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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 Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome is the most common presentation. Hypertensive retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome consists of retinal vascular changes that develop as a direct effect of elevated blood pressure. In acute increases of blood pressure, autoregulation Autoregulation Systemic and Special Circulations results in retinal arteriolar narrowing. In chronic 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, 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 Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension is seen. Management is focused on controlling 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. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with severe hypertensive retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome have an increased risk for coronary artery Coronary Artery Truncus Arteriosus disease and stroke; therefore, detection and treatment of underlying 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 are important.

Last updated: Oct 27, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Hypertensive retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome:

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

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 MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg AND < 80 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma 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 Stage 1 Trypanosoma brucei/African trypanosomiasis 130–139 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg OR 80–89 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma 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 MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg OR ≥ 90 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma 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 Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of hypertensive retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome ranges from 2%17% in nondiabetic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Under 45 years of age: men > women
  • Over 65 years of age: women > men
  • Higher prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency in African Americans and those of Chinese descent
  • Associated with an increased risk of stroke and coronary artery Coronary Artery Truncus Arteriosus disease

Pathophysiology

Vasoconstrictive phase

Sclerotic phase

  • Chronic 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 leads to structural changes in the vessel wall:
    • Intimal thickening 
    • Medial hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation
    • Hyaline degeneration of the arteriolar wall
  • Changes:
    • Severe arteriolar narrowing
    • Accentuated arteriolar light reflex from opacified vessel wall (silver and copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements wiring)
    • Thick arteriole crosses, compresses, and narrows a venule (arteriovenous nicking).

Exudative phase

  • Phases are not necessarily sequential Sequential Computed Tomography (CT).
  • Exudative changes may occur acutely without the sclerotic phase (which is a result of chronically elevated blood pressure).
  • Changes include:
    • 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 disrupts the blood retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy barrier and causes endothelial wall damage and smooth muscle necrosis Muscle Necrosis Rhabdomyolysis.
    • Blood and plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products products leak into the vessel wall, obliterating the vascular lumen.
  • Findings include:
    • Bleeding of vessels into the superficial nerve fibers Nerve Fibers Slender processes of neurons, including the axons and their glial envelopes (myelin sheath). Nerve fibers conduct nerve impulses to and from the central nervous system. Nervous System: Histology (flame-shaped hemorrhages)
    • Bleeding into the inner retinal layer (dot-blot hemorrhages)
    • Retinal ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage → 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 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

  • Severely elevated blood pressure → increased intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension swelling Swelling Inflammation of the optic disc Optic disc The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. Eye: Anatomy ( papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension)
  • Choroidal changes (choroidopathy) occur from poor perfusion:
    • Atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation 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: Histology (RPE): forms pigment lesions with white halo (Elschnig’s spots)
    • Choroidal ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage showing as linear hyperpigmented lesions (Siegrist’s streaks
    • RPE detachments

Clinical Presentation and Diagnosis

Clinical presentation

  • Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are asymptomatic.
  • Possible: headaches and decreased or blurry vision Vision Ophthalmic Exam
  • Rarely causes vision Vision Ophthalmic Exam loss, but can occur with secondary optic atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation 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 Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome: 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 Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome
Grade I Slight or modest narrowing of the retinal arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology, with an arteriovenous ratio of ≥ 1:2
Grade II Modest-to-severe narrowing of retinal arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology 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 Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome
Grade of retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome Retinal findings Systemic risks
None No detectable signs None
Mild
  • Generalized arteriolar narrowing
  • Focal arteriolar narrowing
  • Arteriovenous nicking
  • Copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements 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 Mortality All deaths reported in a given population. Measures of Health Status
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 Mortality All deaths reported in a given population. Measures of Health Status
Malignant Signs of moderate retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome plus optic disc Optic disc The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. Eye: Anatomy swelling Swelling Inflammation Strong association with mortality Mortality All deaths reported in a given population. Measures of Health Status

Prognosis and Management

  • Some retinal changes in malignant 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 regress with control of blood pressure. 
  • Left untreated, the mortality Mortality All deaths reported in a given population. Measures of Health Status rate is 90% in malignant 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.
  • Management includes:
    • Lifestyle modifications (e.g., low-salt diet, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, and regular Regular Insulin exercise)
    • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation
    • Antihypertensive medications
    • Target blood pressure is determined by other risk factors: cardio- and cerebrovascular disease, kidney disease, and diabetes Diabetes 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.
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 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. Diabetic retinopathy is classified as non-proliferative and proliferative retinopathy. Non-proliferative retinopathy is characterized by microaneurysms, intraretinal hemorrhages, exudates, and macular 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, 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, 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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