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Review Article

Hypertensive retinopathy

Kumudini Sharma a,*, Vikas Kanaujia b, Priyadarshini Mishra b,Rachna Agarwal b, Alka Tripathi b

aProfessor & Head, Department of Neuro-Ophthalmology (Neurosurgery), Sanjay Gandhi Post Graduate Institute of

Medical Sciences, Raebareli Road, Lucknow 226 014, Uttar Pradesh, IndiabDepartment of Neuro-Ophthalmology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road,

Lucknow 226 014, Uttar Pradesh, India

a r t i c l e i n f o

Article history:

Received 13 August 2013

Accepted 19 August 2013

Available online 13 September 2013

Keywords:

Hypertension

Flame shaped hemorrhage

Arteriolar attenuation

* Corresponding author.E-mail address: kumud@sgpgi.ac.in (K. Sh

2211-9477/$ e see front matter Copyright ªhttp://dx.doi.org/10.1016/j.cqn.2013.08.001

a b s t r a c t

The term hypertensive retinopathy is used for all the fundus changes caused by increased

systemic arterial blood pressure. Retinal vasculature can be seen non-invasively through

fundoscopy and their similarity to other microvasculature in the body make early diag-

nosis of hypertensive retinopathy very important in hypertensive risk stratification. The

usual features of chronic hypertensive retinopathy are arteriolar attenuation, nerve fiber

layer infarct, superficial flame shaped hemorrhage, lipid exudates, macular edema. In

malignant hypertension choroidopathy and optic neuropathy can be seen in addition to

retinopathy. Many of these changes resolve with time when control of blood pressure is

good. For grading of hypertensive retinopathy Scheie classification and Keith-Wagener-

Barker classification are most commonly used. Diagnosis of hypertensive retinopathy is

clinical by ophthalmoscopy. Others like fundus photography, fluorescein angiography,

optical coherence tomography can be used for added information. Decrease vision if occur

is due to macular edema, secondary retinal pigment epithelial changes and due to optic

neuropathy. Blood pressure lowering is the mainstay of treatment which should be in a

slow and controlled manner in case of malignant hypertensive retinopathy to avoid

ischemic damage.

Copyright ª 2013, Reed Elsevier India Pvt. Ltd. All rights reserved.

1. Introduction amount of research has been done after Liebreich (1859)

Hypertensive retinopathy used as a global term for all the

fundus changes caused by raised blood pressure (BP) indi-

cating an end organ damage although hypertensive cho-

roidopathy and optic neuropathy can be manifested

distinctly in malignant hypertension. Differences in

morphologic and physiologic properties of retinal, choroidal

and optic nerve vasculature is responsible for it. A vast

arma).2013, Reed Elsevier India

whose article albuminuric retinitis first gave the concept of

hypertensive ocular changes1. The retinal circulation shares

similar anatomical and physiological properties with other

microcirculations in the body. As it can be studied easily,

non-invasively, it gives an opportunity to assess the risk of

hypertension at the earliest. Frequently the presence of

other vascular diseases like diabetes confounds the actual

incidence of hypertensive retinopathy. According to the

Pvt. Ltd. All rights reserved.

c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 3 6e1 3 9 137

Beaver Dam eye study, the incidence of pure hypertensive

retinopathy was about 15%.2

Fig. 1 e Hypertensive fundus photograph showing

arteriolar attenuation.

2. Understanding of retinal blood flow

The retinal arteries when considered in view of dimension or

histologic properties behave much like arterioles. Blood

retinal barrier exists at two levels. The inner one at the level of

endothelial cells of the vessels and the outer one at the level of

retinal pigment epithelial cells. The tight junctions between

the cells are responsible in formation of both barriers. Ocular

blood flow is controlled by perfusion pressure that is equal to

mean blood pressure minus intraocular pressure and the

resistance to blood flowwhich is affected by viscosity of blood,

length and radius of the vessels.

Autoregulation has great role in maintaining ocular blood

flow during the fluctuation in perfusion pressure. When there

is rise in BP, the arterioles constrict andwhen there is fall in BP,

arterioles dilate so that blood flow remains relatively constant

but this is applicableovera limited rangeofperfusionpressure.

Beyond that if BP rises suddenly as in malignant arterial hy-

pertension, vascular damage starts. Focal or generalized dila-

tion of arterioles occur. Morphologic studies of the dilated

segments have revealed endothelial cell loss, discontinuity of

endothelial cell layers or inter endothelial separation as the

initial event. These changes result in breakdownof inner blood

retinal barrier and permeability increases. Failure of outer

blood retinal barrier can occur due to damage to retinal

pigment epithelial cells. If BP rises less rapidly, autoregulatory

mechanism improves patient’s tolerance to high blood pres-

sure by an adaptive phenomenon, but simultaneously make

the patient less tolerant to low BP or sudden fall of BP resulting

in ocular or systemic vascular accidents.

Fig. 2 e Fundus photograph of hypertensive retinopathy

showing cotton wool spots.

3. Clinical features and underlyingpathophysiology of hypertensive retinopathy

3.1. Retinal arteriolar changes

In chronic hypertension diffuse arteriolar narrowing (Fig. 1) is

commonlyseen.Thearteriole tovenule ratiowhich isnormally

2:3 is decreased. Reversible focal arteriolar narrowing may be

seen. In acute hypertension, it can be a vasospastic response.

Sometimes pseudo narrowing can be seen due to retinal

edema. With long standing hypertension multiple concentric

layers of elastic tissue is formed in the intima of arterioles,

collagen fibers can replace the muscle coat resulting in onion-

skin appearance. This is well described by Ashton and Harry.

Senile or involutional arteriosclerosis are the similar changes

seen with advancing age in absence of hypertension.3

3.2. Inner retinal ischemic spots (IRIS)/cotton wool spots

These are focal areas of retinal opacity, fluffy white, of irreg-

ular shape obscuring underlying blood vessels, that are clini-

cally evident only in the post equatorial retina where the

nerve fiber layer is of sufficient thickness to render them

visible. These are the neuronal debris within the nerve fiber

layer resulting from disruption of nerve axons due to terminal

arteriole occlusion. The swollen ends of axons are called

cytoid bodies seen on lightmicroscopy as globular structure in

the nerve fiber layer. These ischemic infarcts look like cotton

wool spots (Fig. 2) ophthalmoscopically. IRIS4 typically resolve

in 3e6 weeks, debris are removed by autolysis and phagocy-

tosis. On complete resolution loss of retinal nerve fiber layer

occur in that area.

3.3. Retinal lipid deposits/hard exudates

This occurs in the outer plexiform layer as a result of exuda-

tion. Althoughmacula is themost common site producing the

characteristic macular star (Fig. 3) deposits also occur in other

part of retina and may assume variety of shapes. They are

Fig. 3 e Fundus photograph of malignant hypertensive

retinopathy showing optic disc edema (arrow head), flame

shaped hemorrhage (long arrow), hard exudates forming

macular star (solid white arrow).

KeitheWagenereBarker classification:

Group 1 Mild to moderate narrowing or sclerosis of the arterioles

Group 2 Moderate to marked narrowing of the arterioles

Local and/or generalized narrowing of arterioles

Exaggeration of the light reflex

Arteriovenous crossing changeGroup 3 Retinal arterial narrowing and focal constriction

Retinal edema

Cotton wool patches

HemorrhagesGroup 4 As for group 3 plus papilledema

Scheie classification:

c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 3 6e1 3 9138

usually associated with macular or retinal edema or serous

retinal detachment. The deposits may take months or even

more than a year to resolve.

3.4. Retinal hemorrhages

These are usually described as striate, flame shaped hemor-

rhage (Fig. 3) in the inner layer of retina, the nerve fiber layer.

They are most commonly located in the peripapillary area

where radial capillaries are distributed. These are long,

straight, superficial capillaries from which outflow can be

obstructed by disc and peripapillary edema resulting in

hemorrhage. Other causes could be pathologic changes in the

capillaries like ischemic capillaropathy.4

3.5. Retinal and macular edema and serous retinaldetachment

Retinal edema can be generalized or localized usually in the

macular region. It is a common occurrence in malignant hy-

pertension. Disruption of outer blood retinal barrier due to

ischemic damage of RPE results in increased permeability,

thus fluid, protein and other materials leak from choroid into

subretinal space producing serous RD.

Hypertension

Grade 0 No changes

Grade 1 Barely detectable arteriolar narrowing

Grade 2 Obvious arteriolar narrowing with focal irregularities

Grade 3 Grade 2 plus retinal hemorrhages and/or exudates

Grade 4 Grade 3 plus papilledema

Arteriolar sclerosis

Grade 0 Normal

Grade 1 Barely detectable light reflex changes

Grade 2 Obvious increased light reflex changes

Grade 3 Copper-wire arterioles

Grade 4 Silver-wire arterioles

4. Hypertensive choroidopathy

Typically occurs in young patients experiencing acute hyper-

tension. The main pathologic change is focal necrosis of the

choriocapillaris, overlying RPE and the outer retina due to

acute choroidal ischemia. On ophthalmoscopy these appear

as yellow color patches (acute Elschnig’s spots). As these heal

pigmentary changes appear. Patches of hyperpigmentation

develop surrounded by a margin of hypopigmentation.

Siegrist’s streaks are linear configuration of hyperpigmenta-

tion over choroidal arteries. In this unusual finding the RPE

directly overlying the sclerotic choroidal arteries become hy-

perplastic and the choriocapillaris become attenuated in this

zone.5e7

5. Hypertension optic neuropathy

It presents clinically as disc edema (Fig. 3). Depending on the

degree and chronicity of the hypertension optic neuropathy

has a variable presentation. Anterior ischemic optic neuropa-

thy can result from stasis of axoplasmic flow due to ischemia.8

6. Classification of hypertensive funduschanges

Several clinical classifications have been proposed for grading

hypertensive retinopathy, but no classification is optimum.

High variability in fundus findings, different presenting fea-

tures inmalignant hypertension, also associated systemic risk

factors render it difficult for any classification system to be

satisfactory. So accurate documentation of hypertensive

fundus changes as seen by opthalmoscopy, slit lamp bio-

microscopy and fundus fluoresceine angiography are more

valuable than any classification. Also this is very useful in

follow up of patients. The two classifications most widely

accepted are given by Keith et al9 (1939) and Scheie9 (1953).

Classification of HR by Wong and Mitchell10 can also be used.

Classification of HR by Wong and Mitchell:

Grade Description Systemic association

No retinopathy No detectable retinal signs None

Mild retinopathy

(retinal arteriolar

signs only)

One or more of the following arteriolar

signs: generalized arteriolar narrowing,

focal arteriolar narrowing, arteriovenous

nicking, arteriolar wall opacity (silver wiring)

Modest association with risk of clinical stroke

subclinical stroke, coronary heart disease and mortality

Moderate retinopathy One or more of the following retinal signs.

Hemorrhage (dot, blot or flame shaped),

microaneurysm, cotton wool spot, hard exudates

Strong association with risk clinical stroke,

subclinical stroke and cardiovascular mortality

Malignant retinopathy Moderate retinopathy plus optic disc swelling Strong association with mortality

(Modest: risk and odd ratios of >1 but <2. Strong: risk and odd ratios >2).10

c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 3 6e1 3 9 139

7. Investigations

Diagnosing hypertensive retinopathy is mainly clinical.

Ophthalmoscopy and slit lamp biomicroscopy are usually suf-

ficient, but some additional tests can be done for more in-

formationsanddocumentation.Systemicbloodpressureshould

be measured so that other causes with similar fundus findings

can be excluded. Fundus photography has added a lot to diag-

nosis. Specific software packages have developed to objectively

measure arteriole to venule ratio in selected standardized por-

tions of the retina.11 Fundus fluorescence angiographymay give

some additional information. Flame shaped hemorrhages are

superficial and block all retinal vascular fluorescence. Areas of

capillary non perfusion are seen in the vicinity of cotton wool

spots. Leakageofdye isseen inmacular edema. In central serous

retinopathy pooling of dye occurs slowly. Optical coherence to-

mography (OCT)may be used to evaluate cross sectional images

of retina and subretinal fluid collection.12,13

8. Treatment and prognosis

Retina is theonlypart ofvasculature that canbevisualizednon-

invasively. Hypertensive retinopathy is considered as amarker

of microvascular damage in other vital organs. So earliest sign

of hypertensive retinopathy should alert physician for control

of BP. In case of acute rise, blood pressure should be gradually

lowered in a controlled manner. Too abrupt decline in BP can

cause ischemiaof optic nervehead, brainandother vital organs

leading to permanent damage. There is often improvement in

fundus findings with the treatment of underlying systemic

condition.14Onrareoccasionvision lossmay result fromretinal

pigment changes secondary to retinal detachment and from

optic atrophy due to prolonged papilledema.15

Conflicts of interest

All authors have none to declare.

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