Hypertensive Retinopathy

Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension has many adverse effects on the eye, of which retinopathy is the most common presentation. Hypertensive retinopathy consists of retinal vascular changes that develop as a direct effect of elevated blood pressure. In acute increases of blood pressure, autoregulation results in retinal arteriolar narrowing. In chronic hypertension, structural changes consistent with arteriosclerosis affect the retinal vasculature. Endothelial wall damage ensues and various signs appear including hemorrhages, cotton-wool spots, and exudates. In severe cases of uncontrolled hypertension Uncontrolled hypertension Although hypertension is defined as a blood pressure of > 130/80 mm Hg, individuals can present with comorbidities of severe asymptomatic or "uncontrolled" hypertension (≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic) that carries with it a significant risk of morbidity and mortality. Uncontrolled Hypertension, papilledema is seen. Management is focused on controlling hypertension. Patients with severe hypertensive retinopathy have an increased risk for coronary artery disease and stroke; therefore, detection and treatment of underlying hypertension are important.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

Hypertensive retinopathy:

  • Characterized by microvascular retinal changes and damage from hypertension
  • Arises from an acute increase in blood pressure and/or chronic hypertension

Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension:

Blood pressure category Systolic blood pressure Diastolic blood pressure
Elevated blood pressure 120–129 mm Hg AND < 80 mm Hg
Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension stage 1 130–139 mm Hg OR 80–89 mm Hg
Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension stage 2 ≥ 140 mm Hg OR ≥ 90 mm Hg

Epidemiology

  • In the United States: 
    • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension affects ⅓ of adults. 
    • Prevalence of hypertensive retinopathy ranges from 2%17% in non-diabetic patients. 
  • Under 45 years of age: men > women
  • Over 65 years of age: women > men
  • Higher prevalence in African Americans and those of Chinese descent
  • Associated with an increased risk of stroke and coronary artery disease

Pathophysiology

Vasoconstrictive phase

  • Local autoregulation responds to acute increases in blood pressure.
  • Elevation of blood pressure → increased intraluminal pressure
  • Vasospasm and vasoconstriction occur to reduce the flow (generalized retinal arteriolar narrowing).
  • In arteriosclerotic vessels: Some segments cannot increase the vascular tone, so segmental constriction occurs (focal arteriolar narrowing).

Sclerotic phase

  • Chronic hypertension leads to structural changes in the vessel wall:
    • Intimal thickening 
    • Medial hyperplasia
    • Hyaline degeneration of the arteriolar wall
  • Changes:
    • Severe arteriolar narrowing
    • Accentuated arteriolar light reflex from opacified vessel wall (silver and copper wiring)
    • Thick arteriole crosses, compresses, and narrows a venule (arteriovenous nicking).

Exudative phase

  • Phases are not necessarily sequential.
  • Exudative changes may occur acutely without the sclerotic phase (which is a result of chronically elevated blood pressure).
  • Changes include:
    • Uncontrolled hypertension disrupts the bloodretina barrier and causes endothelial wall damage and smooth muscle necrosis.
    • Blood and plasma products leak into the vessel wall, obliterating the vascular lumen.
  • Findings include:
    • Bleeding of vessels into the superficial nerve fibers (flame-shaped hemorrhages)
    • Bleeding into the inner retinal layer (dot-blot hemorrhages)
    • Retinal ischemia → nerve fiber microinfarctions, seen as fluffy opacification (cotton-wool spots)
    • Lipid residue leakage and accumulation in the area (hard exudates)
    • Vessel wall weakness (microaneurysms)

Malignant hypertension

  • Severely elevated blood pressure → increased intracranial pressure Increased Intracranial Pressure Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP) → swelling of the optic disc (papilledema)
  • Choroidal changes (choroidopathy) occur from poor perfusion:
    • Atrophy of overlying retinal pigment epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium (RPE): forms pigment lesions with white halo (Elschnig’s spots)
    • Choroidal ischemia showing as linear hyperpigmented lesions (Siegrist’s streaks
    • RPE detachments

Clinical Presentation and Diagnosis

Clinical presentation

  • Most patients are asymptomatic.
  • Possible: headaches and decreased or blurry vision
  • Rarely causes vision loss, but can occur with secondary optic atrophy or retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment

Diagnosis

  • Diagnosis is based on a dilated funduscopic exam.
  • Classifications of examination findings:
    • Keith-Wagener-Barker’s classification of hypertensive retinopathy: classification based on severity of retinal findings
    • Mitchell-Wong’s classification: classification based on severity and correlated with pathophysiologic changes
Table: Keith-Wagener-Barker’s classification of hypertensive retinopathy
Grade I Slight or modest narrowing of the retinal arterioles, with an arteriovenous ratio of ≥ 1:2
Grade II Modest-to-severe narrowing of retinal arterioles with an arteriovenous ratio < 1:2 or arteriovenous nicking
Grade III Soft exudates or flame-shaped hemorrhages
Grade IV Bilateral optic edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
Table: Mitchell-Wong’s classification of hypertensive retinopathy
Grade of retinopathy Retinal findings Systemic risks
None No detectable signs None
Mild
  • Generalized arteriolar narrowing
  • Focal arteriolar narrowing
  • Arteriovenous nicking
  • Copper or silver wiring
Modest association with risk of clinical stroke, subclinical stroke, coronary heart disease Coronary heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease, and mortality
Moderate
  • Retinal hemorrhage in the shape of flames, dots, or blots
  • Microaneurysms, cotton-wool spots, or hard exudates
Strong association with risk of clinical stroke, subclinical stroke, cognitive decline, coronary heart disease Coronary heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease, and mortality
Malignant Signs of moderate retinopathy plus optic disc swelling Strong association with mortality

Prognosis and Management

  • Some retinal changes in malignant hypertension regress with control of blood pressure. 
  • Left untreated, the mortality rate is 90% in malignant hypertension.
  • Management includes:
    • Lifestyle modifications (e.g., low-salt diet, weight loss, and regular exercise)
    • Smoking cessation
    • Antihypertensive medications
    • Target blood pressure is determined by other risk factors: cardio- and cerebrovascular disease, kidney disease, and diabetes.
Hypertensive emergency improvement

Improvement in fundus appearance after hypertension treatment.

Fundus photographs taken at time of presentation (A, B): Arteriolar narrowing, retinal hemorrhages, cotton-wool spots, and hard exudates (on the right) are noted.
Four months after diagnosis and treatment of systemic hypertension (C, D): Normalization of blood pressure resulted in the resolution of retinal hemorrhages and cotton-wool spots.
There is interval improvement in hard exudates in the right eye with a residual macular star.

Image: “Improvement in fundus appearance after treatment” by the Department of Ophthalmology and Visual Sciences, University of Michigan, 500 S State St, Ann Arbor, MI MI MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction 48109 USA. License: CC BY 4.0.

Differential Diagnosis

  • Cataract: a decrease in vision due to clouding of the lens, which presents as painless, blurry vision, and glare problems. Cataracts are the leading cause of blindness worldwide, and can occur at any age, but most cases affect those over 60 years of age.
  • Diabetic retinopathy: a visual impairment due to microvascular end-organ damage from diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus. Diabetic retinopathy is classified as non-proliferative and proliferative retinopathy. Non-proliferative retinopathy is characterized by microaneurysms, intraretinal hemorrhages, exudates, and macular edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema. The proliferative type is the presence of retinal or optic disc neovascularization. Patients are initially asymptomatic but in the late stages they present with decreased or fluctuating vision, possibly with floaters.
  • Retinal detachment: separation of the retina from the retinal pigment epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium, which results in rapid photoreceptor damage. Symptoms include painless vision changes such as sudden flashes of light, floaters, worsening peripheral vision, or having a shadow in the field of vision. Vision is described as irregular or curtain-like. Retinal detachment is an emergency requiring corrective surgery.
  • Central retinal artery occlusion: occlusion of the central retinal artery, the main blood supply of the optic nerve, by an embolus or an atheroma. Patients usually present with sudden, painless, monocular visual loss. Funduscopic findings include retinal whitening with a “cherry-red” spot. Central retinal artery occlusion is a medical emergency and visual recovery is dependent on immediate evaluation and treatment.
  • Central retinal vein occlusion: occlusion of the central retinal vein primarily from thrombus formation. Patients usually present with sudden, painless, monocular vision loss. The funduscopic exam reveals dilated tortuous veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins, intraretinal hemorrhages, and cotton-wool spots often described as having a “blood-and-thunder” appearance. Management requires an urgent referral to ophthalmology.

References

  1. American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines (2017). Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults.  J Am Coll Cardiol. 23976. doi: 10.1016/j.jacc.2017.07.745 
  2. Basile, J., et al. (2020). Overview of Hypertension in adults. UpToDate. Retrieved 26 Sept 2020, from https://www.uptodate.com/contents/overview-of-hypertension-in-adults?search=overview
  3. Elliott, W., et al. (2020). Moderate to severe hypertensive retinopathy and hypertensive encephalopathy in adults. UpToDate. Retrieved 25 Sept 2020, from https://www.uptodate.com/contents/moderate-to-severe-hypertensive-retinopathy-and-hypertensive-encephalopathy-in-adults
  4. Grosso, A., et al. (2005). Hypertensive retinopathy revisited: Some answers, more questions. British Journal of Ophthalmology, 89:1646-1654. doi: 10.1136/bjo.2005.072546
  5. Harjasouliha, A., Raiji, V., & Gonzalez, J. (2017) Review of hypertensive retinopathy. Elsevier. https://www.sciencedirect.com/science/article/abs/pii/S0011502916300839?via%3Dihub
  6. Henderson, A., et al. (2011). Hypertension-related eye abnormalities and the risk of stroke. Rev Neurol Dis, 8(1-2): 1–9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448945/
  7. Modi, P., & Arsiwalla, T. (2020). Hypertensive retinopathy. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK525980/
  8. Oh, K., Moinfar, N., & Roy, H. (2018). Ophthalmologic Manifestations of Hypertension. Medscape. Retrieved 25 Sept 2020, from https://emedicine.medscape.com/article/1201779-overview
  9. Townsend, R. Bakris, G., Kunins, L., & Forman, J. (2019). Ocular effects of hypertension. UpToDate. Retrieved 25 Sept 2020, from https://www.uptodate.com/contents/ocular-effects-of-hypertension
  10. Wong, T., & Mitchell, P. (2004). Hypertensive Retinopathy. N Engl J Med, 351:2310-2317. doi: 10.1056/NEJMra032865

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