Retinal vessel analysis

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Retinal vessel analysis is a non-invasive method to examine the small arteries and veins in the retina which allows to draw conclusions about the morphology and the function of small vessels elsewhere in the human body. Retinal vessel analysis is conducted mainly by ophthalmologists, cardiologists, neurologists and other medical specialities dealing with vascular diseases.

Contents

Methods

There are two variants of retinal vessel analysis which are based on a special fundus camera, the Retinal Vessel Analyzer which was developed by Imedos, a medical engineering company in Jena, Germany. Basically, the Retinal Vessel Analyzer measures the diameters of small arteries (arterioles) and vein (venules) in the posterior segment of the eye. In static retinal vessel analysis this is a snapshot, in dynamic vessel analysis (DVA) a 12.5 Hz optoelectric flickering light induces a stimulation of a specific segment of the retina to which the vessels react by a change in their diameter which is quantified by the device. There are different protocols for conducting this examination; a typical procedure consists of applying flicker light three times over 20 seconds each, followed by 80 seconds relaxation time. Usually an area of 0.5–1 optic disc diameter from the optic disc is analyzed by using special analyzing software. The test is conducted after pharmacological dilation of the patient's pupils; apart from applying these eyedrops, the examination is completely non-invasive and non-demanding for the person undergoing retinal vessel analysis.

Selected applications

Retinal vessel dynamics have the potential to serve as a tool for the assessment of risks in other organs since they are thought to reflect the general status of the microvasculature (i.e. the smallest vessels in the human body). The value of the examination with the Retinal Vessel Analyzer has been documented in a number of recent studies. There is growing evidence that in particular the dynamic vessel analysis is able to detect blood vessel damage - for instance as a consequence of aging or metabolic disease - in an early stage. Some examples:

Cardiology

In a recent publication, Andreas Flammer and his group at the Clinic of Cardiology at Zurich University performed retinal vessel analysis in 74 patients with compensated chronic heart failure, 74 patients with cardiovascular risk factors and 74 healthy controls. The primary endpoint, flicker-induced dilatation of retinal arterioles (FIDart), was significantly reduced in patients with chronic heart failure: 0.9% versus 2.3% in persons with risk factors and 3.6% in healthy individuals. The researchers concluded that retinal vessel analysis may represent a new and useful method to non-invasively monitor microvascular abnormalities in heart failure. [1] In patients with diabetes mellitus, those suffering from cardiovascular disease showed significant differences in arterial maximum constriction after flicker light stimulation compared to patients with diabetes but without cardiovascular disease. This difference in reaction pattern and lack of arterial constriction in DM is thought to provide a suitable marker to monitor progression. [2] In a cohort of 10,407 participants, analysing the retinal vessel caliber led to the reclassification of 21% of low-risk women to carrying an intermediate risk. [3] Patients recovering from a myocardial infarction and included in an exercise based cardiac rehabilitation programme showed marked improvement in the retinal microvacular response. [4]

Endocrinology

Hypercholesterolemia is associated with significant retinal microvascular dysfunction as evidenced in a study based on 67 patients with hypercholesterolemia without known cardiovascular disease by a reduction in flicker-induced dilatation of retinal arterioles. [5]

Sports Medicine

Researchers from the Institute of Exercise and Health Sciences at the University of Basel demonstrated that cardiovascular fitness and body composition affect retinal vessel diameters which in turn give an indication of a person's cardiovascular health. One parameter evaluated in retinal vessel analysis, the mean arteriolar to venular diameter ratio (AVR), correlated with individual fitness and normalized in obese individuals after they underwent a training program and weight reduction. This was seen as an indication that regular exercise reverses the subclinical impairment of the retinal microvasculature and thus most likely of small vessels in other organs. [6]

Neurology

In 2019, neurologists and ophthalmologists from Milan, Italy, demonstrated that arterial dilation was decreased in patients with manifest Alzheimer's disease and persons with mild cognitive impairment when performing dynamic vessel analysis. Since non-invasive and affordable methods for the early detection of Alzheimer's disease are scarce, the fact that alterations in vessel reaction could be detected in patients not yet clinically diagnosed was considered noteworthy. The study authors conclude that retinal vascular parameters may prove to be a useful biomarkers for these forms of dementia and to predict the disease progression. [7]

Ophthalmology

In a study with 276 diabetic patients, a reduced retinal arteriolar and venular dilatory response to flickering light in DVA in eyes suffering from diabetic retinopathy was associated with an increased risk of progression. [8]

Related Research Articles

Artery Blood vessels that carry blood away from the heart

An artery is a blood vessel in humans and most other animals that takes blood away from the heart to one or more parts of the body. Most arteries carry oxygenated blood; the two exceptions are the pulmonary and the umbilical arteries, which carry deoxygenated blood to the organs that oxygenate it. The effective arterial blood volume is that extracellular fluid which fills the arterial system.

Diabetic retinopathy Medical condition

Diabetic retinopathy, also known as diabetic eye disease (DED), is a medical condition in which damage occurs to the retina due to diabetes mellitus. It is a leading cause of blindness in developed countries.

Angina Chest discomfort due to not enough blood flow to heart muscle

Angina, also known as angina pectoris, is chest pain or pressure, a symptom of coronary heart disease, usually due to insufficient blood flow to the heart muscle (myocardium).

Hypertensive retinopathy Medical condition

Hypertensive retinopathy is damage to the retina and retinal circulation due to high blood pressure.

Microangiopathy is a disease of the microvessels, small blood vessels in the microcirculation. It can be contrasted to coronary heart disease, an angiopathy that affects the larger vessels.

Fibrate

In pharmacology, the fibrates are a class of amphipathic carboxylic acids. They are used for a range of metabolic disorders, mainly hypercholesterolemia, and are therefore hypolipidemic agents.

Vasodilation Widening of blood vessels

Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, which is the narrowing of blood vessels.

Arteriole Smaller branches of Arteries in the Capillaries

An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries.

Conjunctiva Conjunctiva is Outer protective layer/covering of sclera

The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera. It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epithelium and stratified cuboidal epithelium. The conjunctiva is highly vascularised, with many microvessels easily accessible for imaging studies.

In vascular diseases, endothelial dysfunction is a systemic pathological state of the endothelium. Along with acting as a semi-permeable membrane, the endothelium is responsible for maintaining vascular tone and regulating oxidative stress by releasing mediators, such as nitric oxide, prostacyclin and endothelin, and controlling local angiotensin-II activity.

Hypertensive kidney disease Medical condition

Hypertensive kidney disease is a medical condition referring to damage to the kidney due to chronic high blood pressure. It manifests as hypertensive nephrosclerosis. It should be distinguished from renovascular hypertension, which is a form of secondary hypertension, and thus has opposite direction of causation.

Fenofibrate Drug of the fibrate class, mainly used to reduce cholesterol levels

Fenofibrate, is an oral medication of the fibrate class used to treat abnormal blood lipid levels. It is less commonly used compared than statins because it treats a different type of cholesterol abnormality to statins. While statins have strong evidence for reducing heart disease and death, there is evidence to suggest that fenofibrate also reduces to the risk of heart disease and death. However, this seems only to apply to specific populations of people with elevated triglyceride levels and reduced high-density lipoprotein (HDL) cholesterol. Its use is recommended together with dietary changes.

Cotton wool spots

Cotton wool spots are opaque fluffy white patches on the retina of the eye that are considered an abnormal finding during a funduscopic exam. Cotton wool spots are typically a sign of another disease state, most common of which is diabetic retinopathy. The irregularly shaped white patches are a result of ischemia, or reduced blood flow and oxygen, in the retinal nerve fiber layer, which is located in the distribution of the capillaries of the superficial layer of the retina. These areas with reduced blood flow reflect the obstruction of axoplasmic flow due to mechanical or vascular causes and the consequential accumulation as a result of decreased axonal transport. This reduced axonal transport can then cause swelling or bulging on the surface layer of the retina, increasing the potential for nerve fiber damage.

Intima-media thickness

Intima–media thickness (IMT), also called intimal medial thickness, is a measurement of the thickness of tunica intima and tunica media, the innermost two layers of the wall of an artery. The measurement is usually made by external ultrasound and occasionally by internal, invasive ultrasound catheters. Measurements of the total wall thickness of blood vessels can also be done using other imaging modalities.

Coronary artery aneurysm Medical condition

Coronary artery aneurysm is an abnormal dilatation of part of the coronary artery. This rare disorder occurs in about 0.3–4.9% of patients who undergo coronary angiography.

Diabetic cardiomyopathy Medical condition

Diabetic cardiomyopathy is a disorder of the heart muscle in people with diabetes. It can lead to inability of the heart to circulate blood through the body effectively, a state known as heart failure, with accumulation of fluid in the lungs or legs. Most heart failure in people with diabetes results from coronary artery disease, and diabetic cardiomyopathy is only said to exist if there is no coronary artery disease to explain the heart muscle disorder.

Lipohyalinosis is a cerebral small vessel disease affecting the small arteries, arterioles or capillaries in the brain. Originally defined by C. Miller Fisher as 'segmental arteriolar wall disorganisation', it is characterized by vessel wall thickening and a resultant reduction in luminal diameter. Fisher considered this small vessel disease to be the result of hypertension, induced in the acute stage by fibrinoid necrosis that would lead to occlusion and hence lacunar stroke. However, recent evidence suggests that endothelial dysfunction as a result of inflammation is a more likely cause for it. This may occur subsequent to blood–brain barrier failure, and lead to extravasation of serum components into the brain that are potentially toxic. Lacunar infarction could thus occur in this way, and the narrowing – the hallmark feature of lipohyalinosis – may merely be a feature of the swelling occurring around it that squeezes on the structure.

Complications of hypertension

Complications of hypertension are clinical outcomes that result from persistent elevation of blood pressure. Hypertension is a risk factor for all clinical manifestations of atherosclerosis since it is a risk factor for atherosclerosis itself. It is an independent predisposing factor for heart failure, coronary artery disease, stroke, kidney disease, and peripheral arterial disease. It is the most important risk factor for cardiovascular morbidity and mortality, in industrialized countries.

Complications of diabetes mellitus include problems that develop rapidly (acute) or over time (chronic) and may affect many organ systems. The complications of diabetes can dramatically impair quality of life and cause long-lasting disability. Overall, complications are far less common and less severe in people with well-controlled blood sugar levels. Some non-modifiable risk factors such as age at diabetes onset, type of diabetes, gender and genetics may influence risk. Other health problems compound the chronic complications of diabetes such as smoking, obesity, high blood pressure, elevated cholesterol levels, and lack of regular exercise. Complications of diabetes are a strong risk factor for severe COVID-19 illness.

Sickle cell retinopathy can be defined as retinal changes due to blood vessel damage in the eye of a person with a background of sickle cell disease. It can likely progress to loss of vision in late stages due to vitreous hemorrhage or retinal detachment. Sickle cell disease is a structural red blood cell disorder leading to consequences in multiple systems. It is characterized by chronic red blood cell destruction, vascular injury, and tissue ischemia causing damage to the brain, eyes, heart, lungs, kidneys, spleen, and musculoskeletal system.

References

  1. ↑ Nägele, MR; et al. (2018). ": Retinal microvascular dysfunction in heart failure". European Heart Journal. 39: 47–56. doi: 10.1093/eurheartj/ehx565 .
  2. ↑ R. Heitmar, G.Y.H. Lip, R.E.Ryder, H.D. Blann: Retinal vessel diameters and reactivity in diabetes mellitus and/or cardiovascular disease. Heitmar et al. Cardiovasc Diabetol (2017) 16:56. DOI 10.1186/s12933-017-0534-6
  3. ↑ Seidelman, S; et al. (2016). "Retinal Vessel Calibers in Predicting Long-Term Cardiovascular Outcomes The Atherosclerosis Risk in Communities Study". Circulation. 134: 1328–1338. doi:10.1161/circulationaha.116.023425. PMC   5219936 . PMID   27682886.
  4. ↑ Louwies, T (2019). "Microvascular reactivity in rehabilitating cardiac patients based on measurements of retinal blood vessel diameters". Microvascular Research. 124: 25–29. doi:10.1016/j.mvr.2019.02.006. PMID   30807772.
  5. ↑ Nägele MP et al.: Retinal microvascular dysfunction in hypercholesterolemia.J Clin Lipidol. 2018;12:1523-1531
  6. ↑ Hanssen, H; et al. (2011). "Exercise-induced alterations of retinal vessel diameters and cardiovascular risk reduction in obesity". Atherosclerosis. 216: 433–439. doi:10.1016/j.atherosclerosis.2011.02.009.
  7. ↑ Querques, G; et al. (2019). "Functional and morphological changes of the retinal vessels in Alzheimer's disease and mild cognitive impairment". Scientific Reports. 9: 63. doi: 10.1038/s41598-018-37271-6 . PMC   6329813 . PMID   30635610.
  8. ↑ Lim, LS; et al. (2017). "Dynamic Responses in Retinal Vessel Caliber With Flicker Light Stimulation and Risk of Diabetic Retinopathy and Its Progression". Invest Ophthalmol Vis Sci. 58: 2449–2455. doi: 10.1167/iovs.16-21008 .
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