AUTHOR AND EDITOR INFORMATION
Section 1 of 9  
Author: Kean Theng Oh, MD, Consulting Staff, Associated Retinal Consultants, PC
Kean Theng Oh is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American Society of Retina Specialists, and Association for Research in Vision and Ophthalmology
Coauthor(s):
Bradley M Hughes, MD, Assistant Professor, Department of Ophthalmology, Retina and Vitreous Service, University of Arkansas for Medical Sciences;
Nader Moinfar, MD, Consulting Staff, Vitreoretinal Department, Magruder Eye Institute
Editors: V Al Pakalnis, MD, PhD, Professor of Ophthalmology, University of South Carolina School of Medicine; Chief of Ophthalmology, Dorn Veterans Affairs Medical Center; Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles; Steve Charles, MD, Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri; Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Author and Editor Disclosure
Synonyms and related keywords:
hypertension, high blood pressure, elevated blood pressure, hypertensive ocular changes, hypertensive changes in the eye, ocular hypertension, hypertensive retinopathy, malignant hypertension, hypertensive choroidopathy, hypertensive optic neuropathy, pre-eclampsia, preeclampsia, eclampsia
Background
Hypertension is a leading cause of morbidity and mortality worldwide. This vascular condition involves every organ system. Ocular involvement was first described in 1859 by Liebreich in the setting of malignant hypertension. Hayreh, over the course of the 1970s and 1980s, elucidated pathophysiologic mechanisms and described clinical findings through direct patient management observations and animal models. Fundamentally, ocular effects of hypertension are based on its effects on the ocular vasculature and consequences therefrom. Ocular blood vessels have different characteristics based on their anatomical location that, subsequently, dictate their response to elevated blood pressure. Retinal arterioles and capillaries are similar in anatomy to cerebral vessels in that they exhibit autoregulatory mechanisms and tight junctions to maintain the blood ocular barrier. Choroidal arterioles and capillaries have fenestrations (ie, no blood ocular barrier) and do not exhibit autoregulation. Optic nerve head vessels exhibit intermediary characteristics with autoregulation but an incompetent blood-ocular barrier as a result of the peripapillary choroidal vessels. Ocular changes can be the initial finding in an asymptomatic patient necessitating a primary care referral. Both acute and chronic changes may manifest in the eyes. On the other side, a symptomatic patient may be referred to the ophthalmologist for visual changes due to hypertensive changes. The mechanisms and physical findings of hypertensive changes in the eye are discussed in this article.
Pathophysiology
The pathophysiology of hypertensive ocular changes can be subdivided into acute changes from malignant hypertension and chronic changes from long-term systemic hypertension. Because of the vascular differences between the retina, choroid, and optic nerve, each of these anatomical regions respond differently, but together represent the clinical picture of the ocular response to systemic hypertension. Malignant arterial hypertension - Hypertensive retinal changes (hypertensive retinopathy)
- Changes in the retinal circulation in the acute phase of hypertension primarily involve the terminal arterioles rather than the main retinal arterioles. Main retinal arteriole changes are seen and recognized as a response to chronic systemic hypertension.
- Focal intraretinal periarteriolar transudates (FIPTs)
- First described by Hayreh
- Only observed in malignant arterial hypertension
- One of the earliest lesions seen in the retina as a consequence of malignant hypertension
- Focal, oval, small white lesions deep in the retina, associated with major arteriole vessels
- Not associated with capillary obliteration; hyperfluoresce and leak on fluorescein angiography
- May be related to dilation of terminal arterioles and breakdown of autoregulatory mechanisms due to acute, malignant increase in blood pressure. This results in breakdown of the blood retinal barrier allowing transudation and accumulation of macromolecules.
- Specifically, FIPTs are not cotton-wool spots.
- Inner retinal ischemic spots (cotton-wool spots)
- Hayreh used the term inner retinal ischemic as a more descriptive term than cotton-wool spots.
- Fluffy white lesion at the level of the nerve fiber layer found more commonly in the posterior pole, related to the distribution of the radial peripapillary capillaries.
- Fluorescein angiography appearance is hypofluorescence due to nonperfusion and capillary dropout.
- Last approximately 3-6 weeks before fading away
- Other acute retinal changes
- Capillary obliteration results in development of microaneurysms, shunt vessels, and collaterals.
- Retinal hemorrhages: Hayreh noted that the development of blot retinal hemorrhages are neither an early nor a conspicuous finding associated with malignant hypertension.
- Macular edema can develop as a consequence of hypertensive choroidopathy.
- Hypertensive choroidopathy
- Related to the anatomical and functional differences found in the choroidal vasculature as compared to the retinal vasculature
- Sympathetic innervation makes terminal arterioles more susceptible to vasoconstriction.
- Fenestrations in the capillaries and the consequent lack of a blood ocular barrier allow free passage of macromolecules.
- No autoregulation increases susceptibility to elevated perfusion pressures.
- Retinal pigment epithelial changes
- Acute ischemic changes in the choriocapillaris and overlying retinal pigment epithelium results in acute focal retinal pigment epithelium lesions.
- Focal white spots at the level of retinal pigment epithelium similar to FIPTs
- Serous retinal detachments
- Preferentially affects the macular region causing neurosensory retinal detachments (NSRD) and cystoid macular edema
- Ischemic damage to the retinal pigment epithelium leads to breakdown of the blood retinal barrier.
- Hayreh observed that the presence of a NSRD was correlated to the degree of choroidal circulation disruption.
- Hypertensive optic neuropathy
- Anatomical differences in optic nerve head blood supply
- Optic disc vessels possess autoregulation.
- Lacks a competent blood retinal barrier due to peripapillary choroidal perfusion
- Optic disc edema is a primary manifestation of hypertensive optic neuropathy.
- Ischemic cause for optic disc edema
- Blood supply to the optic nerve is via posterior ciliary arteries and peripapillary choroidal vessels. Vasoconstriction and choroidal ischemia in the setting of malignant hypertension result in optic disc edema and axoplasmic flow stasis.
Chronic hypertensive changes - Retina
- Arteriolosclerosis: Localized or generalized narrowing of vessels
- Copper wiring and silver wiring of arterioles
- Arteriovenous-nicking
- Retinal hemorrhages
- Nerve fiber layer losses
- Increased vascular tortuosity
- Remodeling changes due to capillary nonperfusion, such as shunt vessels and microaneurysms
- Choroid
- Retinal pigment epithelial changes
- Diffuse pigmentary granularity and moth-eaten appearance
- Elschnig spots: Areas of retinal pigment epithelium clumping and atrophy that form from the focal acute white retinal pigment epithelium lesions
- Triangular patches of atrophy as a result of occlusion of a larger caliber choroidal vessel
- Optic nerve: Optic disc pallor
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 United States 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.
History
Most patients are asymptomatic. However, symptomatic patients most commonly present with headaches and blurred vision.
Physical
- Arteriosclerosis
- Arteriosclerotic changes are chronic changes as a result of systemic hypertension.
- 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.
- 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.1 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 (pipe stem sheathing). The patency of such vessels has been demonstrated by fluorescein angiography. When sheathing encircles the wall, it produces a silver-wire vessel.
- 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.
- These are chronic changes due to systemic hypertension.
- AV nicking (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:1
- 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 Albert and Jakobiec, the original crossing angle, the degree of vascular thickening, and the pressure differential influence this phenomenon.2
- 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
- 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 (cotton-wool spots): See Pathophysiology.
- Focal intraretinal periarteriolar transudate (FIPT): See Pathophysiology.
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.
Branch Retinal Artery Occlusion
Branch Retinal Vein Occlusion
Central Retinal Artery Occlusion
Central Retinal Vein Occlusion
Eales Disease
Ocular Manifestations of HIV
Optic Neuropathy, Anterior Ischemic
Papilledema
Pseudopapilledema
Other Problems to be Considered
Diabetic papillopathy
Diabetic retinopathy
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
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 the following: (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 and colleagues. 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, including Hayreh, 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)3
- 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.3
- 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 plus disc swelling
Medical Care
Medical care involves evaluation of secondary causes and appropriate medical management involving life style changes and pharmacotherapy. In the presence of hypertensive optic neuropathy, a rapid reduction of blood pressure may pose a risk of worsening ischemic damage to the optic nerve. The optic nerve demonstrates autoregulation so there is an adjustment in perfusion based on the elevated blood pressure. A precipitous reduction in blood pressure will reduce perfusion to the optic nerve and central nervous system as a result of their autoregulatory changes, resulting in infarction of the optic nerve head and, potentially, acute ischemic neurologic lesions of the central nervous system.
Surgical Care
Surgical management is indicated to address secondary causes of systemic hypertension that require 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.
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
- The prognosis depends on appropriate blood pressure control.
Patient Education
Medical/Legal Pitfalls
- Prompt and accurate diagnosis of hypertensive retinopathy, especially associated with malignant hypertension, is necessary to avoid visual and systemic morbidity.
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Hypertension excerpt Article Last Updated: Nov 17, 2008
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