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Clinically valid conclusions from retinal photographs need the best formulae

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Cardiovascular and cerebrovascular diseases are common causes of morbidity and mortality. Modifiable risk factors such as tobacco smoking, a diet high in saturated fatty acids, physical inactivity, high cholesterol level,… Click to show full abstract

Cardiovascular and cerebrovascular diseases are common causes of morbidity and mortality. Modifiable risk factors such as tobacco smoking, a diet high in saturated fatty acids, physical inactivity, high cholesterol level, hypertension, and a high body mass index are all associated with retinal vascular changes [1]. The retinal superficial vasculature offers a unique possibility to noninvasively and directly observe the microvasculature and, through photographic imaging enables quantitative measuring of the retinal vessels with high reproducibility [1]. Changes in the ocular circulation due to systemic disease may lead to loss of vision due to a lack of perfusion. Observation of the retinal microcirculation may therefore allow the detection of early changes and also serve as a marker to track any changes over time, to assess changes in lifestyle and treatment efficacy. Arterial walls grow thicker during the decades leading to atherosclerosis. Differentiation between mechanisms of action needs physiologically sensible measurements. Central retinal artery caliber is inferred from arteriolar diameters measured on photos. Formulae for such central retinal artery equivalent (CRAE) were developed by Parr, Hubbard, and Knudtson [1–3]. As blood pressure should be an almost linear function of the ratio of arterial and venular caliber (AVR = CRAE / CRVE) [1], the central retinal vein equivalent (CRVE) was defined similarly, adjusting for thinner walls. Blood flow is proportional to the lumen of vessels rather than caliber. Therefore, CRAE and CRVE internally average 2 lumina, before converting back to the caliber. The calculation is repeated for the results to mimic bifurcation. The Parr, Hubbard, and Knudtson formulae can be thought of as weighted means with lower weights for the largest and the smallest calibers measured. If an uneven number of measurements is used, the median gets a higher weight. If an even number of measurements is used, either the limits of the median class get the higher weight, or more extreme measurements. In the case of 4 measurements, even the most extreme values could get the highest weight. The algorithm may thus be robust (5 measurements) or may propagate variability of outliers (4 measurements). CRAE, unweighted average of calibers and root of mean lumen result in different numbers, may not be compared, but they are highly correlated as long as the same measurements are used. Using different numbers of measurements drastically reduces the association. The number of arterioles and venules measured can bias CRAE and CRVE [3]. Choosing the four thickest vessels should result in a greater mean than choosing the six thickest vessels, i.e. considering two thinner ones, too. So, the number of vessels measured should be constant within a study for internal validity. It should be the same as in other studies for external validity. Measurements of blood vessel calibers should all be made in the same region. The standard region would be shifted, if the axial length is disregarded. A recent publication highlights the importance of measurement zone [4]. Figure 1 illustrates the increase of the measurement zone in longer eyes and the additional change in relative location. This shift in size and location impacts all ocular structures, as the corresponding measurement points of the retinal nerve fiber layer (RNFL) can no longer be directly compared to the normative database. The shift in location has therefore relocated the measurement point to a different retinal location and as a consequence, a lower or higher than normal measurement maybe obtained, but still leaving the observer in the dark about the true thickness. This also applies to measurement zones defined for retinal vessel caliber measurements and caliber size. However, while the measurement zone in a longer eye becomes enlarged (as in covering a larger area), the opposite applies to the detail * Rebekka Heitmar [email protected]

Keywords: location; central retinal; number; measurement; crae crve; formulae

Journal Title: Graefe's Archive for Clinical and Experimental Ophthalmology
Year Published: 2021

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