Assessing vascular function using dynamic retinal diameter measurements: a new insight on the endothelium.

Reliable assessment of endothelial function is important for the diagnosis, risk prediction and treatment-monitoring in cardiovascular disease. Numerous techniques exist such as flow mediated dilation (FMD) (1, 2), venous occlusion plethysmography (3, 4), pulse-wave analysis (5) and laser Doppler iontophoresis (6). Individually, each technique provides some information on the state of endothelial function in vivo but reflects mainly large artery function; only limited information is conveyed about the body’s microcirculatory state. Functional in vivo assessment of the microcirculation is largely limited to invasive technology – e.g. coronary angiography (7) – which is not suitable for routine screening. However, novel methods using non-invasive technology such as magnetic resonance imaging and positron emission tomography have shown notable improvements for the assessment of coronary microvasculature (8) but are relatively costly. In a 2005 review on contemporary methods for assessing endothelial function (9) Alam et al. suggested the retinal vascular bed as suitable for non-invasive in vivo assessment. The ocular circulation is unique because it can be viewed directly and strongly resembles cerebral circulation. Measures of ocular circulation can thus be used as surrogate indices of cerebral circulatory mechanisms (10, 11). The focus of Alam’s review, however, was on static retinal vessel analysis and the use of parameters such as diameter measurements obtained by single retinal photographs. Since then, numerous groups have investigated dynamic retinal analysis (12) whereby continuous video recordings are made such that vessel parameters can be assessed over time. Dynamic retinal analysis has the potential to quantify endothelial function noninvasively in vivo over short time periods (usually no more than 5 minutes) by means of continuous vessel diameter measurements (13, 14). In order to achieve optimum imaging quality the pupil must firstly be dilated. The retinal vasculature can then be measured many times a second. Non-invasive stimulation methods (e.g. isometric exercise [15–17] and flickering light [18]) can be used to provoke the retinal vessels to react allowing assessment of endothelial function in retinal arterioles and venules before, during and after stimulation. In contrast to most large artery assessments this is less time consuming, less invasive and more convenient for regular followups. This technology enables both structural and dynamic assessment of microcirculation in humans and a plethora of measures have been introduced to quantify the structural and dynamic properties of retinal circulation (see below). The importance of static retinal vessel analysis with respect to cardiovascular disease has been demonstrated in the results of large population studies (e.g. the Beaver Dam Eye Study [19], the Arteriosclerosis Risk in Community Study [20] and Rotterdam Study [21]). These studies have found that larger retinal venular calibre is associated with an increased risk for stroke (22, 23), reduced arterial wall compliance in large arterial beds is associated with retinal arteriolar narrowing and reduced arterial wall compliance in small arterial beds is associated with retinal venular widening (23). Despite its predictive value for evaluating risk of cardiovascular disease this method only provides a snapshot of an individual’s circulatory state. Assessment of the dynamic properties of the circulatory system could provide additional information about endothelial dysfunction and facilitate early diagnosis of related diseases. Hence, this review is focused on describing dynamic retinal diameter assessments and their potential for assessing endothelial function in vivo in humans.