David P. Crabb

Analysis of visual field progression in glaucoma.

BACKGROUND: Despite the widespread use of computerised perimetry the diagnosis of visual field deterioration in following glaucoma patients over time remains particularly difficult. A new method of analysis using a novel graphical display of longitudinal field data is presented. METHODS: A linear regression model of the luminance sensitivity at each stimulus location against time of follow up transforms the quantitative data from a series of fields into a colour coded form which illustrates the spatial configuration of change to aid the interpretation of field loss. The method of analysis and the developed computer software (PROGRESSOR) is described. Comparison with STATPAC-2 glaucoma change probability analysis is given including levels of agreement between the techniques using series of fields of 10 eyes from patients with normal tension glaucoma. RESULTS: Examples of this new method compare well with STATPAC-2 analysis. The level of agreement between the techniques to separate progressing from stable retinal locations is good (kappa = 0.62; SE = 0.04). CONCLUSIONS: This new technique, which combines the change in perimetric sensitivity over time with colour coding of significant change into one image may provide an efficient method to detect true progression in glaucomatous field loss.

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial

BACKGROUND Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. METHODS In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. FINDINGS We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. INTERPRETATION This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. FUNDING Pfizer, UK National Institute for Health Research Biomedical Research Centre.

Exploring eye movements in patients with glaucoma when viewing a driving scene.

Background Glaucoma is a progressive eye disease and a leading cause of visual disability. Automated assessment of the visual field determines the different stages in the disease process: it would be desirable to link these measurements taken in the clinic with patients actual function, or establish if patients compensate for their restricted field of view when performing everyday tasks. Hence, this study investigated eye movements in glaucomatous patients when viewing driving scenes in a hazard perception test (HPT). Methodology/Principal Findings The HPT is a component of the UK driving licence test consisting of a series of short film clips of various traffic scenes viewed from the drivers perspective each containing hazardous situations that require the camera car to change direction or slow down. Data from nine glaucomatous patients with binocular visual field defects and ten age-matched control subjects were considered (all experienced drivers). Each subject viewed 26 different films with eye movements simultaneously monitored by an eye tracker. Computer software was purpose written to pre-process the data, co-register it to the film clips and to quantify eye movements and point-of-regard (using a dynamic bivariate contour ellipse analysis). On average, and across all HPT films, patients exhibited different eye movement characteristics to controls making, for example, significantly more saccades (P<0.001; 95% confidence interval for mean increase: 9.2 to 22.4%). Whilst the average region of ‘point-of-regard’ of the patients did not differ significantly from the controls, there were revealing cases where patients failed to see a hazard in relation to their binocular visual field defect. Conclusions/Significance Characteristics of eye movement patterns in patients with bilateral glaucoma can differ significantly from age-matched controls when viewing a traffic scene. Further studies of eye movements made by glaucomatous patients could provide useful information about the definition of the visual field component required for fitness to drive.

Modelling series of visual fields to detect progression in normal-tension glaucoma

Abstract• Background: Use of statistical modelling techniques to identify models that both describe glaucomatous sensitivity decay and allow predictions of future field status. • Method: Twelve initially normal fellow eyes of untreated patients with confirmed normal-tension glaucoma were studied. All had in excess of 15 Humphrey fields (mean follow-up 5.7 years). From this cohort individual field locations were selected for analysis if they demonstrated unequivocal deterioration at the final two fields. Forty-seven locations from five eyes satisfied this criterion and were analysed using curve-fitting software which automatically applies 221 different models to sensitivity (y) against time of follow up (x). Curve-fitting was then repeated on the first five fields, followed by projection to the date of the final field to generate a predicted threshold which was compared to the actual threshold. Competing models were therefore assessed on their performance at adequately fitting the data (R2) and their potential to predict future field status. • Results: Models that provided the best fit to the data were all complex polynomial expressions (median R2 0.93). Other simple expressions fitted fewer locations and exhibited lower R2 values. However, accuracy in predicting future deterioration was superior with these less complex models. In this group a linear expression demonstrated an adequate fit to the majority of the data and generated the most accurate predictions of future field status. • Conclusions: A linear model of the pointwise sensitivity values against time of follow-up can provide a framework for detecting and forecasting glaucomatous field progression. Linear modelling allows the clinically important rate of sensitivity loss to be estimated.

Effect of Surgery on Visual Field Progression in Normal-tension Glaucoma+++

PURPOSE The effect of intraocular pressure-lowering surgery on the rate of visual field progression in normal-tension glaucoma (NTG) was studied. METHODS Seventeen patients with NTG who underwent trabeculectomy in one eye for worsening visual field loss were included in the first part of the study. All patients had Humphrey 24-2 visual fields at the rate of 2-3 fields per year. Pointwise linear regression analysis of the visual field data was done separately for the preoperative and postoperative periods. This was performed for both operated and fellow eyes. The mean slope (MS), which indicates rate of visual field progression, was calculated. Change in MS was correlated with change in intraocular pressure (IOP). For the second part of the study, 11 patients who had a minimum of 4 visual fields and 18 months of follow-up before surgery were identified. Using the preoperative fields, the rate of sensitivity loss for each visual field location in the operated eye was ascertained for every patient. This rate of loss was extrapolated to generate the expected visual fields, assuming an unchanged rate of progression. The mean sensitivity of the expected visual field was compared with that of the actual field at the last follow-up. RESULTS The MS in the operated eyes improved from -2.97 +/- 3.21 (mean +/- SD) in the preoperative period to 0.53 +/- 3.83 (P < 0.005; Students t test) postoperatively. In the fellow eyes the MS changed from -1.78 +/- 2.55 to -1.43 +/- 3.01 (P = 0.754). There was a weak correlation between change in MS and percentage IOP decrease (correlation coefficient 0.39). The difference in mean sensitivity between the expected and actual visual fields was -3.72 dB (P = 0.002), and was better in the actual field. CONCLUSIONS In this study, surgical lowering of IOP resulted in a slower rate of visual field loss in the operated eye.

The Functional Consequences of Glaucoma for Eye–Hand Coordination

PURPOSE To examine whether patients with glaucoma exhibit differences in visually guided reaching-and-grasping (prehension) behavior compared with normally sighted control subjects. METHODS Sixteen patients with glaucoma and 16 control subjects with no ocular disease participated. Participants were required to reach out and precision grasp one of two cylindrical objects placed on a table top in front of them in laboratory conditions in three viewing conditions (binocular, right eye alone, left eye alone). Lightweight reflective markers were placed on the subjects preferred hand for recording its movement in three-dimensional space. Three motion capture units recorded the motion of these markers as the subjects reached out and precision grasped household objects. Various indices of prehension planning, execution, and control were quantified. Visual fields (VF) were measured using standard automated perimetry generating monocular mean deviation (MD) scores. Binocular VF sensitivity was estimated by using the integrated visual field (IVF). Stereoacuity was measured with the Frisby stereoacuity test. Significant differences in prehension movement between patients and control subjects in each viewing condition were investigated, and associations between prehension kinematics and VF sensitivity were examined. RESULTS The patients and control subjects were of a similar age (median [range]: patient group, 72.2 years [62.5-86.9]; control group, 69.0 years [64.3-78.3]). The patient group had asymmetrical disease and relatively minor binocular overlapping defects (better eye MD, -5.7 dB [-16.7 to +0.45 dB]; worse eye MD, -11.8 dB [-29.3 to -1.5 dB]; IVF score, 3 [0-36]). They exhibited slightly poorer stereoacuity levels than did the control subjects (patient group, 55 sec arc [40-110]; control group, 40 sec arc [20-80; Mann-Whitney U test, P < 0.05]). They also showed statistically significant delays in average movement onset (MO: approximately 100 ms delay, Mann-Whitney U test P < 0.0001) and overall movement time (OMD: approximately 140 ms delay; Mann-Whitney U test P < 0.05), suggesting impairments in initial movement planning and control. Deficits were exhibited in the reaching component, with data suggesting that glaucomatous patients made more tentative movements when reaching for the object. These deficits correlated with both increasing severity of VF defect and impaired stereoacuity. There were no differences in grasping characteristics between patients and control subjects in this sample. CONCLUSIONS This study provides evidence that patients with glaucoma exhibit deficits in eye-hand coordination compared with the age-matched normally sighted control. Further study is needed to assess the specific effect of field loss location on prehension kinematics.

Interobserver agreement on visual field progression in glaucoma: a comparison of methods

Aim: To examine the level of agreement between clinicians in assessing progressive deterioration in visual field series using two different methods of analysis. Methods: Each visual field series satisfied the following criteria: more than 19 reliable fields, patient age over 40 years, macular threshold at least 30 dB. The first three fields in each series were excluded to minimise learning effects: the following 16 were studied. Five expert clinicians assessed the progression status of each series using both standard Humphrey printouts and pointwise linear regression (progressor). The level of agreement between the clinicians was evaluated using a weighted kappa statistic. Results: A total of 432 tests comprising 27 visual field series of 16 tests each were assessed by the clinicians. The level of agreement on progression status between the clinicians was always higher when they used progressor (median kappa = 0.59) than when they used Humphrey printouts (median kappa = 0.32). This was statistically significant (p = 0.006, Wilcoxon matched pairs signed rank sum test). Conclusions: Agreement between expert clinicians about visual field progression status is poor when standard Humphrey printouts are used, even when the field series studied are long and consist solely of reliable fields. Under these ideal conditions, clinicians agree more closely about patients’ visual field progression status when using progressor than when inspecting series of Humphrey printouts.

Patients have two eyes!: binocular versus better eye visual field indices.

PURPOSE To test the hypothesis that better eye measures overestimate binocular visual field (VF) defect severity in glaucoma. METHODS Humphrey VFs (24-2 SITA standard) from 67 consecutive patients with glaucoma were retrospectively examined (mean age, 65 years; range, 31-88 years). The better mean deviation (MD) from the two eyes was recorded (better eye MD). Binocular integrated visual field (IVF) was constructed for each patient by merging corresponding sensitivity values from monocular VF. An IVF MD was calculated from the average of total deviation values in the IVF. The differences between better eye MD and IVF MD were assessed. RESULTS The average IVF MD was significantly better than the average better eye MD (mean difference, 1.3 dB; 95% confidence interval [CI], 1.0-1.7 dB; P < 0.001). Twenty-four percent of patients had an IVF MD that was at least 2 dB healthier than the MD in the better eye (95% CI, 14%-34%). The size of the differences between better eye and IVF MD was significantly associated with the severity of VF defect (P < 0.001; R² = 0.44). CONCLUSIONS Monocular measures, such as better eye MD, can give the impression that a patients VF loss is more degraded than it might be under binocular viewing. This effect is more pronounced in patients with advanced VF defects. The IVF offers a rapid assessment of a patients binocular VF severity without extra testing.

Visual field progression : comparison of Humphrey Statpac2 and pointwise linear regression analysis

Abstract•Background: Humphrey Statpac2 ‘glaucoma change probability analysis’ is a widely available analysis technique to aid the clinician in the diagnosis of glaucomatous visual field deterioration. A comparison of this technique with the more recently described pointwise linear regression analysis (PROGRESSOR) is given. • Methods: Series of visual field data from a group of nine eyes of nine patients with normal-tension glaucoma were selected. Each series had 16 fields with mean follow up of 5.7 years (SD 0.6 years). Statpac2 ‘glaucoma change probability analysis’ was used to define test locations that had unequivocally deteriorated in the last three fields of each series. The accuracy of both Statpac2 and PROGRESSOR in providing early detection of these deteriorated locations was assessed. • Results: The sensitivity and specificity of the two techniques in predicting deteriorated locations were similar when a rate of luminance sensitivity loss of faster than 1 dB/year (2 dB/year for outer locations beyond 15 deg of eccentricity) with a slope significance ofP<0.10 was used as the regression definition of deterioration. The difficulties of comparing two techniques in the early diagnosis of field progression without a true external standard for field loss are illustrated. • Conclusions: PROGRESSOR closely emulates the performance of Statpac2 in detecting sensitivity deterioration at individual test locations. This new technique, which uses all available data in a field series and gives the rate of sensitivity loss at each location, may provide a clinically useful method for detecting field progression in glaucoma.

Ophthalmic statistics note 5: diagnostic tests—sensitivity and specificity

This is the fifth statistics note produced by the Ophthalmic Statistics Group (OSG) which is designed to be a simple guide to ophthalmic researchers on a statistical issue with an applied ophthalmic example. The OSG is a collaborative group of statisticians who have come together with a desire to raise the statistical standards of ophthalmic researcher by increasing statistical awareness of common issues.