Journal of Human Hypertension (2012) 26, 71–83
& 2012 Macmillan Publishers Limited All rights reserved 0950-9240/12
REVIEW
How does hypertension affect your eyes?
M Bhargava1, MK Ikram1,2 and TY Wong1,3
1
Singapore Eye Research Institute, National University of Singapore, Singapore; 2Department of
Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands and 3Centre for Eye Research
Australia, University of Melbourne, Melbourne, Victoria, Australia
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
Keywords: blood pressure; retinopathy; cardiovascular disease; retinal vascular conditions
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 condi-
tion 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 indi-
cator for systemic morbidity and mortality. How-
ever, 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
Correspondence: Dr TY Wong, Singapore Eye Research Institute,
Singapore National Eye Centre, 11 Third Hospital Avenue 168751,
Singapore.
Email: ophwty@nus.edu.sg
Received and accepted 10 March 2011; published online 21 April
2011
www.nature.com/jhh
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 vas-
cular occlusion (artery and vein occlusion), retinal
arteriolar emboli, macroaneurysm, ischemic optic neu-
ropathy 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.
Journal of Human Hypertension (2012) 26, 71 – 83;
doi:10.1038/jhh.2011.37; published online 21 April 2011
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 re-
sponse 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 hyper-
tensive retinopathy before the onset of sclerosis and
 How does hypertension affect your eyes?
M Bhargava et al
72
Figure 1 Generalized and focal arteriolar (white arrow) narrow-
ing with moderate opacification of arterioles (black arrow).
Figure 2 AVN: mild retinopathy.
can be detected even in children with hyperten-
sion.2 If the blood pressure remains chronically
elevated, there is compression of venules by struc-
tural changes in the arterioles, resulting in arterio-
venous 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.
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 initi-
ally, which further increases the blood pressure and
damages the arterioles.4
The above-mentioned stages of hypertensive
retinopathy are usually not sequential, and retino-
Journal of Human Hypertension
Figure 3 Arteriolar narrowing, AVN, with flame-shaped (blue
arrow) and dot blot hemorrhages: moderate retinopathy.
Figure 4 Arteriolar narrowing, AVN, flame-shaped hemorrhages
along with cotton wool spots (white arrow) and hard exudates
(black arrow): moderate retinopathy.
pathy 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 infec-
tions. Thus, in atypical situation, appropriate
investigations may be necessary to rule out other
important diseases that may masquerade as hyper-
tensive retinopathy.6
Epidemiology
With increasing use of retinal photographs since the
1990s, population-based studies have provided data
about prevalence, risk factors and systemic associa-
tions of hypertensive eye changes.2,5,7–15 The find-
ings from some of the major studies are summarized
 How does hypertension affect your eyes?
M Bhargava et al
73
Table 1 Pathophysiology of hypertensive retinopathy

Pathophysiological mechanism Signs

Acute Vasospasm Generalized arteriolar narrowing

hypertension Increased vascular tone
Chronic Intimal thickening, media wall hyperplasia, Diffuse and focal narrowing (‘copper-wiring’) and opacification
hypertension hyaline degeneration of arterioles (‘silver-wiring’) of arteriolar walls
Compression of venules at their common ‘Arteriosclerotic stage’: arteriovenous nicking
adventitial crossings
Severe Inner blood–retinal barrier breakdown ‘Exudative stage’: exudation of blood (retinal hemorrhages) and
hypertension Necrosis of vascular smooth muscle and lipids (hard exudates)
endothelial cells Nerve fiber layer ischemia (cotton wool spots)
Persistent damage to retinal microvasculature
Accelerated Intracranial pressure elevation Hypertensive optic neuropathy/‘malignant retinopathy’
hypertension Fibrinoid necrosis of choroidal arterioles Optic nerve ischemia
Optic disc swelling (papilloedema)
Hypertensive choroidopathy
Infarction of segment of choriocapillaris
RPE infarcts: Elsching’s spots
Linear RPE hyperplasia over infracted choroidal arterioles
(Siegrist’s streaks)
Localized bullous neurosensory/RPE detachments

Abbreviation: RPE, retinal pigment epithelium.

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

Study Population Prevalence of retinopathy signsa

All persons (%) Hypertensive persons

BDES 4926 persons aged 43–86 years, White 7.8–13.5 2.8–19.4% (MAs+RH ¼ 2.8%; AVN ¼ 5.8%; FAN ¼ 13.8%)
ethnicity, Wisconsin, USA
BMES 3654 persons aged 49 and older, White 7.9–9.9 6.8–15.4% (MAs+RH ¼ 9.9%; AVN ¼ 8.6%; FAN ¼ 7.9%)
ethnicity, Australia
ARIC Study 10 000+ persons aged 51–72 years, White 3.3–7.3 5.0–11.9% (MAs+RH ¼ 2.8%; AVN ¼ 5.8%; FAN ¼ 7.3%)
and Black ethnicity, four USA
communities
CHS 2400+ persons aged 69–97 years, White 8.3–9.6 9.0–12.3% (MAs+RH ¼ 8.3%; AVN ¼ 7.8%; FAN ¼ 9.6%)
and Black ethnicity, four USA
communities
Rotterdam Eye 5674 persons aged 55 and older, White 5 (MAs+RH) –
Study ethnicity, Holland
SiMES 3280 Malays aged 40–80 years, Asians, 4.7 (MAs+RH) 6% (MAs+RH ¼ 5.8%; CWS ¼ 0.3%)
Singapore
Handan Eye 6830 Chinese aged 430 years, China 8.6 12.1%
Study
Beijing Eye 4439 Chinese subjects aged 45–89 years, GAN ¼ 14.6%; GAN ¼ 25.4%; FAN ¼ 12.1%; AVN ¼ 12.3%
Study China FAN ¼ 6.2%;
AVN ¼ 6.1%
Funagata Study 1961 Japanese aged 35 or older, Japan 7.7% (FAN, AVN, MAs/RH)
MESA 6176 subjects aged 45–84 years, four 12.5% (11.9–17.2%) ¼ mostly MAs and RHs
ethnic groups (White, Black, Hispanic and
Chinese)

Abbreviations: ARIC, atherosclerosis risk in community; AVN, arteriovenous nicking; BDES, Beaver Dam Eye Study; BMES, Blue Mountains Eye
Study; CHS, Cardiovascular Health Study; CWS, cotton wool spots; FAN, focal arteriolar narrowing; GAN, generalized arteriolar narrowing; MA,
microaneurysms; MESA, Multi-Ethnic Study of Atherosclerosis; RHs, retinal hemorrhages; SiMES, Singapore Malay Eye Study.
a
Includes GAN, FAN, AVN and RH/MA/CWS in non-diabetic persons.

in Table 2. These studies indicate that many of the
hypertensive retinopathy signs are commonly seen
in 6–15% of non-diabetic adults aged X40 years.13,10
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 narrow-
ing is as high as 25% among hypertensive people,
with FAN and AVN found in 12% of people with

Journal of Human Hypertension

 How does hypertension affect your eyes?
M Bhargava et al
74
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 popula-
tion.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 hyperten-
sion.2,5,7–15,17 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 Further-
more, 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, microaneur-
ysms 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 arter-
iolar and larger venular calibers precede clinical stage
of hypertension20 and predicts upto 5-year risk
of hypertension in initially normotensive indivi-
duals.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 asso-
ciated 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
Journal of Human Hypertension
Willebrand factor),24 and angiogenesis (vascular
growth endothelial factor),26 adiponectin,27 and
leptin.28 Recent data also suggest a positive correla-
tion between serum ferritin levels and degree of
hypertensive retinopathy, presumably due to in-
creased 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 over-
lapped with those that have been previously
associated with essential hypertension, the eNOS-
related pathway, coronary heart disease and vascu-
logenesis.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 poly-
morphism 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 narrow-
ing 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 dimen-
sion, 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.35,37–41 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 cerebro-
vascular disease.9,43–45 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 cere-
bral 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 retino-
pathy.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 hypertro-
phy is increasingly being seen as an important
therapeutic end point of antihypertensive treatment;
newer studies show that angiotensin receptor antago-
nists and calcium antagonists are more effective in
reversing left ventricular hypertrophy than b-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, retino-
pathy 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
How does hypertension affect your eyes?
M Bhargava et al
75
Classification and clinical management
In the past, very detailed classifications of hyper-
tensive retinopathy were developed, including clas-
sifications 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 classifica-
tion system for hypertensive retinopathy,63 a sug-
gested 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.
There is some indication that antihypertensive
medication can reverse hypertensive retinopathy
signs, with clinical case series66,67 showing regres-
sion 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 photo-
graphy 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 b-
blockers, the calcium antagonists show better remo-
deling response in retinal microvasculature attrib-
uted 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
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 How does hypertension affect your eyes?
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76
Table 3 Classification of hypertensive retinopathy and management guidelines

Retinopathy grade Description Systemic associations Management

Mild One or more of the following signs: generalized Weak associations with stroke, Routine care
arteriolar narrowing, focal arteriolar narrowing, coronary heart disease and Closer monitoring of vascular
arteriovenous nicking, arteriolar wall opacity cardiovascular mortality risk
(silver wiring)
Moderate Mild retinopathy with one or more of the Strong association with stroke, Exclude diabetes
following signs: retinal hemorrhage (blot, dot or congestive heart failure, renal Closer monitoring of vascular
flame shaped), microaneurysms, cotton wool dysfunction and cardiovascular risk
spot, hard exudates mortality Possible indication for
hypertension treatment and
other risk factors
Malignant Moderate retinopathy signs plus optic disc Associated with mortality Urgent hypertension treatment
swelling and macular edema

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 mechan-
isms.4 In the presence of hypertension, persons with
diabetes are more likely to have diabetic retinopathy
(Figure 5).71 Some studies have shown an associa-
tion between severity of diabetic retinopathy and
systolic, but not diastolic blood pressure, being
stronger among the younger patients.72
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 retino-
pathy by 10 and 15%, respectively.73 In the United
Kingdom Prospective Diabetes Study,74 participants
with tighter blood pressure control had 37% reduc-
tion 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 redu-
cing the risk of diabetic retinopathy. Angiotensin-
converting enzyme inhibitors have shown to prevent
Figure 5 Concurrent proliferative diabetic retinopathy and
moderate hypertensive retinopathy.
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 progres-
sion 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, normoalbu-
minuric 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

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 How does hypertension affect your eyes?
M Bhargava et al
77
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, hyperli-
pidemia, carotid artery disease, coronary artery Figure 6 Central RVO.
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 abnorm-
alities 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 dislodge-
ment of the embolus within 3 h by digital massage
of the eyeball, paracentesis of anterior chamber Figure 7 Inferior hemiretinal vein occlusion.
fluid to lower intraocular pressure, and induction
of vasodilatation by carbon dioxide rebreathing.80
However, success with these techniques is known retinal vein. Decrease in vision is usually due to
to lead to visual improvement in only 15%.80 macular edema or ischemia (Figure 8).
Recently, more aggressive treatment strategies, Longitudinal population-based studies have
such as intravenous and selective intra-arterial helped to provide an estimate of incidence of vein
thrombolysis of the ophthalmic artery may produce occlusions, though its true incidence is difficult to
notable sight improvement in about 30–40% of establish, as many times patient is asymptomatic
patients.80,85 and RVO is only detected incidentally. The Blue
Venous occlusion (RVO) is a silent and painless Mountains Eye Study found that the 10-year
vascular disease most commonly associated with cumulative incidence of RVO was 1.6%, which
hypertension.86–88 It generally presents with variable was significantly associated with increasing age,
visual loss with any combination of fundal findings especially after the seventh decade.87 Various stu-
consisting of retinal vascular tortuosity, retinal dies have reported the prevalence rates of BRVO
hemorrhages (blot and flame shaped), cotton wool ranging from 0.3 to 1.1%,88 whereas central RVO is
spots, optic disc swelling and macular edema. In a relatively rare with reported incidence of 0.1%–
central RVO, retinal hemorrhages will be found in 0.5%.89 Pooled analysis of population-based studies
all four quadrants of the fundus (Figure 6), whereas from the United States, Europe, Asia and Australia
these are restricted to either the superior or inferior shows that approximately 16 million people world-
fundal hemisphere in a hemiRVO (Figure 7). In a wide may have RVO in at least one eye; a higher
branch RVO (BRVO), hemorrhages are largely prevalence of BRVO noted in Asians and Hispanics
localized to the area drained by the occluded branch compared with Whites.90

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 How does hypertension affect your eyes?
M Bhargava et al
78
Figure 8 Superotemporal BRVO.
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 hyperten-
sion is common among them.81,86–88 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 be-
tween hypertension and both central RVO (odds
ratio ¼ 3.8) and BRVO (odds ratio ¼ 3.0),91,92 with the
risk of developing BRVO being five times higher
even for mild hypertensive retinopathy.88 Addi-
tional risk factors for RVO include diabetes, cigar-
ette smoking and carotid artery disease as well as
various hematological abnormalities (for example,
hyperhomocysteinaemia, anti-cardiolipin antibo-
dies, 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, neovas-
cularization and macular edema. Panretinal photo-
coagulation has been shown to benefit only cases
with evidence of neovascularization, and prophy-
lactic 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 triamci-
nolone91–93 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
Journal of Human Hypertension
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 asym-
ptomatic 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, in-
creased fibrinogen level and diabetes were signifi-
cantly 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. Per-
sons 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 dis-
ease and mortality96,97 as well as frank RAO,84 which
needs an emergency management. In the Athero-
sclerosis 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, concentrat-
ing on modifiable risk factors, such as hyperten-
sion, 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 fusi-
form 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 hydro-
static pressure.4 Hypertension is a significant risk

Figure 9 Retinal arterial macroaneurysm (white arrow) with
hemorrhage and exudation.
factor for retinal arterial macroaneurysms, noted in
up to 80% of patients.99–101 Hypertension can result
in hyaline degeneration of vessel walls, loss of
autoregulatory tone, and arterial dilatation. Hyper-
tensive patients also have raised hydrostatic pres-
sures 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 macro-
aneurysms 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 exuda-
tion (Figure 9). Visual loss from macroaneurysm
may be the initial presentation of patients with
uncontrolled hypertension.100
Visual recovery typically occurs spontaneously
with thrombosis of the macroaneurysm and resolu-
tion 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 in-
volves 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 Is-
chemic 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 neuro-
How does hypertension affect your eyes?
M Bhargava et al
79
Figure 10 Ischemic optic neuropathy.
pathy 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 sig-
nificant 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
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 anecdo-
tal 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 photo-
graphy in assessing cardiovascular risk in hyperten-
sive 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.
Conflict of interest
The authors declare no conflict of interest.
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