Dietary analysis and nutritional behaviour in people with and without age-related macular disease

Background and Aims: Consumption of antioxidant nutrients can reduce the risk of progression of age-related macular degeneration (AMD) - the leading cause of visual impairment in adults over the age of 50 years in the UK. Lutein and zeaxanthin (L&Z) are of particular interest because they are selectively absorbed by the central retina. The objectives of this study were to analyse the dietary intake of a group of AMD patients, assess their ability to prepare and cook healthy food, and to make comparisons with people not affected by AMD. Methods: 158 participants with AMD were recruited via the UK charity The Macular Society, and fifty participants without AMD were recruited from optometric practice. A telephone interview was conducted by trained workers where participants completed a 24 hour food diary, and answered questions about cooking and shopping capabilities. Results: In the AMD group, the average L&Z intake was low in for both males and females. Those able to cook a hot meal consumed significantly more L&Z than those who were not able. Most participants were not consuming the recommended dietary allowance of fibre, calcium, vitamin D and E, and calorific intake was also lower than recommendations for their age-group. The non-AMD group consumed more kilocalories and more nutrients than the AMD group, but the L&Z intake was similar to those with AMD. The main factor that influenced participant’s food choices was personal preference. Conclusion: For an ‘informed’ population, many AMD participants were under-consuming nutrients considered to be useful for their condition. Participants without AMD were more likely to reach recommended daily allowance values for energy and a range of nutrients. It is therefore essential to design more effective dietary education and dissemination methods for people with, and at risk of, AMD.

Understanding the IT-related attitudes and needs of persons with age-related macular degeneration:a case study

In the UK, 20 per cent of people aged 75 years and over are living with sight loss; this percentage is expected to increase as the population ages (RNIB, 2011). Age-Related Macular Degeneration (AMD) is the UK’s leading cause of severe visual impairment amongst the elderly. It accounts for 16,000 blind/partial sight registrations per year and is the leading cause of blindness among people aged 55 years and older in western countries (Bressler, 2004). Our ultimate goal is to develop an assistive mobile application to support accurate and convenient diet data collection on which basis to then provide customised dietary advice and recommendations in order to help support individuals with AMD to mitigate their ongoing risk and retard the progression of the disease. In this paper, we focus on our knowledge elicitation activities conducted to help us achieve a deep and relevant understanding of our target user group. We report on qualitative findings from focus groups and observational studies with persons with AMD and interviews with domain experts which enable us to fully appreciate the impact that technology may have on our intended users as well as to inform the design and structure of our proposed mobile assistive application.

Age-related striatal BOLD changes without changes in behavioral loss aversion

Loss aversion (LA), the idea that negative valuations have a higher psychological impact than positive ones, is considered an important variable in consumer research. The literature on aging and behavior suggests older individuals may show more LA, although it is not clear if this is an effect of aging in general (as in the continuum from age 20 and 50 years), or of the state of older age (e.g., past age 65 years). We also have not yet identified the potential biological effects of aging on the neural processing of LA. In the current study we used a cohort of subjects with a 30 year range of ages, and performed whole brain functional MRI (fMRI) to examine the ventral striatum/nucleus accumbens (VS/NAc) response during a passive viewing of affective faces with model-based fMRI analysis incorporating behavioral data from a validated approach/avoidance task with the same stimuli. Our a priori focus on the VS/NAc was based on (1) the VS/NAc being a central region for reward/aversion processing; (2) its activation to both positive and negative stimuli; (3) its reported involvement with tracking LA. LA from approach/avoidance to affective faces showed excellent fidelity to published measures of LA. Imaging results were then compared to the behavioral measure of LA using the same affective faces. Although there was no relationship between age and LA, we observed increasing neural differential sensitivity (NDS) of the VS/NAc to avoidance responses (negative valuations) relative to approach responses (positive valuations) with increasing age. These findings suggest that a central region for reward/aversion processing changes with age, and may require more activation to produce the same LA behavior as in younger individuals, consistent with the idea of neural efficiency observed with high IQ individuals showing less brain activation to complete the same task.

The role of DNA methylation in aging, rejuvenation, and age-related disease

DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-l-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation. © Copyright 2012, Mary Ann Liebert, Inc. 2012.

Overview of risk factors for age-related macular degeneration

Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make life style choices that may reduce the risk of disease. This review discusses the role of genetics, sunlight, diet, cardiovascular factors, smoking, and alcohol as possible risk factors for AMD. Genetics plays a more significant role in AMD than previously thought, especially in younger patients, histocompatibility locus antigen (HLA) and complement system genes being the most significant. Whether the risk of AMD is increased by exposure to sunlight, cardiovascular risk factors, and diet is more controversial. Smoking is the risk factor most consistently associated with AMD. Current smokers are exposed to a two to three times higher risk of AMD than non-smokers and the risk increases with intensity of smoking. Moderate alcohol consumption is unlikely to increase the risk of AMD. Optometrists as front-line informers and educators of ocular health play a significant role in increasing public awareness of the risks of AMD. Cessation of smoking, the use of eye protection in high light conditions, dietary changes, and regular use of dietary supplements should all be considered to reduce the lifetime risk of AMD.

Multispectral retinal image analysis (MRIA) for the assessment of subretinal fibrosis in neovascular age-related macular degeneration (nAMD)

Purpose: To investigate the use of MRIA for quantitative characterisation of subretinal fibrosis secondary to nAMD. Methods: MRIA images of the posterior pole were acquired over 4 months from 20 eyes including those with inactive subretinal fibrosis and those being treated with ranibizumab for nAMD. Changes in morphology of the macula affected by nAMD were modelled and reflectance spectra at the MRIA acquisition wavelengths (507, 525, 552, 585, 596, 611 and 650nm) were computed using Monte Carlo simulation. Quantitative indicators of fibrosis were derived by matching image spectra to the model spectra of known morphological properties. Results: The model spectra were comparable to the image spectra, both normal and pathological. The key morphological changes that the model associated with nAMD were gliosis of the IS-OS junction, decrease in retinal blood and decrease in RPE melanin. However, these changes were not specific to fibrosis and none of the quantitative indicators showed a unique association with the degree of fibrosis. Moderate correlations were found with the clinical assessment, but not with the treatment program. Conclusion: MRIA can distinguish subretinal fibrosis from healthy tissue. The methods used show high sensitivity but low specificity, being unable to distinguish scarring from other abnormalities like atrophy. Quantification of scarring was not achieved with the wavelengths used due to the complex structural changes to retinal tissues in the process of nAMD. Further studies, incorporating other wavelengths, will establish whether MRIA has a role in the assessment of subretinal fibrosis in the context of retinal and choroidal pathology

Overview of risk factors for age-related macular degeneration (AMD)

Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make life style choices that may reduce the risk of disease. This review discusses the role of genetics, sunlight, diet, cardiovascular factors, smoking, and alcohol as possible risk factors for AMD. Genetics plays a more significant role in AMD than previously thought, especially in younger patients, histocompatibility locus antigen (HLA) and complement system genes being the most significant. Whether the risk of AMD is increased by exposure to sunlight, cardiovascular risk factors, and diet is more controversial. Smoking is the risk factor most consistently associated with AMD. Current smokers are exposed to a two to three times higher risk of AMD than non-smokers and the risk increases with intensity of smoking. Moderate alcohol consumption is unlikely to increase the risk of AMD. Optometrists as front-line informers and educators of ocular health play a significant role in increasing public awareness of the risks of AMD. Cessation of smoking, the use of eye protection in high light conditions, dietary changes, and regular use of dietary supplements should all be considered to reduce the lifetime risk of AMD.

Overview of risk factors for age-related macular degeneration (AMD)

Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make life style choices that may reduce the risk of disease. This review discusses the role of genetics, sunlight, diet, cardiovascular factors, smoking, and alcohol as possible risk factors for AMD. Genetics plays a more significant role in AMD than previously thought, especially in younger patients, histocompatibility locus antigen (HLA) and complement system genes being the most significant. Whether the risk of AMD is increased by exposure to sunlight, cardiovascular risk factors, and diet is more controversial. Smoking is the risk factor most consistently associated with AMD. Current smokers are exposed to a two to three times higher risk of AMD than non-smokers and the risk increases with intensity of smoking. Moderate alcohol consumption is unlikely to increase the risk of AMD. Optometrists as front-line informers and educators of ocular health play a significant role in increasing public awareness of the risks of AMD. Cessation of smoking, the use of eye protection in high light conditions, dietary changes, and regular use of dietary supplements should all be considered to reduce the lifetime risk of AMD.

A longitudinal evaluation of the acceptability and impact of a diet diary app for older adults with age-related macular degeneration

Ongoing advances in technology are increasing the scope for enhancing and supporting older adults’ daily living. The digital divide between older and younger adults raises concerns, however, about the suitability of technological solutions for older adults, especially for those with impairments. Taking older adults with Age-Related Macular Degeneration (AMD) as a case study, we used user-centred and participatory design approaches to develop an assistive mobile app for self-monitoring their intake of food [12,13]. In this paper we report on findings of a longitudinal field evaluation of our app that was conducted to investigate how it was received and adopted by older adults with AMD and its impact on their lives. Demonstrating the benefit of applying inclusive design methods for technology for older adults, our findings reveal how the use of the app raises participants’ awareness and facilitates self-monitoring of diet, encourages positive (diet) behaviour change, and encourages learning.

Evaluation of low vision services on the quality of life of individuals with age-related macular degeneration

Background: Age-related macular degeneration (ARMD) is a major cause of irreversible visual loss in the elderly and a significant threat to their quality of life. Although low vision services often improve the functional outcomes of individuals with macular disease, it remains unclear whether or not they have any impact on quality of life. The principal aim of this study was to determine the effect of a hospital-based low vision clinic on the quality of life of individuals with ARMD. Methods: Forty patients with ARMD attended the low vision clinic at Milton Keynes University Hospital. Quality of life was measured with the vision-specific Low Vision Quality of Life (LVQOL) questionnaire and the general health EuroQol (EQ-5D-5L) questionnaire. Measures were completed at baseline (time zero, T0), and at three- (T3) and six-month (T6) follow-up visits. Results: The near visual acuity of individuals attending the low vision clinic for the first time improved significantly between visits T0 and T3 (p=0.005), reflecting the practiced use of their newly-dispensed low vision aids. As expected, there was no significant change in near acuity over this time period for existing patients. For both new and existing patients, a significant increase in LVQOL score was evident between visits T0 and T3, with a further significant improvement between T3 and T6. Similarly, there was a significant decrease in EQ-5D-5L questionnaire scores between visits T0 and T6. Conclusions: The higher LVQOL scores obtained at the end of the study period (T6) provide evidence that low vision services at Milton Keynes University Hospital served to improve patient quality of life. The reduction in EQ-5D-5L scores over the same time period suggests that low vision services also provide for an improvement in general health-related quality of life. Impact: The findings support the cause of low vision services to improve not only the vision and functional outcomes of individuals with macular disease but also their quality of life. Moreover, the findings suggest that a more efficient allocation of resources at low vision clinics may be possible through the standardisation of patient follow-up frequency.

Effects of advanced glycation end-products (AGEs) on retinal pigment epithelial (RPE) cells lysosomal function:implications for age-related macular degeneration (AMD)

Purpose: RPE lysosomal dysfunction is a major contributor to AMD pathogenesis. Controlled activity of a major class of RPE proteinases, the cathepsins, is crucial in maintaining correct lysosomal function. Advanced glycation end-products (AGEs) accumulate in the Bruch’s membrane (BM) with age, impacting critical RPE functions and in turn, contributing to the development of AMD. The aim of this study was to assess the effect of AGEs on lysosomal function by analysing the expression, processing and activity of the cysteine proteinases cathepsins B, L and S, and the aspartic proteinase cathepsin D. Methods: ARPE-19 cells were cultured on AGE-containing BM mimics (matrigel) for 14 days and compared to untreated substrate. Expression levels and intracellular processing of cathepsins B, D, L and S, were assessed by qPCR and immunoblotting of cell lysates. Lysosomal activity was investigated using multiple activity assays specific to each of the analysed cathepsins. Statistical analysis was performed using the Student’s independent T-test. Results: AGE exposure produced a 36% decrease in cathepsin L activity when compared to non-treated controls (p=0.02, n= 3) although no significant changes were observed in protein expression/processing under these conditions. Both the pro and active forms of cathepsin S decreased by 40% (p=0.04) and 74% (p=0.004), respectively (n=3). In contrast, the active form of the cathepsin D increased by 125% (p=0.005, n= 4). However, no changes were observed in the activity levels of both cathepsins S and D. In addition, cathepsin B expression, processing and activity also remained unaltered following AGE exposure. Conclusions: AGEs accumulation in the extracellular matrix, a phenomenon associated with the natural aging process of the BM, attenuates the expression, intracellular processing and activity of specific lysosomal effectors. Altered enzymatic function may impair important lysosomal processes such as endocytosis, autophagy and phagocytosis of photoreceptor outer segments, each of which may influence the age-related dysfunction of the RPE and subsequently, AMD pathogenesis.

The Effect of nutritional supplementation on subjective and objective measures of visual and retinal function:a random controlled trial

In industrialised countries age-related macular disease (ARMD) is the leading cause of visual loss in older people. Because oxidative stress is purported to be associated with an increased risk of disease development the role of antioxidant supplementation is of interest. Lutein is a carotenoid antioxidant that accumulates within the retina and is thought to filter blue light. Increased levels of lutein have been associated with reduced risk of developing ARMD and improvements in visual and retinal function in eyes with ARMD. The aim of this randomised controlled trial (RCT) was to investigate the effect of a lutein-based nutritional supplement on subjective and objective measures of visual function in healthy eyes and in eyes with age-related maculopathy (ARM) – an early form of ARMD. Supplement withdrawal effects were also investigated. A sample size of 66 healthy older (HO), healthy younger (HY), and ARM eyes were randomly allocated to receive a lutein-based supplement or no treatment for 40 weeks. The supplemented group then stopped supplementation to look at the effects of withdrawal over a further 20 weeks. The primary outcome measure was multifocal electroretinogram (mfERG) N1P1 amplitude. Secondary outcome measures were mfERG N1, P1 and N2 latency, contrast sensitivity (CS), Visual acuity (VA) and macular pigment optical density (MPOD). Sample sizes were sufficient for the RCT to have an 80% power to detect a significant clinical effect at the 5% significance level for all outcome measures when the healthy eye groups were combined, and CS, VA and mfERG in the ARM group. This RCT demonstrates significant improvements in MPOD in HY and HO supplemented eyes. When HY and HO supplemented groups were combined, MPOD improvements were maintained, and mfERG ring 2 P1 latency became shorter. On withdrawal of the supplement mfERG ring 1 N1P1 amplitude reduced in HO eyes. When HO and HY groups were combined, mfERG ring 1 and ring 2 N1P1 amplitudes were reduced. In ARM eyes, ring 3 N2 latency and ring 4 P1 latency became longer. These statistically significant changes may not be clinically significant. The finding that a lutein-based supplement increases MPOD in healthy eyes, but does not increase mfERG amplitudes contrasts with the CARMIS study and contributes to the debate on the use of nutritional supplementation in ARM.

The macular mapping test:a reliability study

Background: Age-related macular degeneration (ARMD) is the leading cause of visual disability in people over 60 years of age in the developed world. The success of treatment deteriorates with increased latency of diagnosis. The purpose of this study was to determine the reliability of the macular mapping test (MMT), and to investigate its potential as a screening tool. Methods: The study population comprised of 31 healthy eyes of 31 participants. To assess reliability, four macular mapping test (MMT) measurements were taken in two sessions separated by one hour by two practitioners, with reversal of order in the second session. MMT readings were also taken from 17 age-related maculopathy (ARM), and 12 AMD affected eyes. Results: For the normal cohort, average MMT scores ranged from 85.5 to 100.0 MMT points. Scores ranged from 79.0 to 99.0 for the ARM group and from 9.0 to 92.0 for the AMD group. MMT scores were reliable to within ± 7.0 points. The difference between AMD affected eyes and controls (z = 3.761, p = < 0.001) was significant. The difference between ARM affected eyes and controls was not significant (z = -0.216, p = 0.829). Conclusion: The reliability data shows that a change of 14 points or more is required to indicate a clinically significant change. This value is required for use of the MMT as an outcome measure in clinical trials. Although there was no difference between MMT scores from ARM affected eyes and controls, the MMT has the advantage over the Amsler grid in that it uses a letter target, has a peripheral fixation aid, and it provides a numerical score. This score could be beneficial in office and home monitoring of AMD progression, as well as an outcome measure in clinical research. © 2005 Bartlett et al; licensee BioMed Central Ltd.

Regional differences in oxygen saturation in retinal arterioles and venules

BACKGROUND: Retinal vessel oxygenation saturation measurements have been the focus of much attention in recent years as a potential diagnostic parameter in a number of ocular and systemic pathologies. This interest has been heightened by the ability to measure oxygen saturation in vivo using a photographic technique. METHODS: Retinal vessel oxygenation in venules and arterioles of 279 retinal vessels of 12 healthy Caucasian participants (mean age: 30 SD (+/- 6) years) were measured consecutively three times to evaluate short-term variation in oxygen saturation and regional variability of retinal vessel oxygen saturation using dual-wavelength technology (Oxymetry Modul, Imedos, Germany). All subjects underwent standard optometric assessment including non-contact intra-ocular pressure assessment as well as having their systemic blood pressure measured. RESULTS: Vessels were grouped as either near-macula or peripheral, depending on their location. Peripheral arterioles and venules exhibited significantly lower oxygen saturation compared to their near-macula counterparts (arterioles: 94.7% (SD 3.9) vs. 99.7% (SD 3.2); venules: 65.1% (SD 7.2) vs. 90.3% (SD 6.7)). Both arterioles and venules, main branches, and those feeding and draining the retina near the macula and periphery showed low short-term variability of oxygen saturation (arterioles: COV 1.2-1.8%; venules: COV 2.9-4.9%). CONCLUSIONS: Retinal arterioles and venules exhibit low short-term variation of oxygen saturation in healthy subjects. Regional differences in oxygen saturation could be a potential useful marker for risk stratification and diagnostic purposes of area-specific retinal pathology such as age-related macula degeneration and diabetic maculopathy.