Health State Utility Values for Age-Related Macular Degeneration: Review and Advice

Health state utility values are a major source of uncertainty in economic evaluations of interventions for age-related macular degeneration (AMD). This review identifies and critiques published utility values and methods for eliciting de novo utility values in AMD. We describe how utility values have been used in healthcare decision making and provide guidance on the choice of utility values for future economic evaluations for AMD. Literature was searched using PubMed, and health technology assessments (HTA) were searched using HTA agency websites to identify articles reporting utility values or approaches to derive utility values in AMD and articles applying utilities for use in healthcare decision making relating to treatments for AMD. A total of 70 studies qualified for data extraction, 22 of which were classified as containing utility values and/or elicitation methods, and 48 were classified as using utility values in decision making. A large number of studies have elicited utility values for AMD, although those applied to decision making have focused on a few of these. There is an appreciation of the challenges in the measurement and valuation of health states, with recent studies addressing challenges such as the insensitivity of generic health-related quality of life (HRQoL) questionnaires and utility in the worse-seeing eye. We would encourage careful consideration when choosing utility values in decision making and an explicit critique of their applicability to the decision problem

Repeatability of swept-source optical coherence tomography retinal and choroidal thickness measurements in neovascular age-related macular degeneration

BACKGROUND: The aim was to determine the intrasession repeatability of swept-source optical coherence tomography (SS-OCT)-derived retinal and choroidal thickness measurements in eyes with neovascular age-related macular degeneration (nAMD). METHODS: A prospective study consisting of patients with active nAMD enrolled in the Distance of Choroid Study at Moorfields Eye Hospital, London. Patients underwent three 12×9 mm macular raster scans using the deep range imaging (DRI) OCT-1 SS-OCT (Topcon) device in a single imaging session. Retinal and choroidal thicknesses were calculated for the ETDRS macular subfields. Repeatability was calculated according to methods described by Bland and Altman. RESULTS: 39 eyes of 39 patients with nAMD were included with a mean (±SD) age of 73.9 (±7.2) years. The mean (±SD) retinal thickness of the central macular subfield was 225.7 μm (±12.4 μm). The repeatability this subfield, expressed as a percentage of the mean central macular subfield thickness, was 23.2%. The percentage repeatability of the other macular subfields ranged from 13.2% to 28.7%. The intrasession coefficient of repeatability of choroidal thickness of the central macular subfield was 57.2 μm with a mean choroidal thickness (±SD) of 181 μm (±15.8 μm). CONCLUSIONS: This study suggests that a change >23.2% of retinal thickness and 57.2 μm choroidal thickness in the central macular subfield is required to distinguish true clinical change from measurement variability when using the DRI OCT-1 device to manage patients with nAMD

Increased gastrin-releasing peptide (GRP) receptor expression in tumour cells confers sensitivity to [Arg6,D-Trp7,9,NmePhe8]-substance P (6-11)-induced growth inhibition.

[Arg(6),D-Trp(7,9),N(me)Phe(8)]-substance P (6-11) (SP-G) is a novel anticancer agent that has recently completed phase I clinical trials. SP-G inhibits mitogenic neuropeptide signal transduction and small cell lung cancer (SCLC) cell growth in vitro and in vivo. Using the SCLC cell line series GLC14, 16 and 19, derived from a single patient during the clinical course of their disease and the development of chemoresistance, it is shown that there was an increase in responsiveness to neuropeptides. This was paralleled by an increased sensitivity to SP-G. In a selected panel of tumour cell lines (SCLC, non-SCLC, ovarian, colorectal and pancreatic), the expression of the mitogenic neuropeptide receptors for vasopressin, gastrin-releasing peptide (GRP), bradykinin and gastrin was examined, and their sensitivity to SP-G tested in vitro and in vivo. The tumour cell lines displayed a range of sensitivity to SP-G (IC(50) values from 10.5 to 119 microM). The expression of the GRP receptor measured by reverse transcriptase-polymerase chain reaction, correlated significantly with growth inhibition by SP-G. Moreover, introduction of the GRP receptor into rat-1A fibroblasts markedly increased their sensitivity to SP-G. The measurement of receptor expression from biopsy samples by polymerase chain reaction could provide a suitable diagnostic test to predict efficacy to SP-G clinically. This strategy would be of potential benefit in neuropeptide receptor-expressing tumours in addition to SCLC, and in tumours that are relatively resistant to conventional chemotherapy

Cost-effectiveness of age-related macular degeneration study supplements in the UK: combined trial and real-world outcomes data

Aims To evaluate the cost-effectiveness of Age-Related Eye Disease Study (AREDS) 1 & 2 supplements in patients with either bilateral intermediate age-related macular degeneration, AREDS category 3, or unilateral neovascular age-related macular degeneration AMD (nAMD), AREDS category 4. Methods A patient-level health state transition model based on levels of visual acuity in the better-seeing eye was constructed to simulate the costs and consequences of patients taking AREDS vitamin supplements. Setting: UK National Health Service (NHS). The model was populated with data from AREDS and real-world outcomes and resource use from a prospective multicentre national nAMD database study containing 92 976 ranibizumab treatment episodes. Interventions Two treatment approaches were compared: immediate intervention with AREDS supplements or no supplements. Main outcome measures: quality-adjusted life years (QALYs) and healthcare costs were accrued for each strategy, and incremental costs and QALYs were calculated for the lifetime of the patient. One-way and probabilistic sensitivity analyses were employed to test the uncertainty of the model. Results For AREDS category 3, the incremental cost-effectiveness ratio was £30 197. For AREDS category 4 compared with no intervention, AREDS supplements are more effective (10.59 vs 10.43 QALYs) and less costly (£52 074 vs 54 900) over the lifetime of the patient. Conclusions The recommendation to publicly fund AREDS supplements to category 3 patients would depend on the healthcare system willingness to pay. In contrast, initiating AREDS supplements in AREDS category 4 patients is both cost saving and more effective than no supplement use and should therefore be considered in public health policy

Characterizing Natural User Interface with Wearable Smart Watches

Background - The emergence of new interaction paradigms makes the use of technology inrealizing the users??? natural ways of exploring the real world the ultimate goal of designers today.Research on interactive and immersive technologies for user interface design is still a challenging chore for engineers and scientists when it comes to designing natural interaction for wearable smart devices. To address the challenge, our study aims to develop guidelines for design practitioners in designing wearable smart watches that could offer natural user experiences. Methods - To better understand natural user experiences with smart watches, an extensive literature review was conducted. A quantitative survey with 80 participants was conducted, of which the focus was on the expected functions of smart watches. Based on the survey results, we selected eight participants in terms of technology familiarity. To achieve the objectives of our research, three studies were conducted: a design workshop (Study 1), a cultural probe (Study 2), and a focus group interview (Study 3). The design workshop was created to figure out the needs and wishes people have forsmart watches. In the cultural probe, the focus was on figuring out natural interactions with smart watches. Finally, the focus group interview aimed to gain more insights from the results of the cultural probe in terms of natural user interaction with particular functions. Results - To address the needs and wishes of the users toward wearable smartwatches, we made a subdivision into three categories, such as functions, input measures, and notification (feedback) methods. According to the results, participants wanted weather notification, health monitoring, and identification as expected functions. Regarding the methodof input, voice command and touch screen were preferred. In order to get feedback, most of the participantswanted vibrations, particularly as a reaction tocompleting the commands or inputs. There was also a suggestion to customize their smart watch. For example, users can select the functions and build their own command system, and even choose the notificationmethods. Considering natural user interface with respect to functions (weather, answering a call, navigation, health monitoring, taking a picture and messaging), specific natural user interfaces were mentioned for particular functions. Conclusions - Throughout the study, people???s needs and wishes and their perceptions about natural interaction were identified and the characteristics of natural user interfacesweredetermined. Based on the results, tenperceptions were specifically defined to provide a better understanding of smart watches in terms of natural interaction: user affinity of form, awareness by familiarity, reality correspondence, behavioral extension, purpose orientation, easiness of performance, timeliness, routine acceptance, generality, and rule of thumb. In addition to that, natural user interfaces were categorized into five groups: user familiarity, realistic interaction, accomplishment assistance, contextual appropriateness, and social awareness. In this study,we tried to identify what constitutes anatural interaction and how it should be created. The limitations and further study are discussed at the end.ope

Modelling Cost Effectiveness in Neovascular Age-Related Macular Degeneration: The Impact of Using Contrast Sensitivity vs. Visual Acuity.

The cost utility of treatments of age-related macular degeneration (AMD) is commonly assessed using health state transition models defined by levels of visual acuity. However, there is evidence that another measure of visual function, contrast sensitivity, may be better associated with utility than visual acuity. This paper investigates the difference in cost effectiveness resulting from models based on visual acuity and contrast sensitivity using the example of bevacizumab (Avastin) for neovascular AMD. The implications of the choice of outcome on structural uncertainty in the model are investigated

Progression of Retinopathy Secondary to Maternally Inherited Diabetes and Deafness – Evaluation of Predicting Parameters

PURPOSE: To investigate the prognostic value of demographic, functional, and imaging parameters on retinal pigment epithelium (RPE) atrophy progression secondary to Maternally Inherited Diabetes and Deafness (MIDD) and to evaluate the application of these factors in clinical trial design. DESIGN: Retrospective observational case series. METHODS: Thirty-five eyes of 20 patients (age range, 24.9-75.9 years) with genetically proven MIDD and demarcated RPE atrophy on serial fundus autofluorescence (AF) images were included. Lesion size and shape-descriptive parameters were longitudinally determined by two independent readers. A linear mixed effect model was used to predict the lesion enlargement rate based on baseline variables. Sample size calculations were performed to model the power in a simulated interventional study. RESULTS: The mean follow-up time was 4.27 years. The mean progression rate of RPE atrophy was 2.33 mm2/year revealing a dependence on baseline lesion size (+0.04 [0.02-0.07] mm2/year/mm2, p<0.001), which was absent after square root transformation. The fovea was preserved in the majority of patients during the observation time. In the case of foveal involvement, the loss of visual acuity lagged behind central RPE atrophy in AF images. Sex, age, and number of atrophic foci predicted future progression rates with a cross-validated mean absolute error of 0.13 mm/year and to reduce the required sample size for simulated interventional trials. CONCLUSIONS: Progressive RPE atrophy could be traced in all eyes using AF imaging. Shape-descriptive factors and patients' baseline characteristics had significant prognostic value, guiding appropriate subject selection and sample size in future interventional trial design

Characteristics and racial variations of polypoidal choroidal vasculopathy in tertiary centers in the United States and United Kingdom

PURPOSE: To evaluate the characteristics and racial variations amongst patients with polypoidal choroidal vasculopathy (PCV) in the United States and the United Kingdom. METHODS: Fundus photos and indocyanine green angiography images were evaluated in a multicenter retrospective study to establish the diagnosis of PCV. Visual acuity (VA) was recorded in ETDRS letter count. RESULTS: Eighty eyes of 71 PCV patients (average age of 69.4 ± 10.4 years) were included in the analysis. Of the total 71 subjects, 46 (65%) were women, 33 (46.5%) were Blacks, 16 (22.5%) were Whites, 19 (26.8%) were Asians and 3 (4.2%) belonged to other races. The Black subgroup had vision gain of 3.5 letters. The White and Asian subgroups had vision loss of 13.1 and 3.5 letters, respectively. There was female predominance in Blacks (67%), Whites (69%), and Asians (58%). PCV was found to be a bilateral disease in 14 patients (20%). There was significant decrease of 7 letters with every decade increase in age (p = 0.005). Final VA was worse in males when compared to females (p = 0.042), and worse in Whites when compared to Blacks (p = 0.005). For every 10 letters worse in initial VA upon diagnosis with PCV, the final VA was worse by 6 letters (p < 0.001). The location of the polypoidal lesion within the macula was associated with significant decrease of 14 letters in BCVA (p = 0.02). The length of follow up was significantly associated with worse visual outcome (p = 0.012). Final VA had no significant correlation with the lens status, or the different treatment modalities. CONCLUSIONS: Based on our cohort from tertiary centers in the United States and United Kingdom, PCV is a bilateral disease in one-fifth of patients. It features a variable female predominance based on ethnicity. Increased age, worse vision upon initial presentation, longer follow up and macular location of the polyp were associated with worse visual outcome

Foveal structure and visual function in nanophthalmos and posterior microphthalmos

Background/aims: The reason for visual impairment in patients with nanophthalmos and posterior microphthalmos is not completely understood. Therefore, this study aims to investigate foveal structure, and the impact of demographic, clinical and imaging parameters on best-corrected visual acuity (BCVA) in these conditions. Methods: Sixty-two eyes of 33 patients with nanophthalmos (n=40) or posterior microphthalmos (n=22), and 114 eyes of healthy controls with high-resolution retinal imaging including spectral-domain or swept-source optical coherence tomography images were included in this cross-sectional case-control study. Foveal retinal layer thickness was determined by two independent readers. A mixed-effect model was used to perform structure-function correlations and predict the BCVA based on subject-specific variables. Results: Most patients (28/33) had altered foveal structure associated with loss of foveal avascular zone and impaired BCVA. However, widening of outer nuclear layer, lengthening of photoreceptor outer segments, normal distribution of macular pigment and presence of Henle fibres were consistently found. Apart from the presence of choroidal effusion, which had significant impact on BCVA, the features age, refractive error, axial length and retinal layer thickness at the foveal centre explained 61.7% of the variability of BCVA. Conclusion: This study demonstrates that choroidal effusion, age, refractive error, axial length and retinal layer thickness are responsible for the majority of interindividual variability of BCVA as well as the morphological foveal heterogeneity in patients with nanophthalmos or posterior microphthalmos. This might give further insights into the physiology of foveal development and the process of emmetropisation, and support clinicians in the assessment of these disease entities