PurposeAge-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future.DesignMeta-analysis of prevalence data.ParticipantsA total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe.MethodsAMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV).Main Outcome MeasuresPrevalence of early and late AMD, BCVA, and number of AMD cases.ResultsPrevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95% CI 13.6%–21.5%) in those aged ≥85 years; for late AMD these figures were 0.1% (95% CI 0.04%–0.3%) and 9.8% (95% CI 6.3%–13.3%), respectively. We observed a decreasing prevalence of late AMD after 2006, which became most prominent after age 70. Prevalences were similar for gender across all age groups except for late AMD in the oldest age category, and a trend was found showing a higher prevalence of CNV in Northern Europe. After 2006, fewer eyes and fewer ≥80-year-old subjects with CNV were visually impaired (P = 0.016). Projections of AMD showed an almost doubling of affected persons despite a decreasing prevalence. By 2040, the number of individuals in Europe with early AMD will range between 14.9 and 21.5 million, and for late AMD between 3.9 and 4.8 million.ConclusionWe observed a decreasing prevalence of AMD and an improvement in visual acuity in CNV occuring over the past 2 decades in Europe. Healthier lifestyles and implementation of anti–vascular endothelial growth factor treatment are the most likely explanations. Nevertheless, the numbers of affected subjects will increase considerably in the next 2 decades. AMD continues to remain a significant public health problem among Europeans.

We have tested whether defocus imposed on local retinal areas can produce local changes in eye growth, even if accommodation is available to clear part of the imposed defocus. Hemi-field lenses were attached to little leather hoods that were worn by young chickens from day 11-15 post-hatching. The lens segments defocused either the nasal or the temporal visual field, or covered the full field. We found that negative lenses (-7.5 D) were incompletely compensated in all three cases but caused significant myopia in the defocused parts of the visual field (differences to fellow eyes with normal vision: nasal visual field -3.13 +/- 1.56 D, P < 0.001; temporal visual field -4.02 +/- 1.38 D, P < 0.001; full field -3.82 +/- 2.48 D, P = 0.01). Myopia was not enhanced if the lenses covered the entire visual field. Positive lenses (+6.9 D) caused larger changes in refraction than negative lenses and, again, there was no significant difference in the amount of induced hyperopia in the nasal or temporal retina, or in the amount of hyperopia with full-field lenses (difference to fellow eyes with normal vision: nasal visual field +6.2 +/- 2.69 D, P < 0.001; temporal visual field +5.95 +/- 2.22 D, full field +7.22 +/- 2.44 D, P < 0.001). To compare the shapes of the excised eyes after lens treatment, we wrote a fully automated image processing program that traced their outlines in digitized video images. We found that the shapes of the eyes treated with positive lenses did scarcely differ from their fellow eyes with normal vision, indicating that hyperopia over this 4 day period was caused mostly by choroidal thickening. Full field negative lenses produced significant axial eye elongation; the effects of locally imposed defocus on eye shape were less conspicuous and were significant only in some areas. That local compensation of defocus was possible for both negative and positive lenses, suggests that the retina can recognize the sign of defocus without accommodation cues. Even more striking is that the presence of accommodation is apparently ignored since the drift in the plane of focus during accommodation does not disturb the compensation process. We re-analyze previous experimental results that argue for different mechanisms for deprivation myopia and lens-induced refractive errors. We propose that lens-induced refractive errors are compensated by similar retinal mechanisms as the ones proposed by Bartmann and Schaeffel [(1994). Vision Research, 34, pp. 873-876] to explain deprivation myopia. The proposed mechanisms can integrate with long time constants over the spatial frequency content in the retinal image while the viewing distances change, and control both choroidal thickening and scleral growth. However, it turns out that the compensation of imposed myopia cannot be explained if only one constant viewing is available. Apparently, there is more than a retinal blur detector to guide refractive development.

Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relation to AMD in a large European dataset, and investigated whether this relationship is driven by certain sub fractions. Design: (Pooled) analysis of cross-sectional data. Participants: 30,953 individuals aged 50+ participating in the E3 consortium; and 1530 individuals from the Rotterdam Study with lipid sub fraction data. Methods: In E3, AMD features were graded per eye on fundus photographs using the Rotterdam Classification. Routine blood lipid measurements were available from each participant. Data on genetics, medication and confounders such as body mass index, were obtained from a common database. In a subgroup of the Rotterdam Study, lipid sub fractions 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 the associations. Main Outcome Measures: early, late or any AMD, phenotypic features of early AMD, lipid measurements. Results: HDL was associated with an increased risk of AMD, corrected for potential confounders (Odds Ratio (OR) 1.21 per 1mmol/L increase (95% confidence interval[CI] 1.14-1.29); while triglycerides were associated with a decreased risk (OR 0.94 per 1mmol/L increase [95%CI 0.91-0.97]). Both were associated with drusen size, higher HDL raises the odds of larger drusen while higher triglycerides decreases the odds. LDL-cholesterol only reached statistical significance in the association with early AMD (p=0.045). Regarding lipid sub fractions: the concentration of extra-large HDL particles showed the most prominent association with AMD (OR 1.24 [95%CI 1.10-1.40]). The CETP risk variant (rs17231506) for AMD was in line with increased-HDL levels (p=7.7x10-7); but LIPC risk variants (rs2043085, rs2070895) were associated in an opposite way (p=1.0x10-6 and 1.6x10-4). Conclusions: Our study suggests that HDL-cholesterol is associated with increased risk of AMD and triglycerides negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL sub fractions seem to be drivers in the relation with AMD, 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 a question to be answered.

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