Central Retinal Arteriolar Research Articles

Retinal vascular diameters in relation to physical activity in Danish children - The CHAMPS Eye Study.

Our objective was to determine associations between retinal vascular caliber and physical activity (PA) in a school-based child cohort. In a prospective study, we created a childhood cumulative average PA-index using objectively measured PA (accelerometry) assessed at four periods between 2009 and 2015. Cumulative exposure to PA intensities was estimated. Cross-sectional examinations on biomarkers, anthropometry, and ophthalmological data including retinal fundus photographs were performed in 2015. Semi-automated measurements of retinal vascular diameters were performed and summarized into central retinal arteriolar and venular equivalents (CRAE, CRVE). We included 307 participants. Mean age in 2015 was 15.4years (0.7). The mean CRAE and CRVE were 156.5μm (2.8) and 217.6μm (7.7), respectively. After adjusting for age, gender, and axial length, more time in PA was independently related to thinner retinal venules (β-coefficient=-1.25μm/%, 95% confidence interval=-2.20, -0.30, P<.01). Sedentary time was associated with wider venules (P<.01). Furthermore, birthweight (β-coefficient=0.56μm/%, 95% confidence interval=0.18, 0.95, P<.01) was associated with CRVE. Blood pressure was associated with thinner retinal arterioles (β-coefficient=-0.19μm/mmHg, 95% confidence interval=-0.36, -0.01, P=.04). We concluded that children with higher PA in childhood had thinner retinal venular caliber. Our results suggest that PA during childhood positively impacts the retinal microcirculation and that retinal vascular analysis may be a possible assessment to detect microvascular impairments in children with an increased risk of future cardiovascular disease.

Cross-sectional association between oral health and retinal microcirculation.

To investigate the relation between oral health status and microcirculation, we analysed the association between periodontitis and number of teeth with retinal vessel diameters in a population-based study. We analysed data from the Study of Health in Pomerania-TREND (SHIP-TREND). All subjects (3,183 for number of teeth, 3,013 for mean probing depth and 2,894 for mean attachment level) underwent nonmydriatic funduscopy and dental examination. We measured central retinal arteriolar (CRAE), venular (CRVE) vessel diameters and calculated arterio-venous ratio (AVR) from static vessel analysis (SVA). Periodontal status was assessed using the case definition of the Center for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP). Data were analysed by linear (CRAE, CRVE, AVR) and logistic regression (AVR<0.8) adjusted for age, sex, smoking status, alcohol consumption, body mass index, systolic blood pressure, hsCRP and type-2-diabetes mellitus. Only in men, significant associations were found between periodontal and retinal conditions. Severe periodontitis [β=-0.0120 (-0.0218; -0.0007 95%-CI)] and mean probing depth [β=-0.0054 (-0.0105; -0.0002 95%-CI)] were inversely associated with AVR; severe periodontitis [β=3.80 (0.61; 6.98 95%-CI)], mean probing depth [β=1.86 (0.23; 3.49 95%-CI)] and mean attachment level [β=1.31 (0.34; 2.27 95%-CI)] with CRVE and mean attachment level with CRAE [β=0.91 (0.14; 1.69 95%-CI)]. Our results point towards an association between periodontal conditions and AVR in men. Periodontitis may impact microvascular endothelium function. Improving oral health to reduce periodontitis might lead to reduced risk for other age-related diseases.

Effects of different endurance exercise modalities on migraine days and cerebrovascular health in episodic migraineurs: A randomized controlled trial.

Aerobic exercise training is a promising complementary treatment option in migraine and can reduce migraine days and improve retinal microvascular function. Our aim was to elucidate whether different aerobic exercise programs at high vs moderate intensities distinctly affect migraine days as primary outcome and retinal vessel parameters as a secondary. In this randomized controlled trial, migraine days were recorded by a validated migraine diary in 45 migraineurs of which 36 (female: 28; age: 36 (SD:10)/BMI: 23.1 (5.3) completed the training period (dropout: 20%). Participants were assigned (Strata: age, gender, fitness and migraine symptomatology) to either high intensity interval training (HIT), moderate continuous training (MCT), or a control group (CON). Intervention groups trained twice a week over a 12-week intervention period. Static retinal vessel analysis, central retinal arteriolar (CRAE) and venular (CRVE) diameters, as well as the arteriolar-to-venular diameter ratio (AVR) were obtained for cerebrovascular health assessment. Incremental treadmill testing yielded maximal and submaximal fitness parameters. Overall, moderate migraine day reductions were observed (ηP2=.12): HIT revealed 89% likely beneficial effects (SMD=1.05) compared to MCT (SMD=0.50) and CON (SMD=0.59). Very large intervention effects on AVR improvement (ηP2=0.27), slightly favoring HIT (SMD=-0.43) over CON (SMD=0), were observed. HIT seems more effective for migraine day reduction and improvement of cerebrovascular health compared to MCT. Intermittent exercise programs of higher intensities may need to be considered as an additional treatment option in migraine patients.

Innovative technology shows impact of glycaemic control on peripheral retinal vessels in adolescents with type 1 diabetes.

Retinal imaging enables non-invasive microvasculature assessment; however, only central retinal vessels have been studied in type 1 diabetes. Peripheral smaller vessels have a major haemodynamic role and may differ from central vessels in their response to the diabetic milieu. We hypothesise that diabetes has a greater impact on peripheral retinal vessels vs central vessels. Retinal photographs from adolescents (n=736; age 12-20years) with type 1 diabetes were graded (Singapore I Vessel Assessment) with vessel calibres measured in the 'central zone' as central retinal arteriolar and venular equivalents (CRAE and CRVE, respectively) and the 'extended zone' as mean width of arterioles and venules (MWa and MWv, respectively). Multivariable linear regression was used to explore associations between vessel calibres and HbA1c, diabetes duration, sex and BP. Mean±SD age was 14.1±1.5years, HbA1c was 8.5±1.3% (69.4±14.1mmol/mol) and median diabetes duration was 4.9years (interquartile range 3.1-7.6years). Wider MWa was associated with HbA1c (β 0.01 [95% CI 0.004, 0.03]), longer diabetes duration (0.07 [0.02, 0.13]) and higher systolic BP (0.04 [0.02, 0.05]). MWv was associated with HbA1c (0.02 [0.009, 0.03]) and higher systolic BP (0.04 [0.03, 0.06]). CRAE was associated with longer diabetes duration (0.93 [0.58, 1.28]) and higher systolic BP (-0.28 [-0.37, -0.19]). CRVE was associated with longer diabetes duration (0.91 [0.42, 1.41]) and higher systolic BP (-0.20 [-0.33, -0.07]). Girls had wider vessels (for all four calibre measurements). In adolescents with type 1 diabetes, higher HbA1c is associated with adverse changes to peripheral smaller retinal vessels but not central vessels. The predictive value of retinal vascular imaging should be evaluated using longitudinal data.

Retinal vascular calibers in contemporary patients with chronic systemic inflammatory diseases: The Greek REtinal Microcirculation (GREM) study

BackgroundChronic systemic inflammatory diseases (CSID) are associated with increased cardiovascular morbidity and mortality. Widening of retinal venular calibers has been independently associated with systemic inflammation and cardiovascular risk in the general population. We aimed to test the hypothesis that retinal vessel calibers are altered in a population with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and spondyloarthropathies (SpA) compared to a reference group (RG). MethodsBetween 2012 and 2014 digital retinal images were obtained from consecutive individuals and retinal vessel calibers were measured with validated software to determine central retinal arteriolar and venular equivalents. ResultsOne hundred eighty-eight patients with CSID [(74 RA, 75 SLE, 39 SpA), (70.2% females, mean age 50.4 ± 12.5 years)] and 512 non-CSID individuals [(187 normotensives and 325 hypertensives, 90 of whom untreated; RG), (43.7% females, mean age 52.3 ± 11.7)] were recruited. Logistic regression analysis after adjustment for all factors associated with retinal vessel calibers in univariate analysis (age, sex, body mass index, blood pressure, anti-hypertensive/lipid modifying drugs and disease duration), showed that both arteriolar and venular retinal vessel calibers were comparable between CSID patients and the RG. No significant differences were found regarding retinal vessel calibers between each patient subgroup and the RG. ConclusionsRetinal vessel calibers were not significantly altered in patients with CSID. Well-controlled disease, as indicated by inflammatory indices, may be an explanation of our results suggesting that sufficient control of inflammation could improve microvascular abnormalities in these populations.

OP.1A.10] CONVENTIONAL AND AMBULATORY BLOOD PRESSURE AS PREDICTORS OF RETINAL ARTERIOLAR NARROWING

Objective: To investigate to what extent conventional (CBP) and daytime ambulatory (ABP) blood pressure predict narrowing of the retinal microvasculature. Design and method: In a population-based longitudinal study, 783 white Flemish participants (mean age, 38.2 years; 51.3% women) were randomly recruited, whose blood pressure was measured at baseline and follow-up and who underwent retinal photography at follow-up. CBP and ABP were averaged of five consecutive auscultatory readings and ambulatory oscillometric readings (10 AM–8 PM) programmed at 20 minute intervals. Systolic/diastolic HT thresholds were 140/90 mmHg for CBP and 135/85 mmHg for ABP. Central retinal arteriolar (CRAE) and venular (CRVE) equivalents and their ratio (AVR) were used as retinal traits post-processed by Vasculomatic ala Nicola software. Results: In multivariable-adjusted models including both CBP and ABP at baseline, CRAE changes after 10.3 years (median) were unrelated to CBP (P > = 0.14), whereas ABP predicted CRAE narrowing (P < = 0.01). Per 1-SD increment in systolic/diastolic blood pressure, the association sizes were -0.95 μm (95% confidence interval, -2.20 to 0.30)/ -0.75 μm (-1.93 to 0.42) for CBP and -1.76 μm (-2.95 to -0.58)/-1.48 μm (-2.61 to -0.34) for ABP. CRVE was not related to CBP or ABP, while associations of AVR with blood pressure mirrored those of CRAE, the numerator of the ratio. In multivariable-adjusted models with baseline ABP and follow-up CBP, CRAE decreased (P < = 0.049) by -1.61/-1.04 μm and by -2.60/-2.40 μm in relation to baseline daytime and follow-up conventional systolic/diastolic blood pressures, respectively. Compared with normotension (normal CBP and ABP; prevalence, 77.6%), HT patients had smaller CRAE (147.5 vs. 152.7 μm; P < 0.001) and AVR (0.68 vs. 0.70; P = 0.001). CRAE and AVR were not different (P > = 0.06) between normotension and white-coat HT (elevated CBP and normal ABP; 5.4%) and between masked HT (normal CBP and elevated ABP; 10.2%) and HT (elevated CBP and ABP; 6.8%). Conclusions: The paradigm that retinal arterial narrowing precedes HT can be explained by the limitations of CBP measurement, including the nonidentification of masked HT.

Retinal microvascular diameter, a hypertension-related trait, in ECG-gated vs. non-gated images analyzed by IVAN and SIVA.

The diameters of the retinal microvasculature reflect intermediate target organ damage and predict adverse health outcomes. In view of the pulsatility of the cerebral blood flow and refinement of software used for off-line analysis, we assessed the repeatability of retinal microvascular diameters in ECG-gated vs. non-gated images using nonmydriatic retinal photographs (Canon Cr-DGi visualization system) postprocessed by IVAN (Vasculomatic ala Nicola, version 1.1) or SIVA (Singapore I Vessel Assessment, version 3.6). Using these algorithms, we determined the central retinal arteriolar (CRAE) and venular (CRVE) equivalents and their ratio (arteriole-to-venule ratio (AVR)). The estimates of CRAE (mean, 158.5 μm), CRVE (222.5 μm) and AVR (0.71) in 10 volunteers were unaffected (P⩾0.059) by ECG gating. We assessed intragrader repeatability by the Bland and Altman approach in 30 participants with non-gated images and 30 with ECG-gated photographs. Repeatability, which was expressed as the percentage of near maximal variability (4-s.d. range), did not improve with ECG gating. Using SIVA, CRAE and CRVE were systematically larger (P⩽0.031), and the AVR estimates were similar (P⩾0.15) compared with IVAN. The differences (IVAN-SIVA) averaged -5.4 μm for CRAE, -3.9 μm for CRVE and -0.012 for AVR in the non-gated images and -3.3 μm, -6.9 μm and 0.006, respectively, in the ECG-gated photographs. In conclusion, ECG gating does not affect estimates of the retinal microvascular diameters or improve intragrader repeatability. SIVA yields slightly but significantly larger estimates of the retinal arteriolar and venular diameters. Combining historical readings analyzed by IVAN with more recent readings by SIVA is possible only for AVR and is not recommended for either CRAE or CRVE.

Association of consumption of dairy products and meat with retinal vessel calibers in subjects at increased cardiovascular risk

Background and aimsAssociation of dairy products and meat consumption with macrocirculation is previously described, but such association with microcirculation is poorly investigated. We aimed to test the hypothesis that the consumption of high- and low-fat dairy products as well as red, white, and processed meat is associated with retinal vessel calibers in adults at an increased risk of cardiovascular disease (CVD). Methods and resultsIn consecutive subjects (n = 181, age: 51.3 ± 12.4 years, 51.4% women) without CVD and diabetes mellitus but with increased CVD risk, we obtained digital left and right retinal images. These images were assessed with validated software to determine central retinal arteriolar and venular equivalents and the arteriolar to venular ratio (CRAE, CRVE, and AVR, respectively). The consumption of dairy products and meat was assessed through 24-h recalls in all volunteers. After adjustment for potential confounders, the following findings were obtained: (i) low-fat milk and yogurt were positively associated with CRAE (b=0.145, p=0.031 left; b=0.141, p=0.038 right) and inversely associated with CRVE (b=−0.155, p=0.026 left; b=−0.146, p=0.041 right); (ii) low-fat cheese was positively associated with CRAE (b=0.164, p=0.011 left and b=0.155, p=0.017 right); and (iii) red meat was inversely associated with CRAE (b=−0.143, p=0.032 left; b=−0.114, p=0.050 right). High-fat milk, yogurt, and cheese or white and processed meat were not found to be associated with retinal vessel calibers. ConclusionsHigh consumption of low-fat milk, yogurt, and cheese and low consumption of red meat could be beneficial for retinal microvascular health. Prospective studies are needed to verify these findings.

Relationship of retinal vascular calibre and diabetic retinopathy in Chinese patients with type 2 diabetes mellitus: the Desheng Diabetic Eye Study.

To describe the relationship of retinal arteriolar and venular calibre with diabetic retinopathy (DR) and related risk factors, including glucose levels and other biomarkers in a Chinese population with type 2 diabetes mellitus (T2DM). A cross-sectional study. Patients with T2DM were recruited from a local community in urban Beijing. Seven fields 30° colour fundus photographs were taken and examined for the presence and severity of DR using a standardised grading system. Retinal vascular calibres were measured and expressed as average central retinal arteriolar and venular equivalent using a computer-based program. A total of 1340 patients with T2DM were included for analysis. Of these, 472 (35.22%) had DR. Wider retinal venular calibre, but not arteriolar calibre, was associated with increasing glucose and glycosylated haemoglobin A1c levels (p<0.006) and dyslipidaemia (p for trend <0.05). After adjusting for possible covariates, the higher quartile of retinal venular calibre was associated with higher prevalence of any DR (OR 2, 95% CI 1.36 to 2.95). Venular calibre increased from 224.33 μm in those without retinopathy to 231.21 μm in those with mild, 241.01 μm in those with moderate and 235.65 μm in those with severe retinopathy (p for trend <0.001). Arteriolar calibre was not associated with DR. In the current study, wider venular calibre, but not arteriolar calibre, was shown to be associated with development and increased severity of DR independently from other risk factors in a Chinese diabetic population.

Separate and Combined Effects of Hypoxia and Horizontal Bed Rest on Retinal Blood Vessel Diameters.

To assess the separate and combined effects of exposure to prolonged and sustained recumbency (bed rest) and hypoxia on retinal microcirculation. Eleven healthy male subjects (mean ± SD age = 27 ± 6 years; body mass index [BMI] = 23.7 ± 3.0 kg m-2) participated in a repeated-measures crossover design study comprising three 21-day interventions: normoxic bed rest (NBR; partial pressure of inspired O2, PiO2 = 133.1 ± 0.3 mm Hg); hypoxic ambulation (HAMB; PiO2 = 90.0 ± 0.4 mm Hg), and hypoxic bed rest (HBR; PiO2 = 90.0 ± 0.4 mm Hg). Central retinal arteriolar (CRAE) and venular (CRVE) equivalents were measured at baseline and at regular intervals during each 21-day intervention. Normoxic bed rest caused a progressive reduction in CRAE, with the change in CRAE relative to baseline being highest on day 15 (ΔCRAE = -7.5 μm; 95% confidence interval [CI]: -10.8 to -4.2; P < 0.0001). Hypoxic ambulation resulted in a persistent 21-day increase in CRAE, reaching a maximum on day 4 (ΔCRAE = 9.4 μm; 95% CI: 6.0-12.7; P < 0.0001). During HBR, the increase in CRAE was highest on day 3 (ΔCRAE = 4.5 μm; 95% CI: 1.2-7.8; P = 0.007), but CRAE returned to baseline levels thereafter. Central retinal venular equivalent decreased during NBR and increased during HAMB and HBR. The reduction in CRVE during NBR was highest on day 1 (ΔCRVE = -7.9 μm; 95 CI: -13.3 to -2.5), and the maximum ΔCRVE during HAMB (24.6 μm; 95% CI: 18.9-30.3) and HBR (15.2 μm; 95% CI: 9.8-20.5) was observed on days 10 and 3, respectively. The diameters of retinal blood vessels exhibited a dynamic response to hypoxia and bed rest, such that retinal vasodilation was smaller during combined bed rest and hypoxia than during hypoxic exposure.

Reliability of retinal vessel calibre measurements using a retinal oximeter.

BackgroundSummarised retinal vessel diameters are linked to systemic vascular pathology. Monochromatic images provide best contrast to measure vessel calibres. However, when obtaining images with a dual wavelength oximeter the red-free image can be extracted as the green channel information only which in turn will reduce the number of photographs taken at a given time. This will reduce patient exposure to the camera flash and could provide sufficient quality images to reliably measure vessel calibres.MethodsWe obtained retinal images of one eye of 45 healthy participants. Central retinal arteriolar and central retinal venular equivalents (CRAE and CRVE, respectively) were measured using semi-automated software from two monochromatic images: one taken with a red-free filter and one extracted from the green channel of a dual wavelength oximetry image.ResultsParticipants were aged between 21 and 62 years, all were normotensive (SBP: 115 (12) mmHg; DBP: 72 (10) mmHg) and had normal intra-ocular pressures (12 (3) mmHg). Bland-Altman analysis revealed good agreement of CRAE and CRVE as obtained from both images (mean bias CRAE = 0.88; CRVE = 2.82).ConclusionsSummarised retinal vessel calibre measurements obtained from oximetry images are in good agreement to those obtained using red-free photographs.

Novel Genetic Loci Associated With Retinal Microvascular Diameter.

There is increasing evidence that retinal microvascular diameters are associated with cardiovascular and cerebrovascular conditions. The shared genetic effects of these associations are currently unknown. The aim of this study was to increase our understanding of the genetic factors that mediate retinal vessel size. This study extends previous genome-wide association study results using 24 000+ multiethnic participants from 7 discovery cohorts and 5000+ subjects of European ancestry from 2 replication cohorts. Using the Illumina HumanExome BeadChip, we investigate the association of single-nucleotide polymorphisms and variants collectively across genes with summary measures of retinal vessel diameters, referred to as the central retinal venule equivalent and the central retinal arteriole equivalent. We report 4 new loci associated with central retinal venule equivalent, one of which is also associated with central retinal arteriole equivalent. The 4 single-nucleotide polymorphisms are rs7926971 in TEAD1 (P=3.1×10(-) (11); minor allele frequency=0.43), rs201259422 in TSPAN10 (P=4.4×10(-9); minor allele frequency=0.27), rs5442 in GNB3 (P=7.0×10(-10); minor allele frequency=0.05), and rs1800407 in OCA2 (P=3.4×10(-8); minor allele frequency=0.05). The latter single-nucleotide polymorphism, rs1800407, was also associated with central retinal arteriole equivalent (P=6.5×10(-12)). Results from the gene-based burden tests were null. In phenotype look-ups, single-nucleotide polymorphism rs201255422 was associated with both systolic (P=0.001) and diastolic blood pressures (P=8.3×10(-04)). Our study expands the understanding of genetic factors influencing the size of the retinal microvasculature. These findings may also provide insight into the relationship between retinal and systemic microvascular disease.

Regarding: Diabetic macular ischaemia is associated with narrower retinal arterioles in patients with type 2 diabetes

I read with great interest the article ‘Diabetic macular ischaemia is associated with narrower retinal arterioles in patients with type 2 diabetes’ by Liew et al. (2015). The authors should be congratulated on this important article regarding diabetic macular ischaemia (DMI) which is a severe vision-threatening condition, even in the anti-VEGF era. The main finding of the article was an independent association between central retinal arteriolar narrowing and DMI. Retinal vascular calibres are important non-invasive biomarkers which are predictive of early-stage (Cheung et al. 2008) as well as end-stage diabetic retinopathy (Broe et al. 2014). However, observations regarding retinal vascular calibres and diabetic macular oedema (DMO) or DMI are still limited. In a retrospective study of 69 eyes from patients with DMO, we found a decrement in macular retinal arteriolar and venular calibres 6 months after focal/grid laser treatment (Lundberg et al. 2013). On the other hand, we did not find a statistically significant change in central retinal arteriolar or venular diameter. Liew et al. (2015) elegantly demonstrated an inverse association between DMI severity and central retinal arteriolar diameter, but this was no longer statistically significant when patients who had panretinal photocoagulation (PRP) were excluded. Panretinal photocoagulation is considered an important confounder because it has been demonstrated that patients who had PRP were more likely to have central retinal arteriolar narrowing (Grauslund et al. 2009). Given that central retinal arteriolar vessel calibres are measured around the optic disc, these might be considered a more ‘global’ measurement of retinal function. Did the authors consider expanding the observations to macular calibre measurements given that this could be a more sensitive marker of macular perfusion?

Impaired coronary and retinal vasomotor function to hyperoxia in Individuals with Type 2 diabetes

PurposeAdults with diabetes are at a high risk of developing coronary heart disease. The purpose of this study was to assess coronary artery vascular function non-invasively in individuals with and without Type 2 diabetes and to compare these coronary responses to another microvascular bed (i.e. retina). We hypothesized that individuals with diabetes would have impaired coronary reactivity and that these impairments would be associated with impairments in retinal reactivity. MethodsCoronary blood velocity (Transthoracic Doppler Echocardiography) and retinal diameters (Dynamic Vessel Analyzer) were measured continuously during five minutes of breathing 100% oxygen (i.e. hyperoxia) in 15 persons with Type 2 diabetes and 15 age-matched control subjects. Using fundus photographs, retinal vascular calibers were also measured (central retinal arteriole and venule equivalents). ResultsIndividuals with diabetes compared to controls had impaired coronary (−2.34±16.64% vs. –14.27±10.58%, P=0.03) and retinal (arteriole: −0.04±3.34% vs. −3.65±5.07%, P=0.03; venule: −1.65±3.68% vs. −5.23±5.47%, P=0.05) vasoconstrictor responses to hyperoxia, and smaller central arteriole–venule equivalent ratios (0.83±0.07 vs. 0.90±0.07, P=0.014). Coronary reactivity was associated with central retinal arteriole equivalents (r=−0.516, P=0.005) and retinal venular reactivity (r=0.387, P=0.034). ConclusionDiabetes impairs coronary and retinal microvascular function to hyperoxia. Impaired vasoconstrictor responses may be part of a systemic diabetic vasculopathy, which may contribute to adverse cardiovascular events in individuals with diabetes.

Intact calibers of retinal vessels in patients with systemic sclerosis.

A primary endothelial cell dysfunction is thought to be involved in systemic sclerosis (SSc)-associated fibroproliferative vasculopathy of the microcirculation and small arterioles, even in sites not affected by fibrosis. Because the role of fibroblasts in pathologic modifications and vascular wall remodeling is relatively unclear, and because the retina provides a unique opportunity to assess microcirculation in the absence of resident fibroblasts, we systematically evaluated retinal vessels in patients with SSc. Digital retinal images were obtained from both eyes of 93 consecutive patients with fully characterized SSc and 29 healthy controls matched 1:1 for age and sex with selected patients without diabetes, hypertension history, or antihypertensive treatment. Internal microvascular calibers (erythrocyte column width in μm) by central retinal arteriolar and venular equivalents and arteriolar to venular ratio were measured using validated software. Arteriolar and venular calibers were similar in patients and their matched controls (mean ± SEM; 187 ± 2 vs 184 ± 3, p = 0.444, and 211 ± 2 vs 216 ± 3, p = 0.314, respectively). Both arteriolar and venular calibers and their ratio in patients with SSc were not associated with disease duration, extent of skin involvement, pulmonary fibrosis, digital ulcers or pitting scars, amputations, digital capillaroscopic findings, inflammatory indices, or autoantibodies. The evidence that retinal microcirculation is spared in SSc suggests that fibroproliferative vasculopathy may depend on specific cellular or soluble factors not present in the retinal environment.

Association between retinal vessel caliber and arterial stiffness in a population comprised of normotensive to early-stage hypertensive individuals.

Although impairment of the micro- and macrocirculation is considered inherent to sustained hypertension, there is a substantial lack of studies investigating whether an association exists between micro- and macrovascular damage, especially in early-stage hypertension. We studied a meticulously selected population, free of diabetes and cardiovascular disease, of 223 individuals: 137 never-treated, newly diagnosed patients with recent onset of hypertension and 86 normotensive individuals. Nonmydriatic retinal photography was used to assess retinal microvascular diameters, including central retinal arteriolar (CRAE) and venular equivalent and arteriovenous ratio (AVR). Arterial stiffness was evaluated by measurement of pulse wave velocity (PWV) and aortic augmentation index (AIx). Compared with normotensive subjects, hypertensive patients exhibited significantly increased PWV (8.1 vs. 7.1 m/sec; P < 0.001) and AIx (23.86% vs. 18.8%; P = 0.01) and decreased CRAE (86.47 vs. 91.44 μm; P = 0.001) and AVR (0.74 vs. 0.78; P = 0.007). A significant inverse association was demonstrated between PWV and CRAE (r = -0.205; P = 0.002), which remained significant after multivariable analysis. Likewise, CRAE (P = 0.04) and AVR (P = 0.02) were independent predictors of AIx. This study shows for the first time an association between quantitatively assessed retinal abnormalities and increased arterial stiffness in a sample of early-stage hypertensive and normotensive individuals, suggesting that micro- and macrocirculation impairment in hypertension is a dynamic, mutual, interdependent process present from its very early stages. Given the predictive value of both retinal arteriolar narrowing and arterial stiffness in terms of cardiovascular mortality and morbidity, identification of combined micro- and macrovascular damage might be helpful in cardiovascular risk stratification of hypertensive patients.

Effects of acute bouts of endurance exercise on retinal vessel diameters are age and intensity dependent

Alterations of retinal vessel diameters are associated with increased cardiovascular risk. We aimed to investigate changes in retinal vessel diameters in response to acute dynamic exercise of different intensities and whether these changes are age dependent. Seventeen healthy seniors (median (IQR) age 68 (65, 69) years) and 15 healthy young adults (median (IQR) age 26 (25, 28) years) first performed a maximal treadmill test (MTT) followed by a submaximal treadmill test (SMTT) and a resting control condition in randomised order. Central retinal arteriolar (CRAE) and central retinal venular (CRVE) diameter equivalents were measured before as well as 5 (t5) and 40 (t40) minutes after exercise cessation using a static retinal vessel analyser. Both exercise intensities induced a significant dilatation in CRAE and CRVE at t5 compared to the control condition (P < 0.001). At t40, the mean increase in CRAE and CRVE was greater for MTT compared to that for SMTT (CRAE 1.7 μm (95 % confidence interval (CI) −0.1, 3.6; P = 0.061); CRVE 2.2 μm (95 % CI 0.4, 4.1; P = 0.019)). However, the estimated difference at t5 between seniors and young adults in their response to MTT compared to SMTT was 5.3 μm (95 % CI 2.0, 8.5; P = 0.002) for CRAE and 4.1 μm (95 % CI −0.4, 8.6; P = 0.076) for CRVE. Wider arteries and veins after maximal versus submaximal exercise for seniors compared to young adults suggest that myogenic vasoconstriction in response to exhaustive exercise may be reduced in seniors. Age-related loss of vascular reactivity has clinical implications since the arteriolar vasoconstriction protects the retinal capillary bed from intraluminal pressure peaks.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-014-9650-3) contains supplementary material, which is available to authorized users.

Cross-sectional Associations of Medication and Supplement Use With Retinal Vascular Diameter in the Beaver Dam Eye Study

Retinal vessel diameters are being measured to examine their relationship with ocular and systemic disease and, in some studies, to calculate the risk of disease. Important factors that directly affect retinal vessel diameters, such as medication use, should be considered when estimating these associations. To quantify the association between selected medications and supplements and retinal vessel diameters. In a prospective cohort investigation, 4926 participants (aged 43-86 years at baseline) in the Beaver Dam Eye Study were evaluated every 5 years during 20 years of follow-up from 1988 to 2010. Central retinal arteriolar equivalent and central retinal venular equivalent measured from the Early Treatment Diabetic Retinopathy Study fundus photograph field 1. After Bonferroni correction, the use of any blood pressure medication (β = 0.75; P = .04), specifically calcium channel blockers (β = -1.02; P < .001), was significantly associated with wider central retinal arteriolar equivalent adjusting for refraction, photograph focus, age, systolic blood pressure, height, examination phase, educational level, smoking and drinking histories, and presence of diabetes mellitus and emphysema. Use of prostaglandin analogues was marginally associated with narrower central retinal arteriolar equivalent (β = -2.04; P = .09); β-blockers (β = -1.02; P = .10) and oral corticosteroids (β = 2.13; P = .07) were marginally associated with changes in the central retinal venular equivalent. Several medications are associated with central retinal arteriolar and venular equivalents. Prostaglandin analogues, calcium channel blockers, and oral corticosteroids have the largest relative effects. After Bonferroni correction was applied, the use of calcium channel blockers was most strongly associated with change in the central retinal arteriolar equivalent. The presence of factors that are associated with retinal vessel diameters should be considered when using retinal vessel diameter as an outcome or when using these measures to assess the risk of systemic or ocular disease.

LOCALIZED CHANGES IN RETINAL VESSEL CALIBER AFTER FOCAL/GRID LASER TREATMENT IN PATIENTS WITH DIABETIC MACULAR EDEMA

To compare retinal vessel caliber changes at the macula region and surrounding the optic disk after focal/grid laser treatment for diabetic macular edema. The study included 69 eyes from 46 patients treated with focal/grid laser for diabetic macular edema. Retinal photographs were taken <6 months before and 2 months and 12 months after focal/grid photocoagulation treatment. The diameters of retinal vessels around macula and the optic disk were measured separately before and after treatment. Optic disk and macular diameters were summarized into central retinal arteriolar and venular equivalent and macular retinal arteriolar and venular equivalent. Median age and duration of diabetes was 60 years and 13 years. There was a statistically significant decrease in diameter of the macular arterioles (macular retinal arteriolar equivalent 73.5 vs. 72.0 μm, P = 0.04) and venules (macular retinal venular equivalent 63.5 vs. 62.4 μm, P = 0.02) after treatment but no difference in central retinal arteriolar equivalent or central retinal venular equivalent before and after treatment. Retinal vascular calibers in control eyes did not change throughout the study. The diameters of macular vessels decreased after focal/grid laser treatment in most eyes. In contrast, vessel calibers at the optic disk did not change. Quantitative measurement of macular vessels may allow physicians to monitor the progress and success of diabetic macular edema treatment.

A Posteriori–Derived Dietary Patterns and Retinal Vessel Caliber in an Elderly Population

To examine the association between a posteriori-derived dietary patterns (DP) and retinal vessel caliber in an elderly population. This was a cross-sectional study of 288 elderly adults (>65 years) who participated in the European Eye study (EUREYE) Northern Irish cohort. DP were extracted using principal component analysis from completed food frequency questionnaires. Semi-automated computer grading was used to determine the mean retinal vessel diameters (central retinal arteriole equivalent [CRAE] and central retinal venule equivalent [CRVE]) from digitized visual field one images using a standard measurement protocol. THREE MAJOR DP WERE IDENTIFIED IN THIS POPULATION, WHICH ACCOUNTED FOR 21% OF THE TOTAL VARIANCE: a "healthy" pattern with high factor loadings for oily fish, fruits and vegetables, and olive oil; an "unhealthy" pattern with high factor loadings for red and processed meat, refined grains, eggs, butter, sugar and sweets; and a "snack and beverage" pattern with high factor loading for pizza, nuts, and coffee. Multivariable linear regression analysis indicated no significant association between major identified DP and mean CRAE or CRVE in all models. This is the first study to investigate associations between a posteriori-derived DP and retinal vessel caliber. There was no evidence of a relationship between extracted DP and retinal vessel measurements in this population. However, it is possible that potentially important relationships exist between single nutrients or foods and vessel diameters that cannot be identified using a DP approach. Further studies to examine the role of dietary factors in the microcirculation are required.