Measurement of the economic impact of visual impairment from age-related macular degeneration in Australia

The purpose of this report was to: (i) outline the potential value of health economic studies into age-related macular degeneration (AMD); (ii) provide an overview of health economic studies pertinent to AMD; and (iii) outline the basic frame work of cost-of-illness studies (a useful first step in applying economic methods). The detection and management of sensory loss in the elderly plays a key role in the Australian Government's Healthy Ageing Strategy. Age-related macular degeneration is currently the leading cause of blindness in elderly Australians. Although a large proportion of AMD cases remain untreatable, the introduction of photo­dynamic therapy provides a relatively expensive and possibly cost-effective innovation for others. Antioxidant therapy has also been proven effective in reducing progression of early to late disease. The discipline of economics can contribute to an understanding of AMD prevention and treatment through: (i) describing the current burden of disease; (ii) predicting the changes in the burden of disease over time, and (iii) evaluating the efficiency of different interventions. Cost-of-illness studies have been performed in many fields of medicine. Little work, however, has been done on describing the economic impact from AMD. A number of different economic evaluation methods can be used in judging the efficiency of possible interventions to reduce the disease burden of AMD. Although complementary in nature, each has specific uses and limitations. Studies of the economic impact of eye diseases are both feasible and necessary for informed health care decision-making.

Effects of task lighting on visual function in age-related macular degeneration

The purpose was to investigate the effects of the spectral power distribution (SPD) and illuminance of task lighting on visual function in age-related macular degeneration (ARMD) compared to normal healthy eyes. Twenty-eight subjects with ARMD and 18 age-matched normal subjects were studied. The effects on visual function were determined for four common task light sources: standard pearl coat incandescent (SP), daylight blue incandescent (DL), warm white fluorescent (WW) and cool white fluorescent (CW). Apart from a small, statistically significant improvement in contrast sensitivity with DL compared to SP lighting (0.5 dB, p = 0.01), there were no significant effects of SPD on other visual functions and no differences in the effects for subjects with ARMD and those with normal vision. Thus, for task lighting typically used in low vision rehabilitation, the SPD would seem to be of minimal clinical importance to visual function. However, increasing the task illuminance had a greater effect on visual function, in particular for subjects with ARMD (p < 0.01). For an increase in illuminance from 300 to 3000 lux, the mean increase in contrast sensitivity and near visual acuity was 1.5 dB and 0.13 log MAR, respectively. Although this effect is not large, we suggest that it is clinically relevant and supports the provision of additional task illuminance as an important part of low vision rehabilitation for patients with ARMD.

Younger siblings, C-Reactive protein, and risk of age-related macular degeneration

In this study, we examined the relationship between exposure to siblings and 1) the risk of age-related macular degeneration (AMD) and 2) C-reactive protein levels. We retrospectively analyzed pooled cross-sectional data from 2 studies: the Cardiovascular Health and Age-Related Maculopathy Study (2001–2002) and the Age-Related Maculopathy Statin Study (2004–2006). Associations between number of siblings and AMD were assessed by using multinomial logistic regression. Associations between number of siblings and C-reactive protein levels were examined by using a generalized linear model for γ distribution. A higher number of younger siblings was associated with significantly lower odds of early AMD in those with a family history of AMD (odds ratio = 0.2, 95% confidence interval: 0.1, 0.8) (P = 0.022) but was unrelated to AMD for those who had no family history of the disease (odds ratio = 1.0, 95% confidence interval: 0.9, 1.2) (P = 0.874). A higher number of younger siblings correlated with lower C-reactive protein levels (β = −0.19, 95% confidence interval: −0.38, −0.01) (P = 0.036). This supports the theory that immune modulation contributes to AMD pathogenesis and suggests that exposure to younger siblings might be protective when there is a family history of AMD.

Relationship between Clinical Macular Changes and Retinal Function in Age-Related Macular Degeneration

Purpose

Association between apolipoprotein E polymorphisms and age-related macular degeneration: a HuGE review and meta-analysis

A possible association between apolipoprotein E polymorphisms and age-related macular degeneration has been investigated numerous times, with conflicting results. A previous analysis pooling results from four studies (Schmidt et al., Ophthalmic Genet 2002;23:209-23) suggested an association, but those investigators did not document allele frequencies, the magnitude of the association, or the possible genetic mode of action. Thus, the authors searched MEDLINE from 1966 to December 2005 for any English-language studies reporting genetic associations. Data and study quality were assessed in duplicate. Pooling was performed while checking for heterogeneity and publication bias. Frequencies of the E2 and E4 alleles in Caucasians were approximately 8% and 15%, respectively. Allele- and genotype-based tests of association indicated a risk effect of up to 20% for E2 and a protective effect of up to 40% for E4. E2 appeared to act in a recessive mode and E4 in a dominant mode. There appears to be a differential effect of the E2 and E4 alleles on the risk of age-related macular degeneration, although the possibility of survivor bias needs to be ruled out more definitively.

Changes in abdominal obesity and age-related macular degeneration: the atherosclerosis risk in communities study

OBJECTIVE: To examine the association between changes in waist-hip ratio (WHR), a measure of abdominal obesity, and age-related macular degeneration (AMD). METHODS: A total of 12 515 persons from a population-based cohort study, aged 45 to 64 years in 1987 to 1989, were followed up over 6 years. The percentage change in WHR during follow-up was ranked into sex-specific deciles; an increase in WHR was defined as the top 10% of change and a decrease in WHR as the bottom 10%. The association of increased or decreased WHR and presence of AMD at follow-up was determined using logistic regression adjusting for potential confounders. RESULTS: The average change in WHR was an increase of 2%, ranging from a decrease of 44% to an increase of 102%. A decrease in WHR of 3% or more was associated with 29% lower odds of any AMD (odds ratio = 0.71; 95% confidence interval, 0.52-0.97). This effect was most pronounced among obese participants at baseline, where a decrease in WHR was associated with 59% lower odds of AMD (odds ratio = 0.41; 95% confidence interval, 0.20-0.82). CONCLUSIONS: Middle-aged persons who had a 3% or greater reduction in WHR over time were less likely to have AMD, particularly among those who were initially obese.

Fabrication of novel metal alloy foams for biomedical applications

Degeneration of the weight bearing bones of the ageing population often requires the inception of metallic biomaterials. Research in this area is receiving increased attention globally. However, most of today's artificial bone materials are dense and suffer from problems of adverse reaction, biomechanical mismatch and lack of appropriate space for the regeneration of new bone tissues. In the present study, novel ZrTi alloy foams with a porous structure and mechanical properties that are very close to those of bone were fabricated. These ZrTi alloy foams are biocompatible, and display a porous structure permitting the ingrowth of new bone tissues.

Ageing effects on knee and ankle joint angles at key events and phases of the gait cycle.

The objective of this research was to determine whether joint angles at critical gait events and during major energy generation/absorption phases of the gait cycle would reliably discriminate age-related degeneration during unobstructed walking. The gaits of 24 healthy adults (12 young and 12 elderly) were analysed using the PEAK Motus motion analysis system. The elderly participants showed significantly greater single (60.3% versus 62.3%, p < 0.01) and double ( p < 0.05) support times, reduced knee flexion (47.7° versus 43.0°, p < 0.05) and ankle plantarflexion (16.8° compared to 3.3°, p = 0.053) at toe off, reduced knee flexion during push-off and reduced ankle dorsiflexion (16.8° compared to 22.0°, p < 0.05) during the swing phase. The plantarflexing ankle joint motion during the stance to swing phase transition (A₂) for the young group (31.3°) was about twice ( p < 0.05) that of the elderly (16.9°). Reduced knee extension range of motion suggests that the elderly favoured a flexed-knee gait to assist in weight acceptance. Reduced dorsiflexion by the elderly in the swing phase implies greater risk of toe contact with obstacles. Overall, the results suggest that joint angle measures at critical events/phases in the gait cycle provide a useful indication of age-related degeneration in the control of lower limb trajectories during unobstructed walking.

Facts on fats

Cardiovascular disease and age-related macular degeneration (AMD) may share common risk factors in their causal pathways. Decades of research from the cardiovascular sciences on fats have led investigators to focus on specific types of fats rather than total fat as a whole. They have established that saturated and trans-unsaturated fats (trans fats) are damaging to cardiovascular health while polyunsaturated fats, particularly the marine omega 3 fatty acids appear protective. This has led to a number of studies investigating the associations of fat and AMD. Though the causal relationship between fats and AMD remain unproven, some studies suggest that an association may be present. To be able to understand and interpret the study results and their implications, an understanding of the fats in the diet is important. This review aims to give an overview of fatty acids, particularly the trans-unsaturated fatty acids, and the relevant food groups.

Editorial

When The Who sang about teenage angst in the 60s, their rock anthem ‘Talking about my Generation’ captured the divide between youth and beyond. Today, another divide – the digital divide – speaks to the issues of access, capital, and input that follow digital technologies. Like the earlier ‘me generation’, the new millennium D(igital) generation remains enigmatic, its members variously praised for their technological wizardry, criticised for their self-absorption, and pathologised for their unsociability. The D generation does not comprise youth alone, but the young are more exposed than others to the influence of new media and digital technologies. And like previous youth generations, they are often viewed as degenerate. A cybernetic degeneration symbolising society’s fears and cultural anxieties concerning the dehumanising prospects of technology appears most vividly in arguments about youth (Green & Bigum’s ‘aliens in the classroom’ [1993] is an apt description in this respect). Such negative rhetoric presents a dystopic view that tempers the more utopian, but equally reductionist visions of new technologies.

The ß-amyloid peptide in Alzheimer's disease decreases adhesion of vascular muscle cells to the basement membrane

Cerebral amyloid angiopathy (CAA) is a major feature of Alzheimer's disease pathology. In CAA, degeneration of vascular smooth muscle cells (VSMCs) occurs close to regions of the basement membrane where the amyloid protein (Aβ) builds up. In this study, the possibility that Aβ disrupts adhesive interactions between VSMCs and the basement membrane was examined. VSMCs were cultured on a commercial basement membrane substrate (Matrigel). The presence of Aβ in the Matrigel decreased cell-substrate adhesion and cell viability. Full-length oligomeric Aβ was required for the effect, as N- and C-terminally truncated peptide analogues did not inhibit adhesion. Aβ that was fluorescently labelled at the N-terminus (fluo-Aβ) bound to Matrigel as well as to the basement membrane heparan sulfate proteoglycan (HSPG) perlecan and laminin. Adhesion of VSMCs to perlecan or laminin was decreased by Aβ. As perlecan influences VSMC viability through the extracellular signal-regulated kinase (ERK)1/2 signalling pathway, the effect of Aβ1–40 on ERK1/2 phosphorylation was examined. The level of phospho-ERK1/2 was decreased in cells following Aβ treatment. An inhibitor of ERK1/2 phosphorylation enhanced the effect of Aβ on cell adhesion. The studies suggest that Aβ can decrease VSMC viability by disrupting VSMC–extracellular matrix (ECM) adhesion.

Stimulation of calcineurin Aα activity attenuates muscle pathophysiology in mdx dystrophic mice

Calcineurin activation ameliorates the dystrophic pathology of hindlimb muscles in mdx mice and decreases their susceptibility to contraction damage. In mdx mice, the diaphragm is more severely affected than hindlimb muscles and more representative of Duchenne muscular dystrophy. The constitutively active calcineurin A transgene (CnA) was overexpressed in skeletal muscles of mdx (mdx CnA*) mice to test whether muscle morphology and function would be improved. Contractile function of diaphragm strips and extensor digitorum longus and soleus muscles from adult mdx CnA* and mdx mice was examined in vitro. Hindlimb muscles from mdx CnA* mice had a prolonged twitch time course and were more resistant to fatigue. Because of a slower phenotype and a decrease in fiber cross-sectional area, normalized force was lower in fast- and slow-twitch muscles of mdx CnA* than mdx mice. In the diaphragm, despite a slower phenotype and a 35% reduction in fiber size, normalized force was preserved. This was likely mediated by the reduction in the area of the diaphragm undergoing degeneration (i.e., mononuclear cell and connective and adipose tissue infiltration). The proportion of centrally nucleated fibers was reduced in mdx CnA* compared with mdx mice, indicative of improved myofiber viability. In hindlimb muscles of mdx mice, calcineurin activation increased expression of markers of regeneration, particularly developmental myosin heavy chain isoform and myocyte enhancer factor 2A. Thus activation of the calcineurin signal transduction pathway has potential to ameliorate the mdx pathophysiology, especially in the diaphragm, through its effects on muscle degeneration and regeneration and endurance capacity.