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

A

nr

nr

h

c

B

Fig. 2.13 Rubella. A, Fundus picture shows mottled “salt-and-pepper” appearance with both fine and coarse pigmentation. B and C, From same eye. Retinal pigment epithelium (RPE) shows areas of hyperpigmentation (B) (h, hypertrophied RPE) and hypopigmentation (C) (a, atrophy). The alternating areas of hyperpigmentation and hypopigmentation cause the salt-and-pepper appearance of the fundus (nr, neural retina; c, choroid). (Modified from Yanoff M: In Tasman W, ed:

a Retinal Diseases in Children, New York, Harper & Row, 1971:223–232. © Lippincott Williams & Wilkins.)

C

IV. The rubella virus can pass through the placenta, infect the fetus, and thereby cause abnormal embryogenesis.

The rubella virus can survive in the lens for at least 3 years after birth. Surgery on rubella cataracts may release the virus into the interior of the eye and cause an endophthalmitis.

V.Histology

A.Retention of lens cell nuclei in the embryonic lens nucleus is characteristic (but not pathognomonic, because it may also be seen in trisomy 13, Leigh’s disease, and Lowe’s syndrome) and posterior cortical lens degeneration and dysplastic lens changes may be seen.

B.The iris shows a poorly developed dilator muscle and necrotic epithelium along with a chronic, nongranulomatous inflammatory reaction.

The combination of the dilator muscle abnormality and chronic inflammation often causes the iris to dilate poorly and to appear leathery.

C.The ciliary body shows pigment epithelium necrosis, macrophagic pigment phagocytosis, and a chronic nongranulomatous inflammatory reaction.

D.Atrophy and hypertrophy, frequently in alternating areas of RPE, are seen in most, if not all, cases, resulting in the clinically observed “salt-and-pepper” fundus of rubella retinopathy.

E.Other findings, such as Peters’ anomaly and Axenfeld’s anomaly, may occasionally be seen.

F.After cataract or iris surgery, complications caused by virus infection may cause a chronic nongranulomatous inflammatory reaction around lens remnants and secondary disruption of intraocular tissues with fibroblastic overgrowth, resulting in cyclitic membrane and neural retinal detachment.

Cytomegalic Inclusion Disease

See p. 77 in Chapter 4.

Congenital Syphilis

See p. 82 in Chapter 4 and p. 267 in Chapter 8.

Toxoplasmosis

See p. 88 in Chapter 4.

DRUG EMBRYOPATHY

Fetal Alcohol Syndrome (FAS) (Fig. 2.14)

I.FAS is a specific, recognizable pattern of malformations caused by alcohol’s teratogenic e ect secondary to maternal alcohol ingestion during pregnancy. The leading cause of mental retardation in the United States, FAS involves various neural crest-derived structures.

II.Systemic findings include developmental delay and retardation; midface hypoplasia (flattened nasal bridge and thin upper lip); smooth or long philtrum; and central nervous system manifestations, including microcephaly, hyperactivity, and seizures.

III.Ocular findings include narrow palpebral fissures, epicanthal folds, ptosis; blepharophimosis; strabismus; severe myopia; microcornea; Peters’ anomaly (see Fig. 2.14); iris dysplasia; glaucoma; hypoplasia of the optic nerve head;

and microphthalmia.

IV. Histology depends on the structures involved.

Thalidomide

I.Thalidomide ingestion during the first trimester of pregnancy may result in a condition known as phocomelia, the condition of having the limbs extremely shortened so that the feet or hands arise close to the trunk.

II.Ocular findings include ocular motility problems (e.g.,

Möbius’ and Duane’s syndromes), uveal colobomas, microphthalmos, and anophthalmos.

III.Histologically, hypoplasia of the iris and colobomas of the uvea and optic nerve may be seen.

Lysergic Acid Diethylamide (LSD)

I.LSD ingestion during the first trimester of pregnancy may result in multiple central nervous system and ocular

abnormalities.

II.Central nervous system abnormalities: arhinencephaly; fusion of the frontal lobes; Arnold–Chiari malformation

with hydrocephalus; and absence of the normal convolutional pattern in cerebral hemispheres and of foliar markings in the cerebellum.

III. Ocular findings include cataract and microphthalmia. IV. Histologically, the lens may show anterior and posterior

cortical degeneration and posterior migration of lens epithelial nuclei, and the neural retina may contain posterior retinal neovascularization and juvenile retinoschisis.

OTHER CONGENITAL ANOMALIES

Cyclopia and Synophthalmos

I.Cyclopia and synophthalmos (Fig. 2.15) are conditions in which anterior brain and midline mesodermal structures

develop anomalously (holoprosencephaly—also called arhinencephaly and holotelencephaly).

A.The conditions are incompatible with life.

B.The prevalence is approximately 1 in 13 000 to 20 000 live births.

Chromosomal studies may show normal or abnormal chromosomes, usually trisomy 13, rarely 13q– and 18p– karyotypes. Embryologically, the gene, ET, acts as a transcription factor and causes the retina in the frog, Xenopus laevis, to emerge early as a single retinal field. A transcription factor is a DNA-binding protein that controls gene activity. A nearby piece of the embryo, the precordial mesoderm, suppresses retinal formation in the median region, resulting in the resolution of the single retinal field into two retinal primordia. The lack or deficiency of the splitting induction, as has been shown also with the PAX6 gene in chick embryos, may result in either cyclops or synophthalmos in humans.

II.The prosencephalon fails to cleave, a large dorsal cyst develops, and midline structures such as the corpus callosum, septum pellucidum, olfactory lobes, and neurohy-

pophysis are lacking.

III.The orbital region is grossly deformed from failure of the frontonasal bony processes to develop; the maxillary processes then fuse, resulting in an absent nasal cavity and a single central cavity or pseudo-orbit. The nose is usually present as a rudimentary proboscis above the

pseudo-orbit.

IV. If only one eye is present (i.e., complete and total fusion of the two eyes) in the pseudo-orbit, the condition is called cyclopia.

A much more common situation is synophthalmos, wherein two eyes are present in di ering degrees of fusion, but never complete fusion.

Even rarer is a supernumerary eye, called diplophthalmos.

V.Histology

A.In cyclopia, the one eye may be relatively normal, completely anomalous, or display all degrees of abnormality in between.

B.In synophthalmos, the partially fused two eyes may be relatively normal, totally anomalous, or display all degrees of abnormality in between.

Anencephaly

I.Anencephaly is the most serious congenital malformation occurring spontaneously in humans that is compatible with completion of pregnancy.

A.The condition is characterized by absence of the cranial vault.

B.The cerebral hemispheres are missing completely or reduced to small masses attached to the base of the skull.

C.The incidence is approximately 1 per 1000 in the general population.

C

D.The condition appears to be caused by a defect in the development of the a ected tissues at the fifth to 10th week of gestation, probably close to the fifth week.

II.Macroscopically, the eyes are normal.

A.Histologically, the main finding is hypoplasia (or atrophy) of the retinal ganglion cell and nerve fiber layers and of the optic nerve.

B.Uncommonly, uveal colobomas, retinal dysplasia, corneal dermoids, anterior-chamber angle anomalies, and vascular proliferative retinal changes may be seen.

Anophthalmos (Fig. 2.16)

I.The di erentiation between anophthalmos (complete absence of the eye) and extreme microphthalmos (a rudimentary small eye) can be made only by the examination of serial histologic sections of the orbit. The di erentiation cannot be made clinically.

The term clinical anophthalmos is applied to the condition where no eye can be found clinically.

II.Three types of anophthalmos are recognized:

A.Primary anophthalmos: caused by suppression of the optic anlage during the mosaic di erentiation of the optic plate after formation of the rudiment of the forebrain (occurs before the 2-mm stage of embryonic development).

B.Secondary anophthalmos: caused by the complete suppression or grossly anomalous development of the entire anterior portion of the neural tube.

C.Consecutive or degenerative anophthalmos: caused by atrophy or degeneration of the optic vesicle after it has been formed initially.

Consecutive anophthalmos has been reported in the focal dermal hypoplasia syndrome (Goltz’s syndrome, congenital cutis hypoplasia).

III.Histologically, serial sections of the orbit fail to show any ocular tissue.

Microphthalmos

I.Microphthalmos (see Figs 2.9–2.11) is a congenital condi-

tion in which the a ected eye is smaller than normal at birth (<15 mm in greatest diameter; normal eye at birth varies between 16 and 19 mm).

Microphthalmos, a congenital abnormality, should be differentiated from atrophia bulbi, an acquired condition wherein the eye is of normal size at birth but shrinks secondary to ocular disease. Rarely, the microphthalmos disproportionately affects the posterior ocular segment, called posterior microphthalmos.

II.Three types of microphthalmos are recognized:

A.Pure microphthalmos alone (nanophthalmos or simple microphthalmos), wherein the eye is smaller than normal in size but has no other gross abnormalities except for a high lens/eye volume

1.Such eyes are usually hypermetropic and may have macular hypoplasia.

2.Nanophthalmic eyes may have thickened sclera and a tendency toward postoperative or spontaneous uveal e usion, secondary neural retinal, and choroidal detachments, and are susceptible to acute and chronic closed-angle glaucoma.

A fraying or unraveling of the collagen fibril into its constituent 2- to 3-nm subunits may occur and may be related to an abnormality of glycosaminoglycan metabolism.

B.Microphthalmos with cyst (see Fig. 2.10, p. 41 in Chapter 9, and p. 531 in Chapter 14).

C.Microphthalmos associated with other systemic anomalies (e.g., in trisomy 13 and congenital rubella). This type of microphthalmos is discussed in the appropriate sections.

III.Histologically, the eye ranges from essentially normal in nanophthalmos to rudimentary in clinical anophthalmos, and all degrees of abnormality in between.

Walker–Warburg Syndrome

I.Walker–Warburg syndrome (Fig. 2.17) is a lethal, autoso- mal-recessive, oculocerebral disorder. The diagnosis is

based on at least four abnormalities: type II lissencephaly; cerebellar malformation; retinal malformation; and congenital muscular dystrophy.

Type II lissencephaly (lissencephaly variant) consists of a smooth cerebral surface [agyria, polymicrogyria, and pachygyria (broad gyri)] and microscopic evidence of incomplete neuronal migration. Type I lissencephaly (classic lissencephaly) also consists of a smooth cerebral surface but excludes polymicrogyria. The most frequent cause of classical lissencephaly is deletions of the lissencephaly critical region in chromosome 17p13.3.

II.Previous names for Walker–Warburg syndrome include Warburg’s syndrome, Walker’s lissencephaly, Chemke’s syndrome, cerebro-ocular–muscular syndrome, cerebro-

ocular dysplasia muscular dystrophy, and cerebro-ocular dysgenesis.

III.Ocular findings include microphthalmia, microcornea,

Peters’ anomaly, anterior-chamber malformations, coloboma, cataracts, persistent hyperplastic primary vitreous, retinal detachment, retinal disorganization, and retinal dysplasia.

Oculocerebrorenal Syndrome of Miller

I.Miller’s syndrome consists of Wilms’ tumor, congenital nonfamilial aniridia* (Fig. 2.18), and genitourinary anomalies.

A.Mental and growth retardation, microcephaly, and deformities of the pinna may be present.

B.Aniridia and Wilms’ tumor have been found in deletion of the short arm of chromosome 11 and are associated with the chromosome band 11p13.

Aniridia is caused by point mutations or deletions affecting the PAX6 gene, located on chromosome 11p13. A rapid polymerase chain reaction-based DNA test can be performed to rule out chromosome 11p13 deletion and its high risk of Wilms’ tumor in patients who have sporadic aniridia.

II.In patients without Wilms’ tumor, the incidence of aniridia is 1 in 50 000; with Wilms’ tumor, the incidence is 1 in 73; the cause of this association is not known.

*Aniridia is a misnomer. The iris is not absent but is hypoplastic and rudimentary.

A case of two monozygous twins has been reported in which both had bilateral aniridia and cataracts, but only one had Wilms’ tumor.

III.Histologically, the iris is hypoplastic. The cataract shows cortical degenerative changes and capsular excrescences similar to those seen in trisomy 21 and Lowe’s syndrome.

Subacute Necrotizing Encephalomyelopathy

(Leigh’s Disease)

I.Leigh’s disease is a mitochondrial enzymatic deficiency

(point mutation at position 8993 in the adenosine triphosphatase subunit gene of mtDNA) that shares similar ocular findings to those seen in Kearns–Sayre syndrome, another mitochondrial disorder (see p. 539 in Chapter 14).

A.Leigh’s disease is a central nervous system disorder characterized by onset between 2 months and 6 years of age, feeding di culties, failure to thrive, generalized weakness, hypotonia, and death in several weeks to 15 years.

B.The disease has an autosomal-recessive inheritance pattern.

C.The symptoms are nonspecific, and a familial history helps make the diagnosis.

II.The disorder is thought to result from inhibition of a thia- mine-dependent enzymatic process and may be modified by increased thiamine intake.

III.Ocular findings include blepharoptosis, nystagmus, strabismus, Parinaud’s syndrome, pupillary abnormalities, field defects, absent foveal retinal reflexes, ophthalmoplegia, and optic atrophy.

Fig. 2.18 Oculocerebrorenal syndrome of Miller. A 6½-month-old, mentally retarded, microcephalic child had clinical “aniridia” and congenital cortical and nuclear cataract in addition to bilateral Wilms’ tumor. Top and bottom show different planes of section to demonstrate rudimentary iris having both uveal and neuroepithelial layers but lacking sphincter and dilator muscles. Almost all cases of clinical aniridia turn out to be iris hypoplasia. (From Zimmerman LE, Font RL: JAMA 196:684, 1966, with permission. © American Medical Association. All rights reserved.)

IV. Histologically, the eyes show glycogen-containing, lacy vacuolation of the iris pigment epithelium; no cataracts but persistence of lens cell nuclei in the deep cortex similar to that seen in congenital rubella, Lowe’s syndrome, and trisomy 13 lenses; atrophy of neural retinal ganglion cell and nerve fiber layers; epineural retinal macular membranes; periodic acid–Schi -positive macrophages; and optic atrophy.

Meckel’s Syndrome (Dysencephalia

Splanchnocystica; Gruber’s Syndrome)

I.Meckel’s syndrome consists of posterior encephalocele, polydactyly, and polycystic kidneys as the most important diagnostic features, but also includes sloping forehead, microcephaly, cleft lip and palate, and ambiguous genitalia.

The condition has an autosomal-recessive inheritance pattern.

II.Ocular findings include cryptophthalmos, dysplasia of the palpebral fissure, hypertelorism or hypotelorism, clinical anophthalmos,microphthalmos (Fig.2.19),Peters’anomaly, aniridia, retinal dysplasia, and cataract.

III.Histologically, microphthalmos, central and peripheral dysgenesis of cornea and iris, cataract, uveal colobomas, retinal dysplasia, and optic atrophy may be found.

The condition resembles trisomy 13, but the karyotype in Meckel’s syndrome is normal.

Potter’s Syndrome

I.Potter’s syndrome is an idiopathic multisystem condition that includes bilateral agenesis or dysplasia of the kidneys, oligohydramnios, pulmonary hypoplasia, and a wizened facial appearance; 75% of cases occur in boys.

II.Ocular findings include dilated intraocular blood vessels, sometimes simulating the vasoproliferative stage of retinopathy of prematurity.

Menkes’ Kinky-Hair Disease

I.Menkes’ kinky-hair disease is characterized by early, progressive psychomotor deterioration, seizures, spasticity, hypothermia, pili torti, bone changes resembling those of scurvy, tortuosity of cerebral arteries from fragmentation of the internal elastic lamina, and characteristic facies.

A.The condition has an X-linked recessive inheritance pattern (defect on chromosome Xq12–13), but about one-third of cases are new mutations.

B.Incidence is 1 in 100 000 to 25 000 live births

II.The disease is caused by a generalized copper deficiency in the body.

A.Levels of serum copper, copper oxidase, and ceruloplasmin are abnormally low.

B.A defect is present in the intracellular transport of copper in the gut epithelium and in the release of copper from these cells into the blood.

C.The lower copper levels in cells and tissue fluid appear to interfere seriously with certain enzyme systems and the maintenance of neural cells and hair.

III.Ocular findings include aberrant lashes, iris anterior stromal hypoplasia, nystagmus, iris depigmentation, tortu-

osity of retinal vessels, and an abnormal electroretinogram that shows moderately decreased photopic β waves (measure of cone function) and almost no scotopic β waves

(measure of rod function) or visually evoked response.

IV. Histologically, the main findings consist of diminished neural retinal ganglion cells and a thinned nerve fiber layer, decrease in and demyelination of optic nerve axons, loss of pigment from retinal and iris pigment epithelial cells, and microcysts of iris pigment epithelial cells

(Fig. 2.20).

Fig. 2.19 Meckel’s syndrome. A 1460-g infant died an hour after birth. Both the right (A) and the left (B) eyes were microphthalmic and showed multiple congenital anomalies, including Peters’ anomaly and retinal dysplasia. (From Daicker B: Presented at the meeting of the European Ophthalmic Pathology Society, 1982.)

Aicardi’s Syndrome

I.Aicardi’s syndrome is characterized by infantile spasms, agenesis of the corpus callosum, severe mental retardation, and an X-linked inheritance pattern (a rare male 47,XXY

has been reported).

II. Clinically, microphthalmia and a characteristic chorioretinopathy with lacunar defects are noted.

III.Histologically, hypoplasia of the optic nerves, coloboma of the juxtapapillary choroid and optic disc, neural retinal detachment, retinal dysplasia, chorioretinal lacunae with focal thinning, and atrophy of the RPE and choroid have been found.

Dwarfism

I.Ocular anomalies occur frequently in many di erent types of dwarfism.

A.Dwarfism secondary to mucopolysaccharidoses (see

p.298 in Chapter 8)

B.Dwarfism secondary to osteogenesis imperfecta (see

p.314 in Chapter 8)

C.Dwarfism secondary to stippled epiphyses (Conradi’s syndrome) with cataracts

D.Dwarfism secondary to Cockayne’s syndrome with retinal degeneration and optic atrophy (see p. 447 in

Chapter 11)

E.Dwarfism secondary to Lowe’s syndrome (see p. 367 in Chapter 10)

F.The syndrome of dwarfism, myotonia, di use bone disease, myopia, and blepharophimosis

G.The syndrome of dwarfism with disproportionately short legs, reduced joint mobility, hyperopia, glaucoma, cataract, and retinal detachment

H.The syndrome of dwarfism, congenital trichomegaly, mental retardation, and retinal pigmentary degeneration

I.Achondroplastic dwarfism with mesodermal dysgenesis of cornea and iris

J.Ateleiotic dwarfism with soft, wrinkled skin of lids

K.Diastrophic dwarfism with mild retinal pigment epithelial disturbance in macular and perimacular areas

L.Spondyloepiphyseal dysplastic dwarfism with retinal

degeneration (including lattice degeneration), retinal detachment, myopia, and cataracts

M. Cartilage-hair hypoplastic dwarfism with fine, sparse hair of eyebrows and cilia and trichiasis

II.The histologic features are described in the appropriate sections under the individual tissues.

Other Syndromes

I.Other syndromes include Williams syndrome (“elfin” facies, congenital cardiac defects that may include supravalvular aortic stenosis, infantile idiopathic hypercalcemia, developmental delay, stellate anterior iris stromal pattern, retinal vessel abnormalities, and strabismus); CHARGE syndrome (coloboma of the uvea and optic nerve, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, and ear anomalies); Klippel–Trenau- nay–Weber syndrome (triad of port-wine hemangiomas or vascular nevi of skin, varicose veins, and soft-tissue and bony hypertrophy; also ocular vascular findings and glaucoma).

II.Many other congenital syndromes occur and are discussed in their appropriate sections.

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