David F. Garway-Heath

Practical recommendations for measuring rates of visual field change in glaucoma.

To date, there has been a lack of evidence-based guidance on the frequency of visual field examinations required to identify clinically meaningful rates of change in glaucoma. The objective of this perspective is to provide practical recommendations for this purpose. The primary emphasis is on the period of time and number of examinations required to measure various rates of change in mean deviation (MD) with adequate statistical power. Empirical data were used to obtain variability estimates of MD while statistical modelling techniques derived the required time periods to detect change with various degrees of visual field variability. We provide the frequency of examinations per year required to detect different amounts of change in 2, 3 and 5 years. For instance, three examinations per year are required to identify an overall change in MD of 4 dB over 2 years in a patient with average visual field variability. Recommendations on other issues such as examination type, strategy and quality are also made.

Corneal Hysteresis but Not Corneal Thickness Correlates with Optic Nerve Surface Compliance in Glaucoma Patients

PURPOSE To investigate relationships between acute intraocular pressure (IOP)-induced optic nerve head surface deformation and corneal hysteresis and thickness in glaucomatous and nonglaucomatous human eyes. METHODS This was a prospective experimental study of 100 subjects (38 with glaucoma, 62 without glaucoma). Data collected included spherical equivalent, optic disc diameter, central corneal thickness (CCT), axial length, cylinder, Goldmann IOP, Pascal IOP, and ocular pulse amplitude and ocular response analyzer (ORA) measurements of corneal hysteresis (CH). Elevation of IOP was induced in the right eye of each subject with a modified LASIK suction ring to an average of 64 mm Hg for less than 30 seconds. Heidelberg Retina Tomography II (HRT) was used to map the optic nerve surface before and during IOP elevation. Mean cup depth was calculated using built-in HRT data analysis software. Change in optic disc depth during IOP elevation was calculated for all right eyes, and tests for correlation with the parameters listed were performed. RESULTS Both CH and CCT were lower in the glaucoma group (8.8 mm Hg and 532 microm) than in the control group (9.6 mm Hg, P = 0.012; 551 microm, P = 0.011, respectively). There were no statistically significant differences in spherical equivalent, cylinder, axial length, optic disc size, or ocular pulse amplitude between the glaucoma and the control groups. There was no difference between the amount of IOP elevation between the two groups (P = 0.41), and the average difference in mean cup depth between baseline (mean cup depth, 247 microm) and during IOP elevation was 33 microm (29.8 microm in glaucoma and 36.1 microm in control; P = 0.5). Multiple variable analysis, controlling for age and sex, showed that CH was correlated with mean cup depth increase (P = 0.032). This relationship persisted (P = 0.032) after controlling for glaucoma status in addition to age and sex. Other factors, including CCT (P = 0.3), axial length (P = 0.9), ocular pulse amplitude (P = 0.22), and spherical equivalent (P = 0.38), were not significant in this model. CONCLUSIONS In the glaucoma patients but not the control patients, CH but not CCT or other anterior segment parameters was associated with increased deformation of the optic nerve surface during transient elevations of IOP. (ClinicalTrials.gov number, NCT00328835.).

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.

Vertical cup/disc ratio in relation to optic disc size: its value in the assessment of the glaucoma suspect

AIMS The vertical cup/disc ratio (CDR) has long been used in the assessment of the glaucoma suspect, though the wide range of CDR values in the normal population limits its use. Cup size is related physiologically to disc size and pathologically to glaucomatous damage. Disc size can be measured at the slit lamp as the vertical disc diameter (DD). The ability of the CDR, in relation to DD, to identify glaucomatous optic discs was investigated. METHODS 88 normal, 53 early glaucoma, and 59 ocular hypertensive subjects underwent stereoscopic optic disc photography and clinical biometry. Photographs were analysed in a masked fashion by computer assisted planimetry. The relation between vertical cup diameter and DD was explored by linear regression, and expressed in terms of CDR. The upper limit of normal was defined by the 95% prediction intervals of this regression (method 1) and by the upper 97.5 percentile for CDR (method 2). The sensitivity and specificity of CDR to identify an optic disc as glaucomatous was tested with these disc size dependent and disc size independent cut offs in small, medium, and large discs. RESULTS The CDR was related to DD by the equation CDR = (−1.31 + (1.194 × DD))/DD. The sensitivity in small, medium, and large discs was 80%, 60%, and 38% respectively for method 1 and 33%, 67%, and 63% respectively for method 2. Specificity was 98.9% (method 1) and 97.7% (method 2). CONCLUSIONS The CDR, relative to disc size, is useful clinically, especially to assist in identifying small glaucomatous discs.

‘Structure–function relationship’ in glaucoma: past thinking and current concepts

An understanding of the relationship between functional and structural measures in primary open‐angle glaucoma is necessary for both grading the severity of disease and for understanding the natural history of the condition. This article outlines the current evidence for the nature of this relationship and highlights the current mathematical models linking structure and function. Large clinical trials demonstrate that both structural and functional change are apparent in advanced stages of disease, and at an individual level, detectable structural abnormality may precede functional abnormality in some patients, whereas the converse is true in other patients. Although the exact nature of the ‘structure–function’ relationship in primary open‐angle glaucoma is still the topic of scientific debate and the subject of continuing research, this article aims to provide the clinician with an understanding of the past concepts and contemporary thinking in relation to the structure–function relationship in primary open‐angle glaucoma.

Clinical Assessment of Stereoscopic Optic Disc Photographs for Glaucoma: The European Optic Disc Assessment Trial

PURPOSE To determine the diagnostic accuracy of judging optic disc photographs for glaucoma by ophthalmologists. DESIGN Evaluation of diagnostic test and technology. PARTICIPANTS A total of 243 of 875 invited ophthalmologists in 11 European countries. METHODS We determined how well each participant classified 40 healthy eyes and 48 glaucomatous eyes with varying severity of the disease on stereoscopic slides. Duplicate slides were provided for determining intraobserver agreement. All eyes were also imaged with the GDx with variable corneal compensation (GDx-VCC) (Carl Zeiss Meditec AG, Jena, Germany) and the Heidelberg Retina Tomograph (HRT) I (Heidelberg Engineering GmbH, Heidelberg, Germany). Diagnostic accuracies of clinicians were compared with those of the best machine classifiers. MAIN OUTCOME MEASURES Accuracy of classification, expressed as sensitivity, specificity, and overall accuracy. Intraobserver agreement (kappa). RESULTS The overall diagnostic accuracy of ophthalmologists was 80.5% (standard deviation [SD], 6.8; range, 61.4%-94.3%). The machine classifiers outperformed most observers in diagnostic accuracy; the GDx-VCC nerve fiber indicator and the HRTs best classifier correctly classified 93.2% and 89.8% of eyes, respectively. The intraobserver agreement (kappa) varied between -0.13 and 1.0 and was on average good (0.7). CONCLUSIONS In general, ophthalmologists classify optic disc photographs moderately well for detecting glaucoma. There is, however, large variability in diagnostic accuracy among and agreement within clinicians. Common imaging devices outperform most clinicians in classifying optic discs. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

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.

Intraocular Pressure Measurement Precision with the Goldmann Applanation, Dynamic Contour, and Ocular Response Analyzer Tonometers

OBJECTIVE To examine the repeatability and reproducibility of intraocular pressure (IOP) measurements obtained with the Goldmann applanation tonometer (GAT), the Pascal dynamic contour tonometer (DCT; Swiss Microtechnology AG, Port, Switzerland), and the Reichert Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments, Buffalo, NY). A secondary objective was to assess agreement between the devices. DESIGN Evaluation of technology. PARTICIPANTS One hundred participants; a mixture of glaucoma suspects, patients, and control volunteers. METHODS The IOP measurements were obtained with the GAT, DCT, and ORA by 2 of 3 experienced clinicians. Keratometry (CC) measurements were made using the IOLMaster (Carl Zeiss Meditech, AG, Jena, Germany). Three ORA corneal compensated IOP (IOPcc) measurements were obtained before the instillation of anesthesia, after which 2 GAT IOP and 3 DCT IOP measurements were obtained in a randomized order. Central corneal thickness (CCT) was measured using an ultrasound pachymeter. The average ORA corneal response factor (CRF) and the average DCT ocular pulse amplitude (OPA) were determined. Intraobserver variability was calculated by the repeatability coefficient. Interobserver variability (measurement reproducibility) and device agreement were calculated by Bland-Altman analysis (mean difference [bias] and 95% limits of agreement [LoA]). The effect of corneal characteristics (CC, CCT, and CRF) on the IOP measurement differences between tonometers also was determined. MAIN OUTCOME MEASURES Repeatability and reproducibility of the GAT, DCT, and ORA IOPcc and agreement between tonometers. RESULTS The repeatability coefficients for GAT, DCT, and ORA were 2.2, 2.3, and 4.3 mmHg, respectively. The intraobserver variability of ORA measurements was shown to be significantly associated with OPA and to a lesser degree with the quality of ORA waveform scans. The interobserver bias (95% LoA) was -0.8 (+/-3.9) mmHg for GAT -0.2 (+/-2.8) mmHg for DCT and -0.3 (+/-3.9) mmHg for ORA IOPcc. On average, GAT under-read both DCT and ORA IOP measurements by approximately 2 mmHg. The IOP measurement differences were better predicted by CRF than CCT. CONCLUSIONS The DCT shows excellent measurement precision, displaying the best repeatability and reproducibility of the 3 tonometers. Corneal stiffness, as defined using CRF, was associated significantly with agreement between devices. The IOP measurements with each device are not interchangeable. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

How Does Glaucoma Look?: Patient Perception of Visual Field Loss

OBJECTIVE To explore patient perception of vision loss in glaucoma and, specifically, to test the hypothesis that patients do not recognize their impairment as a black tunnel effect or as black patches in their field of view. DESIGN Clinic-based cross-sectional study. PARTICIPANTS Fifty patients (age range, 52-82 years) with visual acuity better than 20/30 and with a range of glaucomatous visual field (VF) defects in both eyes, excluding those with very advanced disease (perimetrically blind). METHODS Participants underwent monocular VF testing in both eyes using a Humphrey Field Analyzer (HFA; Carl Zeiss Meditec, Dublin, CA; 24-2 Swedish interactive threshold algorithm standard tests) and other tests of visual function. Participants took part in a recorded interview during which they were asked if they were aware of their VF loss; if so, there were encouraged to describe it in their own words. Participants were shown 6 images modified in a variety of ways on a computer monitor and were asked to select the image that most closely represented their perception of their VF loss. MAIN OUTCOME MEASURES Forced choice of an image best representing glaucomatous vision impairment. RESULTS Participants had a range of VF defect severity: average HFA mean deviation was -8.7 dB (standard deviation [SD], 5.8 dB) and -10.5 dB (SD, 7.1 dB) in the right and left eyes, respectively. Thirteen patients (26%; 95% confidence interval [CI], 15%-40%) reported being completely unaware of their vision loss. None of the patients chose the images with a distinct black tunnel effect or black patches. Only 2 patients (4%; 95% CI, 0%-14%) chose the image with a tunnel effect with blurred edges. An image depicting blurred patches and another with missing patches was chosen by 54% (95% CI, 39%-68%) and 16% (95% CI, 7%-29%) of the patients, respectively. Content analysis of the transcripts from the recorded interviews indicated a frequent use of descriptors of visual symptoms associated with reported blur and missing features. CONCLUSIONS Patients with glaucoma do not perceive their vision loss as a black tunnel effect or as black patches masking their field of view. These findings are important in the context of depicting the effects of glaucomatous vision loss and raising awareness for glaucoma detection. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Experimental assessment of human corneal hysteresis.

Purpose: Hysteresis is a viscoelastic property characterized by the difference in behavior under loading and unloading. The aim of the study was to determine corneal hysteresis using experimental means. Methods: Twenty-nine human corneas with 50–95 year age were subjected to cycles of pressure loading and unloading. Two pressure application rates were adopted to approximate static and dynamic loading conditions. Results: The behavior under both loading and unloading was found to stiffen with increased age. The unloading behavior appeared to be largely independent of the pressure level at which unloading started. The difference between the behavior patterns under loading and unloading was quantified and used as a measure of corneal hysteresis. The hysteresis area was significantly larger with faster loading and with decreased age. Conclusions: The trend for hysteresis to decrease with age is in agreement with previous clinical observations. Hysteresis was also found to increase with faster pressure application.