Hypertensive Retinopathy – Causes, Symptoms, Treatment

Hypertensive retinopathy rarely causes significant visual loss. The retinal changes can be halted when hypertension is treated. However, arteriolar narrowing and AV changes persist. For untreated malignant hypertension, the mortality is high as 50% within 2 months of diagnosis and almost 90% by the end of 1 year. Vision loss in hypertensive retinopathy is because of either secondary optic atrophy after prolonged papilloedema or retinal pigmentary changes after exudative retinal detachment.

Poorly controlled hypertension (HTN) affects several systems such as the cardiovascular, renal, cerebrovascular, and retina. The damage to these systems is known as target-organ damage (TOD). HTN affects the eye causing 3 types of ocular damage: choroidopathy, retinopathy, and optic neuropathy. Hypertensive retinopathy (HR) occurs when the retinal vessels get damaged due to elevated blood pressure. There has been significant evidence that hypertensive retinopathy acts as a predictor of systemic morbidity and mortality due to TOD. A study by Erden et al. showed that the increase in the incidence of retinopathy is related to the degree of severity and duration of HTN.

Types of Hypertensive Retinopathy

The following are classification systems for hypertensive retinopathy based on fundus examination with indirect ophthalmoscopy or +90 D lens.

Keith-Wagner- Barker classification

  • Group 1: Slight constriction of retinal arterioles
  • Group 2: Group 1 + focal narrowing of retinal arterioles + AV nicking
  • Group 3: Group 2 + flame-shaped haemorrhages + cotton-wool spots + hard exudates
  • Group 4: Group 3 + optic disc swelling

Scheie Classification

For Hypertensive Retinopathy

  • Stage 0: No visible abnormalities
  • Stage 1: Diffuse arteriolar narrowing
  • Stage 2: Stage 1 + focal arteriolar constriction
  • Stage 3: Stage 2 + retinal hemorrhage
  • Stage 4:  Stage 3 + hard exudates + retinal edema+ optic disc swelling

For Arteriosclerosis

  • Stage 0: Normal
  • Stage 1: Broadening of arteriolar light reflex
  • Stage 2: Stage 1 + AV crossing changes
  • Stage 3: Copper wiring of arterioles
  • Stage 4: Silver wiring of arterioles

Causes of Hypertensive Retinopathy

Apart from essential and secondary hypertension, there are other factors which play an important role in the development of hypertensive retinopathy. The prevalence of hypertensive retinopathy is more in Afro-Caribbean as compared to Europeans and more in women as compared to men. Genetic factors can also play a role with certain genotypes associated with an increased risk of hypertensive retinopathy. Pontremoli et al. studied the genetic factors linked to hypertensive retinopathy and found the deletion of the allele of the angiotensin-converting enzyme has a higher risk associated with the development of hypertensive retinopathy. Smoking is considered to have a strong association with severe or malignant hypertensive retinopathy as studied by Poulter et al. Renal dysfunction (persistent microalbuminuria and low creatinine clearance) in patients has shown to be a marker for hypertensive retinopathy and end-organ damage. Uckaya et al. found an association with plasma leptin. It was observed that plasma leptin levels were higher in patients with hypertensive retinopathy and postulated that it is associated with vascular endothelium damage.

Retinal blood vessels have distinct features, which differentiate them from other blood vessels:

  •  The absence of sympathetic nerve supply
  •  Autoregulation of blood flow
  •  Presence of blood-retinal barrier

Thus, an increase in blood pressure (BP) is transferred directly to the vessels which initially constrict. However, a further increase in BP overcomes this compensatory tone and damage to the muscle layer and endothelium ensues.

Hypertensive retinopathy has the following phases:

Vasoconstrictive Phase

In this phase, the local autoregulatory mechanisms come into play. This causes vasospasm and retinal arteriole narrowing, which is evident by the decrease in the arteriole to venule ratio (Normal = 2:3). In older patients with arteriosclerosis, focal arteriolar narrowing develops, as affected vascular segments cannot undergo narrowing.

Sclerotic Phase

Persistent increase in BP causes certain changes in vessel wall:

  • Intima layer: Thickening
  • Media layer: Hyperplasia
  • Arteriolar wall: Hyaline degeneration

This leads to a severe form of arteriolar narrowing, arteriovenous (AV) crossing changes, and widening and accentuation of light reflex (silver and copper wiring). AV crossing changes occur when a thickened arteriole crosses over a venule and subsequently compresses it as the vessels share a common adventitious sheath. The vein, in turn, appears dilated and torturous distal to the AV crossing.

Exudative Phase

Seen in patients with severely increased BP; characterized by the disruption of the blood-brain barrier and leakage of blood and plasma into the vessel wall disrupting the autoregulatory mechanisms. In this stage, retinal signs occur such as retinal hemorrhage (flame-shaped and dot blot), hard exudate formation, necrosis of smooth muscle cells and retinal ischemia (cotton-wool spots).

Malignant Hypertension

Severe intracranial hypertension leads to optic nerve ischemia and edema (papilledema). Also, fibrinoid necrosis of choroidal arterioles occurs leading to segmental infarction of choriocapillaries. This gives rise to:

  • Elschnig’s spots: Where the overlying retinal pigment epithelium (RPE) appears yellow
  • Siegrist’s streak: RPE hyperplasia over choroidal infarcts
  • Neurosensory RPE detachments

These signs are termed as choroidopathy.

The other conditions which present with optic disc swelling are

  • Diabetic allopathy
  • Central retinal vein occlusion
  • Anterior ischemic optic neuropathy
  • Neuroretinitis

Conditions that mimic chronic hypertensive retinopathy are

  • Diabetic retinopathy
  • Retinal venous obstruction
  • Hyperviscosity syndrome
  • Ocular ischemic syndrome
  • Radiation retinopathy

Symptoms and Signs of Hypertensive Retinopathy

Signs of damage to the retina caused by hypertension include:

  • Arteriolar changes, such as generalized arteriolar narrowing, focal arteriolar narrowing, arteriovenous nicking, changes in the arteriolar wall (arteriosclerosis) and abnormalities at points where arterioles and venules cross. Manifestations of these changes include Copper wire arterioles where the central light reflex occupies most of the width of the arteriole and Silver wire arterioles where the central light reflex occupies all of the width of the arteriole, and “arterio-venular (AV) nicking” or “AV nipping”, due to venous constriction and banking.
  • advanced retinopathy lesions, such as microaneurysms, blot hemorrhages and/or flame hemorrhages, ischemic changes (e.g. “cotton wool spots”), hard exudates and in severe cases swelling of the optic disc (optic disc edema), a ring of exudates around the retina called a “macular star” and visual acuity loss, typically due to macular involvement.
  • Strongly modulated blood flow pulse in central and branch arteries can result from hypertension. Microangiography by laser Doppler imaging[rx] may reveal altered hemodynamics non-invasively.

Mild signs of hypertensive retinopathy can be seen quite frequently in normal people (3–14% of adult individuals aged ≥40 years), even without hypertension.[rx] Hypertensive retinopathy is commonly considered a diagnostic feature of a hypertensive emergency although it is not invariably present.[rx]

In the early stages, funduscopy identifies arteriolar constriction, with a decrease in the ratio of the width of the retinal arterioles to the retinal venules.

Chronic, poorly controlled hypertension causes the following:

  • Permanent arterial narrowing
  • Arteriovenous crossing abnormalities (arteriovenous nicking)
  • Arteriosclerosis with moderate vascular wall changes (copper wiring) to more severe vascular wall hyperplasia and thickening (silver wiring)
  • Sometimes total vascular occlusion occurs. Arteriovenous nicking is a major predisposing factor to the development of a branch retinal vein occlusion.
  • Superficial flame-shaped hemorrhages
  • Small, white, superficial foci of retinal ischemia (cotton-wool spots)
  • Yellow hard exudates
  • Optic disk edema

Diagnosis of Hypertensive Retinopathy

Clinical Features

Hypertensive retinopathy is usually asymptomatic and is diagnosed on fundoscopic features. The following are signs of hypertensive retinopathy.

AV Crossing Changes

  • Salus’s sign: Deflection of retinal vein as it crosses the arteriole.
  • Gunn’s sign: Tapering of the retinal vein on either side of the AV crossing.
  • Bonnet’s sign: Banking of the retinal vein distal to the AV crossing.

Arterial Changes

  • Decrease in the arteriovenous ratio to 1:3 ( the normal ratio is 2:3).
  • Change in the arteriolar light reflex (light reflex appears as copper and/or silver wiring)

Retinal Changes

  • Retinal hemorrhages: 

    • Dot-blot hemorrhages: Bleeding in the inner retinal layer
    • Flame shaped hemorrhage: Bleeding is in the superficial retinal layer
  • Retinal exudates:

    • Hard exudates: Lipid deposits in the retina
    • Soft exudates: These are also known as cotton wool spots which appear due to ischemia of the nerve fibers

Macular Changes

Macular star formation due to deposition of hard exudates around the macula.

Optic Nerve Changes

Optic disk swelling (also known as hypertensive optic neuropathy)

In a study by Wong et al., they identified certain retinal signs to be associated with increased risk for stroke. The signs are AV nicking, focal arteriolar narrowing (as this is associated with arteriosclerosis), microaneurysms, cotton wool spots, retinal hemorrhages (dot blot and flame-shaped), and decreased AV ratio.

Clinical diagnosis

The signs of malignant hypertension are well summarized by the Modified Scheie Classification of Hypertensive Retinopathy[rx]:

  • 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, exudates, cotton wool spots, or retinal edema
  • Grade 4: Grade 3 plus papilledema

The signs of chronic arteriosclerotic hypertension are also summarized by the Scheie Classification[rx]:

  • Stage 1: Widening of the arteriole light reflex
  • Stage 2: Stage 1 + Arteriovenous crossing sign
  • Stage 3: Copper wiring of arterioles (copper colored arteriole light reflex)
  • Stage 4: Silver wiring of arterioles (silver colored arteriole light reflex).

Another classification schema is the Keith-Wagner-Barker classification proposed in 1939.[rx]

  • Grade 1: Mild, generalized constriction of retinal arterioles
  • Grade 2: Definite focal narrowing of retinal arterioles + AV nicking
  • Grade 3: Grade 2 + flame-shaped hemorrhages + cotton-wool spots + hard exudates
  • Grade 4: Severe Grade 3 retinopathy + papilledema or retinal edema

Of specific interest is the classification of hypertensive retinopathy by Wong and Mitchell (2004) in which the worsening grades of retinopathy were more strongly associated with systemic issues.[tx] The classification is as follows:

  • None: no detectable signs
  • Mild: one or more of the following: generalized arteriolar narrowing, focal arteriolar narrowing, arteriovenous nicking, opacity (“copper wiring”) of the arteriolar wall
  • Moderate: one or more of the following: retinal hemorrhage (blot, dot, or flame-shaped), microaneurysm, cotton-wool spot, hard exudate, or a combination of these signs
  • Severe: moderate retinopathy plus swelling of the optic disc

A new classification has been proposed recently (2014) based on optical coherence tomography (OCT) features such as subretinal fluid (SRF). The study compared the grading system based on OCT findings to the Keith-Wagner-Barker grading system and found that the following classification was significantly correlated to final best-corrected visual acuity.[rx]

  • Mild-Moderate Retinopathy
  • Malignant Retinopathy w/o SRF
  • Malignant R w/ SRF

Lab Test And Imaging

  • Ophthalmoscope – Your doctor will use a tool called an ophthalmoscope to examine your retina. This tool shines a light through your pupil to examine the back of your eye for signs of narrowing blood vessels or to see if any fluid is leaking from your blood vessels. This procedure is painless. It takes less than 10 minutes to complete.
  • Fluorescein angiography – In some cases, a special test called fluorescein angiography is performed to examine retinal blood flow. In this procedure, your doctor will apply special eye drops to dilate your pupils and then take pictures of your eye. After the first round of pictures, your doctor will inject a dye called fluorescein into a vein. They’ll typically do this on the inside of the elbow. Then, they’ll take more pictures as the dye moves into the blood vessels of your eye.

Treatment of Hypertensive Retinopathy

The main purpose of screening for hypertensive retinopathy is that retinal vessels are the only blood vessels visible on routine examination. The effects of chronically elevated HTN are easily visible in the eye as hypertensive retinopathy and choroidopathy, and this reflects the vascular changes occurring in other systems. Ophthalmologists and general physicians should work in collaboration to ensure that hypertensive patients are efficiently screened, and timely managed to reduce the risk of ocular and systemic morbidity and mortality. Henderson et al., however, noted that Hypertensive retinopathy is associated with an increased risk of stroke even after controlling BP and other vascular risk factors.

The management of hypertensive retinopathy depends on the severity of the disease:

  • Mild hypertensive retinopathy: The treatment consists of controlling of BP with regular monitoring.
  • Moderate hypertensive retinopathy: Referral to a physician is essential to exclude other associated factors like diabetes mellitus and to check for any cardiovascular abnormalities. Routine care including BP control and monitoring is a must.
  • Severe hypertensive retinopathy: Requires urgent treatment and referral as it has the strongest association with mortality. Other systems such as renal, cardiovascular, and brain should be monitored for signs of TOD.

Important to note is that BP should be lowered in a controlled fashion. This is crucial to prevent ischemic damage to vital organs such as optic nerve and brain.

Blood Pressure Goals

  • SHEP and HYVET trials have shown significant benefits of antihypertensive treatment in patients with the goal of SBP <150 mmHg.
  • The VALsartan in Elderly Isolated Systolic Hypertension (VALISH) trial showed no significant difference in the primary outcome of sudden death, fatal or nonfatal myocardial infarction and stroke, heart failure death, or other cardiovascular death among patients with strict (< 140 mmHg) and moderate (140 to 150 mmHg) SBP control.
  • However, the VALISH trial was underpowered due to the low number of events.
  • Hence, the optimal SBP in patients with hypertensive disorder remained a controversial topic.
  • The most recent Systolic Blood Pressure Intervention Trial (SPRINT) has shown that intensive SBP target of < 120 mmHg improved the cardiovascular outcomes and the overall survival compared to the standard SBP target of 135 to 139 mmHg.
  • However, aggressive SBP lowering may be harmful in the elderly and incite more adverse effects such as hypotension, end-organ hypoperfusion (causing acute kidney injury, and intracranial hypoperfusion which may link to cognitive decline), and polypharmacy.
  • It is suggested that a goal blood pressure of < 130/80 mmHg is appropriate as long as the patient tolerates it.
  • Otherwise, < 140/90 mmHg is considered reasonable in patients who are in the elderly population and patients with labile blood pressure or polypharmacy.
  • Management strategies should always be patient-centered, with the aim of optimizing blood pressure control and avoiding polypharmacy, especially in the elderly.

J-curve Phenomenon

  • Various studies have shown a J-curve association between blood pressure with risk of myocardial infarction and death.
  • Patients with isolated systolic hypertension who receive antihypertensive treatment may precipitously drop their DBP as well.
  • As myocardial perfusion occurs mainly during diastole, an excessive drop in DBP may increase the risk of cardiovascular disease and death.

Complications of hypertensive retinopathy

People with HR are at risk of developing complications related to the retina. These include the following:

  • Ischemic optic neuropathy, which occurs when high blood pressure blocks off normal blood flow in the eyes, damaging the optic nerve. The optic nerve carries images of what we see to the brain.
  • Retinal artery occlusion, which occurs when the arteries that carry blood to the retina become blocked by blood clots. When this happens, the retina doesn’t get enough oxygen or blood. This results in vision loss.
  • Retinal vein occlusion, which occurs when the veins that carry blood away from the retina become blocked by blood clots.
  • Nerve fiber layer ischemia, or damage to the nerve fibers, which may lead to cotton-wool spots, or fluffy white lesions on the retina.
  • Malignant hypertension, which is a rare condition that causes blood pressure to increase suddenly, interfering with vision and causing sudden vision loss. This is a potentially life threatening condition.
  • Retinal artery occlusion
  • Retinal vein occlusion
  • Macro aneurysm of retinal arteriole
  • Diabetic retinopathy (DR): Both hypertensive retinopathy and DR together in a patient is called as mixed retinopathy. HTN is also known to be a major risk factor for the progression of DR.
  • Anterior ischemic optic neuropathy
  • Age-related macular degeneration
  •  Glaucoma
  • Retinal arteriolar emboli
  • Epiretinal membrane formation
  • Cystoid macular edem

People with HR are also at an increased risk of having a stroke or heart attack. One 2013 study of 2,907 people between the ages of 50 and 73 found that those with HR were more likely to have a stroke than people without the condition.

This was true even in people with blood pressure controlled by treatment. A 2008 study of 5,500 people between the ages of 25 and 74 showed both an increased risk of stroke or cardiovascular disease in those with HR.

Lifestyle changes

You may also need to make some lifestyle changes as part of your ISH treatment plan. These can include:

  • Losing weight. This can help lower your blood pressure. In fact, for every two pounds you lose, you could lower your blood pressure by about 1 mm Hg.
  • Eating a heart-healthy diet. You should also aim to reduce the amount of sodium in your diet. Consider the DASH diet, which emphasizes eating:
    • vegetables
    •  whole grains
    •  low-fat dairy products
    •  fruits
  • Exercising. Not only can exercise help you lower your blood pressure, but it can help you control your weight and stress levels. Aim to perform some sort of aerobic exercise for at least 30 minutes most days of the week.
  • Decreasing alcohol consumption. Healthy alcohol intake is one drink per day for women and two per day for men.
  • Quitting smoking. Smoking can raise your blood pressure and also contribute to a variety of other health problems.
  • Managing stress. Stress can raise your blood pressure, so finding ways to relieve it are important. Examples of techniques to help lower stress are meditation and deep breathing exercises.
  • Eating a heart-healthy diet: Choose fruits, vegetables, grains and low-fat dairy foods.
  • Exercising regularly, at least 30 minutes a day of moderate activity, such as walking (check with your healthcare provider before starting an exercise program).
  • Keeping your weight under control: Check with your healthcare provider for a weight-loss program, if needed.
    Cutting back on alcoholic drinks.
  • Limiting caffeine intake.
  • Limiting sodium (salt) in your diet: Read nutrition labels on packaged foods to learn how much sodium is in one serving.
  • Reducing and avoiding stress when possible: Many people find that regular meditation or yoga helps.