Volume 5, Chapter 22A. Ocular Abnormalities in Congenital Heart Disease

Chapter 22A
Ocular Abnormalities in Congenital Heart Disease
ESHAGH ESHAGHPOUR and GARY R. DIAMOND
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CLASSIFICATION AND PATHOPHYSIOLOGY OF CONGENTIAL HEART DISEASE
PRESENTATION OF PATTERNS OF MALFORMATION
ACQUIRED OCULAR FINDINGS IN CONGENITAL HEART DISEASE
ACKNOWLEDGMENT
REFERENCES

The high prevalence of ocular abnormalities in children who have congenital heart disease (CHD) is in part related to the high incidence of CHD in disease syndromes. The incidence of CHD is approximately 4 to 9 per 1000 live births. Because of the lack of proper reporting of minor abnormalities, the exact incidence of ocular anomalies in CHD is not known. Although there are recognizable patterns of ocular abnormality in certain types of CHD, this combination of anomalies represents an association rather than a cause-and-effect relationship. Considering the temporal relationship between embryogenesis of the heart and the eyes, it is reasonable to assume that an embryopathic insult may result in both cardiac and ocular malformations. In addition, CHD may cause acquired ocular disease. This direct relationship may result from the effects of cyanotic heart disease, from systemic hypertension in coarctation of the aorta, and from obstruction of the superior vena cava (SVC).

CLASSIFICATION AND PATHOPHYSIOLOGY OF CONGENTIAL HEART DISEASE

Cardiovascular malformations of the heart and their related blood vessels are conventionally classified as acyanotic and cyanotic CHD.

ACYANOTIC CONGENITAL HEART DISEASE

Acyanotic cardiac malformations are grouped into three categories, as reviewed under the following headings.

Congenital Heart Disease With Left-to-Right Shunting

These malformations include ventricular septal defect (VSD); patent ductus arteriosus (PDA); atrial septal defect (ASD); partial anomalous pulmonary venous connection (PAPVC), with or without ASD; atrioventricular canal (AVC) malformations; and aortopulmonary fenestration (AP window). The hemodynamic abnormalities are the result of left-to-right shunting and correlate with the degree of the shunt. Neonates, who have high pulmonary vascular resistance, generally have a small and clinically insignificant left-to-right shunt. During the first few days and weeks, as the pulmonary vascular resistance falls, the left-to-right shunting may increase and heart failure may ensue. Physiologically, this failure represents diastolic overload to the left ventricle, with increased pulmonary blood flow and pulmonary hypertension as noted in VSD, complete AVC or transitional AVC with large VSD, PDA, and AP window. Aortic runoff results in low diastolic pressure and increased pulse pressure (bounding pulses) and is found with PDA and AP window. AP windows are rare. ASDs cause right ventricular diastolic overload and do not usually cause congestive heart failure in children. During the childhood years, pressure overload is required to cause heart failure in the volume-overloaded right ventricle. Long-standing high flow and high pressure in the pulmonary vascular bed result in injury to the small pulmonary arteries and arterioles and the development of pulmonary vascular obstructive disease (PVOD). In advanced PVOD, the pulmonary vascular resistance approaches or exceeds the systemic resistance and causes reversal of the shunt (right-to-left shunting), with resulting cyanosis, hypoxemia, erythrocytosis, and increased blood viscosity.

Congenital Heart Disease With Outflow Obstruction

Outflow obstruction may occur at the right or left ventricular outflow tracts, at or distal to the semilunar valves. These anomalies include pulmonic valve stenosis and aortic valve stenosis, subpulmonic stenosis and subaortic stenosis, pulmonary artery stenosis, supravalvar aortic stenosis, and coarctation of the aorta. The hemodynamic abnormalities result from systolic overload of the right or left ventricles. The severity of the disease correlates with the systolic pressure in the ventricle and the systolic pressure gradient across the obstruction. The systolic overload is compensated by maintaining wall stress by developing hypertrophy, which when severe, however, results in decreased compliance of the ventricle and abnormal ventricular function. The clinical findings of obstruction at the semilunar valves or at the ventricular outflow tracts are highlighted by outflow murmurs. In supravalvar aortic stenosis there is a significant systolic pressure gradient between the two arms, with the right arm systolic pressure higher than that in the left arm. The presence of a large systolic pressure difference between the upper and lower extremities, with systemic hypertension of the arms and delayed and barely palpable arterial pulsations in the legs, is diagnostic of coarctation of the aorta.

Uncommon Acyanotic Congenital Heart Disease

Cardiomyopathies, which may be hypertrophic or dilated (congestive), are uncommon anomalies. Hypertrophic cardiomyopathies can be obstructive and result in left ventricular outflow obstruction or can be nonobstructive, as in nonobstructive asymmetric septal hypertrophy and concentric left ventricular hypertrophy. Anomalous origin of the left coronary artery arising from the main pulmonary artery results in anterolateral myocardial infarction and is grouped under the congestive cardiomyopathies.

CYANOTIC CONGENITAL HEART DISEASE

No pathognomonic clinical features are delineated for cyanotic CHD; however, hypoxemia and cyanosis are common clinical denominators. Based on pathophysiology, these anomalies are grouped in the categories described next.

Cyanotic Congenital Heart Disease With Malalignment of the Great Arteries

Complete transposition of the great arteries (d-TGA), which is the most common cyanotic heart disease of neonates, is anatomically signified by the aorta arising from the outflow of the right ventricle and the pulmonary artery from the left ventricle, resulting in severe hypoxemia. Unlike the normal circulation, in which the pulmonary and systemic circuits work in series, in d-TGA, the two circuits function in parallel. This anomaly is incompatible with life unless mixing of systemic and pulmonary venous blood becomes possible by the presence of an additional cardiac defect (ASD, VSD, or common ventricle). An ASD can be created by balloon atrial septostomy (BAS). BAS is an effective method of treatment in neonates while waiting for surgical correction. The Mustard and Senning operations redirect the pulmonary and systemic venous returns and offer a functional correction. The Jatene procedure offers correction by aorta and pulmonary arterial switch.

Cyanotic Congenital Heart Disease With Critical Obstruction to Pulmonary Blood Flow

Anomalies in this category include tricuspid atresia, pulmonary atresia or critical pulmonic valve stenosis with intact ventricular septum, tetralogy of Fallot (right ventricular outflow obstruction with VSD and overriding aorta), severe Epstein's anomaly of the tricuspid valve (adherence of redundant tricuspid valve leaflets to the right ventricular walls resulting in tricuspid regurgitation, small right ventricular cavity, and decreased forward flow), common ventricle (univentricular heart), and double-outlet right ventricle with pulmonary atresia or severe pulmonic stenosis. Severe hypoxemia results from critically decreased pulmonary blood flow and is exaggerated by right-to-left shunting at the atrial level through an ASD or patent foramen ovale or at the ventricular level through a VSD. Immediately after birth, pharmacologic palliation is indicated with prostaglandin E₁ to keep the ductus arteriosus patent while planning for surgical palliation by systemic-to-pulmonary artery shunt (subclavian to pulmonary artery anastomosis or aorta to pulmonary artery shunt by interposition graft) or until more definitive surgery is performed.

Cyanotic Congenital Heart Disease With Venous Admixture and Increased Pulmonary Blood Flow

The mixture of pulmonary and systemic venous blood results in unrestricted large pulmonary blood flow and smaller, usually restricted, systemic blood flow. These anomalies include total anomalous pulmonary venous connection, common ventricle (univentricular heart) and double-outlet right ventricle without pulmonary atresia or severe subpulmonic and pulmonic valve stenosis, persistent truncus arteriosus, and hypoplastic left heart syndrome. Because of markedly increased pulmonary blood flow, hypoxemia and cyanosis are moderate in severity, and congestive heart failure and systemic hypoperfusion dominate the clinical picture. Intensive medical treatment with inotropic and diuretic drugs is indicated. Early surgical palliation or correction is required.

PRESENTATION OF PATTERNS OF MALFORMATION

No patterns of ocular malformations are recognizable in infants and children with acyanotic or cyanotic heart disease, unless the anomalies are of multisystem expression within the context of known syndromes. These syndromes include those caused by chromosomal abnormalities and by inborn errors of metabolism, those related to connective tissue disease, and those caused by congenital infections. The cause of many syndromes is still unknown. Because recognizable patterns of eye and heart disease are found in this context, we have devised Tables 1 through 3. Table 1 is a comprehensive alphabetical list of syndromes with a known incidence of heart disease and names the primary clinical features and specific ocular and cardiac anomalies.^1–35 Table 2 presents those syndromes with occasional reported heart disease.^36–75 Table 3 is organized by ocular findings for the previously mentioned syndromes.

TABLE 1. Syndromes With Ocular Abnormalities and Frequent Congenital Heart Disease

Syndrome	Primary Features	Ocular	Cardiac
Aase¹	Triphalangeal thumb, congenital anemia	Retinopathy	VSD
Arteriohepatic dysplasia² (Alagille)	Cholestasis, unusual facies, peripheral PS	Posterior embryotoxon (prominence of Schwalbe line) occasional retinal degeneration, strabismus	PPS, occasional ASD, VSD, PDA, CoA
Beals³	Contractural arachnodactyly	Occasional iris coloboma	MVP, occasional ASD, VSD
Cat's eye⁴	Coloboma of iris, anal atresia	Mild hypertelorism, down-slanting palpebral fissures, inferior coloboma of iris, choroid, and/or retina	TAPVC, LSVC
CHARGE association⁵	Coloboma, Heart disease, Atresia choanae, Retarded growth and development, Genital anomalies, Ear anomalies and/or deafness	Coloboma ranging from isolated iris coloboma without visual impairment to clinical anophthalmos, retinal coloboma most common	TF, PDA, DORV with AVC, VSD, ASD, right aortic arch
DiGeorge sequence⁶	Defect fourth branchial arch and derivatives of third and fourth pharyngeal pouches (thymus, parathyroids, heart)	Hypertelorism, down-slanting palpebral fissures	Aortic arch anomalies, conotruncal anomalies such as TA and VSD, TF, PDA
Down (trisomy 21)⁷	Mental retardation, hypotonia, flat facies, slanted palpebral fissures, small ears	Inner epicanthal folds, Brushfield spots with peripheral hypoplasia of the iris; fine lens opacity by slit lamp examination (59%); refractive error Occasional strabismus 33%, nystagmus 15%, keratoconus 6%, cataract 1%	AVC, VSD, PDA, ASD, aberrant origin of subclavian artery, TF
Ehlers-Danlos⁸	Hyperextensible joints, hyperextensible skin with poor wound healing	Occasional epicanthal folds, blue sclera, myopia, microcornea, keratoconus, ectopia lentis, retinal detachment, glaucoma	MVP, TVP, aortic root dilatation, occasional ASD, aortic arch anomalies
Fetal alcohol⁹	Intrauterine growth retardation, microcephaly, short palpebral fissures	Short palpebral fissures, occasional ptosis, microphthalmia	VSD, ASD, occasional TF, CoA
Fetal rubella¹⁰	Deafness, cataracts, PDA	Glaucoma, corneal opacity, chorioretinitis, microphthalmia, strabismus, cataract	PDA, PPS, VSD, myocardial disease
Holt-Oram¹¹(cardiac-limb)	Upper limb and shoulder anomalies; ASD,VSD	Occasional hypertelorism	ASD, VSD, occasional PDA, PS
Hurler¹² (mucopolysaccharidosis I H)	Course facies, stiff joints, mental retardation, cloudy corneas by age 1 to 2 years	Corneal clouding, retinal pigmentation, hypertelorism, inner epicanthal folds	Infiltrative disease affecting myocardium, coronary vessels, or cardiac valves; CHF
Marfan¹³	Arachnodactyly, hyperextensibility, lens subluxation, aortic dilatation	Lens subluxation (upward) with defect of suspensory ligament, increased axial globe length, myopia, retinal detachment, occasional iris coloboma	Ascending aorta dilatation and/or dissection, abdominal aortic involvement, AR, MVP
Maternal phenylketonuria fetal effects¹⁴	Microcephaly, growth and mental retardation	Hypotelorism and epicanthal folds, strabismus, occasional microphthalmia	CoA, PDA, ASD, VSD, TF
Mulibrey nanism¹⁵	MUscle	Retinal hypopigmentation with dispersion and clusters of pigment and yellow dots in mid and periphery	Restrictive pericardium
	LIver
	BRain
	EYes
Multiple lentigines¹⁶ (LEOPARD)	Lentigines	Mild hypertelorism	Mild PS, ECG findings of prolonged PR interval and QRS duration and abnormal P waves, occasional sub Ao
	ECG abnormalities
	Ocular hypertelorism
	Pulmonic stenosis
	Abnormalities of genitalia
	Retardation of growth
	Deafness
Noonan¹⁷ (phenotypic Turner)	Webbed neck, pectus excavatum, cryptorchidism, PS	Epicanthal folds, ptosis, hypertelorism, myopia, keratoconus, strabismus, nystagmus	PS, ASD, VSD
Pallister-Hall¹⁸	Hypothalamic hamartoblastoma, hypopituitarism, imperforate anus, polydactyly	Occasional microphthalmia, coloboma	AVC
Partial trisomy 10q¹⁹	Ptosis, short palpebral fissures, camptodactyly	High arched eyebrows, ptosis, short palpebral fissures, microphthalmia, drusen-like macular deposits	AVC, PAH
Pseudo-Hurler polydystrophy²⁰ (mucopolysaccharidosis III)	Coarse facies, stiff joints by 2 to 4 years, no mucopolysacchariduria	Mild corneal opacities by slit lamp examination by 6 to 8 years	Aortic valve disease, often with AR
Retinoic acid embryopathy²¹	Central nervous system defects, microtia, cardiac defects	Occasional hypertelorism, down-slanting palpebral fissures, septo-optic dysphasia	Conotruncal defects, including TGA, TF, DORV, TA, supracristal VSD, hypoplastic aortic arch, type B interrupted aortic arch
Rubinstein-Taybi²²	Mental deficiency, abnormal gait, broad digits, hypoplastic maxilla, down-slanting palpebral fissures, cryptorchidism	Down-slanting palpebral fissures (100%), epicanthal folds (62%), strabismus (79%), refractive error (58%), occasional cataract, coloboma, ptosis, long eyelashes	VSD, PDA
Scheie²³ (mucopolysaccharidosis 1 S)	Broad mouth, full lips, early corneal opacity, normal mental function	Early corneal clouding more dense at periphery	Aortic valve
Shprintzen²⁴ (velocardiofacial)	Small stature, mild intellectual impairment, cleft palate, squared nasal root, slender hypotonic hands and fingers	Occasional small optic discs with tortuous vessels and cataracts	VSD, right aortic arch, TF, aberrant LSCA
Triploidy²⁵	Complete extra set of chromosomes, growth retardation, craniofacial anomalies, syndactyly, abnormal genitalia in males	Coloboma, microphthalmia, occasional iris heterochromia	ASD, VSD
Trisomy 9 mosaic²⁶	Joint contractures, heart disease, low-set malformed ears	Up-slanting, short palpebral fissures, deep eyes, occasional microphthalmia	Position dextrocardia with VSD and PDA, DORV with VSD and CoA, PDA, EFE, LSVC to CS, DORV with VSD
Trisomy 13²⁷ (trisomy D)	Midface anomalies of holoprosencephaly type, mental retardation, polydactyly, nail and skin abnormalities	Microphthalmia, coloboma of iris, absent eyebrows, hypotelorism, anophthalmos, cyclopia	VSD, PDA, ASD, positional dextrocardia
Trisomy 18²⁸	Mental retardation, hand and foot anomalies, clenched hand, short sternum, craniofacial and dermal ridge anomalies	Short palpebral fissures, occasional inner epicanthal folds, ptosis, corneal opacity	VSD, ASD, PDA, AS, PS, CoA, TF
Turner³⁰ (single X chromosome)	Short stature, ovarian dysgenesis, low hairline, webbed neck, broad chest, wide nipples, congenital lymphedema	Occasional ptosis, strabismus, blue sclerae, cataract	CoA, AS, bicuspid aortic valve
Williams²⁹ (elfin facies)	Mental retardation, unusual facies, supravalvar AS, hypercalcemia in infancy	Blue eyes, stellate pattern of iris	Supravalvar AS, PPS, VDS, ASD, aortic arch anomalies
XXXXX³¹ (Penta X)	Growth and mental deficiencies, microcephaly, small hands, clinodactyly	Up-slanting palpebral fissures, occasional coloboma, hypertelorism, inner canthal folds	PDA
4p-³² (chromosome 4 short arm deletion)	“Roman helmet” facies (hypertelorism with broad nose), microcephaly, low-set ears, preauricular dimples	Strabismus, coloboma of iris, hypertelorism, epicanthal folds, occasional exophthalmos, Brushfield spots, cataracts	ASD, VSD, PDA, positional dextrocardia, HLHS, mild PS, AS, LSVC, aortic arch anomalies
9p-³³ (9p monosomy)	Craniostenosis, microcephaly, up-slanting palpebral fissures, hypoplastic supraorbital ridges, choanal atresia	Up-slanting palpebral fissures, hypoplastic supraorbital ridges, apparent prominence of eyes	VSD, PDA, PS
13q-³⁴	Microcephaly, high nasal bridge, eye defect, thumb hypoplasia, neural tube defects	Hypertelorism, ptosis, epicanthal folds, microphthalmia, bilateral retinoblastoma	Uncertain CHD
18q-³⁵ (long arm 18 deletion)	Midfacial hypoplasia, anomalous digital patterns	Occasional inner epicanthal folds, slanted palpebral fissures, hypertelorism, microphthalmia, corneal abnormality, cataract, abnormal optic disc	Uncertain CHD (cardiomegaly reported)

AR, aortic valve regurgitation; AS, aortic valve stenosis; ASD, atrial septal defect; AVC, atrioventricular canal (endocardial cushion) defect; CHD, congenital heart disease; CHF, congestive heart failure; CoA, coarctation of the aorta; CS, coronary sinus: DORV, double-outlet right ventricle; ECG, electrocardiogram; EFE, endocardial fibroelastosis; HLHS, hypoplastic left heart syndrome; LSCA, left subclavian artery; LSVC, persistent left superior vena cava; MVP, mitral valve prolapse; PAH, pulmonary artery hypertension; PDA, patent ductus arteriosus; PPS, peripheral pulmonary arterial stenosis; PS, pulmonary valve stenosis; sub Ao, subaortic stenosis; TA, truncus arteriosus; TAPVC, total anomalous pulmonary venous connection; TF, tetralogy of Fallot; TGA, transposition of the great arteries; TVP, tricuspid valve prolapse; VSD, ventricular septal defect.

TABLE 2. Syndromes With Ocular Abnormalities and Occasional Congenital Heart Disease

Syndrome	Primary Features	Ocular	Cardiac
Antley-Bixler³⁶	Craniosynostosis, choanal atresia, radiohumeral synostosis	Proptosis	ASD
Apert³⁷ (acrocephalosyndactyly)	Craniosynostosis, midfacial hypoplasia, syndactyly—big thumb and big toe	Hypertelorism, strabismus, down-slanting palpebral fissures	Occasional PS, PPS, VSD, conotruncal defects, EFE
Baller-Gerold³⁸	Craniosynostosis, radial aplasia	Occasional epicanthal folds, strabismus, optic atrophy	Sub Ao, VSD
Blepharophimosis³⁹ (familial blepharophimosis)	Inner canthal fold, lateral displacement of inner canthi, ptosis	Inverted inner canthal fold, short palpebral fissure, lateral displacement of inner canthi, ptosis, hypoplasia and fibrosis of levator palpebrae muscle, strabismus	Uncertain CHD
Carpenter⁴⁰	Acrocephaly, poly/syndactyly of feet, lateral displacement of inner canthi	Shallow supraorbital ridges, lateral displacement of inner canthi, inner canthal folds	PDA, VSD, PS, TGA
Coffin-Lowry⁴¹	Down-slanting palpebral fissures, tapering fingers	Down-slanting palpebral fissures, mild hypertelorism	MVP, MR
Cohen⁴²	Hypotonia, obesity, prominent incisors	Mildly down-slanting palpebral fissures, decreased visual acuity, defective vision in bright light, visual field constriction, chorioretinal dystrophy with bull's eye macular pigment deposits, optic atrophy, occasional coloboma, microphthalmia	MVP
Cri du chat⁴³ (5p- partial deletion short arm chromosome 5)	Mental retardation, microcephaly, growth retardation, catlike cry in infancy	Down-slanting palpebral fissures, hypertelorism, epicanthal folds, strabismus (often divergent)	Variable types
Cornelia de Lange⁴⁴	Synophrys, thin downturning upper lip, micromelia	Bushy eyebrows, long eyelashes, occasional myopia, microcornea, astigmatism, optic atrophy, coloboma of optic nerve, strabismus, proptosis	VSD
Facio-auriculovertebral spectrum⁴⁵ (Goldenhar)	Face, eye, ear, and vertebral anomalies, often symmetric (first and second branchial arches)	Occasional epibulbar dermoid, lipodermoid, notch in upper lid, strabismus, microphthalmia	VSD, PDA, TF, CoA
Fabry⁴⁶	Angiokeratoma, hand and foot pain, renal insufficiency	Superficial corneal opacities, occasional saccular retinal vessels	Glycolipid infiltration of myocardium, endocardium, valves, and conduction tissues; HCM
Fanconi⁴⁷	Radial hypoplasia, hyperpigmentation, pancytopenia	Occasional ptosis, strabismus, nystagmus microphthalmia	Uncertain CHD
Fetal hydantoin⁴⁸ (fetal Dilantin)	Mild mental deficiency, hypertelorism, flat nasal bridge, thin upper lip vermilion, digital anomalies	Hypertelorism, occasional strabismus, coloboma, ptosis	PS, AS, CoA, PDA, ASD, VSD
Fetal trimethadione⁴⁹ (tridione)	Mental deficiency, midface hypoplasia, up-slanting eyebrows, genital anomalies	Mild synophrys with unusual up-slanting eyebrows, strabismus ptosis, epicanthal folds	TF, VSD, ASD
Fetal warfarin⁵⁰	Hypoplastic nose with airway obstruction, mental retardation, axial skeletal anomalies (stippled epiphyses)	Optic atrophy, blindness	Uncertain CHD
Fraser⁵¹	Cryptophthalmos, ear and genital anomalies	Cryptophthalmos, variable eye defects	Uncertain CHD
Goltz⁵²	Poikiloderma and focal dermal hypoplasia, syndactyly, dental anomalies	Strabismus, coloboma, microphthalmos, occasional bulbar angiofibroma, basal cell carcinoma	Uncertain CHD
Hay-Wells syndrome of ectodermal dysplasia⁵³	Ectodermal dysplasia with cleft palate or lip and congenital fusion of the eyelids	Ankyloblepharon filiforme adnatum (adhesion between eyelids)	VSD, PDA
Hurler-Scheie⁵⁴ (mucopolysaccharidosis I H/S)	Similar to Hurler	Corneal clouding	Mitral and aortic valve anomalies
Langer-Giedion⁵⁵ (Trichorhinophalangeal syndrome with exostoses)	Redundant skin infancy, multiple exostoses, bulbous nose, peculiar facies	Occasional hypotelorism, ptosis, epicanthal folds, iris coloboma	Uncertain CHD
Linear sebaceous nevus sequence (nevus sebaceous of Jadassohn)⁵⁶	Midfacial nevus sebaceous, seizures, mental deficiency	Occasional esotropia; conjunctival lipodermoid; corneal clouding; coloboma of eyelid, iris, and choroids	CoA, VSD
Maroteaux-Lamy⁵⁷ (mucopolysaccharidosis VI)	Similar to Hurler	Corneal clouding	Infiltrative myocardial and valve disease
Meckel-Gruber⁵⁸	Encephalocele, cystic dysplasia of kidneys, polydactyly	Microphthalmos	ASD, VSD, PDA, CoA, PS
Miller⁵⁹	Abnormal facies, malar and maxillary hypoplasia, lower lid defect, cleft lip and/or cleft palate, hypoplastic cup-shaped ears, accessory nipples, limb defects especially postaxial	Down-slanting palpebral fissures, coloboma of eyelids and ectropion, deficient lower eyelashes	Uncertain CHD
Nager⁶⁰ (acrofacial dysostosis)	Normal intellect, conductive deafness, malar hypoplasia, micrognathia, hypoplasia or dysplasia of thumb and radius	Down-slanting palpebral fissures, deficient lower eyelashes	TF
Opitz⁶¹	Hypertelorism, hypospadias	Hypertelorism	Bicuspid aortic valve, LSVC
Osteogenesis imperfecta⁶²	Fragile bone, blue sclerae, hyperextensibility, odontogenesis imperfecta	Blue sclerae (thin and translucent), occasional embryotoxon, keratoconus, megalocornea	MVP
Roberts-SC phocomelia⁶³	Hypomelia, midfacial defects, severe growth retardation (pseudothalidomide)	Hypertelorism, prominent eyes with blue sclera, occasional corneal clouding, cataract, lid coloboma	ASD
Robinow⁶⁴ (fetal face)	Fetal facial appearance, short arms, genital hypoplasia	Frontal bossing with apparent hypertelorism	ASD
Sly⁶⁵ (mucopolysaccharidosis VII)	Similar to Hurler	Corneal clouding	Infiltrative myocardial and valve disease
Smith-Lemli-Opitz⁶⁶	Eye anomalies, syndactyly, hypospadias	Inner epicanthal folds, ptosis, strabismus	Uncertain CHD
Stickler⁶⁷ (hereditary arthro-ophthalmopathy)	Flat face, depressed nasal bridge, midfacial and mandibular hypoplasia, cleft hard or soft palate, myopia, spondyloepiphyseal dysplasia	Myopia, occasional glaucomaRetinal detachment	MVP
Sturge-Weber⁶⁸	Facial/meningeal hemangioma, seizures	Hemangioma may involve choroid; occasional glaucoma, iris coloboma	CoA
Treacher Collins⁶⁹ (mandibulofacial dysostosis)	Malar hypoplasia with down-slanting palpebral fissures, defect lower eyelid, malformed external ear	Down-slanting palpebral coloboma of eyelids and ectropion, deficient lower eyelashes	Uncertain CHD
Trisomy 4p⁷⁰	Severe mental retardation, growth failure, seizures, pug nose, prominent forehead, hand and foot anomalies, genital anomalies	Synophrys, occasional microphthalmia, retinal anomalies	Uncertain CHD
Trisomy 9p⁷¹	Severe mental retardation, hypoplasia distal phalanges, hypertelorism	Hypertelorism, down-slanting palpebral fissures, occasional epicanthal folds	Uncertain CHD, reported in 5% to 10%
Trisomy 20p⁷²	Blepharophimosis, abnormal large ears, cubitus valgus	Up-slanting palpebral fissures, blepharophimosis, hypo/hypertelorism	VSD, TF
Waardenburg⁷³ syndromes 1 and 2	Congenital deafness, partial albinism, lateral displacement of medial canthi in type 1 only	Isochromic pale blue eyes with hypoplastic iris stroma, occasional iris heterochromia, peripheral retinal pigmentation	VSD
Weill-Marchesani⁷⁴	Small stature, brachydactyly, small spherical lens and myopia	Small spherical lens, myopia, glaucoma, ectopia lentis, blindness	Uncertain CHD
XXXY and XXXXY⁷⁵	Mental retardation, growth deficiency, hypogenitalism, limited pronation of elbow	Up-slanting palpebral fissures, inner epicanthal folds, strabismus, occasional down-slanting palpebral fissures, Brushfield spots, myopia	PDA

AS, aortic valve stenosis; ASD, atrial septal defect; CHD, congenital heart disease; CoA, coarctation of the aorta; EFE, endocardial fibroelastosis; HCM, hypertrophic cardiomyopathy; LSVC, persistent left superior vena cava; MR, mitral regurgitation; MVP, mitral valve prolapse; PDA, patent ductus arteriosus; PPS, peripheral pulmonary arterial stenosis; PS, pulmonary valve stenosis; sub Ao, subaortic stenosis; TF, tetralogy of Fallot; TGA, transposition of the great arteries; VSD, ventricular septal defect.

TABLE 3. Ocular Findings and Syndromes With Congenital Heart Disease

Ocular Findings	Syndrome
Ankyloblepharon filiforme adnatum	Hay-Wells syndrome of ectodermal dysplasia
Anophthalmia	CHARGE association
	Trisomy 13
Blepharophimosis	Blepharophimosis (familial)
	Trisomy 20p
Blindness	Fetal warfarin
	Weill-Marchesani
	Bardet-Biedl
Blue sclerae	Ehlers-Danlos
	Osteogenesis imperfecta
	Turner
	Roberts-SC phocomelia
Brushfield spots	Down
	XXXY and XXXXY
	4p-
Cataract	Down (1%)
	Turner
	Roberts-SC phocomelia
	Rubinstein-Taybi
	Fetal rubella
	Shprintzen
	4p-
Chorioretinitis (coloboma)	Fetal rubella
	Cat's eye
	CHARGE
	Rubinstein-Taybi
	Triploidy
	Penta X
	Fetal hydantoin
	Linear sebaceous nevus sequence
	Treacher Collins
	Miller
	Beals
	Marfan
	Pallister-Hall
	Langer-Giedion
	Roberts-SC phocomelia
	Sturge-Weber
	4p-
Corneal clouding	Fetal rubella
	MPS I (mucopolysaccharidoses)
	MPS III
	MPS VI
	Trisomy 18
	18q-
	Linear sebaceous nevus sequence
	Roberts-SC phocomelia
	Fabry
Cryptophthalmos	Fraser
Cyclopia	Trisomy 13
Dermoid (epibulbar lipodermoid)	Goldenhar
	Linear sebaceous nevus sequence
Ectopia lentis	Weill-Marchesani
	Marfan
Ectropion	Treacher Collin
	Miller
Embryotoxon (corneal opacity)	Osteogenesis imperfecta
	Alagille
Epicanthal folds	Down
	Ehlers-Danlos
	Hurler
	Maternal phenylketonuria
	Noonan
	Rubinstein- Taybi
	Trisomy 18
	4p-
	13q-
	18q-
	Fetal trimethadione
	Trisomy 9p
	XXXY and XXXXY
Esotropia	Linear sebaceous nevus sequence
Exophthalmos	4p-
Glaucoma	Fetal rubella
	Weill-Marchesani
	Ehlers-Danlos
	Stickler
	Sturge-Weber
Hypertelorism	DiGeorge
	Holt-Oram
	Hurler
	Multiple lentigines (LEOPARD)
	Noonan
	Trisomy 13
	Penta X
	4p-
	13q-
	18q-
	Fetal hydantoin
	Opitz
	Roberts-SC phocomelia
	Robinow
	Trisomy 9p
	Trisomy 20p
	5p- (cri du chat)
	Langer-Giedion
	Smith-Lemli-Opitz
Hypotelorism	Maternal phenylketonuria
	Trisomy 13
	Trisomy 20p
	Langer-Giedion
Iris deformity	4p-
Iris heterochromia	Triploidy
	Waardenburg
Iris stellate pattern	Williams
Keratoconus	Down (6%)
	Ehlers-Danlos
	Noonan
	Osteogenesis imperfecta
Microcornea	Ehlers-Danlos
	Cornelia de Lange
Microphthalmia	Fetal alcohol
	Fetal rubella
	Maternal phenylketonuria
	Partial trisomy 10q
	Triploidy
	Trisomy 9 mosaic
	Trisomy 13
	13q-
	18q-
	Goldenhar
	Fanconi
	Meckel-Gruber
	Trisomy 4p
	Pallister-Hall
Myopia	Ehler-Danlos
	Noonan
	Cornelia de Lange
	XXXY and XXXXY
	Weill-Marchesani
	Marfan
	Stickler
Nystagmus	Down (15%)
	Rubinstein-Taybi
	Fanconi
Optic atrophy	Fetal warfarin
	Cohen
Optic disc abnormality	18q-
	Cornelia de Lange
	Shprintzen
Proptosis	Cornelia de Lange
Ptosis	Fetal alcohol
	Noonan
	Partial trisomy 10q
	Rubinstein-Taybi
	Trisomy 18
	Turner
	13q-
	Fetal hydantoin
	Fetal trimethadione
	Blepharophimosis (familial)
	Langer-Giedion
	Smith-Lemli-Optiz
Refractive error	Rubinstein-Taybi
	Cornelia de Lange
Retinal abnormality	Trisomy 4p
	Fabry
Retinal detachment	Ehlers-Danlos
	Marfan
	13q-
Retinal pigmentation abnormality	Hurler (MPS 1)
	Waardenburg
	Mulibrey nanism
Retinoblastoma	13q-
Retinopathy	Aase
Strabismus	Down (33%)
	Fetal rubella
	Maternal phenylketonuria
	Noonan
	Turner
	4p-
	Cornelia de Lange
	Goldenhar
	Fanconi
	Fetal hydantoin
	Cornelia de Lange
	Fetal trimethadione
	Blepharophimosis (familial)
	XXXY and XXXXY
	5p- (cri du chat)
	Langer-Giedion
	Smith-Lemli-Opitz
	Arteriohepatic dysplasia (Alagille)
	Apert
Synophrys	Trisomy 4p
	Fetal trimethadione

ACQUIRED OCULAR FINDINGS IN CONGENITAL HEART DISEASE

Cyanotic CHD when associated with severe hypoxemia and erythrocytosis may result in retinal and disc edema, as well as vascular (primarily venous) tortuosity.⁷⁶ Severe erythrocytosis (hematocrit in the high 60s and greater than 70% may lead to severe vascular dilatation and tortuosity that mimics central retinal vein obstruction; retinal and disc edema may result (Fig. 1). Cerebral abscess occurring in this population may also be present with retinal and disc edema.

Fig. 1. A. Fundus photograph of cyanotic right retina demonstrating violaceous dilated retinal veins secondary to erythrocytosis. B. Fluorescein study of A.

Primarily arteriolar tortuosity is noted in patients who have aortic coarctation.⁷⁷ Arteriolar constriction and arteriovenous crossing changes are rare in hypertensive patients who have aortic coarctation; hemorrhage and cotton-wool spots (retinal nerve fiber layer infarcts) are absent. Another feature of arteriolar tortuosity in patients who have aortic coarctation is the diffuse nature of the arteriolar tortuosity, perhaps resulting from wide pulse pressure; patients who have systemic hypertension from other causes generally have perimacular arteriolar tortuosity.

Acute superior vena caval ligation has been reported to increase intraocular pressure and cause bilateral glaucomatous optic nerve atrophy⁷⁸; the pressure increase was reversible on ligation reversal. Acute SVC obstruction may also cause exophthalmos, periorbital eyelid ecchymoses, and conjunctival chemosis with hemorrhage. Retinal venous engorgement with disc margin blurring has been described.

Although SVC obstructive syndrome after Mustard and Senning procedures, Glenn anastomosis, and Fontan procedure may be noted, it is rare for postoperative glaucoma to occur in children; perhaps adaptive mechanisms avert sustained elevated intraocular pressure. Because lengthy postoperative observation has been limited, patients who have SVC hypertension warrant closer ophthalmologic evaluation.

ACKNOWLEDGMENT

We acknowledge, with gratitude, the previous contributors to this chapter: Paul C. Anisman, M.D., Richard E. Goldberg, M.D., and Larry E. Magargal, M.D.

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