AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Background

Hypertension is a leading cause of morbidity and mortality worldwide. This vascular condition involves every organ system. The eye examination can serve as a window to the systemic circulation through examination of the blood vessels in the retina. Retinal blood vessels are thought to share similar anatomy and physiology with cerebral and coronary blood vessels.

Ocular changes can be the initial finding in an asymptomatic patient necessitating a primary care referral. On the other side, a symptomatic patient may be referred to the ophthalmologist for visual changes due to hypertensive retinopathy. The mechanisms and physical findings of hypertensive changes in the eye are discussed in this article.

Pathophysiology

Retinal blood vessels can be affected in a number of ways by elevated blood pressure.

The initial response to systemic blood pressure elevation is a generalized vasoconstriction. This is due to increased tone of the arterioles from autoregulatory mechanisms that usually serve protective functions. If blood pressure remains persistently elevated, there is thickening of the blood vessel wall and hyaline degeneration. More severe arteriolar narrowing occurs as well as changes in junctions of arteries and veins known as arteriovenous nicking. There are also changes in the arteriolar light reflex known as "copper wiring." More severe changes consist of breakdown of the blood-retinal barrier with exudation of blood and lipids and retinal ischemia. Examination of the retina in this stage shows microaneurysms, hemorrhages, hard exudates, and infarcts of the nerve fiber layer known as cotton-wool spots. These changes will be discussed in more detail in later sections.

These changes are not specific to hypertension; however, they may be seen in other vascular disorders, such as diabetes. These changes also may not be sequential. Dramatic elevation of blood pressure may lead to exudation without intervening changes of the other stages.

Frequency

United States

According to the Centers for Disease Control and Prevention and National Center for Health Statistics, 23.1% of the US population is estimated to have hypertension. According to Ryan, 58 million adults in the US have elevated blood pressure or are taking antihypertensive medications.

International

Worldwide, hypertension has been rated the fourth largest mortality risk in the world, accounting for 6% of all deaths.

Mortality/Morbidity

Cardiac, neurologic, renal, and ophthalmic sequelae lead to morbidity and mortality. Systemic hypertension accelerates progression of diabetic retinopathy and increases the risk of arterial and venous occlusion. Of affected individuals, 30% will have early cardiovascular damage, and acceleration in atherosclerosis will contribute to increased morbidity and mortality.

Race

Hypertension is more common in the African American population. Approximately 30% of the African American population is estimated to have hypertension as opposed to 20% of Caucasians. However, no racial predilection for hypertensive retinopathy has been noted.

Sex

According to the Centers for Disease Control and Prevention and National Center for Health Statistics, 25.3% of men and 20.8% of women have hypertension.

Age

According to the Centers for Disease Control and Prevention and National Center for Health Statistics, 64.2% of men older than 75 years and 77.3% of women older than 75 years had hypertension.

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

History

Most patients are asymptomatic. However, symptomatic patients most commonly present with headaches and blurred vision.

Physical

• Arteriosclerosis
• • According to Duane's Ophthalmology, arteriosclerosis is defined as hardening and thickening of arteries. It is composed of atherosclerosis (changes in the intima), medial sclerosis, and arteriolosclerosis (changes in the intima with or without media). In the retina, atherosclerosis and arteriolosclerosis predominate. The former is characterized by an atheroma, which evolves from the accumulation of fat-laden cells between the intimal elastic lamella and the endothelium of the vessel wall. The latter is characterized by intimal hyalinization, medial hypertrophy, and endothelial hyperplasia.
  • On histology, arteritis leads to an onionskin appearance. According to Spencer, thickening of the tissue between the endothelium and the internal elastic layer is the earliest change. The collagen content increases, the number of muscle cells decreases, and the basement membrane increases in more advanced lesions. Lipid inclusion accumulates in the endothelium and muscle cells. In severe sclerosis, lipid particles also are observed extracellularly in the intima.
  • Arteriosclerosis needs to be differentiated from involutional sclerosis, which is a system-wide, age-related thickening of the small arteries, which occurs in a patient who is not hypertensive.
• Light reflex change
• According to Spencer, the normal light reflex of the retinal vasculature is formed by the reflection from the interface between the blood column and vessel wall. Initially, the increased thickness of the vessel walls causes the reflex to be more diffuse and less bright. Progression of sclerosis and hyalinization causes the reflex to be more diffuse and the retinal arterioles to become red-brown. This is known as copper wiring.
• Advanced sclerosis leads to increased optical density of the vessel wall, visible on ophthalmoscopy as a phenomenon known as sheathing of the vessels. When the anterior surface becomes involved, the entire vessel appears opaque (pipestem sheathing). The patency of such vessels has been demonstrated by fluorescein angiography. When sheathing encircles the wall, it produces a silver-wire vessel. Histologically, Spencer notes that there is an increase and disarrangement of collagen in the walls of retinal vessels that clinically had a sheathed appearance.
• Attenuation
• • Generalized attenuation of the arterioles occurs as a result of diffuse vasospasm, which occurs when a significant elevation of blood pressure has persisted for an appreciable period. A relationship has been noted between the narrowing of the caliber of the arteriole and the height of the diastolic pressure. Increased intraluminal pressure either in the retinal arterioles or in the central artery of the retina causes narrowing of the arterioles.
  • Focal narrowing occurs from spasm of local areas of the vascular musculature. Spencer speculates that either edema in and around the vessel wall, or vascular spasm leads to focal narrowing, which can become permanent with fibrosis.
• AV nicking: The most commonly accepted belief is that the crossing phenomenon was due to venous compression by a thickened arteriole within the shared sheath (the Gunn sign). Impeded circulation results in a dilated or swollen vein peripheral to the crossing, causing hourglass constrictions on both sides of the crossing and aneurysmal-like swellings. Histologically, Spencer notes findings of various authors, to include the following:
  • Ikui noted that arteriole and venous basement membranes are adherent with shared collagen fibers at the crossing points. Thickening of the basement membrane and the media of the arteriole in hypertension impinge on the vein and cause the crossing phenomenon.
  • Mimatsu asserts that the crossing changes were due to sclerotic thickening of the wall of the venule and not by compression by the arteriole.
  • Seitz attributed the crossing phenomenon to vascular sclerosis and perivascular glial cell proliferation and not to venous compression.
• Arterial narrowing and straightening: Sclerosis may shorten or elongate retinal arterioles with the branches coming off at right angles. This change in length deflects the veins at the common sheath and changes the course of the vein (Salus sign). According to Jakobiec, the original crossing angle, the degree of vascular thickening, and the pressure differential influence this phenomenon.
• Extravascular retinal lesions
  • Microaneurysms: Postulated to occur at localized areas of capillary wall weakness, microaneurysms are most visible by angiography. Stasis engorgement of the capillaries may lead to anoxia and poor nutrition, which contributes to microaneurysm formation.
  • Retinal hemorrhages: In addition to microaneurysms, loss of endothelial integrity leads to extravasation of plasma, which leads to retinal hemorrhages. Streak hemorrhages located in the nerve fiber layer predominate over the blot hemorrhages located deeper in the outer plexiform layer.
  • Retinal and macular edema: Two different mechanisms have been proposed. Hayreh believes that the retinal edema occurs from transudation of choroidal fluids that enter the retina after breakdown of the retinal pigment epithelium (RPE). Others traditionally have believed that the edematous fluid arises from autoregulatory failure, leading to increased transmural pressure in the distal arterioles and proximal capillaries with subsequent transudation of fluids into the retinal tissue.
  • Retinal lipid deposits: Absorption of the plasma component of retinal edema leads to protein accumulation. Histologically, there is accumulation of edema residue and lipid-containing macrophages. Although the deposits assume many shapes and appear in many parts of the retina, the macular star is the most predominant appearance, and this appearance is due to the radially oriented nerve fiber layer of Henle.
• Inner retinal ischemic spots: These lesions arise due to an acute focal ischemia of the inner retina. These lesions are located in the nerve fiber layer following the distribution of radial peripapillary retinal capillaries. These typically last 3-6 weeks; they appear as a gray film, expand into a white cloud, and they fragment before disappearing. Fluorescein angiography (FA) reveals capillary nonperfusion in its wake.
• Focal intraretinal periarteriolar transudate: Coined by Hayreh, focal intraretinal periarteriolar transudate (FIPT) is among the earliest retinal lesions seen in accelerated malignant hypertension. These appear as round or oval lesions located in the deeper retinal layers next to major retinal arterioles and their major branches. FA appearance may precede ophthalmoscopic recognition. On resolution, no residual lesions are noted. The proposed mechanism is focal accumulation of plasmatic molecules in retinal tissue due to autoregulation failure.
• Malignant hypertension
  • Malignant hypertension is a phase of hypertension associated with an idiopathic acute blood pressure elevation. Often, a history of hypertension exists, especially of a nephrogenic etiology. It is most common in younger adults, especially in African American men. Toxemia of pregnancy, renal disease, and collagen vascular disease also are associated with malignant hypertension.
  • Necrosis and fibrinoid deposition in the vessel wall occurs, more commonly involving the choroidal arteries than retinal arteries. Retinal edema occurs from breakdown of the blood-ocular barrier at the level of the RPE. The edema fluid may have a fibrinous appearance.
• Hypertensive choroidopathy
  • Hypertensive choroidopathy occurs more prominently in young patients with acute hypertension, pheochromocytoma, and eclampsia. In the acute ischemic phase, arteriolar constriction leads to changes in the choriocapillaris and RPE. Fibrinoid necrosis is seen with papilledema. Patchy choroidal filling is noted even into the late phase of FA.
  • Acute focal RPE lesions overlying the involved area are seen as pale pinpoint lesions distributed in groups. These are called Elschnig spots and leak fluorescein profusely. These lesions are distinguished from Hayreh's FIPTs, since they stain less intensely and for shorter periods of time, in addition to their subretinal location.
  • In the chronic phase, occlusive changes involve choroidal arteries, arterioles, and capillaries. The healed Elschnig spots no longer leak fluorescein but are associated RPE hyperplasia and a margin of hypopigmentation. Siegrist streaks are linear RPE changes that develop over sclerotic choroidal arteries in the chronic phase.
  • Eventually, recanalization of the choroidal vessels with arterialization of the choriocapillaris occurs. This seems to be a defensive mechanism to withstand the raised systemic blood pressure.
• Serous retinal detachment: Decompensation of the RPE in hypertensive choroidopathy leads to breakdown of the outer blood-retinal barrier, leading to subretinal accumulation of protein-rich exudates. Hayreh noted its high frequency. He also noted that the retina overlying the retinal detachment (RD) showed edematous changes consisting of foveal cyst, macular edema, and microcystic changes.
• Hypertensive optic neuropathy
• • Various authors have reported optic nerve edema as a poor or noncontributory prognostic factor. The American Academy of Ophthalmology (AAO) series notes that patients present with hemorrhages at the optic disc margin, blurring of disc margins, congestion of retinal veins, macular exudates, and florid disc edema.
  • The differential diagnosis includes diabetic papillopathy, radiation retinopathy, incomplete central retinal vein occlusion (CRVO), anterior ischemic optic neuropathy, and acute macular neuroretinitis.
  • Histology shows vasoconstriction with subsequent axonal hydropic swelling, axolemma disruption, and glial swelling.
  • Hayreh proposes that optic nerve swelling results from (1) involvement of the peripapillary choroid by vasoconstriction and vasoocclusive changes, or (2) diffusion of angiotensin II and other endogenous vasoconstrictors into the optic nerve head from the peripapillary choroid, with resulting ischemia.

Causes

In general, the degree and the duration of hypertension are the primary determinants of hypertensive retinopathy. However, the changes described above are not unique for hypertension. These changes may be seen in other diseases with vascular risk factors, such as diabetes. The retinopathy may also be more severe and more progressive when diabetes and hypertension are associated. Other factors, such as hyperlipidemia, may make the retinopathy worse as well.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Diabetic papillopathy
Diabetic retinopathy

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Lab Studies

• Blood pressure measurement, urinalysis, hematocrit, blood glucose, potassium, creatinine, fasting serum cholesterol, fasting serum cholesterol and triglyceride, calcium, and uric acid

Imaging Studies

• Fluorescein angiogram, chest x-ray

Other Tests

• Electrocardiogram

Histologic Findings

Arteries are composed of 3 layers. The intima is composed of the endothelium and underlying subintimal connective tissue. The media is composed of the internal and external elastic lamina surrounding the smooth muscle. The adventitia lies at the outermost area comprised of connective tissue in which nerve fibers and vasa vasorum are dispersed.

The arterial system can be seen as being divided into (1) large/elastic arteries including the aorta and its larger branches, (2) medium/muscular arteries comprised of the smaller branches of the aorta (eg, coronary and renal arteries), and (3) small arteries or arterioles that exist within the substance of the end-organs. Capillaries are approximately the size of a red blood cell (8 µm) with absent media. The endothelial cells are supported principally by a thin basement membrane.

Retinal arteries are histologic arterioles with 100 µm calibers and without internal elastic lamina or continuous muscular coat. Changes in the luminal diameter of the arterioles are the most important component in regulating systemic arterial blood pressure. The resistance of flow is equivalent to the fourth power of the diameter. Therefore, a 50% decrease in the lumen results in a 16-fold increase in the pressure.

Staging

The original classification system for hypertensive retinopathy was conceived in 1939 by Keith et al. Since that time, there have been several criticisms of the original system concerning the reproducibility and the relevance of the system to clinical practice. Some believe that the retinopathy grades may not correlate with the severity of systemic hypertension. In addition, there have been other classification schemes proposed. Three of the major schemes are presented here.

• Keith-Wagener-Barker classification (1939): Patients were grouped according to their ophthalmoscopic findings. As such, this was the first system to correlate retinal findings with the hypertensive disease state.
• • Group 1 - Slight narrowing, sclerosis, and tortuosity of the retinal arterioles; mild, asymptomatic hypertension
  • Group 2 - Definite narrowing, focal constriction, sclerosis, and AV nicking; blood pressure is higher and sustained; few, if any, symptoms referable to blood pressure
  • Group 3 - Retinopathy (cotton-wool patches, arteriolosclerosis, hemorrhages); blood pressure is higher and more sustained; headaches, vertigo, and nervousness; mild impairment of cardiac, cerebral, and renal function
  • Group 4 - Neuroretinal edema, including papilledema; Siegrist streaks, Elschnig spots; blood pressure persistently elevated; headaches, asthenia, loss of weight, dyspnea, and visual disturbances; impairment of cardiac, cerebral, and renal function
• Scheie classification (1953)
• • Stage 0 - Diagnosis of hypertension but no visible retinal abnormalities
  • Stage 1 - Diffuse arteriolar narrowing; no focal constriction
  • Stage 2 - More pronounced arteriolar narrowing with focal constriction
  • Stage 3 - Focal and diffuse narrowing with retinal hemorrhage
  • Stage 4 - Retinal edema, hard exudates, optic disc edema
• Scheie classification also grades the light reflex changes from arteriolosclerotic changes.
• • Grade 0 - Normal
  • Grade 1 - Broadening of light reflex with minimal arteriolovenous compression
  • Grade 2 - Light reflex changes and crossing changes more prominent
  • Grade 3 - Copper wire appearance; more prominent arteriolovenous compression
  • Grade 4 - Silver wire appearance; severe arteriolovenous crossing changes
• The Academy series also reports a modified Scheie classification.
• • Grade 0 - No changes
  • Grade 1 - Barely detectable arterial narrowing
  • Grade 2 - Obvious arterial narrowing with focal irregularities
  • Grade 3 - Grade 2 plus retinal hemorrhages and/or exudates
  • Grade 4 - Grade 3 + disc swelling

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical Care

Medical care involves evaluation of secondary causes and appropriate medical management involving life style changes and pharmacotherapy.

Surgical Care

Surgical management is indicated to address secondary causes of systemic hypertension that requires surgical management.

Diet

• Identification and control of cardiovascular risk factors are encouraged.
• • Weight reduction is strongly encouraged in patients who are more than 115% of their ideal body weight.
  • Reduction of dietary saturated fat or increased polyunsaturated fat induces a modest reduction in blood pressure.
  • Alcohol consumption and sodium intake should be moderated.
  • Regular dynamic exercise also should be advised.

Activity

• Regular exercise of at least 30 minutes at a heart rate of 65-70% of patient's maximal predicted heart rate is recommended at least 3 times a week.
• Patients with known coronary artery disease or those older than 40 years with coronary risk factors should be advised to have exercise stress testing before beginning exercise training.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Follow-up care with a qualified primary care physician is necessary to prevent systemic complications.

Complications

• Cerebrovascular accident
• Myocardial infarction
• Encephalopathy
• Renal vascular disease

Prognosis

• Prognosis depends on appropriate blood pressure control.

Patient Education

• Appropriate patient education regarding proper diet, exercise, and medication compliance is crucial.
• For excellent patient education resources, see eMedicine's Glaucoma Center and Diabetes Center. Also, visit eMedicine's patient education articles Ocular Hypertension, High Blood Pressure, and Diabetic Eye Disease.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Prompt and accurate diagnosis of hypertensive retinopathy, especially associated with malignant hypertension, is necessary to avoid visual and systemic morbidity.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

• Albert D, Jakobiec F, Christlieb RA. Hypertension. Based on: Principles and Practice of Ophthalmology (CD-ROM). WB Saunders Co;1993.
• Grand M, Bressler N, Brown C. Retina and vitreous. In: Basic and Clinical Science Course. 9798 ed. BMJ Publishing Group;1998: 68-70.
• Grosso A, Veglio F, Porta M, et al. Hypertensive retinopathy revisited: some answers, more questions. Br J Ophthalmol. Dec 2005;89(12):1646-54. [Medline].
• Iwasaki M, Ishibashi T, Inomata H, Taniguchi Y. Ultrastructure of sheathed vessels in the retina from patients with various diseases. Graefes Arch Clin Exp Ophthalmol. 1987;225(3):177-84. [Medline].
• Kimura T. Studies on the fine structures of retinal blood vessels in arteriolar sclerosis of human retina. Acta Soc Ophthalmol Jpn. 1965;69:1140-1157.
• Klein R, Klein BE, Moss SE, Wang Q. Blood pressure, hypertension and retinopathy in a population. Trans Am Ophthalmol Soc. 1993;91:207-22; discussion 222-6. [Medline].
• Murphy R, Chew E. Hypertension. Retina. 2000;2:1404-9.
• Porta M, Grosso A, Veglio F. Hypertensive retinopathy: there's more than meets the eye. J Hypertens. Apr 2005;23(4):683-96. [Medline].
• Scheie HG. Evaluation of ophthalmoscopic changes of hypertension and arteriolar sclerosis. Arch Ophthalmol. 1953;49:117-138.
• Seitz R. The Retinal Vessels. CV Mosby;1964:60-61.
• Spencer WH. Systemic diseases with retinal involvement: vascular diseases. Based on: Ophthalmic Pathology: An Atlas and Textbook (CD-ROM). WB Saunders Co;1995.
• Tasman WD. Hypertension and arteriolosclerosis. Based on: Ophthalmology on CD-ROM. Lippincott Williams & Wilkins;1999.
• Wong TY, Mitchell P. Hypertensive retinopathy. N Engl J Med. Nov 25 2004;351(22):2310-7. [Medline].

Article Last Updated: Jan 4, 2007