The clinical effectiveness and cost-effectiveness of screening for open angle glaucoma: a systematic review and economic evaluation

Health Services Research Unit, Institute of Applied Health Sciences, University of Aberdeen, UK.
Health technology assessment (Winchester, England) (Impact Factor: 5.12). 11/2007; 11(41):iii-iv, ix-x, 1-190. DOI: 10.3310/hta11410
Source: PubMed

ABSTRACT To assess whether open angle glaucoma (OAG) screening meets the UK National Screening Committee criteria, to compare screening strategies with case finding, to estimate test parameters, to model estimates of cost and cost-effectiveness, and to identify areas for future research.
Major electronic databases were searched up to December 2005.
Screening strategies were developed by wide consultation. Markov submodels were developed to represent screening strategies. Parameter estimates were determined by systematic reviews of epidemiology, economic evaluations of screening, and effectiveness (test accuracy, screening and treatment). Tailored highly sensitive electronic searches were undertaken.
Most potential screening tests reviewed had an estimated specificity of 85% or higher. No test was clearly most accurate, with only a few, heterogeneous studies for each test. No randomised controlled trials (RCTs) of screening were identified. Based on two treatment RCTs, early treatment reduces the risk of progression. Extrapolating from this, and assuming accelerated progression with advancing disease severity, without treatment the mean time to blindness in at least one eye was approximately 23 years, compared to 35 years with treatment. Prevalence would have to be about 3-4% in 40 year olds with a screening interval of 10 years to approach cost-effectiveness. It is predicted that screening might be cost-effective in a 50-year-old cohort at a prevalence of 4% with a 10-year screening interval. General population screening at any age, thus, appears not to be cost-effective. Selective screening of groups with higher prevalence (family history, black ethnicity) might be worthwhile, although this would only cover 6% of the population. Extension to include other at-risk cohorts (e.g. myopia and diabetes) would include 37% of the general population, but the prevalence is then too low for screening to be considered cost-effective. Screening using a test with initial automated classification followed by assessment by a specialised optometrist, for test positives, was more cost-effective than initial specialised optometric assessment. The cost-effectiveness of the screening programme was highly sensitive to the perspective on costs (NHS or societal). In the base-case model, the NHS costs of visual impairment were estimated as 669 pounds. If annual societal costs were 8800 pounds, then screening might be considered cost-effective for a 40-year-old cohort with 1% OAG prevalence assuming a willingness to pay of 30,000 pounds per quality-adjusted life-year. Of lesser importance were changes to estimates of attendance for sight tests, incidence of OAG, rate of progression and utility values for each stage of OAG severity. Cost-effectiveness was not particularly sensitive to the accuracy of screening tests within the ranges observed. However, a highly specific test is required to reduce large numbers of false-positive referrals. The findings that population screening is unlikely to be cost-effective are based on an economic model whose parameter estimates have considerable uncertainty. In particular, if rate of progression and/or costs of visual impairment are higher than estimated then screening could be cost-effective.
While population screening is not cost-effective, the targeted screening of high-risk groups may be. Procedures for identifying those at risk, for quality assuring the programme, as well as adequate service provision for those screened positive would all be needed. Glaucoma detection can be improved by increasing attendance for eye examination, and improving the performance of current testing by either refining practice or adding in a technology-based first assessment, the latter being the more cost-effective option. This has implications for any future organisational changes in community eye-care services. Further research should aim to develop and provide quality data to populate the economic model, by conducting a feasibility study of interventions to improve detection, by obtaining further data on costs of blindness, risk of progression and health outcomes, and by conducting an RCT of interventions to improve the uptake of glaucoma testing.

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Available from: Rodolfo Hernández, Aug 23, 2015
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    • "Cell Tissue Res Fig. 2 a Selected loss of visual function at the foveal location in subjects with glaucoma (n=15). The subgroups are labelled as mild, moderate and severe based on each subject's glaucoma stage (categories derived from their performance on the Humphrey Field Analyzer [HFA] SITA Standard 24–2, according to a method of glaucoma staging based on the global index mean deviation [MD]; Burr et al. 2007). The percentages of subjects that showed loss of visual sensitivity at the fovea for each of the stimulus attributes indicated in the legend are presented for each of the glaucoma stage subgroups. "
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    ABSTRACT: The effects of glaucoma on binocular visual sensitivity for the detection of various stimulus attributes are investigated at the fovea and in four paracentral retinal regions. The study employed a number of visual stimuli designed to isolate the processing of various stimulus attributes. We measured absolute contrast detection thresholds and functional contrast sensitivity by using Landolt ring stimuli. This psychophysical Landolt C-based contrast test of detection and gap discrimination allowed us to test parafoveally at 6 ° from fixation and foveally by employing interleaved testing locations. First-order motion perception was examined by using moving stimuli embedded in static luminance contrast noise. Red/green (RG) and yellow/blue (YB) colour thresholds were measured with the Colour Assessment and Diagnosis (CAD) test, which utilises random dynamic luminance contrast noise (± 45 %) to ensure that only colour and not luminance signals are available for target detection. Subjects were normal controls (n = 65) and glaucoma patients with binocular visual field defects (n = 15) classified based on their Humphrey Field Analyzer mean deviation (MD) scores. The impairment of visual function varied depending on the stimulus attribute and location tested. Progression of loss was noted for all tests as the degree of glaucoma increased. For subjects with mild glaucoma (MD -0.01 dB to -6.00 dB) significantly more data points fell outside the normal age-representative range for RG colour thresholds than for any other visual test, followed by motion thresholds. This was particularly the case for the parafoveal data compared with the foveal data. Thus, a multifaceted measure of binocular visual performance, incorporating RG colour and motion test at multiple locations, might provide a better index for comparison with quality of life measures in glaucoma.
    Cell and Tissue Research 06/2013; DOI:10.1007/s00441-013-1675-x · 3.33 Impact Factor
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    • "No single testing modality is sufficient to discriminate persons with and without glaucoma. The estimates of the sensitivity and specificity of glaucoma tests are also subject to extensive variability (Tuulonen et al. 2003; Burr et al. 2007). "
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    ABSTRACT: Introduction: Glaucoma is a progressive optic neuropathy associated with neural rim loss of the optic disc and the retinal nerve fibre layer typically causing visual field (VF) deterioration. Generally, glaucomatous lesions in the eye and in the visual field progress slowly over the years. In population-based cross-sectional studies, the percentage of unilateral or bilateral visual impairment varied between 3-12%. In screening studies, 0.03-2.4% of patients have been found to suffer visual impairment. Glaucoma has previously been associated with substantial healthcare costs and resource consumption attributable to the treatment of the disease. The disease also causes reduction in health-related quality of life (HRQoL) in patients with glaucoma. Objective and Methods: This study compares patients with diagnosed open-angle glaucoma from two geographically different regions in Finland. A total of 168 patients were examined, 85 subjects from an area with higher per patient treatment costs (Oulu) and 83 patients from a region with lower per patient treatment costs (Turku). All patients had a history of continuous glaucoma medication use for a period of 11 years. For each patient, the total direct costs from glaucoma treatment were calculated and the total amount of resource consumption was determined from registries and patient records. Each patient underwent a clinical examination with visual field assessment and fundus photography. These data were used to determine the current stage of disease for each patient. Health-related quality of life questionnaire (15D) was used in determining each patient's subjective HRQoL score. Results: When applying the current diagnostic criteria for open-angle glaucoma, a total of 40% of patients did not to display any structural or functional damage suggesting glaucoma after 11 years of continuous medical treatment and follow-up. Patients with higher glaucoma stage (worse disease) were found to have statistically higher treatment costs compared with those at lower disease stages. Resource consumption was also greater in the patients in higher glaucoma stage. Patients in the Oulu district consumed more resources, and glaucoma treatment was more expensive than in the Turku area. The total treatment cost in Oulu and Turku was 6010 € and 4452 €, respectively, for the whole 11-year period. There was no statistically significant difference in quality-of-life scores between the two areas. No difference was noted between the higher-spending and lower-spending areas in this respect. However, when the population was analysed as a whole, patients with higher glaucoma stage were found to have lower vision-based 15D scores compared with those at lower disease stages. This observation was made also at both districts independently. Conclusions: Major cost source in open-angle glaucoma treatment is medication, up to 74% of annual costs. In addition, it seems that higher resource consumption and higher treatment costs do not increase the patients' HRQoL as assessed by the 15D instrument.
    Acta ophthalmologica 05/2013; 91(thesis3):1-47. DOI:10.1111/aos.12141 · 2.51 Impact Factor
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    • "We already know that glaucoma represents a huge health problem (Quigley & Broman 2006), and there is also proof of the advantages that treatment has to offer (CNTGSG, 1998; Heijl et al. 2002; Kass et al. 2002; Leske et al. 2003). Furthermore, it has been suggested that glaucoma screening might be cost-effective if high-risk groups are targeted, even if studies have shown that general population screening is not beneficial in relation to cost (Burr et al. 2007; Vaahtoranta- Lehtonen et al. 2007; Hernandez et al. 2008; Tuulonen 2011). However, further research is needed to clarify this matter. "
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    ABSTRACT: This thesis addresses several aspects of glaucoma diagnostics from both a clinical and a screening perspective. New instruments for diagnosing glaucoma have been developed over the past years, but little information is available regarding their performance as screening methods and their usefulness in ordinary clinical practice. Purpose of the research underlying this thesis: The objectives of this research were as follows: to compare the accuracy of results of analysis of the optic nerve head (ONH) achieved by computerized imaging using the Heidelberg Retina Tomograph (HRT) and by subjective assessment performed by physicians with different degrees of experience of glaucoma (paper III); to evaluate the effect of a continuous medical education (CME) lecture on subjective assessment of the ONH for diagnosis of glaucoma (paper II); to investigate subjective assessment of perimetric test results by physicians with varying knowledge of glaucoma with a trained artificial neural network (ANN) and to compare the certainty of the classifications (paper IV); and to compare the diagnostic performance of time-domain Stratus optical coherence tomography (OCT) with that of spectral-domain Cirrus OCT (paper I), frequency doubling technology (FDT) screening perimetry and scanning laser polarimetry with the GDx variable corneal compensator (VCC) in a random population-based sample and in patients with glaucoma of varying disease severity. Methods and results: In evaluation of the ONH, use of the HRT statistical tools, Moorfields regression analysis (MRA) and the Glaucoma Probability Score (GPS) was compared with subjective assessment performed by 45 physicians. Optic nerve head images and photographs from 138 healthy and 97 glaucoma subjects were included. The sensitivity of MRA was higher (87-94%) than that of the average physician (62-82%), considerably greater than that of ophthalmologists with subspecialties other than glaucoma (53-77%) and non-significantly better than that of glaucoma experts (72-88%). Sensitivity achieved by GPS (79-93%) was also greater than that of the average physician. MRA correctly classified all eyes with advanced glaucomatous visual field defects, a result that was not achieved by GPS or even by the glaucoma experts. In eyes with small discs, MRA sensitivity (88%) was comparable with that of glaucoma experts (85%) and much better than that of GPS (50%). Also, the group comprising all physicians provided specificity (75-92%) similar to that of both MRA (69 - 86%) and GPS (72-94%) (Andersson et al. 2011a). A 1-hr CME lecture on ONH assessment led to a significant improvement in sensitivity (from 70% to 80%) and a significant decrease in uncertain assessments (from 22% to 13%), whereas specificity remained unchanged (68%) (Andersson et al. 2011b). A rise in sensitivity was seen in all subgroups of physicians, including glaucoma experts. Thirty physicians assessing standard automated perimetry (SAP) test results as Humphrey Field Analyzer single-field analysis printouts with full StatPac information from 99 patients with glaucoma and 66 healthy subjects were compared with a trained ANN regarding diagnostic performance. ANN reached significantly higher sensitivity (93%) than the average physician (83%), whereas specificity was similar for these two groups (91% and 90%, respectively). Diagnostic accuracy was similar among the different groups of physicians and seemingly rather independent of experience. Sensitivity ranged from 82% in the subgroup of other subspecialists to 87% in the glaucoma expert group, and specificity ranged from 88% among general ophthalmologists to 91% for glaucoma experts. The ANN attained certainty of classification that was in parity with that provided by the glaucoma experts and did not make any completely incorrect classifications of the visual fields (i.e. erroneous classifications were in the borderline zone) (Andersson et al. 2012). From a population-based randomly selected sample (n = 308) of older subjects (aged ≥50 years) living in southern Sweden, 170 subjects underwent a comprehensive examination that included Stratus OCT, Cirrus OCT, an FDT screening programme and the GDx VCC. The same test protocol was applied to 138 randomized clinical patients with different stages of glaucoma. In the population-based sample, both Stratus and Cirrus OCT showed high diagnostic accuracy with area under the receiver-operating curve (aROC) values close to 1.0 (Bengtsson et al. 2012). Both OCT instruments correctly classified all of the clinical glaucoma patients with advanced disease. FDT screening showed high sensitivity (91%) but erroneously gave normal test results for some eyes with advanced disease. GDx VCC had lower sensitivity (73-92%) and also led to a large proportion of examinations with an atypical retardation pattern that is known to affect the diagnostic efficiency of this instrument. Conclusions: The HRT MRA performed better than most physicians and was consistent with the glaucoma experts. These results suggest that MRA can be a valuable tool for diagnosing glaucoma in ordinary practice, particularly when only a few glaucoma experts are available. Even though MRA provided 100% sensitivity in eyes with advanced glaucoma, it probably does not offer sufficient specificity to make it suitable as a screening method. Continuing medical education on ONH analysis had a small, but positive effect on diagnostic accuracy for glaucoma. An ANN trained to classify visual fields seemed to perform at least as well as most of the participating physicians, whose performances were remarkably similar regardless of their level of experience. This indicates that available tools for interpreting SAP findings are helpful in assessments of visual field test results. However, SAP is associated with learning effects (Heijl et al. 1989) that may entail low specificity for untrained subjects, and hence, it is not an ideal screening method for glaucoma. By comparison, the screening test of FDT is rapid and easy, but it is probably less suitable for screening purpose, because some eyes with advanced glaucoma were missed in this investigation. GDx VCC images for a relatively large number of eyes could not be analysed and is thus not appropriate for screening. The OCT instruments offer both high sensitivity and high specificity, and all eyes with advanced disease were correctly classified as glaucomatous in this evaluation. However, these instruments are still expensive and require special operator skills. Additional development to obtain OCT instrument that is more compact, easier to use and less expensive might render such tomography suitable as a screening tool for glaucoma.
    Acta ophthalmologica 02/2013; 91(thesis1):1-32. DOI:10.1111/aos.12072 · 2.51 Impact Factor
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