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

Schwann cells) results in an unencapsulated neurofibroma.

2.The tumor is composed of numerous cells that contain elongated, basophilic nuclei and faintly granular cytoplasm associated with fine, wavy, “maiden-hair,” immature collagen fibers.

a.Special stains often show nerve fibers in the tumor.

b.Vascularity is quite variable from tumor to tumor and in the same tumor.

Histologically, neurofibromas are often confused with dermatofibromas, neurilemmomas, schwannomas (see p. 588 in Chapter 14), or leiomyomas (see p. 350 in Chapter 9).

3.In the eye, the lesion may be a melanocytic nevus (see p. 697 in Chapter 17), slight or massive involvement of the uvea (usually choroid) by a mixture of hamartomatous neural and nevus elements, or a glial hamartoma (see later).

Rarely, a uveal melanoma may arise from the uveal nevus component, although this is probably a coincidental occurrence rather than cause and effect.

II.Neurofibromatosis type 2 (NF-2; central neurofibromatosis, bilateral acoustic neurofibromatosis)

A. General information

1.Diagnosis of NF-2 is made if a person has either bilateral eighth-nerve tumors or a first-degree relative who has NF-2; and either a unilateral eighthnerve tumor or two or more of the following: neurofibroma; meningioma (especially primary nerve sheath meningioma); glioma; schwannoma; ependymoma; or juvenile posterior subcapsular lenticular opacity.

a.NF-2 is transmitted as an irregular autosomaldominant (prevalence about 1 in 40 000).

b.The responsible gene is located on chromosome

22 (band 22q12).

2.Combined pigment epithelial and retinal hamartomas may occur.

The most common ocular abnormalities found in NF-2 are lens opacities (67%—mainly plaque-like posterior subcapsular or capsular, cortical, or mixed lens opacities) and retinal hamartomas (22%).

III.Because of the neuromas, café-au-lait spots, and prominent corneal nerves that may be found, the condition of multiple endocrine neoplasia (MEN) type IIB must be di erentiated from neurofibromatosis.

A.MEN, a familial disorder, is classified into three groups.

1.Type I (autosomal-dominant inheritance) consists of multiple neoplasms of the pituitary, parathyroid, pancreas islets, and less often pheochromocytoma

(as a late feature) and neoplasms of the adrenal and thyroid glands.

The Zollinger–Ellison syndrome consists of gastric, duodenal, and jejunal ulcers associated with gastrin-secreting non-β islet cell tumors of the pancreas (gastrinomas). The tumors may arise in multiple sites in MEN type I.

2.Type IIA (autosomal-dominant inheritance; also called Sipple syndrome) consists of medullary thyroid carcinoma, pheochromocytoma (as an early feature), parathyroid hyperplasia, and prominent corneal nerves (less prominent than in type IIB).

3.Type IIB (Fig. 2.6; 50% autosomal-dominant and 50% sporadic inheritance; also called type III) consists of medullary thyroid carcinoma and, less often, pheochromocytoma.

In addition, marfanoid habitus, skeletal abnormalities, prominent corneal nerves (more prominent than in IIA), multiple mucosal (including conjunctival, tongue, and intestinal) neuromas, café-au-lait spots, and cutaneous neuromas or neurofibromas may occur.

B.Linkage analysis shows:

1.In MEN I, the predisposing genetic linkage is assigned to chromosome region 11q13.

2.In MEN IIA and IIB, predisposing genetic linkage is assigned to chromosome region 10q11.2.

The mutation for MEN IIA and IIB occurs at the site of the human RET proto-oncogene at 10q11.2, the same site where a mutation also causes the autosomal-dominant Hirschsprung’s disease. An oncogenic conversion (not a loss of suppressor function) converts RET into a dominant transforming gene.

Tuberous* Sclerosis (Bourneville’s Disease;

Pringle’s Disease)

I.General information

A.Symptoms usually appear during the first 3 years of life and consist of the triad of mental deficiency, seizures, and adenoma sebaceum (angiofibroma).

B.The prognosis is poor (death occurs in 75% of patients by 20 years of age).

C.The disease is transmitted as an irregular auto- somal-dominant (prevalence approximately 1 in 10 000). Tuberous sclerosis complex (TSC)-determining loci have been mapped to chromosome 9q34 (TSC1) and 16p13.3 (TSC2)

II.Ocular findings (Fig. 2.7)

A.Lids: adenoma sebaceum (angiofibroma)

B.Eyeball

1.Glial hamartoma of retina occurs in 53% of patients.

*The name originates from the shape of the tumor (i.e., like a potato or tuber).

2.Most retinal hamartomas remain stable over time, but some become calcified, and rarely some may show progressive growth.

Hamartomas of the neural retina in infants have a smooth, spongy appearance with fuzzy borders, are gray-white, and may be mistaken for retinoblastoma. Older lesions may become condensed, with an irregular, white surface, resembling a mulberry. The whitened, wrinkled clinical appearance is caused by avascularity, not calcium deposition. The lesions are frequently multiple and vary in size from one-fifth to two disc diameters. New lesions may rarely develop from areas of previously normal-appearing retina.

3.Glial hamartoma of optic disc anterior to lamina cribrosa (giant drusen) may occur.

The giant drusen of the optic nerve head may be mistaken for a swollen disc (i.e., pseudopapilledema). Most patients who have drusen of the optic nerve do not have tuberous sclerosis.

4.Neuroectodermal hamartomas of the iris pigment epithelium and ciliary body epithelium may occur rarely.

III.Systemic findings

A.Glial hamartomas in the cerebrum occur commonly and result in epilepsy in 93% of patients, in mental

deficiency in 62% of patients, and in intracranial calci-

fication in 51% of patients.

B. Adenoma sebaceum (really an angiofibroma) of the skin of the face occurs in 83% of patients.

A.Giant drusen of the optic disc occur anterior to the lamina cribrosa and are glial hamartomas (see p. 520 in Chapter 13).

B.Adenoma sebaceum are not tumors of the sebaceous gland apparatus but are angiofibromas (see Fig. 6.34 in

Chapter 6).

C.Glial hamartomas in the cerebrum (usually in the walls of the lateral ventricles over the basal ganglia) and neural retina are composed of large, fusiform astrocytes separated by a coarse and nonfibrillated, or finer and fibrillated, matrix formed from the astrocytic cell processes.

1.The cerebral tumors are usually well vascularized, but the neural retinal tumors tend to be sparsely vascularized or nonvascularized.

2.Calcospherites may be prominent, especially in older lesions.

Retinal tumors display the same spectrum of aberrant development and morphologic characteristics as other

central nervous system lesions, including the occurrence of giant cell astrocytomas that stain positive for γ-enolase but negative for glial acid fibrillary protein and neural filament protein.

Other Phakomatoses

Numerous other phakomatoses occur. Ataxia–telangiectasia (Louis–Bar syndrome), an immunodeficient disorder, consists of an autosomal-recessive inheritance pattern (gene localized to chromosome 11q22), progressive cerebellar ataxia, oculocutaneous telangiectasia, and frequent pulmonary infections; arteriovenous communication of retina and brain (Wyburn–Mason syndrome) consists of a familial pattern, mental changes, and arteriovenous communication of the midbrain and retina (see p. 545 in Chapter 14) associated with facial nevi. Most other phakomatoses are extremely rare or do not have salient ocular findings.

CHROMOSOMAL ABERRATIONS

I.Normally, the human cell is diploid and contains 46 chromosomes: 44 autosomal chromosomes and two sex chromosomes (XX in a female and XY in a male).

A.Individual chromosomes may be arranged in an array according to morphologic characteristics.

1.The resultant array of chromosomes is called a karyotype.

2.A karyotype is made by photographing a cell in metaphase,cutting out the individual chromosomes, and arranging them in pairs in chart form according to predetermined morphologic criteria (i.e., karyotype; Fig. 2.8).

3.The paired chromosomes are designated by numbers.

4.In genetic shorthand, 46(XX) means that 46 chromosomes occur and have a female pattern; 46(XY) means that 46 chromosomes occur and have a male pattern.

B.To di erentiate the chromosomes, special techniques are used, such as autoradiography or chromosomal band patterns, as shown with fluorescent quinacrine (see Fig.

2.8).

II.Chromosomes may be normal in total number (i.e., 46), but individual chromosomes may have structural alterations.

A.The genetic shorthand for structural alterations is as follows: p = short arm, q = long arm, + = increase in

length, − = decrease in length, r = ring form, and t = translocation.

B.Therefore 46,18p– means a normal number of chromosomes, but one of the pair of chromosomes 18 has a deletion (decrease in length) of its short arms. Similarly, 46,18q– and 46,18r mean a normal number of chromosomes but a deletion of the long arms or a ring form, respectively, of one of the pair of chromosomes

18.

III.Chromosomes may also be abnormal in total number, either with too many or too few.

A.For example, trisomy 13 has an extra chromosome in

the 13 pair (three chromosomes instead of two) and may be written 47,13+, meaning 47 chromosomes with an extra chromosome (+) in the 13 group.

B.Trisomy 18 may be written 47,18+, and trisomy 21

(Down’s syndrome, or mongolism) may be written

47,21+.

C.Finally, too few chromosomes may occur [e.g., in 45(X), Turner’s syndrome, where only 45 chromosomes exist and one of the sex chromosomes is missing].

IV. A chromosomal abnormality has little to do with specific ocular malformations. In fact, except for the presence of cartilage in a ciliary-body coloboma in trisomy 13, no ocular malformations appear specific for any chromosomal abnormality.

Trisomy 8

See later, under Mosaicism.

Trisomy 13 (47,13+; Patau’s Syndrome)

I.General information

A.Trisomy 13 results from an extra chromosome in the

13pair of autosomal chromosomes (i.e., one set of chromosomes exists in triplicate rather than as a pair; see Fig. 2.8).

1.Caused by an accidental failure of disjunction of one pair of chromosomes during meiosis (meiotic nondisjunction).

2.It has no sex predilection.

B.The condition, present in 1 in 14 000 live births, is usually lethal by age 6 months.

C.Because the condition was described in the prekaryotype era, many names refer to the same entity: arhinencephaly, oculocerebral syndrome, encephaloophthalmic dysplasia, bilateral retinal dysplasia (Reese–

Blodi–Straatsma syndrome), anophthalmia, and mesodermal dysplasia (cleft palate).

D.Ocular anomalies, usually severe, occur in all cases (Fig. 2.9; see Fig. 2.15).

II.Systemic findings include mental retardation; low-set and malformed ears; cleft lip or palate or both; sloping forehead; facial angiomas; cryptorchidism; narrow, hyperconvex fingernails; fingers flexed or overlapping or both; polydactyly of hands or feet, or of both; posterior prominence of the heels (“rocker-bottom feet”); characteristic features of the dermal ridge pattern, including transverse palmar creases; cardiac and renal abnormalities; absence or

hypoplasia of the olfactory lobes (arhinencephaly); bicornuate uterus; apneic spells; apparent deafness; minor motor seizures; and hypotonia.

III.Ocular findings

A.Bilateral microphthalmos (<15 mm in greatest diameter) is common and may be extreme so as to mimic anophthalmos (i.e., clinical anophthalmos). In rare

A

r

c

B

Fig. 2.9 Trisomy 13 (see also Fig. 2.15, synophthalmos). A, An inferior nasal iris coloboma and leukoria are present. B, A coloboma of the ciliary body is filled with mesenchymal tissue containing cartilage (c). Note the retinal dysplasia (r). In trisomy 13, cartilage is usually present in microphthalmic eyes smaller than 10 mm. (A, Courtesy of Dr. DB Shaffer; B, reported in Hoepner J, Yanoff M: Am J Ophthalmol 74:729, 1972. Copyright Elsevier 1972.)

instances, synophthalmos (cyclops, see later) or glaucoma can occur.

B.Coloboma of the iris and ciliary body, cataract, and persistent hyperplastic primary vitreous are present in most (approximately 80%) of the eyes.

C.Retinal dysplasia is found in at least 75% of eyes. Retinal folds and microcystoid degeneration of the neural retina are also common findings.

When retinal dysplasia is unilateral and the other eye is normal, the condition is usually unassociated with trisomy 13 or other systemic anomalies.

D.Central and peripheral dysgenesis of the cornea and iris (see pp. 260–263 in Chapter 8) is present in at least 60% of eyes.

IV. Histology

A.The coloboma of the iris and ciliary body often contains a mesodermal connection between the sclera and the retrolental area. Cartilage is present in the mesodermal

tissue in approximately 65% of eyes, most commonly when the eyes are small (i.e., <10 mm).

Ocular cartilage has also been reported in teratoid medulloepithelioma, in chromosome 18 deletion defect, in angiomatosis retinae, in synophthalmos, and in a unilateral anomalous eye in an otherwise healthy individual; however, in none of these conditions is the cartilage present in a coloboma of the ciliary body, as occurs in trisomy 13.

B.The cataract may be similar to that seen in rubella, Leigh’s disease, and Lowe’s syndrome, and shows retention of cell nuclei in the embryonic lens nucleus. Anterior subcapsular, anterior and posterior cortical, nuclear, and posterior subcapsular cataractous changes may also be seen.

Trisomy 18 (47,18+; Edwards’ Syndrome)

I.General information

A.Trisomy 18 has an extra chromosome in the 18 pair of autosomal chromosomes.

B.The condition has approximately the same incidence as trisomy 13 (i.e., 1 in 14 000 live births) and similarly proves fatal at an early age. Girls are predominantly a ected.

C.Ocular malformations, usually minor, occur in approximately 50% of patients.

II.Systemic findings include mental retardation; low-set, malformed, and rotated ears; micrognathia; narrow palatal arch; head with prominent occiput, relatively flattened laterally; short sternum; narrow pelvis, often with luxation of hips; fingers flexed, with the index overlapping the third or the fifth overlapping the fourth; hallux short, dorsi-

flexed; characteristic features of the dermal ridge pattern, including an exceptionally high number of arches; cardiac and renal malformations; Meckel’s diverticulum;

heterotopic pancreatic tissue; severe debility; moderate hypertonicity.

III.Ocular findings tend to be minor and mainly involve the lids and bony orbit: narrow palpebral fissures, ptosis, epi-

canthus, hypoplastic supraorbital ridges, exophthalmos, hypertelorism or hypotelorism, and nystagmus.

Rare ocular anomalies include nictitating membrane, corneal opacities, anisocoria, uveal and optic disc colobomas, cataract, microphthalmos, severe myopia, megalocornea, keratitis, scleral icterus, blue sclera, persistent hyaloid artery, increased or absent retinal pigmentation, and irregular retinal vascular pattern.

IV. Histology—especially related to hyperplasia, hypertrophy, and cellular abnormalities

A.Corneal epithelium, mainly in the basal layer, may show cellular hypertrophy, swelling, disintegration, bizarre chromatin patterns, and atypical mitoses. Focal or di use hyperplasia of the corneal endothelium may be present.

B.Posterior subcapsular cataracts, minor neural retinal changes (gliosis, hemorrhage), and optic atrophy may be seen.

1.The retinal pigment epithelium (RPE) may show hypopigmented or hyperpigmented areas.

2.In addition, severe optic disc colobomas have been reported.

Trisomy 21 (47,21+; Down’s

Syndrome; Mongolism)

I.General information

A.Trisomy 21 results from an extra chromosome in the 21 pair of autosomal chromosomes.

B.The condition is the most common autosomal trisomy, with an incidence of 1 in 700 live births (in white populations). Major ocular malformations are rare.

II.Systemic findings include severe mental retardation; flat nasal bridge; an open mouth with a furrowed, protruding tongue and small, malformed teeth; prominent malformed ears with absent lobes; a flat occiput with a short, broad neck; loose skin at the back of the neck and over the shoulders (in early infancy); short, broad hands; short, curved little fingers with dysplastic middle phalanx; specific features of the dermal ridge, including a transverse palmar crease; cardiovascular defects; Apert’s syndrome;

and anomalous hematologic and biochemical traits.

III.Ocular findings include hypertelorism; oblique or arched palpebral fissures; epicanthus; ectropion; upper-eyelid eversion; speckled iris (Brushfield spots); esotropia, high myopia; rosy optic disc with excessive retinal vessels crossing its margin; generalized attenuation of fundus pigmentation regardless of iris coloration; peripapillary and patchy peripheral areas of pigment epithelial atrophy; choroidal vascular “sclerosis”; chronic blepharoconjunctivitis; kerato-

conus (sometimes acute hydrops); and lens opacities.

IV. Histology

A.Brushfield spots consist of areas of relatively normal iris stroma that are surrounded by a ring of mild iris hypoplasia. They may also show focal stromal condensation or hyperplasia.

B.A cataract may have abnormal anterior lens capsular excrescences similar to that seen in Lowe’s and Miller’s syndromes.

C.Keratoconus may occur (see p. 302 in Chapter 8).

The aforementioned three trisomies are all autosomal chromosomal trisomies. An example of a sex chromosomal trisomy is Klinefelter’s syndrome (47,XXY—a rare case of Klinefelter’s syndrome associated with incontinentia pigmenti has been reported); the ocular pathologic process in this condition is not striking. In XYY syndrome (47,XYY), patients have normal height, psychological and social problems, gonadal atrophy, luxated lenses, and iris and choroid colobomas.

Triploidy

I.General information

A.The anomaly of triploidy refers to that specific defect in which an individual’s cells have 69 chromosomes (three of each autosome and three of each sex chromosome) instead of the normal component of 46 chromosomes (22 pairs of autosomes and two sex chromosomes).

B.Triploidy is common in spontaneous abortions but rare in live births.

Triploid mosaic individuals may survive to adult life.

Survivors have some cell lines with 46 chromosomes and other cell lines with 69 chromosomes.

II.Systemic findings include triangular face; low-set ears; absent nose or nose with single nostril; cleft lip; cleft palate; single transverse palmar crease; talipes equinovarus; syndactyly; meningomyeloceles; cardiac abnormalities; genitourinary abnormalities; and adrenal hyperplasia.

III.Ocular findings include telecanthus; hypotelorism or hypertelorism; blepharophimosis; blepharoptosis; proptosis; microphthalmos; ectopic pupil; anophthalmos (unilat-

eral); microcornea; and iris and cornea colobomas. A. Normal eyes have also been reported.

IV. Histologic ocular findings include microcornea; iris and choroid colobomas; persistent hyaloid vasculature; retinal dysplasia; optic atrophy.

Chromosome 11 Deletion Defect

Deletion of chromosome 11p (aniridia–genitourinary–mental retardation syndrome—AGR triad) shows aniridia as its main ocular finding.

A.The chromosome band 11p13 has been associated with aniridia and Wilms’ tumor.

B.Deletion of chromosome 11q results in trigonocephaly, broad nasal bridge and upturned nose, abnormal pinnae, carp mouth, and micrognathia; and numerous ocular abnormalities.

Chromosome 13 Deletion Defect

See pp. 734 and 735 in Chapter 18.

Chromosome 17 Deletion (17p11.2;

Smith–Magenis Syndrome)

Chromosome 4 Deletion Defect

The chromosome 4 deletion defect (4p–) results from a partial deletion of the short arm of chromosome 14 (46,4p–). Also known as the Wolf–Hirschhorn syndrome (or Wolf ’s syndrome), it consists of profound mental retardation, antimongoloid slant, epicanthal folds, hypertelorism, ptosis, strabismus, nystagmus, cataract, and iris colobomas.

Chromosome 5 Deletion Defect (46,5p–; Cri du Chat Syndrome)

I.General information

A.Chromosome 5 deletion defect results from a deletion of part of the short arm of chromosome 5 (46,5p–).

Only one of the chromosome 5 pair is a ected.

I.General information: the Smith–Magenis syndrome is a multiple-anomaly, mental retardation syndrome associated

with deletions of a contiguous region of chromosome

17p11.2.

II.Systemic findings include dysmorphic facial features (brachycephaly, prominent forehead, synophrys, epicanthal folds, broad nasal bridge, ear anomalies, and prognathism), brachydactyly, self-injurious behaviors, autoamplexation

(self-hugging) stereotypy, speech delay, sleep disturbances,

mental and developmental retardation, and peripheral neuropathy.

III.Ocular findings include ptosis, telecanthus, strabismus, myopia, microcornea, iris abnormalities (Brushfield spots,

colobomas), bilateral cataract, optic nerve hypoplasia, and retinal detachment.

IV. Significant histologic ocular findings have not been reported.

the child grows older.

Chromosome 4 deletion defect differs from cri du chat syndrome in not having the distinctive cry.

C. A ected patients usually live a normal lifespan.

II.Systemic findings include severe mental retardation; lowset ears; microcephaly; micrognathia; moon-shaped face; short neck; transverse palmar creases; scoliosis and kyphosis; curved fifth fingers; limitation of flexion or extension of fingers; and abnormalities of the cardiovascular system and kidneys.

III.Ocular findings include hypertelorism; epicanthus; mongoloid or antimongoloid eyelid fissures; exotropia; optic atrophy; tortuous retinal artery and veins; and pupils supersensitive to 2.5% methacholine.

IV. Significant histologic ocular findings have not been reported.

or 46,18r; Partial 18 Monosomy (Fig. 2.10)

I.General information

A.Chromosome 18 deletion defect results from a straight deletion of part of the short arm of chromosome 18 (46,18p–), part of the long arm (46,18q–), or parts or all of the long and short arms, resulting in a ring form (46,18r). Only one of the chromosome 18 pair is a ected.

B.No specific ocular abnormalities relate to the di erent forms of deletion.

C.A ected patients usually live a normal lifespan.

II.Systemic findings include low-set ears; nasal abnormalities; external genital abnormalities; hepatosplenomegaly; cardiovascular abnormalities; and holoprosencephaly.

III.Ocular findings include hypertelorism; epicanthus; ptosis; strabismus; nystagmus; myopia; glaucoma; microphthalmos; microcornea; corneal opacities; posterior keratoconus; Brushfield spots; cataract; uveal colobomas, including

microphthalmos with cyst; retinal abnormalities; optic atrophy; and “cyclops.”

IV. Histology

A.Microphthalmos with cyst (see p. 531 in Chapter 14) and uveal colobomas are discussed elsewhere (see p. 338 in Chapter 9).

B.Intrascleral cartilage and intrachoroidal smooth muscle may be present anterior to and associated with a coloboma of the choroid.

C.Other findings include hypoplasia of the iris, immature anterior-chamber angle, persistent tunica vasculosa lentis, cataract, retinal dysplasia, and neural retinal nonattachment.

Chromosome 47 Deletion Defect

I.Turner’s syndrome (gonadal dysgenesis; Bonnevie–Ullrich syndrome; ovarian agenesis; and ovarian dysgenesis)

A.Turner’s syndrome is usually caused by only one sex chromosome being present, the X chromosome (45,X), or is due to a mosaic (45,X;46,XY).

B.Some cases, however, are caused by an X long-arm isochromosome [46,X(Xqi)], X deletion defect of the short arm [46,X(Xp-)], or X deletion (partial or complete) of all arms, resulting in a ring chromosome

[46,X(Xr)].

C.Ocular findings include epicanthus, blepharoptosis, myopia, strabismus, and nystagmus.

Noonan’s syndrome (Bonnevie–Ullrich or Ullrich’s syndrome; XX Turner phenotype or “female Turner”; and XY Turner phenotype or “male Turner”) probably is an inherited condition in which the person (either male or female) phenotypically resembles Turner’s syndrome but has a normal karyotype (46,XY or XX).

In Noonan’s syndrome, ocular anomalies are even more frequent than in Turner’s syndrome, and include antimongoloid slant of the palpebral fissures, hypertelorism, epicanthus, blepharoptosis, exophthalmos, keratoconus, high myopia, and posterior embryotoxon.

Mosaicism

I.General information

A.Chromosomal mosaicism refers to the presence of two or more populations of karyotypically distinct chromosomes in cells from a single individual.

Individuals with mixtures of cells derived from different zygotes are usually called chimeras (e.g., in a true hermaphrodite 46,XX; 46,XY), and the term mosaic is reserved for individuals who have cell mixtures arising from a single zygote.

B.Mosaicism may occur in most of the previously described chromosomal abnormalities.

II.Tetraploid–diploid mosaicism (92/46; Fig. 2.11)

A.In tetraploid–diploid mosaicism, two karyotypically distinct populations of cells exist: a large-size cell with increased DNA content containing 92 chromosomes (tetraploid), and a normal-size cell with a normal complement of 46 chromosomes (diploid). The condition is incompatible with longevity.

B.Systemic findings include micrognathia, horizontal palmar creases, deformities of the fingers and toes,

cardiovascular abnormalities, microcephalus, and forebrain maturation arrest.

C.Ocular anomalies include microphthalmos, corneal opacities, and leukokoria.

D.Histologically, the eyes may show iris neovascularization, anterior peripheral synechiae, luxated and cataractous lens, nonattachment of the neural retina, and massive hyperplasia of the pigment epithelium.

III.Most cases of trisomy 8(47,8+) are mosaics. The main ocular findings are strabismus and dense, geographic, stromal corneal opacities.

INFECTIOUS EMBRYOPATHY

Congenital Rubella Syndrome (Gregg’s Syndrome)

I.Congenital rubella syndrome consists of cataracts, cardiovascular defects, mental retardation, and deafness. The syndrome results from maternal rubella infection during pregnancy (50% of fetuses are a ected if mother contracts rubella during first 4 weeks of pregnancy; 20% a ected if contracted during first trimester).

Congenital varicella cataract has been reported in infants whose mothers had varicella during their pregnancies.

II.Systemic findings include low birth weight; deafness; congenital heart defects (especially patent ductus arteriosus); central nervous system abnormalities; thrombocytopenic purpura; diabetes mellitus; osteomyelitis; dental abnormalities; pneumonitis; hepatomegaly; and genitourinary anomalies.

III.Ocular findings include cataract; congenital glaucoma; iris abnormalities; and a secondary pigmentary retinopathy (Figs 2.12 and 2.13).

Rubella retinopathy is the most characteristic finding and, on rare occasions, may be progressive. Approximately 30% of patients with congenital rubella have cataracts and 9% have glaucoma. When rubella cataract is present, congenital glaucoma is present in 9% of cases; when congenital glaucoma is present, cataract is present in 33% of cases. Congenital rubella cataract and glaucoma therefore occur together at the frequency expected of coincidental events occurring independently. Subneural retinal neovascularization has been reported in patients between the ages of 10 and 18 years who have congenital rubella. Persistence of the rubella virus has been implicated in the delayed onset of Fuchs’ heterochromic iridocyclitis.

c

i

cd cb

l cb

A

ac

n

B

Fig. 2.12 Rubella. A, A dense nuclear cataract surrounded by a mild cortical cataract is seen in the red reflex. B, Cortical and nuclear cataract present. Note Lange’s fold, which is an artifact of fixation, at the ora serrata on the left (c, cornea; i, iris; cb, ciliary body; l, lens; cd, cataractous degeneration). C, The dense nuclear cataract shows lens cell nuclei (n) retained in the embryonic nucleus (ac, artifactitious clefts in lens nucleus). (A, Courtesy of Dr. DB Schaffer; B and C, from Yanoff M, et al.: Trans Am Acad Ophthalmol Otolaryngol 72:896. Copyright Elsevier 1968.)