Quality of life and health economic assessments of age-related macular degeneration

In this article, we review measures of patient-reported outcomes that can show whether a treatment for age-related macular degeneration also provides patient-perceived benefits. In addition, we look at health economic measurements currently being used to develop cost-effectiveness models for age-related macular degeneration.     

生命质量及其在年龄相关性黄斑变性研究中的应用进展

生活质量评价是全面评价疾病及治疗对患者造成的生理、心理和社会生活等方面的影响,对于全面认识年龄相关性黄斑变性具有极其重要的意义。年龄相关性黄斑变性是慢性影响50岁以上人群视功能障碍的主要原因,不仅严重影响老年人群的视功能,同时影响老年人群的社会功能、情感及情绪。我们就目前国内外开展相关研究作一简要综述。     

Multimodal evaluation of macular function in age-related macular degeneration

Objective

To evaluate macular function using multimodality in eyes with age-related macular degeneration (AMD) at various stages.

Methods

Macular function in 20 control eyes (20 subjects), 17 eyes (17 patients) with large drusen, 18 eyes (18 patients) with drusenoid pigment epithelial detachment (PED), and 19 eyes (19 patients) with neovascular AMD was examined using a Landolt chart for visual acuity; retinal sensitivity was measured by microperimetry; and focal macular electroretinography (fmERG) was performed. In all of these eyes, retinal morphology was examined using optical coherence tomography.

Results

Eyes with neovascular AMD showed morphologic changes in the neurosensory retina as well as marked deterioration of macular function in all parameters measured with a Landolt chart, fmERG, and microperimetry. Eyes with large drusen showed only minimal morphologic changes in the neurosensory retina. In this large drusen group, although retinal sensitivity at the central point was significantly decreased (P = 0.0063), the other parameters of macular function were well preserved. In eyes with drusenoid PED, the structure of the neurosensory retina was well preserved, while the foveal thickness was significantly increased (P = 0.013). The macular function of these eyes was significantly deteriorated, with the VA, amplitude of the a-wave and b-wave, and retinal sensitivity being markedly decreased. In addition, the area of PED correlated with the latency of the a-wave and b-wave and with the retinal sensitivity within the central 4° or 8° region.

Conclusion

Multimodal evaluation demonstrated a significant decrease in macular function in drusenoid PED and in neovascular AMD.     

Quality of life in patients with age-related macular degeneration: results from the VISION study

PURPOSE: To assess the impact of treatment with pegaptanib sodium vsusual care on vision-related quality of life (VRQoL) in patients with age-related macular degeneration (AMD). METHODS: VRQoL was a secondary end point in the trial, a prospective, randomized, double-masked, multicentre, dose-ranging study. Three doses of pegaptanib (0.3, 1, and 3 mg) were compared with usual care with respect to changes in VRQoL as indicated by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25), administered at baseline and weeks 30 and 54. Four of the NEI-VFQ 25 domains were prospectively designated as primary: near vision, distance vision, role limitations, and dependency. Between-group differences were assessed using an analysis of covariance model with age, gender, and baseline score as covariates. RESULTS: NEI-VFQ 25 data were available for 569 subjects. At week 54, improvements in the distance vision and role limitations domains were greater in pegaptanib than usual care arms. No substantial increase in ocular pain was noted in pegaptanib-treated patients. No clear superiority of any particular dosage strength of pegaptanib was demonstrated, and no significant differences or trends favoured usual care on any domain score or the NEI-VFQ 25 composite score. The greatest VRQoL benefit was seen in responders (lost<3 lines) to treatment. CONCLUSION: The VISION trial provided evidence of trends in quality-of-life benefit associated with effective treatment of AMD using pegaptanib. Treatment with pegaptanib is expected to contribute significantly to VRQoL improvement for responder patients.     

Mechanisms of age-related macular degeneration

AMD is a poorly understood disease at this time. Since it is the leading cause of blindness in the elderly in the developed world, there is a pressing need for better treatment. Therefore, there is extensive ongoing research in both pathogenesis and therapy of AMD. Epidemiological studies have shown significant risk associated with increasing age and cigarette smoking, future studies may identify environmental risk factors though at present studies have been inconclusive. Genetic studies may identify subgroups of disease and thus help provide a selective approach to treatment. The vascular model of AMD may provide better understanding of the blood flow and post capillary resistance and help in early and newer intervention in the disease. Vascular endothelial growth factor has been extensively studied in choroidal neovascularization. It has been demonstrated in human and animal models of CNV and VEGF antagonists are currently in clinical trial. Extensive work is ongoing to prevent and treat CNV with antiangiogenic agents.     

Genetics of age-related macular degeneration

Gene discoveries will lead to more effective them pies for AMD by identifying specific underlying disease mechanisms that might be corrected by drugs or gene therapy. For example, investigations are currently being carried out using pigment epithelium-derived factor (FEDF). The gene for this potent inhibitor of angiogenesis has been incorporated into an adenoviral vector and delivered into the eye by intravitreal injection to inhibit growth of new blood vessels in eyes with neovascular AMD. In the future, as the genetics of this complex disease are unraveled, more effective treatments and preventative measures that target specific molecular defects underlying the development of AMD can be expected.     

Pathophysiology of age-related macular degeneration

The clinical and histopathological features of age-related macular degeneration (AMD) include a relationship with age, and the presence of pigmentary disturbances, drusen, thickening of Bruch's membrane, and basal laminar deposits. AMD is an advanced stage of a deteriorative process that takes place in all eyes. The primary lesion in AMD appears to reside in the retinal pigment epithelium (RPE), possibly resulting from its high rate of molecular degradation. Beginning early in life, and continuing throughout the life span, cells of the RPE gradually accumulate sacs of molecular debris. These residual bodies (lipofuscin) are remnants of the incomplete degradation of abnormal molecules which have been damaged within the RPE cells or derived from phagocytized rod and cone membranes. Progressive engorgement of RPE cells with these functionless residues is associated with the extrusion of aberrant materials which accumulate in Bruch's membrane and aggregate in the form of drusen and basal laminar deposits. These excretions contribute to the further deterioration of the RPE. Loss of vision results from death of visual cells due to degeneration of RPE cells, or the effects of leakage from neovascular membranes that invade the region of abnormal extracellular deposits.     

Prevalence of age-related macular degeneration

Early and late age-related macular degeneration (AMD) have a high prevalence in elderly patients but may be differentiated by medical or environmental factors, eg, hypertension, geographic area, or antioxidant agents. Because nuclear sclerotic cataract is associated with AMD both aging changes may share a common pathogenesis. The genetic predisposition for AMD is indicated by the identical appearance in monozygotic twins, but genetics may be also important for the explanation of the low incidence of late AMD in black individuals. Specific ocular characteristics like light or depigmented iris color, prolonged dark adaptation, and decreased foveal flicker sensitivity are also risk factors for AMD. Early AMD characteristics with high risk for late AMD are confluent drusen, focal hyperpigmentation, or atrophy and slow choroidal fluorescein filling. Therefore specific genetic, environmental, medical, and ocular characteristics determine the individual appearance and progress of AMD. The knowledge of these factors may result in new prophylactic and specific treatments for AMD.     

年龄相关性黄斑变性的遗传学研究

年龄相关性黄斑变性是一类多因子遗传性疾病,其发生可能是遗传因素和环境因素综合作用的结果。这类复杂遗传模式疾病存在着基因型和表现型之间的非共线性,使得对这类疾病的病因分析比较困难。本文从双生子研究、家系研究、人种研究、致病基因研究等角度介绍年龄相关性黄斑变性的遗传学研究进展。     

Mimickers of age-related macular degeneration

In the Western World, the leading cause of irreversible blindness is Age- Related Macular Degeneration (ARMD). It can have significant visual impairment, and it is important that the practicing ophthalmologist is knowledgeable in the diagnosis and treatment of ARMD. Equally important is knowledge in the diagnosis of other disease entities that may mimic ARMD, as this may change the prognosis, treatment and visual outcome of patients. This article discusses those diseases that mimic ARMD and their distinguishing features.     

Prevention of age-related macular degeneration

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula.     

Vision-related quality of life in patients suffering from age-related macular degeneration

PURPOSE: To evaluate the relative impact of best and worst eye on vision-related quality of life in patients suffering from age-related macular degeneration (AMD). DESIGN: Quality of life and visual acuity data were collected at baseline during a randomized clinical trial. METHODS: SETTING: Multicenter (11 centers), international study. PATIENTS: One hundred fourteen patients with a diagnosis of exudative AMD and primary or recurrent subfoveal neovascular membrane (greatest linear dimension of lesion < or =5400 microm; > or =50% of the total lesion was choroidal neovascularization (CNV); classic component of the total CNV > or = 1.0 mm(2)). All patients were over age 50 years, of any race, either sex. INTERVENTION OR OBSERVATION PROCEDURE: NEI-VFQ-39 questionnaire administered to patients at home by trained telephone interviewers. MAIN OUTCOME MEASURES: ETDRS visual acuity (VA) was measured in both eyes separately. Vision-related quality of life (QoL) was assessed using the NEI-VFQ-39. An analysis of variance was performed on the NEI-VFQ scores, including best eye VA (VA > 20/40 vs VA < or = 20/40), worst eye VA (VA > 20/200 vs VA < or = 20/200), and the interaction between the two as independent variables. RESULTS: Best eye VA was 0.34 on average, with VA > 20/40 in 43.0% of patients. Worst eye VA was 0.85 on average, with VA > 20/200 in 32.5% of patients. VA was not linked to general health and ocular pain scores. General Vision, Near Activities, Distance Vision, Driving, Mental Health, Role Difficulties, Dependency, Peripheral Vision, and the Global NEI-VFQ scores were affected by both best eye VA and worst eye VA. CONCLUSION: In the study sample, worst eye VA (< or =20/200) and best eye VA (< or =20/40) contributed independently to vision-related QoL. These results suggest that preserving a minimal visual acuity in the worst eye may contribute to vision-related quality of life.