembling the changes found in Leber’s hereditary optic atrophy. Because the modified trichrome stain colors the abnormal muscle fibers red, the fibers have been called ragged-red fibers.

C.Kearns–Sayre syndrome

1.Kearns–Sayre syndrome consists of the triad of external ophthalmoplegia, pigmentary retinopathy, and heart block. Other findings include mental retardation, hearing loss, endocrinopathy, and cerebellar ataxia.

2.Kearns–Sayre syndrome is inherited through the maternal transmission of one or more mitochondrial large-deletion DNA mutations.

3.Histologically, along with the characteristic raggedred appearance seen under light microscopy with the modified trichrome stain, electron microscopy shows well-preserved, swollen mitochondria containing circular cristae or granular deposits.

D.MELAS (Fig. 14.11)

1.MELAS usually has an abrupt onset before the age of 15 years with symptoms of visual loss, hemiparesis or hemianopia, strokelike episodes, headaches, and convulsions.

2.Patients have short stature and increased serum and cerebrospinal fluid lactate levels.

3.MELAS is inherited through the maternal transmission of one or more mitochondrial point DNA mutations (nucleotide positions 3243 and 3271).

4.Ocular findings include external ophthalmoplegia, atypical pigmentary retinopathy, and nuclear cataract.

5.Histologically, along with the characteristic raggedred appearance seen under light microscopy with the modified trichrome stain, electron microscopy

shows an increased number of mitochondria containing abnormal cristae.

a.The eyes show abnormalities of the macular photoreceptor–retinal pigment epithelium

(RPE)–choriocapillaris complex, namely, absent or degenerated outer segments and hyperpigmented and hypopigmented RPE.

1). The cytoplasm of RPE cells show ballooned, structurally abnormal (“giant”) mitochondria.

2). The photoreceptor inner segments demonstrate markedly altered mitochondria

(increased number, loss of cristae, circular cristae, ballooned mitochondria, and paracrystalline inclusions).

b.Abnormal mitochondria are also found in choriocapillaris endothelial cells and smooth-muscle cells of choroidal and retinal blood vessel walls.

Dermatomyositis

I.Dermatomyositis is a collagen disease of unknown cause with a poor prognosis; death is a frequent outcome.

II.Men predominate and may acquire the disease in childhood.

III.Conjunctivitis, iritis, ptosis, paralysis of external ocular muscles, horizontal nystagmus, and exophthalmos may be present.

Erythematous, edematous patches of skin are frequently seen. A predilection for the face and periorbital region exists, where a violaceous heliotrope may occur around the eyes, on the lids, and on the cheeks.

IV. A retinitis may be seen with superficial whitish exudates in the macula, and round and flame-shaped hemorrhages.

V.Histologically, lymphocytes are present in the muscles

(myositis) and in the walls of blood vessels (vasculitis), giving a picture of a nonspecific chronic nongranulomatous inflammation.

NEOPLASMS AND OTHER TUMORS*

See Table 14.2 for classification of neoplasms and other tumors.

Primary Orbital Tumors

Orbital tumors in the senior adult population are malignant in 63% of cases, malignant lymphoma being the most common.

*In the following text, a dagger (†) after the name of the tumor denotes that the tumor is common, important, or both; a double dagger (‡) denotes that the tumor is uncommon, unimportant, or both.

I.Choristomas—these are congenital tumors not normally present at the involved site.

A.Epidermoid cyst†

1.An epidermoid cyst is composed of epidermis (i.e., stratified squamous epithelium with no epidermal appendages in the wall of the cyst) and contains desquamated keratin in the cyst, which appears as a cheesy material.

a.An epidermoid cyst tends to occur in the superotemporal aspect of the orbit, often anterior to the septum orbitale.

Rarely, an epidermoid cyst may originate in the diploic space of the orbital bone, called an intradiploic epidermoid cyst. Also rarely, squamous cell carcinoma may develop in an epidermoid or dermoid cyst.

b.A much rarer type of congenital epithelial cyst is called primary nonkeratinized epithelial cyst

(“conjunctival cyst”; see Fig. 14.12D and E). It is usually found in the superonasal aspect of the orbit, is lined by nonkeratinizing epithelium that resembles conjunctival epithelium, contains no adnexal structures in its wall, and is filled with clear fluid.

2.Histologically, a congenital epidermoid cyst and an acquired (usually secondary to trauma) epithelial inclusion cyst appear identical.

Rarely, an epithelial conjunctival inclusion cyst may occur in an orbit after enucleation.

B.Dermoid cyst† (Fig. 14.12)

1.A dermoid cyst is probably a result of the sequestration of surface ectoderm pinched o at bony suture lines or along lines of embryonic closure.

a.It is most often found in the superotemporal quadrant of the orbit (rarely, a dermoid may occur in the lateral rectus muscle).

b.A dermoid may have a pedicle attached to the periorbita and may produce bony changes detectable on radiography.

c.A much rarer type, which is lined by nonkeratinizing epithelium (resembling conjunctival epithelium), contains adnexal structures in its wall, and is filled with clear fluid, is called primary nonkeratinized epidermoid cyst (“conjunctival cyst”).

Primary nonkeratinized epidermoid cysts probably represent developmental sequestrations of forniceal or caruncular conjunctival epithelium. They are found in the superonasal quadrant (see Fig. 14.12D and E) and are not associated with an osseous defect. They constitute approximately 75% of the superonasal dermoids, the other 25% being the typical dermoids lined by keratinizing squamous epithelium.