Cost-effectiveness of smoking cessation to prevent age-related macular degeneration

<p>Abstract</p> <p>Background</p> <p>Tobacco smoking is a risk factor for age-related macular degeneration, but studies of ex-smokers suggest quitting can reduce the risk.</p> <p>Methods</p> <p>We fitted a function predicting the decline in risk of macular degeneration after quitting to data from 7 studies involving 1,488 patients. We assessed the cost-effectiveness of smoking cessation in terms of its impact on macular degeneration-related outcomes for 1,000 randomly selected U.S. smokers. We used a computer simulation model to predict the incidence of macular degeneration and blindness, the number of quality-adjusted life-years (QALYs), and direct costs (in 2004 U.S. dollars) until age 85 years. Cost-effectiveness ratios were based on the cost of the Massachusetts Tobacco Control Program. Costs and QALYs were discounted at 3% per year.</p> <p>Results</p> <p>If 1,000 smokers quit, our model predicted 48 fewer cases of macular degeneration, 12 fewer cases of blindness, and a gain of 1,600 QALYs. Macular degeneration-related costs would decrease by $2.5 million if the costs of caregivers for people with vision loss were included, or by$1.1 million if caregiver costs were excluded. At a cost of $1,400 per quitter, smoking cessation was cost-saving when caregiver costs were included, and cost about$200 per QALY gained when caregiver costs were excluded. Sensitivity analyses had a negligible impact. The cost per quitter would have to exceed $77,000 for the cost per QALY for smoking cessation to reach$50,000, a threshold above which interventions are sometimes viewed as not cost-effective.</p> <p>Conclusion</p> <p>Smoking cessation is unequivocally cost-effective in terms of its impact on age-related macular degeneration outcomes alone.</p

Cost-effectiveness of ranibizumab for neovascular age-related macular degeneration

<p>Abstract</p> <p>Background</p> <p>Intravitreal ranibizumab prevents vision loss and improves visual acuity in patients with neovascular age-related macular degeneration, but it is expensive, and efficacy beyond 2 years is uncertain.</p> <p>Methods</p> <p>We assessed the cost-effectiveness of ranibizumab compared with no ranibizumab over 10 years, using randomized trial efficacy data for the first 2 years, post-trial efficacy assumptions, and ranibizumab acquisition costs ranging from the wholesale price ($1,950 per dose) to the price of bevazicumab ($50), a similar molecule which may be equally efficacious. We used a computer simulation model to estimate the probability of blindness, the number of quality-adjusted life-years (QALYs), direct costs (in 2004 U.S. dollars), and cost-effectiveness ratios for a 67-year old woman. Costs and QALYs were discounted at 3% per year.</p> <p>Results</p> <p>The probability of blindness over 10 years was reduced from 56% to 34% if ranibizumab was efficacious for only 2 years, 27% if efficacy was maintained for a further 2 years only (base-case scenario), and 17% if visual acuity at 4 years was then sustained. It was cost-saving under all price assumptions, when caregiver costs were included. When caregiver costs were excluded, the cost per QALY for the base-case ranged from $5,600, assuming the bevazicumab price, to$91,900 assuming the wholesale ranibizumab price. The cost per QALY was < $50,000 when the cost of ranibizumab was less than$1000.</p> <p>Conclusion</p> <p>From a societal perspective, ranibizumab was cost-saving. From a health care funder's perspective, ranibizumab was an efficient treatment when it cost less than $1000 per dose.</p

Comprehensive Analysis of Copy Number Variation of Genes at Chromosome 1 and 10 Loci Associated with Late Age Related Macular Degeneration

Copy Number Variants (CNVs) are now recognized as playing a significant role in complex disease etiology. Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the western world. While a number of genes and environmental factors have been associated with both risk and protection in AMD, the role of CNVs has remained largely unexplored. We analyzed the two major AMD risk-associated regions on chromosome 1q32 and 10q26 for CNVs using Multiplex Ligation-dependant Probe Amplification. The analysis targeted nine genes in these two key regions, including the Complement Factor H (CFH) gene, the 5 CFH-related (CFHR) genes representing a known copy number “hotspot”, the F13B gene as well as the ARMS2 and HTRA1 genes in 387 cases of late AMD and 327 controls. No copy number variation was detected at the ARMS2 and HTRA1 genes in the chromosome 10 region, nor for the CFH and F13B genes at the chromosome 1 region. However, significant association was identified for the CFHR3-1 deletion in AMD cases (p = 2.38×10−12) OR = 0.31, CI-0.95 (0.23–0.44), for both neovascular disease (nAMD) (p = 8.3×10−9) OR = 0.36 CI-0.95 (0.25–0.52) and geographic atrophy (GA) (p = 1.5×10−6) OR = 0.36 CI-0.95 (0.25–0.52) compared to controls. In addition, a significant association with deletion of CFHR1-4 was identified only in patients who presented with bilateral GA (p = 0.02) (OR = 7.6 CI-0.95 1.38–41.8). This is the first report of a phenotype specific association of a CNV for a major subtype of AMD and potentially allows for pre-diagnostic identification of individuals most likely to proceed to this end stage of disease

Can HMG Co-A reductase inhibitors (“statins”) slow the progression of age-related macular degeneration? The Age-Related Maculopathy Statin Study (ARMSS)

Age-related macular degeneration (AMD) is responsible for the majority of visual impairment in the Western world. The role of cholesterol-lowering medications, HMG Co-A reductase inhibitors or statins, in reducing the risk of AMD or of delaying its progression has not been fully investigated. A 3-year prospective randomized controlled trial of 40 mg simvastatin per day compared to placebo in subjects at high risk of AMD progression is described. This paper outlines the primary aims of the Age-Related Maculopathy Statin Study (ARMSS), and the methodology involved. Standardized clinical grading of macular photographs and comparison of serial macular digital photographs, using the International grading scheme, form the basis for assessment of primary study outcomes. In addition, macular function is assessed at each visit with detailed psychophysical measurements of rod and cone function. Information collected in this study will assist in the assessment of the potential value of HMG Co-A reductase inhibitors (statins) in reducing the risk of AMD progression

Test-Retest Repeatability of Microperimetry at the Border of Deep Scotomas

Citation: Wu Z, Jung CJ, Ayton LN, Luu CD, Guymer RH. Test-retest repeatability of microperimetry at the border of deep scotomas. Invest Ophthalmol Vis Sci. 2015;56:2606-2611. DOI:10.1167/iovs.14-15977 PURPOSE. The purpose of this study was to examine the test-retest repeatability of microperimetric sensitivity at the border of deep scotomas. METHODS. Thirty normal participants underwent two examinations, each on the Macular Integrity Assessment (MAIA) microperimeter and on the MP-1 microperimeter (four examinations in total). A customized stimulus pattern allowed microperimetric sensitivity to be measured at the border of the optic nerve head (ONH), which acted as a model for the border of a deep scotoma-and also at the macular and peripapillary region. RESULTS. There were no significant changes in average point-wise sensitivity (PWS) values between the two examinations for all three regions using the MAIA microperimeter (P ‡ 0.262). The PWS coefficient of repeatability (CoR) was 612.99 dB at the border of the ONH, which was significantly larger than points in the macular and peripapillary regions (P &gt; 0.001). A significant decrease in average PWS, using the MP-1 microperimeter at the macular and peripapillary region (P &lt; 0.001), meant that the PWS CoR could not be determined in these regions. No significant changes in average PWS were observed at the border of the ONH (P ¼ 0.223), and the PWS CoR was 67.52 dB in this region. CONCLUSIONS. Microperimetric test-retest repeatability at the border of a deep scotoma was worse than at other areas of normal retina, and this highlights the limitation of applying a single estimate of test-retest repeatability to determine whether significant functional decline has occurred at the border of a deep scotoma

Age-related macular degeneration in a randomized controlled trial of low-dose aspirin: Rationale and study design of the ASPREE-AMD study

Although aspirin therapy is used widely in older adults for prevention of cardiovascular disease, its impact on the incidence, progression and severity of age-related macular degeneration (AMD) is uncertain. The effect of low-dose aspirin on the course of AMD will be evaluated in this clinical trial. A sub-study of the ‘ASPirin in Reducing Events in the Elderly’ (ASPREE) trial, ASPREE-AMD is a 5-year follow-up double-blind, placebo-controlled, randomized trial of the effect of 100 mg daily aspirin on the course of AMD in 5000 subjects aged 70 years or older, with normal cognitive function and without cardiovascular disease at baseline. Non-mydriatic fundus photography will be performed at baseline, 3-year and 5-year follow-up to determine AMD status.The principal ASPREE study has been supported by the National Health and Medical Research Council, Australia (NHMRC) [grant #334047], the National Institutes of Health (NIH) through the National Institute on Aging [grant #RO1-AG029824], the Victorian Cancer Agency (Victorian Government, Australia) and Monash University

Multiallelic copy number variation in the complement component 4A (C4A) gene is associated with late-stage age-related macular degeneration (AMD)

Peer reviewedPublisher PD

Projection of long-term visual acuity outcomes based on initial treatment response in neovascular age-related macular degeneration

PURPOSE To explore various methods for assessing the early response to vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration and investigate their association with 3 year visual acuity (VA) outcomes. DESIGN Observational study from a prospectively collected registry. PARTICIPANTS Treatment-naïve eyes in the Fight Retinal Blindness! outcomes registry that commenced anti-VEGF therapy between 1st January 2007 and 1st March 2014 that received 3 anti-VEGF injections within the first 3 months. METHODS The early response was defined as occurring up until the 4th injection. Various early response metrics, which included both continuous and categorical variables, were explored: 1) achieving good VA (≥70 letters [20/40]), 2) absolute change in VA from baseline, 3) time to first grading of the choroidal neovascular lesion as inactive, 4) maximum rate of VA change between successive injections. MAIN OUTCOME MEASURES Proportion of eyes achieving ≥70 letters at 3 years. RESULTS This study included 2051 treatment-naïve eyes from 1828 patients. Achieving good vision at 3 years was significantly associated with 1) having good vision by the 4th injection (odds ratio [95% CI]: 9.8 [6.5, 14.7] for VA≥70 vs. VA5 letters) early VA gains (1.8 [1.2, 2.6], P = 0.002 and 1.8 [1.3, 2.5], P 3 injections), 4) gradual change (between -4 and 4 letters) or rapid (>5 letters) gains between successive injections (1.7 [1.1, 2.6], P = 0.015 and 1.6 [1.1, 2.3], P = 0.018 for gradual change and rapid gain vs. rapid loss). Eyes that achieved small or large early gains achieved similar vision at 3 years (65.0 and 64.7 letters respectively), and had better vision than eyes with early VA loss (57.2 letters). CONCLUSIONS Attainment of good vision by the 4th injection was strongly associated with 3 year visual outcomes, while other early response parameters had a moderate association. The early response during the initial 3 monthly loading doses can be a useful guide for subsequent treatment decisions

A deep learning framework for the detection and quantification of drusen and reticular pseudodrusen on optical coherence tomography

Purpose - To develop and validate a deep learning (DL) framework for the detection and quantification of drusen and reticular pseudodrusen (RPD) on optical coherence tomography scans. Design - Development and validation of deep learning models for classification and feature segmentation. Methods - A DL framework was developed consisting of a classification model and an out-of-distribution (OOD) detection model for the identification of ungradable scans; a classification model to identify scans with drusen or RPD; and an image segmentation model to independently segment lesions as RPD or drusen. Data were obtained from 1284 participants in the UK Biobank (UKBB) with a self-reported diagnosis of age-related macular degeneration (AMD) and 250 UKBB controls. Drusen and RPD were manually delineated by five retina specialists. The main outcome measures were sensitivity, specificity, area under the ROC curve (AUC), kappa, accuracy and intraclass correlation coefficient (ICC). Results - The classification models performed strongly at their respective tasks (0.95, 0.93, and 0.99 AUC, respectively, for the ungradable scans classifier, the OOD model, and the drusen and RPD classification model). The mean ICC for drusen and RPD area vs. graders was 0.74 and 0.61, respectively, compared with 0.69 and 0.68 for intergrader agreement. FROC curves showed that the model's sensitivity was close to human performance. Conclusions - The models achieved high classification and segmentation performance, similar to human performance. Application of this robust framework will further our understanding of RPD as a separate entity from drusen in both research and clinical settings.Comment: 26 pages, 7 figure

Clinical validation of a genetic model to estimate the risk of developing choroidal neovascular age-related macular degeneration

Predictive tests for estimating the risk of developing late-stage neovascular age-related macular degeneration (AMD) are subject to unique challenges. AMD prevalence increases with age, clinical phenotypes are heterogeneous and control collections are prone to high false-negative rates, as many control subjects are likely to develop disease with advancing age. Risk prediction tests have been presented previously, using up to ten genetic markers and a range of self-reported non-genetic variables such as body mass index (BMI) and smoking history. In order to maximise the accuracy of prediction for mainstream genetic testing, we sought to derive a test comparable in performance to earlier testing models but based purely on genetic markers, which are static through life and not subject to misreporting. We report a multicentre assessment of a larger panel of single nucleotide polymorphisms (SNPs) than previously analysed, to improve further the classification performance of a predictive test to estimate the risk of developing choroidal neovascular (CNV) disease. We developed a predictive model based solely on genetic markers and avoided inclusion of self-reported variables (eg smoking history) or non-static factors (BMI, education status) that might otherwise introduce inaccuracies in calculating individual risk estimates. We describe the performance of a test panel comprising 13 SNPs genotyped across a consolidated collection of four patient cohorts obtained from academic centres deemed appropriate for pooling. We report on predictive effect sizes and their classification performance. By incorporating multiple cohorts of homogeneous ethnic origin, we obtained >80 per cent power to detect differences in genetic variants observed between cases and controls. We focused our study on CNV, a subtype of advanced AMD associated with a severe and potentially treatable form of the disease. Lastly, we followed a two-stage strategy involving both test model development and test model validation to present estimates of classification performance anticipated in the larger clinical setting. The model contained nine SNPs tagging variants in the regulators of complement activation (RCA) locus spanning the complement factor H (CFH), complement factor H-related 4 (CFHR4), complement factor H-related 5 (CFHR5) and coagulation factor XIII B subunit (F13B) genes; the four remaining SNPs targeted polymorphisms in the complement component 2 (C2), complement factor B (CFB), complement component 3 (C3) and age-related maculopathy susceptibility protein 2 (ARMS2) genes. The pooled sample size (1,132 CNV cases, 822 controls) allowed for both model development and model validation to confirm the accuracy of risk prediction. At the validation stage, our test model yielded 82 per cent sensitivity and 63 per cent specificity, comparable with metrics reported with earlier testing models that included environmental risk factors. Our test had an area under the curve of 0.80, reflecting a modest improvement compared with tests reported with fewer SNPs