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How does hypertension affect your eyes?

Abstract

Hypertension has profound effects on various parts of the eye. Classically, elevated blood pressure results in a series of retinal microvascular changes called hypertensive retinopathy, comprising of generalized and focal retinal arteriolar narrowing, arteriovenous nicking, retinal hemorrhages, microaneurysms and, in severe cases, optic disc and macular edema. Studies have shown that mild hypertensive retinopathy signs are common and seen in nearly 10% of the general adult non-diabetic population. Hypertensive retinopathy signs are associated with other indicators of end-organ damage (for example, left ventricular hypertrophy, renal impairment) and may be a risk marker of future clinical events, such as stroke, congestive heart failure and cardiovascular mortality. Furthermore, hypertension is one of the major risk factors for development and progression of diabetic retinopathy, and control of blood pressure has been shown in large clinical trials to prevent visual loss from diabetic retinopathy. In addition, several retinal diseases such as retinal vascular occlusion (artery and vein occlusion), retinal arteriolar emboli, macroaneurysm, ischemic optic neuropathy and age-related macular degeneration may also be related to hypertension; however, there is as yet no evidence that treatment of hypertension prevents vision loss from these conditions. In management of patients with hypertension, physicians should be aware of the full spectrum of the relationship of blood pressure and the eye.

Foreword

Hypertension is associated with profound, often asymptomatic, multisystemic effects. The eye is not spared the effects of elevated blood pressure. However, the eye is distinctive in that it allows the direct sequelae of elevated blood pressure to be visualized early, particularly changes in the retinal microvasculature. The most well-known effect of the hypertension on the eye is therefore the condition called hypertensive retinopathy, in which the retinal circulation undergoes a series of changes in response to high blood pressure. Hypertensive retinopathy has long been regarded as a risk indicator for systemic morbidity and mortality. However, besides hypertensive retinopathy, elevated blood pressure has a key role in the pathogenesis of diabetic retinopathy, a major cause of vision loss in working adults. In fact, control of blood pressure has been shown in large clinical trials to prevent progression of diabetic retinopathy and prevent blindness, an effect that is almost equivalent to control of hyperglycemia. Finally, several retinal diseases such as retinal vascular occlusion (artery and vein occlusion), retinal arteriolar emboli, macroaneurysm, ischemic optic neuropathy and age-related macular degeneration may also be related to hypertension, but these relationships are not as well known to physicians. This review will summarize the broad ocular effects of hypertension, concentrating on literature published in the last decade (2000 onwards).

Hypertensive retinopathy

Pathophysiology and clinical features

Hypertensive retinopathy refers to a spectrum of retinal microvascular signs that typically include retinal arteriolar narrowing, arteriovenous nicking (AVN), retinal hemorrhages, microaneurysms and, in severe cases, optic disc and macular edema. These signs develop due to acute and chronic elevations in blood pressure.1 The initial response is diffuse and localized vasospasm of the retinal arterioles with consequent narrowing (generalized arteriolar narrowing and focal arteriolar narrowing (FAN), respectively). Arteriolar narrowing is a defining sign of hypertensive retinopathy and reflects vasoconstriction as an autoregulatory response in an attempt to control the volume of blood received by the retinal capillary bed (Figure 1). It is most commonly seen in the early phase of hypertensive retinopathy before the onset of sclerosis and can be detected even in children with hypertension.2 If the blood pressure remains chronically elevated, there is compression of venules by structural changes in the arterioles, resulting in arteriovenous nicking (Figure 2). Severe hypertension leads ultimately to progression to an ‘exudative’ stage in which flame-shaped retinal hemorrhages and cotton wool spots are observed (Figures 3 and 4); and finally to a ‘malignant’ stage with optic disc and macular edema.3 These pathophysiological changes and clinical features are depicted in detail in Table 1.

Figure 1
figure1

Generalized and focal arteriolar (white arrow) narrowing with moderate opacification of arterioles (black arrow).

Figure 2
figure2

AVN: mild retinopathy.

Figure 3
figure3

Arteriolar narrowing, AVN, with flame-shaped (blue arrow) and dot blot hemorrhages: moderate retinopathy.

Figure 4
figure4

Arteriolar narrowing, AVN, flame-shaped hemorrhages along with cotton wool spots (white arrow) and hard exudates (black arrow): moderate retinopathy.

Table 1 Pathophysiology of hypertensive retinopathy

Chronic blood pressure elevation can lead to hypertensive choroidopathy generally seen in younger patients with pliable vessels that are not yet sclerotic from long-standing hypertension. Acute elevations in blood pressure that overwhelm the compensatory tone actually harm the choroidal circulation more than the retinal circulation due to the sympathetic innervation of choroid. As a result, the choroidal arterioles constrict considerably initially, which further increases the blood pressure and damages the arterioles.4

The above-mentioned stages of hypertensive retinopathy are usually not sequential, and retinopathy signs reflecting the ‘exudative’ stage (for example, retinal hemorrhages) may be seen in eyes without features of the ‘arteriosclerotic’ stage (for example, AVN). In fact, hypertensive retinopathy signs can be frequently detected even in adults who are not known to have hypertension.5

It is important for physicians to be aware that some retinal microvascular signs of hypertension may also be seen in other systemic and ocular conditions, such as diabetic retinopathy, radiation retinopathy, anemic/leukemic retinopathy, trauma, human immunodeficiency virus and other infections. Thus, in atypical situation, appropriate investigations may be necessary to rule out other important diseases that may masquerade as hypertensive retinopathy.6

Epidemiology

With increasing use of retinal photographs since the 1990s, population-based studies have provided data about prevalence, risk factors and systemic associations of hypertensive eye changes.2, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15 The findings from some of the major studies are summarized in Table 2. These studies indicate that many of the hypertensive retinopathy signs are commonly seen in 6–15% of non-diabetic adults aged 40 years.13, 10

Table 2 Prevalence of hypertensive retinopathy, summary of population-based studies

In particular, isolated retinal hemorrhages and/or microaneurysms are most commonly observed signs (5.7–8%) with presence of cotton wool spots being relatively uncommon (0.2%). Some studies suggest that the incidence of generalized arteriolar narrowing is as high as 25% among hypertensive people, with FAN and AVN found in 12% of people with hypertension.5 The 10-year cumulative incidence of these retinopathy signs is 16% (ref. 16).

Racial variations in the prevalence of retinopathy show that the highest rates of retinopathy are observed among Chinese (17.2%) and the lowest among White (11.9%) and Black populations (13.9%). With respect to gender, higher incidence has been reported among men except for Black populations.10 In Asian populations, Japanese15 and Malays13 living in urban areas, showed lower incidence of retinopathy (7.7 and 6%, respectively) compared with rural Chinese populations (13.6%). This could be attributed to higher prevalence and lower awareness of hypertension, as well as poor blood pressure control among the rural population.14

Relationship with blood pressure and other risk factors

It is well known that hypertensive retinopathy is related to both the presence and severity of hypertension.2, 5, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17 In a recent population-based study, the frequency of generalized arteriolar narrowing (25.4 vs 14.6%), FAN (12.1 vs 6.2%) and AVN (12.3 vs 6.1%) was found to be significantly higher in persons with hypertension than normotensive persons.5 Furthermore, hypertensive persons whose blood pressure was elevated despite the use of medications had a higher risk to develop retinopathy compared with those whose blood pressure was controlled or those who were normotensive.7

However, the pattern of relationship between specific hypertensive retinopathy signs and blood pressure may differ. Generalized retinal arteriolar narrowing and AVN are usually found in patients with long-term hypertension and are independently associated with past blood pressure levels measured up to 10 years before the retinal assessment.18 In contrast, FAN, retinal hemorrhages, microaneurysms and cotton wool spots indicate momentary blood pressure changes and relate to only the concurrent blood pressure measured at the time of the retinal evaluation.19 Data also suggest that the association between blood pressure and retinal microvascular signs is weaker with age, possibly reflecting greater sclerosis of retinal arterioles in older persons.20

Longitudinal data from recent population-based studies have demonstrated that smaller retinal arteriolar and larger venular calibers precede clinical stage of hypertension20 and predicts upto 5-year risk of hypertension in initially normotensive individuals.21, 22 In the Atherosclerosis Risk in Communities study, major systemic determinants of narrower arteriolar caliber were past and current higher blood pressure, whereas wider venular caliber was associated with only current hypertension.23

Besides blood pressure, hypertensive retinopathy signs have also been associated with other risk markers, such as inflammation (C-reactive protein, fibrinogen),8, 24, 25 endothelial cell activation (von Willebrand factor),24 and angiogenesis (vascular growth endothelial factor),26 adiponectin,27 and leptin.28 Recent data also suggest a positive correlation between serum ferritin levels and degree of hypertensive retinopathy, presumably due to increased levels of oxidative stress.29 The significance of these associations with hypertensive retinopathy is inconsistent among various ethnic cohorts10 and warrants further investigation.

Genetic associations

Numerous studies have highlighted the genetic influence on the development of retinal vascular caliber within families and twins. The heritability of the retinal arteriolar caliber, venular caliber and the arteriovenule ratio has been reported to be 0.48, 0.54 and 0.32, respectively, with higher correlation among siblings than parent to child.20 A twin study of retinal vascular caliber reported that heritabilities of retinal arteriolar and venular calibers were 70 and 83%, respectively. Genome-wide linkage studies found that regions for retinal vascular caliber overlapped with those that have been previously associated with essential hypertension, the eNOS-related pathway, coronary heart disease and vasculogenesis.20 Search for potential candidate genes for retinal vascular caliber has yielded weak linage with polymorphisms of apolipoprotein E (APOE) gene.20 Data from the Atherosclerosis Risk in Communities study showed genome-wide significant association of venular dilatation with greater African ancestry at chromosome 6p21.1.30 A recent population-based genome-wide association study has demonstrated four novel loci associated with retinal venular caliber, with locus 12q24 being associated with coronary heart disease and hypertension in two independent samples.31 Newer data also suggest that angiotensin-converting enzyme I/D gene polymorphism may be associated with subclinical structural arteriolar changes related to chronic hypertension among the Japanese.32

Retinal vascular imaging

Novel computer-based imaging analysis allows quantification of subtle hypertensive retinopathy changes.33 Previous studies have already shown retinal arteriolar diameter is strongly and inversely associated with elevation of blood pressure, reflecting systemic peripheral vasoconstriction.19, 25, 34 Studies based on semiautomated computerized analysis have also demonstrated that retinal arteriolar narrowing strongly correlates with higher blood pressures, with increasing numbers of hypertensive retinal vascular signs in persons with higher blood pressure levels.35, 36

Several studies using novel retinal vascular features such as branching angles, bifurcation, fractal dimension, tortuosity, vascular length-to-diameter ratio and wall-to-lumen ratio have shown that these features may also be related to hypertension and may provide additional information in predicting cardiovascular diseases.35, 37, 38, 39, 40, 41 More specifically, increased curvature as reflected by a greater retinal venular tortuosity and wider retinal venular caliber have been linked with elevated blood pressure.35, 42 Furthermore, smaller fractal dimension and smaller arteriolar branching asymmetry ratio have been shown to be associated with uncontrolled and untreated hypertension.35, 37

Relationship with stroke and cardiovascular disease

Numerous studies have reported a strong link between retinal microvascular changes and cerebrovascular disease.9, 43, 44, 45 In the Atherosclerosis Risk in Communities study, persons with hypertensive retinopathy were not only at an increased risk of developing incident stroke45 but also cognitive decline,46 cerebral white matter lesions44 and cerebral atrophy,47 even after controlling for traditional risk factors. Furthermore, it has been shown that retinal microvascular changes are associated with specific subtypes of stroke. Generalized arteriolar narrowing and venular widening are positively linked with lacunar stroke, whereas, retinopathy signs have significant association with non-lacunar thrombotic and cardioembolic strokes.48

Studies have also reported a relationship between hypertensive retinopathy signs and heart disease. The risk of developing congestive heart failure doubled in patients with moderate hypertensive retinopathy as compared with those without retinopathy.49 Other studies have shown retinopathy to be strongly associated with coronary artery disease in elderly hypertensives50 and markers of subclinical or microvascular coronary disease,51 especially in women with type 1 diabetes.52

FAN and AVN are also related to left ventricular hypertrophy.53, 54 Reversing left ventricular hypertrophy is increasingly being seen as an important therapeutic end point of antihypertensive treatment; newer studies show that angiotensin receptor antagonists and calcium antagonists are more effective in reversing left ventricular hypertrophy than β-blockers, whereas the efficacy of diuretics is intermediate.55, 56 However, hypertensive retinal changes have moderate accuracy in predicting coronary artery disease in patients presenting with acute angina.50, 57 Emerging evidence also indicates that risk for coronary heart disease may be higher in women who were previously deemed ‘low risk’ by traditional risk factors.57, 58 In the Multi-Ethnic Study of Atherosclerosis cohort, retinopathy was shown to have significant correlation with increased coronary artery calcium scores.59 Retinal arteriolar narrowing and decreased myocardial blood flow and perfusion reserve are also found to be closely linked.59 Recent Multi-Ethnic Study of Atherosclerosis study found increased internal carotid intima media thickness to be associated with retinopathy in persons without diabetes, especially among the Whites and Hispanics.10

Classification and clinical management

In the past, very detailed classifications of hypertensive retinopathy were developed, including classifications by Marcus Gunn in the nineteenth century60, 61 and the works of Keith Wagner and Barker in 1939.62 The Keith Wagner and Barker classification includes four grades of retinopathy mainly on the basis of changes in caliber of retinal vasculature. Grade 1 retinopathy is the ‘mild’ generalized retinal arteriolar narrowing, whereas grade 2 retinopathy comprises of ‘more severe’ generalized narrowing, FAN and AVN (Figure 2). Presence of microaneurysms, retinal hemorrhages (mostly flame shaped) (Figure 3), hard exudates and cotton wool spots (Figure 4) is considered grade 3 retinopathy. Malignant retinopathy or ‘albuminuric retinitis’, which constitutes the grade 4 retinopathy, consists of optic disc swelling and macular edema in the presence of signs in the previous three stages.

However, for the clinical management of systemic hypertension these detailed classifications may not be necessary. A simpler three-grade classification system63 that overcomes the limitation of the previous classification system where it was difficult to clinically distinguish early retinopathy grades (for example, grade 1 from grade 2) has been proposed.64, 65

On the basis of this simple three-grade classification system for hypertensive retinopathy,63 a suggested management plan for patients with various retinopathy grades is shown in Table 3. Patients with mild retinopathy signs will likely require routine care according to established guidelines. Patients with moderate retinopathy signs may benefit from further assessment of vascular risk (for example, assessment of cholesterol levels) and, if clinically indicated, appropriate risk-reduction therapy (for example, cholesterol lowering agents). Patients with malignant retinopathy will need urgent antihypertensive management.

Table 3 Classification of hypertensive retinopathy and management guidelines

There is some indication that antihypertensive medication can reverse hypertensive retinopathy signs, with clinical case series66, 67 showing regression of some retinopathy signs (for example, hemorrhages, cotton wool spots), but not others (for example, AVN) with control of blood pressure. Newer studies on the basis of digital retinal photography and computerized analysis reveal that blood pressure reduction is associated with reduction in arteriolar narrowing, widening of arteriolar branch angle and increase in arteriolar density among untreated hypertensives.68 Both calcium channel blockers and angiotensin antagonists are shown to cause regression of retinal vascular signs to similar extents.68 Nevertheless, in comparison with β-blockers, the calcium antagonists show better remodeling response in retinal microvasculature attributed to its vasodilatory action.69

Finally, a retinal assessment may be useful to screen for patients with white-coat hypertension or masked hypertension. These patients are reported to represent an intermediate group between healthy people and sustained hypertensives with regard to target-organ damage and cardiovascular risk. Its prevalence ranges between 12 and 30% and found commonly in elderly women.70 Detection of hypertensive retinopathy in subjects with white-coat hypertension may indicate the need for antihypertensive therapy.71

Diabetic retinopathy

Diabetes and hypertension are both vascular risk factors with identical pathophysiological mechanisms.4 In the presence of hypertension, persons with diabetes are more likely to have diabetic retinopathy (Figure 5).71 Some studies have shown an association between severity of diabetic retinopathy and systolic, but not diastolic blood pressure, being stronger among the younger patients.72

Figure 5
figure5

Concurrent proliferative diabetic retinopathy and moderate hypertensive retinopathy.

Various studies have identified hypertension as an important modifiable risk factor for diabetic retinopathy to the extent that every 10 mm Hg increase in systolic blood pressure is known to increase the risk of early and proliferative retinopathy by 10 and 15%, respectively.73 In the United Kingdom Prospective Diabetes Study,74 participants with tighter blood pressure control had 37% reduction in the risk of microvascular disease, 34% decrease in the rate of retinopathy progression by two or more levels on the ETDRS scale, and 47% decline in the deterioration of visual acuity by three or more lines on ETDRS charts. A recent meta-analysis on the progression rates of diabetic retinopathy showed that diabetics who had earlier initiation of medical management of glucose, blood pressure and serum lipids had lower rates of progression to severe visual loss.75 However, strategies to improve awareness are needed among the Asians, in which more than three-quarters of diabetic patients were noted to have poor glycemic and blood pressure control.11

Among the various antihypertensive treatment trials, recent data suggest that drugs targeting the renin–angiotensin system are more efficient in reducing the risk of diabetic retinopathy. Angiotensin-converting enzyme inhibitors have shown to prevent the development of retinopathy in type 1 diabetics by 18–35%,76 with increase in regression of retinopathy by 34% in type 2 diabetes.77 In the Renin–Angiotensin System Study,78 treatment with enalapril and losartan has shown to lessen the risk of retinopathy progression by 65 and 70%, respectively, in type 1 diabetes. However, the antihypertensive treatment produced no statistically significant changes in retinal blood vessel caliber in these younger, normotensive, normoalbuminuric with type 1 diabetics in a randomized controlled trial.79

Other eye conditions associated with hypertension

Retinal vascular occlusion

Hypertension is associated with retinal vascular occlusion, including retinal artery occlusion (RAO) and retinal vein occlusion (RVO).

RAO is a visually disabling ocular vascular disorder with an estimated incidence of 0.85/100 000 population80 noted to occur frequently among hypertensives.81 As a rule, sudden, painless, dramatic visual impairment occurs. Reduction in central visual acuity is also accompanied by visual field loss. Depending on which vessel is affected, the entire visual field (central retinal artery) or part of the visual field (branch retinal artery) may be affected. Retinal emboli may be visible in the vessels at the optic disc or downstream in branch retinal arterioles in up to 20% of central RAO and up to 70% of branch RAO.82, 83 However, retinal embolus is shown to be a poor predictor of hemodynamically significant carotid stenosis on carotid Doppler, as migration of emboli in the retinal vascular bed is a characteristic feature. Microemboli may be derived from non-hemodynamically significant obstruction, due to only a small intraluminal plaque(s), most commonly from carotid arteries (66%), which may be present even in absence of significant stenosis of carotid artery.84

Arterial hypertension, diabetes mellitus, hyperlipidemia, carotid artery disease, coronary artery disease, transient ischemic attack and tobacco smoking are the common risk factors for retinal arterial occlusions, with systemic hypertension showing a significant association in more than 50% of these patients.84 Echocardiographic abnormalities have been documented in patients with RAO with 10% needing systemic management.81 RAO has also been reported to be associated with an increase risk of cardiovascular disease, stroke and mortality. Patients with retinal arterial occlusions have a notably reduced life expectancy after the event, if patients' arterial hypertension is not sufficiently treated with drugs after the initial occlusion.80

A thorough cardiovascular and cerebrovascular assessment, including carotid and cardiac imaging, is necessary in patients with RAO. Central RAO is an ocular emergency, and efforts to restore ocular circulation and preserve vision include dislodgement of the embolus within 3 h by digital massage of the eyeball, paracentesis of anterior chamber fluid to lower intraocular pressure, and induction of vasodilatation by carbon dioxide rebreathing.80 However, success with these techniques is known to lead to visual improvement in only 15%.80 Recently, more aggressive treatment strategies, such as intravenous and selective intra-arterial thrombolysis of the ophthalmic artery may produce notable sight improvement in about 30–40% of patients.80, 85

Venous occlusion (RVO) is a silent and painless vascular disease most commonly associated with hypertension.86, 87, 88 It generally presents with variable visual loss with any combination of fundal findings consisting of retinal vascular tortuosity, retinal hemorrhages (blot and flame shaped), cotton wool spots, optic disc swelling and macular edema. In a central RVO, retinal hemorrhages will be found in all four quadrants of the fundus (Figure 6), whereas these are restricted to either the superior or inferior fundal hemisphere in a hemiRVO (Figure 7). In a branch RVO (BRVO), hemorrhages are largely localized to the area drained by the occluded branch retinal vein. Decrease in vision is usually due to macular edema or ischemia (Figure 8).

Figure 6
figure6

Central RVO.

Figure 7
figure7

Inferior hemiretinal vein occlusion.

Figure 8
figure8

Superotemporal BRVO.

Longitudinal population-based studies have helped to provide an estimate of incidence of vein occlusions, though its true incidence is difficult to establish, as many times patient is asymptomatic and RVO is only detected incidentally. The Blue Mountains Eye Study found that the 10-year cumulative incidence of RVO was 1.6%, which was significantly associated with increasing age, especially after the seventh decade.87 Various studies have reported the prevalence rates of BRVO ranging from 0.3 to 1.1%,88 whereas central RVO is relatively rare with reported incidence of 0.1%–0.5%.89 Pooled analysis of population-based studies from the United States, Europe, Asia and Australia shows that approximately 16 million people worldwide may have RVO in at least one eye; a higher prevalence of BRVO noted in Asians and Hispanics compared with Whites.90

Systemic hypertension is found to be the strongest independent risk factor associated with all types of RVO, especially in the older (over 50 years) age group as uncontrolled or newly diagnosed hypertension is common among them.81, 86, 87, 88 Recurrence of RVO in the same or fellow eye is also noted with poor control of blood pressure. A recent meta-analysis has shown a significant association between hypertension and both central RVO (odds ratio=3.8) and BRVO (odds ratio=3.0),91, 92 with the risk of developing BRVO being five times higher even for mild hypertensive retinopathy.88 Additional risk factors for RVO include diabetes, cigarette smoking and carotid artery disease as well as various hematological abnormalities (for example, hyperhomocysteinaemia, anti-cardiolipin antibodies, protein S and C deficiencies, activated protein C resistance, and factor V Leiden mutation).91, 92 RVO has also been associated with stroke, coronary heart disease and cardiovascular mortality.90

The cause and management of the RVO is closely linked to the underlying systemic disease and its management. However, an ophthalmologic follow-up is also warranted to diagnose and prevent the two main vision-threatening complications, neovascularization and macular edema. Panretinal photocoagulation has been shown to benefit only cases with evidence of neovascularization, and prophylactic treatment does not necessarily prevent this complication.91, 92 Focal laser photocoagulation is useful in avoiding visual loss in patients with macular edema from BRVO, although this treatment does not appear to benefit macular edema associated with central RVO.91, 92 Newer therapeutic options for macular edema in the form of intravitreal triamcinolone91, 92, 93 and anti-vascular endothelial growth factor agents91, 92, 94 currently seem to be at the forefront, and their efficacy and safety is being validated by randomized clinical trials. Although there is no evidence that lowering of blood pressure would reduce the risk of complications associated with RVO, physicians should be more vigilant with the patients' treatment of hypertension after the occurrence of an RVO.

Retinal arteriolar emboli and macroaneurysms

Retinal arteriolar emboli are discrete plaque-like lesions lodged in the lumen of retinal arterioles that are pathologically heterogeneous.3 Emboli are of three types: calcific, cholesterol and platelet–fibrin. The carotid artery and the heart are the sources of embolism to the retinal arterioles. In the carotid artery, plaque is the most common source. In the heart, sources of emboli are valvular lesions and tumors.84, 95 Retinal emboli are usually asymptomatic and detected incidentally during eye examinations.96 Because most retinal emboli are transient, their prevalence is likely to have been underestimated in most epidemiological studies.

Data from various population-based studies reveal that retinal arteriolar emboli can be detected in 1.3–1.4% of individuals above 40 years of age, with a 10-year incidence of 1.5–3.0%.87 Hypertension, hypercholesterolemia, obesity, current smoking, increased fibrinogen level and diabetes were significantly associated with incident emboli.81, 87, 96 Retinal vascular signs such as AVN, arteriolar wall opacification and RVO are documented to correlate considerably with presence of retinal emboli. Persons with hypertension at baseline are shown to be 2.5 times as likely to have prevalent emboli.87

These migratory microemboli in retinal arterioles are markers of incident stroke, cardiovascular disease and mortality96, 97 as well as frank RAO,84 which needs an emergency management. In the Atherosclerosis Risk in Communities study, participants with retinal arteriolar emboli were twice as likely to have coronary heart disease and four times as likely to have carotid artery plaque as those without emboli.98 In the Beaver Dam Eye Study, baseline retinal emboli were associated with a twofold higher risk of stroke mortality than persons without emboli, controlling for blood pressure and other risk factors.96

Management of patients with retinal emboli should include a thorough systemic evaluation, concentrating on modifiable risk factors, such as hypertension, dyslipidemia, smoking, obesity and diabetes. These patients may need carotid ultrasonography and Doppler, though it is suggested that 60–80% of people with asymptomatic retinal emboli do not have significant carotid stenosis.84

Retinal arterial macroaneuryms are acquired fusiform or saccular dilatations of the retinal arterioles common in elderly women (60–80%) after the sixth decade of life attributed to hormonal and heritable causes.99 Histopathologically, aging of arterioles is described by an increase in intimal collagen and medial muscle fiber replacement with collagen. As a result, the arterial wall becomes less elastic and more susceptible to dilatation from elevated hydrostatic pressure.4 Hypertension is a significant risk factor for retinal arterial macroaneurysms, noted in up to 80% of patients.99, 100, 101 Hypertension can result in hyaline degeneration of vessel walls, loss of autoregulatory tone, and arterial dilatation. Hypertensive patients also have raised hydrostatic pressures that might predispose to macroaneurysm formation.

The epidemiology of macroaneurysm is not well described in the literature, but data from large case series suggest that approximately one-fifth of macroaneurysms are bilateral, and 1 in 10 are multiple.101 Macroaneurysm may be noted incidentally in asymptomatic patients, but can also present acutely with visual loss secondary to hemorrhage or exudation (Figure 9). Visual loss from macroaneurysm may be the initial presentation of patients with uncontrolled hypertension.100

Figure 9
figure9

Retinal arterial macroaneurysm (white arrow) with hemorrhage and exudation.

Visual recovery typically occurs spontaneously with thrombosis of the macroaneurysm and resolution of the hemorrhage and exudates.100 However, residual retinal damage from chronic macular edema and hard exudates deposition may lead to poor visual prognosis. Laser treatment could benefit selected cases where exudation threatens or involves the macula, which may lead to branch RAO.

Ischemic optic neuropathy

Hypertension may compromise the optic nerve perfusion in a similar manner to that seen in disturbances of the retinal circulation.102, 103 Ischemic optic neuropathy is noted in patients over 50 years of age, most frequently as an acute phenomenon.104 In 90% of the patients, the anterior segment of the optic nerve is affected and they present with sudden visual loss and optic disc edema (Figure 10), which is absent in patients with posterior ischemia. Ischemic optic neuropathy is classified as arteritic (AION) and non-arteritic (NAION) types. Inflammatory diseases are usually responsible for the arteritic type, with giant cell arteritis being the most common.4 The non-arteritic or atherosclerotic variety of ischemic optic neuropathy is strongly associated with hypertension and other cardiovascular risk factors.102, 103 Up to 50% of the patients with NAION may have hypertension, in contrast to AION, which is not associated with hypertension.4 Furthermore, hypertension, diabetes and hypercholesterolemia appear to be more significant risk factors for AION in younger patients.102 Few existing data on the incidence of non-arteritic AION have shown an estimated annual incidence of NAION to be 10.3 per 100 000 persons 50 years of age and older.105

Figure 10
figure10

Ischemic optic neuropathy.

No known successful management for NAION exists. Surgical interventions like optic nerve sheath decompression are proven to be potentially harmful without any visual improvement.102, 103 Few anecdotal reports suggest that aspirin and intravitreal steroids/anti-vascular endothelial growth factor agents have been tried without much success.102, 103

Conclusion

The diverse development of hypertensive organ damage and their correlation with changes in retinal microvasculature preceding other signs of damage should promote more routine use of fundus photography in assessing cardiovascular risk in hypertensive individuals. However, there are still some gaps in our knowledge of hypertensive retinopathy, which warrant further research. Ultimately, retinal vascular imaging has the potential to be used as non-invasive, economical and reliable method for assessing the microvascular sequelae of hypertension and can be considered as ‘biomarkers’ for target-organ damage.

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Bhargava, M., Ikram, M. & Wong, T. How does hypertension affect your eyes?. J Hum Hypertens 26, 71–83 (2012). https://doi.org/10.1038/jhh.2011.37

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Keywords

  • blood pressure
  • retinopathy
  • cardiovascular disease
  • retinal vascular conditions

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