Screening practices and risk assessment for maculopathy in pentosan polysulfate users across different exposure levels.

In this population-based cohort study, we investigated screening practices for maculopathy and incidences of specific macular/retinal conditions in pentosan polysulfate (PPS) users and assessed the relationship between these outcomes and drug exposure levels. Using a health claims database that covers approximately 50 million Koreans, we identified 138,593 individuals who were prescribed PPS between 2010 and 2021. For the 133,762 PPS users who initiated therapy between 2012 and 2021, the cumulative PPS dose for each participant was evaluated, and based on their cumulative PPS dose, patients were categorized into the high-risk (≥ 500 g), low-risk (50-500 g), and minimal exposure (< 50 g) groups. We analyzed the performance and methods of these examination methods used between 2018 and 2021 and compared them among cumulative dose groups to determine whether high-risk users underwent maculopathy screening more frequently or appropriately. We assessed the cumulative incidence of overall macular degeneration and maculopathy excluding common macular diseases following PPS therapy initiation. Most PPS users (99.7%) received a cumulative PPS dose < 500 g and the high- and low-risk groups comprised 445 (0.3%) and 22,185 (16.6%) patients, respectively. During the study period, monitoring examinations were conducted in 52.6% and 49.4% of high- and low-risk patients, respectively, revealing no significant difference between the two groups (P = 0.156). No significant differences were observed in the annual percentages of patients receiving ophthalmic examinations between the high- and low-risk groups (all P > 0.05). The cumulative incidences of overall macular degeneration and maculopathy excluding common macular diseases in high-risk users were 19.3% and 9.0%, respectively, which were significantly different from those of low-risk users (both P < 0.001). Multivariate Cox regression analysis revealed significantly higher risks of maculopathy excluding common macular diseases in the low- (Hazard ratio [HR] of 1.55 [95% CI 1.13-2.12]) and high-risk groups (HR of 1.66 [95% CI 1.22-2.27]) compared to the minimal exposure group. Our findings suggest a need for increased emphasis on PPS maculopathy screening in high-risk patients, highlighting raising awareness regarding exposure-dependent risks and the establishment of screening guidelines.

Inequalities in Uptake and Use of Digital Applications for Home-Monitoring of Neovascular Age-Related Macular Degeneration in an Elderly Visually Impaired Population: The MONARCH Study.

Purpose: To describe inequalities in the Monitoring for Neovascular Age-related Macular Degeneration Reactivation at Home (MONARCH) diagnostic test accuracy study for: recruitment; participants' ability to self-test; and adherence to testing using digital applications during follow-up. Methods: Home-monitoring vision tests included two tests implemented as software applications (apps: MyVisionTrack and MultiBit) on an iPod Touch device. Patients were provided with all hardware required to participate (iPod and MIFI device) and trained to use the apps. Regression models estimated associations of age, sex, Index of Multiple Deprivation, strata of time since first diagnosis, and baseline visual acuity at study entry on outcomes of willingness to participate, ability to perform tests, and adherence to weekly testing. Results: A minority of patients who were approached were willing-in-principle to participate. Increasing age was associated with being unwilling-in-principle to participate. Patients from the most deprived areas had a 47% decrease in odds of being willing compared to those from the middle quintile deprived areas (odds ratio, 0.53; 95% confidence interval = 0.32, 0.88). Increasing age and worse deprivation were not consistently associated either with ability to self-monitor with the index tests, or adherence to weekly testing. Conclusions: Associations of increasing age and worse deprivation index were associated with unwillingness-in-principle to participate despite the provision of hardware' highlighting the potential for inequality with interventions of the kind evaluated. Translational Relevance: The clear evidence of inequalities in participation should prompt future research on ways to encourage adoption of mobile health technologies by underserved populations.

Assessment of vision-related quality of life and depression in patients with age-related macular degeneration.

PURPOSE: To evaluate the effect of age-related macular degeneration (AMD) on vision-related quality of life (VRQOL) and depression levels. METHODS: This cross-sectional study included 143 patients who are being followed up with a diagnosis of AMD. The Turkish versions of the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) and Geriatric Depression Scale-15 (GDS-15) were directed to the patients. The questionnaire results were analyzed based on the severity, treatment procedures for AMD, and sociodemographic characteristics of patients. RESULTS: The subscale scores obtained from the NEI VFQ-25 ranged from 47.54 for "near activities" to 84.02 for "color vision." Of the patients, 59.4% (85/143) were compatible with depression according to the GDS-15 questionnaire. There was no significant difference in the NEI VFQ-25 subscale scores between the gender groups (P > 0.05), whereas females were statistically significantly more depressive than males (P < 0.05). There were no significant differences between the injection (anti-vascular endothelial growth factors [anti-VEGF]) group and the non-injection group in terms of subscales of the NEI VFQ-25 questionnaire (P > 0.05). The depression ratio in the non-injected group was statistically significantly higher (P < 0.05). CONCLUSION: According to the present study, the association between depression and AMD is a fact that should be highlighted. Patients with depression had lower scores on the quality of life (QOL) test. Previous intravitreal injection did not affect NEI VFQ-25 scores. Female patients with AMD had higher rates of depression and lower visual acuity levels.

DIAGNOSTIC PATTERNS OF AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To characterize prevalence estimates by race, age, sex, and comorbidity (diabetes and hypertension) within the Medicare beneficiary demographic. METHODS: In this US population-based retrospective cohort analysis, the Vision and Eye Health Surveillance System was analyzed for a 100% sample of Medicare Fee-For-Service beneficiary populations of Asians and non-Hispanic Whites between 2014 and 2018. Exclusionary criteria included beneficiaries younger than 40 years. Prevalence rate ratios, defined as prevalence rate for Asians divided by prevalence rate for non-Hispanic Whites, were calculated using multivariate negative binomial regression or Pearson-scaled Poisson regression, stratified by age, sex, and comorbidity. RESULTS: A total of 21,892,200 Medicare beneficiaries fulfilled the inclusionary criteria in 2018. Of the entire cohort, 3.2% of the beneficiaries (N = 714,500) were Asian. For beneficiaries aged 40 to 64 years, Asian male (prevalence rate ratios 1.73, 95% confidence interval 1.64-1.83, P < 0.0001) and female (prevalence rate ratios 1.34, 95% confidence interval 1.28-1.41, P < 0.0001) beneficiaries had an increased prevalence rate of all age-related macular degeneration relative to non-Hispanic Whites. Significant time-wise increases in prevalence rate ratios were observed within several age groups, sexes, and comorbidities (race-time interaction coefficients P < 0.05 ). CONCLUSION: This analysis highlights increased age-related macular degeneration prevalence estimates within the Asian American demographic relative to non-Hispanic Whites. Furthermore, specific Asian subpopulations are experiencing accelerated prevalence rates over time.

Metformin Use and Age-Related Macular Degeneration in Patients Without Diabetes.

Importance: Metformin use may protect against the development of age-related macular degeneration (AMD) based on results from observational studies. However, its potential effectiveness among patients without diabetes remains unclear. Objective: To assess the association between metformin use and the development of AMD in patients without diabetes. Design, Setting, and Participants: This case-control study used data from 2006 to 2017 in the Merative MarketScan Research Database, a nationwide insurance claims database that includes between 27 and 57 million patients in the US with primary or Medicare supplemental health insurance. Cases with AMD and controls without AMD aged 55 years or older were matched 1:1 by year, age, anemia, hypertension, region, and Charlson Comorbidity Index score. Then, cases and matched controls without a diagnosis of diabetes were selected. In subgroup analyses, cases with dry AMD and their matched controls were identified to explore the association between metformin use and AMD staging in patients without diabetes. Data were analyzed between March and September 2023. Exposures: Exposure to metformin in the 2 years prior to the index date (ie, date of AMD diagnosis in cases and date of a randomly selected eye examination for controls) was assessed from the claims database and categorized into quartiles based on cumulative dose (1-270, 271-600, 601-1080, and >1080 g/2 y). Exposure to other antidiabetic medications was also noted. Main Outcomes and Measures: Odds of new-onset AMD development as assessed by multivariable conditional logistic regression after adjusting for known risk factors for AMD, including female sex, hyperlipidemia, smoking, and exposures to other antidiabetic medications. Asymptotic Cochran-Armitage tests for trend were also performed. Results: We identified 231 142 patients with any AMD (mean [SD] age, 75.1 [10.4] years; 140 172 females [60.6%]) and 232 879 matched controls without AMD (mean [SD] age, 74.9 [10.5] years; 133 670 females [57.4%]), none of whom had a diagnosis of diabetes. The sample included 144 147 cases with dry AMD that were matched to 144 530 controls. In all, 2268 (1.0%) cases and 3087 controls (1.3%) were exposed to metformin in the 2 years before their index visit. After data adjustment, exposure to any metformin was associated with reduced odds of any AMD development (adjusted odds ratio [AOR], 0.83; 95% CI, 0.74-0.87), specifically in the dosing quartiles of 1 to 270, 271 to 600, and 601 to 1080 g/2 y. Any metformin use was also associated with a reduced odds of developing dry AMD (AOR, 0.85; 95% CI, 0.79-0.92), specifically in the dosing quartiles of 1 to 270 and 271 to 600 g/2 y. Adjusted odds ratios for any AMD and dry AMD development did not differ across the dosing quartiles. Asymptotic Cochran-Armitage tests for trend revealed 2-sided P = .51 and P = .66 for the any and dry AMD samples, respectively. Conclusions and Relevance: In this case-control study of a population without a diagnosis of diabetes, metformin use was associated with reduced odds of developing AMD. This association does not appear to be dose dependent. These findings provide further impetus to study metformin's usefulness in protecting against AMD in prospective clinical trials.

Patient-Centered Economic Burden of Exudative Age-Related Macular Degeneration: Retrospective Cohort Study.

BACKGROUND: Exudative age-related macular degeneration (AMD), one of the leading causes of blindness, requires expensive drugs such as anti-vascular endothelial growth factor (VEGF) agents. The long-term regular use of effective but expensive drugs causes an economic burden for patients with exudative AMD. However, there are no studies on the long-term patient-centered economic burden of exudative AMD after reimbursement of anti-VEGFs. OBJECTIVE: This study aimed to evaluate the patient-centered economic burden of exudative AMD for 2 years, including nonreimbursement and out-of-pocket costs, compared with nonexudative AMD using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). METHODS: This retrospective cohort study was conducted using the OMOP CDM, which included 2,006,478 patients who visited Seoul National University Bundang Hospital from June 2003 to July 2019. We defined the exudative AMD group as patients aged >50 years with a diagnosis of exudative AMD and a prescription for anti-VEGFs or verteporfin. The control group was defined as patients aged >50 years without a diagnosis of exudative AMD or a prescription for anti-VEGFs or verteporfin. To adjust for selection bias, controls were matched by propensity scores using regularized logistic regression with a Laplace prior. We measured any medical cost occurring in the hospital as the economic burden of exudative AMD during a 2-year follow-up period using 4 categories: total medical cost, reimbursement cost, nonreimbursement cost, and out-of-pocket cost. To estimate the average cost by adjusting the confounding variable and overcoming the positive skewness of costs, we used an exponential conditional model with a generalized linear model. RESULTS: We identified 931 patients with exudative AMD and matched 783 (84.1%) with 2918 patients with nonexudative AMD. In the exponential conditional model, the total medical, reimbursement, nonreimbursement, and out-of-pocket incremental costs were estimated at US $3426, US $3130, US $366, and US $561, respectively, in the first year and US $1829, US $1461, US $373, and US $507, respectively, in the second year. All incremental costs in the exudative AMD group were 1.89 to 4.25 and 3.50 to 5.09 times higher in the first and second year, respectively, than those in the control group (P<.001 in all cases). CONCLUSIONS: Exudative AMD had a significantly greater economic impact (P<.001) for 2 years on reimbursement, nonreimbursement, and out-of-pocket costs than nonexudative AMD after adjusting for baseline demographic and clinical characteristics using the OMOP CDM. Although economic policies could relieve the economic burden of patients with exudative AMD over time, the out-of-pocket cost of exudative AMD was still higher than that of nonexudative AMD for 2 years. Our findings support the need for expanding reimbursement strategies for patients with exudative AMD given the significant economic burden faced by patients with incurable and fatal diseases both in South Korea and worldwide.

Associations Between Autoimmune Disease and the Development of Age-Related Macular Degeneration.

Purpose: The pathogenesis of age-related macular degeneration (AMD) likely implicates the dysregulation of immune response pathways. Several studies demonstrate that the pathogenic elements of AMD resemble those of autoimmune diseases, yet the association between AMD development and most autoimmune diseases remain unexplored. Methods: We conducted a case-control analysis of patients ages 55 and older with new-onset International Classification of Diseases (ICD) coding of dry, wet, or unspecified AMD between 2005 and 2019 in the Merative MarketScan Commercial and Medicare Databases. The diagnosis of an autoimmune disease was defined by an outpatient or inpatient claim with a relevant ICD code in the 12 months before the index visit. Conditional multivariable logistic regression, adjusted for AMD risk factors, was used to calculate odd ratios and 95% confidence intervals. Results: We identified 415,027 cases with new-onset ICD coding for AMD matched with propensity scores to 414,853 controls. In total, 16.1% of cases and 15.9% of controls were diagnosed with any autoimmune disease. The diagnosis of any autoimmune disease did not affect the odds of new-onset ICD coding for AMD in multivariable regression (OR = 1.01; 95% CI, 0.999-1.02). Discoid lupus erythematosus (OR = 1.29; 95% CI, 1.12-1.48), systemic lupus erythematosus (SLE) (OR = 1.21; 95% CI, 1.15-1.27), giant cell arteritis (OR = 1.19; 95% CI, 1.09-1.30), Sjogren's syndrome (OR = 1.17; 95% CI, 1.09-1.26), and Crohn's disease (OR = 1.13; 95% CI, 1.06-1.22) increased the odds of a new-onset ICD coding for AMD. Conclusions: Most autoimmune diseases do not affect the odds of developing AMD but several common autoimmune disorders such as SLE and Crohn's disease were associated with modestly increased odds of AMD. Further studies are needed to validate and investigate the underlying mechanisms of these associations.

Genetic Risk Assessment of Degenerative Eye Disease (GRADE): study protocol of a prospective assessment of polygenic risk scores to predict diagnosis of glaucoma and age-related macular degeneration.

BACKGROUND: Glaucoma and age-related macular degeneration (AMD) account for a substantial portion of global blindness. Both conditions are highly heritable, with recognised monogenic and polygenic inheritance patterns. Current screening guidelines lack decisive recommendations. Polygenic risk scores (PRS) allow for cost-effective broad population risk stratification for these conditions. The predictive potential of PRS could facilitate earlier diagnosis and treatment, and prevent unnecessary vision loss. METHODS: The Genetic Risk Assessment of Degenerative Eye disease (GRADE) study is a prospective study designed to generate high-quality evidence about the feasibility of PRS to stratify individuals from the general population, enabling identification of those at highest risk of developing glaucoma or AMD. The targeted recruitment is 1000 individuals aged over 50 years, from which blood or saliva samples will be used for genotyping and an individual PRS for glaucoma and AMD will be derived. Individuals with PRS values in the bottom decile (n = 100), top decile (n = 100) and middle 80% (n = 100) for both glaucoma and AMD will undergo a detailed eye examination for glaucoma and/or AMD. DISCUSSION: The primary objective will be to compare the prevalence of glaucoma and AMD cases between low, intermediate, and high PRS risk groups. We expect to find a higher prevalence of both diseases in the high PRS risk group, as compared to the middle and low risk groups. This prospective study will assess the clinical validity of a PRS for glaucoma and AMD in the general Australian population. Positive findings will support the implementation of PRS into clinical practice.

[The population affected by neovascular age-related macular degeneration and treated with anti-Vegf through Italian administrative healthcare data.] / La popolazione con degenerazione maculare neovascolare correlata all'età trattata con anti-Vegf attraverso i dati amministrativi sanitari.

INTRODUCTION: The neo-vascular age-related macular degeneration (nAmd) is a frequent cause of vision loss, although the intravitreal (Ivt) injections of anti-Vegf (vascular endothelial growth factor) have improved functional outcomes. This study has assessed the healthcare and economic burden on the Italian national health service (Inhs) for patients with nAmd and new users of anti-Vegf. METHODS: From the database of Fondazione Ricerca e Salute (ReS), people aged ≥55 and with an in-hospital diagnosis of nAmd and/or an injection of anti-Vegf (aflibercept, ranibizumab, pegaptanib; index date) in 2018 are selected. Those with other conditions treated with anti-Vegf and with an Ivt injection before 2018 are excluded. New users of anti-Vegf are analyzed by sex, age, comorbidities, Ivt administrations, switch of anti-Vegf, local outpatient specialist services (with some focuses) and direct healthcare costs charged to the Inhs Results. In 2018, of 8125 inhabitants aged ≥55 with nAmd (4.6x1000 inhab.; mean age 76±9; F: 50%), 1513 (19%) are new users of Ivt anti-Vegf (mean age 74±9), whose incidence (0.9x1000) increased with age until 84 years old. A proportion of 60.7% had ≥2 comorbidities (mainly hypertension, dyslipidemia and diabetes). Within the 2nd follow-up year, only 598 patients are still treated (60% were lost). On average, 4.8 Ivt injections in the first and 3.1 in the second year are registered. On average, the total cost charged to the Inhs per new user of anti-Vegf was € 6726 (Ivt anti-Vegf accounted for the 76%) and € 3282 (hospitalizations for causes different from nAmd accounted for the 47%), during the first and the second year, respectively. CONCLUSIONS: This analysis suggests that in Italy people with nAmd and new users of anti-Vegf are elderly, affected by many comorbidities, treated with Ivt anti-VEGF less than what is required and authorized to achieve a benefit, undergo very few follow-up outpatient specialist visits and tests and, within the 2nd year, their hospitalizations for causes different from nAmd mainly weighs on the total expenditure charged to the Inhs.

Trends in the Diagnosed Prevalence and Incidence of Major Eye Diseases in Medicare Part B Fee-for-Service Beneficiaries 68 Years of Age or Older.

PURPOSE: To study contemporary trends in the diagnosed prevalence and incidence of age-related eye diseases among Medicare Fee-for-Service (FFS) beneficiaries. DESIGN: Analysis of Medicare administrative claims data. PARTICIPANTS: Medicare FFS beneficiaries 68 years of age and older from 2005 through 2020 who were enrolled continuously in both Part A and Part B for 3 years, including the index year and a 2-year lookback period. METHODS: Annual cross-sectional diagnosed prevalence and incidence rates were calculated. Age standardization was performed using the direct standardization method to account for changes in the age structure of the study population. Rates stratified by demographics (age, sex, race, and ethnicity) also were calculated. MAIN OUTCOME MEASURES: Annual prevalence and incidence of diagnosed age-related macular degeneration (AMD), diabetic retinopathy (DR) (among those with diabetes), and glaucoma. RESULTS: At baseline, in 2005, 60% of included beneficiaries were female, 20% were 85 years of age or older, 86% were non-Hispanic White, and one-quarter had a diagnosis of diabetes. From 2005 through 2019, the prevalence of a diagnosis of any of the conditions studied increased from 16.4% (n = 3 628 996) to 17.9% (n = 3 731 281). Diagnosed incidence decreased over this period from 4.9% (n = 954 878) in 2005 to 4.2% in 2019 (n = 757 696). The diagnosed prevalence of AMD increased from 6.8% (n = 1 504 770) to 9.4% (n = 1 965 176); the diagnosed prevalence of any DR among those with diabetes decreased from 9.3% (n = 504 135) to 9.0% (n = 532 859), although the diagnosed prevalence of vision-threatening DR increased from 2.0% to 3.4%; and the diagnosed prevalence of any diagnosed glaucoma decreased from 8.8% (n = 1 951 141) to 8.1% (n = 1 692 837). In 2020, the diagnosed prevalence and incidence of all diagnoses decreased. During the study period, we detected demographic differences in the prevalence and incidence of diagnosis of each condition. CONCLUSIONS: This study presents updated data on the prevalence and incidence of diagnosed major chronic, age-related eye diseases among Medicare FFS beneficiaries. Compared with older epidemiologic estimates, we found that the diagnosed prevalence of each condition studied was higher in more recent years. These findings may inform public health and policy planning and resource allocation to address the eye health of an increasingly older United States population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Trends and disparities in disease burden of age-related macular degeneration from 1990 to 2019: Results from the global burden of disease study 2019.

Objectives: This study aims to estimate the trends and disparities in the worldwide burden for health of AMD, overall and by age, sex, socio-demographic index (SDI), region, and nation using prevalence and years lived with disability (YLDs) from Global Burden of Disease (GBD) study 2019. Methods: This retrospective study presents the prevalent AMD cases and YLDs from 1990-2019, as well as the age-standardized prevalence rate (ASPR) and age-standardized YLD rate (ASYR) of AMD. To measure changes over time, estimated annual percentage changes (EAPCs) of the age-standardized rates (ASRs) were analyzed globally, then studied further by sex, SDI, region, and nation. We included data from the 2019 Global Burden of Disease (GBD) database to examine AMD prevalence and YLDs from 1990-2019 in 204 countries and territories, as well as demographic information such as age, sex, SDI, region, and nation. Results: Globally, the number of prevalent AMD cases increased from 3,581,329.17 (95% uncertainty interval [UI], 3,025,619.4-4,188,835.7) in 1990 to 7,792,530 (95% UI, 6,526,081.5-9,159,394.9) in 2019, and the number of YLDs increased from 296,771.93 (95% uncertainty interval [UI], 205,462.8-418,699.82) in 1990 to 564,055.1 (95% UI, 392,930.7-789,194.64) in 2019. The ASPR of AMD had a decreased trend with an EAPC of -0.15 (95% confidence interval [CI], -0.2 to -0.11) from 1990 to 2019, and the ASYR of AMD showed a decreased trend with an EAPC of -0.71 (95% confidence interval [CI], -0.78 to -0.65) during this period. The prevalence and YLDs of AMD in adults over 50 years of age showed a significant increase. The prevalence and YLDs of AMD were significantly higher in females than males, overall. The ASPRs and ASYRs in low SDI regions was greater than in high SDI regions from 1990 to 2019. In addition, increases in prevalence and YLDs differed by regions and nations, as well as level of socio-economic development. Conclusion: The number of prevalent cases and YLDs due to AMD increased over 30 years and were directly linked to age, sex, socio-economic status, and geographic location. These findings can not only guide public health work but also provide an epidemiological basis for global strategy formulation regarding this global health challenge.

Analysis of the epidemiological burden of age-related macular degeneration in China based on the data of global burden of disease. / 基于GBDæ•°æ®åº“ä¸­å›½å¹´é¾„ç›¸å ³æ€§é»„æ–‘å˜æ€§æµè¡Œç— å­¦è´Ÿæ‹ åˆ†æž.

OBJECTIVES: Age-related macular degeneration (AMD) is one of the 3 major eye diseases recognized by WHO to prevent blindness, and which is the main cause of irreversible visual impairment in the elderly. This study aims to analyze the disease epidemiological burden, and provide a theoretical foundation for the prevention and control of AMD in China based on the data in global burden of disease (GBD) 2019. METHODS: The prevalent cases/prevalence, disability-adjusted life year (DALYs)/DALY rate of AMD and socio-demographic index (SDI) for global and China were searched from the GBD 2019 database to analyze the epidemiological trend, age-period-gender trend of AMD in China from 1990 to 2019, and to evaluate the relations between the prevalence and SDI. RESULTS: In 2019, the prevalence of AMD in China was at a high level in the world, and the number of prevalent cases were 1.93 times of that in 1990. The prevalence and DALY rates continued to rise. The age trend of AMD in China was high at the middle of the age stages and low at the two ends, and which was higher in the female than in the male. With the increase of SDI, the prevalence of AMD was increased linearly. CONCLUSIONS: The disease burden of AMD in China is increased significantly and is positively correlated with the social development from 1990 to 2019. It is of great significance to study the relationship between epidemilolgical data of AMD and social development level for diagnosis treatment and policy of AMD.

An assessment of prevalence of Type 1 CFI rare variants in European AMD, and why lack of broader genetic data hinders development of new treatments and healthcare access.

PURPOSE: Advanced age-related macular degeneration (AAMD) risk is associated with rare complement Factor I (FI) genetic variants associated with low FI protein levels (termed 'Type 1'), but it is unclear how variant prevalences differ between AMD patients from different ethnicities. METHODS: Collective prevalence of Type 1 CFI rare variant genotypes were examined in four European AAMD datasets. Collective minor allele frequencies (MAFs) were sourced from the natural history study SCOPE, the UK Biobank, the International AMD Genomics Consortium (IAMDGC), and the Finnish Biobank Cooperative (FINBB), and compared to paired control MAFs or background population prevalence rates from the Genome Aggregation Database (gnomAD). Due to a lack of available genetic data in non-European AAMD, power calculations were undertaken to estimate the AAMD population sizes required to identify statistically significant association between Type 1 CFI rare variants and disease risk in different ethnicities, using gnomAD populations as controls. RESULTS: Type 1 CFI rare variants were enriched in all European AAMD cohorts, with odds ratios (ORs) ranging between 3.1 and 7.8, and a greater enrichment was observed in dry AMD from FINBB (OR 8.9, 95% CI 1.49-53.31). The lack of available non-European AAMD datasets prevented us exploring this relationship more globally, however a statistical association may be detectable by future sequencing studies that sample approximately 2,000 AAMD individuals from Ashkenazi Jewish and Latino/Admixed American ethnicities. CONCLUSIONS: The relationship between Type 1 CFI rare variants increasing odds of AAMD are well established in Europeans, however the lack of broader genetic data in AAMD has adverse implications for clinical development and future commercialisation strategies of targeted FI therapies in AAMD. These findings emphasise the importance of generating more diverse genetic data in AAMD to improve equity of access to new treatments and address the bias in health care.

Real-world effectiveness of screening programs for age-related macular degeneration: amended Japanese specific health checkups and augmented screening programs with OCT or AI.

PURPOSE: To investigate the effectiveness of screening and subsequent intervention for age-related macular degeneration (AMD) in Japan. STUDY DESIGN: Best-case-scenario analysis using a Markov model. METHODS: The clinical effectiveness and cost-effectiveness of screening for AMD were assessed by calculating the reduction proportion of blindness and the incremental cost-effectiveness ratio (ICER). The Markov model simulation began at screening at the age of 40 years and ended at screening at the age of 90 years. The first-eye and second-eye combined model assumed annual state-transition probabilities in the development and treatment of AMD. Data on prevalence, morbidity, transition probability, utility value, and treatment costs were obtained from previously published reports. Sensitivity analysis was performed to assess the influence of the parameters. RESULTS: In the base-case analysis, screening for AMD every 5 years, beginning at age 40 years and ending at age 74 years (reflecting the screening ages of the current Japanese legal "Specific Health Checkups") showed a decrease of 40.7% in the total number of blind patients. The screening program reduced the number of blind people more than did the additional AREDS/AREDS2 formula supplement intake. However, the ICER of screening versus no screening was ¥9,846,411/QALY, which was beyond what people were willing to pay (WTP) in Japan. Sensitivity analysis revealed that neither OCT nor AI improved the ICER, but the scenario in which the prevalence of smoking decreased by 30% improved the ICER (¥4,655,601/QALY) to the level under the WTP. CONCLUSIONS: Ophthalmologic screening for AMD is highly effective in reducing blindness but is not cost-effective, as demonstrated by a Markov model based on real-world evidence from Japan.

Occurrence of Macular Neovascularization after Retinal Pigment Epithelium-Choroid Translocation Surgery to Treat Complicated Age-Related Macular Degeneration: Incidence, Management, and Outcome.

INTRODUCTION: This study investigates the incidence, clinical characteristics, and treatment response of macular neovascularization (MNV) occurring after retinal pigment epithelium (RPE) and choroid graft translocation surgery (RPE-choroid TS). METHODS: Retrospective analysis of 36 eyes of 36 consecutive patients who underwent RPE-choroid TS. Longer term follow-up of graft survival focusing on the occurrence of MNV was performed using multimodal imaging. RESULTS: Indications for RPE-choroid TS included complications of neovascular age-related macular degeneration in 34 patients and drusenoid pigment epithelial detachment in 2 patients. With a mean follow-up of 30 months, 8 patients out of 36 developed signs of MNV. Of these 8 patients, 4 presented with a drop in visual acuity (VA) due to centrally located type 3 MNV. Early diagnosis and treatment prevented significant functional consequences. Four patients developed type 2 MNV at the border of the graft, which did not tend to affect the VA. CONCLUSION: We report a high incidence of MNV after RPE-choroid TS. Early diagnosis and treatment may preserve function in these patients. The type of MNV and location can be used to guide the management.

Disease burden of age-related macular degeneration in China from 1990 to 2019: findings from the global burden of disease study.

BACKGROUND: To evaluate the disease burden of age-related macular degeneration (AMD) in terms of disability-adjusted life years (DALY) in China from 1990 to 2019. METHODS: Prevalence of blindness and vision loss due to AMD and DALY number, rate, and age-standardized rates of AMD were collected from the Global Burden of Disease Study 2019 database. The characters of variables were analyzed between China and its neighboring countries. RESULTS: From 1990 to 2019, the all-age number and rate for AMD prevalence and DALYs increased significantly in China, while the age standardized DALYs rate in 2019 showed a decrease of 3.63% compared with that in 1990. Females were found to have a higher prevalence and DALYs than males. The 65-69 age group had the highest AMD DALYs number, while the DALYs rate showed a positive association with age. In 2019, when compared to neighboring countries, the age standardized prevalence rate of AMD in China was ranked second after Pakistan, while the age standardized DALYs rate ranked second after Pakistan and India. CONCLUSIONS: Despite a small decrease in age standardized DALYs rate in China in the past three decades, the disease burden of AMD is still considerable and much higher compared to neighboring developed countries. Optimizing health services allocation is needed to further reduce this burden.

Global Burden of Dry Age-Related Macular Degeneration: A Targeted Literature Review.

PURPOSE: Age-related macular degeneration (AMD) is a leading cause of blindness, particularly in higher-income countries. Although dry AMD accounts for 85% to 90% of AMD cases, a comprehensive understanding of the global dry AMD burden is needed. METHODS: A targeted literature review was conducted in PubMed, MEDLINE, Embase, and the Cochrane Database of Systematic Reviews (1995-2019) to identify data on the epidemiology, management, and humanistic and economic burden of dry AMD in adults. A landscape analysis of patient-reported outcome (PRO) instruments in AMD was also conducted via searches in PubMed (1995-2019), ClinicalTrials.gov, PROQOLID, PROLABELS, and health technology assessment reports (2008-2018). FINDINGS: Thirty-seven of 4205 identified publications were included in the review. Dry AMD prevalence was 0.44% globally, varied across ethnic groups, and increased with age. Patients with dry AMD had higher risks of all-cause mortality (hazard ratio [HR] = 1.46; 95% CI, 0.99-2.16) and tobacco-related (HR = 2.86; 95% CI, 1.15-7.09) or cancer deaths (HR = 3.37; 95% CI, 1.56-7.29; P = 0.002) than those without dry AMD. Smoking, increasing age or cholesterol levels, and obesity are key risk factors for developing dry AMD. No treatment guidelines were identified for dry AMD specifically; management focuses on risk factor reduction and use of dietary supplements. In the United States and Italy, direct medical costs and health care resource utilization were lower in patients with dry versus wet AMD. Patients with dry AMD, particularly advanced disease, experienced significant visual function impairment. Dry AMD symptoms included reduced central vision, decreased ability to see at night, increased visual blurriness, distortion of straight lines and text, and faded color vision. Most PRO instruments used in AMD evaluations covered few, if any, of the identified symptoms reported by patients with dry AMD. Although the Quality of Life and Vision Function Questionnaire, 25-item National Eye Institute Vision Function Questionnaire, Low Vision Quality of Life, Impact of Vision Impairment-Very Low Vision, and Functional Reading Independence Index had strong content validity and psychometric properties in patients with dry AMD, they retained limited coverage of salient concepts. IMPLICATIONS: Despite dry AMD accounting for most AMD cases, there are substantial gaps in the published literature, particularly the humanistic and economic burden of disease and the lack of differentiation among dry, wet, or unspecified dry AMD. The significant burden of illness alludes to a high unmet need for tolerable and effective treatment options, as well as PRO instruments with more coverage of dry AMD symptoms and salient concepts.

Impact of neovascular age-related macular degeneration: burden of patients receiving therapies in Japan.

The chronic eye disorder, neovascular age-related macular degeneration (nAMD), is a common cause of permanent vision impairment and blindness among the elderly in developed countries, including Japan. This study aimed to investigate the disease burden of nAMD patients under treatment, using data from the Japan National Health and Wellness surveys 2009-2014. Out of 147,272 respondents, 100 nAMD patients reported currently receiving treatment. Controls without nAMD were selected by 1:4 propensity score matching. Healthcare Resource Utilisation (HRU), Health-Related Quality of Life (HRQoL), and work productivity loss were compared between the groups. Regarding HRU, nAMD patients had significantly increased number of visits to any healthcare provider (HCP) (13.8 vs. 8.2), ophthalmologist (5.6 vs. 0.8), and other HCP (9.5 vs. 7.1) compared to controls after adjusting for confounding factors. Additionally, nAMD patients had reduced HRQoL and work productivity, i.e., reduced physical component summary (PCS) score (46.3 vs. 47.9), increased absenteeism (18.14% vs. 0.24%), presenteeism (23.89% vs. 12.44%), and total work productivity impairment (33.57% vs. 16.24%). The increased number of ophthalmologist visits were associated with decreased PCS score, increased presenteeism and total work productivity impairment. The current study highlighted substantial burden for nAMD patients, requiring further attention for future healthcare planning and treatment development.

Economic burden of age-related macular degeneration in routine clinical practice: the RAMDEBURS study.

PURPOSE: To describe and evaluate the main direct health costs, in routine clinical practice, of age-related macular degeneration (AMD) patients, from hospital perspective, in Spain. METHODS: Retrospective, multicenter, and observational study conducted on five third-level Spanish hospitals, between December 2018 and December 2019. The study included patients who were diagnosed of AMD before December 2018. Direct healthcare costs were obtained from a Spanish database. Study variables included demographic and clinical variables, and resources, such as treatment, diagnostic tests, medical examination, and surgery. Among the 1414 screened AMD patients, 1164 patients were included. In the overall study patients, the total cost was €5,386,511.0, with a mean cost per patient of €4627.6 ± 2383.9. The largest cost items were diagnostic examinations (€2.832.902,0) and vascular endothelial growth factor inhibitors (anti-VEGF) treatment (€2.038.257,2). Bevacizumab was administered to 325 (27.9%) patients, ranibizumab to 328 (28.2%), and aflibercept to 626 (53.8%); 115 (10.7%) patients received two anti-VEGF treatments, while 90 (7.7%) did not receive any. Over the course of the study, a total of 6,057 anti-VEGF injections were administered, with a mean (95% confidence interval) of 4.8 (4.4-5.2) injections per patient. Regarding safety, 29 patients experience injection-related adverse events, among them 12 patients had cataract and 11 ones elevated intraocular pressure (IOP). The incidence of endophthalmitis was 0.5% (6/1164). CONCLUSIONS: AMD was associated with considerable healthcare costs for regional healthcare systems. Diagnostic examinations, particularly OCT examinations, and anti-VEGF treatment represented the largest cost items.

[Age-related macular degeneration and diabetic eye lesion. Socio-economic aspects]. / Vozrastnaya makulyarnaya degeneratsiya i diabeticheskoe porazhenie glaz. Sotsial'no-ekonomicheskie aspekty zabolevaemosti.

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) comprise a significant socio-medical problem for Russia. The article presents an analysis aimed at identifying the prerequisites for further research on the socio-economic consequences of retinal pathology. Studying the epidemiological aspects of DR and AMD, as well as the conditions for receiving medical aid helped define the main approaches to assessing the economic burden of retinal diseases in Russia. It also revealed the problems associated with completeness of registration and accounting of patients, the disparity between the volume of medical aid required and funding, and between the required and provided assistance for patients with these pathologies in clinical practice. Analysis of the disease cost will allow not only to determine the socio-economic consequences of retinal diseases, but also to find further directions for improving the quality of medical care for patients with DR and AMD in order to reduce its economic cost for the state and society. Evidently, there is a need for comprehensive assessment of the total burden of retinal diseases in Russia that would serve as a basis for subsequent assessment of the economic effectiveness of prevention and treatment measures.