Risk Of Age-related Macular Degeneration Research Articles

Association Between Age-Related Macular Degeneration With Visual Disability and Risk of Dementia: A Nationwide Cohort Study

ObjectivesTo investigate the prospective association between the risk of dementia and age-related macular degeneration (AMD) in patients with related visual disability (VD). DesignA nationwide population-based cohort study used authorized data provided by the Korean National Health Insurance Service. Setting and ParticipantsA total of 1,788,457 individuals aged >50 years who participated in the Korean National Health Screening Program were enrolled. MethodsFrom January 2009 to December 2019, participants were tracked for a diagnosis of dementia using registered diagnostic codes from claims data. Participants with VD were defined as those registered in a national disability registration established by the Korean government. The prospective association of AMD and related VD with new-onset dementia was investigated using a multivariate-adjusted Cox proportional hazard model adjusted for age, sex, body mass index, income level, systemic comorbidities, psychiatric diseases, and behavioral factors. ResultsDuring the average follow-up period of 9.7 ± 2.16 years, 4260 of 21,384 participants in the AMD cohort and 137,166 of 1,662,319 participants in the control cohort were newly diagnosed with dementia, respectively. Participants diagnosed with AMD showed a higher risk of new-onset dementia than those in the control group in the fully adjusted model [hazard ratio (HR) 1.11, 95% CI 1.07–1.14]. The risk of dementia was higher in participants diagnosed with AMD and associated VD (HR 1.28, 95% CI 1.15–1.43) compared to those without VD (HR 1.09, 95% CI 1.06–1.13). Conclusions and ImplicationsA diagnosis of AMD was associated with an increased risk of all-cause dementia and its major subtypes. Close monitoring of cognitive function in AMD patients, especially those with VD, may help in early detection of all-cause dementia, which could reduce the socioeconomic burden and improve the quality of life of patients.

The role of complement factor I rare genetic variants in age related macular degeneration in Finland.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the developed world. The alternative pathway (AP) of complement has been linked to the pathogenesis of AMD. In particular, rare variants (RVs) in the complement factor I (CFI) gene encoding the Factor I (FI) protein confer increased AMD risk. The prevalence of CFI RVs are well characterised in European AMD, however little is known about other populations. The Finnish population underwent genetic restriction events which have skewed allele frequencies in unexpected ways. A series of novel or enriched CFI RVs were identified in individuals with dry AMD from the Finnish Biobank Cooperative (FINBB), but the relationship between these genotypes and contribution to disease was unclear. Understanding how RVs impact the ability of FI to regulate the complement system is important to inform mechanistic understanding for how different genotypes contribute to disease development. To explore this a series of in vitro assays were used to functionally characterise the protein products of 3 CFI RVs enriched in FINBB dry AMD, where no prior data were available. The G547R variant resulted in almost complete loss of both classical pathway and AP regulatory potential. The c.982 g>a variant encoding G328R FI perturbed an exon splice enhancer site which resulted in exon skipping and a premature stop codon in vitro and low levels of FI in vivo. Despite detailed analysis no defect in levels or function was demonstrated in T107A. Functional characterization of all Finnish CFI RVs in the cohort allowed us to demonstrate that in Finnish dry AMD, collectively the type 1 CFI RVs (associated with FI haploinsufficiency) were significantly enriched with odds ratio (ORs) of 72.6 (95% confidence interval; CI 16.92 to 382.1). Meanwhile, type 2 CFI RVs (associated with FI dysfunction) collectively conferred a significant OR of 4.97 (95% CI 1.522 to 15.74), and non-impaired or normal CFI RV collectively conferred an of OR 3.19 (95% CI 2.410 to 4.191) although this was driven primarily by G261D. Overall, this study for the first time determined the ORs and functional effect for all CFI RVs within a Geographic Atrophy (GA) cohort, enabling calculations of combined risk scores that underline the risk conferred by type 1 and 2 CFI RVs in GA/AMD.

Adult Onset Foveomacular Vitelliform Dystrophy Shows Genetic Overlap With Age-Related Macular Degeneration.

Adult-onset foveomacular vitelliform dystrophy (AFVD) shares phenotypic similarities with age-related macular degeneration (AMD). The genetic factors associated with AFVD are unknown in >80% of cases. This study evaluated the association of known AMD genetic risk variants with AFVD and compared systemic complement activation in these conditions. Clinical, imaging, and genetic data were collected from 50 patients with AFVD (men/women = 25/25, mean age ± SD 73 ± 10 years), 917 patients with AMD (men/women = 377/540, mean age ± SD 77 ± 9 years), and 432 unaffected healthy controls (men/women = 202/230, mean age ± SD 71 ± 8 years). Genotyping focused on 52 single nucleotide polymorphisms (SNPs) linked to AMD. Weighted genetic risk scores (GRS) for 19 complement system associated variants, 7 lipid metabolism associated variants, the remaining 26 variants (other pathways GRS), and for all 52 variants (global score) were derived and correlated with phenotype. Of the 52 SNPs evaluated, CFH (rs570618) and C2/CFB/SKIV2L (rs116503776 and rs114254831) were associated with AFVD compared with healthy controls (odds ratio [OR] = 2.73, 95% confidence interval [CI] = 1.32-5.73, P = 0.01; OR = 0.31, 95% CI = 0.14-0.71, P = 0.0036; and OR = 0.41, 95% CI = 0.22-0.74, P = 0.0025, respectively). MIR6130/RORB (rs10781182) was negatively associated with AFVD compared with the healthy controls (OR = 0.13, CI = 0.06-0.25, P < 0.0001) and AMD (OR = 0.19, CI = 0.10-0.34, P < 0.0001). Regression analysis showed complement GRS was positively associated with AFVD compared with controls (OR = 1.42, 95% CI = 1.04-1.95, P = 0.03), whereas the other pathways' GRS was negatively associated (OR = 0.46, 95% CI = 0.21-0.98, P = 0.04). AMD was positively associated with the complement score, global score, and ARMS2/HTRA1 compared with controls. Non-monogenic AFVD is associated with AMD risk alleles in the complement cascade, but not in other pathways. Further research is needed to explore complement inhibition for AFVD.

A Comprehensive Health Screening Program Reveals the Prevalence of and Risk Factors for Age-Related Macular Degeneration: A Cross-Sectional Analysis

Background/Objectives: We investigated the prevalence of age-related macular degeneration (AMD) and associated risk factors in Korean subjects who underwent comprehensive health screening examinations. Methods: This single health screening center-based cross-sectional study included a total of 73,574 consecutive participants older than 30 years who underwent a health screening examination, including fundus photography, between October 2003 and December 2010. Weighted prevalence and risk factors for AMD were evaluated. Logistic regression was used to identify AMD risk factors. Results: The weighted prevalence of AMD was 15.42%, with a prevalence of 3.34% among people in their 30s. Advanced age significantly increased the risk for both early/intermediate AMD (p &lt; 0.001 across the age groups of 40, 50, 60, and 70+ years) and advanced AMD (p &lt;0.001 for the age groups of 60 and 70+ years). The male sex was strongly associated with an increased risk of both early/intermediate and advanced AMD (p &lt; 0.001 for both). Retinal arteriosclerosis, whether low- or high-grade, was linked to early/intermediate AMD (p &lt; 0.001 for both grades), whereas only high-grade arteriosclerosis was linked to advanced AMD (p &lt; 0.001). Additionally, hypertension (p &lt; 0.001), the hepatitis B carrier status (p &lt; 0.001), elevated mean corpuscular volume (p &lt; 0.001), and lower serum uric acid levels (p = 0.014) were associated with early/intermediate AMD. Higher education levels protected against early/intermediate AMD (p = 0.004 for high school graduates, p &lt; 0.001 for ≥college graduates). Higher serum inorganic phosphate levels (p = 0.002) and lower total serum ALB levels (p = 0.005) were significant risk factors for advanced AMD. Conclusions: Korean individuals as young as 30 years old are at risk of AMD. This study newly identified associations between retinal arteriosclerosis and both early/intermediate and advanced AMD, as well as associations between serum inorganic phosphate levels and total ALB levels with advanced AMD.

Alcohol Consumption and Risk of Age-Related Macular Degeneration and Geographic Atrophy Progression: AREDS2 Report 34

PurposeTo examine potential relationships between alcohol consumption and age-related macular degeneration (AMD) progression, including progression to late AMD and geographic atrophy (GA) enlargement rate. DesignPost hoc analysis of cohorts within the Age-Related Eye Diseases Study 2 (AREDS2). Participants6670 eyes (of 3673 participants) with no late AMD at baseline; 1143 eyes (of 841 participants) with GA at ≥2 consecutive visits. MethodsColor fundus photographs were collected at annual study visits and graded centrally for late AMD, GA area, and GA proximity. Alcohol consumption was calculated by food frequency questionnaire. Regression analyses of disease progression were performed according to alcohol consumption.Main outcome measures:Progression to late AMD and its subtypes; GA area-based progression; GA proximity-based progression. ResultsOver mean follow-up of 3.8 years, 40.2% of eyes progressed to late AMD. In men, with alcohol tertile 1 (no regular consumption) as reference, hazard ratios for progression to late AMD were 0.69 (95% CI 0.55-0.87, p=0.0015) for tertile 2 and 0.85 (0.71-1.02, p=0.079) for tertile 3. In women, hazard ratios were 1.12 (0.95-1.31, p=0.17) and 0.85 (0.72-1.00, p=0.046), respectively. Over mean follow-up of 3.1 years, GA area-based progression was significantly faster in women than men, at 0.295 (95% CI 0.278-0.311) and 0.260 mm/year (0.241-0.279), respectively (p=0.007). In men, area-based progression differed significantly by alcohol tertile (p=0.0001), at 0.275 (0.248-0.303), 0.183 (0.143-0.223), and 0.280 mm/year (0.254-0.306) in tertiles 1-3, respectively. In women, the area-based rate did not differ significantly by alcohol tertile (p=0.11). In men only, CDC-defined heavy drinking was associated with faster progression (p=0.024), at 0.306 (0.262-0.349) vs 0.252 mm/year (0.233-0.270). In 808 eyes with non-central GA, GA proximity-based progression did not differ significantly by alcohol tertile (p=0.55). ConclusionsModerate alcohol consumption is associated with decreased risk of progression to late AMD in men. GA progression is faster in women, but its relationship with alcohol consumption is much stronger in men. In men, moderate consumption is associated with slower GA progression and higher consumption with faster progression. Although some of these associations may also relate to confounding, they might suggest that individuals with GA should avoid high alcohol consumption.

Risk of Age-Related Macular Degeneration in Patients with Exfoliation Syndrome: The Utah Project on Exfoliation Syndrome (UPEXS)

Objective: To investigate any relationships between exfoliation syndrome or exfoliation glaucoma and age-related macular degeneration utilizing the Utah population database. Design: This was a retrospective, case–control cohort study. Subjects, Participants, and/or Controls: We identified 3405 patients diagnosed with exfoliation syndrome (XFS) or exfoliation glaucoma (XFG) during a dilated eye exam within the UHealth system from 1996 to 2021, whose dry or wet age-related macular degeneration (AMD) status was assessed. A population-based control pool of 257,714 UHealth patients with no XFS/XFG diagnosis and a dilated eye exam history from 1996 to 2021 was compiled, with its patients randomly selected and individually matched 3:1 to cases based on sex and age at index diagnosis of their respective case. Methods: A covariate analysis was performed of characteristics and risk factors associated with XFS/XFG, which included race/ethnicity, residence location, partner/marital status, and family history of XFS/XFG, obesity, tobacco use, alcohol use, osteoporosis/vitamin D deficiency, primary/essential hypertension, ocular hypertension, and cataract surgery. Main Outcome Measure: We studied the trends of non-exudative (dry) or exudative (wet) AMD in a large Utah population study of XFS/XFG patients and controls. Results: Of 3396 XFS/XFG patients, as well as 10,179 individually matched 3:1 control patients, 64% were female and the average age of XFS onset was 74.3 yrs. In a univariate model, we observed a very modest increased risk of wet AMD in XFS/XFG patients (odds ratio, OR = 1.14, 95% confidence interval (CI) 0.99–1.32), which did not achieve statistical significance (p = 0.07). After adjusting for the main effects of potential confounders, there was no greater presentation of AMD in XFS/XFG patients when compared with controls (dry AMD: OR = 0.94, 95% CI 0.85–1.05, p = 031; wet AMD: OR = 0.98, 95% CI 0.83–1.14, p = 0.76). In XFS/XFG patients compared to controls, the risk of having cataract surgery was elevated (OR = 2.39, 95% CI 2.18–2.62). However, after accounting for an interaction with AMD, XFS/XFG patients who underwent cataract surgery did not exhibit an increased risk of either dry or wet AMD (dry AMD: OR = 0.91, 95% CI 0.80–1.03; wet AMD: OR = 0.89, 95% CI 0.75–1.07). The risk of AMD in XFS/XFG patients vs. controls showed no association with osteoporosis/vitamin D deficiency for dry (OR 0.78 95% CI 0.66–0.92 p = 0.004) or wet AMD (OR = 0.72 95% CI 0.56–0.92 p = 0.01), while we found a borderline positive association with both dry and wet AMD if they had osteoporosis/vitamin D deficiency. Conclusion: Using the Utah Population Database, we found that a cataract surgery history significantly impacts the association between AMD and XFS, and that vitamin D deficiency/osteoporosis is a significant confounder of the association. However, no direct association between XFS and AMD was found in this study.

Loss of CFHR5 function reduces the risk for age-related macular degeneration.

Age-related macular degeneration (AMD) is a prevalent cause of vision loss in the elderly with limited therapeutic options. A single chromosomal region around the complement factor H gene ( CFH ) is reported to explain nearly 25% of genetic AMD risk. Here, we used association testing, statistical finemapping and conditional analyses in 12,495 AMD cases and 461,686 controls to deconvolute four major CFH haplotypes that convey protection from AMD. We show that beyond CFH , two of these are explained by Finn-enriched frameshift and missense variants in the CFH modulator CFHR5 . We demonstrate through a FinnGen sample recall study that CFHR5 variant carriers exhibit dose-dependent reductions in serum levels of the CFHR5 gene product FHR-5 and two functionally related proteins at the locus. Genetic reduction in FHR-5 correlates with higher preserved activities of the classical and alternative complement pathways. Our results propose therapeutic downregulation of FHR-5 as promising to prevent or treat AMD.

Machine learning model for age-related macular degeneration based on heavy metals: The National Health and Nutrition Examination Survey 2005 to 2008

Age-related macular degeneration (AMD) is the leading cause of blindness in older people in developed countries. It has been suggested that heavy metal exposure may be associated with the development of AMD, but most studies have focused on the effects of a single metal with traditional methods. In this study, we analyzed the relationship between 13 urinary heavy metal concentrations and AMD using NHANES data between 2005 and 2008. We constructed and compared 11 machine learning models to identify the best model for predicting AMD risk. We further interpreted the models by Permutation Feature Importance (PFI), Partial Dependence Plot (PDP) analysis, and SHapley Additive exPlanations (SHAP) analysis. 216 AMD patients out of 2380 participants. The random forest (RF) model performed optimally in predicting the risk of AMD, with an AUC value of 0.970. PFI analyses revealed that age and urinary cadmium (Cd) were the main factors influencing the risk of AMD. SHAP analyses further confirmed the significance of Cd concentration in predicting the risk of AMD, and we revealed a significant interaction with significant interaction of race. Our study firstly explored the relationship between heavy metal exposure levels and AMD based on machine learning techniques, found that urinary Cd concentration had the greatest impact on AMD, and revealed the superior predictive performance of machine learning methods. Furthermore, our study provided a new perspective for early screening and intervention of AMD.

The causal effects of lifestyle, circulating, pigment, and metabolic factors on early age-related macular degeneration: a comprehensive Mendelian randomization study

PurposeEarly detection of lifestyle factors, skin and hair color, circulating parameters, and metabolic comorbidities is crucial for personalized prevention and treatment of early age-related macular degeneration (AMD). This study aimed to assess the relationships between genetically predicted comprehensive risk factors and early AMD.Methods and resultsPublicly available genome-wide association study (GWAS) data were utilized to identify genetic variants significantly associated with each trait. We applied a Bonferroni-corrected significance level of P < 0.0017. P values between 0.0017 and 0.05 were considered suggestive associations. Univariable Mendelian randomization (MR) analyses revealed that elevated serum HDL-C, lower serum TG, and decreased three circulating fatty acids levels were robust indicators of an increased risk of early AMD (all P < 0.0017), with odds ratios (ORs) and 95% confidence intervals (CIs) of 1.218 (1.140–1.303), 0.784 (0.734–0.837), 0.772 (0.698–0.855), 0.776 (0.706–0.852), and 0.877 (0.798–0.963), respectively. Additionally, the “never eat wheat products”, “age started wearing glasses”, and “skin color” were significantly associated with the risk of early AMD (both P < 0.0017), with ORs (95% CIs) of 23.853 (2.731–208.323), 1.605 (1.269–2.030) and 1.190 (1.076–1.317), respectively. Multivariable MR analysis confirmed that elevated serum HDL-C (OR = 1.187, 1.064–1.324) increased the risk of early AMD, while higher serum TG (OR = 0.838, 0.738–0.950) was associated with a significantly lower risk. Furthermore, validation results indicated that serum HDL-C 1.201 (1.101–1.310) and TG 0.795 (0.732–0.864) were significantly associated with the risk of early AMD. There were suggestive associations of smoothies, chronotype, and hair color (0.0017 < P < 0.05), but sun/UV protection, smoking, BMI, diabetes, high blood pressure, cardiovascular diseases, fresh fruit intake, fish oil/cod liver oil supplement, sleeplessness, serum C-reactive protein level, and iron level were not associated with the risk of early AMD.ConclusionsOur comprehensive MR analysis demonstrated that elevated circulating HDL-C levels increase the risk of early AMD, while TG and fatty acid levels are associated with a decreased risk. These findings provide robust evidence for improved diagnosis and personalized prevention and treatment of early AMD.

Associations between co-exposure to multiple heavy metals and age-related macular degeneration: a cross-sectional study

Background & aimsAccumulating evidence suggests that exposure to single heavy metal can facilitate the progression of age-related macular degeneration (AMD). However, the effects of exposure to mixtures of heavy metals on AMD remain largely unexplored. This study aims to investigate both the joint and individual impacts of arsenic (As), mercury (Hg), cadmium (Cd), and lead (Pb) on AMD within a co-exposure framework. MethodsData from subjects participating the US National Health and Nutrition Examination Survey (NHANES, 2005-2008) were analyzed. Concentrations of As, Hg, Cd, and Pb were determined in urine by inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS) for As and Hg, and inductively coupled plasma mass spectrometry (ICP-MS) for Cd and Pb. The weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were employed to assess the effects of heavy metal mixtures on AMD risk. ResultsBoth WQS and BKMR analyses consistently revealed a significant overall association between heavy metal mixtures and the risk of all types of AMD. The combined effect was more evident among patients with early AMD compared to those with late AMD. Cd and Hg were the main contributors driving these combined effects within the context of metal mixtures. Elevated urinary levels of Cd were positively correlated with an increased risk for all types as well as early AMD. Higher exposure to Hg corresponded with an elevated risk for early AMD. Furthermore, BKMR analysis indicated that the influence of Cd on early AMD exhibited a non-linear pattern. ConclusionsOur findings suggest that co-exposure to As, Hg, Cd, and Pb is associated with an elevated risk for developing AMD, particularly in its early stages. Furthermore, excessive exposure to Cd and Hg has been identified as key contributing factors in this process.

Thyroid Function, Diabetes, and Common Age-Related Eye Diseases: A Mendelian Randomization Study.

Background: Previous Mendelian randomization (MR) studies showed an association between hypothyroidism and cataract and between high-normal free thyroxine (FT4) and late age-related macular degeneration (AMD), but not between FT4, thyroid stimulating hormone (TSH), or hyperthyroidism and diabetic retinopathy or cataract. These studies included a limited number of genetic variants for thyroid function and did not investigate autoimmune thyroid disease (AITD) or glaucoma, include bidirectional and multivariable MR (MVMR), and examine sex differences or potential mediation effects of diabetes. We aimed to address this knowledge gap. Methods: We examined the causality and directionality of the associations of AITD, and FT4 and TSH within the reference range with common age-related eye diseases (diabetic retinopathy, cataract, early and late AMD, and primary open-angle glaucoma). We conducted a bidirectional two-sample MR study utilizing publicly available genome-wide association study (GWAS) summary statistics from international consortia (ThyroidOmics, International AMD Genetics Consortium, deCODE, UK Biobank, FinnGen, and DIAGRAM). Bidirectional MR tested directionality, whereas MVMR estimated independent causal effects. Furthermore, we investigated type 1 diabetes (T1D) and type 2 diabetes (T2D) as potential mediators. Results: Genetic predisposition to AITD was associated with increased risk of diabetic retinopathy (p = 3 × 10-4), cataract (p = 3 × 10-3), and T1D (p = 1 × 10-3), but less likely T2D (p = 0.01). MVMR showed attenuated estimates for diabetic retinopathy and cataract when adjusting for T1D, but not T2D. We found pairwise bidirectional associations between AITD, T1D, and diabetic retinopathy. Genetic predisposition to both T1D and T2D increased the risk of diabetic retinopathy and cataract (p < 4 × 10-4). Moreover, genetically predicted higher FT4 within the reference range was associated with an increased risk of late AMD (p = 0.01), particularly in women (p = 7 × 10-3). However, we neither found any association between FT4 and early AMD nor between TSH and early and late AMD. No other associations were observed. Conclusions: Genetic predisposition to AITD is associated with risk of diabetic retinopathy and cataract, mostly mediated through increased T1D risk. Reciprocal associations between AITD, diabetic retinopathy, and T1D imply a shared autoimmune origin. The role of FT4 in AMD and potential sex discrepancies needs further investigation.

SLC16A8 is a causal contributor to age-related macular degeneration risk

Age-related macular degeneration (AMD), a complex neurodegenerative disease, is a leading cause of visual impairment worldwide with a strong genetic component. Genetic studies have identified several loci, but few causal genes with functional characterization. Here we highlight multiple lines of evidence which show a causal role in AMD for SLC16A8, which encodes MCT3, a retinal pigment epithelium (RPE) specific lactate transporter. First, in an unbiased, genome-wide analysis of rare coding variants we show multiple SLC16A8 rare variants are associated with AMD risk, corroborating previous borderline significant reports from AMD rare variant studies. Second, we report a novel SLC16A8 mutation in a three-generation family with early onset macular degeneration. Finally, mis-expression in multiple model organisms shows functional and anatomic retinal consequences. This study highlights the important role for SLC16A8 and lactate regulation towards outer retina/RPE health and highlights a potential new therapeutic opportunity for the treatment of AMD.

Integrative multiomic analysis unveils the molecular nexus of mitochondrial dysfunction in the pathogenesis of age-related macular degeneration

Mitochondrial dysfunction is linked to age-related macular degeneration (AMD), but its mechanisms and related molecular networks remain unclear. We explored the association between mitochondrial-related genes and AMD by integrating multiomic data. We acquired summary-level data on mitochondrial-related protein abundance, gene expression, and gene methylation from quantitative trait locus studies. Genetic associations with AMD were sourced from the International Age-related Macular Degeneration Genomics Consortium (discovery), FinnGen (replication), and UK Biobank (replication) studies. We used summary-data-based Mendelian randomization to assess the correlations between mitochondrial-related gene molecular characteristics and AMD. Furthermore, colocalization analysis was performed to ascertain if the detected signal pairings had a common causative genetic variation. Mitochondrial-related gene NFKB1 demonstrated a protective role in AMD (tier 1 evidence), whereas HSPA1A and HSPA1B genes were also associated with decreased AMD risk (tier 2 evidence). The methylation of cg09390974 and cg15409712 in NFKB1 was associated with increased NFKB1 expression, consistent with the protective effect on AMD risk, whereas inverse associations were observed between gene methylation and gene expression for HSPA1B (cg04835051 and cg16372051), supporting the risk roles of methylation in AMD. At circulating protein level, genetically predicted higher levels of HSPA1A (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.19−0.41, P < 0.001), HSPA1B (OR 0.13, 95% CI 0.06−0.27, P < 0.001), and NFKB1 (OR 0.43, 95% CI 0.27−0.68, P < 0.001) were inversely associated with AMD risk. These associations were corroborated in the colocalization analysis. We identified AMD-linked mitochondrial-related genes, potentially improving the understanding of its pathophysiological mechanisms and aiding the identification of novel pharmaceutical targets.

Curcuma-Based Nutritional Supplements and Risk of Age-Related Macular Degeneration

Curcuma-based nutritional supplements (CBNS) are natural anti-inflammatory and antioxidant agents that may confer benefits against age-related macular degeneration (AMD). To examine the association between the use of CBNS and the risk of development or progression of AMD. This was a retrospective cohort study with data collection in June of 2024. Data were gathered from the aggregated electronic health records research network, TriNetX (Cambridge, Massachusetts). Patients without AMD were included in the study before propensity score matching (PSM); these included those taking and not taking CBNS. Patients with no history of AMD were stratified by instances of CBNS prescription records. Patients with a history of early nonexudative AMD stratified by instances of CBNS prescription records were also identified. PSM was performed to control for baseline demographics and medical comorbidities. Patients were stratified by whether or not they were taking CBNS using RxNorm (National Library of Medicine) codes. Relative risk (RR) of developing nonexudative AMD, exudative AMD, advanced nonexudative AMD or geographic atrophy (GA), blindness, or requiring intravitreal anti-vascular endothelial growth factor (VEGF) therapy. A total of 66 804 patients (mean [SD] age, 64.9 [10.1] years; 44 124 female [66.1%]) taking CBNS and 1 809 440 patients (mean [SD] age, 67.0 [9.5] years; 999 534 female [55.2%]) not taking CBNS were included in this study. Among patients without a history of AMD aged 50 years or older, CBNS use was associated with lower rates of developing nonexudative AMD (RR, 0.23; 95% CI, 0.21-0.26; P < .001), advanced nonexudative AMD or GA (RR, 0.11; 95% CI, 0.07-0.17; P < .001), exudative AMD (RR, 0.28; 95% CI, 0.24-0.32; P < .001), blindness (RR, 0.46; 95% CI, 0.36-0.59; P < .001), or requiring intravitreal anti-VEGF therapy (RR, 0.15; 95% CI, 0.13-0.17; P < .001) when compared with matched patients not taking CBNS. Results were consistent among subsets of patients 60 and 70 years or older, respectively. Among patients with early nonexudative AMD, subsequent instances of CBNS prescription records were associated with lower rates of developing advanced nonexudative AMD or GA (RR, 0.58; 95% CI, 0.41-0.81; P < .001) when compared with matched patients with early nonexudative AMD without a CBNS prescription record. Results of this cohort study suggest that a reduced risk of developing AMD or progression to later stages of AMD was associated with subsequent use of CBNS. Further investigation to validate these findings, safety, and potential pharmacoprotective mechanisms of CBNS in AMD are suggested.

Association between axial length and uveitis.

Multiple studies have examined the association between myopia and various ocular diseases, but there is no clinical report of the relationship between myopia and uveitis. This study aimed to elucidate the relationship between myopia and uveitis by comparing axial lengths (AL) of uveitis patients with control individuals. This study included 1052 eyes (663 patients; 288 males, 375 females; median age 56.0years) with uveitis referred to Tokyo Medical University Hospital. Controls were 738 eyes with cataract but no other ocular diseases. AL was measured by IOLMaster or conventional A-mode ultrasound system. Uveitis eyes were grouped into various types of non-infectious uveitis, infectious uveitis, and unidentified uveitis. Median AL of each uveitis group was compared with control group using Mann-Whitney U-test, and also compared with adjustment for age and sex using multiple regression analysis. Binary logistic analysis was performed to examine whether AL plays a role in the risk of developing uveitis. Of 1052 eyes, 808 eyes (76.8%) were diagnosed with non-infectious uveitis [sarcoidosis (176 eyes, 16.7%), Vogt-Koyanagi-Harada disease (122 eyes, 11.6%), Behçet's disease (130 eyes, 12.4%), and others (380 eyes, 36.1%)], 146 eyes (13.9%) with infectious uveitis, and 98 eyes (9.3%) with unidentified uveitis. Median AL in all uveitis eyes was significantly shorter than in control eyes (23.73 vs 24.31mm, p < 0.001 unadjusted), and AL remained significantly shorter in uveitis than in control after age- and sex-adjustment (p < 0.001). Median AL was significantly shorter in non-infectious uveitis (23.72mm) and in infectious uveitis (23.99mm) compared to controls (p < 0.001 and < 0.05, respectively), and was significantly shorter in non-infectious uveitis than in infectious uveitis (p < 0.05). Each millimeter decrease in AL was associated with 1.266-fold increase in unadjusted risk [odds ratio (OR), 1.266; 95% confidence interval (CI), 1.196-1.341; p < 0.001) and 1.446-fold in age- and sex-adjusted risk (OR, 1.446; 95% CI, 1.349-1.549; p < 0.001) of developing uveitis. Median AL of uveitis eyes with infectious or non-infectious etiologies was significantly shorter than that in control eyes, suggesting an increased risk of developing uveitis in eyes with shorter AL. This feature should be considered when exploring new pathogenetic mechanisms of uveitis. What is known Shorter axial length may be associated with the pathogenesis of central serous chorioretinopathy and increased risk of early age-related macular degeneration. What is new Here we assessed the relationship between myopia and uveitis by comparing axial lengths of uveitis patients. Median axial length in all uveitis eyes was significantly shorter than in control eyes, and axial length remained significantly shorter in uveitis than in control after age- and sex-adjustment. Each millimeter decrease in axial length was associated with 1.266-fold increase in unadjusted risk and 1.446-fold in age- and sex-adjusted risk of developing uveitis.

Incidence and progression of age-related macular degeneration among patients with and without obstructive sleep apnea: a national cohort study.

Obstructive sleep apnea (OSA) may increase the risk of age-related macular degeneration (AMD) due to repetitive oxygen deprivation or other mechanisms, though whether OSA increases the risk of AMD progression is unknown. We analyzed associations between OSA and AMD risk in the Taiwanese population. We identified patients diagnosed with OSA between 2000 and 2018 in the Taiwan National Health Insurance Research Database and used 1:1 propensity score matching on demographics and co-morbidities to create a non-OSA cohort. We used Cox proportional hazard modeling to investigate the risk of AMD and the risk of progression from nonexudative to exudative AMD in OSA versus non-OSA patients. A total of 66,869 OSA patients were matched with 66,869 non-OSA patients. The hazard ratio (HR) of AMD in the OSA cohort was 1.36 (95% confidence interval[CI]: 1.31-1.43, p<.0001). The HR for progression from nonexudative to exudative AMD for the OSA cohort was 0.94 (95%CI: 0.77-1.14, p=0.5073). OSA is associated with a higher risk of developing AMD. However, no increased risk of AMD progression is observed among people with OSA and existing non-exudative AMD.

Associations of mediterranean diet score and age-related macular degeneration in Korean elderly

BackgroundPrevious studies have reported associations between individual nutrients or specific foods and the risk of age-related macular degeneration (AMD). However, the relationship between overall dietary quality, specifically the alternative Mediterranean diet (aMED) score, and AMD remains unclear. Therefore, this study aimed to investigate the association between the aMED score, as an indicator of overall diet quality, and AMD in the Korean population.MethodsWe conducted a cross-sectional analysis using nationally representative samples of older adults aged ≥ 65 years (895 men and 1,191 women) from the Korea National Health and Nutrition Examination Survey (2017–2018). Food intake and the aMED score were estimated using 24-h recall. AMD was diagnosed by an ophthalmologist based on fundus photography. The associations of aMED score tertiles with AMD were determined using odds ratios (ORs) from multivariate logistic regressions.ResultsMultiple logistic regression analysis revealed a significantly negative association between the aMED score and AMD (adjusted ORs = 0.58; 95% confidence interval = 0.39–0.88; p-trend = 0.021) in older men after adjusting for confounding factors such as age, body mass index, family monthly income, current smoking, alcohol consumption, physical activity, chronic disease status, and energy intake. Notably, this association was exclusively observed in men, and no significant association was observed between the aMED score and AMD in women (adjusted OR = 0.88; 95% CI = 0.61–1.29; p-trend = 0.691).ConclusionsThis study’s findings suggest that a high aMED score may be associated with a reduced risk of AMD in older men. Future studies with larger sample sizes and a prospective or interventional design are required to enhance current understanding regarding the association between diet quality and AMD.

Investigating the Link between Psychological Well-Being and Early-Stage Age-Related Macular Degeneration: A Mendelian Randomization Analysis

Purpose While some studies have started to focus on the link between psychological well-being and age-related macular degeneration (AMD), the relationship remains uncertain. Our research aims to provide new insights into this association, laying a foundation for future interventions and addressing existing knowledge gaps. Methods We utilized the “TwoSampleMR” package in R for a bidirectional Mendelian randomization analysis of psychological well-being (subjective well-being, depression, neuroticism, and Sensitivity to Environmental Stress and Adversity) and early-stage AMD. Causal effects were estimated using the inverse-variance weighted method, and additional methods included weighted median and MR-Egger regression. Sensitivity analyses included Cochran’s Q test, MR-Egger intercept analysis, MR-PRESSO, and leave-one-out analysis. Results The study found that the population with genetic predisposition to neuroticism had a 39.7% lower risk of early-stage AMD (OR = 0.603, 95% CI = 0.385–0.945, p = 0.027). Conversely, the population with genetic predisposition to subjective well-being had a 3.2% increased risk of early-stage AMD (OR = 1.032, 95% CI = 1.003–1.063, p = 0.029). No significant causal relationships were found from depression or Sensitivity to Environmental Stress and Adversity to early-stage AMD, nor from early-stage AMD to psychological well-being. Conclusion This study provides preliminary evidence that the relationship between psychological well-being and early-stage AMD may be complex and multifaceted. It suggests that moderate neuroticism levels might reduce early-stage AMD risk through health behaviors, pathophysiological mechanisms, and other factors, while high subjective well-being levels might increase this risk similarly. However, these findings are insufficient for preventive strategies due to a lack of substantial evidence and still require extensive experimental research for further validation.

Ultra-processed foods consumption and risk of age-related eye diseases: a prospective cohort study with UK biobank.

Consumption of ultra-processed foods (UPF) has been associated with increased risks of various age-related diseases. However, the potential association between UPF consumption and age-related eye diseases (AREDs) remains unclear. We aim to assess the associations between consumption of UPF and risk of AREDs including age-related macular degeneration (AMD), cataract and glaucoma. We included 156,232 individuals aged 50 or older, who were free from AREDs from UK biobank study. Dietary intake data were collected using 24-h dietary assessments. UPF is defined according to the NOVA classification, and all participants are divided into four quartiles based on the weight proportion (%) of UPF. During a median of 10years of follow-up. Cox proportional hazards were used to estimate the association between the proportion of UPF in the diet and the subsequent risk of various AREDs. After adjusting for multiple variables, individuals in the highest quartiles for UPF consumption exhibited an increased risk of AMD (hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.01-1.63; p = 0.03), cataract (HR: 1.10; 95% CI: 1.01-1.20; p = 0.04), and glaucoma (HR: 1.27; 95% CI: 0.98-1.63; p = 0.06) compared to those in the lowest quartiles. Moreover, a 10% increase in the weight of UPF in diet was associated with an 8% higher risk of AMD (HR: 1.08; 95% CI: 1.01-1.15; p = 0.03), a 3% higher risk of cataract (HR: 1.03; 95% CI: 1.00-1.06; p = 0.04), and a 7% higher risk of glaucoma (HR: 1.07; 95% CI: 1.00-1.15; p = 0.05). Our results suggest that a higher proportion of UPF in the diet was significantly link with an elevated risk of AMD and cataract. While additional research is necessary to validate these findings in diverse populations and settings, these results offer initial evidence to endorse public health initiatives that encourage limiting consumption of UPF.

Investigating the causal link between gut microbiota and dry age-related macular degeneration: a bidirectional Mendelian randomization study.

To assess the causal link between 211 gut microbiota (GM) taxa and dry age-related macular degeneration (dAMD) risk. Mendelian randomization using instrumental factors taken from a genome-wide association study (GWAS) were used. Inverse variance weighted (IVW) analysis and sensitivity analysis were performed on the FinnGen project, which included 5095 cases and 222 590 controls. The IVW analysis showed substantial genus- and family-level relationships between GM taxa and dAMD risk. Specifically, the family Peptococcaceae (P=0.03), genus Bilophila (P=3.91×10-3), genus Faecalibacterium (P=6.55×10-3), and genus Roseburia (P=0.04) were linked to a higher risk of developing dAMD, while the genus Candidatus Soleaferrea (P=7.75×10-4), genus Desulfovibrio (P=0.04) and genus Eubacterium ventriosum group (P=0.04) exhibited a protective effect against dAMD. No significant causal relationships were observed at higher taxonomic levels. Additionally, in the reverse IVW analysis, no meaningful causal effects of the 7 GM taxa. These findings give support for the gut-retina axis participation in dAMD and shed light on putative underlying processes. Investigations on the connection between GM and dAMD have not yet revealed the underlying mechanism.