Andrew I. McNaught

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.

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.

Trabeculectomy in the 21st century: a multicenter analysis.

OBJECTIVE To evaluate the efficacy and safety of current trabeculectomy surgery in the United Kingdom. DESIGN Cross-sectional, multicenter, retrospective follow-up. PARTICIPANTS A total of 428 eyes of 395 patients. METHODS Consecutive trabeculectomy cases with open-angle glaucoma and no previous incisional glaucoma surgery from 9 glaucoma units were evaluated retrospectively. Follow-up was a minimum of 2 years. MAIN OUTCOME MEASURES Surgical success, intraocular pressure (IOP), visual acuity, complications, and interventions. Success was stratified according to IOP, use of hypotensive medications, bleb needling, and resuturing/revision for hypotony. Reoperation for glaucoma and loss of perception of light were classified as failures. RESULTS Antifibrotics were used in 400 cases (93%): mitomycin C (MMC) in 271 (63%), 5-fluorouracil (5-FU) in 129 (30%), and no antifibrotic in 28 (7%). At 2 years, IOP (mean ± standard deviation) was 12.4 ± 4 mmHg, and 342 patients (80%) achieved an IOP ≤ 21 mmHg and 20% reduction of preoperative IOP without IOP-lowering medication, whereas 374 patients (87%) achieved an IOP ≤ 21 mmHg and 20% reduction of preoperative IOP overall. An IOP ≤18 mmHg and 20% reduction of preoperative IOP were achieved by 337 trabeculectomies (78%) without IOP-lowering treatment and by 367 trabeculectomies (86%) including hypotensive medication. Postoperative treatments included suture manipulation in 184 patients (43%), resuturing or revision for hypotony in 30 patients (7%), bleb needling in 71 patients (17%), and cataract extraction in 111 of 363 patients (31%). Subconjunctival 5-FU injection was performed postoperatively in 119 patients (28%). Visual loss of >2 Snellen lines occurred in 24 of 428 patients (5.6%). A total of 31 of the 428 patients (7.2%) had late-onset hypotony (IOP <6 mmHg after 6 months). In 3 of these, visual acuity decreased by >2 Snellen lines. Bleb leaks were observed in 59 cases (14%), 56 (95%) of which occurred within 3 months. Two patients developed blebitis. Bleb-related endophthalmitis developed in 1 patient within 1 month postoperatively and in 1 patient at 3 years. There was an endophthalmitis associated with subsequent cataract surgery. CONCLUSIONS This survey shows that good trabeculectomy outcomes with low rates of surgical complications can be achieved, but intensive proactive postoperative care is required.

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.

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.

Simulating binocular visual field status in glaucoma

AIMS To simulate the central binocular visual field using results from merged left and right monocular Humphrey fields. To assess the agreement between the simulation and the binocular Humphrey Esterman visual field test (EVFT). METHOD 59 consecutive patients with bilateral glaucoma each recorded Humphrey 24-2 fields for both eyes and binocular EVFT on the same visit. EVFT results were used to identify patients exhibiting at least one defect (<10 dB) within the central 20° of the binocular field. This criterion is relevant to a patient’s legal fitness to drive in the UK. Individual sensitivity values from monocular fields are merged to generate a simulated central binocular field. Results are displayed as a grey scale and as symbols representing defects at the <10 dB level. Agreement between patients failing the criterion using the simulation and the EVFT was evaluated. RESULTS Substantial agreement was observed between the methods in classifying patients with at least one defect (<10 dB) within the central binocular field (kappa 0.81; SE 0.09). Patients failing this criterion using the EVFT results were identified by the binocular simulation with high levels of sensitivity (100%) and specificity (86%). CONCLUSIONS Excellent agreement exists between the simulated binocular results and EVFT in classifying glaucomatous patients with central binocular defects. A rapid estimate of a patient’s central binocular field and visual functional capacity can be ascertained without extra perimetric examination.

Surgery for normal tension glaucoma.

The long term follow up of surgery in normal tension glaucoma is presented. One eye of 18 patients with bilateral progressive disease underwent fistulising surgery. Over follow up periods ranging from 2 to 7 years (50% > or = 5 years) the operated eye showed on average a 30% reduction in intraocular pressure (IOP). This was associated with a marked difference in the rate and number of retinal locations showing a progressive decline in retinal function, suggesting some protective function for lowering IOP in patients with normal tension glaucoma.

Image processing of computerised visual field data.

BACKGROUND--Computerised perimetry is of fundamental importance in assessing visual function. However, visual fields are subject to patient response variability which limits the detection of true visual loss. METHODS--A method of improving the repeatability of visual field data was demonstrated by applying techniques used in image processing. An illustrative sample of nine normals and nine patients with field loss was used. Two successive Humphrey fields were selected for each subject. Repeatability was defined as the standard deviation of the pointwise differences between sensitivity values of the reference field and repeat field. The field data were then separately subjected to Gaussian and median image processing filters and the repeatability was compared with the unprocessed field results. RESULTS--Improvement in repeatability, by a factor of approximately 2, was demonstrated by both processes. CONCLUSION--These techniques may improve the reliable detection of loss of visual function using computerised perimetry.

Improving the Prediction of Visual Field Progression in Glaucoma Using Spatial Processing

PURPOSE The authors show how the predictive performance of a method for determining glaucomatous progression in a series of visual fields can be improved by first subjecting the data to a spatial processing technique. METHOD Thirty patients with normal-tension glaucoma, each with at least ten Humphrey fields and 3.5 years of follow-up, were included. A linear regression model of sensitivity against time of follow-up determined rates of change at individual test locations over the first five fields (mean follow-up 1.46 years; standard deviation = 0.08) in each field series. Predictions of sensitivity at each location of the field nearest to 1 and 2 years after the fifth field were generated using these rates of change. Predictive performance was evaluated by the difference between the predicted and measured sensitivity values. The analysis was repeated using the same field data subjected to a spatial filtering technique used in image processing. RESULTS Using linear modeling of the unprocessed field series, at 1 year after the fifth field, 72% of all predicted values were within +/- 5 dB of the corresponding measured threshold. This prediction precision improved to 83% using the processed data. At the 2-year follow-up field, the predictive performance improved from 56% to 73% with respect to the +/- 5 dB criterion. CONCLUSIONS Predictions of visual field progression using a pointwise linear model can be improved by spatial processing without increased cost or patient time. These methods have clinical potential for accurately detecting and forecasting visual field deterioration in the follow-up of glaucoma.