Applications of Retinal Vessel Analysis
The goal of cardiometabolic prevention is to avoid or at least delay the development and manifestation of vascular changes or diseases at an early stage. This is in line with the concept of EVA (Early Vascular Aging) and ADAM (Aggressive Decrease of Atherosclerosis Modifiers).
Retinal Vessel Analysis parameters offer new opportunities to extend this concept to include the microcirculation and to place microvascular parameters in the context of established macrovascular gold standards such as flow mediated dilation, intima media thickness, pulse wave velocity and others.
The microvascular risk parameters represent an additional benefit in cardiovascular risk stratification especially for women. It is desirable to record retinal microvascular parameters already in early childhood, because vascular aging starts very early. Studies show that already in children first changes of microvascular parameters are detectable by Retinal Vessel Analysis.
The individual influences of lifestyle changing measures are also reflected in the parameters of the vascular analysis. Of particular importance are the parameters of static vessel analysis, as these can be determined nonmydriatically, quickly and easily in screening. These parameters provide indicators of cardiovascular risk. Studies have shown that lifestyle changes and preventive measures lead to a significant individual reduction in vascular risk. The effect of a measure can be easily observed and is highly motivating for the patient.
Hypertension leads mainly to arterial vasoconstriction and arterial dysregulation in the retinal vessels. The parameters of the retinal vessel analysis are available to the hypertensiologist for therapy control and evaluation of therapy success as additional objective parameters or risk factors.
Studies have shown that these microvascular parameters provide additional value in individual risk stratification, especially in women.
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Further reading:
European Society of Cardiology/European Society of Hypertension versus the American College of Cardiology/American Heart Association guidelines on the cut-off values for early hypertension: a microvascular perspective.
Sci Rep. 2021 Feb 10;11(1):3473. doi: 10.1038/s41598-021-83096-1. PMID: 33568754; PMCID: PMC7876123.
From a developmental point of view, at least the retina with the optic nerve head can be considered as an outsourced part of the brain. Not only from the point of view of the optic nerves, but also with regard to the microcirculation, there are many similarities and close connections to the brain. Studies linking vascular status and autoregulatory functions of the retina to depression, Alzheimer’s disease, vascular dementia and stroke are therefore hardly surprising.
The parameters of the Static and Dynamic Vessel Analysis allow conclusions to be drawn about the risks of cerebrovascular events such as strokes and the severity of so-called “small vessel diseases”. Changes in retinal vascular parameters are associated with the frequency of white matter lesions on MRI and with the severity of dementia. There is evidence that retinal vessel analysis parameters can also be used to subtype between microvascular and macrovascular strokes.
Dynamic vascular analysis can be used to study not only NO-dependent endothelial function but also neurovascular coupling, myogenic autoregulation and their changes in various systemic diseases such as diabetes mellitus and arterial hypertension and to obtain important information about brain physiology and pathophysiology.
Retinal Vessel Analysis examines static and dynamic vascular parameters that quantify steady-state vascular status and vascular function or regulatory capacity of the microcirculation and are well-validated cardiovascular risk indicators. Systemic changes in the small arteries and veins of the microcirculation and their regulation occur in many organs as well as in the kidney in a similar form.
A large number of scientific publications present the associations between retinal vascular changes, arterial hypertension and renal changes. A very good evidence for the informative value of retinal vessel analysis are study results showing that venous dysregulation of retinal vessels is a predictor for mortality in patients with end-stage chronic renal failure.
The kidney plays an essential role in the development of systemic arterial hypertension. Conversely, arterial hypertension leads to changes in the microcirculation that can ultimately be studied in the eye as end-organ damage with retinal vascular analysis.
Organs can only function well with an adequate blood supply. This is especially true for the eye. The blood supply to the eye must be adapted to momentary needs at all times, among other things to compensate for fluctuations in perfusion pressure, to adapt to changing neuronal activities, or to keep the temperature at the fundus constant despite variations in the external temperature. Therefore, blood flow at rest and the ability of the vessels to regulate blood flow are of central importance.
Often disturbed blood flow is the cause of many eye diseases or an important co-factor for the occurrence or progression of eye disease. Imedos technology makes it possible to diagnose these vascular components and subsequently monitor the influence of a therapy.
Interdisciplinary approach: In many systemic diseases such as diabetes, hypertension, lipid metabolism disorders or rheumatism, the ophthalmologist can, by examining the blood vessels in the eye, provide colleagues from other specialties with crucial information about the general health of the vessels (the vascular health) and about the response to a therapy or prophylaxis, even in the early stages.
Consequences of circulatory disorders for the eye:
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The relatively rare acute reductions in blood supply lead to infarction, e.g., of the retina or optic disc
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The much more common chronic inferior perfusion favors severe disease outcomes and in extreme cases, the formation of neovascularizations
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Fluctuating oxygen supply due to impaired regulation increases local oxidative stress, a central factor in the pathogenesis of many diseases
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Hypoxia and oxidative stress damage the blood-brain barrier, favoring the formation of edema and hemorrhage
The focus of Imedos technology is on the retinal vessels because:
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A functioning retina is essential,
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The vessels of the retina are optically accessible,
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The activity of the retina can be increased in a controlled manner by flicker light and thus the ability and capacity of the regulation of the blood vessels can be measured,
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The retinal blood vessels are not autonomously innervated and vascular endothelial cell function can thus be specifically measured.
Why are vascular endothelial cells of particular interest?
The endothelial cells are crucially involved in the regulation of retinal blood flow. A human being has several trillion of these endothelial cells. Interestingly, from the health status of these cells in the retina, one can very well infer the health status of these cells in the whole body. In cardio- and cerebrovascular diseases as well as in primary vascular dysregulations, the vascular endothelial cells are always affected first.
Fields of application (clinical pictures in ophthalmology)
Retinal arterial occlusions
Examination with the VesselMap on the partner eye provides information on the general health of the blood vessels and thus on the risk of further vascular occlusions, whether in the eye or in other organs.
Retinal venous occlusion
Whether a venous occlusion is due to arterial disease is shown by SVA in the fellow eye. Often retinal venous pressure (RVP) is also elevated in the fellow eye. Lowering RVP with medication improves the prognosis of the affected eye and decreases the risk of venous occlusion in the second eye. RVP can be determined using the IOPstim.
Glaucoma
If damage progresses in a glaucoma patient despite normal or normalized eye pressure, then SVA and examination with the Imedos Dynamic Analyzer (IDA) shows whether and in what form a vascular disease is present. If both are clinically striking, the problem is usually one of atherosclerosis and its risk factors. If, on the other hand, the static vessel parameters are unremarkable and the examination with the IDA shows a limited endothelial function, a treatable primary vascular dysregulation is present.
If the RVP is elevated, this also reduces the blood flow to the optic disc. In this case, not only the eye pressure but also the RVP must be lowered.
Diabetic Retinopathy
Static Vessel Analysis with our VesselMap software early reveals the risk for developing diabetic retinopathy. If non-proliferative retinopathy is already visible, it indicates the risk for vascular complications, including the development of proliferative retinopathy.
The examination with the Imedos Dynamic Analyzer shows whether and how well the retinal blood flow can still be regulated. Elevated retinal venous pressure (RVP) increases hypoxia and thus the formation of cotton-wool spots and neovascularization. High RVP also increases transmural pressure, contributing to the formation of edema, hard exudates and hemorrhage.
Chorioretinopathy centralis serosa
In CRCS, ICG angiography can detect local dysregulation of the choroidal vessels. However, the frequent underlying dysregulation is also indicated by decreased responses in DVA and an increase in RVP.
Retinopathia pigmentosa (RP)
Here, the blood supply to the eye is partly secondary and partly primary reduced. If the examination with the DVA shows an endothelial dysfunction, this provides an indication that one component of it is primary. In most cases, RVP is also increased. Both can be improved therapeutically.
Perioperative vision loss
Acute vision loss associated with surgery, e.g., after spinal procedures are rare but severe. A disturbed regulatory ability, visible in the DVA, explains a missing or insufficient adaptation, e.g. to a special positioning. If the RVP is elevated, this is a further explanation of the event and allows prophylaxis.
Altitude sickness
If the oxygen partial pressure decreases, some people develop altitude sickness. Those affected usually have preexisting decreased responses in DVA and then increase their RVP more than others at altitude.
Flammer Syndrom (FS)
The FS is a general predisposition to react differently with the blood vessels to stimuli. The consequences are particularly common in the eye. Often the RVP is increased, the response in the DVA is decreased, but the vessel diameters in the SVA are normal. If this constellation is present, the risk of developing FS-associated disease is greater.
