Increased High Density Lipoprotein-levels associated with Age-related Macular degeneration. Evidence from the EYE-RISK and E3 Consortia

Purpose Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. Design Pooled analysis of cross-sectional data. Participants Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. Methods AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. Main Outcome Measures AMD features and stage; lipid measurements. Results HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14–1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91–0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10–1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10–7), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10–6 and P = 1.6 × 10–4). Conclusions Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered.</p

Age-related Macular Degeneration in Older Populations: Long-Term Incidence, Progression and Associations

Purpose: To assess the long-term incidence and progression of age-related macular degeneration (AMD) and its associated factors. Methods: The Blue Mountains Eye Study is a population-based cohort study of older Australians (n=3654) with 15-year follow-up. The presence and characteristics of AMD lesions were assessed from fundus photographs taken at each visit using the Wisconsin Age-Related Maculopathy Grading System. Results: After adjusting for competing risk of death, the 15-year incidence of early and late AMD were 15.1% and 4.1%, respectively. Larger macular areas involved by, and central location of early AMD lesions, and the co-presence of two lesion types, predicted increased progression to late AMD. A milder spectrum of early AMD was found in Singaporeans compared to Australians. Smoking was consistently found associated with incidences of late AMD, geographic atrophy and reticular drusen, and with the progression from unilateral to bilateral involvement in 5 years. Weekly fish consumption and high intake of dietary lutein-zeaxanthin were associated with reduced risks of late AMD, after controlling for other risk factors. Conclusion: This thesis work provides in-depth knowledge of long-term trajectory of AMD lesions and factors associated with their progression, including modifiable factors that could be intervened to prevent blindness from this condition