Risk Factor For Age-related Macular Degeneration Research Articles

Longer recreational screen time contributes to the risk of age-related macular degeneration: a UK Biobank cohort study and two-sample Mendelian randomisation.

Recreational screen time (RST) has been found to be associated with cognitive decline and neurodegenerative diseases. However, the association between RST and age-related macular degeneration (AMD), an ocular neurodegenerative disease, is still unclear. We aimed to elucidate the association between RST and AMD. This study consisted of three parts: 1) a prospective cohort study with 482 939 UK Biobank participants and a 12.8-year median follow-up to explore the association between RST and incident AMD; 2) a two-sample Mendelian randomisation (MR) analysis using summary-level genome-wide association analysis data for RST based on 526 725 European individuals to assess causality between RST and AMD; and 3) a cross-sectional study involving 38 478 UK Biobank individuals with optical coherence tomography data to investigate the link between RST and retinal thickness. Multivariable Cox proportional-hazards models showed that an increase in total daily RST was associated with a greater risk of developing AMD (hazard ratio (HR) per standard deviation (SD) increase = 1.05; 95% confidence interval (CI) = 1.03, 1.07, P < 0.001). With further analysis, we revealed that daily high RST (>4 h/d) significantly increased the risk of AMD compared with low RST (0-3 h/d) (HR = 1.09; 95% CI = 1.04, 1.15, P = 0.001), while moderate RST (3.5-4 h/d) had no significant effect on AMD. Restricted cubic spline plots revealed a linear dose-response association between RST and AMD. With MR analysis we confirmed the potential causal association between RST and AMD (odds ratio per SD = 1.26; 95% CI = 1.01, 1.59, P = 0.042). Multivariable linear models suggested that an increase in RST was associated with thinning of the outer and inner retinal layers and total macular thickness. Longer RST may be a potential causal risk factor for AMD and may lead to pathological retinal thinning. Reducing RST could be beneficial for preventing AMD, and future research should identify the most effective time points for intervening on RST.

High Density Lipoproteins Associate with Age-Related Macular Degeneration in the All of Us Research Program.

Extracellular lipoprotein aggregation is a critical event in AMD pathogenesis. In this study, we sought to analyze associations between clinical and genetic-based factors related to lipoprotein metabolism and risk for age-related macular degeneration (AMD) in the All of Us research program. Cross-sectional retrospective data analysis. 5028 healthy and 2328 AMD patients from All of Us. Participants with and without AMD were age, race, and gender-matched in a 1:2 ratio respectively. Smoking status, history of hyperlipidemia, and statin use were extracted in a binary manner. Statin use was further subcategorized into hepatically vs. non-hepatically metabolized statins. Laboratory values for low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) were also extracted, and outliers were excluded from analysis. The PLINK toolkit was used to extract single-nucleotide polymorphisms (SNPs) associated with LDL and HDL dysregulation, as published in prior work. Odds ratio curves were computed to assess the risk between LDL, TG, and HDL versus AMD. All clinical and genetic variables were input into a multivariable logistic regression model, and odds ratios and p-values were generated. Statistical significance of risk factors for AMD, thresholded at p ≤ 0.05. On multivariable regression analysis, statin use, and low and high HDL were significantly associated with increased AMD risk (p <0.001, <0.001, 0.004, <0.001 respectively). Additionally, the multivariable regression implicated HDL associated SNPs increased risk for AMD. Lastly, LPA was identified (p =0.007) as a novel SNP associated with increased AMD risk. There exists a U-shaped relationship between HDL and AMD risk, such that high and low HDL are significantly associated with increased AMD risk. Additionally, SNPs associated with HDL metabolism are associated with AMD risk. This analysis further establishes the role of HDL in AMD pathogenesis.

Evaluating TAB2, IKBKB, and IKBKG Gene Polymorphisms and Serum Protein Levels and Their Association with Age-Related Macular Degeneration and Its Treatment Efficiency.

Background and Objectives: Age-related macular degeneration (AMD) is the leading cause of blindness, affecting millions worldwide. Its pathogenesis involves the death of the retinal pigment epithelium (RPE), followed by photoreceptor degeneration. Although AMD is multifactorial, various genetic markers are strongly associated with the disease and may serve as biomarkers for evaluating treatment efficacy. This study investigates TAB2 rs237025, IKBKB rs13278372, and IKBKG rs2472395 variants and their respective serum protein concentrations in relation to AMD occurrence and exudative AMD treatment response to anti-VEGF treatment. Materials and Methods: The case-control study involved 961 individuals, and they were divided into three groups: control, early AMD, and exudative AM patients. Genotyping of selected SNPs were conducted using a real-time polymerase chain reaction method (RT-PCR). Based on the clinical OCT and BCVA data, patients with exudative AMD were categorized into one of two groups: responders and non-responders. The data obtained were analyzed using the "IBM SPSS Statistics 29.0" software program. Results: Our study revealed that TAB2 rs237025 allele A was identified as a risk factor for early and exudative AMD development. The same associations remained only in females with exudative AMD but not in males, suggesting gender-specific pathogenetic pathways in exudative AMD. Analysis of IKBKB rs13278372 or serum IKBKB protein associations with early or exudative AMD occurrence in the Lithuanian population revealed no significant associations. On the other hand, we found that each A allele of IKBKB rs13278372 was associated with a worse response to anti-VEGF treatment (OR = 0.347; 95% CI: 0.145-0.961; p = 0.041). These results suggest a potential marker for future studies evaluating anti-VEGF treatment for exudative AMD patients. IKBKG rs2472395 was a protective variant for early AMD in males and for exudative AMD in females only. Also, IKBKG protein concentration was lower in exudative AMD relative to the control group (median (IQR): 0.442 (0.152) vs. 0.538 (0.337), p = 0.015). Moreover, exudative AMD patients who carry the GG genotype of IKBKG rs2472394 exhibited significantly reduced serum IKBKG concentrations compared to the controls (median (IQR): 0.434 (0.199) vs. 0.603 (0.335), p = 0.012), leading to the hypothesis that the IKBKG rs2472394 variant might play a role in protein concentration differences and exudative AMD development. Conclusions: Our study identified the TAB2 rs237025 allele A as a significant risk factor for both early and exudative AMD, with gender-specific associations observed in females with exudative AMD, suggesting distinct pathogenetic pathways. While IKBKB rs13278372 and serum IKBKB protein levels showed no significant association with AMD development, the A allele of IKBKB rs13278372 was associated with a worse response to anti-VEGF treatment, indicating its potential as a marker for treatment outcomes. Additionally, the IKBKG rs2472395 variant was found to be protective for early AMD in males and exudative AMD in females, and lower IKBKG protein levels were associated with exudative AMD, particularly in patients with the GG genotype of IKBKG rs2472394, suggesting its role in protein concentration and disease progression. These findings highlight genetic markers that may contribute to AMD pathogenesis and treatment response.

The Potential Causal Association of Apolipoprotein A and B and Age-Related Macular Degeneration: A Mendelian Randomisation Study.

Research has suggested a potential relationship between apolipoproteins A (ApoA) and B (ApoB) and age-related macular degeneration (AMD). This study explored the potential causal relationship between ApoA/ApoB levels and AMD/AMD subtypes using two-sample Mendelian randomisation (MR). We selected 308 single nucleotide polymorphisms (SNPs) for ApoA and 198 SNPs for ApoB from the UK Biobank data. Summary statistics for AMD were collected from the genome-wide association study of the FinnGen project. We performed two-sample MR to assess the causal effects of ApoA/ApoB on AMD and its subtypes. Potential confounders, including body mass index, C-reactive protein level, and smoking status, were assessed using a multivariable MR analysis. ApoA showed a significant causal association with AMD (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.05-1.25, p = 0.003) and was linked to both dry (p = 0.004) and wet (p = 0.025) AMD. ApoB showed a decreasing trend in dry AMD risk (p = 0.074), though not significant, and was not associated with overall or wet AMD. The multivariable MR analysis showed no significant association of ApoA with any AMD subtype (p > 0.05). ApoB decreased dry AMD risk (OR = 0.89, 95% CI = 0.80-0.99, p = 0.039), with trends for overall and wet AMD that were not significant (p = 0.070 and p = 0.091, respectively). These findings suggest that ApoB is associated with lower AMD risk, particularly for dry AMD. Further research is needed to clarify lipid biomarker's role as AMD risk factors.

Five-Year Incidence of Age-Related Macular Degeneration and Its Risk Factors in Adult Chinese Population: The Tongren Health Care Study.

To examine the 5-year incidence of age-related macular degeneration (AMD) and its associated factors in an adult Chinese population. The Tongren Health Care Study included individuals attending regular health care check-up examinations in the Beijing Tongren Hospital. Baseline examinations were performed from 2014 to 2015, with 5-year follow-up examinations conducted between 2019 and 2020. Fundus photographs were graded according to the Beckman Initiative guidelines. A total of 5658 participants with gradable photographs at both examinations were included in the study, comprising 58.0% women, with a mean age of 54.9 ± 11.0years. The 5-year incidence of any, early, intermediate, and late AMD were 6.1% (95% confidence interval [CI], 5.5%-6.8%), 5.0% (95% CI, 4.4%-5.6%), 3.4% (95% CI, 2.9%-3.9%), and 0.3% (95% CI, 0.2%-0.4%), respectively. In multivariate analysis, incident early AMD was associated with older age (P < 0.001; odds ratio [OR], 1.04; 95% CI, 1.02-1.06), female sex (P = 0.011; OR, 1.42; 95% CI, 1.08-1.86), and a higher estimated glomerular filtration rate (P = 0.020; OR, 1.15; 95% CI, 1.02-1.30), whereas having diabetes was a protective factor (P = 0.019; OR, 0.61; 95% CI, 0.41-0.92). Incident intermediate AMD was associated with older age (P < 0.001; OR, 1.05; 95% CI, 1.04-1.07), a higher high-density lipoprotein cholesterol level (P < 0.001; OR, 1.97; 95% CI, 1.38-2.83) and a lower triglyceride level (P = 0.008; OR, 0.77; 95% CI, 0.64-0.93). A higher estimated glomerular filtration rate level was a risk factor for incident early AMD. A higher high-density lipoprotein cholesterol level and lower triglyceride level were risk factors for incident intermediate AMD. This finding may point to the role of renal circulation and lipid metabolism in incident AMD. This community-based longitudinal study may provide a valuable understanding of AMD and its associated factors for targeted prevention and management strategies.

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.

Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

The most prevalent reason for vision impairment in aging inhabitants is age-related macular degeneration (AMD), a posterior ocular disease with a poor understanding of the anatomic, genetic, and pathophysiological progression of the disease. Recently, new insights exploring the role of atrophic changes in the retinal pigment epithelium, extracellular drusen deposits, lysosomal lipofuscin, and various genes have been investigated in the progression of AMD. Hence, this review explores the incidence and risk factors for AMD, such as oxidative stress, inflammation, the complement system, and the involvement of bioactive lipids and their role in angiogenesis. In addition to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and other therapeutic interventions such as oral kinase inhibitors, photodynamic, gene, and antioxidant therapy, as well as their benefits and drawbacks as AMD treatment options, strategic drug delivery methods, including drug delivery routes with a focus on intravitreal pharmacokinetics, are investigated. Further, the recent advancements in nanoformulations such as polymeric and lipid nanocarriers, liposomes, etc., intended for ocular drug delivery with pros and cons are too summarized. Therefore, the purpose of this review is to give new researchers an understanding of AMD pathophysiology, with an emphasis on angiogenesis, inflammation, the function of bioactive lipids, and therapy options. Additionally, drug delivery options that focus on the development of drug delivery system(s) via several routes of delivery can aid in the advancement of therapeutic choices.

Truncated Complement Factor H Y402 Gene Therapy Cures C3 Glomerulonephritis.

Patients with both age-related macular degeneration (AMD) and C3 glomerulonephritis (C3G) are challenged by the absence of effective therapies to reverse and eliminate their disease burden. Capitalizing on complement dysregulation as both a significant risk factor for AMD and the known pathophysiology of C3G, we investigated the potential for adeno-associated virus (AAV) delivery of complement factor H (CFH) to rescue C3G in a Cfh-/- mouse model of C3G. While past efforts to treat C3G using exogenous human CFH resulted in limited success before immune rejection led to a foreign protein response, our findings demonstrate the capacity for long-term AAV-mediated delivery of truncated CFH (tCFH) to restore inhibition of the alternative pathway of complement and ultimately reverse C3G without immune rejection. Comparing results from the administration of several tCFH vectors also revealed significant differences in their relative efficiency and efficacy. These discoveries pave the way for subsequent development of AAV-mediated tCFH replacement therapy for patients with C3G, while simultaneously demonstrating proof of concept for a parallel AAV-mediated tCFH gene augmentation therapy for patients with AMD.

Impact of COVID-19 pandemic on ocular disease: KNHANES 2015–2021

The aim of this study was to evaluate the impact of COVID-19 on ocular diseases and changes in risk factors before and after the COVID-19 pandemic. This study was conducted using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2015–2021, a national cross-sectional health examination and survey. Associations between ocular diseases and risk factors were determined using the chi-squared test and logistic regression analysis. Bivariable adjusted logistic regression analysis was performed to examine the odds ratio (OR) and 95% confidence interval (CI) to evaluate of the impact of COVID-19 on ocular diseases. Individuals were divided into two age groups (< 60 and ≥ 60 years). A total of 50,158 people were diagnosed, of whom 7270 were diagnosed with cataract, 921 with glaucoma, and 439 with age-related macular degeneration (AMD). Risk factors for cataract were COVID-19 pandemic (OR 1.161), hypertension (OR 1.608), diabetes (OR 1.573), dyslipidemia (OR 1.167), stroke (OR 1.272), and depression (OR 1.567). Risk factors for AMD were COVID-19 pandemic (OR 1.600), dyslipidemia (OR 1.610), and depression (OR 1.466). Risk factors for glaucoma were hypertension (OR 1.234), dyslipidemia (OR 1.529), diabetes (OR 1.323), and depression (OR 1.830). The COVID-19 pandemic was a risk factor for cataracts and AMD, but not for glaucoma. Cataracts and AMD may be more influenced by the acquired health conditions or the environment.

Exposure to per- and polyfluoroalkyl substances and age-related macular degeneration in U.S. middle-aged and older adults

Despite various health effects of per- and polyfluoroalkyl substances (PFAS) exposure, the association between PFAS exposure and age-related macular degeneration (AMD) has not been investigated. We aimed to assess associations of PFAS exposure with AMD, using data from 1722 U.S. adults aged 40 years or more participating in the National Health and Nutrition Examination Survey 2005-2008 with complete data on PFAS measurement, AMD diagnosis, and covariates. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were measured. An overall PFAS burden score was calculated using item response theory scoring. Individual PFAS concentration and overall PFAS burden score were categorized into low (reference), medium, and high groups. Diagnosis of AMD was based on retinal image examination. Any AMD was defined as the presence of early or late AMD. Survey-weighted logistic regression adjusted for potential confounders was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for presence of AMD according to PFAS exposure. Overall, 132 (6.5%) individuals were diagnosed as any AMD, including 115 (5.7%) individuals with early AMD. A significant dose-response association was observed between serum PFOS concentration and any AMD (p-trend=0.03), with a significant OR of 1.99 (95% CI: 1.05, 3.79) for the high group compared to the reference. Overall PFAS burden showed a non-monotonic association with any AMD, with a significant OR of 2.18 (95% CI: 1.18, 4.04) for the medium. Inverted U-shaped associations were observed by restricted cubic spline analyses. Also, early AMD showed similar patterns in PFOS and overall PFAS burden and additionally an inverted U-shape association in PFNA. Our findings suggest that exposure to PFAS estimated by serum PFOS and PFNA as well as overall PFAS burden might be a risk factor for AMD in middle-aged and older population.

Shared whole environmental etiology between Alzheimer’s disease and age-related macular degeneration

The comorbidity of Alzheimer’s disease (AD) and age-related macular degeneration (AMD) has been established in clinical and genetic studies. There is growing interest in determining the shared environmental factors associated with both conditions. Recent advancements in record linkage techniques enable us to identify the contributing factors to AD and AMD from a wide range of variables. As such, we first constructed a knowledge graph based on the literature, which included all statistically significant risk factors for AD and AMD. An environment-wide association study (EWAS) was conducted to assess the contribution of various environmental factors to the comorbidity of AD and AMD based on the UK biobank. Based on the conditional Q-Q plots and Bayesian algorithm, several shared environmental factors were identified, which could be categorized into the domains of health condition, biological sample parameters, body index, and attendance availability. Finally, we generated a shared etiology landscape for AD and AMD by combining existing knowledge with our novel findings.

Genetic Influence of Oily Fish Intake on Age-Related Macular Degeneration Risk: A Two-Sample Mendelian Randomization Analysis.

Emerging research indicates a link between the intake of fatty fish and age-related macular degeneration (AMD). However, observational studies fall short in establishing a direct causal link between oily fish intake and AMD. We wanted to determine whether causal association lies between oily fish intake and age-related macular degeneration (AMD) risk in human beings. This two-sample mendelian randomization (MR) study used the MR method to probe the genetic causality in the relationship between oily fish intake and AMD. The genome-wide association study (GWAS) data for AMD were acquired from a Finnish database, whereas the data on fish oil intake came from the UK Biobank. The analysis used several approaches such as inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode MR. In addition, the Cochran's Q test was used to evaluate heterogeneity in the MR data. The MR-Egger intercept and MR-pleiotropy residual sum and outlier (MR-PRESSO) tests were used to assess the presence of horizontal pleiotropy. A leave-one-out sensitivity analysis was conducted to determine the reliability of the association. The IVW method revealed that the intake of oily fish is an independent risk factor for AMD (P = 0.034). It also suggested a minimal likelihood of horizontal pleiotropy affecting the causality (P > 0.05), with no substantial heterogeneity detected in the genetic variants (P > 0.05). The leave-one-out analysis confirmed the reliability and stability of this correlation. This research used a two-sample MR analysis to provide evidence of a genetic causal relationship between the eating of oily fish and AMD. This discovery held potential significance in AMD prevention.

Clinical performance of predicting late age-related macular degeneration development using multimodal imaging.

To examine whether the clinical performance of predicting late age-related macular degeneration (AMD) development is improved through using multimodal imaging (MMI) compared to using colour fundus photography (CFP) alone, and how this compares with a basic prediction model using well-established AMD risk factors. Individuals with AMD in this study underwent MMI, including optical coherence tomography (OCT), fundus autofluorescence, near-infrared reflectance and CFP at baseline, and then at 6-monthly intervals for 3-years to determine MMI-defined late AMD development. Four retinal specialists independently assessed the likelihood that each eye at baseline would progress to MMI-defined late AMD over 3-years with CFP, and then with MMI. Predictive performance with CFP and MMI were compared to each other, and to a basic prediction model using age, presence of pigmentary abnormalities, and OCT-based drusen volume. The predictive performance of the clinicians using CFP [AUC = 0.75; 95% confidence interval (CI) = 0.68-0.82] improved when using MMI (AUC = 0.79; 95% CI = 0.72-0.85; p = 0.034). However, a basic prediction model outperformed clinicians using either CFP or MMI (AUC = 0.85; 95% CI = 0.78-91; p ≤ 0.002). Clinical performance for predicting late AMD development was improved by using MMI compared to CFP. However, a basic prediction model using well-established AMD risk factors outperformed retinal specialists, suggesting that such a model could further improve personalised counselling and monitoring of individuals with the early stages of AMD in clinical practice.

Potential Causal Association between C-Reactive Protein Levels in Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study.

Researchers have proposed a possible correlation between age-related macular degeneration (AMD) and inflammation or C-reactive protein (CRP) levels. We investigated the potential causal relationship between CRP levels and AMD. Single-nucleotide polymorphisms (SNPs) associated with CRP exposure were selected as the instrumental variables (IVs) with significance (p < 5 × 10-8) from the genome-wide association study (GWAS) meta-analysis data of Biobank Japan and the UK Biobank. GWAS data for AMD were obtained from 11 International AMD Genomics Consortium studies. An evaluation of causal estimates, utilizing the inverse-variance-weighted (IVW), weighted-median, MR-Egger, MR-Pleiotropy-Residual-Sum, and Outlier tests, was conducted in a two-sample Mendelian randomization (MR) study. We observed significant causal associations between CRP levels and AMD (odds ratio [OR] = 1.13, 95% CI = [1.02-1.24], and p = 0.014 in IVW; OR = 1.18, 95% CI = [1.00-1.38], and p = 0.044 in weight median; OR = 1.31, 95% CI = [1.13-1.52], and p < 0.001 in MR-Egger). The causal relationship between CRP and AMD warrants further research to address the significance of inflammation as a risk factor for AMD.

The Association between Diabetic Retinopathy and Macular Degeneration: A Nationwide Population-Based Study.

Age-related macular degeneration (AMD), particularly its exudative form, is a primary cause of vision impairment in older adults. As diabetes becomes increasingly prevalent in aging, it is crucial to explore the potential relationship between diabetic retinopathy (DR) and AMD. This study aimed to assess the risk of developing overall, non-exudative, and exudative AMD in individuals with DR compared to those without retinopathy (non-DR) based on a nationwide population study in Taiwan. A retrospective cohort study was conducted using the Taiwan National Health Insurance Database (NHIRD) (2000-2013). A total of 3413 patients were placed in the study group (DR) and 13,652 in the control group (non-DR) for analysis. Kaplan-Meier analysis and the Cox proportional hazards model were used to calculate the hazard ratios (HRs) and adjusted hazard ratios (aHRs) for the development of AMD, adjusting for confounding factors, such as age, sex, and comorbid conditions. Kaplan-Meier survival analysis indicated a significantly higher cumulative incidence of AMD in the DR group compared to the non-DR group (log-rank test, p < 0.001). Adjusted analyses revealed that individuals with DR faced a greater risk of overall AMD, with an aHR of 3.50 (95% CI = 3.10-3.95). For senile (unspecified) AMD, the aHR was 3.45 (95% CI = 3.04-3.92); for non-exudative senile AMD, it was 2.92 (95% CI = 2.08-4.09); and for exudative AMD, the aHR was 3.92 (95% CI = 2.51-6.14). DR is a significant risk factor for both overall, senile, exudative, and non-exudative AMD, even after adjusting for demographic and comorbid conditions. DR patients tend to have a higher prevalence of vascular comorbidities; however, our findings indicate that the ocular pathologies inherent to DR might have a more significant impact on the progression to AMD. Early detection and appropriate treatment of AMD is critically important among DR patients.

The Association Between Metformin Use and New-Onset ICD Coding of Geographic Atrophy.

Metformin has been suggested to protect against the development of age-related macular degeneration (AMD) in multiple observational studies. However, the association between metformin and geographic atrophy (GA), a debilitating subtype of AMD, has not been analyzed. We conducted a case-control study of patients ages 60years and older with new-onset International Classification of Diseases (ICD) coding of GA in the Merative MarketScan Commercial and Medicare Databases between 2017 and 2021. Cases were matched with propensity scores estimated by age, region, hypertension, and Charlson Comorbidity Index to a control without GA of the same year. Exposure to metformin was assessed for cases and controls in the year prior to their index visit. Conditional multivariable logistic regression, adjusting for AMD risk factors, was used to calculate odd ratios and 95% confidence intervals (CIs). This study design and analysis were repeated in a sample of patients without diabetes. In the full sample, we identified 10,505 cases with GA and 10,502 matched controls without GA. In total, 1149 (10.9%) cases and 1277 (12.2%) controls were exposed to metformin, and in multivariable regression, metformin decreased the odds of new-onset ICD coding of GA by 12% (95% CI, 0.79-0.99). In the sample of patients without diabetes, we identified 7611 cases with GA and 7608 matched controls without GA. Twenty-nine (0.4%) cases and 63 (0.8%) controls were exposed to metformin, and in multivariable regression, metformin decreased the odds of new-onset ICD coding of GA by 47% (95% CI, 0.33-0.83). Metformin may hold promise as a noninvasive, alternative agent to prevent the development of GA. This finding is notable due to shortcomings in recently approved therapeutics for GA and metformin's overall ease of use and few adverse effects. Additional studies are required to explore our findings further and motivate a clinical trial.

Risk Factors of Age-Related Macular Degeneration in a Population-Based Study: Results from SHIP-TREND-1 (Study of Health in Pomerania-TREND-1).

BACKGROUND Age-related macular degeneration (AMD) is the most common cause of visual impairment in the elderly population in industrialized countries. The Study of Health in Pomerania (SHIP) with its cohort SHIP-TREND was designed to investigate risk factors and clinical disorders in the general population of northeast Germany. This work focused on the first follow-up of SHIP-TREND and determined associated modifiable risk factors of AMD. Modifying risk factors is important to slow the progression of early AMD as there is currently no treatment for the late stage of geographic atrophy. Understanding AMD-associated risk factors also plays an important role in the development of therapeutic concepts. MATERIAL AND METHODS Between 2016 and 2019, data were collected from a total of 2507 initially randomly selected subjects from the general population aged 28 to 89 years. Non-mydriatic fundus photography of the right eye was performed in 2489 subjects. Grading of AMD was performed using the Rotterdam classification system. RESULTS We included 1418 gradable fundus photographs in the analysis. The risk of AMD changes increased with age and was positively correlated with HDL cholesterol, fT3, and low educational level. In men, BMI and cigarette smoking were also positively associated with AMD changes. CONCLUSIONS This study emphasizes the consideration of various metabolic pathways for the development of therapeutic concepts.

Prevalence and Risk Factors of Age-Related Macular Degeneration in South Korea: Korea National Health and Nutrition Examination Survey

ABSTRACT Purpose To evaluate the prevalence and risk factors of age-related macular degeneration (AMD) in the Korean population. Methods In this cross-sectional study based on the Korea National Health and Nutrition Examination Survey (2017–2020) data 13,737 participants aged ≥ 40 years with assessable fundus images were included. The prevalence and risk factors of AMD were evaluated. The prevalence of early AMD, geographic atrophy (GA), and neovascular AMD were also assessed. Logistic regression analyses were used to identify risk factors. Results The prevalence (95% confidence interval [CI]) of AMD was 13.94% (13.15–14.72). The prevalence (95% CI) of early AMD, GA, and neovascular AMD was 13.07% (12.29–13.85), 0.26% (0.17–0.35), and 0.61% (0.47–0.75), respectively. The prevalence increased with age; it was 3.61%, 11.33%, 20.31%, 31.37%, and 33.98% in participants in their 40s, 50s, 60s, 70s, and ≥ 80 years, respectively. In multivariate analysis, AMD was positively associated with older age (p < 0.001; odds ratio [OR], 1.08; 95% CI, 1.07–1.09), male sex (p = 0.014; OR, 1.27; 95% CI, 1.05–1.53), and lower degree of education (p < 0.001; OR, 1.36 (for junior high school graduates); 95% CI, 1.12–1.65). Conclusions AMD was detected in approximately one-third of individuals aged ≥ 70 years, thus indicating that AMD is a common disease among older Koreans. Regular fundus examinations in populations with risk factors for AMD as well as education on methods to prevent or delay AMD progression, such as the Mediterranean diet, are necessary.

Associations of drusen location with risk factors and incidence of late age-related macular degeneration in the Alienor study.

To test the hypothesis that central drusen location is strongly linked with known Age-related Macular Degeneration (AMD) risk factors and risk of incident late AMD. The Alienor study is a prospective population-based cohort study of residents of Bordeaux, France, followed from 2009 to 2017. On retinal photographs, we defined central drusen as at least one soft drusen (>63 μm) within 500 μm from fovea and pericentral drusen as at least one drusen 500-3000 μm from fovea, in the absence of any central drusen. Late AMD (atrophic and/or neovascular) was diagnosed using multimodal imaging. In total, 481 eyes were included in the analysis: 160 central and 321 pericentral. We investigated associations with systemic (age, sex, smoking, medical prescriptions, plasma concentrations of lipids and nutrients, UV exposure, blood pressure), ocular (retinal thickness, cataract extraction) and genetic risk scores (GRS). In multivariate logistic regression central drusen were associated with smoking (OR, 2.95 for smoking more than 20 pack-years, p = 0.02), HDL-cholesterol (OR, 1.57 for 1 standard deviation (SD) increase, p = 0.0048), pulse pressure (OR, 0.77 for 1 SD increase, p = 0.04), Age-Related Maculopathy Susceptibility 2 (ARMS2) GRS (OR, 1.42; 95% CI, 1.11-1.83) and complement GRS (OR, 1.55; 95% CI, 1.15-2.10). In Cox modelling, the central location of drusen (at baseline or during the follow-up) was associated with a 4.41-fold increased risk (95% CI,1.98-9.81) for an incident late AMD. Central drusen were strongly associated with AMD risk factors and incident late AMD, suggesting that it represents a key marker for AMD progression.

Incidence and risk factors of age-related macular degeneration in patients with Parkinson's disease: a population-based study.

The association between age-related macular degeneration (AMD) and Parkinson' disease (PD) remains unclear. The aim of the present study was to assess the incidence of AMD in patients with PD, elucidate differences by age and sex, and investigate potential risk factors for AMD. Data were extracted from the Korean National Health Insurance System database, which covers 97% of the Korean population (2002 through 2019). We calculated the incidence of newly diagnosed AMD in patients with PD and used Cox proportional-hazards models to estimate risk factors for AMD, presenting adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Of 172,726 patients with PD, 15,800 were newly diagnosed with AMD during the follow-up, including 5,624 men and 10,176 women. The overall incidence of AMD in patients with PD was 13.59 per 1,000 person-years. Stratified by age group and sex, the incidence was higher in women aged 40-69, and conversely higher in men aged 70-89. Risk of AMD was high in older age groups (aHR = 4.36, 95% CI: 3.74-5.09 in the 70 s), female sex (aHR = 1.07, 95% CI: 1.04-1.11), patients with diabetes mellitus (DM) (aHR = 1.14, 95% CI: 1.10-1.18), and patients with hyperlipidemia (aHR = 1.17, 95% CI: 1.13-1.21). Our findings suggest that the AMD incidence is higher in patients with PD than in the general population, with varying patterns of sex differences across age groups. Particularly, old age, female sex, presence of DM, and hyperlipidemia are potential risk factors. Therefore, clinicians should pay greater attention to AMD in patients with PD.