Hypertensive Retinopathy - Yanoff and Duker

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Yanoff & Duker: Ophthalmology, 3rd ed.

Copyright 2008 Mosby, An Imprint of Elsevier

section5 VASCULAR DISORDERS

Chapter 6.15 Hypertensive Retinopathy

Adam H. Rogers

CHRONIC HYPERTENSIVE RETINOPATHY

MALIGNANT ACUTE HYPERTENSIVE RETINOPATHY

Definition: Retinal vascular changes occurring from chronically elevated systemic arterialhypertension.

Key features

Narrowing and irregularity of retinal arteries.

Arteriovenous nicking (narrowing of retinal veins at arteriovenous crossing sites).

Blot retinal hemorrhages.

Microaneurysms.

Cotton-wool spots.

Associated features

Retinal venous obstruction.

Retinal neovascularization.

Retinal arterial emboli.

Definition: Retinal, choroidal, and optic nerve changes secondary to acutely elevated

systemic arterial blood pressure.

Key features

Retinal arteriolar spasm.

Superficial retinal hemorrhages.

Cotton-wool spots.

Serous retinal detachment.

Optic disc edema.

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INTRODUCTION

Hypertensive retinopathy represents the ophthalmic findings of end-organ damage secondary to

systemic arterial hypertension. Although its name implies only retinal involvement, changes inboth the choroid and the optic nerve are observed, depending on the chronicity and severity of

the disease. Ocular changes in malignant hypertension can be striking, with optic neuropathy,choroidopathy, and retinopathy. Changes from essential hypertension are subtler, affecting

primarily the retinal vasculature. Because hypertension is so prevalent in industrialized countries,hypertensive retinopathy is a common condition encountered by all ophthalmologists and health-

care professionals.

EPIDEMIOLOGY AND PATHOGENESIS

Systemic arterial hypertension is one of the most common diseases of adults in industrializedcountries. Although the medical literature subdivides hypertension into multiple groups, only

essential (primary) and malignant hypertension are relevant to a discussion of hypertensiveretinopathy. Essential hypertension is of unknown cause and is diagnosed when the average

blood pressure measures greater than 140mmHg systolic or 90mmHg diastolic on at least two

subsequent visits. In the United States alone, it is estimated that more than 25% of all adults and

60% of persons older than 60years are affected. Blacks have a higher prevalence ofhypertension than whites, and men are affected more than women. [1] However, over age 50,women have a higher prevalence than men. [2] Elevated blood pressure is rare in agrarian

societies and in individuals who are physically active. [1]

Because high blood pressure is an asymptomatic disease, most patients remain undiagnosed or

inadequately treated despite the relative ease of detection. In the National Health and NutritionStudy (NHANES III) that evaluated hypertensive adults aged 18-74years, 68.4% were aware of

their hypertension, 53.6% were receiving treatment, and only 27.4% had their hypertension under

control. [3] Untreated or inadequately treated hypertension carries significant cardiovascular

mortality. In patients with borderline hypertension, the relative risk of cardiovascular disease and

end-stage renal disease is nearly double compared with patients with optimal blood pressure. [4]

The incidence of hypertensive retinal changes is variable and is often confounded by thepresence of other retinal vascular disease, such as diabetes. In the Beaver Dam Eye Study, [5]

which evaluated hypertensive patients without coexisting, confounding vascular diseases, the

overall incidence of hypertensive retinopathy was about 15%; specifically, 8% showedretinopathy, 13% showed arteriolar narrowing, and 2% showed arteriovenous nicking. The

predictive value of diagnosing systemic hypertension from ophthalmic findings on examinationwas only 4753%, demonstrating that measurement of blood pressure is a more accurate means

of diagnosis. The highest frequency of hypertensive retinopathy in the study population was

identified in subjects with poor blood pressure control

Malignant hypertension is a rare syndrome consisting of rapid and severe elevation of blood

pressure, with the systolic component above 200mmHg or the diastolic blood pressure greaterthan 140mmHg. Although the absolute blood pressure measurement is important, the presence

of systemic findings defines malignant hypertension. These include ocular, cardiac, renal, andcerebral injury. Persistently elevated malignant hypertension can lead to a rapidly fatal course,

Associated features

Choroidal ischemia.

Retinal pigment epithelial changes.

Optic neuropathy.

Cortical blindness.

Proteinuria, stroke, kidney failure, encephalopathy.




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with heart failure, myocardial infarction, stroke, or renal failure. [1]

Nearly 1% of hypertensive patients develop malignant hypertension, and it is rare for patients topresent initially with this form of elevated blood pressure. Most have a pre-existing diagnosis of

either primary or secondary hypertension. Malignant hypertension rarely occurs in individuals

receiving treatment for hypertension. The average age at diagnosis is 40years, with men affected

more than women. With the advent of effective antihypertensive treatment, nearly 50% of

patients survive more than 5years. [6]

Heredity and environmental factors have been implicated in the pathogenesis of essentialhypertension. In the elderly, an increase in basal smooth muscle tone occurs as a result of

sympathetic overactivity with increases in the renin-angiotensin system. Other factors include salt

sensitivity, low systemic calcium, and insulin resistance with hyperinsulinemia. [7] Secondaryhypertension is due to an identifiable cause, usually related to an alteration in hormone secretion

or renal function. With correction of the underlying cause, this form of hypertension can be cured.[6] The pathogenesis of malignant hypertension, similar to essential hypertension, is unknown.

Research has focused on overactivity of the renin-angiotensin-aldosterone system, with high

plasma renin-angiotensin levels as the cause. [7]

OCULAR MANIFESTATIONS

Chronic Hypertensive Retinopathy

Patients with hypertensive retinopathy are usually asymptomatic. Common clinical findings

include focal constriction and dilatation of the retinal arterioles, tortuosity of the retinal arterioles,

an increase in the arteriolar light reflex, and loss of transparency of the intra-arterial blood column( Fig. 6-15-1 ). Arteriovenous nicking is a highly specific finding and the hallmark of chronic

hypertensive retinopathy. At the arteriovenous crossings in the retina, the vessels share acommon adventitial sheath. Arteriovenous nicking is diagnosed when the crossing retinal vein

becomes less apparent or even disappears on either side of the artery ( Fig. 6-15-2 ). The course

of the vein may change to a more perpendicular direction as well. If there is impedance to flow,

the segment of the vein distal to the constriction appears larger, darker, and more tortuous.Additional signs of impedance to flow are retinal hemorrhages, macular edema, and cotton-woolspots ( Fig. 6-15-3 ). In areas of frank obstruction, the presence of venous-venous collaterals

may be long standing. Secondary ocular complications of chronic systemic arterial hypertensioninclude retinal vascular occlusive disease, macroaneurysm formation, and nonarteritic anterior

ischemic optic neuropathy. [8] For the differential diagnosis, see Box 6-15-1 .




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Fig. 6-15-1 Mild to moderate chronic hypertensive retinopathy. Note the color change in the retinal arterioles and the

early arteriovenous crossing changes.

Fig. 6-15-2 In this 15 view, note the arteriovenous crossing changes, presence of collateral vessels, and dilated

capillary bed.




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BOX 6-15-1

The appearance of the ocular fundus in hypertension is related directly to the status of the retinalarteries and the rate of rise and degree of systemic blood pressure. The age of the patient maycomplicate interpretation of the clinical fundus changes. Although arteriolar sclerosis is a finding

of long-standing hypertension, these changes, categorized as involutional sclerosis, also occur in

the normal aging population. [9] With atherosclerosis alone, mild thickening of the arteriolar wall

occurs. Clinically, focal narrowing and straightening of the retinal arterioles are seen in the

absence of arteriovenous crossing changes. [10] Because the chronic effects of elevated systemicblood pressure occur along with arteriosclerotic thickening of the blood vessel walls, it can be

difficult to categorize fundus changes solely on the basis of elevated blood pressure.

Malignant Hypertensive Retinopathy

Visual disturbances are common in malignant hypertension. Symptoms include headache,scotoma, diplopia, dimness in vision, and photopsia. [11] Ocular findings in malignant arterial

hypertension are divided into three distinct categories: hypertensive retinopathy, hypertensivechoroidopathy, and hypertensive optic neuropathy. The causes of these clinical findings includes

Fig. 6-15-3 A 60 view of the same patient as shown in Fig. 6-15-2 . Note the telangiectatic vessels on the optic nerve

head and intraretinal hemorrhages temporal to the macula.

Differential Diagnosis of Chronic Hypertensive Retinopathy

Diabetic retinopathy

Retinal venous obstruction

Hyperviscosity syndromes

Congenital hereditary retinal arterial tortuosity

Ocular ischemic syndrome

Radiation retinopathy




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constriction of vascular beds from circulating catecholamines, obstruction of arterioles, and

breakdown in the blood-retina barrier. Ophthalmic findings in acute malignant hypertensive

retinopathy include focal arteriolar narrowing, cotton-wool spots, intraretinal transudates, macular

edema, and retinal hemorrhages. Retinal hemorrhages are linear, occurring in the nerve fiber

layer in the peripapillary region. Cystoid macular edema, lipid deposits, and arteriolar changesare signs of more chronic malignant hypertensive retinopathy. [12]

Arteriolar narrowing observed on ophthalmoscopy has been challenged by Hayreh, who refers tothis clinical finding as pseudonarrowing secondary to retinal edema creating a visual effect of

narrowing of the retinal arteriole. Fluorescein angiography performed in rhesus monkeys withacute malignant hypertension has demonstrated normal retinal arteriolar caliber, casting doubt on

the long-standing belief that arteriolar spasm occurs. [13] Cotton-wool spots are fluffy, elevated,

tanwhite areas of retinal opacity occurring within a few disc diameters of the optic nerve, causedby occlusion of terminal retinal arterioles. Capillary nonperfusion is present on angiography ( Fig.

6-15-4 ). Cotton-wool spots typically resolve in 36weeks and are associated with permanentnerve fiber layer loss in the vicinity of the lesion. [12] Periarteriolar intraretinal transudates are tan

white retinal lesions occurring in the vicinity of an arteriole. The lesions measure about onequarter of the disc area but are clinically larger, as they coalesce with adjacent lesions.

Intraretinal transudates occur secondary to focal areas of arteriolar leakage identified on

angiography and resolve without residual retinal damage in 23weeks. [14] Macular edema andsubretinal fluid are retinal findings related to hypertensive choroidal changes affecting the retinal

pigment epithelium (RPE), with alterations in the blood-retina barrier.




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Clinical changes from hypertensive choroidopathy are directly related to the release ofendogenous vasoconstrictor agents (e.g., angiotensin II, epinephrine, vasopressin) duringsystemic hypertension. Angiographically, there is delayed, patchy choroidal filling. [12] Gitter et al.

[15] demonstrated through the use of fluorescein angiography that the delay in choroidal filling isfollowed by late leakage from choroidal vessels into the subretinal space. The leakage is

enhanced by infarction and damage to the RPE cells or transudation of fluid into the subretinal

space in response to increased pressure in the choroidal vessels. [16] [17] Focal occlusion of the

choriocapillaris leads to necrosis and atrophy of the RPE, forming Elschnigs spots ( Fig. 6-15-

5 ). [18] [ 19] Acutely, Elschnigs spots are punctate, tanwhite lesions that leak on fluorescein andindocyanine green angiography from breakdown in the bloodretina barrier. Subretinal fluid

accumulates, with the eventual formation of macular edema, a common finding associated withhypertensive choroidopathy [14] ( Fig. 6-15-6 ). With time, the focal RPE lesions become confluent

and more extensive. Diffuse pigmentary changes with atrophy give a mottled appearance onophthalmoscopy. Linear configurations of pigmentation along choroidal arteries are known asSiegrists streaks. [19]

Fig. 6-15-4 The right eye of the same patient as shown in Figs. 6-15-2 and Fig. 6-15-3 . (A) A prominent cotton-wool spot

in the papillomacular bundle is seen, with an adjacent intraretinal hemorrhage. (B) Fluorescein angiography shows capillary

nonperfusion in the area corresponding to the cotton-wool patch; note the hypofluorescence of the intraretinal hemorrhage,

caused by blockage.

Fig. 6-15-5 Elschnigs spots.




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Hypertensive optic neuropathy presents clinically as disc edema ( Fig. 6-15-7 ). This occurs from

vasoconstriction of the posterior ciliary arteries supplying the optic nerve head, resulting from the

release of angiotensin II and other vasoconstricting agents. Ischemia occurs in the optic nerve,leading to stasis of axoplasmic flow, which is a form of anterior ischemic optic neuropathy. [20] Forthe differential diagnosis, see Box 6-15-2 .

Fig. 6-15-6 Serous detachment of the retina in a 27- ear-old patient who has pregnancy-induced hypertension, 3

days post partum. Blood pressure measured 158/100 mmHg. Note the subretinal fibrin and folds in the retina. (Courtesy of

Franklin L. Myers.)




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described earlier are more common in malignant hypertension. Measurement of systemic blood

pressure is necessary to rule out other causes with similar clinical pictures.

Several classification schemes have been used to stage hypertensive retinal changes. The two

most widely accepted are the Keith-Wagener-Barker classification and the Scheie classification.

The Keith-Wagener-Barker scheme ( Table 6-15-1 ) combines the clinical findings of

hypertension and atherosclerosis. [21] The Scheie classification ( Table 6-15-2 ) keeps the two

disease processes separate. [22] Unfortunately, no classification is satisfactory because of thehigh variability of clinical findings. [23] They are of historical value only and are not used clinically;

accurate description of the ocular findings is more valuable than any classification system.

Table 6-15-1 -- KEITH-WAGENER-BARKER CLASSIFICATION

Group 1 Mild-to-moderate narrowing or sclerosis of the arterioles

Group 2 Moderate to marked narrowing of the arterioles

Local and/or generalized narrowing of arterioles

Exaggeration of the light reflex Arteriovenous crossing

changes

Group 3 Retinal arteriolar narrowing and focal constriction

Retinal edema Cotton-wool patches

Hemorrhage

Group 4 As for Group 3, plus papilledema

(Adapted from Walsh JB. Hypertensive retinopathy. Description, classification and prognosis.Ophthalmology. 1981;89:112731.)

Table 6-15-2 -- SCHEIE CLASSIFICATION

Although newer imaging techniques, such as scanning laser ophthalmoscopy, allow

quantification of retinal capillary density and flow velocity in patients who have essentialhypertension, these results are still preliminary in terms of their application to the long-term

prevention of retinal disease. [21] Optical coherence tomography may be used to evaluate cross-

sectional images of the retina and subretinal fluid collections. [24]

SYSTEMIC ASSOCIATIONS

HYPERTENSION

Grade 0 No changes

Grade 1 Barely detectable arteriolar narrowing

Grade 2 Obvious arteriolar narrowing with focal irregularities

Grade 3 Grade 2 plus retinal hemorrhages and/or exudates

Grade 4 Grade 3 plus papilledema

ARTERIOLAR SCLEROSIS

Grade 0 NormalGrade 1 Barely detectable light reflex changes

Grade 2 Obvious increased light reflex changes

Grade 3 Copper-wire arterioles

Grade 4 Silver-wire arterioles

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Essential hypertension is the most common cause of chronically elevated blood pressure and is

typically of unknown cause. Screening for secondary systemic causes is not pursued unlessother symptoms are present or the hypertension is resistant to treatment. The causes of

secondary hypertension include pheochromocytoma, renovascular stenosis, and primary

hyperaldosteronism. [1] [7]

In nearly all cases of malignant hypertension, a systemic cause can be elucidated via systemicevaluation. Potential causes include renal disease, such as polycystic kidney or renovascular

stenosis; pheochromocytoma; and pregnancy. Rarely, untreated essential hypertension may leadto an acute hypertensive crisis. Systemic abnormalities accompany accelerated hypertension

with evidence of end-organ damage, including acute left ventricular heart failure, myocardial

infarction, pulmonary edema, dissecting aortic aneurysm, stroke, encephalopathy, andintracranial hemorrhage. [1] [7]

PATHOLOGY

Microscopically, early changes from hypertension demonstrate sclerosis and thickening of thearteriolar walls with luminal narrowing. These findings become more prominent with long-

standing systemic hypertension. Arteriole thickening in the choroidal vessels is typically moresevere than in the retinal arterioles and more closely resembles systemic arterial changes. [19] In

malignant hypertension, the arterioles are similarly thickened, but necrosis and fibrinoid

deposition in the vessel wall occur. Electron micrographs of retinal arterioles in malignanthypertension eventually demonstrate dilatation of the lumen, with focal breaks in the endothelium

surrounded by lipid and fibrin, as the autoregulatory mechanisms of the arterioles areexceeded. [14] [ 19] Other pathological findings include optic nerve edema, cotton-wool spots,

microaneurysms, and focal infarcts. [19]

TREATMENT, COURSE, AND OUTCOME

By itself, chronic hypertensive retinopathy rarely, if ever, results in significant loss of vision.Treatment of the underlying systemic condition can halt the progress of the retinal changes, but

arteriolar narrowing and arteriovenous nicking usually are permanent.

Treatment of malignant hypertensive retinopathy, choroidopathy, and optic neuropathy consists

of lowering blood pressure in a controlled fashion to a level that minimizes end-organ damage.The actual level of blood pressure is less important in gauging the urgency of the situation than is

the ongoing end-organ damage. In hypertensive patients, the autoregulatory mechanism thatmaintains constant blood flow to tissues is elevated to a higher level. This allows for the tolerance

of higher blood pressures, and lowering blood pressure below the regulatory range can prevent

adequate blood flow from reaching vital organs. [12] Therefore, blood pressure should be loweredin a slow, deliberate, controlled fashion to prevent end-organ damage. Too rapid a decline can

lead to ischemia of the optic nerve head, brain, and other vital organs, resulting in permanentdamage. Medications used to treat hypertensive emergencies include sodium nitroprusside,

nitroglycerin, calcium channel blockers, beta blockers, and angiotensin-converting enzymeinhibitors. Treatment should be initiated in a controlled, monitored setting under the auspices of a

physician skilled in the use of antihypertensive medications.

From a systemic viewpoint, the diagnosis of a malignant hypertensive crisis represents a medical

emergency. Untreated, the mortality rate is 50% at 2 months and 90% at 1 year. [25] [ 26] Most

patients resume normal vision. On the rare occasion when vision loss occurs, this may resultfrom retinal pigment changes secondary to retinal detachment or from optic atrophy due to

prolonged papilledema.

REFERENCES

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2.. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood




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3.. Burt V.L., Cutler J.A., Higgins M.: Trends in the prevalence, awareness, treatment and control of

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4.. National High Blood Pressure Education Program Working Group : Report on primary preventionof hypertension. Arch Intern Med 1993; 153:186.

5.. Klein R., Klein B.E., Moss S.E., Wang Q.: Hypertension and retinopathy, arteriolar narrowing, andarteriovenous nicking in a population. Arch Ophthalmol 1994; 112:92-98.

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8.. Panton R.W., Goldberg M.F., Farber M.D.: Retinal arterial macroaneurysm: risk factors and natural

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