Age-related Macular Degeneration In Persons Research Articles

Age-related Macular Degeneration: Nutrition, Genes and Deep Learning—The LXXVI Edward Jackson Memorial Lecture

To evaluate the importance of nutritional supplements, dietary pattern, and genetic associations in age-related macular degeneration (AMD); and to discuss the technique of artificial intelligence/deep learning to potentially enhance research in detecting and classifying AMD. Retrospective literature review. To review the studies of both prospective and retrospective (post hoc) analyses of nutrition, genetic variants, and deep learning in AMD in both the Age-Related Eye Disease Study (AREDS) and AREDS2. In addition to demonstrating the beneficial effects of the AREDS and AREDS2 supplements of antioxidant vitamins and zinc (plus copper) for reducing the risk of progression to late AMD, these 2 studies also confirmed the importance of high adherence to Mediterranean diet in reducing progression of AMD in persons with varying severity of disease. In persons with the protective genetic alleles of complement factor H (CFH), the Mediterranean diet had further beneficial effect. However, despite the genetic association with AMD progression, prediction models found genetic information added little to the high predictive value of baseline severity of AMD for disease progression. The technique of deep learning, an arm of artificial intelligence, using color fundus photographs from AREDS/AREDS2 was superior in some cases and noninferior in others to clinical human grading (retinal specialists) and to the gold standard of the certified reading center graders. Counseling individuals affected with AMD regarding the use of the AREDS2 supplements and the beneficial association of the Mediterranean diet is an important public health message. Although genetic testing is important in research, it is not recommended for prediction of disease or to guide therapies and/or dietary interventions in AMD. Techniques in deep learning hold great promise, but further prospective research is required to validate the use of this technique to provide improvement in accuracy and sensitivity/specificity in clinical research and medical management of patients with AMD.

Genetic and Environmental Risk Factors for Age-Related Macular Degeneration in Persons 90 Years and Older

We studied associations of genetic polymorphisms in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) in nonagenarians with age-related macular degeneration (AMD). This case-control study comprised 2737 persons (1204 controls, 1433 AMD cases), including 166 nonagenarians (52 controls, 114 AMD cases). Single nucleotide polymorphisms (SNPs) in the genes ARMS2 and CFH were determined. Risk scores were computed by multiple logistic regression analysis, including genetic and environmental risk factors (smoking, hypertension, body mass index, diabetes) for different age groups (<70, 70-79, 80-89, ≥ 90 years [nonagenarians]). In nonagenarians, ARMS2 showed the weakest associations with AMD (odds ratio [OR] = 1.52, P = 0.127) compared to the other groups (OR, 70 years = 2.23, P = 1.03 × 10(-13); OR, 70-79 years = 2.70, P = 1.00 × 10(-13); OR, 80-89 years = 3.11, P = 6.56 × 10(-8)). For CFH, ORs for AMD increased with age (<70 years OR = 1.96, P = 1.80 × 10(-11); 70-79 years OR = 1.89, P = 4.48 × 10(-13); 80-89 years OR = 2.71, P = 1.28 × 10(-7)), but decreased again in the nonagenarians (OR = 2.21, P = 0.005). Compared to the group <70 years, reduced minor allele frequencies (MAFs) for AMD patients were observed in the nonagenarians (CFH 0.54 vs. 0.43, P = 0.009; ARMS2 0.44 vs. 0.29, P = 2.97 × 10(-5)), while the MAFs in controls were not significantly different. The genetic risk score revealed the lowest discriminative power in the nonagenarians with an area-under-curve (AUC) of 0.658 for receiver-operating characteristics (AUC 80-89 years = 0.768, 70-79 years = 0.704, <70 years = 0.682), while no significant difference was seen for the environmental risk score (AUC < 70 years = 0.579, 70-79 years = 0.567, 80-89 years = 0.600, >90 years = 0.608). Risk alleles in CFH and ARMS2 have a significantly smaller effect on AMD development in nonagenarians, while environmental factors retain a similar effect.

Analysis of Rare Variants in the Complement Component 2 (C2) and Factor B (BF) Genes Refine Association for Age-Related Macular Degeneration (AMD)

Several single-nucleotide polymorphisms (SNPs) in the C2 and BF genes have been associated with age-related macular degeneration (AMD) in Caucasian populations from the United States. The study was conducted to evaluate whether these SNPs are also associated with AMD in persons of Anglo-Celtic ethnicity in an Australian population. Included in the study were 565 persons with AMD and 204 ethnically matched control subjects. All participants completed a standard health questionnaire, were given a fundus examination, and provided a blood sample for DNA extraction. Alleles were determined by a matrix-assisted desorption ionization-time of flight (MALDI-TOF)-based approach followed by statistical analysis. The C2 and BF genes indicated significant association with AMD of only two SNPs; rs547154 (IVS10) in the C2 gene (P=9.1 x 10(-5)) and rs641153 (R32Q) in the BF gene (P=7.0 x 10(-5)). No association with AMD was found for SNP rs9332739 (E318D) in the C2 gene or for rs4151667 (L9H), rs1048709 (R150R), rs4151659 (K565E), or rs2072633 (IVS17) in the BF gene. A protective haplotype of variants IVS10 and R32Q was associated with AMD (OR 0.29, 95% CI 0.20-0.42). In this study, the association of the IVS10 and R32Q variants in the C2 and BF genes in AMD was replicated. Haplotype analysis indicated association of these variants with AMD in an Australian population. Both IVS10 and R32Q variants were in strong linkage disequilibrium with each other (r(2)=0.96). Although the E318D and L9H variants have shown association with AMD in previous studies, the findings were not in agreement. This demonstrates a refined pattern of association of these rare variants with AMD.

National Institutes of Health State-of-the-Science Conference Statement: Multivitamin/Mineral Supplements and Chronic Disease Prevention

National Institutes of Health State-of-the-Science Conference Statement: Multivitamin/Mineral Supplements and Chronic Disease Prevention

Smoking, Alcohol Intake, Estrogen Use, and Age-related Macular Degeneration in Latinos: The Los Angeles Latino Eye Study

To assess the association between smoking, alcohol intake, estrogen use, and both early age-related macular degeneration (AMD) (soft indistinct drusen, retinal pigment abnormalities) and advanced AMD (exudative AMD, geographic atrophy) in the Latino community. Population-based, cross-sectional study. Complete ophthalmic examination included stereoscopic macular photographs graded with a modified Wisconsin Age-related Maculopathy Grading System. A history of smoking, alcohol intake, and exogenous estrogen use was obtained by interview. Logistic regression was performed, and odds ratios (OR) were calculated with each AMD lesion as a dependent variable. There were 5875 participants (92.4%) with gradable photographs. Having ever smoked was associated with a higher risk of having advanced AMD (OR, 2.4). Heavy consumption of alcohol (>5 drinks per session) was significantly associated with a greater risk of having exudative AMD (OR, 5.8) and geographic atrophy (OR, 12.7) Beer drinking was associated with a higher risk of having advanced AMD (OR, 2.9), whereas wine drinking appeared to be protective for increased retinal pigment (OR, 0.7). Exogenous estrogen use also appeared to be protective from soft indistinct drusen (OR, 0.5) and increased retinal pigment (OR, 0.6), but power was limited in the assessment of its association with advanced AMD. Smoking and heavy alcohol consumption, particularly beer, was associated with a greater risk of having advanced AMD; exogenous estrogen use appeared to have a weak protective effect in Latino participants. Similar modifiable risk factors have been identified previously in non-Hispanic white patients, which suggests that common pathogenic mechanisms may be associated with AMD in persons of different ethnicities.