Progression To Advanced Age-related Macular Degeneration Research Articles

Predict and Protect: Evaluating the Double-Layer Sign in Age-Related Macular Degeneration.

Advanced age-related macular degeneration (AMD) is a major cause of vision loss. Therefore, there is interest in precursor lesions that may predict or prevent the onset of advanced AMD. One such lesion is a shallow separation of the retinal pigment epithelium (RPE) and Bruch's membrane (BM), which is described by various terms, including double-layer sign (DLS). In this article, we aim to examine and clarify the different terms referring to shallow separation of the RPE and BM. We also review current evidence on the outcomes associated with DLS: firstly, whether DLS is predictive of exudative neovascular AMD; and secondly, whether DLS has potential protective properties against geographic atrophy. The range of terms used to describe a shallow separation of the RPE and BM reflects that DLS can present with different characteristics. While vascularised DLS appears to protect against atrophy but can progress to exudation, non-vascularised DLS is associated with an increased risk of atrophy. Optical coherence tomography (OCT) angiography (OCTA) is the principal method for identifying and differentiating various forms of DLS. If OCTA is unavailable or not practically possible, simplified classification of DLS as thick or thin, using OCT, enables the likelihood of vascularisation to be approximated. Research is ongoing to automate DLS detection by applying deep-learning algorithms to OCT scans. The term DLS remains applicable for describing shallow separation of the RPE and BM. Detection and classification of this feature provides valuable information regarding the risk of progression to advanced AMD. However, the appearance of DLS and its value in predicting AMD progression can vary between patients. With further research, individualised risks can be confirmed to inform appropriate treatment.

Risk Prediction for Progression of Macular Degeneration: 10 Common and Rare Genetic Variants, Demographic, Environmental, and Macular Covariates.

To determine the association between genetic variants and transition to advanced age-related macular degeneration (AMD), and to develop a predictive model and online application to assist in clinical decision making. Among 2951 subjects in the Age-Related Eye Disease Study, 834 progressed from no AMD, early AMD, or intermediate AMD to advanced disease. Survival analysis was used to assess which genetic, demographic, environmental, and macular covariates were independently associated with progression. Attributable risk, area under the curve statistics (AUCs), and reclassification odds ratios (ORs) were calculated. Split-sample validation was performed. An online risk calculator was developed and is available in the public domain at www.seddonamdriskscore.org. Ten genetic loci were independently associated with progression, including newly identified rare variant C3 K155Q (hazard ratio: 1.7, 95% confidence interval: 1.2-2.5, P = 0.002), three variants in CFH, and six variants in ARMS2/HTRA1, CFB, C3, C2, COL8A1, and RAD51B. Attributable risk calculations revealed that 80% of incident AMD is attributable to genetic factors, adjusting for demographic covariates and baseline macular phenotypes. In a model including 10 genetic loci, age, sex, education, body mass index, smoking, and baseline AMD status, the AUC for progression to advanced AMD over 10 years was 0.911. Split-sample validation showed a similar AUC (0.907). Reclassification analyses indicated that subjects were categorized into a more accurate risk category if genetic information was included (OR 3.2, P < 0.0001). Rare variant C3 K155Q was independently associated with AMD progression. The comprehensive model may be useful for identifying and monitoring high-risk patients, selecting appropriate therapies, and designing clinical trials.

Age-related Eye Disease Study 2

This review provides a perspective on the Age-related Eye Disease Study 2 (AREDS2) including a summary of the goals and rationale of the study, major findings, subsequent management recommendations, and questions that remain to be answered. The primary goal of the AREDS2 was to evaluate the efficacy and safety of lutein plus zeaxanthin and/or omega-3 long-chain polyunsaturated acid supplementation in reducing the risk of developing advanced age-related macular degeneration (AMD). AREDS2 also investigated the effects of omitting β-carotene and reducing the concentration of zinc from the original AREDS formulation. Although primary analysis from the AREDS2 did not reveal a benefit of daily supplementation with lutein/zeaxanthin on AMD progression, secondary exploratory analyses suggested that lutein/zeaxanthin were helpful in reducing this risk. Comparison of low-dose to higher-dose zinc showed no significant benefit. The overall evidence on the beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than β-carotene in AREDS-type supplements. Questions remain regarding the AREDS2 study results such as: whether the findings are generalizable to the population as a whole, what is the long-term safety profile of lutein/zeaxanthin supplementation, should other carotenoids be included in AREDS-type supplements, and at what optimal doses?

Does eating particular diets alter the risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?

Background:Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and reducing dietary glycaemic index (dGI) are protective against...

Responsiveness of the National Eye Institute Visual Function Questionnaire to Progression to Advanced Age-Related Macular Degeneration, Vision Loss, and Lens Opacity

To describe the ability of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to detect meaningful change over time (responsiveness) to the primary Age-Related Eye Disease Study outcomes. The 25-item NEI-VFQ plus appendix was administered at 2 visits at 1- to 4-year intervals to 4119 participants in the Age-Related Eye Disease Study. Events evaluated were progression to advanced age-related macular degeneration (AMD), visual acuity (VA) loss of at least 15 letters, and lens opacity progression. Responsiveness was measured by the t statistic, effect size (ES), responsiveness statistic, and area under the receiver operating characteristic curve. Variance components were used to estimate the contributions of events to variability of the NEI-VFQ score. Overall NEI-VFQ score was responsive to AMD progression (t = 14.0; P< .001; ES = 0.81) and VA (t = 16.2; P< .001; ES = 0.74). Mean changes ranged from 11 to 25 points for the subscales of general vision, near and distance activities, social functioning, mental health, role difficulties, dependency, and driving. The NEI-VFQ was unresponsive to lens opacity progression, although when the event occurred in the eye with the best vision at the first administration, the lens opacity ES was moderate for the color vision (ES = 0.62) and driving subscales (ES = 0.66). Progression to advanced AMD and VA loss contributed significantly to the variation in the mean difference in overall VFQ score. Changes in the NEI-VFQ overall and subscale scores of 10 points or more are associated with clinically significant changes in vision and AMD. This finding may assist the design of interventional studies of AMD and VA loss that include the NEI-VFQ as an outcome measure.

AREDS—Two Years Later

Objective: To estimate the potential public health impact of the findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced age-related macular degeneration (AMD) during the next 5 years in the United States. Methods: The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dose nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during 5 years if those at risk were to take a supplement such as that used in AREDS. Results: An estimated 8 million persons at least 55 years old in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300000 (95% confidence interval, 158000-487000) of them would avoid advanced AMD and any associated vision loss during the next 5 years. Conclusion: If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the United States would be considerable during the next 5 years.

Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11.

To estimate the potential public health impact of the findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced age-related macular degeneration (AMD) during the next 5 years in the United States. The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dose nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during 5 years if those at risk were to take a supplement such as that used in AREDS. An estimated 8 million persons at least 55 years old in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300,000 (95% confidence interval, 158,000-487,000) of them would avoid advanced AMD and any associated vision loss during the next 5 years. If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the United States would be considerable during the next 5 years.