Investigation of factors that may affect the foveal avascular zone: An optical coherence tomography angiography study.

SIGNIFICANCE: An understanding of factors that affect the foveal avascular zone (FAZ) in healthy eyes may aid in the early identification of patients at risk of retinal pathology, thereby allowing better management and preventive measures to be implemented. PURPOSE: The size and shape of the FAZ can change due to retinal diseases associated with oxidative stress, including diabetic retinopathy, glaucoma, and macular degeneration. This study aimed to assess the relationship, if any, between factors that may affect the superficial FAZ (i.e., vessel density, vessel perfusion, overweight/obesity) and possible links with macular pigment optical density in young, healthy participants. METHODS: One hundred thirty-nine participants aged 18 to 35 years were recruited to this cross-sectional study. The superficial FAZ area, foveal vascularity, and central macular thickness (CMT) were assessed using the Cirrus 5000. Health parameters, body mass index, trunk fat %, and macular pigment were analyzed to determine possible associations with the superficial FAZ. RESULTS: Mean FAZ area was 0.23 ± 0.08 mm2. Females had a significantly larger mean FAZ area than males (p=0.002). The FAZ area was positively correlated with body mass index (Pearson's r = 0.189, p=0.026). Significant correlates of the FAZ area in the multivariate model included vessel perfusion (central), CMT, and trunk fat %, collectively explaining 65.1% of the overall variability. CONCLUSIONS: Study findings suggest that reduced vessel perfusion, thinner CMT, and higher trunk fat % are plausible predictors of a larger FAZ area in healthy Caucasian adults. Low macular pigment optical density was, however, not associated with increased FAZ size in young healthy eyes. Noninvasive optical coherence tomography angiography testing, in association with these predictors, may aid in the early detection and monitoring of retinal diseases associated with oxidative stress.

Normative data on the foveal avascular zone in a young healthy Irish population using optical coherence tomography angiography.

PURPOSE: To establish normative data on the size, shape and vascular profile of the foveal avascular zone (FAZ) in a young, healthy, Irish population, using the Cirrus 5000 HD-OCT. Certain diseases may alter FAZ appearance. Normative databases provide normal baseline values for comparison, thus improving diagnostic ability. METHODS: One hundred and fifty-four subjects aged 18-35 years old were recruited. Superficial FAZ area, diameter, circularity, ganglion cell layer, central macular thickness (CMT), vascular perfusion and density were measured using the Cirrus 5000. Axial length was measured with the IOL Master and blood pressure was measured using the Omron sphygmomanometer. RESULTS: Mean FAZ area was 0.22 ± 0.07 mm2, mean CMT was 263.08 ± 18.73µm. Both were larger in females than males (p = 0.022, p = 0.000). Mean vessel density and perfusion central were 14.11 ± 2.77 mm/mm2 and 24.70 ± 4.96% respectively. Both were lower in females (p = 0.010, p = 0.019). Vessel density and perfusion inner correlated positively with minimum ganglion cell layer plus inner plexiform layer (GCL + IPL) thickness (p = 0.001, p = 0.019). CMT correlated positively with vessel density and perfusion central (p = 0.000 for both) and negatively with FAZ area (p = 0.000). CONCLUSIONS: This study provides normative data for FAZ appearance and vascularity for the first time in a young, healthy, Irish population, using the Cirrus 5000 HD-OCT. Establishing machine and population specific normative data, particularly in relation to vessel density and perfusion is paramount to the early identification of ocular disease using Optical Coherence Tomography Angiography.

Investigation of Surrogate Biomarkers Associated with Macular Pigment Status in a Group of Older Irish Adults.

SIGNIFICANCE: Macular pigment (MP) confers potent antioxidant and anti-inflammatory effects at the macula; however, its optical density in the eye is not routinely measured in clinical practice. PURPOSE: This study explored a range of surrogate biomarkers including anthropometric, clinical, and plasma measures that may be associated with lower MP optical density (MPOD). METHODS: Two thousand five hundred ninety-four subjects completed a full MP assessment as part of wave 1 of The Irish Longitudinal Study of Aging. Macular pigment optical density was measured using customized heterochromatic flicker photometry. Clinical (blood pressure), plasma (lipoproteins, inflammatory markers), and anthropometric (waist, hip, height, weight) biomarkers were measured for each participant. RESULTS: Mean (standard deviation) MPOD for the study group was 0.223 (0.161), with a range of 0 to 1.08. One-way ANOVA revealed that MPOD was significantly lower among participants with low plasma high-density lipoprotein (HDL; P = .04), raised plasma triglyceride-to-HDL ratio (P = .003), and raised total cholesterol-to-HDL ratio (P = .03). Subjects with an elevated waist circumference (WC) had a significantly lower MPOD (mean, 0.216 [0.159]) compared with those with an ideal WC (mean, 0.229 [0.162]; P = .03). Significant correlates of MPOD on mixed linear model analysis included education, smoking status, and WC. CONCLUSIONS: Higher abdominal fat is associated with lower MPOD in this representative sample of older Irish adults. Although altered lipoprotein profiles (low HDL, raised triglyceride-to-HDL ratio, raised total cholesterol-to-HDL ratio) may affect the transport, uptake, and stabilization of carotenoids in the retina, these plasma biomarkers were not predictive of low MPOD after adjustment for abdominal circumference. Although WC emerged as a viable anthropometric predictor of lower MPOD, its effect size seems to be small.

Can Protanopia Be Correctly Diagnosed in Clinical Practice? An Evaluation of Diagnosis by Four Screening Tests.

SIGNIFICANCE: Protanopia is a color vision deficiency (CVD) that is unacceptable for certain occupations. This study compares simultaneously for the first time the ability of three recently revised or developed clinical tests of color vision with the Ishihara test to diagnose protanopia from other color vision deficiencies. PURPOSE: The objectives were to examine the ability of four clinical tests to differentiate (1) between protan and deutan CVDs in patients with protanopia and deuteranopia, and (2) protanopes and deuteranopes as "strong" deficiencies. METHODS: The Hardy-Rand-Rittler (4th ed.), City University (3rd ed.), Ishihara, and Mollon-Reffin tests were evaluated against the Oculus Heidelberg Multi-Color anomaloscope for 18 protanopes and 9 deuteranopes. Diagnosis by anomaloscopy was subsequent to administration of screening tests. RESULTS: The Ishihara test misdiagnosed all 18 protanopes as having a deutan deficiency. In contrast, the Hardy-Rand-Rittler and Mollon-Reffin tests correctly identified protan CVD in 100% of protanopes. No screening test was able to reliably diagnose protanopia on the basis of a strong protan CVD. CONCLUSIONS: The Ishihara test is not suitable for screening for protanopia; its failure to diagnose protanopes as having a protan CVD was far greater than that in previous studies. The Hardy-Rand-Rittler and Mollon-Reffin are the most reliable tests for this purpose. None of the screening tests were able to reliably differentiate dichromacy from strongly anomalous trichromacy.

A review of the putative causal mechanisms associated with lower macular pigment in diabetes mellitus.

Macular pigment (MP) confers potent antioxidant and anti-inflammatory effects at the macula, and may therefore protect retinal tissue from the oxidative stress and inflammation associated with ocular disease and ageing. There is a body of evidence implicating oxidative damage and inflammation as underlying pathological processes in diabetic retinopathy. MP has therefore become a focus of research in diabetes, with recent evidence suggesting that individuals with diabetes, particularly type 2 diabetes, have lower MP relative to healthy controls. The present review explores the currently available evidence to illuminate the metabolic perturbations that may possibly be involved in MP's depletion. Metabolic co-morbidities commonly associated with type 2 diabetes, such as overweight/obesity, dyslipidaemia, hyperglycaemia and insulin resistance, may have related and independent relationships with MP. Increased adiposity and dyslipidaemia may adversely affect MP by compromising the availability, transport and assimilation of these dietary carotenoids in the retina. Furthermore, carotenoid intake may be compromised by the dietary deficiencies characteristic of type 2 diabetes, thereby further compromising redox homeostasis. Candidate causal mechanisms to explain the lower MP levels reported in diabetes include increased oxidative stress, inflammation, hyperglycaemia, insulin resistance, overweight/obesity and dyslipidaemia; factors that may negatively affect redox status, and the availability, transport and stabilisation of carotenoids in the retina. Further study in diabetic populations is warranted to fully elucidate these relationships.

Identification of Surrogate Biomarkers for the Prediction of Patients at Risk of Low Macular Pigment in Type 2 Diabetes.

Purpose: This cross-sectional study compared macular pigment (MP) levels among persons with Type 2 diabetes relative to healthy controls. Additionally, a range of behavioral, anthropometric, clinical and serum measures were explored as possible predictors of low MP optical density (MPOD) in diabetes.Methods: Two health status groups; Group 1: Type 2 diabetes (n = 188), and Group 2: Healthy controls (n = 2,594) completed a full MP assessment using customized heterochromatic flicker photometry, as part of The Irish Longitudinal Study on Aging (TILDA). Clinical [blood pressure; cataract status; MPOD] and anthropometric [waist (cm); weight (kg); hip (cm)] measurements were taken, and a blood sample drawn for analysis of serum biomarkers [lipoproteins; inflammatory markers (C reactive protein and vitamin-D)].Results: One-way ANOVA revealed lower MPOD in subjects with Type 2 diabetes relative to controls (p = .047). Amongst participants with diabetes, those with low serum vitamin D (≤50 nmol/L) had significantly lower mean MPOD compared to those with sufficient serum vitamin D levels >50 nmol/L (0.173(0.148) vs. 0.226(0.145); p = .006). Concomitantly, MP was significantly lower in diabetes participants with raised serum triglyceride (TG) to high density lipoprotein (HDL) ratio (TG/HDL); values >1.74 mmol/L (0.172 (0.140) vs 0.215 (0.152); p = .039). Body mass index, waist-to-height ratio and waist circumference, were all significantly negatively correlated with MPOD (Pearson's correlation, p < .05 for all). Significant correlates of MPOD in the multivariate regression model included smoking, cataract, and vitamin D, which collectively contributed 18.5% of the overall variability in MPOD status amongst participants with Type 2 diabetes.Conclusions: This study provides additional evidence that low MP may indeed be a feature of Type 2 diabetes, and further identifies smoking, cataract and vitamin D status as plausible predictors of low MPOD amongst persons with Type 2 diabetes.

MACULAR PIGMENT OPTICAL DENSITY IS LOWER IN TYPE 2 DIABETES, COMPARED WITH TYPE 1 DIABETES AND NORMAL CONTROLS.

PURPOSE: This study was designed to investigate the optical density of macular pigment in Type 1 and Type 2 diabetes subjects relative to normal controls. METHODS: One hundred and fifty subjects were recruited to the study and divided into one of the three study groups on the basis of their health status, as follows: Group 1: Healthy controls; Group 2: Type 1 diabetes; Group 3: Type 2 diabetes. Macular Pigment Optical Density, at 0.5° of retinal eccentricity, was measured using customized heterochromatic flicker photometry. Dietary intake of macular carotenoids was quantified using a lutein and zeaxanthin food frequency questionnaire. Diabetes type, duration, medication, smoking habits, glycosylated hemoglobin (HbA1C), and serum lipid levels were recorded, whereas visual acuity, body mass index, and diabetic retinopathy grade were measured for each participant. RESULTS: One-way analysis of variance revealed a statistically significant difference in body mass index, age, high-density lipoprotein cholesterol and HbA1C between the three groups (P < 0.01 for all). Chi-square analysis revealed a statistically significant difference in diabetic retinopathy distribution (P < 0.01). None of these variables exhibited a statistically significant correlation with macular pigment optical density for any study group (P > 0.05 for all). There was no difference in dietary carotenoid intake between groups. Macular pigment optical density was lower among Type 2 diabetes subjects (0.33 ± 0.21) compared with Type 1 diabetes (0.49 ± 0.23) and controls (0.48 ± 0.35). General linear model analysis, including age, body mass index, diabetes duration, diabetic retinopathy status, high-density lipoprotein cholesterol, and HbA1C as covariates, revealed a statistically significant effect of diabetes type on macular pigment optical density (F = 2.62; P = 0.04). CONCLUSION: Macular pigment optical density was statistically significantly lower in Type 2 diabetes compared with Type 1 diabetes and normal controls. Although body mass index was higher in the Type 2 diabetes group, the lower macular pigment optical density levels observed among Type 2 diabetes seem not to be attributable to differences in dietary carotenoid intake or to the specific presence of diabetes, diabetic control, duration, or diabetic retinopathy.

An evaluation of a novel instrument for measuring macular pigment optical density: the MPS 9000.

PURPOSE: Of the antioxidants found in the human retina, only the macular carotenoid quantities can be estimated noninvasively (albeit in a collective fashion), thus facilitating study of their role in that tissue. The aim of this study was to evaluate concordance between macular pigment optical density (MPOD) values recorded on a commercially available instrument, the MPS 9000, with those of an already validated heterochromatic flicker photometry instrument. Also, we assessed and compared test-retest variability for each instrument. METHODS: Macular pigment optical density at 0.5 retinal eccentricity was measured using two different heterochromatic flicker photometers, the MPS 9000 and the Macular Densitometer(TM), in 39 healthy subjects. Test-retest variability was evaluated separately for each instrument by taking three readings over a 1-week period in 25 subjects. RESULTS: There was a moderate positive correlation for MPOD at 0.5° of retinal eccentricity between the MPS 9000 and the Macular Densitometer described by the linear equation y = 0.763x + 0.172 (r = 0.68, p < 0.001, r(2) = 0.46); however, a paired-samples t-test showed a significant difference in terms of mean values, with a bias of lower MPOD values being yielded by the MPS 9000 (t = -4.103, p < 0.001). Bland-Altman analysis indicated only moderate agreement between the two instruments, reflected in 95% limits of agreement of 0.1 ± 0.27. Inter-sessional repeatability, expressed as a coefficient of repeatability, ranged from 0.18 to 0.21 [mean (±SD): 0.19 (0.02)] for the MPS 9000 and from 0.11 to 0.12 [mean (±SD): 0.12 (0.01)] for the Macular Densitometer. CONCLUSION: The results demonstrate that the MPS 9000 consistently yields MPOD readings, which are lower than that found with the Macular Densitometer, and exhibits substantial test-retest variability.

Macular pigment: its associations with color discrimination and matching.

PURPOSE: Macular pigment (MP) acts as a prereceptoral filter which selectively absorbs short wavelengths. It has the potential to alter color vision but the literature is conflicting on whether it does and, if so, to what extent, possibly reflecting differences between color mechanisms and color tests. This study was designed to identify and investigate relationships, if any, between MP optical density (MPOD) and color sensitivity using a battery of techniques to quantify the color vision of color-normal observers. METHODS: Color vision was assessed with the Farnsworth-Munsell 100-Hue test (FM100), Moreland match on the HMC anomaloscope, and a customized short wavelength automated perimetry (SWAP) technique at the foveola and at 1, 2, 3, 4, and 5° eccentricity. MPOD spatial profile was measured using customized heterochromatic flicker photometry. RESULTS: Total error scores and % partial error scores on the FM100 were uncorrelated to MPOD. Moreland matches showed a significant long wavelength shift with MPOD at between 1 and 3° (at 1.75°, r=0.489, p<0.001). Sensitivities on customized SWAP (cSWAP) using foveal targets were significantly inversely correlated with MPOD at both 1.75° (r=-0.461, p<0.001) and 3° (r=-0.393, p<0.001). Partial correlation analysis suggests that none of these findings can be attributed to age effects within the range 18 to 40 years. CONCLUSIONS: Our findings suggest that dietary supplementation to increase MPOD is unlikely to adversely affect hue discrimination. The association of MPOD with cSWAP may be a temporally limited effect to which the visual system normally adapts. We suggest that cSWAP may provide a clinical tool for assessing short-wavelength foveal sensitivity.

The impact of macular pigment augmentation on visual performance in normal subjects: COMPASS.

This study was conducted to investigate whether augmentation of macular pigment (MP) enhances visual performance (VP). 121 normal subjects were recruited. The active (A) group consumed 12 mg of lutein (L) and 1mg of zeaxanthin (Z) daily. MP optical density (MPOD) was assessed by customized heterochromatic flicker photometry. VP was assessed as best corrected visual acuity (BCVA), mesopic and photopic contrast sensitivity (CS), glare disability, photostress, and subjective visual function. Subjects were assessed at baseline; 3; 6; 12 months (V1, V2, V3 and V4, respectively). Central MPOD increased significantly in the A group (p < 0.05) but not in the placebo group (p > 0.05). This statistically significant increase in MPOD in the A group was not, in general, associated with a corresponding improvement in VP (p>0.05, for all variables), with the exception of a statistically significant time/treatment effect in "daily tasks comparative analysis" (p = 0.03). At V4, we report statistically significant differences in mesopic CS at 20.7 cpd, mesopic CS at 1.5 cpd under high glare conditions, and light/dark adaptation comparative analysis between the lower and the upper MP tertile groups (p < 0.05) Further study into the relationship between MP and VP is warranted, with particular attention directed towards individuals with low MP and suboptimal VP.

The relationship between macular pigment and visual performance.

This study was designed to assess whether macular pigment optical density (MPOD) is associated with visual performance. One hundred and forty-two young healthy subjects were recruited. Macular pigment optical density and visual performance were assessed by psychophysical tests including best corrected visual acuity (BCVA), mesopic and photopic contrast sensitivity, glare sensitivity, photostress recovery time (PRT). Measures of central visual function, including BCVA and contrast sensitivity, were positively associated with MPOD (p<0.05, for all). Photostress recovery and glare sensitivity were unrelated to MPOD (p>0.05). A longitudinal, placebo-controlled and randomized supplementation trial will be required to ascertain whether augmentation of MPOD can influence visual performance.