Risk Of Age-related Macular Degeneration Research Articles

Correlation between genetic and environmental risk factors for age-related macular degeneration in Brazilian patients.

To analyze the correlations between age-related macular degeneration (AMD) and genetic and environmental risk factors for in a Brazilian population. Cross-sectional study with a control group. We collected data on 236 participants 50 years of age or older (141 with AMD and 95 controls without the disease). Data was obtained using a questionnaire and included information on demographics, ocular and medical history, family history of AMD, lifestyle, and smoking and drinking habits. Genetic evaluations included direct sequencing for the LOC387715 (rs10490924) variant, as well as PCR and enzymatic digestion for the CFH Y402H (rs1061170) and HTRA1 (rs11200638) variants. We performed a risk assessment of environmental risk factors and genetic variants associated with AMD and determined correlations between AMD and the data collected using multiple linear regression analysis. Of the 141 AMD cases, 99 (70%) had advanced AMD in at least one eye (57% neovascular AMD and 13% geographic atrophy), and 42 (30%) had not-advanced AMD. Family history of AMD (OR: 6.58; 95% CI: 1.94-22.31), presence of cardiovascular disease (CVD) (OR: 2.39; 95% CI: 1.08-5.28), low physical activity level (OR: 1.39; 95% CI: 0.82-2.37), and high serum cholesterol (OR: 1.49; 95% CI: 0.84-2.65) were associated with an increased risk for AMD. There was a significant association between CVD and incidence of advanced AMD (OR: 2.29; 95% CI 0.81-6.44). The OR for the risk allele of the LOC387715 gene, the CFH gene and the HTRA1 gene were 2.21 (95% CI: 1.47-3.35), 2.27 (95% CI: 1.52-3.37), and 2.76 (95% CI: 1.89-4.03), respectively. In the stepwise multiple linear regression analyses, the HTRA1 and CFH risk alleles, family history of AMD, the LOC387715 risk allele, and CVD were associated with an increased risk of AMD for a total of 25.6% contribution to the AMD phenotype. The analysis correlating environmental and genetic risk factors such as family history of AMD, and CVD and the variants of HTRA1, CFH, and LOC387715 genes showed an expressive contribution for the development of AMD among this admixed population.

Characterization of polymorphisms in CFI and ARMS genes and their association with exudative age-related macular degeneration in Algerian patients.

Increasing evidence shows that polymorphisms in CFI and ARMS2 genes can influence exudative age-related macular degeneration (nAMD) risk. The aim of this study was to assess the role of CFI rs10033900 and ARMS2 rs3750846 polymorphisms in susceptibility to nAMD for the first time in the Algerian population. A total of one hundred twenty four controls and seventy two nAMD cases were included in the present study. Genomic DNA was extracted from venous blood leukocytes. CFI rs10033900 and ARMS2 rs3750846 variants were determined by using the real‑time polymerase chain reaction method. Differences in allele and genotype distribution between the cases and controls were tested with adjustment for age by logistic regression analysis. A stratification of case and control groups by age (<65 or ≥65) and by gender (male and female) was also performed. Statistical analyses were done using SPSS21.0. No statistically significant association was observed between CFI rs10033900 and ARMS2 rs3750846 polymorphisms and nAMD risk (p>0.05 for all comparisons). Stratification by age and gender did not show any significant association between these two polymorphisms and nAMD in a sample of the Algerian population. In our study, CFI rs10033900 and ARMS2 rs3750846 polymorphisms did not predispose alone to nAMD in our population. This study is a contribution to the enrichment of the bank data concerning the CFI and ARMS2 genes, reporting, for the first time, the allelic and genotypic frequencies of these genes polymorphisms characterizing the Algerian population.

Reticular Pseudodrusen: The Third Macular Risk Feature for Progression to Late Age-Related Macular Degeneration: Age-Related Eye Disease Study 2 Report 30

To analyze reticular pseudodrusen (RPD) as an independent risk factor for progression to late age-related macular degeneration (AMD), alongside traditional macular risk factors (soft drusen and pigmentary abnormalities) considered simultaneously. Post hoc analysis of 2 clinical trial cohorts: Age-Related Eye Disease Study (AREDS) and AREDS2. Eyes with no late AMD at baseline in AREDS (6959 eyes, 3780 participants) and AREDS2 (3355 eyes, 2056 participants). Color fundus photographs (CFPs) from annual visits were graded for soft drusen, pigmentary abnormalities, and late AMD. Presence of RPD was from grading of fundus autofluorescence images (AREDS2) and deep learning grading of CFPs (AREDS). Proportional hazards regression analyses were performed, considering AREDS AMD severity scales (modified simplified severity scale [person] and 9-step scale [eye]) and RPD presence simultaneously. Progression to late AMD, geographic atrophy (GA), and neovascular AMD. In AREDS, for late AMD analyses by person, in a model considering the simplified severity scale simultaneously, RPD presence was associated with a higher risk of progression: hazard ratio (HR), 2.15 (95% confidence interval [CI], 1.75-2.64). However, the risk associated with RPD presence differed at different severity scale levels: HR, 3.23 (95% CI, 1.60-6.51), HR, 3.81 (95% CI, 2.38-6.10), HR, 2.28 (95% CI, 1.59-3.27), and HR, 1.64 (95% CI, 1.20-2.24), at levels 0-1, 2, 3, and 4, respectively. Considering the 9-step scale (by eye), RPD presence was associated with higher risk: HR, 2.54 (95% CI, 2.07-3.13). The HRs were 5.11 (95% CI, 3.93-6.66) at levels 1-6 and 1.78 (95% CI, 1.43-2.22) at levels 7 and 8. In AREDS2, by person, RPD presence was not associated with higher risk: HR, 1.18 (95% CI, 0.90-1.56); by eye, it was HR, 1.57 (95% CI, 1.31-1.89). In both cohorts, RPD presence carried a higher risk for GA than neovascular AMD. Reticular pseudodrusen represent an important risk factor for progression to late AMD, particularly GA. However, the added risk varies markedly by severity level, with highly increased risk at lower/moderate levels and less increased risk at higher levels. Reticular pseudodrusen status should be included in updated AMD classification systems, risk calculators, and clinical trials.

Association of Diabetes Medication With Open-Angle Glaucoma, Age-Related Macular Degeneration, and Cataract in the Rotterdam Study

Recent studies suggest that the diabetes drug metformin has a protective effect on open-angle glaucoma (OAG) and age-related macular degeneration (AMD). However, studies have not addressed the critical issue of confounding by indication, and associations have not been evaluated in a large prospective cohort. To determine the association between diabetes medication and the common eye diseases OAG, AMD, and cataract and to evaluate their cumulative lifetime risks in a large cohort study. This cohort study included participants from 3 independent cohorts from the prospective, population-based Rotterdam Study between April 23, 1990, and June 25, 2014. Participants were monitored for incident eye diseases (OAG, AMD, cataract) and had baseline measurements of serum glucose. Data on diabetes medication use and data from ophthalmologic examinations were gathered. Type 2 diabetes (T2D) and the diabetes medications metformin, insulin, and sulfonylurea derivatives. Diagnosis and cumulative lifetime risk of OAG, AMD, and cataract. This study included 11 260 participants (mean [SD] age, 65.1 [9.8]; 6610 women [58.7%]). T2D was diagnosed in 2406 participants (28.4%), OAG was diagnosed in 324 of 7394 participants (4.4%), AMD was diagnosed in 1935 of 10 993 participants (17.6%), and cataract was diagnosed in 4203 of 11 260 participants (37.3%). Untreated T2D was associated with a higher risk of OAG (odds ratio [OR], 1.50; 95% CI, 1.06-2.13; P = .02), AMD (OR, 1.35; 95% CI, 1.11-1.64; P = .003), and cataract (OR, 1.63; 95% CI, 1.39-1.92; P < .001). T2D treated with metformin was associated with a lower risk of OAG (OR, 0.18; 95% CI, 0.08-0.41; P < .001). Other diabetes medication (ie, insulin, sulfonylurea derivates) was associated with a lower risk of AMD (combined OR, 0.32; 95% CI, 0.18 to 0.55; P < .001). The cumulative lifetime risk of OAG was lower for individuals taking metformin (1.5%; 95% CI, 0.01%-3.1%) than for individuals without T2D (7.2%; 95% CI, 5.7%-8.7%); the lifetime risk of AMD was lower for individuals taking other diabetes medication (17.0%; 95% CI, 5.8%-26.8% vs 33.1%; 95% CI, 30.6%-35.6%). Results of this cohort study suggest that, although diabetes was clearly associated with cataract, diabetes medication was not. Treatment with metformin was associated with a lower risk of OAG, and other diabetes medication was associated with a lower risk of AMD. Proof of benefit would require interventional clinical trials.

Mast cell infiltration of the choroid and protease release are early events in age-related macular degeneration associated with genetic risk at both chromosomes 1q32 and 10q26.

Age-related macular degeneration (AMD) is a leading cause of visual loss. It has a strong genetic basis, and common haplotypes on chromosome (Chr) 1 (CFH Y402H variant) and on Chr10 (near HTRA1/ARMS2) contribute the most risk. Little is known about the early molecular and cellular processes in AMD, and we hypothesized that analyzing submacular tissue from older donors with genetic risk but without clinical features of AMD would provide biological insights. Therefore, we used mass spectrometry–based quantitative proteomics to compare the proteins in human submacular stromal tissue punches from donors who were homozygous for high-risk alleles at either Chr1 or Chr10 with those from donors who had protective haplotypes at these loci, all without clinical features of AMD. Additional comparisons were made with tissue from donors who were homozygous for high-risk Chr1 alleles and had early AMD. The Chr1 and Chr10 risk groups shared common changes compared with the low-risk group, particularly increased levels of mast cell–specific proteases, including tryptase, chymase, and carboxypeptidase A3. Histological analyses of submacular tissue from donors with genetic risk of AMD but without clinical features of AMD and from donors with Chr1 risk and AMD demonstrated increased mast cells, particularly the tryptase-positive/chymase-negative cells variety, along with increased levels of denatured collagen compared with tissue from low–genetic risk donors. We conclude that increased mast cell infiltration of the inner choroid, degranulation, and subsequent extracellular matrix remodeling are early events in AMD pathogenesis and represent a unifying mechanistic link between Chr1- and Chr10-mediated AMD.

Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension.

AimsSeveral observational studies have examined the potential protective effect of angiotensin‐converting enzyme inhibitor (ACE‐I) use on the risk of age‐related macular degeneration (AMD) and have reported contradictory results owing to confounding and time‐related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE‐I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK.MethodsIn this study, 53 832 and 43 106 new users of ACE‐I and CCB were included between 1995 and 2019, respectively. In an on‐treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow‐up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE‐I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD.ResultsDuring a median follow‐up of 2 years (interquartile range 1–5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2–2.6) and 2.2 (2.0–2.4) per 1000 person‐years among the weighted new users of ACE‐I and CCB, respectively. There was no association of ACE‐I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on‐treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90–1.27] and 0.87 [0.71–1.07], respectively).ConclusionWe found no evidence that the use of ACE‐I is associated with risk of AMD in patients with hypertension.

Osteoarthritis Is Associated With an Increased Risk of Age-Related Macular Degeneration: A Population-Based Longitudinal Follow-Up Study.

AimsTo investigate the long-term risk of age-related macular degeneration (AMD) in persons with osteoarthritis (OA).MethodsThis retrospective cohort study first enrolled 71,609 subjects diagnosed with OA, and 236,169 without such a diagnosis between January 1, 2002 and December 31, 2005, from the Longitudinal Health Insurance Database 2005. All were aged 40–69. After excluding subjects who had pre-existing AMD and/or who had missing socioeconomic data, frequency matching by sex and age was performed. This resulted in there being 60,274 subjects in each of the final matched OA and non-OA groups. The study participants were followed up to the occurrence of AMD, death, or the end of 2011. We used Cox proportional-hazards regression to estimate the impact of OA on the risk of developing AMD, and performed subgroup analyses stratified by sex and age.ResultsThe median follow-up time was 8.9 years, with an interquartile range of 1.4 years. The incidence rate of AMD in the OA group was 2.77 per 1,000 person-years [95% confidence interval (CI), 2.62–2.92], and in the non-OA group, 2.06 per 1,000 person-years (95% CI, 1.94–2.19). The adjusted hazard ratio (HR) of AMD for the OA group was therefore 1.30 (95% CI, 1.20–1.41). In the subgroup analysis stratified by sex for the OA group, the adjusted HRs of AMD were 1.29 in the women's stratum and 1.31 in the men's. When stratified by age, the adjusted HRs of AMD for the younger (40–54 years) and older (55–69 years) strata were 1.28 and 1.31, respectively.ConclusionsPersons with OA have an increased risk of developing AMD, regardless of age and sex.

The Relationship between Statin and Risk of Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.

Methods Web of Science, PubMed, and Scopus databases were searched for articles that addressed the relationship between statin consumption and risk of AMD. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. Subgroup analyses and sensitivity analyses were also conducted. Cochran's Q test and the I2 statistic were used to evaluate the heterogeneity. To assess potential publication bias, Begg's test was used. Results In total, 22 studies were reviewed in the meta-analysis that included 2063195 participants and 313702 (15.20%) AMD patients compared to individuals not receiving statins. The OR of AMD in statin-receiving participants was 0.93 (95% CI; 0.83–1.05, P=0.225). The OR of AMD in those that received statins was 0.92 (95% CI; 0.75–1.13, P=0.440) in case-control studies, 0.95 (95% CI; 0.82–1.09, P=0.458) in cohort studies, 0.951 (95% CI; 0.59–1.53, P=0.831) in cross-sectional studies, 0.94 (95% CI; 0.80–1.10, P=0.468) in North America, 0.81 (95% CI; 0.54–1.21, P=0.308) in Europe, 1.05 (95% CI; 0.94–1.18, P=0.362) in Asia, and 0.52 (95% CI; 0.26–1.04, P=0.125) in Australia. No publication bias was observed in this study (P=0.114). Conclusion According to the results of this study, taking statins does not increase or decrease the risk of AMD development. Therefore, this drug group cannot be considered a protective or risk factor for the occurrence of AMD.

RISK OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION IN PATIENTS WITH CENTRAL SEROUS CHORIORETINOPATHY: A Nationwide Cohort Study.

To estimate the risk of incident age-related macular degeneration (AMD) in patients with central serous chorioretinopathy (CSC). This population-based cohort study was finally conducted from January 2015 to December 2019. All patients with CSC from the entire population aged between 30 and 80 years were included. The incidence of CSC was estimated. Log-rank analysis and Cox proportional hazards regression analysis was used to evaluate the risk of exudative AMD in the CSC group compared with the non-CSC group. During a recent 5-year study period, 36,053 patients were identified as having incident CSC. The annual incidence in the latest year was 19.61 (95% confidence interval, 19.58 to 19.63) per 100,000 people. A total of 11,492 patients were included in the study group and 22,984 in the non-CSC group. The CSC and non-CSC groups included 166 (1.44%) and 73 (0.32%) cases of exudative AMD, respectively. The risk of exudative AMD was significantly higher in the CSC group than in the non-CSC group (adjusted hazard ratio: 4.86; 95% confidence interval: 2.98 to 5.88; P < 0.001). This study showed that subjects with CSC are at an increased risk of exudative AMD. This evidence supports a possible link between CSC and exudative AMD, particularly in Asian populations.

The Association Between Consumption of 100% Fruit Juice and Risk of Age-Related Macular Degeneration: Data From the National Health and Nutrition Examination Survey Database.

Age-related macular degeneration (AMD) is the main irreversible blindness disease worldwide. The current study aimed to investigate whether the consumption of 100% fruit juice increases the risk of age-related macular degeneration and find approaches to prevent and reduce the development of age-related macular degeneration from the aspect of dietary habits. A cross-sectional clinical study design was adopted. We screened participants from the 2005 to 2006 NHANES database. The logistic regression model was used to evaluate the relationship between 100% fruit juice consumption and advanced AMD and to adjust variables such as demographics, general health status, body mass index (BMI), health-related behaviors, systemic complications, and ophthalmic complications. The results show that 100% fruit juice consumption did not affect early AMD and any AMD. High consumers of 100% fruit juice are more likely to develop advanced age-related macular degeneration than those who never drink 100% fruit juice.

Association of CFI, IL-8, TF and TFR2 Genetic Polymorphisms with Age-Related Macular Degeneration in a Northeastern Chinese Population

Purpose: To explore the relationship between single-nucleotide polymorphisms (SNPs) in complement factor I (CFI), interleukin-8 (IL-8), transferrin (TF), and transferrin receptor 2 (TFR2) and age-related macular degeneration (AMD) in a northeastern Chinese population. Methods: A total of 400 AMD patients (200 wet AMD and 200 dry AMD) and 200 controls were enrolled in this study, and genetic polymorphisms in the above genes were detected by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The χ2 test was used to compare differences in allele frequencies in each group, and the associations of genotype frequencies with AMD were determined by multivariate logistic regression analysis. Results: Our research shows that CFI rs141853578, IL-8 rs2227543, TF rs8177178 and TFR2 rs2075674 are associated with the incidence of AMD. In wet AMD, allele T of CFI rs141853578, IL-8 rs2227543 and TFR2 rs2075674 may be a risk factor. Allele A of TF rs8177178 may increase the risk of dry AMD. Conclusions: CFI rs141853578, IL-8 rs2227543, TF rs8177178 and TFR2 rs2075674 genetic polymorphisms are associated with the occurrence of AMD in a northeastern Chinese population, especially wet AMD.

Association between metformin use and the risk of age-related macular degeneration in patients with type 2 diabetes: a retrospective study

ObjectivesTo investigate the effect of metformin on the decreased risk of developing age-related macular degeneration (AMD) in patients with type 2 diabetes mellitus (T2DM) for ≥10 years.DesignA retrospective study.ParticipantsPatients aged...

Incidence and risk of advanced age-related macular degeneration in eyes with drusenoid pigment epithelial detachment

To investigate the incidence and risk of advanced age-related macular degeneration (AMD), including geographic atrophy (GA) and macular neovascularization (MNV), in eyes with drusenoid pigment epithelial detachment (PED). Eighty-five eyes with drusenoid PED from 85 patients (77.2 ± 7.0 years, male/female: 44/41) were included in this study. Patients were followed up every 1–3 months via spectral-domain optical coherence tomography (SD-OCT) and color fundus photography. If exudation was observed on SD-OCT, fluorescein and indocyanine green angiography were performed to confirm the MNV subtype accordingly. The maximum follow-up period was 60 months. During the study period, GA developed in 8 eyes while MNV also developed in 8 eyes. The Kaplan–Meier estimator revealed that the cumulative incidence for 60 months was 17.9% and 12.2% for GA and MNV, respectively. In eyes developing MNV, retinal angiomatous proliferation was the most common. Cox regression analysis revealed that baseline PED width was the only factor associated with advanced AMD. (p = 0.0026, Cox regression analysis). The 5-year cumulative incidence of advanced AMD, including GA and MNV, was approximately 30% in eyes with drusenoid PED among the Japanese elderly. A larger baseline PED width was the only risk factor for advanced AMD.

Characterization of West African Crystalline Macular Dystrophy in the Ghanaian Population

West African crystalline maculopathy (WACM) is characterized by the presence of macular hyperrefractile crystal-like deposits. Although the underlying pathophysiology has not been elucidated, a few biologic drivers have been proposed. We analyzed a large WACM case series to gain a more robust understanding of its features and etiology. Prospective, cross-sectional cohort study. Participants with WACM were selected from the large cohort recruited in the Ghana Age-Related Macular Degeneration Study. Demographic and detailed medical histories, full ophthalmic examinations, digital color fundus photographs, and OCT images were obtained. All cases with WACM were evaluated by 3 retina experts. Crystal numbers, location, and distribution were determined. Associations between WACM and White age-related macular degeneration (AMD) risk variants were assessed using Firth's bias-reduced logistic regression, including age and sex as covariates. Phenotypic features of, and genetic associations with, WACM. West African crystalline maculopathy was identified in 106 eyes of 53 participants: 22 were bilateral and 24 were unilateral. Grading for AMD was not possible in 1 eye in 7 participants with WACM; therefore, laterality was not assessed in these subjects. Thirty-eight participants were women and were 14 men; sex was unrecorded for 1 participant. The mean age was 68.4 years (range, 45-101 years). Typical WACM crystals were demonstrated on OCT, which were more easily identified at high contrast and predominantly located at the inner limiting membrane. In eyes with copathology, crystals localized deeper in the inner retina, with wider retinal distribution over copathology lesions. There was no association with age or sex. A significant association was observed between the complement factor H (CFH) 402H risk variant and WACM. This study confirms the localization of crystals adjacent to the inner limiting membrane and distribution over lesions in eyes with copathology. The evaluation of OCT images under high contrast allows improved identification. West African crystalline maculopathy may be associated with the CFH-CFHR5 AMD risk locus identified among Whites; however, it is also possible that the combination of crystals and the CFH 402H allele increases the risk for developing late AMD. Further analyses using larger sample sizes are warranted to identify causalities between genotype and WACM phenotype.

Rare complement factor I variants associated with reduced macular thickness and age-related macular degeneration in the UK Biobank.

To evaluate potential diagnostic and therapeutic biomarkers for age-related macular degeneration (AMD), we identified 8433 UK Biobank participants with rare complement Factor I gene (CFI) variants, 579 with optical coherence tomography-derived macular thickness data. We stratified these variants by predicted gene expression and measured their association with retinal pigment epithelium-Bruch’s membrane (RPE-BM) complex and retinal thicknesses at nine macular subfields, as well as AMD risk, using multivariable regression models adjusted for the common complement Factor H gene (CFH) p.Y402H and age-related maculopathy susceptibility protein 2 gene (ARMS2) p.A69S risk genotypes. CFI variants associated with low Factor I levels predicted a thinner mean RPE-BM (95% confidence interval [CI] −1.66 to −0.37 μm, P = 0.002) and retina (95% CI −5.88 to −0.13 μm, P = 0.04) and a higher AMD risk (odds ratio [OR] = 2.26, 95% CI 1.56 to 3.27, P < 0.001). CFI variants associated with normal Factor I levels did not impact mean RPE-BM/retinal thickness (P = 0.28; P = 0.99) or AMD risk (P = 0.97). CFH p.Y402H was associated with a thinner RPE-BM (95% CI −0.31 to −0.18 μm, P < 0.001 heterozygous; 95% CI −0.62 to −0.42 μm, P < 0.001 homozygous) and retina (95% CI −0.73 to −0.12 μm, P = 0.007 heterozygous; 95% CI −1.08 to −0.21 μm, P = 0.004 homozygous). ARMS2 p.A69S did not influence RPE-BM (P = 0.80 heterozygous; P = 0.12 homozygous) or retinal thickness (P = 0.75 heterozygous; P = 0.07 homozygous). p.Y402H and p.A69S exhibited a significant allele–dose response with AMD risk. Thus, CFI rare variants associated with low Factor I levels are robust predictors of reduced macular thickness and AMD. The observed association between macular thickness and CFH p.Y402H, but not ARMS2 p.A69S, highlights the importance of complement dysregulation in early pathogenesis.

Point-of-care tools to support optometric care provision to people with age-related macular degeneration: A randomised, placebo-controlled trial.

PurposeAge‐related macular degeneration (AMD) is a leading cause of vision impairment. This randomised placebo‐controlled trial investigated whether point‐of‐care tools can improve optometrists' AMD knowledge and/or care provision.MethodsAustralian optometrists (n = 31) completed a demographics survey and theoretical AMD case study multiple‐choice questions (MCQs) to assess their confidence in AMD care provision and AMD knowledge. Participants were then randomly assigned to one of three point‐of‐care tools (online ‘Classification of Age‐related macular degeneration and Risk Assessment Tool’ (CARAT), paper CARAT, or ‘placebo’) to use when providing care to their subsequent 5–10 AMD patients. Participants self‐audited the compliance of their AMD care to best practice for these patients, and a similar number of consecutive patients seen prior to enrolment. Post‐intervention, participants retook the AMD knowledge MCQs and confidence survey.ResultsA total of 29 participants completed the study. At the study endpoint, clinical confidence relative to baseline improved with the paper CARAT, relative to placebo, for knowledge of AMD risk factors, asking patients about these factors and referring for medical retinal sub‐specialist care. There were no between‐group differences for the change in AMD knowledge scores. Considering record documentation for patients with any AMD severity, there were no significant between‐group differences for documenting patient risk factors, AMD severity, clinical examination techniques or management. In a sub‐analysis, the change from baseline in compliance for documenting discussions about patient smoking behaviours for early AMD patients was higher with use of the online CARAT relative to placebo (p = 0.04). For patients with intermediate AMD, the change from baseline in documenting the risk of progression to late AMD was greater among practitioners who used the paper CARAT, relative to placebo (p = 0.04).ConclusionsThis study demonstrates that point‐of‐care clinical tools can improve practitioner confidence and aspects of the documentation of AMD clinical care by optometrists as assessed by self‐audit.

Fine particulate matter measured by satellites predicts the risk of age-related macular degeneration in a longitudinal cohort study.

Although studies have revealed that ambient particulate matter (PM) has detrimental effects on the ocular surface, there have been limited reports detailing the effect of ambient PM on the posterior segment of the eye. A large-scale longitudinal cohort study evaluating the association between fine PM, especially PM2.5, and the retina could elucidate the risk of ambient pollutants for retinal diseases. We investigated the association between PM2.5 and the development of age-related macular degeneration (AMD). We conducted a population-based cohort study of 4,284,128 participants in Taiwan between 2001 and 2011. PM2.5 was continuously measured by satellites and subsequently assigned to each geographic district along with its postcode. A time-dependent Cox proportional-hazard model was used to assess the overall effects of average PM2.5. We used distributed lag non-linear models to evaluate the dose-response relationship between PM2.5 and AMD development. The annual mean of PM2.5 exposure was 34.23 ± 7.17μg/m3. The PM2.5 concentrations were highest in spring, followed by those in winter, autumn, and summer. Twelve thousand ninety-five new AMD cases were reported during the study period. After adjusting for covariates, the AMD risk increased by 19% (95% confidence interval 1.13-1.25) for a 10μg/m3 PM2.5 increase. The present study demonstrated that chronic exposure to PM2.5 increases the risk of AMD. Almost half of the Taiwanese live in a polluted area where the PM2.5 levels are higher than the World Health Organization recommended air quality guideline of 10μg/m3 had a 1.4-fold risk, which significantly increases concern about their visual health and social burden.

The Phenotypic Course of Age-Related Macular Degeneration for ARMS2/HTRA1: The EYE-RISK Consortium

Age-related maculopathy susceptibility 2 (ARMS2) is considered the most enigmatic of the genes for age-related macular degeneration (AMD). We investigated the phenotypic course and spectrum of AMD for the risk haplotype at the ARMS2 and high-temperature requirement A serine peptidase 1 (HTRA1) locus in a large European consortium. Pooled analysis of 4 case-control and 6 cohort studies. Individuals (N = 17 204) aged 55 years or older participating in the European Eye Epidemiology consortium. Age-related macular degeneration features and macular thickness were determined on multimodal images; data on genetics and phenotype were harmonized. Risks of AMD features for rs3750486 genotypes at the ARMS2/HTRA1 locus were determined by logistic regression and were compared with a genetic risk score (GRS) of 19 variants at the complement pathway. Lifetime risks were estimated with Kaplan-Meier analyses in population-based cohorts. Age-related macular degeneration features and stage. Of 2068 individuals with late AMD, 64.7% carried the ARMS2/HTRA1 risk allele. For homozygous carriers, the odds ratio (OR) of geographic atrophy was 8.6 (95% confidence interval [CI], 6.5-11.4), of choroidal neovascularization (CNV) was 11.2 (95% CI, 9.4-13.3), and of mixed late AMD was 12.2 (95% CI, 7.3-20.6). Cumulative lifetime risk of late AMD ranged from 4.4% for carriers of the nonrisk genotype to 9.4% and 26.8% for heterozygous and homozygous carriers. The latter received the diagnosis of late AMD 9.6 years (95% CI, 8.0-11.2) earlier than carriers of the nonrisk genotype. The risk haplotype was not associated with hard or soft drusen < 125 μm (OR, 1.2; 95% CI, 0.9-1.7), but risks increased significantly for soft drusen ≥ 125 μm (OR, 2.1; 95% CI, 1.5-3.0), up to an OR of 7.2 (95% CI, 3.8-13.8) for reticular pseudodrusen. Compared with persons with a high GRS for complement, homozygous carriers of ARMS2/HTRA1 showed a higher risk of CNV (OR, 4.1; 95% CI, 3.2-5.4); risks of other characteristics were not different. Carriers of the risk haplotype at ARMS2/HTRA1 have a particularly high risk of late AMD at a relatively early age. Data suggest that risk variants at ARMS2/HTRA1 act as a strong catalyst of progression once early signs are present. The phenotypic spectrum resembles that of complement genes, only with higher risks of CNV.

Deficiency of thyroid hormone receptor protects retinal pigment epithelium and photoreceptors from cell death in a mouse model of age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. Progressive dystrophy of the retinal pigment epithelium (RPE) and photoreceptors is the characteristic of dry AMD, and oxidative stress/damage plays a central role in the pathogenic lesion of the disease. Thyroid hormone (TH) regulates cell growth, differentiation, and metabolism, and regulates development/function of photoreceptors and RPE in the retina. Population-/patient-based studies suggest an association of high free-serum TH levels with increased risk of AMD. We recently showed that suppressing TH signaling by antithyroid treatment reduces cell damage/death of the RPE and photoreceptors in an oxidative-stress/sodium iodate (NaIO3)-induced mouse model of AMD. This work investigated the effects of TH receptor (THR) deficiency on cell damage/death of the RPE and photoreceptors and the contribution of the receptor subtypes. Treatment with NaIO3 induced RPE and photoreceptor cell death/necroptosis, destruction, and oxidative damage. The phenotypes were significantly diminished in Thrα1−/−, Thrb−/−, and Thrb2−/− mice, compared with that in the wild-type (C57BL/6 J) mice. The involvement of the receptor subtypes varies in the RPE and retina. Deletion of Thrα1 or Thrb protected RPE, rods, and cones, whereas deletion of Thrb2 protected RPE and cones but not rods. Gene-expression analysis showed that deletion of Thrα1 or Thrb abolished/suppressed the NaIO3-induced upregulation of the genes involved in cellular oxidative-stress responses, necroptosis/apoptosis signaling, and inflammatory responses. In addition, THR antagonist effectively protected ARPE-19 cells and hRPE cells from NaIO3-induced cell death. This work demonstrates the involvement of THR signaling in cell damage/death of the RPE and photoreceptors after oxidative-stress challenge and the receptor-subtype contribution. Findings from this work support a role of THR signaling in the pathogenesis of AMD and the strategy of suppressing THR signaling locally in the retina for protection of the RPE/retina in dry AMD.

The level and efficacy of lutein in patients with age-related macular degeneration: a comprehensive systematic review and meta-analysis.

BackgroundLutein has been linked with various visual performance disorders, including age-related macular degeneration (AMD). However, previous studies evaluating the association between serum lutein and the risk of AMD showed results, and the efficacy of lutein intake in AMD patients remains unclear.MethodsTo comprehensively estimate the relationship between lutein and AMD, a systematic review and meta-analysis was conducted by searching eligible randomized clinical trials (RCT) and case-control studies to study the association between lutein and AMD on the Cochrane Library, MEDLINE, Elsevier, PubMed, Web of Knowledge, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) databases until April 2020. The weighted mean difference (WMD) with 95% confidence interval (95% CI) was adopted as the primary effect estimate. Meta-analysis was conducted using STATA 12.0.ResultsNine studies with 855 participants were included in this meta-analysis. The NOS scoring of five case-control studies ranged 5–9. For RCTs, two studies were rated with a low risk of bias, one study with a moderate risk of bias and one with a high risk of bias. The results increased significantly in macular pigment optical density (MPOD) (WMD =0.069; 95% CI: 0.040–0.098, P=0.000) among AMD patients taking lutein supplementation, while there was no difference in circulating lutein levels between AMD patients and controls (WMD =0.00; 95% CI: −0.01 to 0.00, P=0.310). Subgroup analysis suggested that the dose and duration of supplementation could significantly influence the MPOD level in AMD patients. In particular, we observed a larger increase in MPOD of AMD patients using a higher dose (20 mg/d) and longer treatment (>6 months).ConclusionsAlthough current evidence does not support circulating lutein as a biomarker for early screening of the high-risk AMD population, this study is the first meta-analysis to explore the relationship between lutein in blood and AMD patients. Given that lutein has a high safety profile as indicated by many studies, it is reasonable to give the current analysis result that high dose (20 mg/d) and long duration (>6 months) of lutein intake could be beneficial to AMD patients.