Vascular Caliber Research Articles

Association between head injury and concussion with retinal vessel caliber.

The adverse long-term consequences following traumatic brain injury are poorly understood, particularly on the cerebral microvasculature. Retinal vessels are a surrogate marker of cerebral vascular changes. We therefore aimed to examine the cross-sectional association between serious head injury or being knocked unconscious, and/or concussion and retinal microvascular signs, specifically, mean retinal arteriolar and venular calibre, in older adults after accounting for potential confounders. This cohort study involved 2,624 adults with mean age of 66.9 (±9.1) years who self-reported head injury and concussion parameters, and had gradable retinal photographs. Face-to-face interviews with trained interviewers allowed participants to report prior serious head injury or being knocked unconscious, and/or a previous diagnosis of concussion by a medical professional. Fundus photographs were taken and retinal vascular calibre measured using computer-assisted techniques and summarized. There were 25.9%, 15.3% and 10.1% who reported a prior serious head injury or being “knocked unconscious”, concussion, and both, respectively. Participants in the first group compared to non-injured participants had significantly wider (~2 μm) mean retinal venular calibre (p = 0.02), after adjusting for age, sex, smoking, body mass index, mean arterial blood pressure, type 2 diabetes and fellow vessel calibre. No significant associations were observed in people reporting medically diagnosed concussion or with mean retinal arteriolar calibre. Our exploratory study suggests that head injury is independently associated with wider retinal venular caliber. These findings warrant further investigation in longitudinal cohort studies.

INVESTIGATING DIAGNOSTIC BIOMARKERS OF COGNITIVE IMPAIRMENT BY UTILIZING VASCULAR AND NEUROGENIC CHANGES IN THE RETINA

Previous studies have demonstrated that Alzheimer's disease (AD) it is not limited to the brain but also affects the retina. We investigated the correlation between the retinal vascular complexity and neurodegenerative changes in patients with mild cognitive impairment (MCI). Quantification of the retinal structure and function using advanced retinal imaging and full-field electroretinogram (ERG) was performed. Also, visual performance exams were conducted using the Rabin cone contrast test (CCT). Retinal images and ERGs from each subject were obtained. Retinal vascular parameters were calculated using the Singapore Institute Vessel Assessment (SIVA) software which was also used to calculate the fractal dimension (FD) of the retinal vasculature network and retinal vascular caliber, summarized as central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE). The Montreal Cognitive Assessment (MoCA) was used to assess cognitive dysfunction. Spearman's linear correlation was performed between variables, the level of significance was set at 5%. For the analysis, Statistics 7.0 software was used (Statsoft Inc., Tulsa, OK). Of the 55 participants, 21 had cognitive impairment (38%), 34 served as healthy controls. We found that the complexity of the branching pattern and caliber of retinal vessels were lower in patients with MCI (FD (mean±SE): 1.310±0.020; CRVE (92.65±1.60; age range [76-86]) in comparison to healthy controls (FD: 1.382±0.002; CRVE: 202.15±0.76; age range [76-86]). Also, drusen and retinal pigment mottling were noted in some elderly MCI subjects. For all full-field ERG measurements, smaller amplitudes and larger peak times were observed in the MCI subjects. The visual performance test with the computerized Rabin CCT revealed functional loss in color vision. Interestingly, FD significantly correlated with CRVE (p=0.0212, r=-0.4628) and with the ERG's implicit time (p=0.0240, r=0.4910) in MCI individuals. To our knowledge, this is the first study to examine the association between FD and full field ERG implicit time in patients with MCI. Our preliminary findings also show that our approach to evaluating visual capacities in elderly individuals may add predictive value of early visual pathway injury associated with MCI and facilitate the introduction of a novel multimodal eye biomarker for the early detection of AD.

Rationale and design of the PHYSICALFAV trial: a randomized controlled trial to evaluate the effect of preoperative isometric exercise on vascular calibre and maturation of autologous arteriovenous fistulas.

ABSTRACTBackgroundA good vascular access (VA) is vital for haemodialysis (HD) patients. HD with an autologous arteriovenous fistula (AVF) is associated with higher survival, lower health care costs and fewer complications. Although a distal forearm AVF is the best option, not all patients are good candidates for this approach and the primary failure rate ranges from 20% to 50%. The optimal AVF depends mainly on the anatomical and haemodynamic characteristics of the artery and the vein chosen for the anastomosis. These characteristics can be modified by performing physical exercise. VA guidelines suggest that isometric exercises should be performed both before and after the AVF is created. While the literature contains few data on the potential efficacy of preoperative exercise, small observational studies point to an improvement in venous and arterial calibre. Postoperative exercise also seems to improve maturation, although there is no consensus on the appropriate exercise protocol.MethodsThe PHYSICALFAV trial (NCT03213756) is an open-label, multicentre, prospective, controlled, randomized trial designed to evaluate the usefulness of preoperative isometric exercise (PIE) in pre-dialysis patients or in prevalent HD patients who are candidates for a new AVF. Patients are randomized 1:1 to the PIE group (isometric exercises for 8 weeks) or the control group (no exercise). The main endpoint is whether the rate of primary failure is lower in the PIE group than in the control group.ResultsThe trial has already started, with 40 patients having been enrolled as of 21 March 2018; 26.5% of the estimated sample.

The effect of oral hydration and localised heat on peripheral vein diameter and depth: A randomised controlled trial

BackgroundAccessing the peripheral veins for blood sampling and short-term peripheral intravenous catheter insertion is common in contemporary healthcare. Clinicians may apply heat or promote oral hydration to increase vein diameter and reveal veins to improve success rates. However, there is limited research that has examined the effect of these interventions on vein diameter and depth. ObjectivesTo determine the effect of localised heat and oral hydration on vein diameter and depth. DesignA three arm parallel randomised controlled trial was undertaken with 39 healthy participants from a University. All participants fasted from food and fluid from midnight. At 10 am the next day, a mark was made at the cephalic (120 mm proximal from the radial styloid) and median cubital veins (at cubital fossa) with non-permanent ink and participants underwent baseline vein diameter and depth measurement using ultrasound. Participants were randomised to either a control, heat or hydration group. Participants in the hydration arm consumed 1 L of room temperature tap water, those in the heat group had a wheat bag applied to the area for 10 min and those in the control group had no intervention and were asked to sit quietly. A second measurement was undertaken immediately after the heat intervention and 1 h after the baseline measurement for those in the hydration and control groups. ResultsThe application of localised heat and oral hydration did not affect the depth of the cephalic vein. Whilst hydration had no effect on median cubital vein depth, the application of heat did make this vein more superficial compared to the control group (p = 0.033). The application of heat resulted in a statistically significant (p = 0.006) increase in cephalic vein diameter compared to the control group, this effect did not occur with the median cubital vein (p = 0.087). Oral hydration resulted in a reduction in the mean diameter of both veins. Compared to the control group, the average median cubital vein diameter decreased by 0.57 mm (p = 0.003; 95% CI −0.940 to −0.193) and the cephalic vein reduced by 0.33 mm (p = 0.015; 95% CI −0.593 to −0.064) after oral hydration. ConclusionThe use of localised heat was inconsistent in its effect on vein diameter and depth. Oral hydration caused a reduction in vascular calibre in both the cephalic and median cubital veins. The promotion of water consumption to improve venepuncture success is not supported.

Association between blood pressure and retinal arteriolar and venular diameters in Chinese early adolescent children, and whether the association has gender difference: a cross-sectional study

BackgroundTo establish the independent association between blood pressure (BP) and retinal vascular caliber, especially the retinal venular caliber, in a population of 12-year-old Chinese children.MethodsWe have examined 1501 students in the 7th grade with mean age of 12.7 years. A non-mydriatic fundus camera (Canon CR-2, Tokyo, Japan) was used to capture 450 fundus images of the right eyes. Retinal vascular caliber was measured using a computer-based program (IVAN). BP was measured using an automated sphygmomanometer (HEM-907, Omron, Kyoto, Japan).ResultsThe mean retinal arteriolar caliber was 145.3 μm (95% confidence interval [CI], 110.6–189.6 μm) and the mean venular caliber was 212.7 μm (95% CI, 170.6–271.3 μm). After controlling for age, sex, axial length, BMI, waist, spherical equivalent, birth weight, gestational age and fellow retinal vessel caliber, children in the highest quartile of BP had significantly narrower retinal arteriolar caliber than those with lower quartiles (P for trend< 0.05). Each 10-mmHg increase in BP was associated with narrowing of the retinal arterioles by 3.00 μm (multivariable-adjusted P < 0.001), and the results were consist in three BP measurements. The association between BP measures and retinal venular caliber did not persist after adjusting for fellow arteriolar caliber. And there was no significant interaction between BP and sex, age, BMI, and birth status.ConclusionsIn a large population of adolescent Chinese children, higher BP was found to be associated with narrower retinal arterioles, but not with retinal venules. Sex and other confounding factors had no effect on the relationship of BP and retinal vessel diameter.

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.

Retinal microvascular parameters are not associated with reduced renal function in a study of individuals with type 2 diabetes

The eye provides an opportunistic “window” to view the microcirculation. There is published evidence of an association between retinal microvascular calibre and renal function measured by estimated glomerular filtration rate (eGFR) in individuals with diabetes mellitus. Beyond vascular calibre, few studies have considered other microvascular geometrical features. Here we report novel null findings for measures of vascular spread (vessel fractal dimension), tortuosity, and branching patterns and their relationship with renal function in type 2 diabetes over a mean of 3 years. We performed a nested case-control comparison of multiple retinal vascular parameters between individuals with type 2 diabetes and stable (non-progressors) versus declining (progressors) eGFR across two time points within a subset of 1072 participants from the GoDARTS study cohort. Retinal microvascular were measured using VAMPIRE 3.1 software. In unadjusted analyses and following adjustment for age, gender, systolic blood pressure, HbA1C, and diabetic retinopathy, no associations between baseline retinal vascular parameters and risk of eGFR progression were observed. Cross-sectional analysis of follow-up data showed a significant association between retinal arteriolar diameter and eGFR, but this was not maintained following adjustment. These findings are consistent with a lack of predictive capacity for progressive loss of renal function in type 2 diabetes.

Health-related quality of life in adolescents and the retinal microvascular structure

We aimed to investigate whether health-related quality of life (HRQoL) is associated with retinal vascular caliber, an indicator of subclinical cardiovascular disease risk. 1600 students aged between 11–19 years (821 girls and 779 boys) were examined during 2009–2011. Retinal vessel caliber was measured from digital retinal images. HRQoL was assessed by the Pediatric Quality of Life Inventory (PedsQL). In the overall cohort, each 1-unit increase in PedsQL total score and the psychosocial summary score was associated with ~0.05 μm narrowing in retinal arteriolar caliber (multivariable-adjusted p-value = 0.01). Participants in the lowest versus highest tertile of PedsQL total score, psychosocial summary, social and school item scores had significantly wider retinal arteriolar caliber: 161.7 μm versus 160.2 μm (p = 0.02); 161.6 μm versus 160.0 μm (p = 0.02); 161.6 μm versus 159.9 μm (p = 0.002); and 161.6 μm versus 159.9 μm (p = 0.01), respectively. Significant interactions (p < 0.05) were observed between gender and PedsQL total score with retinal arteriolar calibre. In boys, inverse associations were observed between PedsQL total score (p = 0.01), psychosocial summary (p = 0.01), and social scores (p = 0.01) and retinal arteriolar caliber. No significant associations were observed between PedsQL scores and retinal vessel caliber in girls. Diminished HRQoL in adolescents was independently associated with structural retinal microvascular changes.

Association of Retinal Vascular Caliber and Age-Related Macular Degeneration in Patients With the Acquired Immunodeficiency Syndrome.

PurposeTo evaluate the relationship between retinal vascular caliber and AMD in patients with AIDS.MethodsParticipants enrolled in the Longitudinal Study of the Ocular Complications of AIDS had retinal photographs taken at enrollment. Retinal vascular caliber (central retinal artery equivalent [CRAE] and central retinal vein equivalent [CRVE]) and intermediate-stage AMD were determined from these retinal photographs. Photographs were evaluated by graders at a centralized reading center, using the Age-Related Eye Disease Study grading system for AMD and semiautomated techniques for evaluating retinal vascular caliber.ResultsOf the 1171 participants evaluated, 110 (9.4%) had AMD and 1061 (90.6%) did not. Compared with participants without AMD, participants with AMD had larger mean CRAEs (151 ± 16 μm versus 147 ± 16 μm; P = 0.009) and mean CRVEs (228 ± 24 μm versus 223 ± 25 μm; P = 0.02). The unadjusted differences were: CRAE, 4.3 μm (95% confidence interval [CI] 1.1–7.5; P = 0.009) and CRVE, 5.5 μm (95% CI 0.7–10.3; P = 0.02). After adjustment for age, race/ethnicity, sex, human immunodeficiency syndrome (HIV) transmission category, smoking, enrollment and nadir CD4+ T cells, and enrollment and maximum HIV load, the differences between patients with and without AMD were as follows: CRAE, 5.4 μm (95% CI 2.3–8.5; P = 0.001) and CRVE, 6.0 μm (95% CI 1.4–10.6; P = 0.01).ConclusionsIn patients with AIDS, AMD is associated with greater retinal arteriolar and venular calibers, suggesting a role for shared pathogenic mechanisms, such as persistent systemic inflammation.

The Adolescent Cardio-Renal Intervention Trial (AdDIT): retinal vascular geometry and renal function in adolescents with type 1 diabetes

Aims/hypothesisWe examined the hypothesis that elevation in urinary albumin creatinine ratio (ACR) in adolescents with type 1 diabetes is associated with abnormal retinal vascular geometry (RVG) phenotypes.MethodsA cross-sectional study at baseline of the relationship between ACR within the normoalbuminuric range and RVG in 963 adolescents aged 14.4 ± 1.6 years with type 1 diabetes (median duration 6.5 years) screened for participation in AdDIT. A validated algorithm was used to categorise log10 ACR into tertiles: upper tertile ACR was defined as ‘high-risk’ for future albuminuria and the lower two tertiles were deemed ‘low-risk’. RVG analysis, using a semi-automated computer program, determined retinal vascular calibres (standard and extended zones) and tortuosity. RVG measures were analysed continuously and categorically (in quintiles: Q1–Q5) for associations with log10 ACR and ACR risk groups.ResultsGreater log10 ACR was associated with narrower vessel calibres and greater tortuosity. The high-risk group was more likely to have extended zone vessel calibres in the lowest quintile (arteriolar Q1 vs Q2–Q5: OR 1.67 [95% CI 1.17, 2.38] and venular OR 1.39 [0.98, 1.99]) and tortuosity in the highest quintile (Q5 vs Q1–Q4: arteriolar OR 2.05 [1.44, 2.92] and venular OR 2.38 [1.67, 3.40]). The effects of retinal vascular calibres and tortuosity were additive such that the participants with the narrowest and most tortuous vessels were more likely to be in the high-risk group (OR 3.32 [1.84, 5.96]). These effects were independent of duration, blood pressure, BMI and blood glucose control.Conclusions/interpretationHigher ACR in adolescents is associated with narrower and more tortuous retinal vessels. Therefore, RVG phenotypes may serve to identify populations at high risk of diabetes complications during adolescence and well before onset of clinical diabetes complications.

The relationship of dietary fish intake to diabetic retinopathy and retinal vascular caliber in patients with type 2 diabetes

In this cross-sectional study, we evaluated the association of dietary fish intake with varying severity of diabetic retinopathy (DR) and retinal vascular caliber in Asians with type 2 diabetes mellitus. 357 Asians (median age: 58 years; 31% women; 78% Chinese) were recruited from a tertiary eye care institution in Singapore. Fish consumption was evaluated using a validated food frequency questionnaire. Digital retinal photographs assessed for DR severity and retinal vascular caliber. Ordered logistic and linear regression models were used to investigate the association of fish intake with DR severity and vascular caliber. Increasing frequency of fish consumption was significantly associated with lower odds of having severe DR (odds ratio [OR] = 0.91, 95% CI: 0.84–0.99 per 1-unit increase of fish intake; P = 0.038). Among those with no retinopathy, persons in quartile 4 fish intake had a wider retinal vascular caliber for arteriolar (β = 22.27 µm, 95% CI: 12.64–31.90; P-trend < 0.001) and venular (β = 32.00 µm, 95% CI: 17.56–46.43; P-trend < 0.001), than those in quartile 1 fish intake. Persons with higher fish intake had a decreased likelihood of having severe DR. In diabetics without retinopathy, higher fish intake was associated with wider retinal vascular caliber. Future research is needed to reinforce the direction of the casualty.

Dietary Patterns and Retinal Vessel Caliber in the Irish Nun Eye Study

BackgroundRetinal vessel abnormalities are associated with cardiovascular disease risk. Widening of retinal venules is associated with increased risk of stroke while narrowing of retinal arterioles independently predicts incident hypertension, coronary heart disease and diabetes. Dietary factors are known to play an important role in cardiovascular health. However, few studies have examined the association between dietary patterns (DPs) and retinal microvascular health.ObjectiveTo examine the association between ‘a posteriori’- derived DPs and retinal vascular caliber (RVC) in older women with a restricted lifestyle.MethodsThis was a cross-sectional study of 1233 participants (mean age: 76.3 years) from the Irish Nun Eye Study (INES). Computer-assisted software was used to measure RVC from digital eye images using standardized protocols. Dietary intake was assessed using a food frequency questionnaire (FFQ). DP analysis was performed using principal component analysis from completed FFQs. Regression models were used to assess associations between DPs and retinal vessel diameters, adjusting for age, body mass index, refraction, hypertension, diabetes mellitus, ischemic heart disease, cerebrovascular accident and fellow eye RVC.ResultsTwo DPs were identified: a ‘healthy’ pattern with high factor loadings for fruit, vegetables, wholegrains and oily fish and an ‘unhealthy’ pattern with high factor loadings for sugar and sweets, chips, high fat dairy products and French fries. Adjusted linear regression analysis revealed that those who adhered most closely to the unhealthy DP had wider central retinal venular equivalent (CRVE) (p=0.03) and narrower central retinal arteriolar equivalent (CRAE) (p=0.01) compared to the least unhealthy DP. No independent relationship was observed between the healthy DP and RVC.ConclusionIn this cohort of older women with a restricted lifestyle, an unhealthy DP was independently associated with an unfavorable retinal profile, namely a widening of retinal venules and narrowing of retinal arterioles.

Retinal Vascular Caliber Changes After Topical Nepafenac Treatment for Diabetic Macular Edema

ABSTRACTPurpose: To assess changes in retinal vascular caliber in response to short-term use of nepafenac eye drops in patients with mild diabetic macular edema.Materials and methods: Thirty-four patients with previously untreated bilateral mild diabetic macular edema were included in this prospective study. For each participant, one eye was randomly assigned to nepafenac treatment (0.1%, three times/day) and the other eye was left untreated throughout the study. Using digital fundus photographs, retinal vascular calibers were calculated and compared in treated and untreated eyes at the baseline, week 1, and week 6.Results: Baseline vessel diameters did not differ in treated and fellow eyes (p > 0.05). Over the 6 weeks of the study, significant vasoconstriction of the retinal arteriolar caliber was observed at weeks 1 (p < 0.05) and 6 (p < 0.05), while an unchanged retinal venular caliber was noted between the treated and untreated eyes (p > 0.44). Significant macular thickness difference was only observed at week 6 (p = 0.002).Conclusions: Topical nepafenac has a significant narrowing effect on the retinal arteriolar diameter and a significant reductive effect on central macular thickness in eyes with mild diabetic retinopathy.

A New Pedicled Internal Mammary Osteomyocutaneous Chimeric Flap (PIMOC) for Salvage Head and Neck Reconstruction: Anatomic Study and Clinical Application

Well-vascularized composite tissue offers improved outcomes for complex head and neck reconstruction. Patients with vessel-depleted necks and failed reconstructions require alternative reconstructive options. We describe a pedicled internal mammary artery osteomyocutaneous chimeric flap (PIMOC) for salvage head and neck reconstruction. Bilateral dissections of 35 fresh cadavers were performed to study individual tissue components and vascular pedicles to develop the PIMOC technique. The flap was then utilized in a series of patients with vessel-depleted neck anatomy. The PIMOC was dissected bilaterally in all cadavers and there were no statistical differences in vascular pedicle caliber or length with regards to laterality or gender. Five patients subsequently underwent this procedure. The flaps included a vertical rectus abdominis myocutaneous component and a 6th or 7th rib with adjacent muscle and skin to restore bone defects, internal lining, and external coverage. All donor sites were closed primarily. There were no flap losses and all patients gained improvements in facial contour, speech and swallow. Although technically complex, the PIMOC is reproducible and provides a safe and reliable option for salvage head and neck reconstruction. The harvest of the 6th or 7th rib and rectus abdominis muscle renders an acceptable donor site.

Update on retinal vascular caliber.

Retinal vessels are the only blood vessels that can be viewed directly, in vivo, repetitively and non-invasively. Retinal vessel caliber is influenced by physiological (age, sex, race, blood pressure, blood glucose, body mass index) and pathological (atherosclerosis, dyslipidemia, smoking) determinants. There are studies on large population groups that demonstrate the associations between retinal vasculature and subclinical or clinical changes in systemic diseases (hypertension, diabetes, stroke, renal or cardiac diseases). The assessment of retinal vessels can provide information about the pathophysiology of many diseases, but it also has a direct applicability in clinic, being used as a screening method that predicts the risk of their occurrence.

Common Femoral Artery Caliber Changes after Percutaneous versus Surgical Access in Endovascular Aneurysm Repair in the Asian Population

Western studies showed vascular caliber changes post-endovascular aneurysm repair (EVAR). This study aims to evaluate for postoperative changes of the common femoral artery inner diameter (CFA ID) in the Asian population. From January 2011 to June 2016, 202 patients who underwent EVAR were reviewed. CFA IDs were evaluated at 3 fixed levels on computed tomography (CT) aortograms. Preoperative and postoperative measurements were compared. Per-groin analysis was carried out after division into percutaneous access endovascular aneurysm repair (PEVAR) and surgical access endovascular aneurysm repair (SEVAR) groups. Independent sample t-test compared for differences in overall CFA ID changes between PEVAR andSEVAR groups. Paired sample t-test evaluated CFA ID changes in each group. P value < 0.05 was considered significant. One hundred and twenty patients were included, with 200 groins subsequently analyzed. The PEVAR and SEVAR groups have no significant demographic differences, except in sheath size and duration of CT aortogram follow-up. No significant differences in overall CFA ID changes comparing PEVAR and SEVAR groups (-0.12±1.05mm, -0.10±0.81mm, P=0.36). No significant overall CFA ID changes in both PEVAR (7.92±1.23mm, 7.80±1.38mm, P=0.34) and SEVAR groups (7.47±1.44mm, 7.36±1.64mm, P=0.15). No significant differences in CFA caliber changes comparing PEVAR and SEVAR. No significant CFA caliber changes in either group.

Clinical review of 24\u201335\xa0year olds conceived with and without in vitro fertilization: study protocol

BackgroundChildren conceived by assisted reproductive technologies (ART) currently comprise 4% of Australian births. The manipulation of biological parameters related to fertilization and implantation are integral to successful ART but potentially pose a risk to the longer-term health of the offspring. There is consensus that many common adult health problems (particularly cardiovascular, metabolic and respiratory conditions) have their origins in early life, possibly before birth, and that risk trajectories track through childhood until clinical disease manifests in adulthood. Early life epigenetic variation may play a role in this process. However little is known about the long-term health of individuals conceived by ART. In a previous study, based on telephone-interviews, we found that young adults conceived by in vitro fertilization (IVF) had significantly more maternal reported atopic respiratory, endocrine, nutritional, and metabolic conditions than non-IVF conceived matched controls. Here we outline the protocol for a follow-up biomedical assessment of this cohort and a questionnaire to obtain information on potential confounders.MethodsWe are conducting a clinical review of an existing, well characterised cohort comprising 547 IVF-conceived adults and 549 matched controls. We are measuring cardiovascular intermediate phenotypes, metabolic parameters and respiratory function, complemented by epigenome-wide DNA methylation analysis. A pilot study demonstrated the feasibility of our proposed protocol and its acceptability to participants. Participants attend a 2–3 h clinical assessment and complete a study-specific online questionnaire. Measurements include: 1) cardiovascular phenotypes: carotid artery intima-media thickness and distensibility, retinal vascular calibre, resting blood pressure, pulse wave velocity and pulse wave analysis; 2) respiratory function: spirometry, plethysmography, multiple breath washout; 3) auxology: height, weight, waist circumference, bio-impedance. Blood is collected for 4) biomarkers of cardiometabolic profile including inflammatory markers and 5) epigenetic analysis.DiscussionRecruitment for this clinical review is challenging as many of the participants have moved to regional, interstate or international locations. Additionally, many female participants are pregnant or breastfeeding, and are therefore ineligible. Nevertheless, comprehensive strategies have been developed to optimize recruitment. Given the increasing use of IVF and related technologies, the potential long-term consequences for risk of common adult diseases is an important clinical and public health issue.

Retinal vascular fractal dimension and cerebral blood flow, the CRESCENDO study

PurposeThe retinal vascular fractal dimension (FD) is a marker of retinal complexity of vascular tree. It has been associated with neurodegenerative and cerebrovascular diseases. Arterial spin labelling is a non‐invasive technique to evaluate the cerebral blood flow (CBF). The purpose of this study was to explore the relationship between retinal vascular FD and CBF.MethodsCross sectional analysis comprising 29 individuals aged 65 years and over from the Cognitive REServe and Clinical ENDOphenotype (CRESCENDO) cohort of healthy older adults. Retinal vascular FD was measured from fundus photographs using semi‐automated standardized imaging software “Singapore Eye Vessel Assessment (SIVA)” system. CBF was estimated in various gray matter regions from a 2D Pulsed arterial spin labelling sequence from MRI.ResultsA higher venular FD was associated with higher CBF in all cerebral regions of interest (p &lt; 0.01). No significant associations were found between CBF and other parameters derived from SIVA or the central retinal arterial or venular equivalent. This association was stronger for opposite eye to handedness (p = 0.03). No relationship was observed between arterial FD and CBF (p &gt; 0.07).ConclusionsVenular FD was the main parameter associated to cerebral perfusion whereas retinal vascular calibers were not. It may be evaluated in clinical studies for early and non‐invasive detection of subclinical cerebro‐vascular pathologies including dementia and stroke.

Gestational hypertensive disorders and retinal microvasculature: the Generation R Study

BackgroundChanges in the microvasculature associated with pre-eclampsia and gestational hypertension have been proposed as a potential pathway in the development of cardiovascular disease. We examined whether gestational hypertensive disorders, such as pre-eclampsia and gestational hypertension, are related to the maternal retinal microvasculature status after pregnancy.MethodsThis study is part of an ongoing population-based prospective cohort study. During pregnancy and 6.2 years after the index pregnancy (90% range 5.7–7.4 years), we examined 3391 women with available information on pre-eclampsia, gestational hypertension, and retinal vascular calibers. Retinal arteriolar and venular calibers were measured in the left eye from digitized retinal photographs.ResultsWomen with pre-eclampsia had smaller retinal arteriolar calibers 6 years after pregnancy than women with a normotensive pregnancy (adjusted difference: –0.40 standard deviation score [SDS]; 95% confidence interval [CI]: –0.62, –0.19). For women with previous gestational hypertension, similar trends were observed (–0.20 SDS; 95% CI: –0.34, –0.05). With respect to retinal venular calibers, we did not observe consistent trends for women with previous pre-eclampsia. However, in women with previous gestational hypertension, we observed larger venular calibers (0.22 SDS; 95% CI: 0.07–0.36) than in women with a previous normotensive pregnancy. The association of gestational hypertensive disorders with retinal vessel calibers was mediated through mean arterial pressure at the time of retinal imaging.ConclusionsCompared to women with a previous normotensive pregnancy, women with pre-eclampsia and gestational hypertension show an altered status of the microvasculature 6 years after the index pregnancy. This is reflected by smaller retinal arteriolar calibers and wider retinal venular calibers. These microvascular changes may possibly contribute to the development of cardiovascular disease in later life.

Quantitative Retinal Vascular Changes in Obstructive Sleep Apnea

To examine the relationship between both static and dynamic retinal vascular caliber and the severity of obstructive sleep apnea (OSA). Prospective cross-sectional study. Adult patients undergoing diagnostic polysomnography studies at a private Australian university teaching hospital were recruited. OSA severity was defined by the apnea-hypopnea index (AHI): severe >30, moderate >15-30, mild 5-15, and controls <5. Of 115 patients recruited (73 male; mean age 58 ± 13 years), there were 41 severe, 35 moderate, and 25 mild OSA patients and 14 controls. Static retinal vascular caliber was measured as the average diameter of retinal arterioles (CRAE) and venules (CRVE), and summarized as the arteriovenous ratio (AVR). Dynamic retinal vascular caliber was evaluated as the average pulsation amplitude of retinal arterioles (SRAP) and venules (SRVP). Comparisons across groups were performed using multivariate linear regression analysis. All results were adjusted for age, body mass index, and mean arterial pressure. Increasing AHI was significantly associated with decreasing AVR (P= .008) and CRAE (P= .016). A significant relationship was demonstrated between increasing AHI and attenuated retinal vascular pulsation amplitude (arterioles P= .028; venules P < .0001). Increasing OSA severity is independently associated with retinal arteriolar narrowing and attenuated vascular pulsation amplitude. The retinal vasculature is easily imaged, and may be a surrogate biomarker of cerebral and systemic vascular risk in patients with OSA requiring further comprehensive investigation.