OBJECTIVES: 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. DATA SOURCES: Major electronic databases were searched up to December 2005. REVIEW METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

PURPOSE. The Ocular Response Analyzer (ORA) is a new instrument that measures the corneal biomechanical response (corneal hysteresis, CH) to rapid indentation by an air jet. CH is the difference in applanation pressures (P1, P2) between the rising and falling phases of the air jet. The investigation had two parts: a characterization study and a validation study. In the characterization study, the purposes were to investigate the intraocular pressure (IOP)– dependence of CH and to characterize the performance of the ORA. In the validation study, the purposes were to investigate the association between CH and both age and central corneal thickness (CCT) and the agreement between ORA and Goldmann applanation tonometer (GAT) IOP measurements. METHODS. For the characterization study, data were collected from 105 untreated subjects (45 ocular hypertensive patients and 60 normal subjects; mean age, 60 years, range, 26 – 82). GAT and ORA measurements were performed before and after IOP lowering of one randomly selected eye with apraclonidine drops. The change in P1 and P2 (arbitrary units) in relation to change in GAT IOP was analyzed to calibrate the instrument. The relation between P1, P2, and CCT was explored and ORA IOP was derived from the analyses. For the validation study, ORA and GAT IOP and CCT were measured in 144 eyes of 144 untreated subjects (mean age, 58 years; range, 19 – 83). The characterization calculations were applied to the dataset and values of CH and ORA IOP were calculated. The relationship between CH and both subject age and CCT was determined. The associations between CH and CCT and between ORA and GAT IOPs, were investigated by linear regression analysis. The agreement between measuring devices was calculated. RESULTS. In the characterization study, P1 changed by 6.41 arbitrary units for every 1-mm Hg change in GAT IOP. CH (P1 P2) changed by 1.60 arbitrary units for every 1-mm Hg change in GAT IOP. For each unit change in P2, P1 changed by 1.27 units. From this association a new IOP-independent corneal factor was derived [P1 (P2/1.27)] and is termed the corneal constant factor (CCF; mm Hg). ORA IOP normalized for CCF was defined as P2 – CCF (mm Hg). The CCF (mm Hg) was associated with CCT (micrometers) and with age: CCF [(0.036 CCT) (0.028 age)] 1.06 (adjusted r 2 0.34; P 0.0001 for CCT, P 0.007 for age). Normalized ORA IOP measurements were not associated with CCT. GAT IOP was associated with CCT and CCF—more strongly with the latter: GAT IOP (0.03 CCT)1.52 (r 2 0.06, P 0.002); GAT IOP (0.65 CCF) 4.5 (r 2 0.13, P 0.0001). The mean difference (95% limits of agreement) between GAT and normalized ORA IOP was 0.1 (6.6 to 6.8) mm Hg. CONCLUSIONS. The CCF describes an IOP-independent biomechanical property of the cornea that increases with thicker CCT and decreases with greater age. It is moderately strongly associated with CCT and yet explains more of the interindividual variation in GAT IOP than does CCT. Normalized ORA IOP measurements are not associated with CCT. (Invest Ophthalmol Vis Sci. 2006;47:5337–5347) DOI:10.1167/iovs.060557

Corneal Thickness- and Age-Related Biomechanical Properties of the Cornea Measured with the Ocular Response Analyzer

Purpose: The aim of this study was to determine the stress-strain behavior of corneal tissue and how the behavior was affected by age. Methods: Human corneal specimens ranging in age between 50 and 95 years were tested under inflation conditions to determine their stress-strain behavior. The corneas were subjected to two load rates that represent dynamic and static loading conditions. The pressure-deformation results were analyzed using shell theory to derive the stress-strain behavior. Results: The corneas demonstrated clear nonlinear behavior with an initial low stiffness stage and a final high stiffness stage. The transition between the two stages coincided with intraocular pressures between 12 and 20 mmHg. There was a considerable increase in stiffness associated with both age and load rate. Equations were derived to describe the nonlinear stress-strain relationship of corneal tissue for any age between 50 and 95 years, and these equations are presented in a form suitable for use in numerical simulati...

Assessment of Corneal Biomechanical Properties and Their Variation with Age

PURPOSE To determine the intraexaminer repeatability and intersession reproducibility of corneal deformation measurement using Scheimpflug noncontact tonometry (Corvis ST) on normal subjects. METHODS Thirty-seven adults aged 20 to 48 years were invited to have their corneal deformation and curvature measurements taken using Corvis ST and Pentacam, respectively. Three consecutive measurements were taken for each instrument between 9:00 and 11:00 AM for intraexaminer repeatability analysis. Participants returned between 3:00 and 5:00 PM the same day for intersession reproducibility analysis. RESULTS The most repeatable corneal parameter measured by Corvis ST was central corneal thickness ([CCT] ICC, 0.96; precision, 10.85 μm; repeatability, 15.34 μm; CV, 1.01%), followed by deformation amplitude ([DA] ICC, 0.80; precision, 0.08 mm; repeatability, 0.13 mm; CV, 4.33%), first applanation time ([1st A-time] ICC, 0.77; precision, 0.22 milliseconds; repeatability, 0.31 milliseconds; CV, 1.42), and intraocular pressure ([IOP] ICC, 0.75; precision, 1.39 mm Hg; repeatability, 1.97 mm Hg; CV, 4.98). Other parameters showed poor repeatability. The DA and 1st A-time showed good intersession reproducibility. The 95% limits of agreement were +0.13 to -0.13 mm for DA and +0.27 to -0.33 milliseconds for 1st A-time. The DA was negatively correlated with central corneal thickness (r = -0.53, p < 0.001) but not with corneal curvatures (flattest curvature, r = 0.13, p = 0.46; steepest curvature, r = 0.05, p = 0.75). CONCLUSIONS Corneal deformation parameters DA and 1st A-time were repeatable and reproducible. A thinner cornea was associated with a higher corneal deformation. Measurement of DA serves as an indicator of corneal biomechanical properties.

Corneal deformation measurement using Scheimpflug noncontact tonometry.

Objectives: To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways. Design: A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model. Setting: Primary and secondary care. Participants: Adults with ocular hypertension (IOP > 21mmHg) and the public (surveillance preferences). Interventions: We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community. Main outcome measures: Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs). Results: The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence. Limitations: Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates. Conclusions: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment. Funding: The National Institute for Health Research Health Technology Assessment Programme. © Queen's Printer and Controller of HMSO 2012.

https://njl-admin.nihr.ac.uk/document/download/2002258

Surveillance for Ocular Hypertension: An Evidence Synthesis and Economic Evaluation

Aims: To evaluate the influence of central corneal thickness (CCT) on intraocular pressure (IOP) measurements made with the Goldmann applanation tonometer (GAT), Tono-Pen XL, ocular blood flow tonograph (OBF), and Canon TX-10 non-contact tonometer (NCT). Methods: CCT was recorded for either eye (randomly selected) of each of 105 untreated patients with ocular hypertension and glaucoma attending the glaucoma research unit at Moorfields Eye Hospital. For each of the selected eyes, IOP was measured with the GAT (two observers), Tono-Pen, OBF, and NCT in a randomised order. The relation of measured IOP and of inter-tonometer differences with CCT and subject age was explored by linear regression analysis. Results: A significant association between measured IOP and CCT was found with each instrument. The change in measured IOP for a 10 μm increase in CCT was 0.28, 0.31, 0.38, and 0.46 for the GAT, Tono-Pen, OBF, and NCT, respectively (all p⩽0.05). There was a significant association between the NCT/GAT differences and CCT, with a tendency of NCT to overestimate GAT in eyes with thicker corneas. There was a significant association between GAT/Tono-Pen and OBF/Tono-Pen differences and age, with a tendency of GAT and OBF to overestimate the Tono-Pen in eyes of older subjects. Conclusion: IOP measurement by all four methods is affected by CCT. The NCT is affected by CCT significantly more than the GAT. Subject age has a differential effect on the IOP measurements made by the GAT and OBF compared to the Tono-Pen.

https://bjo.bmj.com/content/bjophthalmol/89/7/851.full.pdf

The influence of central corneal thickness and age on intraocular pressure measured by pneumotonometry, non-contact tonometry, the Tono-Pen XL, and Goldmann applanation tonometry

Aim: To compare the inter-method agreement in intraocular pressure (IOP) measurements made with four different tonometric methods. Methods: IOP was measured with the Goldmann applanation tonometer (GAT), Tono-Pen XL, ocular blood flow tonograph (OBF), and Canon TX-10 non-contact tonometer (NCT) in a randomised order in one eye of each of 105 patients with ocular hypertension or glaucoma. Three measurements were made with each method, and by each of two independent GAT observers. GAT interobserver and tonometer inter-method agreement was assessed by the Bland-Altman method. The outcome measures were 95% limits of agreement for IOP measurements between GAT observers and between tonometric methods, and 95% confidence intervals for intra-session repeated measurements. Results: The mean differences (bias) in IOP measurements were 0.4 mm Hg between GAT observers, and 0.6 mm Hg, 0.1 mm Hg, and 0.7 mm Hg between GAT and Tono-Pen, OBF, and NCT, respectively. The 95% limits of agreement were smallest (bias ±2.6 mm Hg) between GAT observers, and larger for agreement between the GAT and the Tono-Pen, OBF, and NCT (bias ±6.7, ±5.5, and ±4.8 mm Hg, respectively). The OBF and NCT significantly underestimated GAT measurements at lower IOP and overestimated these at higher IOP. The repeatability coefficients for intra-session repeated measurement for each method were ±2.2 mm Hg and ±2.5 mm Hg for the GAT, ±4.3 mm Hg for the Tono-Pen, ±3.7 mm Hg for the OBF, and ±3.2 mm Hg for the NCT. Conclusions: There was good interobserver agreement with the GAT and moderate agreement between the NCT and GAT. The differences between the GAT and OBF and between the GAT and Tono-Pen probably preclude the OBF and Tono-Pen from routine clinical use as objective methods to measure IOP in normal adult eyes.

https://bjo.bmj.com/content/bjophthalmol/89/7/847.full.pdf

PA Tonnu

Papers

The influence of central corneal thickness and age on intraocular pressure measured by pneumotonometry, non-contact tonometry, the Tono-Pen XL, and Goldmann applanation tonometry

A comparison of four methods of tonometry: method agreement and interobserver variability.