Chapter 22
Ocular Abnormalities in Acquired Heart Disease
SUNIR J. GARG, ARUNAN SIVALINGAM, JAMES BOLLING, RICHARD E. GOLDBERG, JOCELYN SIVALINGAM and LARRY MAGARGAL
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INFECTIVE ENDOCARDITIS
NONBACTERIAL THROMBOTIC ENDOCARDITIS
MITRAL VALVE PROLAPSE
AORTIC ARCH SYNDROME
REFERENCES

In contrast to congenital heart disease, in which patients have cyanotic ocular findings (dilated, tortuous veins with or without retinal edema), patients with acquired cardiac diseases usually have symptoms secondary to embolic phenomena. These symptoms may vary from transient visual obscuration to complete visual loss. The major categories of acquired heart disease that have ocular findings include infective endocarditis, nonbacterial thrombotic endocarditis, myxoma, mitral valve prolapse, and aortic arch syndrome, including inflammatory conditions that affect the major arteries, specifically Takayasu's disease and syphilis. Ocular signs of these disorders include white-centered retinal hemorrhages (Roth spots), cotton wool spots, capillary nonperfusion, branch and central retinal artery obstruction, collateral arteriovenous communications, and endogenous endophthalmitis.
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INFECTIVE ENDOCARDITIS
Infective endocarditis is infection of the heart's endothelial lining classically manifested by vegetations on the cardiac valve surface. The development of endocarditis depends upon several factors. The valve surface must be altered to allow for colonization. The surface can be altered by blood turbulence, hypercoagulable states, congenital cardiac disease, rheumatic and degenerative valvular disease,1–4 intravenous drug abuse,5–7 prosthetic heart valves,8,9 indwelling catheters, and pacemaker wires.6–9 The damaged endothelial cell surface triggers local deposition of fibrin and platelets, which produce the vegetations that characterize thrombotic endocarditis. The vegetations usually are located along the line of closure of the valve leaflet. Infective endocarditis develops when circulating microorganisms colonize the vegetation.10 Streptococcus spp. (viridans), Staphylococcus aureus, coagulase-negative Staphylococci, and Enterococci are the most common pathogens responsible for infective endocarditis. Escherichia coli, salmonella, klebsiella, and fungi also have been found.11

Endocarditis may present with myriad nonspecific symptoms, including malaise, fevers, chills, night sweats, anorexia, and dyspnea.1 On systemic examination, patients may have a heart murmur, splenomegaly, and petechial hemorrhages in their mouth or on their skin. Larger, painless, hemorrhagic macules on the palms and soles are called Janeway lesions, whereas painful nodules on the fingers and toes are called Osler nodes. The laboratory findings include anemia and leukocytosis. The erythrocyte sedimentation rate and C-reactive protein levels may be elevated and urinary abnormalities, such as proteinuria and hematuria, are frequent. At least three sets of sterile cultures should be drawn within 24 hours. Positive blood cultures are present in more than 90% of cases. Cardiac echography is helpful; transthoracic echography has excellent specificity for detecting endocarditis (98%) but variable sensitivity. If clinical suspicion is still high despite a negative transthoracic echocardiogram, transesophageal echocardiography can be performed. It has a higher sensitivity than transthoracic echocardiography, with excellent specificity as well.12,13

Both cardiac and extracardiac complications of endocarditis can occur. Cardiac complications vary from arrhythmia to cardiac failure.14 The extracardiac manifestations usually result from thromboembolic phenomena. Distant embolization causes arterial obstruction, with resultant ischemia and tissue infarction, localized abscesses, and mycotic aneurysm formation. Central nervous system manifestations of infectious endocarditis include stroke, transient ischemic attack, brain abscess, meningitis, or mycotic aneurysm.15–20

Conjunctival petechial hemorrhages, iris abcesses,21 superficial or deep retinal hemorrhages,22 focal abscesses, vasculitis, choroidal neovascular membrane formation, and endogenous endophthalmitis23,24 are the major complications of infective endocarditis. The classic ocular sign of infective endocarditis is a Roth spot (a white-centered hemorrhage; see Fig. 1). The white center is believed to be either a focal microabscess caused by a septic embolus or a fibrin and platelet clot, as seen in other disorders, such as leukemia (Fig. 2). 25 Retinal arteriole occlusion may produce cotton wool spots, and branch or central retinal artery obstruction.26,27 The inflammatory emboli also can cause a choroiditis that can lead to choroidal neovascular membrane formation.28 Endogenous endophthalmitis is the most severe ocular complication of infective endocarditis. The treatment of endogenous endophthalmitis usually involves identification of the underlying organism and aggressive systemic treatment with the appropriate antibiotics. If there is clinical evidence of virulent endophthalmitis associated with significant vitritis or hypopyon (Fig. 3), the physician also should consider intravitreal antibiotics, possibly in conjunction with pars plana vitrectomy.29 Several small, retrospective, nonrandomized reports suggest that systemic treatment with vitrectomy and intravitreal antibiotics may have better visual results than systemic treatment alone.30,31 Conversely, endogenous endophthalmitis may be the initial presenting sign of infectious endocarditis in a small subset of patients. A full systemic evaluation, including cardiac ultrasonography, should be performed in all patients with endogenous endophthalmitis.

Fig. 1. A. Roth spots in endocarditis. Note Roth spot (white centered hemorrhage) superonasal to the macula. There are associated intraretinal hemorrhages as well. (Photo from Retina Service of Wills Eye Hospital Photo collection.) B. More extensive and prominent Roth spots. (Photo from Retina Service of Wills Eye Hospital Photo collection.)

Fig. 2. Histopathology of a Roth spot. The white center is called a cytoid body, and it is a fibrin-platelet clot. (Courtesy of Mort Smith, MD, St. Louis, MO.)

Fig. 3. Endogenous endophthalmitis usually presents with a red, uncomfortable eye. There is a hypopyon present. This patient had endogenous Moraxella endophthalmitis.

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NONBACTERIAL THROMBOTIC ENDOCARDITIS
Nonbacterial (noninfective) thrombotic endocarditis (NBTE), also known as marantic endocarditis, is characterized by white or tan masses made up of fibrin, platelets, erythrocytes, and leukocytes. Unlike infective endocarditis, the masses of NBTE are sterile. This condition is usually seen in severely ill patients and is often associated with pancreatic adenocarcinomas. It also has been seen in patients with other conditions that cause hypercoagulable states, including systemic lupus erythematosus, sepsis, severe burns, AIDS, and the antiphospholipid antibody syndrome.32–34 Injury to the endocardium, such as from indwelling catheters, can predispose patients to this condition.35

The two main complications of NBTE are valve damage and embolic events. Valve damage often causes cardiorespiratory difficulties resulting from hemodynamic alterations. Emboli can cause infarctions of many organ systems, including the kidney, central nervous system, and gastrointestinal tract. The size of the vegetations varies from microscopic to about 4 mm. Autopsy studies have shown systemic embolization in approximately 40% of patients with NBTE.34,36

The ocular findings of NBTE include intraretinal hemorrhages, and branch (Fig. 4) and central retinal artery occlusion.37 Patients also may present with visual disturbances resulting from stroke, including gaze and visual field abnormalities.38,39

Fig. 4. A branch retinal artery occlusion (BRAO) from a cardiac calcification. The white color is more commonly seen from cardiac source. Emboli from the carotid artery are usually atherosclerotic in nature, and thus appear more yellow. (Photo from Retina Service of Wills Eye Hospital.)

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MITRAL VALVE PROLAPSE
Mitral valve prolapse syndrome has been given many names, including myxomatous mitral valve syndrome, systolic click-murmur syndrome, Barlow syndrome, and floppy valve syndrome.40–42 Historically, the prevalence of mitral valve prolapse in the general population was estimated to be as high as 5% to 10%,43,44 but more recent studies suggest that the prevalence is around 3%.45 It is twice as common in women as in men, but older men often have more severe clinical symptoms because of mitral valve regurgitation.46 Mitral valve prolapse may occur as an isolated finding or may be associated with other systemic conditions, including connective tissue diseases (Marfan's and Ehlers-Danlos syndromes), collagen vascular diseases, rheumatic heart disease, congenital heart disease, and coronary heart disease.47,48 The underlying defect within the valve is unknown. Histopathology reveals myxomatous proliferation of the middle layer of the valve leaflet.48,49 Other investigators have noted that the quantity of acid mucopolysaccharide is increased, possibly secondary to an unidentified abnormality of collagen metabolism.50,51

Most patients with mitral valve prolapse are asymptomatic. Some patients report syncope, palpitations, or atypical chest pain.52 The diagnosis of mitral valve prolapse may be made on physical examination as well as by echocardiography. A systolic click is heard on cardiac auscultation. The click sometimes is followed by a mid- to late-systolic murmur, depending on the severity of mitral regurgitation.49 Echography is very helpful in establishing the diagnosis.53 Recent evidence suggests that a transesophageal echocardiogram may be more sensitive for the diagnosis of mitral valve prolapse than transthoracic echography.54

Abnormal hemodynamics on the valve surface promote platelet coagulation and subsequent platelet emboli, which can lead to cerebral and retinal ischemic events. Central nervous system complications vary from transient ischemic attacks to strokes. Ocular complications from mitral valve prolapse include amaurosis fugax and central and branch retinal artery occlusions.55–57 It is believed that these complications occur secondary to platelet emboli. As mentioned earlier, some believe that mitral valve prolapse is a manifestation of a generalized collagen disorder. There have been conflicting reports of an association between mitral valve prolapse and keratoconus.58,59 Patients with mitral valve prolapse also may have unusually deep anterior chamber angles with prominent iris processes.60

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AORTIC ARCH SYNDROME
Aortic arch syndrome is caused by diseases that affect the proximal aorta and the major branches of the aortic arch, including the innominate, left common carotid, and subclavian arteries. Abnormalities of the aortic arch and these major tributaries can be seen in patients with atherosclerosis, collagen vascular disease, and inflammatory diseases such as tuberculosis, syphilis,61 polyarteritis nodosa, and Takayasu's disease.

The ocular manifestations of aortic arch disease depend upon the underlying condition, the site of occlusion, and the pattern of blood flow. Widening of the aortic arch, as seen in tertiary syphilis, may be associated with aortic valve insufficiency and may produce ocular manifestations of valvular disease, such as calcific emboli and endocarditis. Retinal arteriovenous crossing changes, widening of the arterial light reflex, and arterial narrowing are seen in atherosclerosis and polyarteritis nodosa.

Signs of ocular ischemia and hypoperfusion may be seen in aortic arch syndrome. At an early stage, venous dilation, venous beading, cotton wool spots, and microaneurysms may occur. Retinal artery pressures are uniformly low in patients whose circulation is reduced enough to cause ocular signs and symptoms. Peripheral retinal hemorrhages followed by nonperfusion of the peripheral retina often precede the development of retinal neovascularization. Neovascularization of the iris with resultant neovascular glaucoma is a potentially devastating complication of hypotensive oculopathy.62 Signs of ocular inflammation, such as vascular injection, flare in the anterior chamber, and cataract formation, are also seen in the later stages of this disease.

Takayasu's disease (also known as pulseless disease) is a chronic granulomatous vasculitis of the large arteries that causes narrowing and occlusion of the major branches of the aorta, including the carotid arteries. This condition typically occurs in young women, and it may be associated with scleritis or iritis.63 It also may cause hypotensive retinopathy that has been divided into four stages: stage 1, dilation retinal vessels; stage 2, microaneurysm formation; stage 3, arteriovenous anastomosis; and stage 4, blinding complications as a result of profound ocular ischemia, including retinal detachment, vitreous hemorrhage, neovascular glaucoma, optic atrophy,64 and cataract.65

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REFERENCES

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