Imaging, Genetic, and Demographic Factors Associated With Conversion to Neovascular Age-Related Macular Degeneration

Hallak, Joelle; Sisternes, Luís de; Osborne, Aaron; Yaspan, Brian L.; Rubin, Daniel L.; Leng, Theodore

doi:10.1001/jamaophthalmol.2019.0868

Cited by 36 publications

(46 citation statements)

References 30 publications

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“…Our study found that in low-HDI areas, people had a higher global AMD health burden, and females had a higher burden than males. A study conducted in Chicago was consistent with our ndings, suggesting that more women had converted to neovascular AMD than men [41], resulting in a higher global AMD burden. However, in our results, the global AMD burden of veryhigh-HDI countries did not show the same regularities (Fig.…”

Section: Discussionsupporting

confidence: 90%

Association of Sex with the Global Burden of Age-related Macular Degeneration

Wu¹,

Zhou²,

Tang³

et al. 2020

Preprint

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Background: Age-related macular degeneration (AMD) is the third leading cause of blindness and affects approximately 196 million people. This study aims to explore the association of sex with the global burden of AMD by year, age, and socioeconomic status using disability-adjusted life-years (DALYs).Methods: Global, national sex-specific DALY numbers, crude DALY rates, and age-standardized DALY rates caused by AMD, by year and age, were extracted from the Global Burden of Disease Study 2017. The human development index (HDI) in 2017 was extracted as an indicator of national socioeconomic status from the Human Development Report 2018 (HDR 2018). Pearson correlation and linear regression analyses were conducted to investigate the association between socioeconomic status and sex inequality of AMD.Results: Differences in the sex-specific global burden of AMD have persisted since 1990 to 2017. Female individuals had higher burden than male individuals of the same age in 2017, and the differences gradually increased after 55 years and maximized at 80 years or older with 105.41 DALYs rates in female vs 81.00 DALYs rates in male. The paired Wilcoxon signed rank test indicated that female had higher age-standardized DALY rates than male had (Z = -6.520, P < 0.001) and countries with lower HDI values had higher age-standardized DALY rates among both sexes. DALY rate ratio and sex differences in age-standardized DALY rates were positively associated with HDI in both Pearson correlation analyses and linear regression analyses of AMD. (P < 0.05).Conclusions: Although global blindness and vision impairment health care is progressing, sex inequality in AMD burden remained persistent since the past few decades. These findings might raise more public attention to the gender differences in global AMD burden and the association between the sex-related global burden and socioeconomic status.

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Section: Discussionsupporting

confidence: 90%

Association of Sex with the Global Burden of Age-related Macular Degeneration

Wu¹,

Zhou²,

Tang³

et al. 2020

Preprint

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“…The total number of drusen or measured drusen area or volume, are risk factors for the progression to GA and nAMD . Also, the location of the drusen is of predictive value for disease progression, since eyes with drusen near the fovea have a higher probability of developing late AMD compared to eyes with drusen outside the fovea . Although CFP is useful for assessing the appearance of drusen, multimodal imaging can be used to distinguish subtypes of drusen …”

Section: Phenotypic Risk Factorsmentioning

confidence: 99%

“…There are many modifiable and non‐modifiable risk factors that have been linked to increased risk of the progression of AMD. As the name already suggests, age is the most important demographic risk factor for AMD . A recent meta‐analysis, combining data of 14 population‐based studies, showed an increase in the prevalence of early AMD from 3.5% in people aged 55–59 years up to 17.6% in people 85 years and older.…”

Section: Demographic and Environmental Risk Factorsmentioning

confidence: 99%

Risk factors for progression of age‐related macular degeneration

Heesterbeek

Lorés‐Motta

Hoyng

et al. 2020

Ophthalmic Physiologic Optic

255

224

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Purpose Age‐related macular degeneration (AMD) is a degenerative disease of the macula, often leading to progressive vision loss. The rate of disease progression can vary among individuals and has been associated with multiple risk factors. In this review, we provide an overview of the current literature investigating phenotypic, demographic, environmental, genetic, and molecular risk factors, and propose the most consistently identified risk factors for disease progression in AMD based on these studies. Finally, we describe the potential use of these risk factors for personalised healthcare. Recent findings While phenotypic risk factors such as drusen and pigment abnormalities become more important to predict disease progression during the course of the disease, demographic, environmental, genetic and molecular risk factors are more valuable at earlier disease stages. Demographic and environmental risk factors such as age and smoking are consistently reported to be related to disease progression, while other factors such as sex, body mass index (BMI) and education are less often associated. Of all known AMD variants, variants that are most consistently reported with disease progression are rs10922109 and rs570618 in CFH, rs116503776 in C2/CFB/SKIV2L, rs3750846 in ARMS2/HTRA1 and rs2230199 in C3. However, it seems likely that other AMD variants also contribute to disease progression but to a lesser extent. Rare variants have probably a large effect on disease progression in highly affected families. Furthermore, current prediction models do not include molecular risk factors, while these factors can be measured accurately in the blood. Possible promising molecular risk factors are High‐Density Lipoprotein Cholesterol (HDL‐C), Docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), zeaxanthin and lutein. Summary Phenotypic, demographic, environmental, genetic and molecular risk factors can be combined in prediction models to predict disease progression, but the selection of the proper risk factors for personalised risk prediction will differ among individuals and is dependent on their current disease stage. Future prediction models should include a wider set of genetic variants to determine the genetic risk more accurately, and rare variants should be taken into account in highly affected families. In addition, adding molecular factors in prediction models may lead to preventive strategies and personalised advice.

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“…Previous studies have suggested potential functions for ACAD10 protein in the central nervous system, metabolism, and immunity, but no functional studies were performed [ 7 ]. A randomized clinical trial has identified an association of an ACAD10 variant with neovascular age-related macular degeneration (AMD) [ 9 ]. We recently have characterized an Acad10 gene trap knockout mouse model [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

ACAD10 protein expression and Neurobehavioral assessment of Acad10-deficient mice

et al. 2020

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Acyl-CoA dehydrogenase 10 (Acad10)-deficient mice develop impaired glucose tolerance, peripheral insulin resistance, and abnormal weight gain. In addition, they exhibit biochemical features of deficiencies of fatty acid oxidation, such as accumulation of metabolites consistent with abnormal mitochondrial energy metabolism and fasting induced rhabdomyolysis. ACAD10 has significant expression in mouse brain, unlike other acyl-CoA dehydrogenases (ACADs) involved in fatty acid oxidation. The presence of ACAD10 in human tissues was determined using immunohistochemical staining. To characterize the effect of ACAD10 deficiency on the brain, micro-MRI and neurobehavioral evaluations were performed. Acad10-deficient mouse behavior was examined using open field testing and DigiGait analysis for changes in general activity as well as indices of gait, respectively. ACAD10 protein was shown to colocalize to mitochondria and peroxisomes in lung, muscle, kidney, and pancreas human tissue. Acad10-deficient mice demonstrated subtle behavioral abnormalities, which included reduced activity and increased time in the arena perimeter in the open field test. Mutant animals exhibited brake and propulsion metrics similar to those of control animals, which indicates normal balance, stability of gait, and the absence of significant motor impairment. The lack of evidence for motor impairment combined with avoidance of the center of an open field arena and reduced vertical and horizontal exploration are consistent with a phenotype characterized by elevated anxiety. These results implicate ACAD10 function in normal mouse behavior, which suggests a novel role for ACAD10 in brain metabolism.

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Imaging, Genetic, and Demographic Factors Associated With Conversion to Neovascular Age-Related Macular Degeneration

Cited by 36 publications

References 30 publications

Association of Sex with the Global Burden of Age-related Macular Degeneration

Association of Sex with the Global Burden of Age-related Macular Degeneration

Risk factors for progression of age‐related macular degeneration

ACAD10 protein expression and Neurobehavioral assessment of Acad10-deficient mice

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