Rebekka Heitmar

Retinal vessel tortuosity measures and their applications

Structural retinal vascular characteristics, such as vessel calibers, tortuosity and bifurcation angles are increasingly quantified in an objective manner, slowly replacing subjective qualitative disease classification schemes. This paper provides an overview of the current methodologies and calculations used to compute retinal vessel tortuosity. We set out the different parameter calculations and provide an insight into the clinical applications, while critically reviewing its pitfalls and shortcomings.

Regional differences in oxygen saturation in retinal arterioles and venules.

BackgroundRetinal vessel oxygenation saturation measurements have been the focus of much attention in recent years as a potential diagnostic parameter in a number of ocular and systemic pathologies. This interest has been heightened by the ability to measure oxygen saturation in vivo using a photographic technique.MethodsRetinal vessel oxygenation in venules and arterioles of 279 retinal vessels of 12 healthy Caucasian participants (mean age: 30 SD (+/− 6) years) were measured consecutively three times to evaluate short-term variation in oxygen saturation and regional variability of retinal vessel oxygen saturation using dual-wavelength technology (Oxymetry Modul, Imedos, Germany). All subjects underwent standard optometric assessment including non-contact intra-ocular pressure assessment as well as having their systemic blood pressure measured.ResultsVessels were grouped as either near-macula or peripheral, depending on their location. Peripheral arterioles and venules exhibited significantly lower oxygen saturation compared to their near-macula counterparts (arterioles: 94.7% (SD 3.9) vs. 99.7% (SD 3.2); venules: 65.1% (SD 7.2) vs. 90.3% (SD 6.7)). Both arterioles and venules, main branches, and those feeding and draining the retina near the macula and periphery showed low short-term variability of oxygen saturation (arterioles: COV 1.2–1.8%; venules: COV 2.9–4.9%).ConclusionsRetinal arterioles and venules exhibit low short-term variation of oxygen saturation in healthy subjects. Regional differences in oxygen saturation could be a potential useful marker for risk stratification and diagnostic purposes of area-specific retinal pathology such as age-related macula degeneration and diabetic maculopathy.

Altered Blood Vessel Responses in the Eye and Finger in Coronary Artery Disease

PURPOSE Cardiac function, such as heart rate variability, is abnormal in coronary artery disease, but its relation with the function of ocular and nail-fold blood vessels is unknown. The hypothesis was that there is abnormal retinal and peripheral microvascular endothelial function compared with large blood vessel and cardiac function. Twenty-four patients with coronary artery disease (CAD) and 30 healthy, age- and sex-matched control subjects were enrolled in the study. METHODS Peripheral microcirculatory function was measured with continuous retinal vessel diameter assessment and nail-fold capillaroscopy. Systemic vascular function was evaluated by 24-hour blood pressure, arterial stiffness, low (LF)- and high (HF)-frequency heart rate variability, ECG monitoring, and the plasma markers von Willebrand factor (vWf) and soluble E selectin. RESULTS Peripheral nail-fold capillary (P = 0.009) and retinal vessel (average baseline corrected flicker response [BFR]; P = 0.034) responses and reaction time in response to flicker (P = 0.016) were significantly different in patients compared with controls. Furthermore, patients demonstrated higher arterial stiffness (P = 0.005), LF and HF heart rate variability (P = 0.004, P = 0.006), and vWf level (P = 0.044), but there was no difference in soluble E selectin level (P = 0.278). In the CAD patients, LF and HF heart rate variability both correlated with average BFR (r = 0.58, P = 0.004; r = -0.6, P = 0.003, respectively). There was no such relationship in the healthy controls. CONCLUSIONS Microcirculatory abnormalities of the retina and nail-fold vessels are present in CAD. The two indices of heart rate variability correlated with an index of ocular vessel responses. The latter may be a surrogate marker of abnormal heart rate variability in CAD.

Abnormal retinal vascular function and lipid levels in a sample of healthy UK South Asians

Background/aims To investigate ethnic differences in retinal vascular function and their relationship to traditional risk indicators for cardiovascular disease (CVD). Methods A total of 90 normoglycaemic subjects (45 South Asian (SA) and 45 age- and gender-matched white Europeans (WEs)) were recruited for the present study. Retinal vessel reactivity to flickering light was assessed by means of the dynamic retinal vessel analyser according to a modified protocol. Fasting plasma glucose, triglycerides (TG), total, LDL and HDL cholesterol were also measured in all individuals. Results SA individuals showed higher fasting triglyceride (p=0.001) and lower HDL levels (p=0.007), leading to a higher TG:HDL-C ratio (p=0.001) than age-matched WE subjects. Additionally, in SAs, the retinal arterial reaction time in response to flicker stimulation was significantly longer in the last flicker cycle than in the WEs (p=0.039), and this change correlated positively with measured plasma TG levels (r=0.60; p=0.01). No such relationship was observed in the WEs (p>0.05). Conclusion Even in the absence of overt vascular disease, in otherwise healthy SAs there are potential signs of retinal vascular function impairment that correlates with established plasma markers for CVD risk.

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

Assessing vascular function using dynamic retinal diameter measurements: A new insight on the endothelium -

The influence of simulated cataract on retinal vessel oximetry measurements

To assess the impact of human crystalline lens opacification and yellowing, similar to that observed in patients with cataracts, on retinal vessel blood oxygen saturation measurements using custom manufactured soft contact lenses.

Transient cardiac ischaemia and abnormal variations in systemic blood pressure in unselected primary open angle glaucoma patients

Purpose:  To investigate the relationship between the occurrence of transient cardiac ischaemic episodes and variations in the ambulatory 24‐h blood pressure and heart rate measurements in a group of unselected glaucoma patients.

The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses.

PurposeTo test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease.MethodsOcular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index.ResultsCentral retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p < 0.05). Arterial reaction time was linked to serum creatinine (p = 0.036) and eGFR (p = 0.039); venous reaction time was linked to creatinine clearance (p = 0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p < 0.001 and p = 0.003, respectively) and the dilatation amplitude (p = 0.038 and p = 0.048, respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p = 0.004) and dilatation amplitude (p = 0.017), vWf was linked to the maximum constriction response (p = 0.016), and creatinine clearance to the baseline diameter fluctuation (p = 0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p = 0.022).ConclusionsSeveral retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses.

Comparison of subjective and objective methods to determine the retinal arterio-venous ratio using fundus photography

PURPOSE To assess the inter and intra observer variability of subjective grading of the retinal arterio-venous ratio (AVR) using a visual grading and to compare the subjectively derived grades to an objective method using a semi-automated computer program. METHODS Following intraocular pressure and blood pressure measurements all subjects underwent dilated fundus photography. 86 monochromatic retinal images with the optic nerve head centred (52 healthy volunteers) were obtained using a Zeiss FF450+ fundus camera. Arterio-venous ratios (AVR), central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were calculated on three separate occasions by one single observer semi-automatically using the software VesselMap (ImedosSystems, Jena, Germany). Following the automated grading, three examiners graded the AVR visually on three separate occasions in order to assess their agreement. RESULTS Reproducibility of the semi-automatic parameters was excellent (ICCs: 0.97 (CRAE); 0.985 (CRVE) and 0.952 (AVR)). However, visual grading of AVR showed inter grader differences as well as discrepancies between subjectively derived and objectively calculated AVR (all p<0.000001). CONCLUSION Grader education and experience leads to inter-grader differences but more importantly, subjective grading is not capable to pick up subtle differences across healthy individuals and does not represent true AVR when compared with an objective assessment method. Technology advancements mean we no longer rely on opthalmoscopic evaluation but can capture and store fundus images with retinal cameras, enabling us to measure vessel calibre more accurately compared to visual estimation; hence it should be integrated in optometric practise for improved accuracy and reliability of clinical assessments of retinal vessel calibres.

Total arterial compliance:the future of cardiovascular risk assessment?

In recent years, cardiovascular risk assessment has developed into an important area of research in the management of patients at risk of developing cardiovascular disease (CVD) and to gain more insight into the risk progression of those suffering from CVD. A multitude of new invasive and non-invasive assessments, questionnaires and combinations of the aforementioned have been introduced and tested in order to determine their clinical utility in the stratification of cardiovascular risk. Circulating markers of endothelial function and inflammation, such as endothelin, von Willebrand factor and C-reactive protein, have been identified as useful markers not only in the diagnosis of CVD but also in disease monitoring, progression and risk assessment. Nevertheless, there are limitations as to how much information these markers are able to provide with respect to CVD risk and local structure and organ integrity. Thus, other technologies assessing more structural and functional parameters have been evaluated with regard to their strength and value in CVD risk assessment. Lifestyle factors, age and other environmental factors have added to the list of risk identifiers and predictors. All of these facets provide valuable information describing an individual’s cardiovascular health. However, the sheer multitude of the available assessments has rather caused confusion than clarification, because of the lack of a common basis, structure and guidelines not only in administering those tests but also in their interpretation. More recently, total arterial compliance (TAC) has been added to this list and has been shown to be a valuable assessment not only for CVD risk evaluation but also for assessment of the relationship between structural and functional changes in the vascular system with respect to its elasticity and capacity. The study presented in the current issue by Haluska et al. highlights the strength of TAC over more traditional evaluation techniques such as pulse pressure and echocardiography. The assessment of TAC has also proven to be capable of differentiating between hypertensive, elderly and healthy individuals, which is of particular importance in an increasingly ageing society.