Ocular Manifestations of Cardiac Disease

Fig. 4.1
Dilated and tortuous retinal veins and arteries characteristic of cyanosis retinae [2]

Carpenter, in 1894, described the “everyday experience” of extracardiac malformations in patients with CHD, including ocular defects, such as corneal opacity, iris coloboma , orbital defects, and ptosis. He also described cyanosis retinae, emphasizing the dark, cyanotic color of the red reflex, as well as an increased number of vessels of the optic disc. He proposed that the cyanotic fundus in combination with the tortuosity of retinal vessels indicated a complex cyanotic heart defect involving pulmonary stenosis (later known as TOF). He emphasized the importance of the fundus exam in patients with cyanotic CHD [3].

Tyson described his own patient with findings suggestive of TOF . In addition to the characteristic fundus with violet color of cyanosis retinae , there was a bluish tint to the palpebral conjunctiva with dilation of conjunctival vessels encroaching on the cornea. Color fields were markedly contracted. Vision was 20/20 [4].


The incidence of congenital heart disease (CHD) varies depending on methodologies of research. The incidence of moderate to severe forms of CHD is about 6/1,000 live births. The incidence is as high as 75/1,000 live births if small, trivial lesions are included [1]. While the cause of most CHD is classically thought to be multifactorial in origin, genetic syndromes cause a significant number of cases. The prevalence of extracardiac malformations associated with CHD was reviewed in the Nationwide Inpatient Sample database from 1998 to 2008 by Egbe, et al. Their group found the total prevalence of extracardiac malformations to be 13.6 %. The prevalence for nonsyndromic malformations was 11.4 % and the prevalence for genetic syndromes was 2.2 %. The most common malformations involved the musculoskeletal, central nervous system, and renal-urinary systems. They hypothesized that the epidemiology of patients with congenital anomalies has been altered by changes in prenatal factors, such as termination of pregnancy for fetal anomalies and prenatal vitamin supplementation [5]. Indeed, other studies have found higher rates of extracardiac malformations , ranging from 25 to 44 % [6, 7].

It is not widely known, but many patients with CHD have a much higher incidence of ocular manifestations as well. In a review of 500 patients with CHD aged six days to fifteen years, Alfano noted that 14.4 % of these patients had an abnormality of either the eyes or the ocular adnexa [8]. A large number of recognizable syndromes consist of abnormalities involving multiple systems. The specific association of these abnormalities may be important in delineating the etiology and pathogenesis of the syndrome. The association of cardiac and eye defects is common in many of these multiple malformation syndromes. See Table 4.1 for a complete listing of disorders that contain cardiac and ocular abnormalities.

Table 4.1
Cardiac defects and associated eye defects


Eye abnormality

Cardiac abnormality

Chromosomal abnormality syndromes

Trisomy 21

(Down syndrome)

Up-slanted palpebral fissures, epicanthus, Brushfield spots with peripheral hypoplasia of iris, strabismus, high percentage of refractive errors, amblyopia, nystagmus, blepharitis, optic nerve abnormalities, cataract, glaucoma, acute keratoconus with corneal hydrops [41, 42]

Cardiac abnormalities in 40–65 %; most commonly atrioventricular septal defect , ventricular septal defect, also isolated atrial septal defect, patent ductus arteriosus, tetralogy of Fallot, aortic arch abnormalities, aberrant subclavian artery [43]

Trisomy 18 (Edwards syndrome)

Hypertelorism, hypoplastic supraorbital ridge, colobomatous microphthalmia, corneal opacity, cataract, microcornea, retinal depigmentation, congenital glaucoma [44, 45]

Cardiac abnormalities in > 90 %; most commonly ventricular septal defect , patent ductus arteriosus, atrial septal defect , also bicuspid aortic and/or pulmonic valve, pulmonic stenosis, coarctation of the aorta, transposition of the great arteries [46]

Trisomy 13 (Patau syndrome)

Colobomatous microphthalmia, cataract, corneal opacity , glaucoma, persistent fetal vasculature, intraocular cartilage, retinal dysplasia [44, 47]

Cardiac abnormalities in >80 %; ventricular septal defect , patent ductus arteriosus, atrial septal defect, dextroposition, in decreasing order of frequency [46]

Deletion 4p syndrome

Strabismus, iris coloboma, ocular hypertelorism, epicanthal folds [44]

Ventricular septal defect, patent ductus arteriosus [46]

Deletion 5p (Cri du Chat syndrome)

Hypertelorism , epicanthus, strabismus [44]

Ventricular and atrial septal defects , patent ductus arteriosus [46]

Deletion 13q syndrome

Epicanthal folds, ptosis, hypertelorism, microphthalmia, iris coloboma, retinoblastoma [44]

Ventricular septal defect, atrial septal defect [46]

Deletion 18q syndrome

Optic disc pallor, nystagmus, pigmentary retinopathy [44]

Cardiac defects of variable type in 25 %[46]

Trisomy 22 (Cat eye syndrome)

Coloboma; microphthalmia, macular hypoplasia, pale discs [44]

Cardiac abnormalities in 33 %; total anomalous pulmonary venous return, persistence of the left superior vena cava [46]

XO (Turner syndrome)

Strabismus in 33 %. Ptosis, hypertelorism, red-green color deficiency, epicanthus, downward-slanting palpebral fissures, blue sclera, nystagmus [44, 48]

Cardiac defects in about 20 %, the majority are coarctation of the aorta, bicuspid aortic valve, aortic stenosis [46]

Syndromes of very small stature, not skeletal dysplasia [46]

Cornelia de Lange syndrome

Long curly eyelashes, bushy eyebrows, synophrys; strabismus, myopia, ptosis [44]

Cardiac defects in about 30 %, most commonly ventricular septal defect [46]

Rubenstein-Taybi syndrome

Epicanthus, strabismus, refractive error, cataract, coloboma, ptosis, long eyelashes, hypertrichosis [44]

Cardiac abnormalities in 33 %; most commonly ventricular septal defect, patent ductus arteriosus most common [46]

Syndromes of moderate short stature, facial, ± genital defects [46]



Bilateral ptosis, epicanthus, strabismus [44]

Endocardial cushion defect, coarctation of the aorta, tetralogy of Fallot, ventricular septal defect , pulmonary valve atresia and stenosis [46]

Williams syndrome

Epicanthal folds, ocular hypertelorism, strabismus [46], hyperopia, retinal vascular tortuosity

Cardiac abnormalities in 75 %; most commonly supravalvular aortic stenosis, peripheral pulmonary artery stenosis, pulmonic valve stenosis, ventricular and atrial septal defect , also renal artery stenosis with hypertension, hypoplasia of the aorta [46]

Noonan syndrome

Ptosis of one or both eyelids , exophthalmos, hypertelorism, myopia, keratoconus, strabismus, nystagmus [13, 46, 49]

Cardiac defects in about 67 %. Most common are pulmonary stenosis, ventricular and atrial septal defects, patent ductus arteriosus, branch stenosis of pulmonary arteries [13, 46]

Syndromes with facial features as major feature [46]

Treacher-Collins syndrome

Lower lid coloboma [46]

Variable congenital heart defects in minority [46]

CHARGE association

Colobomatous malformation sequence in 80 %, ranging from isolated iris coloboma without visual impairment to clinical anophthalmos, most commonly retinal coloboma [46, 4951]

Cardiac abnormalities in 64 %; most commonly conotruncal defects (tetralogy of Fallot, double outlet right ventricle), aortic arch anomalies [49, 51, 52]

Storage disorders [46]

Hurler syndrome

Corneal clouding, ptosis, strabismus, thickened eyelids, glaucoma, pigmentary degeneration of retina [44]

Coronary artery disease, aortic and mitral insufficiency [53]

Scheie syndrome

Corneal clouding but central area less severely affected, open angle glaucoma, frequently in fourth to fifth decade [44]

Aortic valve disease [46, 53]

Hunter syndrome

Cornea usually clear, pigmentary degeneration of retina often seen [44]

Coronary artery disease, valvular disease [53]

Morquio syndrome (Types A, B)

Corneal clouding by age five to ten years [44]

Aortic valve disease [53]

Maroteaux-Lamy syndrome

Corneal clouding in early life [44]

Aortic valve disease [53]

Connective tissue disorders [46]

Marfan syndrome

Lens subluxation, increased axial globe length, myopia, retinal detachment [44, 54]

Ascending aorta dilatation, mitral valve prolapse, mitral regurgitation, aortic regurgitation, aortic dissection [46]


Dislocated lenses, cataract, secondary glaucoma, peripheral cystic degeneration of retina [44]

Arterial and venous thrombosis, medial degeneration of the aorta and large arteries [46]

Ehlers-Danlos syndrome

Epicanthal folds, blue sclera, keratoconus, lens subluxation, retinal detachment [44]

Mitral valve prolapse ± tricuspid valve prolapse, aortic root and/or sinus of Valsalva dilatation, increased susceptibility to dissecting aneurysm [46]

Hamartoses [46]

Incontinentia pigmenti

Peripheral retinal nonperfusion [44]

Patent ductus arteriosus, hypertension [46]

Tuberous sclerosis syndrome

Hamartomatous tumors of the disc and retina, intracranial lesions producing papilledema or optic atrophy [55]

Myocardial rhabdomyoma [46]


Neurofibromas within the soft tissues of the lids and orbits, visual pathway glioma, Lisch nodules [55]

Coarctation of the aorta, renal artery stenosis [46]

Multiple lentigines (LEOPARD) syndrome

Hypertelorism, ptosis [46, 56]

Hypertrophic cardiomyopathy, mostly involving the left ventricle, pulmonic stenosis, ECG conduction abnormalities (prolonged PR interval) [46, 56]

Environmental agents [46]

Fetal alcohol syndrome

Tortuosity of retinal vessels, optic nerve hypoplasia or atrophy, esotropia on downward gaze, blepharophimosis, hypotelorism, ptosis, epicanthus, thickened eyebrows [44]

Ventricular septal defect , atrial septal defect, tetralogy of Fallot, coarctation of the aorta [46]

Fetal hydantoin syndrome

Epicanthus, mild hypertelorism, ptosis, strabismus [44]

Pulmonary or aortic valvular stenosis, coarctation of the aorta, patent ductus arteriosus, septal defects [46]

Congenital rubella syndrome

Ocular abnormalities in 78 %; most commonly retinopathy, cataract, strabismus, nystagmus, microphthalmia, also glaucoma, coloboma, optic atrophy, corneal opacity, dacryostenosis [57]

Cardiac abnormalities in 58 %; most commonly patent ductus arteriosus, pulmonic stenosis, ventricular septal defect; also tetralogy of Fallot, coarctation of the aorta, mitral stenosis, atrial septal defect [57]


Arteriohepatic dysplasia (Alagille) syndrome

Posterior embryotoxon [46]

Peripheral pulmonic stenosis, atrial and ventricular septal defect, patent ductus arteriosus, coarctation of the aorta [46]

Leber congenital amaurosis syndrome

Poor vision with often normal-appearing fundus, markedly reduced or absent electroretinogram, chorioretinal degeneration later in life [44, 58]

Dilated cardiomyopathy [58]

Kearns-Sayre syndrome

Chronic progressive external ophthalmoplegia with ptosis presenting in childhood, pigmentary degeneration of the retina [5962]

Atrioventricular block [59, 60, 63]

Kartagener syndrome

Retinal pigmentary degeneration, cataract [44]

Dextrocardia, heart block [46]

Goldenhar (Oculo-Auriculo-Vertebral) syndrome

Epibulbar dermoid involving conjunctiva and cornea, coloboma of upper lid, strabismus, lacrimal drainage system anomalies [44, 64]

Most commonly tetralogy of Fallot, also ventricular septal defect [46, 65]

Axenfeld-Rieger syndrome (FOXC1 mutation)

Anterior segment abnormalities, glaucoma [46, 66]

Valve abnormalities, atrial septal defect [46]

Bardet-Biedl syndrome

Pigmentary retinopathy [46]

Aortic stenosis [46]

Mowat-Wilson syndrome

Microphthalmia, coloboma, Axenfeld anomaly, pupillary atrophy, ptosis, cataract, retinal aplasia, strabismus, nystagmus [46, 67]

Cardiac abnormalities in 45 %; patent ductus arteriosus, atrial septal defect , ventricular septal defect , tetralogy of Fallot, pulmonary atresia, pulmonary stenosis, aortic valve abnormalities [46, 67]

PHACES syndrome

Ocular abnormalities in 33 %; morning glory disc, choroidal hemangiomas, cryptophthalmos, exophthalmos, colobomas, posterior embryotoxon, optic atrophy, microphthalmia, strabismus, cataract, glaucoma, optic nerve hypoplasia [68]

Cardiac abnormalities in 44 %; aortic aneurysm, coarctation of the aorta, arterial anomalies [69]

Graves disease

Ocular abnormalities in 50 %; lid retraction, proptosis, mild corneal exposure, chemosis, fat pad enlargement, restrictive strabismus [70, 71]

Sinus tachycardia, mitral valve prolapse, and mitral regurgitation [72]

Systemic Manifestations

Heart disease presents in the newborn and young infant in a variety of ways, including respiratory distress, cyanosis , shock, arrhythmia, and heart murmur. The older infant or child generally presents with feeding difficulties, tachypnea, failure to thrive, and heart murmur. Many children with CHD are asymptomatic. Diagnostic modalities include electrocardiography, echocardiography, cardiac catheterization, and cardiac magnetic resonance imaging. Echocardiography is the primary diagnostic tool used to define cardiac anatomy in children.

Rare complications of CHD include stroke and cerebral abscess. Stroke tends to occur in young children less than two years of age, and the predisposing conditions include endocarditis, a right to left shunt that allows paradoxical emboli to the brain, and increased blood viscosity. Neurologic signs include acute hemiplegia, local or generalized seizures, and ataxia. Cerebral abscess results from a local suppurative infection of brain tissue, and the most important mechanism predisposing to this condition is the right to left shunting of blood. Signs of increased intracranial pressure are predominant in cerebral abscess. Neuro-ophthalmologic signs may be common to both, including papilledema, third and sixth cranial nerve palsies resulting in diplopia, abnormal pupillary findings, and ptosis [9].

Infective endocarditis is defined as a bacterial or fungal infection of the endocardium, heart valves, or related structures. Risk factors for endocarditis include congenital heart disease, intravascular hardware such as central venous catheters, intravenous drug use, immunosuppression, and a previous diagnosis of endocarditis. The American Heart Association recommends antibiotic prophylaxis prior to procedures known to cause bacteremia for people with cyanotic heart disease, a previous diagnosis of endocarditis, within six months of intracardiac surgery, after surgery for congenital heart disease with a residual lesion adjacent to prosthetic material, or after cardiac transplantation with valvulopathy. The most common presenting symptoms include prolonged fever, malaise, and arthralgias. Common exam findings include weight loss, splenomegaly, petechiae, new or changing heart murmur , heart failure, and embolic events. Emboli to the cerebral circulation are not very common [10].

Ophthalmic Manifestations

A prospective study from 1968 attempted to define the types of eye defects in a group of 85 children with various types of both cyanotic and acyanotic heart disease [11]. This study had some notable design flaws: these children were all over the age of six years, had no major congenital malformations, and the study was completed before corrective cardiac surgery was available for many of these heart defects. The eye conditions that were surveyed were amblyopia, strabismus, structural defects, and refractive anomalies.

Patients with cyanotic disease, including tetralogy of Fallot (TOF) and dextrotransposition of the great arteries (TGA), had the highest incidence of ophthalmic abnormalities at 86 %. Patients with acyanotic lesions characterized by obstruction including aortic stenosis and pulmonary stenosis, had a 64 % incidence of eye abnormalities. Acyanotic left to right shunts, such as atrial septal defect , ventricular septal defects, and patent ductus arteriosus had ophthalmic abnormalities in 49 % [11].

All four types of ophthalmic defects were more common in the cyanotic patients. The overall incidence of strabismus was 14 %, but this incidence doubled in the cyanotic patients at 28 %. Structural defects were highest in the cyanotic patients. Amblyopia was present in one or both eyes of 50 % of the cyanotic TOF patients. In contrast, only 15 % of children with other heart lesions had amblyopia. Overall, 12 % were hyperopic and 24 % myopic. In cyanotic TOF patients, 38 % were myopic [11].

This study required strict criteria for eye normality, and many of these eye defects were minor and did not require intervention. The eyes of children with left to right shunts were probably little different from normal populations since many of their defects were of a trivial nature. The results as a whole showed a trend for more ocular lesions in the acyanotic obstructive group, and an even higher incidence in cyanotic patients [11].

Of the total group of 85 children, 23 had eye lesions reducing their visual acuity to 6/18 or less. With thorough ophthalmologic evaluation nine of these patients had severe visual defects not detected previously. The authors concluded that screening exams were certainly warranted in cyanotic patients [11]. In the modern era it is difficult to generalize these data to current practice, however, because medical and surgical therapy for most forms of congenital heart disease is quite different now than it was in 1968.

Several investigators have noted the association of ptosis with CHD [1214]. Larned reviewed the records of 156 cases of congenital ptosis that presented to the pediatric ophthalmologic clinic at a major eye hospital [12]. Seven cases of documented structural heart defects were detected, with an observed frequency of 4.4 % (five times the incidence of CHD in the general population). Of note was the fact that all the heart defects were acyanotic, which was also noted in the 12 patients described by Sonoda [14]. The conclusion of these investigators is that the association of ptosis with acyanotic heart disease might be specific, but the etiology of this association is unknown [12].

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Jul 20, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Ocular Manifestations of Cardiac Disease

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