Economic cost of age-related macular degeneration: a review of recent research

As the population of most developed countries ages so the prevalence of diseases such as age-related macular degeneration (AMD) are likely to increase. To facilitate planning and informed debate regarding making provisions for this disease it is important that we have a clear understanding of the economic impact of visual impairment associated with AMD. In this paper we assess the state of current knowledge based on a review of published evidence in scientific journals. Based on our assessment of the evidence we argue that the paucity of research studies on the subject and wide variation in estimates produced from the few studies available make it difficult to assess with confidence the likely average direct cost-of-illness associated with AMD. We further argue that significant gaps in our understanding of the costs of AMD (particularly in respect of indirect costs) also exist. Current research should be augmented by more comprehensive studies.

Further assessment of the complement component 2 and factor B region associated with age-related macular degeneration

PURPOSE. Polymorphic variation in genes involved in regulation of the complement system has been implicated as a major cause of genetic risk, in addition to the LOC387715/HTRA1 locus and other environmental influences. Previous studies have identified polymorphisms in the complement component 2 (CC2) and factor B (CFB) genes, as potential functional variants associated with AMD, in particular CFB R32Q and CC2 rs547154, both of which share strong linkage disequilibrium (LD). METHODS. Data derived from the HapMap Project were used to select 18 haplotype-tagging SNPs across the extended CC2/ CFB region for genotyping, to measure the strength of LD in 318 patients with neovascular AMD and 243 age-matched control subjects to identify additional potential functional variants in addition to those originally reported. RESULTS. Strong LD was measured across this region as far as the superkiller viralicidic activity 2-like gene (SKIV2L). Nine SNPs were identified to be significantly associated with the genetic effect observed at this locus. Of these, a nonsynonymous coding variant SKIV2L R151Q (rs438999; OR, 0.48; 95% confidence interval [CI], 0.31- 0.74; P < 0.001), was in strong LD with CFB R32Q, rs641153 (r2 = 0.95) and may exert a functional effect. When assessed within a logistic regression model measuring the effects of genetic variation at the CFH and LOC387715/HTRA1 loci and smoking, the effect remained significant (OR, 0.38; 95% CI, 0.22- 0.65; P < 0.001). Additional variation identified within this region may also confer a weaker but independent effect and implicate additional genes within the pathogenesis of AMD. CONCLUSIONS. Because of the high level of LD within the extended CC2/CFB region, variation within SKIV2L may exert a functional effect in AMD. Copyright © Association for Research in Vision and Ophthalmology.

Association of diabetes with age-related macular degeneration in the EUREYE study

Objective: To examine the association between self-reported diabetes history and early or late age-related macular degeneration (AMD) in the European population.

An Ecological Correlation Study of Late Age-Related Macular Degeneration and the Complement Factor H Y402H Polymorphism

PURPOSE:
To investigate whether variation in the distribution of the risk allele frequency of the Y402H single-nucleotide polymorphism (SNP) across various ethnicities and geographic regions reflects differences in the prevalence of late age-related macular degeneration (AMD) in those ethnicities.

METHODS:
Published data were obtained via a systematic search. Study samples were grouped into clusters by ethnicity and geographic location and the Spearman correlation coefficient of the prevalence of late AMD and risk allele frequencies was calculated across clusters.

RESULTS:
Across all ethnicities, AMD prevalence was seen to increase with age. Populations of European descent had both higher risk allele frequencies and prevalence of late AMD than did Japanese, Chinese, and Hispanic descendants. Results for African descendants were anomalous: although allele frequency was similar to that in European populations, the age-specific prevalence of late AMD was considerably lower. The correlation coefficient for the association between allele frequency and AMD prevalence was 0.40 (95% confidence interval [CI] = -0.36 to 0.84, P = 0.28) in all populations combined and 0.71 (95% CI = 0.02-0.94, P = 0.04) when people of African descent were excluded.

CONCLUSIONS:
Evidence was found at the population level to support a positive association between the Y204H risk allele and the prevalence of AMD after exclusion of studies undertaken on persons of African ancestry. Data in African, Middle Eastern, and South American populations are needed to provide a better understanding of the association of late AMD genetic risk across ethnicities.

Prevalence of Early and Late Age-Related Macular Degeneration in India: The INDEYE Study

PURPOSE. To estimate the prevalence of early and late age-related macular degeneration (AMD) in India.

Sunlight exposure, antioxidants, and age-related macular degeneration

Objective: To examine the association of sunlight exposure and antioxidant level with age-related macular degeneration (AMD). Methods: Four thousand seven hundred fifty-three participants aged 65 years or older in the European Eye Study underwent fundus photography, were interviewed for adult lifetime sunlight exposure, and gave blood for antioxidant analysis. Blue light exposure was estimated by combining meteorologic and questionnaire data. Results: Data on sunlight exposure and antioxidants were available in 101 individuals with neovascular AMD, 2182 with early AMD, and 2117 controls. No association was found between blue light exposure and neovascular or early AMD. Significant associations were found between blue light exposure and neovascular AMD in individuals in the quartile of lowest antioxidant level - vitamin C, zeaxanthin, vitamin E, and dietary zinc - with an odds ratio of about 1.4 for 1 standard deviation unit increase in blue light exposure. Higher odds ratios for blue light were observed with combined low antioxidant levels, especially vitamin C, zeaxanthin, and vitamin E (odds ratio, 3.7; 95% confidence interval, 1.6-8.9), which were also associated with early stages of AMD. Conclusions: Although it is not possible to establish causality between sunlight exposure and neovascular AMD, our results suggest that people in the general population should use ocular protection and follow dietary recommendations for the key antioxidant nutrients. ©2008 American Medical Association. All rights reserved.

Oily fish consumption, dietary docosahexaenoic acid and eicosapentaenoic acid intakes, and associations with neovascular age-related macular degeneration

Background: Fish intake, the major source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may reduce the risk of age-related macular degeneration (AMD). Objective: We investigated the association of oily fish and dietary DHA and EPA with neovascular AMD (NV-AMD). Design: Participants aged =65 y in the cross-sectional population-based EUREYE study underwent fundus photography and were interviewed by using a food-frequency questionnaire. Fundus images were graded by the International Classification System for Age Related Maculopathy. Questionnaire data were converted to nutrient intakes with the use of food-composition tables. Survey logistic regression was used to calculate odds ratios (ORs) and 95% CIs of energy-adjusted quartiles of EPA or DHA with NV-AMD, taking into account potential confounders. Results: Dietary intake data and fundus images were available for 105 cases with NV-AMD and for 2170 controls without any features of early or late AMD. Eating oily fish at least once per week compared with less than once per week was associated with a halving of the odds of NV-AMD (OR = 0.47; 95% CI: 0.33, 0.68; P = 0.002). Compared with the lowest quartile, there was a significant trend for decreased odds with increasing quartiles of either DHA or EPA. ORs in the highest quartiles were 0.32 (95% CI: 0.12, 0.87; P = 0.03) for DHA and 0.29 (95% CI: 0.11, 0.73; P = 0.02) for EPA. Conclusions: Eating oily fish at least once per week compared with less than once per week was associated with a halving of the OR for NV-AMD. © 2008 American Society for Nutrition.

Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis

Background: Age-related macular degeneration (AMD) is the leading cause of blindness in Western countries. Numerous risk factors have been reported but the evidence and strength of association is variable. We aimed to identify those risk factors with strong levels of evidence which could be easily assessed by physicians or ophthalmologists to implement preventive interventions or address current behaviours.