Age and Gender Variations in Age-related Macular Degeneration Prevalence in Populations of European Ancestry: A Meta-analysis

doi:10.1016/j.ophtha.2011.09.027

Ophthalmology

Volume 119, Issue 3, March 2012, Pages 571-580

https://doi.org/10.1016/j.ophtha.2011.09.027 Get rights and content

Objective

To obtain prevalence estimates of age-related macular degeneration (AMD; late, geographic atrophy, neovascular) by age and gender amongst populations of European ancestry taking into account study design and time trends.

Design

Systematic review of population-based studies published by September 2010 with quantitative estimates of geographic atrophy (GA), neovascular (NV), and late AMD prevalence. Studies were identified by a literature search of MEDLINE (from 1950), EMBASE (from 1980), and Web of Science (from 1980) databases.

Participants

Data from 25 published studies (57 173 subjects: 455 with GA, 464 with NVAMD, and 1571 with late AMD).

Methods

Bayesian meta-regression of the log odds of AMD with age, gender, and year of study allowing for differences in study design characteristics, to estimate prevalences of AMD (late, GA, NVAMD) along with 95% credible intervals (CrI).

Main Outcome Measures

Log odds and prevalence of AMD.

Results

There was considerable heterogeneity in prevalence rates between studies; for late AMD, 20% of the variability in prevalence rates was explained by differences in age and 50% by study characteristics. The prevalence of AMD increased exponentially with age (odds ratio [OR], 4.2 per decade; 95% CrI, 3.8–4.6), which did not differ by gender. There was some evidence to suggest higher risk of NVAMD in women compared with men (OR, 1.2; 95% CrI, 1.0–1.5). Compared with studies using fundus imaging and international classification systems, studies using fundus imaging with alternative classifications were more likely (OR, 2.7; 95% CrI, 1.1–2.8), and studies using alternative classifications without fundus imaging most likely to diagnose late AMD (OR, 2.9; 95% CrI, 1.3–7.8). There was no good evidence of trends in AMD prevalence over time. Estimated prevalence of late AMD is 1.4% (95% CrI, 1.0%–2.0%) at 70 years of age, rising to 5.6% (95% CrI, 3.9%–7.7%) at age 80 and 20% (95% CrI, 14%–27%) at age 90.

Conclusions

Studies using recognized classifications systems with fundus photography reported the lowest prevalences of AMD taking account of age and gender, and were stable over time, with a potentially higher risk of NVAMD for women. These prevalence estimates can be used to guide health service provision in populations of European ancestry.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Section snippets

Systematic Review Process

The review followed the Meta-analysis of Observational Studies in Epidemiology guidelines for the conduct of systematic reviews and meta-analyses of observational studies.⁸ We searched MEDLINE (1950 onward), EMBASE (1960 onward), and Web of Science (1970 onward) electronic databases. The literature search was updated to September 2010 using automatic Ovid alerts. A combination of text words for AMD (age related macula$ degeneration/age related maculopathy/senile macula$ degeneration) and

Statistical Analysis

The extent of heterogeneity in AMD prevalence estimates was quantified with the I² statistic (which gives the percentage of variation between studies due to heterogeneity rather than chance)¹¹ using STATA/SE (StataCorp, College Station, TX), and the degree to which age and study level covariates contribute to heterogeneity was examined. Levels of heterogeneity were high, so random-effect models were used throughout. The reported mean (or median) age or midpoint of the age range reported was

Results

The analyses include data from 25 published papers in 31 distinct populations involving 1571 cases of late AMD among 51 173 individuals of European ancestry (Table 1). One study¹² was in men and therefore only contributes to the meta-analysis by gender, leaving 30 populations (counting each country in the EUREYE¹³ study as a distinct population) for the meta-analysis for men and women combined. A subset of studies defining AMD type involved 455 cases with GA, and 464 cases with NVAMD. Most

Discussion

This systematic review and meta-analysis represents an update on earlier reviews carried out in European ancestry populations, with the inclusion of many more studies (31 study populations with 51 173 participants as opposed to a maximum of 7 studies with 29 658 participants used in earlier reviews).3, 4 Pooling prevalence from a larger number of studies provides considerably more precise estimates of overall prevalence, although the degree of precision is affected by heterogeneity between

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Critical Dependence on Area in Relationship between ARMS2/HTRA1 Genotype and Faster Geographic Atrophy Enlargement: Age-Related Eye Disease Study 2 Report Number 33
2024, Ophthalmology
To analyze ARMS2/HTRA1 as a risk factor for faster geographic atrophy (GA) enlargement according to (1) GA area and (2) contiguous enlargement versus progression to multifocality.
Age-Related Eye Disease Study 2 (AREDS2) cohort analysis.
Eyes with GA: 546 eyes of 406 participants.
Geographic atrophy area was measured from color fundus photographs at annual visits. Mixed-model regression of square root of GA area and proportional hazards regression of progression to multifocality were analyzed by ARMS2 genotype.
Change in square root GA area and progression to multifocality.
Geographic atrophy enlargement was significantly faster with ARMS2 risk alleles (P < 0.0001) at 0.224 mm/year (95% CI, 0.195–0.252 mm/year), 0.298 mm/year (95% CI, 0.271–0.324 mm/year), and 0.317 mm/year (95% CI, 0.279–0.355 mm/year), for 0 to 2 risk alleles, respectively. However, a significant interaction (P = 0.011) was observed between genotype and baseline area. In eyes with very small area (< 1.9 mm²), enlargement was significantly faster with ARMS2 risk alleles (P < 0.0001) at 0.193 mm/year (95% CI, 0.162–0.225 mm/year) versus 0.304 mm/year (95% CI, 0.280–0.329 mm/year) for 0 versus 1 to 2 risk alleles, respectively. With moderately small (1.9–3.8 mm²) or medium to large (≥ 3.8 mm²) area, enlargement was not significantly faster with ARMS2 risk alleles (P = 0.66 and P = 0.70, respectively). In nonmultifocal GA, enlargement was significantly faster with ARMS2 risk alleles (P = 0.001) at 0.175 mm/year (95% CI, 0.142–0.209 mm/year), 0.226 mm/year (95% CI, 0.193–0.259 mm/year), and 0.287 mm/year (95% CI, 0.237–0.337 mm/year) with 0 to 2 risk alleles, respectively. ARMS2 genotype was not associated significantly with progression to multifocal GA.
The relationship between ARMS2/HTRA1 genotype and faster GA enlargement depends critically on GA area: risk alleles represent a strong risk factor for faster enlargement only in eyes with very small area. They increase the growth rate more through contiguous enlargement than progression to multifocality. ARMS2/HTRA1 genotype is more important in increasing risk of progression to GA and initial GA enlargement (contiguously) than in subsequent enlargement or progression to multifocality. These findings may explain some discrepancies between previous studies and have implications for both research and clinical practice.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Progression of Geographic Atrophy: Retrospective Analysis of Patients from the IRIS® Registry (Intelligent Research in Sight)
2023, Ophthalmology Science
To evaluate disease progression and associated vision changes in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) in 1 eye and GA or neovascular AMD (nAMD) in the fellow eye using a large dataset from routine clinical practice.
Retrospective analysis of clinical data over 24 months.
A total of 256 635 patients with GA from the American Academy of Ophthalmology (Academy) IRIS® Registry (Intelligent Research in Sight) Registry (January 2016 to December 2017).
Patients with ≥ 24 months of follow-up were grouped by fellow-eye status: Cohort 1, GA:GA; Cohort 2, GA:nAMD, each with (subfoveal) and without subfoveal (nonsubfoveal) involvement. Eyes with history of retinal disease other than AMD were excluded. Sensitivity analysis included patients who were managed by retina specialists and had a record of imaging within 30 days of diagnosis.
Change in visual acuity (VA), occurrence of new-onset nAMD, and GA progression from nonsubfoveal to subfoveal.
In total, 69 441 patients were included: 44 120 (64%) GA:GA and 25 321 (36%) GA:nAMD. Otherwise eligible patients (57 788) were excluded due to follow-up < 24 months. In both GA:GA and GA:nAMD cohorts, nonsubfoveal study eyes had better mean (standard deviation) VA at index (67 [19.3] and 66 [20.3] letters) than subfoveal eyes (59 [23.9] and 47 [26.9] letters), and 24-month mean VA changes were similar for nonsubfoveal (−7.6 and −6.2) and subfoveal (−7.9 and −6.5) subgroups. Progression to subfoveal GA occurred in 16.7% of nonsubfoveal study eyes in the GA:GA cohort and 12.5% in the GA:nAMD cohort. More new-onset study-eye nAMD was observed in the GA:nAMD (21.6%) versus GA:GA (8.2%) cohorts. Sensitivity analysis supported the robustness of the observations in the study.
This retrospective analysis describes the natural progression of GA lesions and the decline in VA associated with the disease.
Proprietary or commercial disclosure may be found after the references.
Clinical Characteristics and Progression of Geographic Atrophy in a Japanese Population
2023, Ophthalmology Retina
To elucidate the clinical characteristics and progression rate of geographic atrophy (GA) associated with age-related macular degeneration (AMD) in a Japanese population.
Retrospective, multicenter, observational study.
A total of 173 eyes from 173 patients from 6 university hospitals in Japan were included. Of 173 study eyes, 101 eyes from 101 patients were included in the follow-up group. All patients were Japanese, aged ≥ 50 years and had definite GA associated with AMD in at least 1 eye.
The GA area was measured semiautomatically using fundus autofluorescence (FAF) images. In the follow-up group followed for > 6 months with FAF images, the GA progression rate was calculated by 2 methods: mm² per year and mm per year using the square-root transformation (SQRT) strategy. Simple and multiple linear regression analyses were used to identify the baseline factors associated with the GA progression rate.
Clinical characteristics of GA and the GA progression rate.
The mean age was 76.8 ± 8.8 years, and 109 (63.0%) were males. Sixty-two (35.8%) patients had bilateral GA. The mean GA area was 3.06 ± 4.00 mm² (1.44 ± 1.00 mm [SQRT]). Thirty-eight eyes (22.0%) were classified as having pachychoroid GA. Drusen and reticular pseudodrusen were detected in 115 (66.5%) and 73 (42.2%) eyes, respectively. The mean subfoveal choroidal thickness was 194.7 ± 105.5 μm. In the follow-up group (follow-up period: 46.2 ± 28.9 months), the mean GA progression rate was 1.01 ± 1.09 mm² per year (0.23 ± 0.18 mm/year [SQRT]). In the multivariable analysis, the baseline GA area (SQRT; P = 0.002) and the presence of reticular pseudodrusen (P < 0.001) were significantly associated with a greater GA progression rate (SQRT).
Certain clinical characteristics of GA in Asian populations may differ from those in White populations. Asian patients with GA showed male dominance and relatively thicker choroid than White patients. There was a group with GA without drusen but with features of pachychoroid. The GA progression rate in this Asian population was relatively lower than that in White populations. Large GA and reticular pseudodrusen were associated with a greater GA progression rate.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Geographic Atrophy in Age-Related Macular Degeneration: A Tale of Two Stages
2023, Ophthalmology Science
To examine disease progression in age-related macular degeneration (AMD) at 2 distinct stages, progression to geographic atrophy (GA) versus GA expansion, by comparison of the risk and protective factors at each stage.
Perspective.
Individuals at risk of GA or with GA.
Progression to GA and GA expansion rate.
Critical synthesis of the literature on risk and protective factors, both environmental and genetic, for progression to GA versus GA expansion in AMD.
Comparison of the risk and protective factors demonstrates partially overlapping but partially distinct risk and protective factors for progression to GA versus GA expansion. Some factors are shared (i.e., operating in the same direction at both stages), others are not shared, and others seem to operate in different directions at each stage. Risk variants at ARMS2/HTRA1 increase both risk of progression to GA and GA expansion rate, presumably through the same mechanism. By contrast, risk and protective variants at CFH/CFHR alter risk of GA but not GA expansion rate. A risk variant at C3 increases risk of GA but is associated with slower GA expansion. In environmental factors, cigarette smoking is associated with increased risk of GA and faster GA expansion, whereas increased age is associated with the former but not the latter. The Mediterranean diet is associated with decreased progression at both stages, although the food components with the largest contributions seem to differ between the 2 stages. Some phenotypic features, such as reticular pseudodrusen and hyperreflective foci, are associated with increased progression at both stages.
Analysis of the risk and protective factors for progression to GA and GA expansion demonstrates partially overlapping but partially distinct elements at each stage: some are shared, some are relevant to 1 stage only, and some even seem active in opposite directions at each stage. Aside from ARMS2/HTRA1, the overlap between the genetic risk factors for the 2 stages is minimal. This suggests that the biologic mechanisms differ at least partially between the 2 disease stages. This has implications for therapeutic approaches and suggests that treatment aimed at the underlying disease processes may need to be tailored by stage.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Retinal pigment epithelial cells can be cultured on fluocinolone acetonide treated nanofibrous scaffold
2023, Materials and Design
Engineered tissue currently lacks requisite capacity to sustain cell viability and functionality. Here we demonstrate that human RPE cell lines (ARPE-19) can be cultured on ultrathin suspended electrospun nanofibre scaffolds (ENS) composed of hydrophobic polymer polyacrylonitrile (PAN) and a water-soluble aliphatic diamine, without (untreated) or with (treated) fluocinolone acetonide (FA). Cells survived and retained their characteristic morphology for up to 150 days with FA-treated ENS and manifested a morphological epithelial phenotype with expression of biomarkers critical for maintaining retinal physiological characteristics. This novel technique for producing culture substrates provides suitable hydrophilicity and a protective environment for prolonged RPE culture and has immense potential for subretinal transplantation. The findings indicate that FA-treated ENS is an excellent matrix for retaining the differentiated and epithelial phenotype.
Reticular Pseudodrusen Status, ARMS2/HTRA1 Genotype, and Geographic Atrophy Enlargement: Age-Related Eye Disease Study 2 Report 32
2023, Ophthalmology
To determine whether reticular pseudodrusen (RPD) status, ARMS2/HTRA1 genotype, or both are associated with altered geographic atrophy (GA) enlargement rate and to analyze potential mediation of genetic effects by RPD status.
Post hoc analysis of an Age-Related Eye Disease Study 2 cohort.
Eyes with GA: n = 771 from 563 participants.
Geographic atrophy area was measured from fundus photographs at annual visits. Reticular pseudodrusen presence was graded from fundus autofluorescence images. Mixed-model regression of square root of GA area was performed by RPD status, ARMS2 genotype, or both.
Change in square root of GA area.
Geographic atrophy enlargement was significantly faster in eyes with RPD (P < 0.0001): 0.379 mm/year (95% confidence interval [CI], 0.329–0.430 mm/year) versus 0.273 mm/year (95% CI, 0.256–0.289 mm/year). Enlargement was also significantly faster in individuals carrying ARMS2 risk alleles (P < 0.0001): 0.224 mm/year (95% CI, 0.198–0.250 mm/year), 0.287 mm/year (95% CI, 0.263–0.310 mm/year), and 0.307 mm/year (95% CI, 0.273–0.341 mm/year) for 0, 1, and 2, respectively. In mediation analysis, the direct effect of ARMS2 genotype was 0.074 mm/year (95% CI, 0.009–0.139 mm/year), whereas the indirect effect of ARMS2 genotype via RPD status was 0.002 mm/year (95% CI, –0.006 to 0.009 mm/year). In eyes with incident GA, RPD presence was not associated with an altered likelihood of central involvement (P = 0.29) or multifocality (P = 0.16) at incidence. In eyes with incident noncentral GA, RPD presence was associated with faster GA progression to the central macula (P = 0.009): 157 μm/year (95% CI, 126–188 μm/year) versus 111 μm/year (95% CI, 97–125 μm/year). Similar findings were observed in the Age-Related Eye Disease Study.
Geographic atrophy enlargement is faster in eyes with RPD and in individuals carrying ARMS2/HTRA1 risk alleles. However, RPD status does not mediate the association between ARMS2/HTRA1 genotype and faster enlargement. Reticular pseudodrusen presence and ARMS2/HTRA1 genotype are relatively independent risk factors, operating by distinct mechanisms. Reticular pseudodrusen presence does not predict central involvement or multifocality at GA incidence but is associated with faster progression toward the central macula. Reticular pseudodrusen status should be considered for improved predictions of enlargement rate.
Proprietary or commercial disclosure may be found after the references.

View all citing articles on Scopus

: Manuscript no. 2011-579.

: Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

: The work was supported by a grant from the Macular Diseases Society, UK and commissioned on behalf of the Macular Interest Group of Vision 2020, UK.

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Original articleAge and Gender Variations in Age-related Macular Degeneration Prevalence in Populations of European Ancestry: A Meta-analysis

Objective

Design

Participants

Methods

Main Outcome Measures

Results

Conclusions

Financial Disclosure(s)

Section snippets

Systematic Review Process

Statistical Analysis

Results

Discussion

Ophthalmology

Surv Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Lancet

Ophthalmology

Ophthalmology

Prog Retin Eye Res

Ophthalmology

Ophthalmology

Vision 2020: Right to SightBlindness and Visual Impairment: Global Facts

Causes of blind certifications in England and Wales: April 1999–March 2000

Eye (Lond)

How big is the burden of visual loss caused by age related macular degeneration in the United Kingdom?

Br J Ophthalmol

Prevalence of age-related macular degeneration in the United States

Arch Ophthalmol

Prevalence of age-related macular degeneration in the US population

Arch Ophthalmol

Variations in primary open-angle glaucoma prevalence by age, gender, and race: a Bayesian meta-analysis

Invest Ophthalmol Vis Sci

Meta-analysis of observational studies in epidemiology: a proposal for reporting

JAMA

Original article
Age and Gender Variations in Age-related Macular Degeneration Prevalence in Populations of European Ancestry: A Meta-analysis