A randomised controlled trial investigating the effect of nutritional supplementation on visual function in normal, and age-related macular disease affected eyes: design and methodology [ISRCTN78467674]

BACKGROUND: Age-related macular disease is the leading cause of blind registration in the developed world. One aetiological hypothesis involves oxidation, and the intrinsic vulnerability of the retina to damage via this process. This has prompted interest in the role of antioxidants, particularly the carotenoids lutein and zeaxanthin, in the prevention and treatment of this eye disease. METHODS: The aim of this randomised controlled trial is to determine the effect of a nutritional supplement containing lutein, vitamins A, C and E, zinc, and copper on measures of visual function in people with and without age-related macular disease. Outcome measures are distance and near visual acuity, contrast sensitivity, colour vision, macular visual field, glare recovery, and fundus photography. Randomisation is achieved via a random number generator, and masking achieved by third party coding of the active and placebo containers. Data collection will take place at nine and 18 months, and statistical analysis will employ Student's t test. DISCUSSION: A paucity of treatment modalities for age-related macular disease has prompted research into the development of prevention strategies. A positive effect on normals may be indicative of a role of nutritional supplementation in preventing or delaying onset of the condition. An observed benefit in the age-related macular disease group may indicate a potential role of supplementation in prevention of progression, or even a degree reversal of the visual effects caused by this condition

The role of the carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: A review based on controversial evidence

PURPOSE: A review of the role of the carotenoids, lutein and zeaxanthin, and their function in altering the pathogenesis of age-related macular degeneration (AMD). METHODS: Medline and Embase search. RESULTS: Recent evidence introduces the possibility that lutein and zeaxanthin, carotenoids found in a variety of fruits and vegetables may protect against the common eye disease of macular degeneration. This potential and the lack to slow the progression of macular degeneration, has fueled high public interest in the health benefits of these carotenoids and prompted their inclusion in various supplements. The body of evidence supporting a role in this disease ranges from basic studies in experimental animals to various other clinical and epidemiological studies. Whilst some epidemiological studies suggest a beneficial role for carotenoids in the prevention of AMD, others are found to be unrelated to it. Results of some clinical studies indicate that the risk for AMD is reduced when levels of the carotenoids are elevated in the serum or diet, but this correlation is not observed in other studies. Published data concerning the toxicity of the carotenoids or the optimum dosage of these supplements is lacking. CONCLUSION: An intake of dietary supplied nutrients rich in the carotenoids, lutein and zeaxanthin, appears to be beneficial in protecting retinal tissues, but this is not proven. Until scientifically sound knowledge is available we recommend for patients judged to be at risk for AMD to: alter their diet to more dark green leafy vegetables, wear UV protective lenses and a hat when outdoors. Future investigations on the role of nutrition, light exposure, genetics, and combinations of photodynamic therapy with intravitreal steroid (triamcinolone-acetonide) injections hold potential for future treatment possibilities

Lutein and inflammation

It has been shown that, besides absorbing blue light and quenching free oxygen radicals, lutein also has anti-inflammatory properties. This may have implications in Age related Macular Degeneration (AMD), because an inflammatory mechanism involving the alternative complement pathway has been implicated in the pathogenesis of this disease. In addition, various complement activation products were increased in the circulation of AMD patients, providing evidence for a systemic inflammatory component to the disease pathogenesis. It may well be lutein administration affects the inflammatory component of AMD. First clues came from studies showing that administering lutein had a beneficial effect in an experimental model of AMD. Recently, we have reported that daily supplementation with lutein over a time period of 12 months led to a significant decrease in the plasma levels of the complement factors Factor D (FD), C3d, C5a, and sC5b-9. However, the mechanism of this finding is not clear. The activation of the alternative complement pathway involves a number of cleavage reactions and amplification steps whereby complement components interact with each other in a strictly regulated manner. FD is a rate limiting enzyme in the activation sequence of the alternative pathway and as such a key player in this complement homeostasis. FD is also known as adipsin, since its main source is adipose tissues, where it is secreted by mature adipocytes. Since adipose tissue is also a main storage site for carotenoids such as lutein and zeaxanthin, we setup a study to investigate whether lutein influences FD secretion by adipose cells as a possible mechanism for the results above. Data, showing that lutein suppresses FD expression by mature adipose cells, both at the protein and the mRNA level, will be discussed

Objective evaluation of negative dysphotopsia with Goldmann kinetic perimetry

PurposeTo compare the extension of peripheral visual fields in phakic and pseudophakic patients and to evaluate whether Goldmann kinetic perimetry can be used as an objective measure of negative dysphotopsia.\u3cbr/\u3eSettingUniversity Eye Clinic, Maastricht University Medical Centre, Maastricht, the Netherlands.\u3cbr/\u3eDesignProspective and case-control study.MethodsKinetic perimetry was performed with V4e and I4e stimuli. Visual fields were assessed in the following 4 quadrants: superior temporal, superior nasal, inferior temporal, and inferior nasal. In the control group, patients were evaluated before and 1 month after cataract surgery. Biometric and perimetric data in the control group were compared with data in the patients with negative dysphotopsia (study group).ResultsEach group comprised 10 patients. In the control group, the extension of visual field did not change after surgery. Patients in the study group had a significantly shorter axial length and higher intraocular lens powers than those in the control group. The inferior temporal and inferior nasal quadrants were, respectively, 10 degrees and 6 degrees (P < .05) smaller in the study group than in the control group. In 3 patients with negative dysphotopsia, a shadow was drawn in the superior temporal and the inferior temporal quadrants during perimetry and the position of this shadow matched their subjective description of negative dysphotopsia.\u3cbr/\u3eConclusionsThe peripheral visual field did not change after cataract surgery in patients without negative dysphotopsia. Kinetic perimetry can be used for objective evaluation of patients with negative dysphotopsia because these patients had constricted peripheral visual fields or a relative temporal scotoma corresponding to the position of the shadow

Lipoprotein changes following consumption of Lutein-enriched eggs are associated with enhanced Lutein bioavailability

Lutein is concentrated in the retina and since it cannot be synthesized by the human body, its uptake depends on nutritional intake. Lutein-enriched eggs are a good lutein source, but whether changes in lipoprotein status following lutein-enriched egg consumption may affect an individual’s lutein response is not yet clear. Data from three intervention trials with lutein-enriched eggs or products made from the enriched egg yolks were combined (n=294) and analyzed to investigate the dynamics of the lutein response in relation to lipoprotein levels. Cross sectional correlation was tested at baseline between lutein and lipoprotein profiles in all participants. Subsequently two groups were selected from the combined database whereby individuals receiving lutein-enriched egg yolks (n=137) were compared with controls not receiving eggs (n=117). Significant correlations between blood lutein concentrations and total cholesterol (r=0.309; p<0.001), HDL-C (r=0.246; p<0.001), LDL-C (r=0.241; p<0.001), ApoA1 (r=0.301; p<0.001), and ApoB100 (r=0.199; p<0.005) concentrations, but not with serum triglycerides were found at baseline. Following a three to twelve month intervention, blood lutein concentrations increased from 238 to 463 ng/ml (p<0.001) in the lutein group, whereas levels in controls remained unchanged. The lutein increase in the lutein-enriched egg group correlated significantly with changes in total cholesterol, HDL-C, LDL-C, ApoA1 and ApoB100 concentrations. To conclude, individuals showing the largest lipoprotein increase following egg consumption were also those with the strongest increase in blood lutein concentration. This indicates that therapies directed at altering lipoprotein levels may indirectly affect lutein bioavailability

Lutein and factor D: two intriguing players in the field of age-related macular degeneration

Age-related macular degeneration (AMD) is a progressive eye disease that impairs central vision among elderly populations in Western, industrialized countries. In this review we will focus on the role of factor D (FD) and lutein in AMD. FD is a rate-limiting enzyme of the alternative complement activation pathway that may play an important role in the development of AMD. Several independent studies have shown a significant increase in the level of a number of complement factors of the alternative pathway, including factor D in the blood of AMD patients as compared to healthy individuals, which suggests a systemic involvement in the pathogenesis of AMD.\u3cbr/\u3e\u3cbr/\u3eFD, also called adipsin, is mainly produced by adipose tissue. Besides playing a role in the activation of the alternative pathway, FD is also known to regulate the immune system. Of interest is our preliminary finding that lutein supplementation of early AMD cases was shown to lower the level of systemic FD. If confirmed, these findings provide further support for the application of anti-factor D intervention as a new approach to control the development of this disease