The effect of nutritional supplementation on visual function

The aim of this research was to determine the effect of a lutein-based nutritional supplemented on measures of visual function in normal and ARMD-affected eyes. Thirty participants were recruited to the ARMD cohort (aged between 55 and 82 years, mean ± SD: 69.2 ± 7.8) and 46 were recruited into the normal cohort (aged between 22 and 73 years, mean ± SD: 50.0 ± 15.9). Outcome measures were distance (DVA) and near (NVA) visual acuity, contrast sensitivity (CS), photostress recovery time measured with the Eger Macular Stressometer (EMS), central visual function assessed with the Macular Mapping test (MMT), and fundus photography. Reliability studies were carried out for the EMS and the MMT. A change of 14 s is required to indicate a clinically significant change in EMS time, and a change of 14 MMT points is required to indicate a clinically significant change in MMT score. Sample sizes were sufficient for the trial to have 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures in the normal cohort, and for CS in the ARMD cohort. The study demonstrated that a nutritional supplement containing 6mg lutein, 750 mg vitamin A, 250 mg vitamin C, 34 mg vitamin E, 10 mg zinc, and 0.5 mg copper had no effect on the outcome measures over nine or 18 months in normal or ARMD affected participants. The finding that nine months of antioxidant supplementation, in this case, has no significant effect on CS in ARMD-affected participants adds to the literature, and contrasts with previous RCTs, the AREDS and the LAST. This project has added to the debate about the use of nutritional supplementation prior to the onset of ARMD.

Abnormal retinal vascular reactivity in individuals with impaired glucose tolerance:a preliminary study

To investigate the relationship between vascular function parameters measured at the retinal and systemic level and known markers for cardiovascular risk in patients with impaired glucose tolerance (IGT). Sixty age- and gender- matched White-European adults (30 IGT and 30 normal glucose tolerance -NGT) were recruited for the study. Fasting plasma glucose, lipids and 24-hour blood pressure (BP) was measured in all subjects. Systemic vascular and endothelial function was assessed using carotid-artery intimal media thickness (cIMT) and flow mediated dilation (FMD). Retinal vascular reactivity was assessed by the Dynamic Retinal Vessel Analyser (DVA). Additionally, blood glutathione (GSH, GSSG and tGSH) and plasma von-Willebrand (vWF) factor levels were also measured. Individuals with IGT demonstrated higher BP values (p<0.001), fasting TG and TG:HDL ratios (p<0.001) than NGT subjects. Furthermore, Total:HDL-C ratios and Framingham scores were raised (p=0.010 and p<0.001 respectively). Blood glutathione levels (GSH, GSSG and tGSH) were lower (p<0.001, p=0.039 and p<0.001 respectively) while plasma vWF was increased (p=0.014) in IGT subjects compared to controls. IGT individuals also demonstrated higher IMT in right and left carotid arteries (p=0.017 and p=0.005, respectively) alongside larger brachial artery diameter (p=0.015), lower FMD% (p=0.026) and GTN induced dilation (GID) (p=0.012) than healthy controls. At the retinal arterial level, the IGT subjects showed higher baseline fluctuations (BDF) (p=0.026), longer reaction time (RT) (p=0.032) and reduced baseline-corrected flicker response (bFR) (p=0.045). In IGT subjects retinal BDF correlated with and Total:HDL (p= 0.003) and HDL-C (p= 0.004). Arterial RT also correlated with FMD (p=0.017) in IGT but not NGT subjects. In IGT individuals there is a relationship between macro- and microvascular function, as well as a direct correlation between the observed retinal microcirculatory changes and established plasma markers for CVD. Multifactorial preventive interventions to decrease vascular risk in these individuals should be considered.

Patients with early age-related macular degeneration exhibit signs of macro- and micro-vascular disease and abnormal blood glutathione levels

Background: This pilot study aimed to investigate systemic and retinal vascular function and their relationship to circulatory markers of cardiovascular risk in early age-related macular degeneration (AMD) patients without any already diagnosed systemic vascular pathologies. Methods: Fourteen patients diagnosed with early AMD and 14 age- and gender-matched healthy controls underwent blood pressure, carotid intima-media thickness (C-IMT) and peripheral arterial stiffness measurements. Retinal vascular reactivity was assessed by means of dynamic retinal vessel analysis (DVA) using a modified protocol. Blood analyses were conducted for glutathione levels and plasma levels of total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Results: The AMD patients showed significantly greater C-IMT (p = 0.029) and augmentation index (AIx) (p = 0.042) than the age-matched controls. In addition, they demonstrated a shallower retinal arterial dilation slope (Slope AD) (p = 0.005) and a longer retinal venous reaction time (RT) to flickering light (p = 0.026). Blood analyses also revealed that AMD patients exhibited higher oxidized glutathione (GSSG) (p = 0.024), lower redox index (p = 0.043) and higher LDL-C (p = 0.033) levels than the controls. Venous RT parameter correlated positively with blood GSSG levels (r = 0.58, p = 0.038) in AMD subjects, but not in the controls (p > 0.05). Conclusions: Patients diagnosed with early AMD exhibit signs of systemic and retinal vascular alterations that correlated with known risk markers for future cardiovascular morbidity. © 2013 Springer-Verlag Berlin Heidelberg.

Primary open-angle glaucoma vs normal-tension glaucoma:the vascular perspective

Objective: To compare and contrast the presence of ocular and systemic vascular function in newly diagnosed and previously untreated primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients with comparable, early stage, functional loss. Methods: The systemic vascular function of 19 POAG patients, 19 NTG patients and 20 healthy controls was assessed by means of 24 hour ambulatory blood pressure (ABPM), peripheral pulse wave analysis (PWA) and carotid intima-media thickness (IMT). Retinal vascular reactivity to flicker light was assessed using dynamic retinal vessel analysis (DVA,IMEDOS, GmbH, Jena, Germany). Results: When compared to normal controls, both POAG and NTG patients exhibited similarly increased nocturnal systemic blood pressure variability (p=0.011); peripheral arterial stiffness (p=0.015), carotid IMT (p=0.040) and reduced ocular perfusion pressure (OPP) (p<0.001). Furthermore, on DVA analysis, both groups of glaucoma patients also exhibited steeper retinal arterial constriction slopes (slope AC) following cessation of flicker (p=0.007) and a similarly increased fluctuation in arterial and venous baseline diameter (p=0.008 and p=0.009 respectively) in comparison to controls. Conclusion: POAG and NTG patients exhibit similar alterations in both ocular and systemic circulation at the early stages of their disease process. This highlights not only the importance of considering vascular risk factors in both conditions, but also raises questions about the current separation of the two conditions into completely distinct clinical entities.

Systemic circulatory influences on retinal microvascular function in middle-age individuals with low to moderate cardiovascular risk

Purpose: To investigate the relationship between retinal microvascular reactivity, circulatory markers for CVD risk and systemic antioxidative defence capacity in healthy middle-aged individuals with low to moderate risk of CVD. Methods: Retinal vascular reactivity to flickering light was assessed in 102 healthy participants (46-60 years) by means of dynamic retinal vessel analysis (DVA). Other vascular assessments included carotid intima-media thickness (C-IMT) and blood pressure (BP) measurements. Total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and blood glutathione levels in its reduced (GSH) and oxidized (GSSG) forms were also determined for each participant, along with Framingham risk scores (FRS). Results: Retinal arterial baseline diameter fluctuation (BDF) was independently, significantly and negatively influenced by LDL-C levels (β = -0.53, p = 0.027). Moreover, the arterial dilation slope (SlopeAD) was independently, significantly and positively associated with redox index (GSH: GSSG ratio, β = 0.28, p = 0.016), while the arterial constriction slope (SlopeAC) was significantly and negatively influenced by blood GSH levels (β = -0.20, p = 0.042), and positively associated with FRS (β = 0.25, p = 0.009). Venous BDF and dilation amplitude (DA) were also negatively influenced by plasma LDL-C levels (β = -0.83, p = 0.013; and β = -0.22, p = 0.028, respectively). Conclusions: In otherwise healthy individuals with low to moderate cardiovascular risk, retinal microvascular dilation and constriction responses to stress levels are influenced by systemic antioxidant capacity, and circulating markers for cardiovascular risk.

Retinal microvascular dysfunction occurs similarly in Alzheimer's disease and primary open angle glaucoma patients

Purpose: The exact nature of the relationship between Alzheimer’s disease (AD) and primary open angle glaucoma (POAG) is still the subject of debate. One factor attributed to the aetiology of both conditions is vascular dysfunction. This study aimed to investigate the similarities and differences in retinal microvascular function between mild AD patients, early stage POAG patients and healthy controls Methods: Retinal vessel reactivity to flickering light was assessed in 10 AD, 19 POAG and 22 healthy age matched control patients by means of dynamic retinal vessel analysis (DVA, IMEDOS, GmbH, Jena, Germany) according to an established protocol. All patients additionally underwent BP measurements and blood analysis for glucose and lipid metabolism markers Results: AD and POAG patients demonstrated comparable alterations in retinal artery reactivity, in the form of an increased arterial reaction time (RT) to flicker light on the final flicker cycle (p=0.014), which was not replicated in the healthy age and cardiovascular risk matched controls (p>0.05). Furthermore, the sequential changes in RT on progressing from flicker one to flicker three were found to differ between healthy controls and the two disease groups (p=0.001) Conclusions: AD and POAG patients demonstrate comparable signs of vascular dysfunction in their retinal arteries at the early stages of their disease process. These comparable signs may reflect similarities in the pathophysiological processes that occur in the development of both conditions

Overweight status is associated with extensive signs of microvascular dysfunction and cardiovascular risk

The aim of this present study was to investigate if overweight individuals exhibit signs of vascular dysfunction associated with a high risk for cardiovascular disease (CVD). One hundred lean and 100 overweight participants were recruited for the present study. Retinal microvascular function was assessed using the Dynamic Retinal Vessel Analyser (DVA), and systemic macrovascular function by means of flow-mediated dilation (FMD). Investigations also included body composition, carotid intimal-media thickness (c-IMT), ambulatory blood pressure monitoring (BP), fasting plasma glucose, triglycerides (TG), cholesterol levels (HDL-C and LDL-C), and plasma von Willebrand factor (vWF). Overweight individuals presented with higher right and left c-IMT (p = 0.005 and p = 0.002, respectively), average 24-h BP values (all p <0.001), plasma glucose (p = 0.008), TG (p = 0.003), TG: HDL-C ratio (p = 0.010), and vWF levels (p = 0.004). Moreover, overweight individuals showed lower retinal arterial microvascular dilation (p = 0.039) and baseline-corrected flicker (bFR) responses (p = 0.022), as well as, prolonged dilation reaction time (RT, p = 0.047). These observations emphasise the importance of vascular screening and consideration of preventive interventions to decrease vascular risk in all individuals with adiposity above normal range.