Ophthalmology (Eye & Ear Hospital) - Research Publications
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ItemNo Preview AvailableCan HMG Co-A reductase inhibitors ("statins") slow the progression of age-related macular degeneration? The Age-Related Maculopathy Statin Study (ARMSS)(DOVE MEDICAL PRESS LTD, 2008)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.
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ItemCost-effectiveness of ranibizumab for neovascular age-related macular degeneration.(Springer Science and Business Media LLC, 2008-06-24)BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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ItemNovel measures of cardiovascular health and its association with prevalence and progression of age-related macular degeneration: the CHARM study(BMC, 2008)BACKGROUND: To determine if novel measures of cardiovascular health are associated with prevalence or progression of age-related macular degeneration (AMD). METHODS: Measures of the cardiovascular system: included intima media thickness (IMT), pulse wave velocity (PWV), systemic arterial compliance (SAC), carotid augmentation index (AI). For the prevalence study, hospital-based AMD cases and population-based age- and gender-matched controls with no signs of AMD in either eye were enrolled. For the progression component, participants with early AMD were recruited from two previous studies; cases were defined as progression in one or both eyes and controls were defined as no progression in either eye. RESULTS: 160 cases and 160 controls were included in the prevalence component. The upper two quartiles of SAC, implying good cardiovascular health, were significantly associated with increased risk of AMD (OR = 2.54, 95% CL = 1.29, 4.99). High PWV was associated with increased prevalent AMD. Progression was observed in 82 (32.3%) of the 254 subjects recruited for the progression component. Higher AI (worse cardiovascular function) was protective for AMD progression (OR = 0.30, 95%CL = 0.13, 0.69). Higher aortic PWV was associated with increased risk of AMD progression; the highest risk was seen with the second lowest velocity (OR = 6.22, 95% CL = 2.35, 16.46). CONCLUSION: The results were unexpected in that better cardiovascular health was associated with increased risk of prevalent AMD and progression. Inconsistent findings between the prevalence and progression components could be due to truly different disease etiologies or to spurious findings, as can occur with inherent biases in case control studies of prevalence. Further investigation of these non-invasive methods of characterizing the cardiovascular system should be undertaken as they may help to further elucidate the role of the cardiovascular system in the etiology of prevalent AMD and progression.
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ItemCost-effectiveness of smoking cessation to prevent age-related macular degeneration.(Springer Science and Business Media LLC, 2008-09-11)BACKGROUND: Tobacco smoking is a risk factor for age-related macular degeneration, but studies of ex-smokers suggest quitting can reduce the risk. METHODS: 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. RESULTS: 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. CONCLUSION: Smoking cessation is unequivocally cost-effective in terms of its impact on age-related macular degeneration outcomes alone.
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ItemCholesterol-lowering medications reduce the risk of age-related maculopathy progression(Australasian Medical Publishing, 2001-09)Age-related macular degeneration (AMD) is the leading cause of blindness in elderly Australians. Currently, there are limited treatment options, and current research efforts are focused on determining the risk factors for AMD and developing effective treatment strategies. Some risk factors for cardiovascular disease have been shown to be associated with AMD, and one study has suggested that Alzheimer's disease is associated with age-related maculopathy. It has also been suggested that alleles of the apolipoprotein E (ApoE) gene may be associated with AMD, cardiovascular disease and Alzheimer's disease. Given this, it is interesting that statins - cholesterol-lowering medications - have been shown to decrease the risk of dementia and diabetes mellitus.
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ItemNo Preview AvailableAnalysis of the EFEMP1 gene in individuals and families with early onset drusen(Nature Publishing Group, 2005-01)Aims Age-related macular degeneration (AMD) is considered a complex genetic disease, although the genetic influences are not yet fully understood. Genetic analysis is hampered by the late onset of disease and the difficulty in obtaining multigenerational families. To investigate this problem further we studied our population of early onset drusen cases. The Arg345Trp mutation on exon 10 of the EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) gene causes two clinical phenotypes of early onset drusen (Doyne honeycomb retinal dystrophy and Malattia Leventinese), yet does not appear to be involved in other early onset drusen phenotypes or typical AMD. We wished to ascertain the involvement of the EFEMP1 gene in our population of sporadic and familial subjects presenting with early onset drusen! and t heir affected relatives.Methods Individuals presenting with drusen/end-stage maculopathy at 60 years or under were identified from retinal clinics in Melbourne. All available first- and second-degree relatives were also examined. In all, 116 ethnically matched controls were collected from the same community for comparison.Results Single stranded conformational polymorphism (SSCP) analysis and subsequent sequencing revealed four previously described and three novel sequence variations. Most occurred at similar frequencies in the case and control populations and were not thought to be disease associated.ConclusionThe term early onset drusen encompasses a wide range of phenotypes and our findings indicate that it is likely that more than one gene is involved in its causation. It is essential that these clinical phenotypes are well described and categorised to allow greater possibility! of su ccess in the search for other disease genes.