Hypertensive Retinopathy

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, 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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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:

Blood pressure categorySystolic blood pressureDiastolic blood pressure
Elevated blood pressure120–129 mm HgAND< 80 mm Hg
Hypertension stage 1130–139 mm HgOR80–89 mm Hg
Hypertension stage 2 ≥ 140 mm HgOR ≥ 90 mm Hg

Epidemiology

  • In the United States: 
    • 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 → swelling of the optic disc (papilledema)
  • Choroidal changes (choroidopathy) occur from poor perfusion:
    • Atrophy of overlying retinal pigment 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

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 ISlight or modest narrowing of the retinal arterioles, with an arteriovenous ratio of ≥ 1:2
Grade IIModest-to-severe narrowing of retinal arterioles with an arteriovenous ratio < 1:2 or arteriovenous nicking
Grade IIISoft exudates or flame-shaped hemorrhages
Grade IVBilateral optic edema
Table: Mitchell-Wong’s classification of hypertensive retinopathy
Grade of retinopathyRetinal findingsSystemic risks
NoneNo detectable signsNone
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, 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, and mortality
MalignantSigns of moderate retinopathy plus optic disc swellingStrong 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 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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