Key Features

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  Arteriolar narrowing.

  
  
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  Arteriovenous nicking.

  
  
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  Microaneurysms.

  
  
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  Silver/copper wiring.

Associated Retinal Findings

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  Branch retinal vein occlusion.

  
  
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  Central retinal vein occlusion.

  
  
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  Macroaneurysm.

Key Features

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  Retinal hemorrhages.

  
  
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  Cotton–wool spots.

  
  
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  Serous retinal detachment.

  
  
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  Optic disc edema.

  
  
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  Choroidal ischemia.

Associated Feature

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  Malignant hypertension, encephalopathy, pre-eclampsia, eclampsia, kidney disease, and pheochromocytoma.

Introduction

Hypertensive retinopathy represents ophthalmic findings secondary to systemic elevated blood pressure. Retinal as well as choroidal and optic nerve circulations can be affected. Both chronic structural damage and acute changes due to rapid elevation of blood pressure can be observed. Chronic changes include arteriolar narrowing, arteriovenous nicking, and copper and silver wiring. Microaneurysms, retinal blot and flame-shaped hemorrhages, hard exudates, and cotton–wool spots commonly are associated with exudative retinopathy. Acute changes associated with episodes of rapidly elevated blood pressure can include disc edema, choroidal infarction, along with exudative retinopathy.

Hypertensive retinopathy and hypertension are associated with development and progression of such vision-threatening disorders as retinal vein and artery occlusion, macroaneurysms, and diabetic retinopathy. Retinopathy is also an independent risk factor for stroke, cardiovascular mortality, renal disease, and cognitive decline. Given the high prevalence of hypertension, its association with cardiovascular complications and end organ damage, and poor blood pressure control among particular groups of patients, ophthalmologists play a role in establishing a diagnosis and educating patients about potential ramifications.

Epidemiology and Pathogenesis

Hypertension (HTN) is defined as systolic blood pressure greater than or equal to 140 mm Hg or diastolic blood pressure greater than or equal to 90 mm Hg. Essential HTN, not secondary to another disease process, is most common. Prevalence of HTN among US adults was 29% in 2011–2014; it increases with age and was found in 65% of those age 60 years and older. HTN prevalence is highest among non-Hispanic African Americans, and affects approximately 1 billion adults worldwide. Systolic blood pressure represents an independent risk predictor for coronary events, stroke, heart failure, and end-stage renal disease. However, among adults with HTN, only 53% had controlled blood pressure during 2011–2014, and young adults aged 18–39 tend to have lower awareness, treatment, and control (37%) of their HTN.

The hypertensive retinal changes are often associated with and masked by the presence of other retinal vascular diseases such as diabetes and vein occlusion. The prevalence of retinopathy has been reported to range from 6.6% to 17.2% and varies with race and ethnicity. Retinopathy without diabetes could also be related to increasing age, hyperglycemia, dyslipidemia, higher body mass index, and systemic inflammatory markers. It has, however, been shown that HTN is the major cause of retinopathy without diabetes.

HTN itself is a risk factor for development and progression of diabetic retinopathy, retinal vein and artery occlusion, retinal–arteriolar emboli, nonarteritic ischemic optic neuropathy, and retinal arterial macroaneurysm. It has also been reported to be a risk factor for age-related macular degeneration and glaucoma. Moreover, after risk factors such as systolic blood pressure and diabetes are controlled, advanced retinopathy is independently associated with clinical and subclinical stroke and cardiovascular mortality, congestive heart failure, renal disease, and cognitive decline and dementia. The relationship of hypertensive retinopathy with cerebrovascular disease is the strongest.

Ocular Manifestations

Hypertensive Retinopathy

The pathophysiology of hypertensive retinopathy is believed to occur in overlapping and not always sequential phases: a vasoconstrictive phase, an exudative phase, a sclerotic phase, and complications of the sclerotic phase. The arterioles and capillaries are affected.

In the early vasoconstrictive phase, a rise in systemic blood pressure excites pliable and nonsclerotic retinal vessels to increase their vascular tone. It usually presents as generalized retinal arteriolar narrowing. Persistently elevated blood pressure leads to intimal thickening, hyperplasia of the media wall, and hyaline degeneration. In this sclerotic stage, there are areas of severe generalized and focal arteriolar narrowing. Arteriovenous nicking occurs due to arteriolar compression of venules at their junctions as they share a common adventitial sheath ( Fig. 6.18.1 ). Alterations in the arteriolar light reflex are described as copper and silver wiring. The complications of the sclerotic phase include formation of macro- and microaneurysms of the retinal artery, artery or vein occlusion, and epiretinal membrane formation ( Fig. 6.18.2 ).

Mild to Moderate Chronic Hypertensive Retinopathy.

Note the nerve fiber layer hemorrhage and sporadic areas of arteriovenous nicking. Blood pressure measured 168/93.

Collateral Vessels in the Superior Macula of a Patient With Hypertensive Retinopathy and a Resolved Branch Retinal Vein Occlusion.

A few microaneurysms and retinal hemorrhages persist from the occlusion.

In the exudative phase, which is usually associated with an acute rise in blood pressure, the blood–retinal barrier is disrupted, resulting in exudation of blood and lipids and retinal ischemia. Clinically, microaneurysms, focal intraretinal periarteriolar transudates, retinal blot (inner retinal) and flame-shaped (nerve fiber layer) hemorrhages, hard exudates, and cotton–wool spots are seen ( Fig. 6.18.3 ). Cotton–wool spots represent focal ischemic areas of the nerve fiber layer. In cases of acute blood pressure elevation, the swelling of the optic disc and choroidal ischemia may occur as described later.

Moderate Hypertensive Retinopathy.

Microaneurysms, retinal blot and flame-shaped hemorrhages, arteriovenous nicking, and cotton–wool spots.

Generalized arteriolar narrowing and arteriovenous nicking is usually seen in chronic hypertensive damage and might correspond to historic and not to current blood pressure levels. On the other hand, focal arteriolar narrowing, retinal hemorrhages, microaneurysms, and cotton–wool spots are associated with concurrently measured blood pressure.

There have been several classification systems of hypertensive retinopathy ( Box 6.18.1 ). These have not been extensively utilized, as interobserver variability has been reported. Suggestions have been made to establish a photographic classification of the retinal signs similar to diabetic retinopathy.

Box 6.18.1

Classifications of Hypertensive Retinopathy

Keith-Wagener-Barker Classification

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  Grade 1: Generalized arteriolar narrowing

  
  
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  Grade 2: Focal narrowing and arteriovenous nicking/nipping

  
  
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  Grade 3: Grade 2 plus exudates, hemorrhages, and cotton–wool spots

  
  
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  Grade 4: Grade 3 plus optic disc swelling

Mitchell-Wong Classification

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  Mild: generalized and/or focal arteriolar narrowing, arteriovenous nicking/nipping, opacity of arteriolar wall (copper/silver wiring)

  
  
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  Moderate: retinal hemorrhages (flame, dot, blot), exudates, cotton–wool spots

  
  
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  Malignant: moderate plus optic disc swelling

For differential diagnosis of hypertension retinopathy, see Box 6.18.2 .

Box 6.18.2

Differential Diagnosis of Chronic Hypertensive Retinopathy

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  Diabetic retinopathy

  
  
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  Retinal venous obstruction

  
  
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  Hyperviscosity syndromes

  
  
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  Congenital hereditary retinal arterial tortuosity

  
  
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  Ocular ischemic syndrome

  
  
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  Radiation retinopathy

Hypertensive Choroidopathy

Hypertensive choroidopathy usually occurs in association with acutely elevated blood pressure and more frequently affects younger patients whose blood vessels are pliable and not sclerotic. Hypertensive emergencies are characterized by severe elevations in blood pressure above 180/120 mm Hg. Malignant hypertension and encephalopathy might be present. It can be seen in patients with pre-eclampsia, eclampsia, essential hypertension, kidney disease, and pheochromocytoma. The retinal changes, as described above, include focal intraretinal periarteriolar transudates, microaneurysms, retinal flame-shaped hemorrhages, hard exudates, and cotton–wool spots. Optic nerve swelling can be present as well. Choroidal changes involve patchy perfusion of choriocapillaris. Histologically, it is due to fibrinoid necrosis of the choroidal arteries and arterioles with occlusion of the choriocapillaris. Areas of focal choroidal ischemia called Elschnig’s spots appear as pale, yellow, well-demarcated lesions that with time become pigmented as a secondary consequence of tissue infarction ( Fig. 6.18.4 ). Global choroidal dysfunction affects the pumping capacity of the retinal pigment epithelium, leading to exudative retinal detachments that are usually posterior in location ( Fig. 6.18.5 ). Siegrist’s streaks are the rarest finding and present as linear configurations of hyperpigmentation that develop over choroidal arteries. The pigmentation has been attributed to hypertrophy and hyperplasia of the retinal pigment epithelium. The streaks usually radiate out to the periphery, passing deep to the retinal vessels along the course of sclerosed choroidal vessels.

Elschnig’s Spots.

Serous Detachment of the Retina in a 27-Year-Old Patient Who Has Pregnancy-Induced Hypertension, 3 Days Postpartum.

Blood pressure measured 158/100 mm Hg. Note the subretinal fibrin and folds in the retina .

(Courtesy Franklin L. Myers.)

Hypertensive Optic Disc Edema

Optic nerve edema is usually seen in acutely elevated blood pressure. Raised intracranial pressure and concomitant optic nerve ischemia have been implicated to lead to disc swelling ( Fig. 6.18.6 ). Subsequent optic nerve pallor can occur. Acute and significant lowering of the blood pressure can result in optic nerve head infarction and subsequent marked optic atrophy and permanent vision loss.

Bilateral Malignant Hypertensive Retinopathy in a Patient With Blood Pressure of 260/140.

(A) Right and (B) left eyes. Disc edema, exudate, retinal hemorrhages, venous dilation, narrowing of the arterioles, Elschnig’s spots, and Siegriest’s streaks are all present.

(Courtesy Thomas Hedges III, MD.)

For differential diagnosis of acute hypertension retinopathy, see Box 6.18.3 .

Box 6.18.3

Differential Diagnosis of Acute Hypertensive Retinopathy

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  Bilateral central serous chorioretinopathy

  
  
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  Bilateral central retinal vein obstruction

  
  
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  Collagen vascular diseases

  
  
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  Diabetic retinopathy (especially in the setting of diabetic papillopathy)

Diagnosis and Ancillary Testing

Hypertensive retinopathy is a clinical diagnosis made when characteristic retinal vascular, choroidal, or optic disc changes are visualized on slit-lamp biomicroscopy. Ancillary studies can help confirm the diagnosis. Fluorescein angiography (FA) demonstrates narrowing of the retinal arteries, arterioles, and capillary bed, which is the earliest angiographic feature of systemic hypertension. Multiple focal areas of severe retinal ischemia secondary to focal arteriolar narrowing or occlusion are seen. Dilated retinal capillaries and microaneurysms develop at the margins of these areas, which are typically located around the optic disc or along the major retinal vessels ( Fig. 6.18.7 ). In malignant HTN, the optic nerve hyperfluorescence and leakage are seen.

The Right Eye of the Same Patient as Shown in Fig. 6.18.3 .

(A) A prominent cotton–wool spot in the papillomacular bundle is seen with an adjacent intraretinal hemorrhage. (B) Fluorescein angiography shows capillary nonperfusion in the area corresponding to the cotton–wool patch; note the hypofluorescence of the intraretinal hemorrhage, caused by blockage.

Cotton–wool spots are due to ischemia of the nerve fiber layer. On optical coherence tomography (OCT), they are seen as hyperreflectivity of the nerve fiber layer that subsequently results in permanent damage and thinning.

FA and OCT are also useful in conditions associated with HTN and hypertensive retinopathy such as macroaneurysms, retinal artery or vein occlusion, and diabetic retinopathy.

Treatment and Future Directions

The US Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII), the Canadian Hypertension Education Program, and the World Health Organization (WHO) International Society of Hypertension identify hypertensive retinopathy as target organ damage. Documented target organ damage can affect patients’ treatment and follow-up schedule. The British Hypertension Society 2004 Guidelines (BHS IV) indicated that severe HTN and grade III–IV retinopathy are suggested indications for specialist referral. Advanced hypertensive retinopathy is also a risk factor for subclinical and clinical stroke, cognitive decline, and cardiovascular mortality.

One of the challenges in hypertensive retinopathy research is a lack of a single classification scheme. Hypertensive changes are often seen in patients with diabetes and arteriosclerotic vascular disease. In the past, it has also been noted that the assessment of retinal microvascular changes varied between observers. Recent advances in digital retinal imaging provide an opportunity to quantify and monitor hypertensive retinopathy, including such imaging biomarkers as retinal vessel width. These objective findings could also be utilized in the emerging world of telemedicine.

The newer imaging modalities of wide-field imaging, adaptive optics, and OCT angiography might contribute to our understanding of hypertensive retinopathy. For instance, adaptive optics are used to describe the shapes of microaneurysms and to quantitatively examine the retinal vasculature. Study of retinal vessel caliber provides a noninvasive approach that could allow evaluation of systemic microvascular morphology.